SARS-CoV-2 and COVID-19 David H. Spach, MD - PowerPoint Presentation

SARS-CoV-2 and COVID-19 David H. Spach, MD
SARS-CoV-2 and COVID-19 David H. Spach, MD

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Professor of Medicine Division of Infectious Diseases University of Washington Last Updated December 7 2020 Gretchen Snoeyenbos Newman MD Senior Fellow Division of Infectious Diseases University of Washington ID: 904365 Download

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Slide1

SARS-CoV-2 and COVID-19

David H. Spach, MDProfessor of MedicineDivision of Infectious DiseasesUniversity of Washington

Last Updated: December 7, 2020

Gretchen Snoeyenbos Newman, MDSenior FellowDivision of Infectious DiseasesUniversity of Washington

Treatment: Tocilizumab

Sarah A. McGuffin, MD MS

Senior Fellow

Division of Infectious Diseases

University of Washington

Slide2

Tocilizumab (

Actemra)

Slide3

Tocilizumab

Medication Class

: Interleukin-6 (IL-6) receptor blockerFDA Approved for: Cytokine release syndrome

Rheumatoid arthritis and other rheumatologic conditionsDose for Cytokine Release SyndromeWeight ≥30 kg: 8 mg/kg IV x 1 dose (max 800 mg)Weight ≤30 kg: 12 mg/kg IV x 1 dose (max 800 mg)Dose for COVID-19Range of doses used in studiesAdverse EffectsInjection site reactionsIncreases in ALT and/or AST levels

Slide4

Rationale for Use of Tocilizumab Persons with COVID-19

Source: Kellum JA, et al, Crit Care

Med. 2017 Mar; 45:438–45.Chen N, et al. Lancet

2020; 395(10223):507-13.Huang C, et al. Lancet 2020;395:497-506.Le RQ, et al. Oncologist. 2018;23:943-7.Elevated levels of inflammatory cytokines, including IL-6 have been associated with increased mortality from ARDS

Patients with COVID-19 have elevated levels of IL-6 and other inflammatory markers consistent with cytokine stormTocilizumab has been effective in treating the cytokine storm associated with CAR-T cell therapy

Slide5

Tocilizumab: Recombinant Humanized Anti-IL6 Receptor Monoclonal Antibody

Illustration: David H. Spach, MD

Mouse Monoclonal Antibody

Humanized Monoclonal Antibody

Mouse variable region

Mouse constant region

Human heavy chain

Human light chain

Complementary Determining Region

Slide6

Tocilizumab (

Actemra)Illustration: David H. Spach, MD

Humanized Murine Monoclonal Antibody IgG1 Subclass

Binds to:

- Soluble IL-6 receptor

- Membrane bound IL-6 receptor

Human heavy chain

Human light chain

Complementary Determining Region

Slide7

IL-6 Signaling via Membrane IL-6 Receptor:

Classic IL-6 Pathway

gp130

Signal Transduction

IL-6

gp130

Recruitment of gp130

gp130

Host Cell

Membrane

IL-6 Receptor

Slide8

IL-6 Signaling via Membrane IL-6 Receptor:

Classic IL-6 Pathway – Image Series (1 of 3)

IL-6

gp130

Host Cell

Membrane

IL-6 Receptor

Slide9

IL-6 Signaling via Membrane IL-6 Receptor:

Classic IL-6 Pathway – Image Series (2 of 3)

IL-6

gp130

Recruitment of gp130

gp130

Host Cell

Membrane

IL-6 Receptor

Slide10

IL-6 Signaling via Membrane IL-6 Receptor:

Classic IL-6 Pathway – Image Series (3 of 3)

gp130

Signal Transduction

IL-6

gp130

Recruitment of gp130

gp130

Host Cell

Membrane

IL-6 Receptor

Slide11

IL-6 Signaling via Membrane IL-6 Receptor:

Trans Signaling IL-6 Pathway

IL-6

ADAM-10

ADAM-17

gp130

Signal Transduction

Soluble

IL-6 Receptor

IL-6 and Soluble IL-6 Receptor Complex

gp130

Slide12

IL-6 Signaling via Membrane IL-6 Receptor:

Trans Signaling IL-6 Pathway – Image Series (1 of 4)

ADAM-10

ADAM-17

Soluble

IL-6 Receptor

Slide13

IL-6 Signaling via Membrane IL-6 Receptor:

