Clinical course and mortality risk of severe COVID-19

Abstract

Several published reports of early clinical descriptions of coronavirus disease 2019 (COVID-19) have emerged from Hubei province in China, and many more will come. These early reports, typically simple descriptive case series of patients hospitalised with COVID-19 (mostly with pneumonia), provide valuable information on the more severe end of the disease spectrum. We tend to hear more about the most severe cases in the early stages of a new disease, as these are the ones first brought to the public’s attention and are associated with deaths. However, it is important to bear in mind that the current best estimate is that about 81% of people with COVID-19 have mild disease and never require hospitalisation. These cases have not yet featured much in published clinical descriptions. In The Lancet, Fei Zhou and colleagues provide further insight into the clinical course and mortality risk for adults with COVID-19 severe enough to require hospitalisation. They report findings from 191 patients with COVID-19 from Wuhan during the first month of the outbreak, and follow them through to discharge (n=137) or death (n=54). The follow-up until discharge or death is a point of difference from other case series to date. Their cohort had many characteristics in common with other reports—a median age of 56·0 years (IQR 46·0–67·0), a high percentage (62%) of men, and nearly half (48%) of patients with comorbidities. In-hospital death was associated with, on admission, older age (odds ratio 1·10, 95% CI 1·03–1·17; p=0·0043), a higher Sequential Organ Failure Assessment score (5·65, 2·61–12·23; p<0·0001), and blood d-dimer greater than 1 μg/mL (18·42, 2·64–128·55; p=0·0033), findings known to be associated with severe pneumonia. The study also presents early data on changes in clinical and laboratory findings over time, which could help clinicians to identify patients who progress to more severe disease. In-hospital mortality was high (28%), much higher than in other reports that had incomplete follow-up data, and was very high among the 32 patients requiring invasive mechanical ventilation, of whom 31 (97%) died. This might reflect a higher proportion of patients admitted with severe disease in the early stages of the outbreak. In another report from Wuhan, mortality was 62% among critically ill patients with COVID-19 and 81% among those requiring mechanical ventilation. While the world awaits further information from other locations, including from outside China, the current message is that mortality is high among the minority of people with COVID-19 who get severe disease. The cohort design of this study provides excellent front-line information about mortality risk. It is essential for readers to understand that this truly is a retrospective cohort design, even if it might appear otherwise at first. Careful consideration of the design is essential to understanding the findings. The authors were able to collect a wealth of information from admission to discharge on many of the earliest known cases of coronavirus in the world. By identifying this large group of patients united by their disease and tracking them to these endpoints, the authors have provided us with insight into risk factors for in-hospital death. Even though their cohort does not include the censored observations of patients admitted during the study timeframe but not discharged by the end timepoint, these results can still be considerably useful for epidemiological description of the disease in terms of person-level risk. By excluding incomplete observations, it is possible that the reported mortality rate is biased to appear larger than it is, as data from those patients who were not discharged by the end timepoint were not included. However, as a true population at risk of mortality, these patients are representative of the earliest onset of COVID-19. Excluding patients