Contents · super-rich, and by using Corporate Social Responsibility (CSR) funds of all national...

ContentsBreakthrough, Vol.21, No.4, May 2020

News & Views

• Press Statement on the AYUSH Advisory on Coronavirus . . . . . . . . . . . . . . . . . . . . . . . . . . . .1

• Open Letter sent to the President of India . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2

• Letter from India March for Science to the Prime Minister of India . . . . . . . . . . . . . . . . . 4

• Press statement on the Vizag Gas Leak tragedy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

General Articles

• A Primer on SARS-CoV-2 and the Evolving Covid-19 PandemicSubramani Mani . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .8

• Will a coronavirus vaccine stop the present wildfire of misery?Raju Mukherjee . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28

• SARS-CoV-2 and COVID-19: Where from and whither to?Mahipal Sriram . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35

• Some New Findings to Track the Origin of Novel CoronavirusKumar S. K. Varadwaj . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45

Organizational News

• Report on programmes and relief work undertaken . . . . . . . . . . . . . . . . .48

Press Statement on the AYUSH Advisory onCoronavirus

Dated 30 January 2020

The Breakthrough Science Society ex-presses shock and anguish that thePress Information Bureau (PIB), Govern-ment of India has released a statementrecommending members of the public touse untested Ayurveda, Homoeopathy andUnani medicines to prevent and treat theillnesses caused by Coronavirus . Even asthe World Health Organisation (WHO) hasonly advised the public to stick to basic pre-ventive measures like avoiding contact withpeople suffering from cold, washing hands,staying away from crowded places, farmor wild animals etc, Indian government af-ter giving similar hygiene recommendationshas also advised people to take to ayurvedicpractices, homoeopathic drugs and Unanimedicines . A homeopathic drug namelyArsenicum album30, or Unani medicineslike Sharbat Unnab or Ayurvedic prepa-rations like Shadang Paniya are advisedto be taken either as preventive medicinesor for symptomatic management againstCoronavirus infections. But there are no

supporting evidence that these medicinesare effective against the virus. How arethese drugs even relevant in the fightagainst novel Coronavirus (2019-nCov),which is itself a new organism is notclear. In the absence of proper studieson the effectiveness of these medicinesthe government advisory on Coronavirus isirresponsible, misleading, dangerous to thepublic health and against medical ethics.

The Coronavirus (2019-nCoV) has al-ready claimed 132 lives. It has affectedover a dozen of countries. According tothe Health Ministry, 9150 passengers havebeen screened for the Coronavirus. Healthministry has asked travellers from Chinato report to the nearest health facility incase they do not feel well. It is essential totake adequate preventive measures againstCoronavirus and issue proper advisories tothe people. We expect that these advisoriesshould go through scientific validation be-fore being publicly communicated.

Breakthrough, Vol.21, No. 4, May 2020 1

Open Letter sent to the President of India

Dated 20 March 2020

ToThe Honourable President of IndiaNew Delhi

Subject: Request for taking effective stepsto contain COVID-19 infections in India

Respected Sir,We are writing to request your urgent

intervention to prevent an impending publichealth emergency in the country. Indiais currently in Stage 2 of a COVID-19pandemic where cases are being reportedin those with travel history and those whohave been in contact with them. Thegovernment must heed the advice of healthexperts the world over, who tell us thatprogression to ‘Stage 3’, community trans-mission, should be avoided at all costs.

This requires urgent action by the Centraland State governments, working together,in the following directions.

1. The foreign nationals and Indians re-turning from the affected countries needto be mandatorily tested and, if anysuspicion arises, should be quarantined.

2. Since this has not been done effectivelyover the past two months, it is highlylikely that many infected individuals areout in the open, mixing with the publicand passing on the infection to others.Detection and containment is the onlyway to control the outbreak. Thisrequires a far larger number of testingfacilities than is available at present.

3. The government should rapidly enhance

the facilities for treating large numbersof patients, set up large number ofcritical care facilities equipped with life-supporting equipment like ventilators.Isolation wards should be created inall government hospitals at the state,district, and subdivision levels.

4. Private and corporate hospitals shouldbe requisitioned to give service to thepublic at this hour of crisis.

5. The government should ensure avail-ability of masks, hand sanitizers,medicines, etc., free of cost to preventexploitation of people by unscrupulousprofiteers, who should be severely dealtwith.

6. The government should take effectivemeasures to provide essential commodi-ties to people who are not able to earntheir livelihood because of the situationcreated by Covid-19.

7. Most importantly, effective steps mustbe taken to impose social distancing byavoiding gatherings of large number ofpeople for religious occasions, marriageparties, and other social events. In thisregard we would like to bring to yournotice that the Ram Navami celebrationsbeing planned by the UP governmentin Ayodhya and other places from 25March to 2 April will be a certain recipefor disaster. Lakhs of people are ex-pected to congregate in various places.Such large gatherings, which can hastenthe uncontrolled spread of the epidemic,

2 Breakthrough, Vol.21, No. 4, May 2020

Opinions

must be banned to prevent the potentialpandemic.

Finally, we are dismayed that the AYUSHMinistry, without any supporting evidenceand clinical trials, has prescribed a home-opathic drug Arsenicum album 30 and anarray of Ayurvedic and Unani drugs aspreventive medicines against the Coron-avirus infection. Such unscientific and mis-leading advisories should immediately bewithdrawn. In addition, the superstitiouspractices of drinking gomutra and dunkingin cow-dung, claiming them as cures forCOVID-19, should be banned as these

animal waste products are harmful forhealth.

We are hopeful that you will take themuch-needed steps to ensure proper han-dling and management of the threat posedby the COVID-19 virus.

Thanking you,Yours truly,

Prof. Dhrubajyoti MukhopadhyayPresident

Prof. Soumitro BanerjeeSecretary


Letter from India March for Science to thePrime Minister of India

Dated 21 April 2020

ToThe Prime MinisterGovernment of India

Sir,We welcome the measures the govern-

ment has taken to ensure physical distanc-ing to arrest the COVID-19 pandemic. How-ever, the experiences of Singapore, SouthKorea, and Japan have shown that socialdistancing by itself does not suffice; it isnecessary to embark on testing on a verylarge scale to identify and isolate not onlythe symptomatic patients but also the in-fected asymptomatic individuals. Moreover,the country also has to prepare the health-care system to be able to treat millions ofpatients, if the situation arises. In thiscontext we would like to put forth a fewconcrete proposals to deal with the crisis.

1. Whenever anybody tests positive, ex-tensive testing has to be done covering thewhole neighbourhood, the nearby marketarea, and the places that the individualvisited over the past few days, at leastby random sampling. That will requireincreasing the rate of testing to a substan-tially higher level compared to what is beingdone presently. This will require not only alarger number of test-kits, but also a largenumber of trained personnel. We proposethat unemployed science graduates be spe-cially recruited for this purpose and shouldbe trained on a war footing.

2. Most biology departments in research

institutions and universities have RT-PCRmachines in BSL2 facilities which can beused for COVID-19 detection. Faculty andstudents of many of these institutions areprepared to offer their services in this crisisperiod. Effective steps should be taken toutilize these facilities to enhance the testingcapability of the nation.

3. India is lagging way behind in geneticsequencing of the novel coronavirus. We donot have sufficient data on which mutatedvariants of the virus are there in India,neither do we know anything about therate at which it is mutating—all of whichare crucial for effective management of thepandemic. Therefore, we request you toincrease the number of genomic sequencingof the coronavirus isolated from Indianpatients, and to make the results publiclyavailable.

4. Isolation wards should be createdin district and subdivision-level hospitals,and even in the primary health centres,equipping them with the necessary infras-tructure to treat COVID-19 patients. Thegovernment should use the facilities inprivate hospitals to create special wardsto provide free treatment to COVID-19 pa-tients. All indoor stadiums and similarindoor spaces should be turned into COVIDfield hospitals. Private doctors, nurses, andsemi-skilled helpers should be recruited toserve these makeshift hospitals. Completesafety should be ensured for the peopleserving in these hospitals.


Opinions

5. The emerging situation will requirelarge-scale production of PPE gear forhealth-care personnel, and masks and san-itizers for common people. The governmentshould initiate planned production of theseessential items by requisitioning closedfactory spaces and by engaging workersrendered jobless by the lock-down.

6. The nation needs to produce a largenumber of ventilators in a short time.Many relatively inexpensive designs of ven-tilators (including mechanized Ambu bags)have been proposed by Indian investigators.Some international companies have alsomade their ventilator designs public. In-dian pharmaceutical companies and othermanufacturers should be requisitioned tomass produce such ventilators to meet thenation’s requirement. Building an Indianinnovation-development-production infras-tructure is the need of the hour.

7. Migrant labourers are stuck in differ-ent states due to sudden announcement ofthe lock-down. Most of them are living incrowded places and it will not be possiblefor them to maintain physical distancingapractice necessary to prevent the spread of

COVID-19. The Central Governmentshould initiate a dialogue with the statesto provide transit of these helpless peopleto their home states by means of specialtrains. Once they reach their respectivesubdivisions, they should be quarantinedin primary health centres or school build-ings for 14 days before allowing them togo home. Adequate financial and materialsupport should be provided to daily wagelabourers and poor people who have losttheir livelihood due to the lock-down.

8. The expenses of the above programmesshould be raised by levying taxes on thesuper-rich, and by using Corporate SocialResponsibility (CSR) funds of all nationaland multinational companiesnot by taxingthe common people. Since health is a statesubject, the Union Government should al-locate adequate funds to the states forcombating this critical situation. Sinceresearch scholars are losing valuable re-search time due to the lock-down, theirtenure of fellowship should be extended byat least 6 months.

We hope that the government will givedue consideration to the above proposals.

Signed by

Soumitro Banerjee IISER KolkataAlladi Sitaram Indian Statistical Institute (Retd.)Jayant Murthy Indian Institute of AstrophysicsDebashis Mukherjee S N Bose National Centre for Basic SciencesDebabrata Ghosh All India Institute of Medical Sciences DelhiD S Ray Indian Association for the Cultivation of ScienceNaba K Mondal INSA Senior Scientist, SINP, KolkataPartha Majumder National Inst. of Biomedical Genomics & ISIDipankar Chatterji Indian Institute of ScienceDhrubajyoti Mukhopadhyay Raman Centre for Applied and Interdisciplinary SciencesAyan Banerjee IISER KolkataPradipta Bandyopadhyay Jawaharlal Nehru University


Opinions

Signed by

Parongama Sen University of CalcuttaDamodar Maity IIT KharagpurSarbari Bhattacharya Bangalore UniversityNilesh Maiti Shishuram Das College, Calcutta UniversitySrikanth Sastry JNCASR, BengaluruPartho Sarothi Ray IISER KolkataAnupam Basu IIT KharagpurAmitabha Basu Retired Scientist, CSIR-NPL, New DelhiAjit Srivastava Institute of Physics BhubaneswarReeteka Sud NIMHANS, BangaloreR Ramanujam Institute of Mathematical Sciences, ChennaiAnindita Bhadra IISER KolkataAniket Sule HBCSE-TIFR, MumbaiRaju Mukherjee IISER TirupatiEnakshi Bhattacharya IIT MadrasPradipta Bandyopadhyay Indian Statistical InstituteG Nagarjuna HBCSE-TIFR, MumbaiPranab Roy Institute of Child HealthSiddhartha Sen IIT KharagpurPabitra Banik Indian Statistical InstituteDebabrata Bera Jadavpur University

· · · And 800 others.


Press statement on the Vizag Gas Leak tragedy

Presently the people all over the countryare passing through a very critical situationdue to lockdown and Covid-19 pandemic.During this lockdown period, the horrificincident happened at L.G. Polymers Ltd.at Vizag, Andhra Padesh, on 7th Maymorning, where the styrene gas leak causeddeath of 11 persons and thousands of peo-ple have been hospitalized falling seriouslyill. In this situation, the BreakthroughScience Society has issued the followingpress statement:

The Breakthrough Science Society ex-presses severe shock and concern over thedeath of 11 persons and severe illness ofmore than a thousand people in Vizag (A.P.),due to inhalation of styrene gas leakedfrom the L.G. Polymers Ltd factory. Thispoisonous gas leakage incident in Vizagreminds us of the Bhopal gas tragedy wherethousands of innocent people of neighbor-ing localities and labourers of this industrydied due to methyl isocyanide (MIC) gasleakage from Union Carbide factory in1984.This Vizag incident again proves that thecentral and state governments of our coun-try do not take any lesson from the gasleakage tragedy in Bhopal, the deadliestin industrial history. The Vizag gas leakincident is but a mini Bhopal gas tragedyand neither the neighboring inhabitantsnor the respective government authoritieswere aware about the hazardous chemicalsused in such factories and their impacton people if any accident occurs. Break-through Science Society demands that theharmful effects due to gas leak from L.G.

Polymers Ltd. should be combated on a warfooting and the government has to providefree and quality health care for the affectedand suspected victims of the gas leak. Wealso demand a high level scientific enquiryon causes of the styrene gas leak and tobring the guilty to the book.

Lastly, the Breakthrough Science Societydraws attention to the fact that in recentyears many investors (foreign as well as In-dian) are establishing hazardous chemicalindustries in different places of India. Manyof such chemical industries are alreadybanned in developed countries due to theirdangerously toxic waste materials whichcause environment pollution and destroybiodiversity. These investors do not getpermission from the government and desig-nated authority to establish such chemicalindustry in developed countries like USA,Japan, Germany, England, etc., while inIndia the investors get quick clearanceand license from our government to es-tablish such hazardous chemical industrieswithout proper verification. The effort ofchemical hub formation in Nandigram,WestBengal by Salem Group and Dow Chemicalswas such an example.

We demand that hazardous Industriesmust be situated at a safe distance fromhabitation as per the Hazardous ChemicalAmendment Rules, 1989, and the environ-mental norms prescribed by the state andcentral Pollution Control Bureaus should tobe strictly enforced. We also demand thatappropriate compensation must be given tothe bereaved families and the people whosehealth was adversely affected.


A Primer on SARS-CoV-2 and the EvolvingCovid-19 Pandemic

Subramani Mani∗

AbstractIn this article we first provide a primer on SARS-CoV-2 and Covid-19 delineating the etiopatho-genesis, epidemiology, clinical manifestationsand the natural history of the disease. We thentrace the evolution of the Covid-19 pandemichighlighting the characteristics of the epidemicin China where the pandemic originated, selectcountries of Europe which peaked during April,and Brazil, USA and India where the pandemichas taken serious turns recently. We also projectsome possible trajectories for the mega cities ofIndia based on the demographic characteristicsof these cities in comparison to New York city.This is an updated version of the article frommid-April published online [2].

Introduction

Corona virus disease 2019 (Covid-19)caused by severe acute respiratory syn-drome corona virus 2 (SARS-CoV-2) origi-nated in the city of Wuhan, China in late2019. After infecting tens of thousandsof people in Wuhan and the province ofHubei where Wuhan is located, the diseasespread to various other cities of Chinaand internationally. It peaked recently inmany countries of Europe (Italy, Spain,France, Germany, United Kingdom) and

∗Dr Mani is a Retired professor of Medicine andTranslational Informatics (University of New MexicoSchool of Medicine) and former professor of Biomed-ical Informatics and Computer Science (VanderbiltUniversity School of Medicine), USA; alumnus ofMedical College, Trivandrum and Government CentralHigh School (Attakulangara), Trivandrum. Email<[email protected]>

Figure 1: Eckert and Higgins illustration ofSARS-CoV-2, Centers for Disease Control andPrevention, USA.

Asia (Iran, South Korea), is changing coursein the United States and currently ragingin Brazil, Peru, Russia and India. Ithas spread to more than 200 countriesand is challenging the healthcare resourcesof both the developed and the developingworld. With a global case count in excessof 6 million, and with a mortality of morethan 360,000 over a five-month period, theCovid-19 pandemic has become the mostdangerous global infectious disease of the21st century [3].

Humans are susceptible to a range ofmicrobes which include parasites, bacteriaand viruses. However, most of the newlyidentified emerging pathogens are viruses


General Article

Figure 2: SARS-CoV-2 Genome.

that are carried by vectors, or cause pri-mary disease in animals and then jump tohumans (zoonotic). These are opportunisticviruses that mutate at high rates, easilyadapting to the new human host, therebyenabling human-to-human transmission.The most prominent of these emergingpathogens are the Zika virus and the newerzoonotic respiratory coronaviruses [4, 5]which also include the current pandemic-causing virus SARS-CoV-2.

The first SARS-CoV outbreak occurred inlate 2002 and soon became a pandemic inearly 2003, resulting in the death of morethan 700 people with a large cluster offatalities reported from Hong Kong. ThisSARS-CoV virus is thought to have orig-inated in a single or multiple species ofbats [4]. A more recent coronavirus (CoV)pathogen is the Middle Eastern respiratorysyndrome (MERS) CoV, which first emergedin 2012 in Saudi Arabia, and spread tomany countries in the region. By 2018MERS-CoV had infected more than twothousand people, causing 803 deaths, themajority of them in Saudi Arabia. Camelsand bats are considered to be reservoirs ofthis pathogen [6].