Trans Signaling IL-6 Pathway – Image Series (2 of 4)

IL-6

ADAM-10

ADAM-17

Soluble

IL-6 Receptor

IL-6 and Soluble IL-6 Receptor Complex

Slide14

IL-6 Signaling via Membrane IL-6 Receptor:

Trans Signaling IL-6 Pathway – Image Series (3 of 4)

IL-6

ADAM-10

ADAM-17

Soluble

IL-6 Receptor

IL-6 and Soluble IL-6 Receptor Complex

gp130

Slide15

IL-6 Signaling via Membrane IL-6 Receptor:

Trans Signaling IL-6 Pathway – Image Series (4 of 4)

IL-6

ADAM-10

ADAM-17

gp130

Signal Transduction

Soluble

IL-6 Receptor

IL-6 and Soluble IL-6 Receptor Complex

gp130

Slide16

Tocilizumab Binds to Both Soluble and Membrane IL-6 Receptors

gp130

Soluble

IL-6 Receptor

Membrane

IL-6 Receptor

gp130

Tocilizumab

Slide17

Tocilizumab and Inhibition of IL-6 Signaling

IL-6

Soluble

IL-6 Receptor

Signal Transduction

gp130

gp130

Membrane Bound IL-6 Receptor: Classic Pathway

Tocilizumab

Soluble IL-6 Receptor: Trans Signaling Pathway

Tocilizumab

Signal Transduction

gp130

Membrane

IL-6 Receptor

Slide18

Efficacy of Tocilizumab in Patients Hospitalized with Covid-19

Published Data

— Randomized Clinical Trial

Source: Stone JH, et al. N

Engl

J Med. 2020 Oct 21.

doi

: 10.1056/NEJMoa2028836. Online ahead of print

Slide19

Efficacy of Tocilizumab in Patients Hospitalized with COVID-19

Study DesignSource: Stone JH, et al. N Engl J Med. 2020 Oct 21. doi: 10.1056/NEJMoa2028836. Online ahead of print

Study Design

Background

: Randomized, d

ouble-blind, placebo-controlled, multicenter trial conducted at 7 hospitals in Boston between April 20 and June 15, 2020 to evaluate the effectiveness of tocilizumab in patients with severe COVID-19 infection.

Location:

Boston, Massachusetts, USA

Inclusion

Criteria (n = 242)

-

SARS-CoV-2 infection confirmed by nasopharyngeal swab PCR or serum IgM antibody assay

- At least 2 of following: fever <72 hours,

pulmonary infiltrates, or need for supplemental oxygen

- At least 1 of following: CRP >50 mg/L, ferritin >500 ng/mL, D-dimer >1000 ng/mL, or LDH >250 U/L

- Age 19-85 years

Exclusion

Criteria

-

Supplemental oxygen at a rate >10 L/min, recent treatment with biologic agents or small molecule immunosuppressive therapy, if they were receiving other immunosuppressive therapy that the investigator believed placed them at higher risk for an infection, or if they had had diverticulitis. Randomization: 2:1Primary Endpoint- Intubation (or death for patients who died before intubation)

Slide20

Efficacy of Tocilizumab in Patients Hospitalized with COVID-19

Study Design*Source: Stone JH, et al. N Engl J Med. 2020 Oct 21. doi: 10.1056/NEJMoa2028836. Online ahead of print

Tocilizumab

(single dose)

(8 mg per kilogram of body weight administered intravenously, not to exceed 800 mg)

Placebo

or

Treatment Groups*

Concomitant treatments allowed: Antiviral therapy, hydroxychloroquine, and glucocorticoids

2x

1x

Slide21

Efficacy of Tocilizumab in Patients Hospitalized with COVID-19

Baseline CharacteristicsSource: Stone JH, et al. N Engl J Med. 2020 Oct 21. doi: 10.1056/NEJMoa2028836. Online ahead of print

Baseline Characteristics

Tocilizumab (n = 161)

Placebo (n = 82)

Median age (IQR) –

yr

61.6 (46.4–69.7)

56.5 (44.7–67.8)

Age >65 years – no. (%)

60 (37)

22 (27)

Male sex — no. (%)

96 (60)

45 (55)

Race or ethnic group – no. (%) †

American Indian or Alaska Native

1 (1)

0

Asian

7 (4)2 (2)Black24 (15)16 (20)Native Hawaiian or Pacific Islander01 (1)White71 (44)33 (40)

Other35 (22)15 (18)

Unknown

23 (14)15 (18)Hispanic or Latino ethnic group — no. (%)†Hispanic or Latino70 (43)39 (48)Hispanic or Latino84 (52)35 (43)Unknown7 (4)8 (10) † Race and ethnic group were reported by the patients.

