Association Between Early Treatment With Tocilizumab and Mortality Among Critically Ill Patients With COVID-19

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Abstract

Therapies that improve survival in critically ill patients with coronavirus disease 2019 (COVID-19) are needed. Tocilizumab, a monoclonal antibody against the interleukin 6 receptor, may counteract the inflammatory cytokine release syndrome in patients with severe COVID-19 illness.

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Most cited references 34

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Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study

Xiaobo Yang, Yuan Yu, Jiqian Xu … (2020)

Summary Background An ongoing outbreak of pneumonia associated with the severe acute respiratory coronavirus 2 (SARS-CoV-2) started in December, 2019, in Wuhan, China. Information about critically ill patients with SARS-CoV-2 infection is scarce. We aimed to describe the clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia. Methods In this single-centered, retrospective, observational study, we enrolled 52 critically ill adult patients with SARS-CoV-2 pneumonia who were admitted to the intensive care unit (ICU) of Wuhan Jin Yin-tan hospital (Wuhan, China) between late December, 2019, and Jan 26, 2020. Demographic data, symptoms, laboratory values, comorbidities, treatments, and clinical outcomes were all collected. Data were compared between survivors and non-survivors. The primary outcome was 28-day mortality, as of Feb 9, 2020. Secondary outcomes included incidence of SARS-CoV-2-related acute respiratory distress syndrome (ARDS) and the proportion of patients requiring mechanical ventilation. Findings Of 710 patients with SARS-CoV-2 pneumonia, 52 critically ill adult patients were included. The mean age of the 52 patients was 59·7 (SD 13·3) years, 35 (67%) were men, 21 (40%) had chronic illness, 51 (98%) had fever. 32 (61·5%) patients had died at 28 days, and the median duration from admission to the intensive care unit (ICU) to death was 7 (IQR 3–11) days for non-survivors. Compared with survivors, non-survivors were older (64·6 years [11·2] vs 51·9 years [12·9]), more likely to develop ARDS (26 [81%] patients vs 9 [45%] patients), and more likely to receive mechanical ventilation (30 [94%] patients vs 7 [35%] patients), either invasively or non-invasively. Most patients had organ function damage, including 35 (67%) with ARDS, 15 (29%) with acute kidney injury, 12 (23%) with cardiac injury, 15 (29%) with liver dysfunction, and one (2%) with pneumothorax. 37 (71%) patients required mechanical ventilation. Hospital-acquired infection occurred in seven (13·5%) patients. Interpretation The mortality of critically ill patients with SARS-CoV-2 pneumonia is considerable. The survival time of the non-survivors is likely to be within 1–2 weeks after ICU admission. Older patients (>65 years) with comorbidities and ARDS are at increased risk of death. The severity of SARS-CoV-2 pneumonia poses great strain on critical care resources in hospitals, especially if they are not adequately staffed or resourced. Funding None.

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COVID-19: consider cytokine storm syndromes and immunosuppression

Puja Mehta, Daniel McAuley, Michael Brown … (2020)

As of March 12, 2020, coronavirus disease 2019 (COVID-19) has been confirmed in 125 048 people worldwide, carrying a mortality of approximately 3·7%, 1 compared with a mortality rate of less than 1% from influenza. There is an urgent need for effective treatment. Current focus has been on the development of novel therapeutics, including antivirals and vaccines. Accumulating evidence suggests that a subgroup of patients with severe COVID-19 might have a cytokine storm syndrome. We recommend identification and treatment of hyperinflammation using existing, approved therapies with proven safety profiles to address the immediate need to reduce the rising mortality. Current management of COVID-19 is supportive, and respiratory failure from acute respiratory distress syndrome (ARDS) is the leading cause of mortality. 2 Secondary haemophagocytic lymphohistiocytosis (sHLH) is an under-recognised, hyperinflammatory syndrome characterised by a fulminant and fatal hypercytokinaemia with multiorgan failure. In adults, sHLH is most commonly triggered by viral infections 3 and occurs in 3·7–4·3% of sepsis cases. 4 Cardinal features of sHLH include unremitting fever, cytopenias, and hyperferritinaemia; pulmonary involvement (including ARDS) occurs in approximately 50% of patients. 5 A cytokine profile resembling sHLH is associated with COVID-19 disease severity, characterised by increased interleukin (IL)-2, IL-7, granulocyte-colony stimulating factor, interferon-γ inducible protein 10, monocyte chemoattractant protein 1, macrophage inflammatory protein 1-α, and tumour necrosis factor-α. 6 Predictors of fatality from a recent retrospective, multicentre study of 150 confirmed COVID-19 cases in Wuhan, China, included elevated ferritin (mean 1297·6 ng/ml in non-survivors vs 614·0 ng/ml in survivors; p 39·4°C 49 Organomegaly None 0 Hepatomegaly or splenomegaly 23 Hepatomegaly and splenomegaly 38 Number of cytopenias * One lineage 0 Two lineages 24 Three lineages 34 Triglycerides (mmol/L) 4·0 mmol/L 64 Fibrinogen (g/L) >2·5 g/L 0 ≤2·5 g/L 30 Ferritin ng/ml 6000 ng/ml 50 Serum aspartate aminotransferase <30 IU/L 0 ≥30 IU/L 19 Haemophagocytosis on bone marrow aspirate No 0 Yes 35 Known immunosuppression † No 0 Yes 18 The Hscore 11 generates a probability for the presence of secondary HLH. HScores greater than 169 are 93% sensitive and 86% specific for HLH. Note that bone marrow haemophagocytosis is not mandatory for a diagnosis of HLH. HScores can be calculated using an online HScore calculator. 11 HLH=haemophagocytic lymphohistiocytosis. * Defined as either haemoglobin concentration of 9·2 g/dL or less (≤5·71 mmol/L), a white blood cell count of 5000 white blood cells per mm3 or less, or platelet count of 110 000 platelets per mm3 or less, or all of these criteria combined. † HIV positive or receiving longterm immunosuppressive therapy (ie, glucocorticoids, cyclosporine, azathioprine).