Before the emergence of SARS, humancoronaviruses typically caused only mildupper respiratory infections, resulting inthe common cold. All this changed withthe emergence of SARS-CoV, MERS-CoVand the newest member SARS-CoV-2, thecausative agent of the Covid-19 pandemic.

Etiology

Covid-19 is caused by the recently iden-tified respiratory tract virus SARS-CoV-2,which belongs to the viral family coron-aviridae, also referred to as the coronavirusfamily [7]. Other prominent members ofthe respiratory tract group of viruses arethe rhinovirus, the respiratory syncytialvirus (RSV) and the influenza and parain-fluenza viruses. The coronaviruses aresingle-stranded RNA viruses, containing anRNA inner core with an outer oily lipidenvelope from which crown-like spikes ofproteins project outwards. These char-acteristic crown-like projections on theirsurface give the virions the appearance ofa solar corona in electron micrographs andhence the nomenclature corona. See Figure1. The corona viruses are heat sensitive


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Figure 3: A transmission model from bat toman with pangolin as reservoir.

and are susceptible to lipid solvents such asacetone, ether, and vinegar (which containsacetic acid). The lipid envelope of the virusalso breaks apart on contact with soap.

The viral sequence of SARS-CoV-2 iden-tified by Zhu etal. contains 29,892 nu-cleotides [7] and the viral genome reportedby Wu etal. contains 29903 nucleotides [8].See Figure 2 for additional genetic details.

Phylogenetic analysis revealed the closerelationship to SARS-like coronavirusespreviously found in bats in China. Thepangolin is also likely to be an intermediatehost and a natural reservoir of SARS-CoV-2-like coronaviruses [9]. Recently, a jumpfrom human to a tiger in New York city hasalso been demonstrated when a tiger in theBronx zoo turned positive. See Figure 3.There are also recent reports of domesticpets such as cats and dogs becoming sus-ceptible to SARS-CoV-2 infection [10].

Isolation Missed Symptomatic Infectionsperiod per 10,000 Monitored Persons

Low Medium High Infectedrisk risk risk sample

(1/10,000) (1/1000) (1/100) (1/1)14 days 0 0.1 1 10128 days 0 0 0 1.4

Table 1: Expected number of symptomaticSARS-CoV-2 infections missed during activemonitoring using 14-day and 28-day protocolswith varying risks for infection following expo-sure (modified from [18]).

Laboratory diagnosis

The lab diagnosis of SARS-CoV-2 infectionis performed by real-time reverse transcrip-tion polymerase chain reaction (RT-PCR)assay for a genetic sequence matching thegenome of SARS-CoV-2. This is accom-plished by SARS-CoV-2 specific primersand probes. SARS-CoV-2 is a respiratoryvirus which is shed in respiratory droplets.A swab taken from the deep nasopharynxis used to isolate the virus from an infectedperson. Figure 4 provides additional detailsof the SARS-CoV-2 RT-PCR test.

Epidemiology

This description is based predominantly onthe following studies—the first 425 con-firmed cases in Wuhan, China [11], thesecond reporting data on 1099 patientsadmitted to various hospitals in mainlandChina [12], the third on 138 hospitalizedpatients in Wuhan [13], the fourth a re-view article based on 19 studies (18 fromChina and 1 from Australia) which alsoincluded the three primary studies [14], thefifth a retrospective cohort study of 191hospitalized patients in Wuhan with follow-up [15], the sixth a retrospective study of1591 consecutive patients admitted to ICUin the Lombardy region of Italy [16] andthe seventh a study of 5700 hospitalized


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Figure 4: SARS-CoV-2 Diagnostic Test Using RT-PCR.

patients in New York city [17]. Covid-19is a highly contagious disease, that is, itis easily transmitted from one person toanother. The transmissibility factor, alsocalled the basic reproductive number R0,is defined as the number of new casesan existing case is likely to generate onaverage. The R0 of Covid-19 is estimatedto be 2.2.

Incubation period

The incubation period is the duration fromthe time of exposure to the manifestationof symptoms of the disease. The meanincubation period is 5.5 days with a rangeof 2 days to 12 days. But there couldbe outliers and the following table adaptedfrom [18] shows the number of positivecases which could be missed using a 14-day and 28-day protocol of isolation (seeTable 1).

The mode of transmission is by res-piratory droplets but the virus has also

been isolated from the stools of patients.Both symptomatic patients and asymp-tomatic persons infected with SARS-CoV-2 can transmit the virus [19]. The viruscan remain suspended in aerosols for 3hours raising the possibility of transmis-sion through the air in closed spaces andin a crowded and congested environment.The virus can also remain viable for up to72 hours on different surfaces as varied asplastic, steel, copper and cardboard [20].

Figure 5 provides the dynamics of in-fectiousness, susceptibility to infection anddisease manifestation. The top panel showshow a person could get infected, remainasymptomatic and be contagious. Thebottom panel shows how a person can becontagious during a part of the incubationperiod when the symptoms have not mani-fested.


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Figure 5: Dynamics of infection and disease (modified from [1])

Demographics

The median age of patients in differ-ent studies varied between 47 and 63years. Males were disproportionately af-fected ranging from 50-82 percent. Amongthe first 425 confirmed cases in Wuhanthere were no children below 15 years ofage [11]. In the study of 1099 patients, thenumber of children below 15 years was 9[12]. Out of the 5700 hospitalized patientsin New York City only 26 were childrenbelow the age of 10 years [17]. About 15% ofthe hospitalized patients were categorizedas severe who were on average older by7 years, and were more likely to have co-existing medical conditions compared to theless severe hospitalized group of patients.

Pathogenesis

The SARS-CoV2 virus enters the humanbody via droplets through the nose, mouthor eyes. The virus enters the cells in theairway by binding the viral surface spikeprotein to the human angiotensin convert-ing enzyme 2 (ACE2) receptor. This followsactivation of the spike protein by trans-membrane protease serine 2 (TMPRSS2).

ACE2 is expressed in the alveolar cells ofthe lung, heart, vascular endothelium andthe kidneys but the main portal of viralentry seems to be the lung alveolar cells [21,22].

Clinical characteristics

Fever was present in 40% of the patients onadmission and in 80% of patients duringthe hospitalization period. Cough was thesecond most prevalent symptom and wasreported by 70% of the patients. Half ofthe patients also reported feeling fatigued.Breathlessness was also observed in 30%of the patients. Nausea, vomiting, sorethroat and headache were uncommon (lessthan 10%). A third of the patients hadone or more co-existing conditions such ashigh blood pressure, chronic obstructivepulmonary disease, diabetes, or coronaryartery disease and this was more pro-nounced among patients with severe dis-ease.

Cardiovascular manifestations

There have been some reports of patientspresenting with chest pain and showing


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ST-segment elevation in the EKG withoutany evidence of coronary artery disease. Inthese patients, echocardiography revealedLV dysfunction with reduced ejection frac-tion and elevated cardiac biomarkers suchas troponin. Patients with SARS-CoV-2infection can also present with myocarditis,stress cardiomyopathy, cardiac failure orthey may present with palpitations andchest pain without fever and cough. Pa-tients can also present with shortness ofbreath, supra-ventricular tachycardia andcardiogenic shock [23]. The exact mecha-nism of cardiac pathogenesis is not clear[22] but it could be a consequence of sys-temic hyperinflammation, lymphocytopeniaand elevated cardiac stress due to respira-tory failure and hypoxemia [24].

Neurological manifestations

Patients have presented with dizziness,headache, ataxia, altered sensorium andother clinical features suggestive of braininflammation [25]. A small subset of pa-tients developed stroke and seizures. Thereare also reports of acute necrotizing en-cephalopathy in Covid-19 patients. Somepatients develop tingling and numbnessin the upper and lower limbs referred toas acroparesthesia. Patients have alsopresented with loss of smell and tastesuggesting involvement of the olfactory,facial and glossopharyngeal nerves [26]. Ina study of Covid-19 patients in Wuhan,based on a sample of 113 patients whodied and 161 patients who recovered, theresearchers found that 20% of deceasedpatients developed hypoxic encephalopathywhile among the recovered group of pa-tients it was observed in only 1% [27].

Cutaneous manifestations

In a study of 88 patients in the Lombardyregion of Italy skin lesions were found in

20% [28]. The cutaneous manifestationsreported are erythematous rash, urticaria,and chickenpox-like vesicles mainly dis-tributed in the trunk. There has alsobeen a report of erythematous chilblain-likelesions on feet and hands in asymptomaticcorona virus positive patients [29].

Children and Covid-19

Compared to adults, children in generalhave been found to be less susceptible toserious manifestations of Covid-19. World-wide, patients under eighteen years haveso far accounted for only 2% of severelyaffected patients even though they canbe carriers and transmit the virus [30].Based on an analysis of 2135 pediatricpatients (728 lab-confirmed and 1407 sus-pected) Dong etal. reported that more than90% were asymptomatic, mild, or moderatecases. The distribution was similar inboth sexes and they found that youngerchildren, particularly infants, were morevulnerable [31]. Researchers have hypothe-sized that this disparity in the susceptibilityto Covid-19 between adults and childrencould be due to differences in the ACE2receptors in the renin-angiotensin system(which are used by the SARS-CoV-2 virusto enter the respiratory epithelial cells),and altered inflammatory responses to thepathogen [30, 32].

There have also been recent reports ofa multisystem inflammatory syndrome inchildren due to SARS-CoV-2 infection in theUK and USA [33, 34].

Radiology and lab features

Eighty percent of the CT scans of pa-tients with non-severe disease and 96%of the scans of patients in the severedisease category revealed abnormal find-ings. The typical patterns on chest CTwere ground-glass opacity and bilateral


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patchy shadowing. These abnormal pat-terns were also visible in chest X-rays.Less frequent findings found towards thelater stages of the disease include septalthickening, bronchiectasis and thickeningof the pleura. Other infrequent CT find-ings reported with disease progression werepleural effusion, pericardial effusion, lym-phadenopathy, lung cavities, CT halo signand pneumothorax [35].

More than 80% of patients had a lowlymphocyte count. About a third of patientshad low white cell counts and another thirdhad low platelet counts. Most patientsalso showed reduced albumin, high levelsof C-reactive protein and elevated ESR. Thelaboratory findings were more pronouncedin patients with severe form of the disease.In a study of 2874 SARS-CoV-2 positivepatients RNAemia, that is, detection of viralRNA in blood was found in 97% [14].

Treatment, clinical course andoutcomes

No specific anti-viral treatment is currentlyavailable broadly for Covid-19. A majority ofthe patients (60%) were given intravenousantibiotics, and oxygen was administered toabout 40% of the patients. Twenty percentof the patients typically needed admissionto the intensive care unit, out of whom halfhad to be put on ventilators. More than90% had pneumonia, 10% of patients devel-oped acute respiratory distress syndromeand five percent of patients went into shock.The median duration of hospitalization was12-20 days in different studies with themortality rate varying from 2 to 20 percentin various studies.

Drug pipeline

Three drugs that are undergoing studiesfor effectiveness in the treatment of Covid-19 are Remdesivir, Hydroxychloroquine and

Chloroquine. There is some preliminaryevidence that these drugs have the poten-tial to inhibit SARS-CoV-2 [36]. Remde-sivir is an antiviral compound originallydeveloped as a potential drug for Ebola,and Hydroxychloroquine and Chloroquineare time-tested drugs used in the treatmentof malaria. Hydroxychloroquine is alsoindicated in the treatment of discoid, sys-temic lupus erythematosus and rheuma-toid arthritis. A recent placebo-controlledrandomized trial of intravenous Remdesivirin hospitalized Covid-19 patients reporteda reduction in recovery time by 4 days(from 15 days to 11 days) [37]. An ob-servational study of more than 1300 hos-pitalized patients did not find any benefitresulting from Hydroxychloroquine admin-istration [38]. A multinational retrospectivestudy of the efficacy of hydroxychloroquineand chloroquine for Covid-19 found highermortality and increased occurrence of ven-tricular arrhythmias in both the hydroxy-chloroquine treated group and chloroquineadministered group compared to the con-trol group [39]. Another drug Tocilizumab,an interlukin-6 receptor antagonist used inthe treatment of rheumatoid arthritis is alsobeing tested for the treatment of Covid-19[22].

Recently, a small study involving tenseriously sick Covid-19 patients, who wereadministered a single dose of 200 ml of con-valescent plasma (CP) from recently recov-ered donors, showed that CP therapy waswell-tolerated with resulting improvementin clinical symptoms. CP holds promise forimproving clinical outcomes by neutralizingthe virus circulating in blood [40].

Vaccine trials

There are various candidate vaccines basedon RNA, DNA, recombinant protein, viral-vector-based, as well as the time-testedinactivated, and live attenuated versions


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Figure 6: Covid-19 mortality rate.

under pre-clinical evaluation. Currently,there are no existing licensed human vac-cines using RNA and DNA platforms [41].Two candidate vaccines, one from Univer-sity of Oxford/AstraZeneca, and anotherfrom CanSino Biological Inc./Beijing In-stitute of Biotechnology, based on non-replicating viral vector platform are cur-rently in phase II trials. Two candidatevaccines based on RNA being developedby Moderna/National Institute of Allergyand Infectious Diseases (NIAID) and BioN-Tech/Fosun Pharma/Pfizer are also movinginto phase II trials. Six other candidatevaccines are also undergoing clinical eval-uation.

However, availability of a safe and ef-fective vaccine for SARS-CoV-2 on a massscale is at least 12-18 months down theroad.

Covid-19 pandemic story so far

Here we present the story of the Covid-19 pandemic from an analytical perspectivebased on the numbers available from theworldometer website as of May 27, 2020 [3].In this analysis we include the top fifteencountries based on the reported number ofcases, which includes India and the global

figures. A total of 6 million cases and morethan 360,000 deaths have been reportedworldwide. The United States tops the listwith a reported total caseload approach-ing 1.75 million with more than 100,000deaths. India has reported more than158,000 cases and 4534 deaths throughMay 27th. Brazil has counted close to400,000 cases with total deaths approach-ing 25,000, and Russia is close behindwith a caseload exceeding 370,000 butwith a much lower reported death toll ap-proaching 4,000. Spain, United Kingdom,Italy, France and Germany together havereported more than 1.1 million cases witha combined death toll exceeding 134,000.USA also leads the countries in the totalnumber of tests with more than 15 milliontests followed by Russia with more than 9.4million tests. But the testing rate (numberof tests per million people) is highest inSpain with more than 76,000 people testedper million inhabitants.

The number of new cases reported dailyis an indicator of the evolution of thepandemic on a daily basis in each country.In this measure, USA and Brazil top thelist with more than twenty thousand newcases in one day. Figure 6 provides themortality rate of Covid-19 for the variouscountries. The worldwide mortality rate is6.2% with a range of 1.0% for Chile to ¿14%for Italy and the UK. The mortality rate forIndia stands at 2.9%. For an epidemio-logical comparison, the fatality rates andreproductive rates of common and emergingvirus infections are shown in Table 2.

Discussion

The pandemic continues to spread andevolve on a global scale. It has overwhelmedthe healthcare capabilities and capacitiesof various cities and countries includingWuhan (China), Italy, Spain, France, UKand New York, causing fatalities in the


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Virus Fatality rate Transmissibility Deaths(%) Factor (R0)

SARS-CoV-2 (2019) 3 2.2 369,000+ (till May 30th, 2020)SARS-CoV (2002) 10 2-5 700MERS-CoV (2012) 40 < 1 800

H1N1 (2009) 0.03 1.2-1.6 18,600-300,000H1N1 (1918) 3 1.4-3.8 17-50 million (1918-1920)Measles virus 0.3 12-18 140,000 in 2018Seasonal flu < 0.1 1.2-2.4 0.3-0.6 million per year

currentlyEbola virus (2014-16) 40 1.5-2.5 11,300 (2014-2016)

HIV 80 (without 2-4 30 million totaldrug therapy) deaths so far

Small pox virus 17 5-7 300 million in 20th century

Table 2: Fatality rate and reproductive rate (R0) of common and emerging virus infections (modifiedfrom [42]).

thousands, tens of thousands and even onehundred thousand. As countries attempted(and continuing) to block the spread ofCovid-19 by proclamations of stay-in-placeand lockdown orders in cities, states andnation-wide, the economies of these coun-tries are taking a huge hit and slidingtowards recession.

Recall that the transmissibility of a conta-gion is defined by the reproductive numberR0 in epidemiological terms. There aretwo basic strategies to tackle the spreadof Covid-19 referred to as containment andmitigation. When the R0 is two or greaterthere will be an exponential spread as eachcase will generate two or more new cases onaverage and the total number of cases in acommunity or a geographical region startsdoubling every few days. A containmentstrategy is typically used at the beginningof an epidemic and involves testing per-sons exposed to the virus, isolating andquarantining them individually, and tracingtheir contacts if they test positive or developsymptoms. In the containment approachthe goal is to keep R0 below one to breakthe community transmission chain.

