COVID-19 outbreak in Italy: ICU response and patient clinical

characteristics

Prof . Giacomo Grasselli

• Associate Professor of Anesthesiology and Intensive Care Medicine, Dept of Pathophysiology and Transplantation, University of Milan

• Medical Director, Intensive Care Unit «E. Vecla», Ospedale Maggiore Policlinico Foundation, Milan

• Coordinator, Lombardy COVID-19 ICU Network

Was this seasonal flu?

Background

• February 20, 2020: first patient diagnosed with COVID-19 diagnosed in Lombardy

• March 11, 2020: WHO declares the SARS-CoV-2 outbreak as a pandemic

• March 20, 2020: Italy is the second most affected country in the world, after China

• Information on the clinical characteristics of critically ill pts is still limited

• In China the proportion of hospitalized pts requiring ICU care has varied from 5% to 32%

• Knowledge of the baseline characteristics and outcomes of critically ill patients is crucial for Health Care Systems preparedness

Epidemiological situation in Italy

https://www.epicentro.iss.it/en/coronavirus/bollettino/Infografica_3giugno%20ENG.pdf

Epidemiological situation in Italy

https://www.epicentro.iss.it/coronavirus/bollettino/Infografica_26mar%20ENG.pdf

The case of mortality

• Testing strategy (denominator)

• Population age

• Definition of COVID-19 related deaths

Onder et al, JAMA 2020

• February 20: a healthy 30-year-old man with atypical pneumonia unresponsive to treatment is tested positive in Codogno

• February 21: 36 new positive cases, without links to patient 1

• Pre-crisis total regional ICU capacity: 750 beds (2.9% of total hospital beds)

Emergency task force by the Government of Lombardy

Grasselli et al., JAMA March 2020

Grasselli et al., JAMA March 2020

March 20: 1218 pts in ICU

The response in Lombardy

• Increased ICU surge capacity to 1750 ICU beds (250 for non-COVID pts)

• Network of COVID-19 ICUs with central coordination

• Hospital Network reorganized: few hubs for specific diseases

• Stopped elective surgical procedures

• Containment measures

Grasselli et al., JAMA March 2020

Pts admitted to COVID-19 ICUs

• 95 COVID-ICUs in 72

Hospitals

• Total patients: 3963

•Discharged: 1487

•Dead: 1440

•Currently in ICU: 1079

1079

1511

Pts admitted to COVID-19 ICUs

• 95 COVID-ICUs in 72

Hospitals

• Total patients: 4585

•Discharged: 2558

•Dead: 1920

•Currently in ICU: 118

Pts admitted to COVID-19 ICUs

Take-home message: GET READY!!!

• Significant mismatch between the number of pts requiring ICU admission and available ICU beds

• Increase ICU capacity and establish a network of cohorted “COVID-19 ICUs” with central coordination to optimize patient allocation

• Healthcare workers should be trained on the proper use of personal protective equipments

• Define protocols for triage and treatment of COVID-19 patients

Clinical Presentation

• COVID-19 typically presents with systemic and/or respiratorymanifestations

• Common

‒ fever (85-90%)

‒ cough (65-70%)

‒ fatigue (35-40%)

‒ sputum production (30-35%)

‒ shortness of breath (15-20%)

Clinical Presentation

• Attn: some individuals are asymptomatic and can act as carriers!

• LESS COMMON:

myalgia/arthralgia (10-15%)

headaches (10-15%)

sore throat (10-15%)

chills (10-12%)

pleuritic pain

• RARE:

nausea (<10%)

vomiting (<10%)

nasal congestion (<10%)

diarrhea (<5%)

palpitations (<5%)

chest tightness (<5%)

Clinical Presentation

• 81% Mild disease: non-pneumonia and mild

pneumonia.

• 14% Severe disease: dyspnea, RR ≥ 30/min,

blood oxygen saturation (SpO2) ≤ 93%,

PaO2/FiO2 ratio or P/F < 300, and/or lung

infiltrates > 50% within 24 to 48 hours.