Slide22

Efficacy of Tocilizumab in Patients Hospitalized with COVID-19

Baseline CharacteristicsSource: Stone JH, et al. N Engl J Med. 2020 Oct 21. doi: 10.1056/NEJMoa2028836. Online ahead of print

Baseline Characteristics

Tocilizumab (n = 161)

Placebo (n = 82)

Median BMI (IQR)

29.9 (26.0–34.2)

30.2 (25.7–33.8)

BMI ≥30 — no. (%)

80 (50))

42 (51)

Median time symptom onset to randomization (IQR) — days

9.0 (6.0–13.0)

10.0 (7.0–13.0)

Hypertension — no. (%)

80 (50)

38 (46)

Heart failure — no. (%)

17 (11)

7 (9)

Heart failure — no. (%)15 (9)6 (7)Chronic obstructive pulmonary disorder — no. (%)15 (9)7 (9)Asthma — no. (%)15 (9)7 (9)Smoking status — no. (%) Current smoker

7 (4) 0

Former smoker46 (29)

26 (32)Lifelong nonsmoker99 (61) 48 (59)Unknown9 (6) 8 (10)Diabetes— no. (%)45 (28)30 (37)Chronic kidney disease — no. (%)29 (18) 13 (16)History of cancer — no. (%) 22 (14) 8 (10)

Slide23

Efficacy of Tocilizumab in Patients Hospitalized with COVID-19

Baseline CharacteristicsSource: Stone JH, et al. N Engl J Med. 2020 Oct 21. doi: 10.1056/NEJMoa2028836. Online ahead of print

7-Point Ordinal Scale

1: Discharged (or "ready for discharge" as evidenced by normal body temperature and respiratory rate, and stable oxygen saturation on ambient air or ≤ 2L supplemental oxygen)

2: Non-ICU hospital ward (or "ready for hospital ward") not requiring supplemental oxygen

3:

Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen

4:

ICU or non-ICU hospital ward, requiring non-invasive ventilation or high-flow oxygen

5:

ICU, requiring intubation and mechanical ventilation

6:

ICU, requiring ECMO or mechanical ventilation and additional organ support (e.g. vasopressors, renal replacement therapy)

7: Death

Slide24

Efficacy of Tocilizumab in Patients Hospitalized with COVID-19

Baseline CharacteristicsSource: Stone JH, et al. N Engl J Med. 2020 Oct 21. doi: 10.1056/NEJMoa2028836. Online ahead of print

Baseline Characteristics

Tocilizumab (n=161)

Placebo (n=82)

Ordinal scale score — no. (%)

2

23 (14)

15 (18)

3

133 (83)

61 (74)

4

5 (3)

5 (6)

5

0

1 (1)

Median laboratory values (IQR)

Absolute lymphocyte count — cells/mm

31040 (700–1400)1030 (680–1360)C-reactive protein level — mg/liter116.0 (67.1–190.6)

94.3 (58.4–142.0)Ferritin level — ng/ml

723 (413–1212)

686 (382–1228)d-Dimer level — ng/ml857 (536–1695)980 (500–1739)Lactate dehydrogenase level — U/liter351 (287–420)324 (290–395)Serum interleukin-6 level — pg/ml 23.6 (14.0–49.9)25.4 (14.6–40.3)Erythrocyte sedimentation rate — mm/hr61 (42–90)63 (42–87)Troponin level — ng/liter8 (6–22)9 (6–24)NT-proBNP level — pg/ml110 (50–438)93 (33–431)

Procalcitonin level — ng/ml

0.2 (0.1–0.4)

0.2 (0.1–0.3)

Slide25

Outcome

No. of Patients

with Event within

28 Days

Percentage of Patients

with Event (95% CI)†

Hazard Ratio

(95% CI)

Log-Rank

P Value‡

Day 14

Day 28

Primary outcome: mechanical ventilation or death

Tocilizumab

17

9.9 (6.2–15.7)

10.6 (6.7–16.6)

0.83 (0.38–1.81)

0.64

Placebo

10

10.0 (5.1–18.9)