To tackle an exponential spread and

when the number of cases overwhelmscontainment approaches, a mitigation ap-proach is taken using various types of non-pharmacological interventions (NPI) withthe goal of lowering R0 as much as feasi-ble but not to reduce it to one or belowone. The common NPIs involve the stepsof extensive testing, isolation/quarantineand social distancing measures for certainpopulation groups such as senior citizensand people with pre-existing medical con-ditions, or the population as a whole withlockdowns and stay-in-place declarations.

Mitigation steps also involve the closureof schools and colleges, shutting downplaces of entertainment such as perfor-mance venues, religious congregations andplaces of worship, and sports events. Like-wise, a drastic reduction in gatheringssuch as marriages and funerals are alsoenforced. Both these approaches may needto be applied in tandem in large parts ofa country or geographical region facing theonslaught of Covid-19.


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Figure 7: Wuhan Covid-19 outbreak timeline

Covid-19 run in China, South Korea,Europe and USA

China

The novel corona virus originated in De-cember in the city of Wuhan in Chinaand started spreading in the province ofHubei which includes Wuhan. When casesstarted multiplying and authorities sus-pected human to human transmission ofthe new virus, containment measures wereinstituted. By the end of December, aviral sequence was completed and a weeklater the novel corona virus was officiallyannounced as the causative pathogen ofthe outbreak by China CDC [11]. By 13thJanuary a test kit became available fordetecting SARS-CoV-2. Within a period often days hundreds of people had testedpositive for the virus. Moreover, within thattimespan more than two thousand peoplehad started showing symptoms of the newdisease and visiting hospitals in Wuhan.Even though the authorities hesitated ini-tially, the city of Wuhan was put underlockdown on January 23rd. By that timemany other cities in China were also seededwith the virus as more than seven million

residents of Wuhan had left the city tocelebrate the Chinese New Year. On Jan-uary 24th, fifteen other cities within Hubeiprovince, in which Wuhan is situated, werealso put under lockdown and on January30th, WHO declared an international publichealth emergency [43]. Figure 7 provides atimeline of the Wuhan outbreak.

China was able to control the smalleroutbreaks that occurred outside Hubeiprovince by initiating effective containmentmeasures. However, in the city of Wuhan,and broadly in the Hubei province, thehealthcare facilities were overwhelmed bythe outbreak. The lockdown in the cityof Wuhan was in place for 76 days, andrestrictions on the movement of people putin place during the lockdown were slowlyrelaxed over the last few weeks. At the timeof writing (May 27th), China has reported atotal of 83,000 cases and more than 4,600deaths, mostly in Wuhan and the rest ofHubei province. The country reached themilestone of 80,000 cases in early marchwhich has only increased by 3,000 casesover the last three months.


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South Korea

The first case of Covid-19 was reportedon January 20th and by February 21stthe caseload increased to 346, with theoutbreak concentrated in the city of Daeguin the southern part of the country [44].South Korea cancelled mass gatherings inDaegu and effected containment measuresincorporating mass testing, contact trac-ing, isolation of exposed individuals andquarantining those who tested positive. Inlate February and early March, the countryreported more than 500 cases daily and bymid-March, the outbreak was under controlreporting less than 250 new cases. And bymid-April, the number of daily new caseshad come down to about 25. It fluctu-ated between single-digit numbers and fortyfrom 1st through the 27th of May. Thetotal number of deaths through May 27thstands at 269 for a total positive case countof 11,344. South Korea did not institute acountrywide shutdown or social distancingmeasures applicable to the whole of thecountry.

Europe

The Covid-19 pandemic opened its accountin Europe with the first reported case inFrance on January 21st and by May 25th,the case count had gone up to more than1.3 million. As of May 25th, the total num-ber of deaths has exceeded 161,000 in thewhole of the European Union (EU) includingUK [45]. We consider five countries—Italy, Spain, France, Germany and UK inadditional detail here.

Italy

Covid-19 first emerged in Italy on January31st when two tourists from China testedpositive. Three weeks later, a cluster ofcases was reported from the Lombardyregion of Italy which includes Milan, and

by early March positive cases were reportedfrom many parts of the country [46]. ByMarch 1st, the daily case count had in-creased to more than 500. The epidemicraged in Italy throughout March and thefirst two weeks of April with the total casecount reaching more than 178,000 with adeath toll exceeding 23,600 by April 19th.The peak started flattening by mid-Apriland the daily caseload has started decliningfrom the high three-thousands in mid-Aprilto a few hundred new cases by the last weekof May. The total case count tops 231,000with a cumulative death count exceeding33,000 as of May 27th, 2020.

Spain

The country reported its first case on Jan-uary 31st, and by mid-March the diseasehad spread to all the 50 provinces [47].By the 10th of March, the daily new casecount had increased to more than 500 andthe country reached its peak during thelast week of March, and the plateau wassustained through the first week of April.As of April 19th, the total case count hadreached close to 200,000 with a total deathtoll exceeding 20,000. Five weeks later, asof 27th of May, the total case count exceeds230,000 with a total death toll topping27,000.

France

The epidemic raised its head first in Franceon January 24th, and the first set of caseswas in travelers returning from China. Theannual assembly of the Christian OpenDoor Church attended by 2,500 people wasa significant watermark in the spread of thevirus, and almost half of the congregantscontracted the virus [48]. By March 12th,the number of daily reported new caseshad gone up to more than 500 and thecountry reached its peak in the first week


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Figure 8: Italy Spain France and United Kingdom Covid-19 outbreak timeline.

of April. By April 19th, the total case counthad exceeded 152,500 with a death tollnearing 20,000. On May 4th, retroactivetesting of samples in a French hospitaldemonstrated the presence of Covid-19 asearly as December 27th, four weeks beforethe official confirmation of the countrysfirst case. As of 27th May, the countrystotal case count exceeds 185,000 with acumulative death toll of 28,600. From adaily new case-count exceeding 5K in earlyand mid-April the daily case count hascome down to a few hundred in the lastweek of May.

Germany

Covid-19 emerged in Germany in late Jan-uary, with the first case confirmed nearMunich on January 27th. On March 8th,the government recommended cancellationof events with more than one thousandparticipants and in mid-March, schools andnurseries were closed. Only the state ofBavaria declared a curfew on March 20th,but after two days, the Federal Government

decided to forbid gatherings of more thantwo people. Social distancing measureswere also introduced but no formal coun-trywide stay-in orders were issued [49]. Atits peak in late March/early April, the dailynew case count exceeded 6,000 but by mid-April it had fallen to about 2,000. As ofApril 19th, the total case count exceeded144,000 with a total fatality count of 4,500.As of May 27th, the total case load isnearing 180,000 with a total death tollexceeding 8,300. From a peak of more than6,000 daily cases reached late March/earlyApril, the daily case count has come downto a few hundred in the last week of May.

United Kingdom

In UK also, Covid-19 was detected first inlate January, and by the end of Februarycommunity transmission within UK wasalso confirmed [50]. By March 18th, thenumber of daily reported new cases had ex-ceeded 500. As of April 19th, the total casecount was more than 120,000 with a totaldeath toll over 16,000. The epidemic hascontinued to rage in the country through


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April and May and the total case countexceeds 267,000 as of May 27th, with atotal death count that tops 37, 400. From adaily new case-count hovering between 4Kand 6K during most of April, and between3K and 5K in the first two weeks of May,the daily case load has declined to 2K inthe last week of May.

See Figure 8 for the evolution of theoutbreak through mid-April and the inter-ventions instituted by the respective au-thorities in Italy, Spain, France and the UK.

United States

The first Covid-19 case was reported inthe USA on January 20th, when a personwho had returned from Wuhan, China,five days earlier tested positive for thevirus. Community transmission was firstconfirmed in late February, when a personwithout any history of recent internationaltravel or exposure to a known infectedindividual tested positive [51]. The numberof daily new cases exceeded 500 on March13th. Though a travel restriction was insti-tuted on passengers coming from China onJanuary 31st, no significant interventionmeasures were instituted during the wholeof February or the first two weeks of March.Containment measures such as extensivetesting, isolation and quarantine measureslagged behind considerably in the country.Starting mid-March, when the total casecount approached 4,000, various statesstarted instituting mitigation strategies toenforce social distancing measures. Stay athome orders were issued in various statesstarting with California on March 19th, andcovered most states of USA by April 7th.

Starting early May the country startedopening up in stages. By May 27th, sev-enteen states have ended stay-at-home or-ders. Many non-pharmacological interven-tions such as social distancing measures,restrictions on large gatherings, school

closures and wearing of masks in publicplaces are still in place in many regions ofthe country.

New York has been the most affected statein the United States. The state had a totalcase count nearing 250,000 and deathsexceeding 18,000 as of April 19th. And asof May 27th, the total case load is nearing375,000 with a total death count exceeding29,500. The USA is also the worst affectedcountry in the world. The country hada total caseload exceeding 750,000 andfatalities exceeding 40,000 as of April 19th.This has increased to 1.75 million totalcases and a total death count that exceeds102,000 as of May 27th.

Brazil

The coronavirus was confirmed to havespread to Brazil on February 25th witha Sao Paulo resident who had earlier re-turned from the Lombardy region of Italytesting positive. It also turned out to bethe first positive case in the whole of SouthAmerica. By March 26th, the country had2,915 confirmed cases and 77 deaths. Bythe end of April, Brazil overtook China inthe number of confirmed cases and thecountry has currently emerged as a hotspot for the virus. Brazil has not institutedcountrywide lockdown measures to combatthe virus but some cities in the north of thecountry issued lockdown measures in thefirst week of May. As of May 27th, the totalcase-load exceeds 411,000 with a cumula-tive death count in excess of 25,500. Juston May 27th the country added 22,301 newcases and reported 1,148 deaths [52].

Russia

The first cases in Russia were reported onJanuary 31st, when two Chinese citizensturned positive in the Russian Far East


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region. Russia was relatively late in expe-riencing a serious outbreak but currentlyranks behind US and Brazil with the third-most number of confirmed cases [53]. Asof May 27th, the total case load exceeds370,000 with a total death count approach-ing 4,000.

India

Covid-19 raised its head in India in lateJanuary with a positive case reported onJanuary 30th, in the state of Kerala [54].By March 24th, the total case count hadexceeded 500 and the same day the govern-ment declared a nationwide lockdown forthree weeks, which was further extendedon April 14th till May 3rd with a phasedrelaxation of some restrictions expected tooccur after April 20th. But the lockdownwas further extended by another two weeksthrough May 17th. Based on the successof containment of spread in various statessome relaxation was instituted starting inMay but the general countrywide lockdownhas been extended through the end of themonth. By April 19th, the total case countexceeded 17,600 with a total death countof 559. As of May 27th, the total case loadexceeds 158,000 with a total death countin excess of 4,500. For a country with apopulation of 1.37 billion, the case countappears low but the country has conductedonly about 3 million tests with a testing rateof just 2350 per one million people, whilethe testing rate for Spain and Russia areabout thirty times more with a rate of 76Kand 64K per one million people respectively.

There are some country-specific trendsdiscernible in the evolution of the pan-demic till now, in terms of total numberof infected people, hospitalizations, theresulting mortality and the ability of thehealthcare systems in coping up with theincreased demand on their resources. Letus consider the analogy of a primary and

its concomitant secondary metastases tofollow some of these trends.

China had a clear source, it was unifocaland the outbreak started in Wuhan andmore specifically at the Huanan seafoodmarket there. Even though other regionsof Hubei province and the rest of thecountry got multiple-seeded from this out-break, containment measures were suc-cessful in controlling the epidemic outsideHubei province. In Wuhan, and broadly inHubei, intervention measures began withcontainment but the hospitals were soonoverwhelmed. So, they had to institutestrong mitigation efforts in the city ofWuhan and the rest of Hubei provinceover a period of 75 days to suppress thecommunity transmission. But the primarysource was clear to them.

The South Korea outbreak was seededby travelers from China but it becameconcentrated in the southern city of Daegu.The country quickly instituted contain-ment measures with extensive testing ofthe population, contact tracing, isolationand quarantine. The hospitals were neveroverwhelmed with a total death toll under300. Their testing rate stands at 17,000per million population. The country couldprevent a disastrous outbreak in a majorpopulation center such as Seoul.

Italy, Spain, France and the UK havesome commonalities. They are all well con-nected globally with extensive travel amongthem and also with China. It is likely thatthey were all multiple-seeded and they wereslow in scaling up containment measures,starting with extensive testing. Thesecountries were also hesitant in the begin-ning to initiate strong mitigation efforts.Their health systems, in particular thoseof Italy, Spain and France were clearlyoverwhelmed, with a combined death tollwhich exceeded 65,000 by April 19th. Thecumulative death count currently stands at


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126,000 as of May 27th. UK had a longplateau stretching from early April to mid-May putting many of its hospitals underpressure.

Germany was much better prepared eventhough it is one of the most well-connectedcountries. The country quickly institutedstrong containment measures with exten-sive testing in the early stages. Germanywas also able to keep the mortality ratevery low initially which then crept upsomewhat, possibly because hospitalizedpeople started dying after long stays. Butthe countrys healthcare system was notoverwhelmed.

USA is well connected to China, Europeand most other parts of the world. It isclear from the evolution of the Covid-19pandemic that the public health infrastruc-ture is lacking in the country. From thestart, the country ran into difficulties withits testing strategy. Though initially contacttracing of returning travelers who testedpositive was instituted, the machinery formanaging and organizing strong contain-ment measures soon broke down, andcommunity transmission started occurringin many population centers in differentparts of the country. The tri-state regionof New York, New Jersey and Connecticutwas severely affected, with hot spots alsopopping up in Michigan, California andLouisiana. Some hot spots were broughtunder control by stay-at-home directives,but New York City bore the brunt of theepidemic and many hospitals in the citywere overwhelmed exacting a large deathtoll. Though the first wave of the outbreakis being brought under control, it is notclear how the epidemic will evolve as socialdistancing measures are relaxed and thebusinesses open up.

Brazil was in denial about the signifi-cance of the pandemic and was late in in-stituting containment and mitigation mea-

sures. Once the country ramped up testing,case counts started to increase and itcurrently holds the 2nd spot behind USAfor the total number of positive cases. Inparticular, the top political leadership ofBrazil has opposed many of the restrictivemeasures announced by city and stateleaders.

India is a large populous country withmany dense population centers. However,the health infrastructure lacks consider-ably when compared with most of the coun-tries discussed earlier. For example, SouthKorea has 12 beds per thousand people andGermany 8 while India has just 0.5. ForItaly, China and US, the number is close to4.

The first cluster of cases in India wasfrom students traveling back home fromWuhan to the state of Kerala in the south-ern part of India. Kerala instituted promptcontainment measures with isolation ofcontacts and quarantining people testingpositive. Soon other parts of the countryalso got seeded and dense population cen-ters are now under serious threat. Testinglags considerably with a rate of 2K permillion population or 2 per one thousandpeople.

Though mitigation efforts in the form of acountrywide lockdown have been institutedrelatively early, when compared to manyother countries, these cannot be sustainedfor months in the absence of resources tofeed and sustain the population. More-over, the minimal healthcare facilities arelikely to be overrun once the lockdown isrelaxed. Some relaxation of the lockdown isalready happening with a phased openingof businesses and institutions in variousstates. Domestic flights and long-distancepassenger trains have also started to be-come operational in the last week of May.

Based on the experience of New York City,we provide an outbreak scenario for the


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City Total Population Population Beds per Covid cases Total deathsin millions Density/Sq. mile 1000 people

NYC 8.7 28,000 3 206,000 21,000Bombay 21 73,000 0.5 35,485 1,135

Delhi 30 30,000 0.5 16,281 316Calcutta 15 63,000 0.5 1,895 194Chennai 11 69,000 0.5 12,761 109

Table 3: Four mega cities of India compared with New York City (NYC).

four major population centers of IndiaBom-bay, Delhi, Calcutta and Chennai. Theprojections are based on the total popu-lation, population density, the quality ofhealthcare infrastructure as reflected in thebeds per one thousand population and thereported city-specific mortality data. SeeTable 3 for these parameters and see Figure9 for the projected cases and fatalities. Thelower projections are based on maintainingmoderate social distancing measures inplace, and the higher range will be reachedif mitigation efforts cannot be sustainedand compliance is eroded. If mitigation ef-forts are completely withdrawn, the countscould rise by an order of magnitude.

The demographics of the state of Ker-ala provide a set of opportunities, whileposing some unique challenges. The statehas a total population of 35 million, withan average population density of 2,200per square mile, which is three timesthe national average. Again, the coastalregions are more than two times denserthan the state average [55]. The coastalplains of Kerala, running north to southfrom Kasaragod to Trivandrum, act asa metropolitan corridor well-connected bytrains and long-distance buses. The regionalso has three major airports with frequentflights to the countries in the Middle Eastand the rest of India. Kerala also has a highHuman Development Index, which informsfavorably on the literacy, life expectancyand the public health infrastructure of thestate in general. Kerala has managed to

contain the spread of Covid-19 by testingtravelers, isolating contacts and quaran-tining people testing positive. However,testing has lagged behind considerably inassessing penetration in the community toget a clear handle on the prevalence ofCovid-19. There are four dense metro areasin the state with a population of 1 to 2million - Kochi, Trivandrum, Calicut, andQuilon, and only by extensive testing canhot spots be quickly picked up and snuffedout in time to prevent flare ups. Extensivetesting is critical when social distancingmeasures are relaxed.

