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ISARIC (International Severe Acute Respiratory and emerging Infections Consortium) partnerships and outbreak preparedness initiatives enabled the rapid launch of standardised clinical data collection on COVID-19 in Jan 2020. Extensive global participation has resulted in a large, standardised collection of comprehensive clinical data from hundreds of sites across dozens of countries. Data are analysed regularly and reported publicly to inform patient care and public health response. This report, our 17th report, is a part of a series published over the past 2 years. Data have been entered for 800,459 individuals from 1701 partner institutions and networks across 60 countries. The comprehensive analyses detailed in this report includes hospitalised individuals of all ages for whom data collection occurred between 30 January 2020 and up to and including 5 January 2022, AND who have laboratory-confirmed SARS-COV-2 infection or clinically diagnosed COVID-19. For the 699,014 cases who meet eligibility criteria for this report, selected findings include: O_LImedian age of 58 years, with an approximately equal (50/50) male:female sex distribution C_LIO_LI29% of the cohort are at least 70 years of age, whereas 4% are 0-19 years of age C_LIO_LIthe most common symptom combination in this hospitalised cohort is shortness of breath, cough, and history of fever, which has remained constant over time C_LIO_LIthe five most common symptoms at admission were shortness of breath, cough, history of fever, fatigue/malaise, and altered consciousness/confusion, which is unchanged from the previous reports C_LIO_LIage-associated differences in symptoms are evident, including the frequency of altered consciousness increasing with age, and fever, respiratory and constitutional symptoms being present mostly in those 40 years and above C_LIO_LI16% of patients with relevant data available were admitted at some point during their illness into an intensive care unit (ICU), which is slightly lower than previously reported (19%) C_LIO_LIantibiotic agents were used in 35% of patients for whom relevant data are available (669,630), a significant reduction from our previous reports (80%) which reflects a shifting proportion of data contributed by different institutions; in ICU/HDU admitted patients with data available (50,560), 91% received antibiotics C_LIO_LIuse of corticosteroids was reported in 24% of all patients for whom data were available (677,012); in ICU/HDU admitted patients with data available (50,646), 69% received corticosteroids C_LIO_LIoutcomes are known for 632,518 patients and the overall estimated case fatality ratio (CFR) is 23.9% (95%CI 23.8-24.1), rising to 37.1% (95%CI 36.8-37.4) for patients who were admitted to ICU/HDU, demonstrating worse outcomes in those with the most severe disease C_LI To access previous versions of ISARIC COVID-19 Clinical Data Report please use the link below: https://isaric.org/research/covid-19-clinical-research-resources/evidence-reports/
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BackgroundSevere COVID-19 can manifest in rapid decompensation and respiratory failure with elevated inflammatory markers. This presentation is consistent with cytokine release syndrome in chimeric antigen receptor T cell therapy, for which IL-6 blockade is approved treatment. MethodsWe assessed effectiveness and safety of IL-6 blockade with tocilizumab in a single-center cohort of patients with COVID-19 requiring mechanical ventilation. The primary endpoint was survival probability post-intubation; secondary analyses included an ordinal illness severity scale integrating superinfections. Outcomes in patients who received tocilizumab compared to tocilizumab-untreated controls were evaluated using multivariable Cox regression with propensity score inverse probability weighting (IPTW). Findings154 patients were included, of whom 78 received tocilizumab and 76 did not. Median follow-up was 47 days (range 28-67). Baseline characteristics were similar between groups, although tocilizumab-treated patients were younger (mean 55 vs. 60 years), less likely to have chronic pulmonary disease (10% vs. 28%), and had lower D-dimer values at time of intubation (median 2.4 vs. 6.5 mg/dL). In IPTW-adjusted models, tocilizumab was associated with a 45% reduction in hazard of death [hazard ratio 0.55 (95% CI 0.33, 0.90)] and improved status on the ordinal outcome scale [odds ratio per 1-level increase: 0.59 (0.36, 0.95)]. Though tocilizumab was associated with an increased proportion of patients with superinfections (54% vs. 26%; p<0.001), there was no difference in 28-day case fatality rate among tocilizumab-treated patients with versus without superinfection [22% vs. 15%; p=0.42]. InterpretationIn this cohort of mechanically ventilated COVID-19 patients, tocilizumab was associated with a decreased likelihood of death despite higher superinfection occurrence. Randomized controlled trials are urgently needed to confirm these findings. KEY POINTSO_ST_ABSQuestionC_ST_ABSCan therapy with the IL-6 receptor antagonist tocilizumab improve outcomes in patients with severe COVID-19 illness requiring mechanical ventilation? FindingsIn this observational, controlled study of 154 patients, receipt of tocilizumab was associated with a 45% reduction in the hazard of death, despite twice the frequency of superinfection (54% vs 26%), both of which were statistically significant findings. MeaningTocilizumab therapy may improve survival in patients with COVID-19 illness requiring mechanical ventilation. These results can inform clinical practice pending the results of randomized clinical trials.