12.5 (6.9–22.0)Secondary outcome: clinical worsening on ordinal scale§Tocilizumab3118.0 (12.9–24.9) 19.3 (14.0–26.2)1.11 (0.59–2.10) 0.73Placebo1414.9 (8.7–24.7)17.4 (10.7–27.7)Tertiary outcome: mechanical ventilation

Tocilizumab11

6.8 (3.6–11.4) 6.8 (3.6–11.4)

0.65 (0.26–1.62)-

Placebo

8

10.0 (4.6–17.7)

10.0 (4.6–17.7)

Tertiary outcome: death

-

Tocilizumab

9

4.4 (2.1–8.9)

5.6 (3.0–10.5)

1.52 (0.41–5.61)

Placebo

3

1.3 (0.2–8.7)

3.8 (1.2–11.3)

Efficacy of Tocilizumab in Patients Hospitalized with COVID-19

Outcomes

Source: Stone JH, et al. N

Engl

J Med. 2020 Oct 21.

doi

: 10.1056/NEJMoa2028836. Online ahead of print† Percentages were estimated from the Kaplan–Meier curve. ‡ P values are not reported for tertiary outcomes.

§ Def

ined as an increase in score by at least 1 point if receiving supplemental oxygen at baseline or at least 2 points otherwise

Slide26

Efficacy of Tocilizumab in Patients Hospitalized with COVID-19

OutcomesPrimary Outcome: Mechanical Ventilation or DeathSource: Stone JH, et al. N

Engl J Med. 2020 Oct 21. doi: 10.1056/NEJMoa2028836. Online ahead of print

Slide27

Efficacy of Tocilizumab in Patients Hospitalized with COVID-19

OutcomesSource: Stone JH, et al. N Engl J Med. 2020 Oct 21. doi: 10.1056/NEJMoa2028836. Online ahead of print

Outcome

No. of Patients

with Event within

28 Days

Percentage of Patients

with Event (95% CI)†

Median No. of Days to Event (95% CI)

Hazard Ratio

(95% CI)

Log-Rank

P Value‡

Day 14

Day 28

Secondary outcome: discontinuation of supplemental O

2

Tocilizumab

114

75.4 (67.9–82.2)

82.6 (75.9–88.4)

5.0 (3.8–7.6)0.94 (0.67–1.30)

0.69Placebo5678.8 (68.3–87.7)84.9 (75.2–92.2)4.9 (3.8–7.8)Tertiary outcome: clinical improvement on ordinal scale§Tocilizumab14786.3 (80.6–91.1)91.3 (86.3–95.1)6.0 (5.0–6.0)1.06 (0.80–1.41)Placebo7381.5 (72.4–89.0)88.9 (81.0–94.5)5.0 (4.0–7.0)

Tertiary outcome: initial discharge

Tocilizumab

147

86.3 (80.6–91.1)

91.3 (86.3–95.0)

6.0 (4.0–7.0)

1.08 (0.81–1.43)

Placebo

72

81.5 (72.4–89.0)

88.9 (81.0–94.5)

6.0 (5.0–6.0)

†Percentages were estimated from the Kaplan–Meier curve. ‡ P values are not reported for tertiary outcomes;

§

Def

ined as an increase in score by >2 points

Slide28

Efficacy of Tocilizumab in Patients Hospitalized with COVID-19

OutcomesSource: Stone JH, et al. N Engl J Med. 2020 Oct 21. doi: 10.1056/NEJMoa2028836. Online ahead of print

*Patients who did not receive supplemental oxygen were assigned a value of 0. Patients who died before discontinuation of supplemental oxygen were assigned a value equal to the number of days from when supplemental oxygen began until the end of the 28-day follow-up period.

† The median and IQR for duration of mechanical ventilation were estimated from Kaplan–Meier curves generated within patients who received mechanical ventilation (11 in the tocilizumab group and 8 in the placebo group). Data for patients who died without discontinuation of mechanical ventilation were censored at 28 days.