An outlook similar to India is likely inmany of the densely populated countries ofAsia (for example, Indonesia, Bangladesh,Pakistan, Japan) and most countries ofAfrica, South America and also Mexico.One worrying common denominator is thenumber of people tested per million whichstands very much under 3 per 1,000 in allthese regions.

There is also a line of thinking that op-poses social distancing measures by meansof shut downs and stay-in orders; theyoppose closure of educational institutions,businesses and events. They want theyounger working populace to acquire herdimmunity, and segregate the older peopleand others who are at risk of developingsevere manifestations with poor outcomes.However, it is becoming clearer that manyyounger people are also getting hospital-ized and losing their lives. Moreover, theUSA alone lost more than 37,000 seniors


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Figure 9: Projected cases and deaths for New York City, Bombay, Delhi, Calcutta and Chennai

and staff members to Covid-19 in nursinghomes and other long-term care facilitieswhere they are kept typically separate fromthe younger population.

In a country such as India, with joint-family households where children, parentsand grandparents live in the same house-hold, segregating seniors is not a viableproposition. Riding out the pandemic with-out instituting containment and mitigationmeasures will overwhelm the healthcaresystem, resulting in carnage in almostall population centers. For a contagiousdisease with a high mortality rate, herdimmunity has to be acquired with effectivevaccines.

Summary and conclusion

Covid-19 originated in China and within afew weeks, it had infected tens of thou-sands of people, overwhelmed hospitals,and caused thousands of deaths. It thenquickly spread to many other countries inAsia, Europe and the Americas. It has alsoslowly found its way into many countriesof Africa and has truly emerged as a globalpandemic. But the magnitude and severity

of the spread in different countries variesconsiderably. Currently Covid-19 is ragingin the United States, Brazil, Russia, UK,India and other countries. The virus is likea slow-moving tsunami that has acquiredthe ability to launch outbreaks at the timeand place of its choosing. There are someknowns but many unknowns surroundingthe SARS-CoV-2 virus.

An effective vaccine which can conferdefinitive protection against Covid-19 ap-pears to be at least 18 to 24 months away,though many scientists are in a race todevelop such a vaccine and ten candidatevaccines are currently in phase I/II tri-als. Likewise, there is no definitive drugtreatment for the condition though a hand-ful of drugs including the anti-viral drugRemdesivir and the anti-malarial drugsHydroxychloroquine and Chloroquine arebeing evaluated in clinical studies for theirefficacy. Because of the increased mortalityand cardiac arrhythmias reported by onelarge study [39] and lack of clinical benefitobserved in another [38], Hydroxychloro-quine and Chloroquine are quickly goingout of favor.

In the absence of vaccines and definitive


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drugs, the only effective resistance againstthe contagion seems to be vigorous con-tainment and mitigation efforts to allevi-ate the onslaught of Covid-19. Effectivepublic health measures, improved publicsanitation and meticulous observation ofthe best practices of personal hygiene willalso help in breaking the chain of commu-nity transmission of the contagion. Thepandemic has reinforced the age-old butoften sidelined aphorism that prevention isbetter than cure.

After providing a primer on Covid-19,we have charted the early stage of thepandemic which started in China and thenmoved quickly mainly to the countries ofthe western world, picking through theirhealth systems and decimating many se-nior living facilities. The pandemic has alsolaid bare the disparities and inequities inhealthcare access and delivery to differentsegments of the population in all the af-fected countries. We have also provideda window to the next stage where thepathogen is spreading its tentacles to thedeveloping countries of Asia, Africa andSouth America. As the pandemic evolvesfurther, the virus is also likely to cycle backduring fall into the countries ravaged ear-lier. Covid-19 is likely to remain endemicand get entrenched in many parts of theworld till an effective vaccine emerges tostop the SARS-CoV-2 virus in its tracks.

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21. Hoffmann M, Kleine-Weber H, Schroeder S, KrgerN, Herrler T, Erichsen S, Schiergens TS, HerrlerG, Wu N-H, Nitsche A: SARS-CoV-2 cell entrydepends on ACE2 and TMPRSS2 and is blocked bya clinically proven protease inhibitor. Cell 2020.

22. Clerkin KJ, Fried JA, Raikhelkar J, Sayer G, GriffinJM, Masoumi A, Jain SS, Burkhoff D, KumaraiahD, Rabbani L: Coronavirus Disease 2019 (COVID-19) and Cardiovascular Disease. Circulation 2020.

23. Fried JA, Ramasubbu K, Bhatt R, Topkara VK,Clerkin KJ, Horn E, Rabbani L, Brodie D, Jain SS,Kirtane A: The variety of cardiovascular presenta-tions of COVID-19. Circulation 2020.

24. Akhmerov A, Marbn E: COVID-19 and the Heart.Circulation research 2020, 126(10):1443-1455.

25. Mao L, Wang M, Chen S, He Q, Chang J, Hong C,Zhou Y, Wang D, Miao X, Hu Y: Neurological Man-ifestations of Hospitalized Patients with COVID-19 in Wuhan, China: a retrospective case seriesstudy. 2020.

26. Wu Y, Xu X, Chen Z, Duan J, Hashimoto K, YangL, Liu C, Yang C: Nervous system involvement afterinfection with COVID-19 and other coronaviruses.Brain, Behavior, and Immunity 2020.

27. Chen T, Wu D, Chen H, Yan W, Yang D, Chen G,Ma K, Xu D, Yu H, Wang H: Clinical characteristics

of 113 deceased patients with coronavirus disease2019: retrospective study. BMJ 2020, 368.

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29. Landa N, MendietaEckert M, FondaPascual P,Aguirre T: Chilblainlike lesions on feet and handsduring the COVID19 Pandemic. InternationalJournal of Dermatology.

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31. Dong Y, Mo X, Hu Y, Qi X, Jiang F, Jiang Z, TongS: Epidemiology of COVID-19 among children inChina. Pediatrics 2020.

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34. Riphagen S, Gomez X, Gonzalez-Martinez C,Wilkinson N, Theocharis P: Hyperinflammatoryshock in children during COVID-19 pandemic. TheLancet 2020.

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Will a coronavirus vaccine stop the presentwildfire of misery?

Raju Mukherjee∗

Usually, when we visit our friendly neigh-borhood general practitioner with symp-toms for upset tummy, the doctor sends usback with medicines that contain at leasttwo different antibiotics. Upset tummyassociated diarrhea is caused by eating foodcontaminated with waterborne bacteria.The first of the two broad-spectrum antibi-otics stop the bacterial genome duplicationwhile the other one targets bacterial proteinproduction, thereby ensuring a quick cure.Most often, the second antibiotic is alsoprescribed for symptoms of common coldand flu. This is not given to eliminatethe influenza virus, which causes the sea-sonal flu, but on most occasions to satisfythe patient who would not return withoutan antibiotic and sometimes to prevent asuspected secondary infection by bacteria.One can achieve protection from an infec-tious or communicable disease caused bybacteria, viruses, and parasites by gettingvaccinated. However, when it comes to theseasonal flu that requires yearly vaccina-tion, only a handful can afford to buy.

Vaccination is a method of creating amild disease like condition in order to allowthe human body to train and prepare itselffor a future attack by the same infection.Early records of vaccination (then calledVariolation) in India can be traced back tothe sixteenth century when it was prac-

∗Dr. Mukherjee is in the faculty of Bi-ology at the Indian Institute of Science Edu-cation and Research (IISER), Tirupati. Email:[email protected]

ticed by a mysterious group of Brahminswandering along the course of the Gangesin undivided Bengal [1]. They vaccinatedyoung children from smallpox, prevalent inthe region, by dipping a needle into a driedpustule and puncturing the skin repeatedlyin a small circle on the upper arm. A severesmallpox epidemic followed the famine inBengal in the 1770s that left the victimsdisfigured and blind if not dead. Its sheerscale and severity saw the re-emergenceof “Shitala Devi” the Goddess of smallpox,which received large-scale community wor-ship [2]. All of these were much beforeLady Mary Wortley Montague, the wife ofthe British ambassador, informed the RoyalSociety of London about the technique ofVariolation being practiced in the Turkishcountryside [1]. Perhaps, variolation orvaccination against smallpox is one suchearly medical intervention, which Indians


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can be proud of, rather than the mythicizedstories of innovation of ancient India, weoften get to read. This article on thedevelopment of vaccines against COVID-19is written for readers who love science andfor those who fear studying life sciences. Itgives a simplified description of vaccination,different types of vaccine and an update onthe present excitements and challenges invaccine development for COVID-19.

What is a vaccine, and why is it helpfulto get vaccinated?

A vaccine can be defined as a biologicalagent derived from the microorganism thatcauses the infectious disease. It is generallypresented as a preparation of the infectiousagent or one of its components, that whenintroduced into our body allows us to expe-rience the symptoms of a mild disease andthus helps to develop protective immunity.Our immune system thus stimulated pro-vides this protection through the two mainarms: Innate immunity mediated by fewparticular types of white blood cells thathave the non-specific ability to kill infectedcells, and Adaptive immunity mediated bythe generation of some more specific killercells and production of neutralizing an-tibody directed against the invading mi-croorganism. This protective immunity alsohas a memory and once developed, canlast throughout the lifetime, sometime withthe help of repeated vaccination (boosterdoses). Vaccination during an epidemic hasmultiple benefits and can be efficiently usedto i) reduce disease severity among the in-fected individuals, ii) control transmissionof the agent by reducing its release intothe environment and iii) lastly to preventinfections during future outbreaks.

Hundred years back, wildfires of miseryburnt the whole world, with millions ofdeaths caused by measles each year. Thefamous Spanish flu, which also reached

India, wiped away nearly 5% of the humanpopulation. Until decades ago, polio usedto leave many children with life-limitingdisabilities. We cannot imagine a worldwithout vaccination, which has managed tosave millions of lives. Therefore, it can bequite astounding to see the anti-vaccinationmovement gaining support from the ed-ucated parents and leaders of the devel-oped nations, leading to the resurgenceof measles fifty years after a vaccine wasdeveloped. Today, we have vaccines formost of the infectious diseases that canbe taken at a specified age during one’slifetime or during travel to a country wherea disease is prevalent [3]. Research isactively being pursued to also have vaccinesto prevent cancers, but we will not discussit here.

What do we need to know about thecoronavirus to make the best vaccine?

It is necessary to know as much as possibleabout the causative agent of the disease, inthis case, the new coronavirus (SARS-CoV-2) to design a vaccine. This virus is theseventh member of the coronavirus familythat caused the severe acute respiratorysyndrome (SARS) epidemic of 2002-04 andthe rather colonially named Middle Eastrespiratory syndrome (MERS) that is stillprevalent since 2012. This coronavirus isbelieved to have originated from the bats,its natural reservoir, in Hubei province ofChina and spilled over to humans or first topangolins before reaching the humans [4,5]. This conclusion is made by identifyingsimilarities in the genetic material to thatof the bat and the pangolin coronaviruses.

Like other microbial entities, viruses havetheir own genetic material, which is eithermade of DNA or RNA, packed together withsome proteins inside a shell that is againmade from proteins. Most of the time thisshell is decorated with proteins (in this


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case, spike protein) projecting outwards,giving a look of a corona, but whose mainfunction is to dock at its receptor (inthis case, ACE2 protein), another proteinpresent on the surface of the human cell,

very politely called as the host. Thisencounter with the host cell becomes thefirst step towards establishing an infection,so if one can prevent this interaction be-tween the two proteins, one can achieveprotection from the infection. However, wemust understand that not much is knownabout the mechanism of coronavirus infec-tion and all of our assumptions on how ourimmune system will react to SARS-CoV-2proteins is based on the large number ofsimilarities that were observed between theproteins present on SARS-CoV and SARS-CoV-2 viral surface [6].

The viral genome also undergoes changes(mutation) to adapt to the environment pro-vided by the new host, the humans. In caseof viruses like this, the genetic material(RNA) usually has higher mutation rates∼ 10−4 substitutions per position per year,so it becomes very important to continu-ously monitor these changes that generatevariability in the genetic material [5]. Thisinformation is crucial in identifying the beststrain or the variety (Chinese, American,Italian, or Iranian) of the new coronavirusto develop a good vaccine.

A vaccine candidate is chosen from theseveral options available as per the leveland type of protection required. The sim-plest way to vaccinate is to introduce thevirus into the body after inactivation us-ing chemicals, ultra-violet or gamma rays,or simply heat. Proteins present on thedead viral surface will serve as antigensand induce the production of neutralizingantibodies, as seen in the case of the earlypolio vaccine.

Another method involves introducing aweaker version of the virus that grows

slowly inside the host cell but producesenough antigens to induce an immuneresponse that finally eliminates the virus.This procedure is practiced for the oral poliovaccine, rabies vaccine, or the BCG vaccinegiven at birth to protect from childhoodtuberculosis. Administering a weaker virusis less safe than a dead virus and has beenthe cause for a few disease outbreaks butthey are superior in terms of mimicking aninfection that is necessary for mounting asuccessful immune response [7]. Develop-ing this live-attenuated vaccine in a shorttime is challenging, as it requires isolatingthe weak virus through rounds of time-consuming culturing in the laboratory.

One each of the above type is currentlyunder development to estimate their ef-ficiency. Formaldehyde inactivated for-mulation is being developed by SinovacBiotech in China while a genetically mod-ified growth deficient coronavirus is beingdeveloped in a partnership between Coda-genix, USA and the Serum Institute of India[8]. A relatively newer method of introduc-ing the surface proteins (spike protein) orits fragments to induce the production ofneutralizing antibody constitutes the “sub-unit based vaccines”, like in the case ofthe hepatitis-B vaccine. A virus being anobligate intracellular entity, meaning it re-quires the host cell for its multiplication, allvaccine strategies are aimed at preventingattachment and fusion of the virus to thehost cell surface. However, choosing theright vaccine candidate is as much an art asa science since finding the viral componentthat won’t trigger severe inflammation butcan provide a protective immune memoryis not so easy. This is more difficult incase of COVID-19 when nothing much isknown about how much damage is causedduring the disease and how and where thevirus hides itself to escape from the body’simmune army.


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Is there any quicker way to develop avaccine?

Based on the popular concept of “plug-and-play,” several new methods have beendeveloped that can be used to prepare avaccine against multiple agents and in ashort time, although they largely followthe same principles as mentioned above.This is possible only because the safetyfeatures of modern vaccines are determinedpredominantly by the technology used inthe method of preparation rather than onthe virus of interest.

The viral protein in subunit vaccines,when injected into the body, might not bestable and can lose their three-dimensionalshape, which might result in a sub-optimalimmune response. To circumvent thisproblem, a new method called “Molecularclamps” was devised at the University ofQueensland, Australia, in which short seg-ments of known protein can be stitched atseveral places on the viral protein to helpretain its original shape [9]. In anothermethod, which is based on nanotechnol-ogy and is quite popular, viral proteinswere genetically modified such that whenmixed with other structural protein canself-assemble into a nanostructure, enclos-ing the viral protein inside a “virus-likeparticle.” They are non-living particles anddo not cause infection, but because of theirvirus-like structure can stimulate strongimmune protection [10].

Further, with rapid advances in under-standing the life cycle and the damagecaused by a wide variety of viruses, alongwith the development of tools required formanipulating the viral genome, it has nowbeen possible to generate safer vaccinesexpressing viral proteins using a proxy in-fection [11]. This technology involves using“viral vectors,” which have the backboneof harmless viruses that can be used asvehicles for delivering the gene of interest

(in this case, the gene corresponding to thespike protein). This new piece of DNA willeventually give rise to the required proteinof interest, and as this harmless virusmultiply, it mimics the natural infectioncycle without causing any damage. Tomake this process completely safe from anyrare events of the harmless virus becominghostile, the genome of the virus can bemodified to stop from multiplying inside thebody. Viral vectors based on measles virushave been used to prepare safe vaccinesagainst HIV-AIDS, SARS, Ebola and Zika.

Nucleic acid (DNA and RNA) based vac-cines have emerged as a better alternativeto live and inactivated vaccines for treat-ments against emerging viruses as the DNAcoding for the viral protein can be producedin a short time. This does not involve grow-ing the virus in the laboratory and givesequivalent protective immunity as othervaccines. In case of “DNA vaccines”, theDNA is introduced directly into the humanbody and once they make their way into thenucleus of a host cell, the viral surface pro-tein production is outsourced to the cell’snatural machinery [12]. “mRNA vaccines”represent the new generation therapies,and unlike DNA vaccines it avoids the riskof being integrated into the human genome.The RNA can produce the spike protein ofinterest in the cytoplasm in high numbersbut cannot package itself into a functionalvirus [13]. All of the above innovations arebeing rapidly utilized to develop multiplevaccines against the new coronavirus.