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Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area

Safiya Richardson, Jamie Hirsch, Mangala Narasimhan … (2020)

There is limited information describing the presenting characteristics and outcomes of US patients requiring hospitalization for coronavirus disease 2019 (COVID-19).

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Author and article information

Journal

Title: JAMA Internal Medicine

Abbreviated Title: JAMA Intern Med

Publisher: American Medical Association (AMA)

ISSN (Print): 2168-6106

Publication date (Electronic): October 20 2020

Affiliations

[1 ]Division of Renal Medicine, Brigham and Women’s Hospital, Boston, Massachusetts

[2 ]Departments of Medicine and Neurology, Brigham and Women’s Hospital, Boston, Massachusetts

[3 ]Division of Cardiology, Department of Medicine, University of Michigan, Ann Arbor

[4 ]Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York

[5 ]Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York

[6 ]Department of Emergency Medicine, Icahn School of Medicine at Mount Sinai, New York, New York

[7 ]Department of Medicine, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, New York

[8 ]Department of Internal Medicine, Hackensack Meridian School of Medicine at Seton Hall, Nutley, New Jersey

[9 ]Department of Internal Medicine, Hackensack Meridian Health, Hackensack University Medical Center, Hackensack, New Jersey

[10 ]Renal-Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia

[11 ]Divison of Pulmonary and Critical Care Medicine, Department of Medicine, Weill Cornell Medicine Center, New York, New York

[12 ]Department of Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey

[13 ]Department of Medicine, Rush University Medical Center, Chicago, Illinois

[14 ]Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus Aurora, Aurora

[15 ]Center for Translational Metabolism and Health, Institute for Public Health and Medicine, Division of Nephrology and Hypertension, Northwestern University Feinberg School of Medicine, Chicago, Illinois

[16 ]Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Medical College of Wisconsin, Milwaukee

[17 ]Department of Medicine, Division of Infectious Diseases, New Jersey Medical School, Rutgers University, Newark

[18 ]Division of Critical Care, Cooper University Health Care, Camden, New Jersey

[19 ]Division of Nephrology, Kings County Hospital Center, New York City Health and Hospital Corporation, Brooklyn, New York

[20 ]Division of Pulmonary, Critical Care and Sleep Medicine, Tufts Medical Center, Boston, Massachusetts

[21 ]Division of Nephrology, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania

[22 ]Department of Nephrology, Ochsner Health System, New Orleans, Louisiana

[23 ]Ochsner Clinical School, University of Queensland, Brisbane, Australia

[24 ]Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts

[25 ]Division of Nephrology, Johns Hopkins School of Medicine, Baltimore, Maryland

[26 ]Division of Nephrology, Department of Medicine, NYU (New York University) Langone Medical Center, New York, New York

[27 ]Division of Nephrology, Cook County Health, Chicago, Illinois

[28 ]Department of Medicine, Indiana University School of Medicine/Indiana University Health, Indianapolis

[29 ]ProMedica Research, ProMedica Toledo Hospital, Toledo, Ohio

[30 ]University of Vermont Larner College of Medicine, Burlington

[31 ]Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor

[32 ]Department of Learning Health Sciences, University of Michigan Medical School, Ann Arbor

[33 ]Institute for Healthcare Policy & Innovation, University of Michigan, Ann Arbor

[34 ]Division of Pulmonary, Critical Care, and Sleep Medicine, University of Miami Miller School of Medicine, Miami, Florida

[35 ]Division of Critical Care Medicine, Albert Einstein College of Medicine, Bronx, New York

[36 ]Department of Anesthesiology, University of Colorado School of Medicine, Aurora

[37 ]Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, Tennessee

[38 ]Department of Epidemiology and Biostatistics, Harvard T. H. Chan School of Public Health, Boston, Massachusetts

[39 ]Harvard-MIT (Massachusetts Institute of Technology) Program in Health Sciences and Technology, Boston, Massachusetts

Article

DOI: 10.1001/jamainternmed.2020.6252

PMC ID: 7577201

PubMed ID: 33080002

SO-VID: bae90843-f22d-4629-af03-6effe6882638

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Association Between Early Treatment With Tocilizumab and Mortality Among Critically Ill Patients With COVID-19

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Novel Coronavirus Disease COVID-19

Most cited references 34

Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study

COVID-19: consider cytokine storm syndromes and immunosuppression

Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area

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