Abstract
The methods to ascertain cases of an emerging infectious disease are typically biased toward cases with more severe disease, which can bias the average infection-severity profile. Here, we conducted a systematic review to extract information on disease severity among index cases and secondary cases identified by contact tracing of index cases for COVID-19. We identified 38 studies to extract information on measures of clinical severity. The proportion of index cases with fever was 43% higher than for secondary cases. The proportion of symptomatic, hospitalized, and fatal illnesses among index cases were 12%, 126%, and 179% higher than for secondary cases, respectively. We developed a statistical model to utilize the severity difference, and estimate 55% of index cases were missed in Wuhan, China. Information on disease severity in secondary cases should be less susceptible to ascertainment bias and could inform estimates of disease severity and the proportion of missed index cases.
Highlights
The methods to ascertain cases of an emerging infectious disease are typically biased toward cases with more severe disease, which can bias the average infection-severity profile
We assessed how the presence of different types of symptoms, case severity, symptom status, hospitalization status and fatality status could differ between index and secondary cases in contact tracing studies for COVID-19
For these measures of severity, we found that index cases were generally more severe secondary cases
Summary
The methods to ascertain cases of an emerging infectious disease are typically biased toward cases with more severe disease, which can bias the average infection-severity profile. One possible approach to avoid this selection bias, and obtain improved disease severity, is to focus on the severity of secondary cases that are prospectively identified, such as contact tracing studies with household transmission study as a special case[13]. In these studies, index cases ascertained either by presenting for medical attention or reporting symptoms are not likely to be representative of all infections, because milder cases would have a lower probability of being ascertained. We conducted a simulation to determine the sample size requirement of household transmission studies to characterize the severity of emerging infectious diseases
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