Do we need multiple vaccines forCOVID-19?

Vaccine development is as challenging asdeveloping a new drug, and in case ofCOVID-19 this is even harder due to thepresence of so many unknowns associatedwith the disease and unavailability of ananimal model to test the vaccine. Despite


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all of these difficulties, the scale and sever-ity of the current pandemic has attractedaround 65 companies, both multi-nationalpharmaceuticals, small biotechnology firmsand even university spinoffs, to developa vaccine for COVID-19 [8]. Thanks tothe attractive funding from the governmentof the USA, work has been initiated onmultiple candidates, which are currentlyin clinical trials and in the laboratory.In addition to this, the Coalition for Epi-demic Preparedness Innovations (CEPI), aglobal alliance based funder for vaccinedevelopment, co-founded in 2017 by thegovernments of India and Norway, withsupport from several philanthropic orga-nizations including the Bill and MelindaGates Foundation of Microsoft fame, hasenabled several small biotechnology firmsand academic institutions to join this globaleffort.

The new candidates are not only basedon traditional approaches, they are alsobeing built on the existing vaccines andleveraging on platforms used to develop theSARS vaccines. It is important to note thatvaccines for COVID-19 do not have to besimilar to the ones proposed against othercoronaviruses. Pasteur Institute, France,has proposed to use the measles vaccinevirus backbone, earlier used to preparevaccines for Ebola and Zika, to develop avaccine specific to new coronavirus [8].

Clinical trials were started on healthyadult volunteers with funding from CEPI,for a nanoparticle encapsulated mRNA vac-cine co-developed by the National Instituteof Health, USA, and a company namedModerna. Another frontrunner in start-ing the clinical trials is CanSino Biolog-ics in partnership with China’s Academyof Military Medical Sciences’ Institute ofBiotechnology. This candidate is basedon a viral vector used earlier for Ebola.The University of Oxford’s Jenner Institute

has started trials for another viral vectorbased vaccine backbone. Among others,prominent candidates that are undergoingtesting are mRNA based vaccines fromtwo German companies that are re-usingtheir cancer vaccine technology and themolecular clamp based protein subunitvaccine from the University of Queensland.A very ambitious DNA vaccine candidatethat will be injected through the skin isbeing developed by Inovio Pharmaceuticals,USA, with funding both from CEPI and BillGates, though DNA based vaccines havenot received any regulatory approvals in thepast [14].

It is hard to predict when and which can-didate might see a dead end and successfinally depends on the results of the hu-man clinical trials which has been starteddirectly for the first time in the history ofvaccine development. For the first time,an unprecedented amount of governmentfunding has been sanctioned for multiplevaccine candidates. This is being donewith a single hope of hitting one successthat can make it self-reliant in protectingits citizens. Since it might take a whileuntil the results of the clinical trials arepublished, the famous BCG vaccine thatis given for protecting children from tu-berculosis has found some interest amongscientists. This is due to the non-specificprotection that BCG gives against viralinfections [15]. Although not scientificallyproven yet, large-scale trials have startedin Australia where nurses and healthcareworkers are receiving BCG vaccines withthe hope of getting protected from COVID-19 disease [16].

Will the battle be won by developing avaccine?

Usually, it takes more than 10 years to de-velop a vaccine following the classical pathof inactivated or live-attenuated vaccines,


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after collecting safety and efficacy data overa long period. This involves first testing inlaboratory cultures and on animal modelsfor its efficiency in producing the requiredantibodies and absence of any toxic sideeffects. Once it clears this stage, thesame tests are repeated on healthy humanvolunteers (Phase I of clinical trials) beforebeing given to a small number of infectedpersons (Phase II). Based on the resultsof this, a larger phase III trial is initiatedto check for long term protection amongdifferent age groups, genders, ethnic pop-ulations, children and expecting mothers.Safety data from all of these studies areabsolutely required by the regulatory bodiesto approve a new vaccine.

One cannot short circuit these proce-dures but can perform the last two stepssomewhat together as were done during theEbola emergency in 2014 when timelineswere brought down to 5 years. As theCOVID-19 contagion rapidly spreads acrossall the continents except Antarctica, InovioPharmaceutical has ambitiously placed atimeline to complete human clinical trialswithin a year [14]. This is understandable,keeping in mind that there may not beenough volunteer patients available laterto participate in the trials, though it isnot clear how one will collect informationon vaccination-induced severe illness thathappens in a vaccinated patient upon re-exposure to coronavirus later in life.

When it comes to manufacturing and de-livery, the process will face a number of newchallenges. Large quantities of the vaccinepreparation are generally required to startfull scale phase-III trials, which also needsto be produced quickly. Moreover, eachproduct will require a customized scale-uptechnology that will have to be developed.In a market driven economy, more andmore companies have shifted focus to thesafer lifestyle disease business and has

resulted in losing the skillset and expertiserequired for vaccine development. Theseunits need to be re-built with continuousfinancial commitments, with no guaranteefor the best rewards. Furthermore, themanufacturing units will have to be readybefore the success of the human trials,raising the most challenging question ofchoosing the best candidate vaccine forproduction.

More than the technical challenges,a strong long term international politi-cal commitment will be required to con-vince big pharmaceuticals to forget wor-rying about the plummeting future de-mands after the pandemic is over, foolishanti-vaccine campaigns and the lack ofprospects of creating wealth. These havebeen the foremost reasons for reluctanceto develop cures for neglected diseases thatare prevalent in countries with poor socio-economic conditions and high global healthequity. However, since no single companywill be able to supply the billions of dosesrequired for worldwide deployment allowingseveral different versions to be produced,an advance purchasing commitment willcertainly motivate them to come forward.

Another important question that mayarise and needs some clarity is selectingthe target population for delivery. Willwe vaccinate the healthier individuals whomight be naturally protected and the olderpeople who might show problems of a poorimmune response? Certainly, healthcareworkers need them the most in our pre-paredness for the next wave of infectionand perhaps also the traders in Chinese liveanimal markets.

Once we have the vaccines and hopefully,after the peak of the pandemic is over, aneffective policy needs to be carefully writtento develop a global access framework forequitable distribution of the coronavirusvaccine in the developing world while at the


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same time protecting intellectual propertyand marketing rights of the innovator. Wemay not be able to solve this global crisisif we fail to eliminate the virus from itslast reservoir. Distribution of the vaccinesshould be made strictly based on humani-tarian benevolence, and centrally throughagencies like the Global Alliance for Vac-cines and Immunization (GAVI) and WHO.The global leadership should not permit thevaccine manufacturers to sell to the highestbidder, nor should the vaccine producingcountries and the richest economies beallowed to stockpile the doses for their citi-zens in the absence of a national emergency[17]. History has seen this happeningduring the H1N1 influenza virus epidemicin 2009, and such acts will ensure ourdefeat in this global fight against COVID-19. However, there has been some recentdevelopment with world leaders pledging toraise 8.3 billion dollars to support creatinga “development and manufacturing coop-erative” to deliver available, accessible andaffordable vaccines for the world [18].

References

1. Boylston, A. (2012) The origins of inocula-tion. J R Soc Med,. 105(7): p. 309-13.

2. Nicholas, R. W. (1981) The Goddess tal andEpidemic Smallpox in Bengal. The Journalof Asian Studies 41(1) 21-44

3. WHO (2020) who.int/immunization/diseases/en/

4. Cui, J., F. Li, & Z.L. Shi. (2019) Origin andevolution of pathogenic coronaviruses. NatRev Microbiol. 17(3) 181-192.

5. Lu R, Zhao X, Li J, Niu P, Yang B et al. (2020)Genomic characterisation and epidemiologyof 2019 novel coronavirus: implications forvirus origins and receptor binding. Lancet395 565-574

6. Andersen KG, Rambaut, A., Lipkin, W.I., Holmes, E. C., & Garry, R. F. (2020)The proximal origin of SARS-CoV-2. Na-

ture Medicine doi.org/10.1038/s41591-020-0820-9

7. Afrough B, Dowall S & Hewson R (2019)Emerging viruses and current strategies forvaccine intervention. Clin Exp Immunol 196157-166

8. WHO (2020) DRAFT landscape of COVID-19candidate vaccines. who.int March 20

9. University of Queensland (2020) Significantstep in COVID-19 vaccine quest. uq.edu.auFebruary 21

10. Syomin, B.V & Ilyin, Y.V (2019) Virus-LikeParticles as an Instrument of Vaccine Pro-duction. Mol Biol 53 323-334

11. Humphreys, I.R. & Sebastian, S. (2018)Novel viral vectors in infectious diseases.Immunology 153 1-9

12. Hobernik, D. & M. Bros, (2018) DNAVaccines-How Far From Clinical Use? Int JMol Sci. 19(11)

13. Pardi, N., Hogan, M.J., Porter, F.W. & Weiss-man, D. (2018) mRNA vaccines –a new erain vaccinology. Nat Rev Drug Discov 17 261-279

14. Inovio Pharmaceuticals (2020) Inovio Ac-celerates Timeline for COVID-19 DNA Vac-cine INO-4800. Press release, ir.inovio.comMarch 3

15. Moorlag. S., Arts, R.J.W., van Crevel, R.& Netea, M.G. (2019) Non-specific effectsof BCG vaccine on viral infections. ClinMicrobiol Infect 25 1473-1478

16. Byrne, B. (2020) Murdoch Childrens Re-search Institute to trial preventative vaccinefor COVID-19 healthcare workers. MurdochChildrens Research Institute. March 27

17. Fidler, D.P (2010) Negotiating equitable ac-cess to influenza vaccines: global healthdiplomacy and the controversies surround-ing avian influenza H5N1 and pandemicinfluenza H1N1. PLoS Med 7 e1000247.

18. Emmott, R and Guarascio, F (2020) Worldleaders pledge $8 billion to fight COVID-19but U.S. steers clear. Reuters. May 4


SARS-CoV-2 and COVID-19:Where from and whither to?

Mahipal Sriram

The first reports of atypical pneumonia(COVID-19) caused by SARS-CoV-2 (SevereAcute Respiratory Syndrome Corona Virus2) from Wuhan, Hubei province, Chinacame into light on 30th November, 2019 [1,2, 3]. Since then, COVID-19 infectionis now widespread and the WHO (WorldHealth Organization) declared this infectionas a pandemic on 11th March, 2020; asof 19th May, 2020 more than 48.94 lakhcases have been confirmed in more than213 countries, with more than 3.2 lakhdeaths [4]. In 2002, an epidemic mediatedby SARS-CoV-1 (Severe Acute RespiratorySyndrome Corona Virus 1, another coron-avirus which originated in China) occurredand infected 8098 people causing 774deaths before the end of the epidemic [5].Thereafter, in 2013, infection mediated byanother coronavirus, MERS-CoV (Middle-East Respiratory Syndrome Corona Virus)occurred in the Middle East and this virusinfected 2521 people causing total 866deaths, as of today, this disease is stillprevalent [5].

As per available data, SARS-CoV-1 wasmuch more fatal than SARS-CoV-2 but itsinfectivity was not as high. SARS-CoV-1 transmission occurred predominantly inhospital settings (hubs), transmission oc-curred only 24-36 h after the appearance ofsymptoms, and lack of asymptomatic caseswere reported, leading to effective imple-mentation of barrier nursing. In contrast,COVID-19 displays widespread community

transmission and patients remain asymp-tomatic but infective for the first 7-10 daysof infection.

As it is highly contiguous in nature, mostparts of the world are under lockdown atpresent with people staying at home andmaintaining physical distancing to containthe infection in the absence of any availabletherapy. In these worrying times, peopleare uncertain about their future and theduration of this pandemic, and significantanxiety exists regarding the origin of thisvirus.

In the midst of the global COVID-19public-health emergency, it is reasonableto wonder why the origin of the pandemicmatters; it matters because detailed un-derstanding of the origin of this virus willhelp to mitigate further spread and to pre-vent future outbreaks. Scientific data hasconfirmed that SARS-CoV-1 and MERS-CoV originated from bat coronaviruses withcivet cats and camels, respectively, as thespillover reservoirs. Such knowledge isuseful in culling the chain of infection,but in the case of COVID-19, the spilloverreservoir is unknown.

There are many theories being discussedregarding the proximal origin of this virus.Conspiracy theories regarding the virus be-ing human-made arose primarily because itwas first reported in China which has beenengaged in coronavirus-related research ina BSL4 (Bio Safety Level 4) laboratory nearthe Wuhan market. Another school of


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thought is that like other SARS coron-aviruses, this novel human virus SARS-CoV-2 also originated from bats throughnatural selection followed by adaptationand then jumped the species boundaryof animals and subsequently infected hu-mans.

In this article, these theories will be an-alyzed on the basis of published biologicaldata and scenarios by which they couldhave arisen will be discussed.

SARS-CoV-2 is a super-virus

The SARS-CoV-2 virus has an oily lipidmembrane packed with genetic instructionsto make millions of copies of itself (Figs1A and 1B). The instructions are encodedin 30,000 ‘letters’ of RNA comprising A, C,G, and U (adenine, cytosine, guanine anduracil), which the infected host cell readsand translates into several kinds of viralproteins. Like other coronaviruses, SARS-CoV-2 contains a spike protein to gain entryinto host cells but differs from them inthat the SARS-CoV2 spike protein (S) hasdistinct characteristics which enhance itsrate of infectivity making it a super virus(Fig. 1B) [6].

SARS-CoV-2 performs the following ac-tions: 1) attaches to the host cell membrane2) binds to a human cell 3) enters the hostcell 4) transfers its genetic material into thehost cells and 5) makes millions of copies ofitself (Figs 1B and 1C).

When a COVID-19 patient sneezes, thewater droplets carrying viruses enter themouth, nose, and throat of a nearbyperson. Then, the sticky and oily lipidmembrane of the virus attaches to themembrane of the host lung cells. Next,the virus binds to a cellular receptor calledACE2 (Angiotensin-converting enzyme 2).These ACE2 receptors, which stick outfrom the surface of lung cells act like littleantennae and are designed to sense signals

that change our blood pressure; our lungsare involved in the fine adjustment of bloodpressure. (Fig 1C). These receptors are alsopresent in the arteries, heart, kidneys, andintestine.

The above sequence of steps is only thebeginning of the infection process. OnceSARS-CoV-2 is stuck to a cell, it needs toget in. SARS-CoV-2 is covered in spikes.The spike protein acts like a key to openthe lock and enter cells. For unlocking,the correct key needs to be inserted intothe groove of the lock, the key turned inthe right direction, and sufficient pressureexerted (this step is known here as thetrigger). However, this pressure cannot beexerted randomly; if it is too early or toolate, the lock will not be opened.

The spike protein consists of three sub-units namely S1, S2 and S3. The virusbinds to the cell receptor through the S1subunit of the spike protein very tightlyand then the spike protein pulls the surfaceof the cell and the virus together. Now,the trigger has to act. The junction ofthe S1 and S2 subunits of the viral spikeprotein contains a signature motif of atrigger sequence. To trigger the spikeprotein at just the right time, viruses relyon a human protein enzyme in our bloodcalled Furin. Furin cleaves this triggersequence and allows both the membranesto fuse, thus playing the role of a perfecttrigger. Our bodies produce large amountof Furin. “Basically, you can work out ifa virus is going to be highly pathogenic ornot if it is activated by Furin”, according toProf. Turner [7]. After fusion, the geneticmaterial of the viral genome is transferredinto the host cells. The virus then makesmillions of copies of itself exploiting thehost’s ingredients (Figs 1B and 1C).


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Figure 1: How does virus enter the cells and replicate? A) An electron-microscope image of theCOVID-19 virus, isolated from the first Australian coronavirus case.Note the bubble in the centresurrounded by spikes. Credit: CSIRO (7) B) Schematic diagrams of SARS-CoV-2 and C) a host lungcell. Representation of the five sequential steps of viral entry into the host cell and its replication.1) The viral sticky lipid membrane attaches to the host cell membrane; 2) S1 subunit of the viralspike protein binds to the ACE2 receptor protein of the host cell; 3) Furin cleaves the S2 subunitof the viral spike protein causing fusion of the viral membrane with the host cell membrane; 4) theviral genome is transferred into the host cells; and 5) the virus replicates and makes many copiesof itself.

Notable genomic features ofSARS-CoV-2

The genetic material of SARS-CoV-2 is aplus-stranded RNA molecule. This RNAencodes information to make viral proteins(∼ 30), each of which is involved in adifferent step of the synthesis and assemblyof millions of new virus particles (virions).The key first step is to make copies ofthe viral RNA. How does the virus copy itsgenetic material? An enzyme called RNA-dependent RNA polymerase (RdRP) copiesthe genetic instruction from this plus-

stranded RNA and thus helps in its replica-tion. The characteristic feature of this virusis that the same plus-stranded RNA is usedboth for translation (to synthesize proteins)and replication (to make millions copies ofits own genetic material).