• 5% Critical disease: respiratory failure,

septic shock, and/or multiple organ

dysfunction (MOD) or failure (MOF)

Wu Z, McGoogan JM; JAMA 2020

Radiological Presentation

Chest RX: patchy or diffuse asymmetricairspace opacities

Radiological Presentation

Chest CT: ground-glassopacification with or without consolidative abnormalities, with peripheraldistribution, more likely bilateral and atlower lobes

• Data collection: 1591 pts with confirmed SARS-CoV-2 infection admitted to

the Lombardy COVID-19 ICU Network from February 20 to March 18

• Data recorded on an electronic worksheet during daily telephone calls

• Data recorded at ICU admission: age, sex and medical comorbidities; mode

of respiratory support (PEEP, FiO2, PaO2, PaO2/FiO2); use of ECMO and

prone positioning; outcome (dead/alive/still in ICU)Grasselli et al., JAMA April 2020

Demographic data: gender

18%

82%

similarly distributed among age groups

Critically illOverall population

CFR higher in males (15% vs 8%)

Demographic data: age

Median (IQR): 63 (56-70) years

456

570

939

22

0

100

200

300

400

500

600

700

800

900

1000

0-19 20-40 41-60 61-80 81-100

Grasselli et al., JAMA April 2020

Comorbidities

• 68% had at least one comorbidity

• All patients >80 years and 76% of patients >60 years had at least one comorbidity

• Hypertension was the most common comorbidity (49%)

• The second most common comorbidities were cardiovascular disease (21%), other (20%) and hypercholesterolemia (18%)

• Only 4% had a previous history of COPD

Grasselli et al., JAMA April 2020

Respiratory support

• Among 1300 patients with available data, 99% needed respiratory support:

‒88% required mechanical ventilation

‒11% required non-invasive ventilation

• At admission, 27% of patients were treated with prone ventilation (N = 875)

• Only 5 patients (1%) required ECMO (N = 498)

• Relatively high compliance (low Pplat, low ΔP) and high MV

Respiratory supportP

EEP

(cm

H2O

)

0

2

4

6

8

10

12

14

16

18

20

22

PaO

2/F

iO2

(mm

Hg)

50

100

150

200

250

300

350

400

450

500

550

Median: 14 (12-16) mmHg Median 70% Median: 160 (114-220) mmHg N = 999

Not statistically different between ages

Higher in older patients(median difference -10, P=.006)

Higher in younger patients(median difference 7, P=.02)

Grasselli et al., JAMA April 2020

Outcome: mortality

• 920 (58%) of patients were still admitted in ICU

• 256 (16%) were discharged from ICU

• 405 (26%) had died in ICU

ICU mortality

0

10

20

30

40

50

60

70

80

90

100

Allages

00-19yrs

20-40yrs

41-50yrs

51-60yrs

61-70yrs

71-80yrs

81-90yrs

91-100yrs

ICU

de

ath

rat

e w

ith

in d

iffe

ren

t ag

e g

rou

ps

29,4

70,6

00-63 yrs 64-100 yrs

(difference -21 p<.001)

Length of stay in ICU: 9 (6-13) days

Grasselli et al., JAMA April 2020

Outcome: ICU length of stay

N Mean ± SD Median (IQR) Min Max

Deaths 189 (34%) 8.6 ± 5.2 8 (4-12) 0 24

Discharged 173 (31%) 8.3 ± 5.4 8 (4-12) 0 24

Still in ICU 191 (35%) 16.8 ± 5.3 17 (15-20) 1 32

Total 553 11.4 ± 6.6 12 (5-17) 0 32

Pts admitted to ICU until March 8 – outcome on March 23

ICU Hospital

All* Dead in

ICU

Discharged

from ICU

Still in

ICU

Dead in

Hospital

Discharged

from

Hospital

Still in

Hospital

No.

