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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
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COVID-19 outbreak in Italy: ICU response and patient ... › Library › Content › Global... · Clinical Presentation •81% Mild disease: non-pneumonia and mild pneumonia. •14%

Jun 30, 2020

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Page 1: COVID-19 outbreak in Italy: ICU response and patient ... › Library › Content › Global... · Clinical Presentation •81% Mild disease: non-pneumonia and mild pneumonia. •14%

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

Page 2: COVID-19 outbreak in Italy: ICU response and patient ... › Library › Content › Global... · Clinical Presentation •81% Mild disease: non-pneumonia and mild pneumonia. •14%

Was this seasonal flu?

Page 3: COVID-19 outbreak in Italy: ICU response and patient ... › Library › Content › Global... · Clinical Presentation •81% Mild disease: non-pneumonia and mild pneumonia. •14%

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

Page 4: COVID-19 outbreak in Italy: ICU response and patient ... › Library › Content › Global... · Clinical Presentation •81% Mild disease: non-pneumonia and mild pneumonia. •14%

Epidemiological situation in Italy

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

Page 5: COVID-19 outbreak in Italy: ICU response and patient ... › Library › Content › Global... · Clinical Presentation •81% Mild disease: non-pneumonia and mild pneumonia. •14%

Epidemiological situation in Italy

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

Page 6: COVID-19 outbreak in Italy: ICU response and patient ... › Library › Content › Global... · Clinical Presentation •81% Mild disease: non-pneumonia and mild pneumonia. •14%

The case of mortality

• Testing strategy (denominator)

• Population age

• Definition of COVID-19 related deaths

Onder et al, JAMA 2020

Page 7: COVID-19 outbreak in Italy: ICU response and patient ... › Library › Content › Global... · Clinical Presentation •81% Mild disease: non-pneumonia and mild pneumonia. •14%

• 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

Page 8: COVID-19 outbreak in Italy: ICU response and patient ... › Library › Content › Global... · Clinical Presentation •81% Mild disease: non-pneumonia and mild pneumonia. •14%

Grasselli et al., JAMA March 2020

March 20: 1218 pts in ICU

Page 9: COVID-19 outbreak in Italy: ICU response and patient ... › Library › Content › Global... · Clinical Presentation •81% Mild disease: non-pneumonia and mild pneumonia. •14%

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

Page 10: COVID-19 outbreak in Italy: ICU response and patient ... › Library › Content › Global... · Clinical Presentation •81% Mild disease: non-pneumonia and mild pneumonia. •14%

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

Page 11: COVID-19 outbreak in Italy: ICU response and patient ... › Library › Content › Global... · Clinical Presentation •81% Mild disease: non-pneumonia and mild pneumonia. •14%

Pts admitted to COVID-19 ICUs

• 95 COVID-ICUs in 72

Hospitals

• Total patients: 4585

•Discharged: 2558

•Dead: 1920

•Currently in ICU: 118

Page 12: COVID-19 outbreak in Italy: ICU response and patient ... › Library › Content › Global... · Clinical Presentation •81% Mild disease: non-pneumonia and mild pneumonia. •14%

Pts admitted to COVID-19 ICUs

Page 13: COVID-19 outbreak in Italy: ICU response and patient ... › Library › Content › Global... · Clinical Presentation •81% Mild disease: non-pneumonia and mild pneumonia. •14%

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

Page 14: COVID-19 outbreak in Italy: ICU response and patient ... › Library › Content › Global... · Clinical Presentation •81% Mild disease: non-pneumonia and mild pneumonia. •14%

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%)

Page 15: COVID-19 outbreak in Italy: ICU response and patient ... › Library › Content › Global... · Clinical Presentation •81% Mild disease: non-pneumonia and mild pneumonia. •14%

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%)

Page 16: COVID-19 outbreak in Italy: ICU response and patient ... › Library › Content › Global... · Clinical Presentation •81% Mild disease: non-pneumonia and mild pneumonia. •14%

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

Page 17: COVID-19 outbreak in Italy: ICU response and patient ... › Library › Content › Global... · Clinical Presentation •81% Mild disease: non-pneumonia and mild pneumonia. •14%

Radiological Presentation

Chest RX: patchy or diffuse asymmetricairspace opacities

Page 18: COVID-19 outbreak in Italy: ICU response and patient ... › Library › Content › Global... · Clinical Presentation •81% Mild disease: non-pneumonia and mild pneumonia. •14%

Radiological Presentation

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

Page 19: COVID-19 outbreak in Italy: ICU response and patient ... › Library › Content › Global... · Clinical Presentation •81% Mild disease: non-pneumonia and mild pneumonia. •14%

• 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

Page 20: COVID-19 outbreak in Italy: ICU response and patient ... › Library › Content › Global... · Clinical Presentation •81% Mild disease: non-pneumonia and mild pneumonia. •14%

Demographic data: gender

18%

82%

similarly distributed among age groups

Critically illOverall population

CFR higher in males (15% vs 8%)

Page 21: COVID-19 outbreak in Italy: ICU response and patient ... › Library › Content › Global... · Clinical Presentation •81% Mild disease: non-pneumonia and mild pneumonia. •14%

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

Page 22: COVID-19 outbreak in Italy: ICU response and patient ... › Library › Content › Global... · Clinical Presentation •81% Mild disease: non-pneumonia and mild pneumonia. •14%

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

Page 23: COVID-19 outbreak in Italy: ICU response and patient ... › Library › Content › Global... · Clinical Presentation •81% Mild disease: non-pneumonia and mild pneumonia. •14%

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

Page 24: COVID-19 outbreak in Italy: ICU response and patient ... › Library › Content › Global... · Clinical Presentation •81% Mild disease: non-pneumonia and mild pneumonia. •14%

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

Page 25: COVID-19 outbreak in Italy: ICU response and patient ... › Library › Content › Global... · Clinical Presentation •81% Mild disease: non-pneumonia and mild pneumonia. •14%

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

Page 26: COVID-19 outbreak in Italy: ICU response and patient ... › Library › Content › Global... · Clinical Presentation •81% Mild disease: non-pneumonia and mild pneumonia. •14%

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

Page 27: COVID-19 outbreak in Italy: ICU response and patient ... › Library › Content › Global... · Clinical Presentation •81% Mild disease: non-pneumonia and mild pneumonia. •14%

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)

Page 28: COVID-19 outbreak in Italy: ICU response and patient ... › Library › Content › Global... · Clinical Presentation •81% Mild disease: non-pneumonia and mild pneumonia. •14%

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

Page 29: COVID-19 outbreak in Italy: ICU response and patient ... › Library › Content › Global... · Clinical Presentation •81% Mild disease: non-pneumonia and mild pneumonia. •14%

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

Page 30: COVID-19 outbreak in Italy: ICU response and patient ... › Library › Content › Global... · Clinical Presentation •81% Mild disease: non-pneumonia and mild pneumonia. •14%

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**

Page 31: COVID-19 outbreak in Italy: ICU response and patient ... › Library › Content › Global... · Clinical Presentation •81% Mild disease: non-pneumonia and mild pneumonia. •14%

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

Page 32: COVID-19 outbreak in Italy: ICU response and patient ... › Library › Content › Global... · Clinical Presentation •81% Mild disease: non-pneumonia and mild pneumonia. •14%

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