More than 500 coronaviruses have beenidentified so far in China with esti-mates of unknown bat coronavirus diver-sity reaching > 5000 [5]. There areseven coronaviruses associated with hu-man diseases. Alpha-coronaviruses suchas HKU1, NL63, OC43 and 229E are


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associated with mild symptoms whereasbeta-coronaviruses such as SARS-CoV-1,MERS-CoV and SARS-CoV-2 can cause se-vere diseases in human. SARS-CoV-2 is theseventh coronavirus known to infect hu-mans (6). Comparative genomic analysis isa scientific tool which identifies variation ingenomic sequences among different typesand different strains. SARS-CoV-2 viruseshave been isolated from infected patients,and their genomes (+ strand RNA) havebeen isolated and sequenced.

Genomic comparison of alpha- and beta-coronaviruses reveals the following notablegenomic features of SARS-CoV-2 (6) (Fig 2):

• Its genome is ∼ 96.1% identical/similarto Bat RaTG13 coronavirus genome

• The region of the Spike protein in the S1subunit, which is important for ACE2binding, is called the receptor bindingdomain (RBD). Intriguingly, six impor-tant contact amino acid residues ofSARS-CoV-2 RBD match 100% with theRBD of the Pangolin coronavirus Spike,but with only one amino acid residue ofthe Bat RaTG13 Spike! (Figs 2A and 2B)

• The SARS-CoV-2 Spike has a unique Fu-rin enzyme cleavage site at the junctionof S1 and S2 subunits and the enzymeacts like a trigger and helps in viral entryin host cells (Fig 2C).

• The SARS-CoV-2 Spike has acquiredthree O-linked glycans near the Furin-cleavage site and these are used asa mucin shield for immune-evasion sothat production of antibodies in the hostagainst viral proteins is delayed (Fig 2C)

Bat RaTG13 coronavirus: ∼96%genomic homology withSARS-CoV-2

In 2013, in the province of Yunnan, about2000 kilometers west of Wuhan, a horse-

shoe bat was caught in a trap. Thesebats stay in dark caves and maintain socialand physical distancing from humans! Ifone were to put this bat on one’s palmand try to feel its weight, it will be evi-dent that the weight of this small creatureapproximately equals the weight of a ball-point pen; not significant at all! Scientistsswabbed the mouth of this bat and testedit. Surprisingly, they found that this batcontained a virus, named RaTG13 whosegenomic sequence had similarity to otherisolated coronaviruses. The copy numberof this virus in the bat was very low. Itis clear that viruses and bats maintain asymbiotic relationship and the viruses donot harm the bats. While such viruses werebeing found in bats, life moved on, peoplestayed busy with other things and neverworried about these Chinese viruses. Ironi-cally, SARS-CoV-2, which has caused thispandemic and has now infected millions,killed lakhs of people, and continues toterrorize mankind, shares 96.1% per centof its genetic code with the above virus,RaTG13. This is the main reason for thefrequent mention of the RaTG13 bat virusin the news.

Interaction of the viral receptor bindingdomain (RBD) with the host ACE2receptor: Used by the virus to enterhost cells

SARS-CoV-2 binds to the host cell usingthe S1 subunit of the spike protein. ItsS1 subunit contains the Receptor Bind-ing Domain (RBD) which binds with thehost ACE-2 protein; six important contactamino acid residues (-L-F-Q S-N-Y-, Fig2B) in SARS-CoV2-RBD match 100% withthe RBD of a Pangolin (an endangered ani-mal) coronavirus, but with only one aminoacid residue (-L-Y-R -D-H-) of Bat RaTG13(Fig 2B) (6). This is why the pangolincoronavirus may be able to infect humans


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Figure 2: Features of the Spike protein in SARS-CoV-2 and related coronaviruses. A) Schematicdiagrams of the S1 and S2 subunits of the Spike protein of SARS-CoV-2. B) Important contactamino acids of SARS-CoV-2 Spike receptor-binding domain (RBD) mediating interaction with ACE2protein and their homology with that of others coronaviruses. C) A unique Furin-cleavage site(RRAR) of SARS-CoV-2 is located at the S1-S2 junction of the Spike protein but is absent in othercoronaviruses; SARS-CoV-2 acquires three O-linked glycans at Serine (S), Threonine (T) and Serine(S) amino acids located near the Furin-cleavage site.

effectively but the Bat RaTG13 cannot.This also suggests that the bat RaTG13coronavirus might have acquired RBD ofthe pangolin coronavirus. How is thispossible? Could this have occurred throughmutation or through gene recombination?A typo (mistake) occurring while writingequals a mutation in genetics, but a groupof words being replaced with another groupof words equals recombination (insertionand/or deletion).

SARS-CoV-2 has exonuclease activity(proofreading capacity) and may not allowmany mutations to occur in the RBD of theS1 subunit (though it is a highly potentialmutable region) of bat RaTG13, leading to

the speculation that SARS-CoV-2 acquiredthe main residues in its RBD domain fromthat of pangolin coronavirus most probablythrough recombination. However, detailedstudy is required to confirm this RNA re-combination theory.

Furin cleavage site: Helps in viral entryinto cells and enhances infectivity

As discussed earlier, Furin (trigger) cleavesits cognate cleavage site at the S1-S2 junc-tion and helps in virus-host cell fusion,impacting transmissibility and pathogene-sis. SARS-CoV-2 has an RRAR sequenceknown as a polybasic Furin cleavage site(named polybasic because three out of the


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total four amino acids are the basic aminoacid Arginine (R), Fig 2C), but bat andpangolin virus spike proteins have onlyone Arginine (- - - R); these two virusesthus have incomplete Furin cleavage sites(known as sub-optimal cleavage sites) (6).A consequent question that arises is: If anoptimal Furin cleavage site is inserted inthe bat and pangolin coronaviruses, couldthese viruses then act like SARS-CoV-2?

This can only be verified experimentally,in vitro (in tissue culture experiments),and/or in vivo (in animal experiments).Experiments with SARS-CoV have shownthat insertion of a Furin cleavage site atthe S1-S2 junction enhances cellcell fu-sion (8). In addition, efficient cleavageof the MERS-CoV spike enables MERS-like coronaviruses from bats to infect hu-man cells (9). Avian influenza virusesencode the hemagglutinin (HA) protein (10),which serves a function similar to thatof the coronavirus spike protein. Whilereplicating widely in dense chicken pop-ulations, this virus acquired a polybasiccleavage site in HA, either through insertionor recombination. Acquisition of such apolybasic site converts the virus from alow pathogenic to a high pathogenic virus.This fact indicates that acquisition of aFurin site played a role in the crossing ofspecies boundaries. Thus far, data hasshown that bat or pangolin viruses do notcontain a Furin polybasic site though theanalysis has involved under-sampling (6).The question that remains is: From whichsource did SARS-CoV-2 acquire its Furincleavage site? Could it be from humans?

Three O-linked glycans: Used forimmune evasion and protection againsthost antibody responses to virusproteins

There is another interesting insertion in theFurin polybasic cleavage site of the SARS-

CoV-2 spike protein. The amino acid Pro-line (P) is present before the arginine andthe corresponding sequence is PRRARS (6).This insertion of proline has remarkablesignificance because proline is known tocause turns in proteins and change theiroverall conformation. In the present case,such a turn generated by proline mighthelp to acquire three O-linked glycans inSARS-CoV-2. But these glycans are absentin bat and pangolin coronaviruses thoughthese viruses contain the specific Serine(S) or Threonine (T) amino acids to be O-linked glycosylated. In general, these O-linked glycans are used as a mucin shield tohide viral epitopes resulting in delayed re-sponses in eliciting antibody generation inthe body after infection (known as immuneevasion). While no published data is yetavailable to assess whether this is in factthe case with SARS-CoV-2, this hypothesispoints to explore the asymptomatic natureof COVID-19 for the first 7-10 days afterinfection.

The birth of a virus

Here is one potential scenario: Naturalselection in an animal host before zoonotictransfer.

“These bat viruses are, in evolutionaryterms, very stable. They do not changemuch. It is unlikely that RaTG13 turnedinto SARS-CoV-2 within a bat”, accordingto Baker [7].

However, things change when a bat virusjumps to another animal.

RaTG13 has the ability to bind to ACE2but not very effectively (Fig 3A). It ispossible that RaTG13 jumped from a batinto a pangolin – a small, scaly anteaterand highly valued in traditional Chinesemedicine [7]. Pangolins have the ACE2receptor as do other animals like ferrets,and the pangolin may have been infectedwith RaTG13 and another bat coronavirus


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at the same time (Fig 3B). When two virusesinfect the same host, they can possiblyrecombine in a process leading to swappingof their genes; this may represent the firstinstance of gene tweaking resulting in avirus containing a bat genetic backboneand a pangolin RBD site (Fig 3C). Sucha virus could have infected humans butwould not be very infectious because itlacks a Furin cleavage site (trigger site).

Then, such a virus could have infectedhumans at a low level and via human-to-human transmission, could have acquiredthe Furin cleavage site representing thesecond instance of gene tweaking; in thecourse of time, the virus could have beenO-glycosylated in humans.

This may be one of the potential routesvia which this virus originated and gainedthe ability to both bind to ACE2 and useFurin to quickly enter human cells (Fig 3D).

Another potential scenario:Natural selec-tion in humans following zoonotic transfer

It is conceivable that a progenitor ofSARS-CoV-2 jumped into humans duringshort undetected human-to-human trans-mission and acquired the genomic featuresdescribed above through adaptation. Onceacquired, these adaptations would enablethe pandemic to take off in due course oftime.

Can this virus be generated bypurposeful manipulation in thelaboratory?

So far, we have discussed notable geneticfeatures of the SARS-CoV-2 and describedthe most likely pathway of the origin ofSARS-CoV-2 from bat via pangolin throughnatural selection followed by adaptation.Let us now examine the conspiracy theoryof the origin of the virus.

The availability of a viral backbone formanipulation

In a laboratory, scientists use a viral back-bone to manipulate viruses. The genomeof SARS-CoV-2 has ∼96.1% similarity withthe Bat RTG13 coronavirus genome. Tomanipulate all the notable genetic features,some viral backbones closely similar to thegenome of Bat RaTG13 should have beenavailable and would have been reported;however, no such reports can be founduntil the pandemic occurred, suggestingthat SARS-CoV-2 has not originated fromthe laboratory.

Viral Receptor Binding Domain (RBD)which binds ACE-2

SARS-CoV-2 contains the RBD of pangolincoronavirus in the Bat RaTG13 backbone.This RBD sequence binds to the ACE2 hostreceptor and these two proteins interactwith each other through a few crucial aminoacid residues. To manipulate this RBD,scientists need to know its exact sequence.What is typically done in such cases? Con-sider an example. You lost your house key;you call a key smith. He first assessesthe shape and mold of the lock. Then hebrings a dummy key and conducts manytrials by polishing and cutting the key andultimately, comes up with a duplicate keythat works. Similarly, scientists wouldpredict the optimal sequence of the RBD ofthe viral protein which binds to ACE2 andtest several combinations by changing theamino acids in the RBD with the help ofa computational method called molecularmodeling, and ultimately predict an optimalsequence. This prediction may or may notmatch with the living system.

However, in the case of COVID-19, thescenario was different. After the outbreak,the genomic sequence of the virus hasbeen determined revealing the viral RBD


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Figure 3: The birth of SARS-CoV-2; the most likely pathway: Tweaking of two genes – naturalselection followed by adaptation. A) Bat RaTG13 coronavirus with 96% genome homology toSARS-CoV-2 but unable to bind well to the ACE2 receptor. B) Pangolin coronavirus withlow genome homology to SARS-CoV-2 but able to bind tightly to the ACE2 receptor. C)The first instance of gene tweaking occurring when an RaTG13-infected pangolin givesrise to an RaTG13 derivative containing the RBD of the pangolin coronavirus, and D) Asecond instance of gene tweaking occurring when the above RaTG13 derivative infectshumans and acquires the Furin trigger cleavage site, giving rise to SARS-CoV-2. Thesketches of bat, pangolin and human have been taken from the article [7].

sequence as well. Scientists subsequentlytested this RBD sequence using computer-based molecular modeling and predictedthat while it has high affinity for ACE2, it isnot the ideal sequence for ACE2 interaction(11). If it was a result of manipulation, whywould this sequence be less than ideal?

Thus, the high-affinity binding of theSARS-CoV-2 spike protein to human ACE2is most likely the result of natural selectionwith a pangolin or pangolin-like ACE2, ordirectly with a human ACE2. This isstrong evidence that SARS-CoV-2 is not theproduct of purposeful manipulation.

Acquisition of both the polybasic cleav-age site and predicted O-linked glycans

Generation of any manipulated virus needscell culture-based experiments, requiringseveral rounds of cell culture in Petri dishesthrough several passages. It has beenexperimentally shown that new polybasiccleavage sites arose in avian influenza virusafter prolonged passaging; but in that case,the virus backbone was known to the scien-tists while in the present case, a progenitorvirus with high genetic similarity to BatRaTG13 has not been described. Moreover,generation of predicted O-linked glycans


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needs the involvement of the immune sys-tem which is not possible in cell culturebut is feasible only in vivo (in a wholeliving organism with the relevant immunesystem) [12].

Counter arguments

Wuhan wet animal market and BSL4laboratory

Near the Wuhan wet market, a BSL4 (Bio-Safety Level 4) laboratory was carrying outcoronavirus-related research since manyyears. This type of BSL4 laboratory canhouse animals for experiments and so ma-nipulations can be done. Of relevance, asper available data, rats and mice are notcarriers of COVID-19. There is no evidenceof the housing or breeding of Bat RaTG13and pangolins in this laboratory. As theseanimals contain low level of viruses, hugenumbers of bats and pangolins would beneeded at the laboratory for generationof viable number of viruses. Such largenumbers of these animals are available onlyin nature. These facts suggest that SARS-CoV-2 is a product of natural selectionfollowed by adaptation.

Spillover theory of the ready-to-infect-human virusSpillover theory of theready-to-infect-human virus

The ready-to-infect-human SARS-CoV-2has been spilled over in the wet marketof Wuhan and the infection began. If thevirus was ready to infect humans, thenwhat was the necessity to bring it to the wetanimal market? It could have been spreadin any human groups. The medical journalLancet published the analysis of the first41 COVID-19 patients. They found that 27out of 41 patients had direct exposure tothe Wuhan market. But the same analysisalso reported that the first known COVID-19 patient did not have any exposure to the

Wuhan wet market [13].

Requirement of additional data

More scientific data could swing the bal-ance of evidence to favor one hypothesisover another.

1. The availability of data on patient “Zero”will throw more light on the origin of thevirus. This will also give additional in-formation about how this virus crossedthe species barrier.

2. Analysis of sufficient serological data ofthe initially infected patients near theWuhan wet market is required to knowwhether unidentified but short dura-tions of human-to-human transmissionof the virus occurred. Some data isavailable in this regard but more isrequired.

3. More animal viruses are to be sequencedto understand their genetic content andhow similar they are with respect toSARS-CoV-2.

Whatever may be the theory behind theorigin of SARS-CoV-2, one lesson is weshould be extremely careful about the waywe deal with nature. Bats and pangolinsmaintain real social distancing, not onlyphysical distancing with human. They donot come to us rather we go to them.This is very important. SARS-CoV-1 wasmore fatal than SARS-CoV-2 but infectiv-ity is lower. SARS-CoV-2 is less fatalcompared to SARS-CoV-1 but highly infec-tious. Through natural selection followedby adaptation if a new strain arises, havingfeatures of the high fatality and infectivity,then humankind will be in much moretrouble. In this such a scenario, humansmay not get enough time to respond.

Lastly, in this troubled time, people haverealized that only science can save thehumankind. They do not believe in the


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influence of any supernatural power behindthe origin of this virus. Rather, even apalmist who touches the palms of anotherperson is now wearing a face mask onhis mouth and gloves on his hands. Isa semblance of scientific temper and ap-proach finally making an appearance in oursociety?

References[1] Zhou, P., Yang, X., Wang, X. et al. A

pneumonia outbreak associated with a newcoronavirus of probable bat origin. Nature579, 270273 (2020)

[2] Wu, F., Zhao, S., Yu, B. et al. A new coro-navirus associated with human respiratorydisease in China. Nature 579, 265269 (2020).

[3] Gorbalenya, A.E., Baker, S.C., Baric, R.S.et al. The species Severe acute respiratorysyndrome-related coronavirus: classifying2019-nCoV and naming it SARS-CoV-2. NatMicrobiol 5, 536544 (2020).

[4] www. Worldometers.info/corona

[5] Totura, 2019, https://doi.org/10.1080/174460441.2019.1581171

[6] Anderson K. G. et al. Nat Med. 26 (4):450(2020).

[7] https://www.smh.com.au/national/ the-perfect-virus-two-gene-tweaks- that-turned-covid-19-into-a -killer-20200327-p54elo.html

[8] Follis, K. E., York, J., and Nunberg, J. H.Virology 350, 358-369 (2006).

[9] Menachery, V. D. et al. J. Virol.https://doi.org/10.1128/JVI.01774- 19(2019).

[10] Alexander, D. J. and Brown, I. H. Rev. Sci.Tech. 28, 19-38 (2009).