Outcome

Tocilizumab

(n = 161)

Placebo

(n = 81)

Relative Risk

Median duration of receipt of supplemental oxygen (IQR) — days*

4.0 (1.8–11.6)

3.9 (1.1–9.2)

-

Median duration of mechanical ventilation (IQR) — days†

15.0 (12.6–NR)

27.9 (16.3–NR)

-

Admission to ICU or death — %

15.9

15.80.97 (0.50-1.88)

Slide29

Efficacy of Tocilizumab in Patients Hospitalized with COVID-19

Adverse EffectsSource: Stone JH, et al. N Engl J Med. 2020 Oct 21. doi: 10.1056/NEJMoa2028836. Online ahead of print

Event

Tocilizumab

(n = 161)

Placebo

(n = 81)

P value

Death, no. (%)

9 (5.6)

4 (4.9)†

0.81

Hypersensitivity reaction to infusion

2 (1.2)

2 (2.4)

0.52

Infection of grade ≥3

13 (8.1)

14 (17.1)

0.03

Grade 3Grade 4Myocardial infarction0

1 (1.2)

0.15Deep venous thrombosis

2 (1.2)3 (3.7)0.18Pulmonary embolism2 (1.2)2 (2.4)0.47Stroke 2 (1.2)00.31Seizure0 1 (1.2) 0.13Arterial ischemia1 (0.6)00.49Gastrointestinal perforation00-Demyelinating disorder

00-

Bleeding

01 (1.2)

0.15

† One patient who died was intubated before receiving placebo and was excluded from the modified intention-to-treat population but included in the safety population.

Slide30

Efficacy of Tocilizumab in Patients Hospitalized with COVID-19

Adverse EffectsSource: Stone JH, et al. N Engl J Med. 2020 Oct 21. doi: 10.1056/NEJMoa2028836. Online ahead of print

Event

Tocilizumab

(n = 161)

Placebo

(n = 81)

P value

Elevated liver-function values

ALT, grade ≥3

8 (5.0)

4 (4.9)

0.99

Grade 3

8 (5.0)

4 (4.9)

Grade 4

0

0

AST, grade ≥3

6 (3.7)3 (3.7)0.99Grade 36 (3.7)

2 (2.4)

Grade 40

1 (1.2)Neutropenia, grade ≥322 (13.7)1 (1.2)0.002Grade 321 (13.0)1 (1.2)Grade 41 (0.6)0Thrombocytopenia1 (0.6)00.51Grade 31 (0.6)0Grade 400Other

21 (13.0)

14 (17.1)0.15

Slide31

Efficacy of Tocilizumab in Patients Hospitalized with COVID-19

Authors’ Conclusions

Conclusions:

In this randomized, double-blind, placebo-controlled trial, we did not find any efficacy of interleukin-6 receptor blockade for the treatment of hospitalized patients with Covid-19.”

Source: Stone JH, et al. N

Engl

J Med. 2020 Oct 21.

doi

: 10.1056/NEJMoa2028836. Online ahead of print

Slide32

Tocilizumab Treatment of 15 Patients with COVID‐19:

A Single Center Experience (China)

Source: Luo P, et al.  J Med

Virol

. 2020;92:814-8.

Published Data —

Retrospective Case Series

Slide33

Tocilizumab Treatment of 15 Patients with COVID‐19: Study Design

Study Design

Background

:

Retrospective case series study of 15 patients with variable severity of COVID-19 disease who received one or more doses of tocilizumab, with or without methylprednisolone during January 27– March 5, 2020 in China

Setting

: Wuhan, China

Inclusion

Criteria for Patients

-

Infected with SARS-CoV-2/COVID-19

- Received tocilizumab treatment

Treatment

- 1 or more doses of intravenous tocilizumab: 80-600 mg per dose*

- Option to receive methylprednisolone^

Source: Luo P, et al.  J Med

Virol

. 2020;92:814-8.

*5 patients received >1 dose of tocilizumab (3 received 2 doses and 2 received 3 doses)

^8 of 15 received

methylprednisolone (range 4 to 7 days) of treatment

Slide34

Tocilizumab Treatment of 15 Patients with COVID‐19:

Patient CharacteristicsSource: Luo P, et al.  J Med Virol. 2020;92:814-8.

Baseline Characteristic

Patients

(n = 15)

Age (median, range), years

73 (62 – 80)

Male, Female

12, 3

Clinical Status*

Moderate

2

Severe

6

Critical

7

Comorbidities (HTN, CVD, DM)

10

Also received methylprednisolone

8

*Defined by guidance Diagnosis and Treatment of Pneumonia Infected by Novel Coronavirus issued by the National Health Commission of China

Slide35

Tocilizumab Treatment of 15 Patients with COVID‐19:

ResultsSource: Luo P, et al.  J Med Virol. 2020;92:814-8.3 of 7 critically ill patients progressed to death despite therapy

2 patients experienced worsening of their illnessCRP levels decreased in 14 of 15 patientsIL-6 levels remained persistently elevated in 1 seriously ill and 4 critically ill patients, including the 3 who died

IL-6 levels initially spiked after tocilizumab and then decreased in all patients experiencing clinical stabilization or improvement

Slide36

Tocilizumab Treatment of 15 Patients with COVID‐19: Study Design

: Authors’ Conclusions

Source: Luo P, et al.  J Med Virol. 2020;92:814-8.