(%)

1715

(100)

836

(49)

865

(50)

14

(1)

915

(53)

673

(39)

127

(7)

ICU Hospital

All* Dead in

ICU

Discharg

ed from

ICU

Still in

ICU

P Dead in

Hospital

Discharg

ed from

Hospital

Still in

Hospita

l

P

Male1398

(81)

700

(50)

688

(49)

10

(1)0.03

763

(55)

534

(38)

101

(7)0.046

Female317

(185)

136

(43)

177

(56)

4

(1)

152

(48)

139

(44)

26

(8)

Age,

median

(IQR), y

64

(56-70)

67.5

(62-73)

59

(52-66)

62

(52-65)

<0.001

**

68

(62-73)

58

(51-64)

62

(55-67)

<0.001

**

**p value for Dead vs Discharge

ICU

All* Dead in ICU Discharged from

ICU

Still in ICU P

Dead vs

Discharged

Comorbidities 594 (55.1) 474 (44.0) 10 (0.9) <0.001

None 574/1652 (34.7) 211 (36.8) 359 (62.5) 4 (0.7) <0.001

Hypertension 890/1703 (52.3) 500 (56.2) 382 (42.9) 8 (0.9) <0.001

Hypercholesterole

mia

302/1652 (18.3) 191 (63.2) 110

(36.4)

1 (0.3) <0.001

Heart diseasea 318/1652 (19.3) 198 (62.3) 117 (36.8) 3 (0.9) <0.001

Diabetes 284/ 1652 (17.2) 182 (64.1) 100 (35.2) 2 (0.7) <0.001

Malignancy 191/1652 (11.6) 113 (59.2) 78 (40.8) 0 (0.0) 0.004

COPD 58/1652 (3.5) 39 (67.2) 19 (32.8) 0 (0.0) 0.007

CKD 52/1652 (3.1) 41 (78.8) 11 (21.2) 0 (0.0) <0.001

Liver diseases 45/1652 (2.7) 19 (42.2) 26 (57.8) 0 (0.0) 0.43

Other diseases 271/1652 (16.4) 141 (52.0) 128 (47.2) 2 (0.7) 0.26

ICU Hospital

All* Dead in

ICU

Discharged

from ICU

Still in

ICU

P

Dead vs

Discharg

ed

Dead in

Hospital

Discharged

from

Hospital

Still in

Hospital

P

Dead vs

Discharged

Time from

onset of

symptoms to

ICU admission

8 (4-11)

(N=1588)

7 (4-10)

(N=769)

8 (5-11)

(N=807)

8.5 (3.5-

10.5)

(N=12)

0.14 7 (4-10)

(N=844)

8 (5-11)

(N=631)

8 (4-11)

(N=113)

0.07

Length of ICU

stay (days)

12 (7-20)

(N=1711)

10 (5-16)

(N=836)

15 (8-24)

(N=861)

76 (74-

80)

(N=14)

<0.001*

*

10 (5-16)

N=(915)

14 (8-22)

(N=669)

33 (18-54)

(N=127)

<0.001**

Length of

Hospital stay

(days)

22 (12-42)

(N=1618)

12 (8-19)

(N=766)

39 (24-

61)

(N=838)

79 (74-

84)

(N=14)

<0.001*

*

13 (8-20)

(N=838)

37 (23-53)

(N=658)

84 (79-88)

(N=122)

<0.001**

Length of MV

(days)

10 (6-16)

(N=1171)

9 (5-15)

(N=787)

12 (7-18)

(N=370)

74 (73-

78)

(N=14)

<0.001*

*

9 (5-15)

(N=812)

11 (7-17)

(N=297)

19.5 (13-

65)

(N=62)

<0.001**

Limitations

• Retrospective study

• Missing data (difficulty to obtain detailed information due to the critical situation in the Region)

• The follow up is still too short compared to the course of the disease

Grasselli et al., JAMA April 2020

Conclusions

• In this case series of critically ill patients admitted to ICUs in Lombardy with

laboratory-confirmed COVID-19:

the majority of patients were older males

a large proportion required mechanical ventilation and relatively high

levels of PEEP

ICU mortality was 26%

Grasselli et al., JAMA April 2020