[11] Wan, Y., Shang, J., Graham, R.,Baric, R. S. and Li, F. J. Virol.https://doi.org/10.1128/JVI.00127-20(2020).

[12] Bagdonaite, I. and Wandall, H. H. Glycobi-ology 28, 443-467 (2018).

[13] Huang et al. The Lancet, 395, 10223, p 497-506, (2020)


Some New Findings to Track the Origin of NovelCoronavirus

Kumar S. K. Varadwaj ∗

The human species has locked itself downin homes due to the attack of an enemywhich, till date, is very little understood.The strategy that has evolved to fightCOVID-19 is to avoid human touch or closeproximity or even indirect contact throughsome inanimate object. This behaviour isquite contrary to any mammalian species,including homo-sapiens.

The first COVID-19 patient was detectedon 12th December, 2019 from Wuhan inHubei province in China. The scientistsin China realised the devastating potentialof the virus and the Chinese Governmentofficially reported the outbreak to WHO(World Health Organisation) on 31st De-cember 2019. Due to high global mobility ofthe modern day, and highly efficient humanto human transmission, the virus spreadvery quickly to every corner of the Globe.On 30th January 2020, WHO declared theoutbreak a Public Health Emergency ofInternational Concern. This devastatingpandemic caused by a virus hitherto un-known affected ten lakh people, of whichalmost fifty thousand died by 5th April2020.

From where did this virus come from? Ifit came from some other species, then howdid it cross the species boundary? How didit became so efficient in terms of humanto human transmission? What is the modeof its transmission? Scientists around the

∗Dr Varadwaj is with the Department of Chemistry,Ravenshaw University, Odisha

globe are working hard to find answersto these questions which are intimatelyrelated to the origin of this new virus. Otherstudies have gained momentum to under-stand factors such as how long does thevirus stay active outside the human bodyand on different objects, and what are thechemical formulations that can effectivelyneutralize the virus. These investigationsare essential in the long journey to fight theviral infection by finding medicines, vac-cines and technologies to stop its spread.The sheer amount of scientific effort beingdeployed can be gauged by the fact thatmore than 900 English language publica-tions have appeared on this new virus till12th March 2020.

In December 2019, cases of influenzawith severe infections in respiratory trackemerged in Wuhan, China. Initial inves-tigations showed that the infected peoplehad either visited or were related somehowto a seafood market at Hubei province.Scientists at Wuhan institute of virologytook blood and swab samples from theaffected patients and tried to detect themicrobe responsible for this disease.

The unique character of every life formis encoded in chemical entities in its genes- arranged in particular order called thegenome sequence. A group of scientistsfrom China, first did the genome sequenc-ing of this virus and put their findings inpublic domain [1]. The study of genomesequence from samples collected from dif-


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ferent patients showed that this was anew virus. It belongs to a family ofvirus known as coronavirus. The chemicalbackbone of this virus has similarity withthat of another coronavirus, which causedepidemics in 2002 to 2003 in southernChina. That epidemic is since known asSevere Acute Respiratory Syndrome (SARS).The previously known virus was namedas SERS-CoV. The new virus that hasstarted the pandemic in 2019 is named asSERS-CoV-2 by special bodies for namingand characterising viruses. Viruses arenamed based on their genetic structureto facilitate the development of diagnostictests, vaccines and medicines. Virologistsand the wider scientific community in theInternational Committee on Taxonomy ofViruses (ICTV) are responsible for namingthe viruses.

The coronavirus is a large family ofviruses, which causes diseases in mammalsand birds. The first corona virus in humanbeings was discovered in 1960. The earliestone was studied from patients sufferingfrom common cold and it was named ashuman corona virus 229E. Apart from thepresently discovered novel coronavirus i.eSARS-CoV-2, six other corona viruses areknown to infect humans. In last twodecades, another coronavirus epidemic oc-curred in 2012, which is known as MiddleEast Respiratory Syndrome (MERS). But,the other four coronaviruses, namely 229E(alpha), NL63 (alpha), OC43 (beta) andHKU1 (beta) only cause mild symptoms ofcold in human.

The viruses do not show any signatureof a living body outside a host animal. Infact, some animals such as cattle, horse,pig, mice, dromedary camels and alsobirds, bats, pangolins and chickens actas reservoirs for different types of viruses.The viruses have gone through a parallelevolutionary process with the evolution of

their host animals. Certain viruses stayin certain animals but do not cause anydisease in those animals. But when theseviruses leave their host animal and entersinto the body of some other animal, theycause disease in their new host. It hasbeen established by scientific studies thatthe dromedary camels found in the MiddleEast are hosts for MERS-CoV coronavirus.They crossed the species boundary and en-tered into the human body due to intimateman- camel contact. But the host forSERS-CoV coronavirus which caused theepidemic in 2002 is not exactly known yet.However, studies have shown that differentbat species available in China are host forSERS like coronaviruses.[2]

In the present case, therefore just afterknowing the sequence for the chemical enti-ties in the novel coronavirus, i.e the genomesequence, it was matched with that of otherviruses and a 96% similarity was observedwith a particular coronavirus present inbats. Therefore, the Chinese researcherswrote that the virus has a probable batorigin. In this situation of panic anddistress, another leading research groupin the field of virology from the ScrippsResearch Institute, from California, USAmade a detailed study regarding the originof this novel corona virus [3]. Before goinginto details of their study, it needs to bediscussed how a virus from its originalanimal or bird host jump the species barrierand infect the human body.

If any virus from an animal host, by anychance, comes in contact with a humancell, it cannot cause any damage to the cell.The virus needs to have a site, which canefficiently bind to the human cell throughsome chemical interactions. The Scrippsresearch group studied these binding sitesof the novel coronavirus and compared itwith that found from the bats and pan-golins. They showed that, although there


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is 96% similarity in the genome sequenceof virus from bat with that of the novelcoronavirus, the binding sites for both theviruses are not the same. It has moresimilarity with that of pangolin. However,the genome sequence of the virus presentin pangolin has many differences with thatof the novel corona virus. Therefore, atpresent there is ambiguity in deciding theimmediate ancestor of the virus and thehost animal from which it has come tohuman body. However, in their com-munication to Nature Medicines Magazinethe group reported “Our analyses clearlyshow that SARS-CoV-2 is not a laboratoryconstruct or a purposefully manipulatedvirus.”

Nevertheless, the authors have proposedtwo theories for its transfer. The first oneis that the virus might have changed itsgenetic code in the host animal so thatnecessary changes have been incorporatedin their binding sites, which makes it ableto attack the human cells, penetrate intoit and cause disease. The second oneis that the virus first transferred to thehuman body, stayed dormant there tillit underwent required genetic changes forhuman to human transfer. In both thecases changes occur in the arrangement ofbasic chemical backbone of the virus bythe process of natural selection suggestedby Darwin some 150 years ego. However,the primary difficulty in knowing the exactancestor of the virus and the host animalfrom which it has come from is that thewhole family of coronaviruses present inbats and different species are ‘massivelyunder sampled’.

In the last two decades, we witnessedthree such events of virus spill overs fromtheir animal host causing massive healthhazards. Therefore, a detailed understand-ing of how an animal virus jumped speciesboundaries to infect humans so effectively

Figure 1: An electron microscope image ofSARS-Cov2 particles. Every virus particle showsspikes around it, which looks like a crown.These are the spike proteins covering the surfaceof the lipid bilayer. The size of each virusparticle is around 100 nanometers (1nm = 109

meter). These extremely small virus particlescan easily float in air along with water droplets,which is one of the modes of its man to mantransmission.

will help in the prevention of such futureevents. The identification of closest viralrelatives circulating in different animalswill also be important to understand theiraction.

References

1. “A pneumonia outbreak associated with anew coronavirus of probable bat origin” Na-ture, 579, 270273 (2020).

2. “Bats Are Natural Reservoirs of SARS-LikeCoronaviruses” Science, 310, 5748, 676-679(2005).

3. “The proximal origin of SARS-CoV-2” NatureMedicines, correspondence 2020.


Organizational News

Telangana

A social media protest campaign by holdingplacards on the Vizag gas leak issue wasorganized throughout the state of Telan-gana. The response was overwhelming fromdifferent sections of people including theacademia. At BSS office, a candlelightprogram held on May 8.

The protest against Vizag gas tragedy

In the background of COVID-19, an on-line State level science cultivation programwas organized. The program included es-say writing, cartoons, poster presentationsand short flim making. Students from 9districts of Telangana participated actively.On May 15, a felicitation function wasorganized in which the chief guest was DrVikas Sharma, Asst Professor of Biotech-nology, University College of Science, Os-mania University. The winners in variouscompetitions were felicitated.

A webinar was held on the Vizag gas leak

Poster of the webinar on the Vizag gas leak tragedy

tragedy on May 21. Dr Babu Rao, RetdChief Scientist, IICT, Hyderabad was thespeaker.

Odisha

Relief support to migrant workers

Starting from 10th May to 16th May, vol-unteers of Bigyana Chetana Macha (BCM)affiliated to Breakthrough Science Societyprovided food and water to distressed mi-grant workers travelling on the nationalhigh way on their way to distant placesin Jharkhand, West Bengal etc. Everyday scores of men, women and kids wereseen travelling on foot, on bicycles, ontop of trucks loaded with goods and othervehicles. They were thirsty and hungry.Seeing the plight of those hapless peoplemembers of BCM from Cuttack started


Organizational News

Volunteers distributing food and water among the migrant labourers in Odisha

providing relief like food and water.On 21st May, after the cyclone Am-

phan made land-fall causing havoc in WestBengal, coastal Odisha including Cuttack.These areas experienced heavy rain andwind. Several hundred labourers weretaking shelter below the flyover at Manguli.Trucks loaded with goods and labourerswere also ferrying on the road. A youthgroup from Peyton Sahi, a place in centralCuttack, collected fund and distributedpacked dry food to the distressed laborers.The culture of ‘Sahi Bhai’ that is the livingsoul and driving force of the thousand yearold city, was again at its best. The ‘GoodSamaritan’ was again out on the street.

Kerala

Trivandrum district

Science Orientation Program for school

students: An online Science OrientationProgram for students in 9th and 10thstandards was organized from April 20 to26. More than 250 students applied forparticipating in the program.

To ensure the quality of the program,admission was restricted to 50 students. Aselection list was prepared by giving prefer-ence to the students from Trivandrum dis-trict with a limit of four students from oneschool. Online sessions were conductedfrom 9:45 am to 12:00 noon every day.

Classes conducted:Dr. Sarita Vig, ‘Wonders of the Cosmos’,Dr. K.B.Jinesh, ‘Seeing and Playing withAtoms’Dr.Sojomon Mathew, ‘Microbes and Immu-nity’Dr. Umesh R Kadhane, ‘Who wants to bethe next Archimedes?’Ms. Medha Surendranath, ‘Mendeleev and


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periodic table’Dr. Rajeevan P.P, ‘A Brief History of Scienceand Evolution of Scientific Method’

All lectures were followed by an activity-based session in which the students wereadvised to do a few activities related to thetopic of the session.

Students were grouped into small teamsfor the ease of management. Each teamconsisted of 5 students and 3 BSS volun-teers. Volunteers played a remarkable rolethroughout the program. They were keento help the students in their activities andensured the active participation of studentsin every session.

Each day, the session started with pre-sentations by students. One student fromeach group presented the activity carriedout by them based on the previous day’ssession.

Students were also advised to conductan experiment using the materials availableat their homes to demonstrate or prove aconcept in any branch of science based ontheir interests and present it on the finalday. The response was tremendous. Almostall of them performed at least one exper-iment. Students posted short videos ontheir experiments in the common Whatsappgroup before the final presentations.

In the concluding session Dr. SoumitroBanerjee, Professor in the Department ofPhysical Sciences, IISER, Kolkata and Gen-eral Secretary, Breakthrough Science Soci-ety delivered a lecture titled ‘What actuallyis science?’ and interacted with the partici-pants.

Alappuzha district

The Alappuzha BSS chapter organised athree day science camp for students from8th class to 11th class from May 11 to May13, 2020. The timing was from 10.30.amto 12.30.noon. About 110 students in-cluding science activists registered. On the

average about 30 to 45 students attendedthe classes. The program was inauguratedby Dr.C.Muraleedharan Pillai, Asst.Directorof Health Services and Adv Sajeev T Prab-hakaran made a presentation on ‘Evolutionof stars’. The second day began with aspeech by Dr. K. G. Padmakumar, Agri-cultural Scientist. Shri P. P. Sajeevkumarmade a presentation on ‘An introductionto sky watching’. On the third day Dr.Godfrey Louis, Former Pro V C, CUSAT gavea talk on ‘The method of science’. The lastsession was on ‘Learning science throughexperiments’. Seven students presentedvideos of their experiments and explainedthe science behind the experiments. Theparticipants enthusiastically took part inthe discussions on each experiment.

It was also decided to form a what-sapp group of the student participants andcontinue science discussions and ‘learningthrough experiment’ activities.

Idukki district

BSS Idukki chapter in association with theNewman College, Thodupuzha organized awebinar on May 13, 2020. The topic was“Beyond the stars”. Prof Joe Jacob, HoD,Dept of Physics, Newman College and arenowned astronomer made the presenta-tion.

The Idukki chapter of BSS in associationwith the Newman College, Thodupuzha or-ganized a science quiz program for collegestudents on May 15, 2020. 35 studentsparticipated in the quiz program.

Thrissur district

BSS Thrissur Chapter organized a series ofonline talks.April 5: Talk on ‘How man conquereddiseases’, by Dr. Babu P S.April 11: Talk on ‘History of Astronomy’ byDr. Sheeba, Associate Prof, Dept of Physics,MES College, Kodungallur.


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April 22: Talk on ‘Earth and the skyseen from the Earth’ by Mr SurendranPunnassery, Amateur Astronomer.April 23: Talk on ‘The past and future ofthe Universe’ by Dr.Sheeba, Associate Prof,Dept of Physics, MES College, Kodungallur.

Ernakulam district

BSS Ernakulam chapter organized a seriesof webinarsApril 22: ‘Louis Pasteur – life and contribu-tions’ by Mr Harikumar K S, Former SafetyOfficer, FACT, KochiApril 19: ‘Comets – Ice from space’ byAdv Sajeev T Prabhakaran , Amateur as-tronomerApril 25: ‘Diseases and treatments in theera of science’ by Shri C Ramachandran,Retd scientist, ISRO.May 16: ‘Covid19 – A view from USA’by Mr Martin Kalathungal, Independentresearcher of Nutrition and well-being, USA

Science camp for school students:Breakthrough Science Society, Ernakulamchapter organized an Online Science Orien-tation Program for students of 9, 10 and 11classes. The camp was conducted in twobatches with more than 50 students in eachbatch. The first batch was from May 2,3and 4 and the second batch from May 9, 101nd 11. Each day there were 2 sessions ofone hour duration from 10 am to 12.30pm.

The program schedule for the two batcheswere as follows.

Batch 1 Day 1Session 1: ‘Evolution of the method ofscience’ – Dr Rajeevan P PSession 2: ‘Evolution of stars’ – Shri. SajeevT Prabhakaran

Day 2Session 1: Learning through experiments–Chemistry- Mr Alwyn GeorgeSession 2: Learning through experiments –

Physics- Smt. Rajani S

Day 3Session 1: Basics of sky watch – Shri.Sajeevkumar P PSession 2: ‘World of microbes andimmunity’ – Smt Soniya Mohandas

Batch 2 Day 1Session 1: Basics of sky watch – Shri.Sajeevkumar P PSession 2: ‘Louis Pasteur and the world ofmicrobes’ – Shri. Harikumar K S

Day 2Session 1: ‘Universe in a nutshell’ – ProfJoe JacobSession 2: Learning through experiments –Chemistry - Smt Lasitha and Smt. Aswathy

Day 3Session 1: ‘Evolution of the method ofscience’ – Dr Rajeevan P PSession 2: Learning through experiments –Physics - Smt. Rajani S

A whatsapp group of the participants wasformed to continue science discussions and‘learning through experiment’ activities.

Tamilnadu

In the lockdown situation, a series of webi-nars were organized in Tamilnadu. 10 May,2020 : Mr T Pradeep Kumar, a student of MSc Physics, A V C College Myladumthuraimade a presentation on “How to measurethe circumference of earth using a stick”.It was in fact a re-enactment of the his-toric experiment by the Greek astronomerEratosthenes more than 2000 years back.17 May, 2020: Shri Ilango Subramanian, ascience communicator gave a talk on “Thewave particle duality of matter”.21 May: Mr Parthasarathy, a student of BSc Physics, A V C College Myladumthuraimade a presentation on ‘The history and


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use of MORSE code’24 May: Dr S Jagannathan, Pasteur In-stitute, Coonoor, Tamilnadu gave a talkon ‘Louis Pasteur and Vaccination’. Thetalk covered a history of the development ofvaccines and a life sketch of Louis Pasteur.29 May: Prof Joseph Prabagar, Dept ofPhysics, Loyola College, Chennai made apresentation on ‘Mountains on Moon –How to measure their heights’. It was arecapture of the famous experiment doneby Galileo Galilee in the sixteen hundreds.Quiz program

May 27: The BSS unit of Coimbatoreorganized an online science quiz for undergraduate students. 260 students took partin the first round. The entire programwas visualized and executed by a team ofstudent members of BSS.