Conclusions

: “Tocilizumab appears to be an effective treatment option in COVID-19 patients with a risk of cytokine storms. And for these critically ill patients with elevated IL-6, repeated dose of the Tocilizumab is recommended.”

Slide37

Tocilizumab Treatment of 21 Patients with Severe COVID-19 (China)

Published Data —

Retrospective Analysis

Source: Xu X, et al. Proc Natl

Acad

Sci U S A. 2020:117:10970-5.

Slide38

Tocilizumab Treatment of 21 Patients with Severe COVID-19:

Design

Study Design

Background

:

Uncontrolled, observational study to evaluate the effectiveness of intravenous tocilizumab in patients with severe COVID-19 in Wuhan, China during February 5 – February 14, 2020.

Inclusion

Criteria (n = 21)

-

PCR-confirmed SARS-CoV-2

infection on throat swab

-

Severe COVID-19

(any of following):

RR ≥ 30/min

or

SpO

2

≤93% on room air or PaO2/FiO2 ≤300 mm Hg- Critical COVID-19 (any of following): Mechanical ventilation or shock or multiorgan failure plus ICU admitTreatment - Tocilizumab: 400 mg intravenous infusion x 1 plus- Standard of care at hospital: lopinavir, methylprednisolone, supportive careSource: Xu X, et al. Proc Natl Acad Sci U S A. 2020:117:10970-5.

Slide39

Tocilizumab Treatment of 21 Patients with Severe COVID-19:

Baseline Characteristics

Baseline Characteristic*

Patients

(n = 21)

Age,

mean

± SD (range

)

56.8 ± 16.5 (25-88)

Male

, n

(%)

18 (85.7)

Comorbidity

Hypertension,

n

(%)

9 (42.9)

Diabetes, n (%)5 (23.8)Illness SeveritySevere, n (%)17 (81)Critical, n (%)4 (19)Mechanical ventilation2 (10)Pretreatment IL-6, mean ± SD* 132.38 ± 278.54 pg/mLSource: Xu X, et al. Proc Natl Acad Sci U S A. 2020:117:10970-5.

Slide40

Tocilizumab Treatment of 21 Patients with Severe COVID-19:

Baseline Characteristics

Laboratory Markers of Inflammation Before

and After Tocilizumab (mean ± SD)

Before

Day 1 after Tocilizumab

Day 5 after Tocilizumab

WBC

(x 10

9

/L)

6.30 ± 2.77

8.05 ± 4.39

5.25 ± 2.11

Lymphocyte

percentage

15.52 ± 8.89

11.78 ± 11.36

22.62 ± 13.48

CRP

75.06 ± 66.80

38.13 ± 54.21

2.72 ±3.60

Procalcitonin, ng/mL0.33 ± 0.780.21 ± 0.35

0.12 ± 0.15

Interleukin-6,

pg

/mL

153.44 ± 296.63

129.18 ± 131.79

274.90 ± 414.08

Source: Xu X, et al. Proc Natl

Acad

Sci U S A. 2020:117:10970-5.

Slide41

Tocilizumab Treatment of 21 Patients with Severe COVID-19: Results

Fever in all patients resolved on day 1 after tocilizumab infusion21 of 21 (100%) experienced improvement in SpO2 and/or ventilator requirements15 of 20 (75%) had lower O2 intake <5 days after tocilizumab21 of 21 (100%) discharged from hospitalMean hospitalization time 15.1 ± 5.8 days after tocilizumab

Source: Xu X, et al. Proc Natl

Acad Sci U S A. 2020:117:10970-5.

Slide42

Tocilizumab Treatment of 21 Patients with Severe COVID-19 Infection:

Authors’ Conclusions

Conclusion

: “Preliminary data show that tocilizumab, which improved the clinical outcome immediately in severe and critical COVID-19 patients, is an effective treatment to reduce mortality.”

Source: Xu X, et al. Proc Natl

Acad

Sci U S A. 2020:117:10970-5.

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