Analysis proposals for test-negative design and matched case-control studies during widespread testing of symptomatic persons for SARS-Cov-2.

An increasing number of countries expands testing of symptomatic persons for infection with SARS-CoV-2. It is important to consider efficient ways to collect information that will allow to understand the COVID-19 pandemic. We propose two types of case-control studies that can be carried out in test-settings for symptomatic persons. The first, the test-negative case-control design (TND) is the easiest to set up, since all symptomatic persons will be tested; it only demands collecting information from these persons, some which will be collected routinely. The second, standard matched case-control studies (CC) demands that one person who accompanies the symptomatic persons to the test facility is asked the same information. We first summarize the TND and explain how to add it to large-scale testing of persons with signs and symptoms. The TND shows differences in risk factors between symptomatic persons with COVID-19 and persons with other respiratory infections. Factors that are risk factors of equal magnitude for both COVID-19 and other respiratory infections will not be identified by the TND. Second, we discuss how to add standard matched case-control studies (separately for SARS-CoV-2 test-positives and test-negatives) by asking accompanying persons to the test facilities to become controls. Those case-control studies give a contrast between COVID-19 patients and matched persons from the general population. We give suggestions for other types of population controls. Such studies distinguish between exposures that are risk factors for both COVID-19 and other respiratory infections, and exposures that are risk factors for just COVID-19 or just for other respiratory infections. Incorporating the test-negative design into on-going testing efforts is useful in itself, but it would be more useful with the addition of the matched case-control designs.