Responding to the call of IMFS commit-tee, the members and supporters of thestate chapter participated enthusiasticallyin the Online Campaign on the PandemicCovid19 situation.

Jharkhand

A two day state level online science camp forstudents was organized on May 30 and 31.The topics discussed were mainly related toCOVID 19. In continuation of the Camp,two webinars were organized on 7 June:“Can animals think?” by Prof SoumitroBanerjee“What can we do and how can we developour society by our power of thinking?” bySri Debashis Roy

BSS Zonal Workshop in New Delhi

On behalf of Breakthrough Science SocietyAll India Committee, a two day workshopfor Central and North zonal activists washeld on 14th and 15th of March in NewDelhi. Representatives from Jharkhand,Bihar, UP, MP, Chattisgarh, Rajasthan,

The North and Central zonal workshop in Delhi

Uttarakhand, Haryana and Delhi attendedthe workshop. The main subject mat-ter of discussion was the setting up of‘Breakthrough Science Learning Centres’.A set of experiments was demonstrated andexplained by Dr Manabendra Bera and MrVijay Kumar. A session on the history ofscience was conducted by Prof SoumitroBanerjee, General Secretary, BSS. The con-cluding session on organizational issueswas conducted by Shri Debashis Roy, Vice-President, BSS.

West Bengal

27 January, 2020: At the call ofNazrul Smriti Sangha, Subhasgram, ateam of BSS demonstrated several anti-superstation programs and also a fewmethods for the detection of common adul-terants in food.29 January to 9 February, 2020: BSSparticipated and put up stall at the 44thKolkata International Book Fair.17 February, 2020: Science Martyrs’ Daywas observed throughout the state. Floraltribute was offered to Giordano Bruno – thefirst martyr of science by several scienceclubs and institutional chapters of BSS.Besides, debates and discussions were alsoorganised.


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The anti-superstition demonstration at Subhasgram,

WB

The stall at the Kolkata Book Fair

21st February, 2020: A state level trainingcamp was organised on ‘Sky Watching andTelescope handling’ at Mourigram, Howrah.Nearly forty members from different ScienceClubs participated. The camp was con-ducted by Dr. Safique Ul Alam, Dr. TapanKumar Si and Dr. Radhakanta Konar.22-23rd February, 2020: In collaborationwith BSS, a two day Science Fair wasorganised by Charu Mohan Dutta MemorialHigh School, Dumdum. Dr. DebabrataBera of Jadavpur University inauguratedthe Science Fair. Sri Dipankar Dutta (Head-master), Prof. Saugata Roy (Member of

Parliament) and local councillors were alsopresent in the fair. More than 130 studentsdemonstrated their models. During thesecond session of the day two, a seminarwas organised on the subject ‘Science andScientific Outlook’. Prof. Amitava Dutta,INSA Emeritus Professor of Calcutta Uni-versity was the main speaker of the session.Dr. Nirmal Duari, Assistant Secretary, BSSWB chapter, handed over the prizes to thewinners of the different groups.

The Science Martyr’s Day observation in Kolkata

The telescope handling training camp in Mourigram


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Prof Amitava Datta speaking at the Science Fair,Kolkata

Science Cultivation

Since physical gatherings were not possibleduring the lockdown, the W.B. Chapter ofBSS organised an online state level ‘ScienceCultivation’ program. Science essay writ-ing, poster drawing, ‘Corona in cartoon’ andexperiment demonstration were the topicsof the Science Cultivation program. Thetopics were meant mainly for the school andcollege students. More than 800 studentsparticipated in this online initiative.

Corona Relief Work

BSS WB Chapter initiated the Corona reliefwork from the middle of April. Some ofour affiliated science clubs took a leadingrole during this phase. As the time andsituation was really tough in holding the re-lief camps publicly, our members did theirwork with all the required precautions.

As our members were unable to collectmoney directly from public, this time wehad to rely fully on the online bank trans-actions. People responded spontaneouslyto the call of Breakthrough Science Society.During this time, the IIT Kharagpur Chap-ter of BSS collected more than One lakhrupees and donated to our relief account.The students from the Physics Departmentof Calcutta University (Rajabazar Science

Relief work in North 24 Parganas district, WB

College Campus) donated their full amountof Eleven thousand nine hundred rupeesfrom their farewell Account of 2nd yearstudents. A free coaching centre, meantfor the poor and needy students named‘Adhayan’ donated an amount of Fifteenthousand rupees from their collection.

Meghnad Saha Bigyan Sanstha, North24 Parganas, has been conducting reliefwork every Sunday to help the people belowpoverty line in several areas of Duttapukur,Bira, Bamangachi and Chotojagulia.

Panskura Science Centre and MahisadalScience Centre of East Midnapore dis-trict, Marie Curie Science Club of NBU,Boson Science Centre of Birbhum alsoconducted relief works in their respectiveareas. Mainly food and sanitizing materialswere distributed during the first phase oflockdown.

On 3rd May, 2020, on behalf of IndiaMarch for Science (IMFS), Kolkata Organis-ing Committee, Gloves and Sanitary Maskswere handed over to Calcutta Heart Clinicand Research Centre.


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BSS volunteer Dr Nirmal Duari handing over glovesand sanitary masks to the Calcutta Heart Clinic and

Hospital

Cyclone ‘Amphan’ Relief Work

In West Bengal, at a time when the peoplewere struggling hard to fight the Covid-19 pandemic, the super-cyclone ‘Amphan’struck and caused large-scale devastation.Telecommunication systems were razed tothe ground, trees along with electric poleswere uprooted, thousands of dwellings weredestroyed, and roads, bridges and embank-ments were ravaged. It was a massive blowwithin a short period of time.

In this grave situation, the volunteers ofBSS extended their helping hands inspite ofmany odds and difficulties.

Meghnad Saha Bigyan Sanstha, North24 Parganas, started Community Kitchen(Acharya Prafulla Chandra Roy Kitchen) atDuttapukur area after the cyclone. Since23rd May they are continuing their serviceamid acute fund crisis. Cooked food isserved among slum dwellers who are af-fected due to Amphan.

Our volunteers have removed collapsedtrees to clear roads, lanes and streets from20th to 26th May.

Block No.1 of Barasat is one of theworst affected areas in North 24 Parganas.Meghnad Saha Bijnan Sanstha is workingdirectly here.

BSS unit of Kanchrapara and Basirhat

are also doing relief work.The Progressive Science Forum of Habra

has already conducted a relief camp.30th May, 2020: At Nalgora of Joynagar

Block 2, South 24 Parganas relief workalong with medical camp was organised byBreakthrough Science Society along withMedical Service Centre (MSC), India Marchfor Science (IMFS) Committee and Reliefand Public Welfare Society.

On the same day, sanitary masks alongwith gloves were handed over to SouthJoynagar Health Centre on behalf of theIMFS Committee.

31st May, 2020: Relief Camp was or-ganised by BSS East Midnapore districtchapter at Nandigram. Food material alongwith soap and detergent were distributed toone hundred families.

Besides, a representative team visited theseveral households of Tengua, Chowrangiand Kanchannagar. The situation is stillvery bad even after ten days. There isthe crisis for drinking water. Most of thevillages are without electricity. The up-rooted trees have still not been cleared. Thepolluted ponds are spreading foul smell.2nd June, 2020: Relief Camp was or-ganised at Bhubaneshwari of Kultali Blockand Ghatiharaniya of Joynagar Block 2by BSS South 24 parganas Chapter. In

Cyclone relief work at Joynagar, South 24 Parganasdistrict, WB


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Bhubaneshwari two hundred families werebenefitted and in Ghatiharaniya, relief ma-terials were distributed to seventy affectedfamilies.3rd June, 2020: On behalf of KolkataDistrict BSS, relief work was conducted atJadavpur area. It was assisted by themembers of C.V. Raman Science Society.Nearly 85 cyclone affected families wereserved with food material and soap.6th June, 2020: Relief Camp was organizedat Daktargheri of Kankandighi (Mathura-pur Block), South 24 Parganas on behalfof S N Bose Science Society (BSS affiliated)and DRSO jointly. Nearly 150 families weresupplied with relief material.7 May, 2020: A webinar was organisedon the Covid-19 pandemic Prof. ParthaPratim Majumdar, founder Director, NIBMGKalyani and President, Indian Academy ofScience, Bangalore was the speaker. Thewebinar was in the form of question andanswer, with questions like ‘How danger-ous is the Coronavirus?’, ‘What is theview of science regarding this Pandemic?’,‘What precautions are needed to be taken?’,etc. More than 500 people participateddirectly in the webinar, more than 600others watched through Fb and Youtubelive streaming.

Relief work at Panskura, East Midnapore district, WB

Cyclone relief work at Bhubaneswari, South 24Parganas district, WB

Online Campaign

At the call of the India March for Sci-ence, the members and supporters of thestate chapter participated enthusiasticallyin the Online Campaign on the Covid-19Pandemic situation. The campaign startedon 9th May and continued till 14th May.During this period nearly 800 supportersof BSS came up with colourful, printed aswell as hand written posters and placardsand presented on several platforms of socialmedia. Besides, scientists from differentinstitutes came up with advocacies in theform of short videos.

Movement to save AJC Bose IndianBotanic Garden

Super cyclone ‘Amphan’ has caused severedamage to the rare collection of trees inthe 233 year old AJC Bose Indian BotanicGarden. This garden is the richest, oldestand largest of its kind in whole of SouthEast Asia and is a National Heritage.

From various news sources, it is clearthat around one thousand trees and plantswere partially or fully uprooted due to thecyclone. The 260 year old Great BanyanTree suffered 20 to 25 percent damage.Many rare species were destroyed com-pletely.


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The programme in front of the Botanical Garden,Howrah

From BSS Howrah district chapter, amemorandum was submitted to the Direc-tor of Botanical Survey of India, with copyto the District Magistrate of Howrah, Cen-tral and State Ministries of Environment,and The Governor of WB. We requested theauthorities to take quick measures to savethe damaged trees.

The BSS Howrah chapter gave a call toobserve 5th June as “Save AJC Bose IndianBotanic Garden Day”.

Karnataka

Bangalore

28 March: Webinar on ‘Going to spacewithout money’. Speaker: Dr JayanthMurthy, Senior Professor, IIAp. This talkwas to show the what is the minimumcost required for space exploration and thedifference in the space research carriedout by ISRO and IIAp and in the fundsby the two organisations, along with thedifferent research that is carried by IIAp.The webinar was conducted and presidedby Dipti.B and Amjad Syed.27 April: Sending quotes of scientists tocontacts in the state. So far 21 quotes havebeen shared and published on our socialmedia.5 May: BSS members and contacts, alongwith members overseas participated in theonline campaign with various demands ofthe India March for Science on COVID-19.

8 May: Vizag Styrene Gas Tragedy onlineprotest State level online protest was heldstanding in solidarity with the victims ofVizag Styrene gas leak victims, with BSSmembers holding slogan placards demand-ing justice for the victims and publicizedthem on social media with the #SaveVizag#BSSwithVizagVictims.

State level Online Science Fest

Online poster making, cartoon and sciencepoetry writing fest was held from 10th to31st May 2020. Participants had to registerfor the events and submit their work by31st May. Submission evaluation is underprogress. Online Certificates for all partici-pants and prizes for winners will be givenin the month of June. 300 participantsregistered across Karnataka.

A whatsapp group consisting of all mem-bers made during various programs con-ducted across the states was formed, as away to further consolidate those who havesigned for membership.

An online membership campaign wascarried out during the month of April-May. A good number of scientists, teachers,professors, IT professionals, engineers, stu-dents of colleges and schools have joined as

Online protest in solidarity with the Vizag gas leakvictims


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members. A few from overseas also joined.

Dharwad

BSS Dharwad raised funds from contactsand made ration kits. More than 25ration kits were distributed to migrant andslum area people during the COVID-19pandemic.

Relief distribution among migrant workers and slumdwellers in Dharwad

Mysuru

BSS Mysuru raised funds from contactsand distributed relief material to migrantand slum dwellers during the COVID-19pandemic.

Davangere

May 2 and 3: Webinar on ‘Immune systemvs corona’. Speaker: Dr. D.S. Shihupala,Professor, Department of Microbiology, Da-vangere University.7 May: ‘Relevance of Louis Pasteur: Thenand Now’. Speaker: Rajani .K.S, Secretary,BSS Karnataka State.9 May: ‘Snakes and Science’. Speaker: Dr.D.S. Shishupala, Professor, Department ofMicrobiology, Davangere University.

16 May: ‘Important lessons humans canlearn from honey bees’. Speaker: Dr.B. E. Rangaswamy, Dean, Research andDevelopment, Professor and Head, Depart-ment of Biotechnology,Bapuji Institute ofEngineering and Technology, Davangere.17 May: ‘Beautiful World of birds’. Speaker:Dr. D.S. Shishupala, Professor, Dept. ofMicrobiology, Davangere University.

Gulbarga

15 May: Webinar on ‘Relevance of scientificthinking in the era of social media’ Speaker:Satish Kumar.G, President, BreakthroughScience society, Karnataka State.

In midst of various wrong informationand news coming from various platforms,it has become very much necessary to findout what is right and how to find out whatis right. The talk addressed these questionsand was well received by the people whoattended. Around 70 contacts attended andall were given participation certificates.24 May: Webinar on ‘Relevance of LouisPasteur: Then and Now’ Speaker: Ra-jani.K.S, Secretary, BSS Karnataka state.The talk covered the life of Louis Pasteurand his contributions in the field of Biology.Apart from this she also discussed aboutviruses and immunity.

Programmes on National ScienceDay

The National Science Day this year wasdedicated to the struggle of the womenscientists in the country. BreakthroughScience Society observed the day with theobjective of taking the life struggles andcontributions of the great men and womenin science to the people at large to fostera scientific bent of mind and to cultivatescientific temper in the society. A detailedaccount of the programmes can be foundhere.


https://breakthroughindia.org/national-science-day-feb-28-2020-women-in-science/



Vol.21, No. 4, May 2020 BREAKTHROUGH Registration No: 53166/92

Founder Chairman, Advisory Board:Professor Sushil Kumar Mukherjee

Former Vice-Chancellor, University of Calcutta and Kalyani University,Former Director, Bose Institute, Kolkata.

ADVISORY BOARD

Amitabha Ghosh, Former Director, IIT Kharagpur, and former Professor, IIT KanpurP. Balaram, Former Director, IISc Bangalore, and former Editor, Current ScienceS. Mahadevan, Professor, Dept. of Molecular Reproduction, Development & Genetics, IISc BangaloreAnimesh Chakravorty, Emeritus Professor, Indian Assn. for the Cultivation of Science, KolkataBabu Joseph, Former VC, Cochin University of Science & Technology, Kerala

EDITOR-IN-CHIEF:Dhrubajyoti Mukhopadhyay, Retired Professor of Geology, University of Calcutta

EDITORIAL BOARD:Prof. Soumitro Banerjee, Ms. Rajani K S, Prof. K P Saji, Mr. George Joseph, Dr.Manabendra Bera, Prof. A P Chattopadhyay, Mr. V P Nandakumar

PUBLISHER: Dr. Tarun Kanti Naskar

Contact persons

Kerala: P N Thankachan <[email protected]>; Karnataka: Satish K G <[email protected]>;

Telangana: R Gangadhar <[email protected]>; AP: Thabrez Khan <[email protected]>, Delhi:

Vinay Kumar <[email protected]>; Haryana: Harish Kumar <[email protected]>; Tamil

Nadu: George Joseph <[email protected]>; UP: Jai Prakash Maurya <[email protected]>;

Madhya Pradesh: Sadhna Jakre, Gwalior, and Vikas Bansal, Guna <[email protected]>; Odisha:

Sidhartha Varadwaj <[email protected]>; Assam: Pintu Debnath <[email protected]>; Jharkhand:

Kanai Barik <[email protected]>; Gujarat: Dilip Satashiya <[email protected]>; Bihar:

Kamal Mishra <[email protected]>; Tripura: Raju Acharjee <[email protected]>,

Sikkim: Raju Chhetri <[email protected]>; Chattisgarh: Pooja Sharma <[email protected]>;

West Bengal: Nilesh Maity <[email protected]>, Damodar Maity <[email protected]> (IIT Kharag-

pur), Kartick Ghanta <[email protected]> (NIT Durgapur), Debabrata Bera <[email protected]>

(JU), Tapan Si <[email protected]>

This science news magazine is published by Mr. T. K. Naskar on behalf of Mr. Debashis Roy, from8A Creek Lane, Kolkata – 700014, WB, India (registered office: 57/1 Keshab Chandra Sen St. 2ndFloor, Kolkata-9), and printed by him at Ashok Lithographing Co., 128 Keshab Chandra Sen St.,Kolkata-700009. Contact: E-mail: [email protected]

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