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 .
Testing of symptomatic persons for infection with SARS-CoV-2 is increasingly used in different countries. To collect information to understand the causes of the COVID-19 pandemic , we propose two types of case-control studies that can be carried out jointly in test-settings for symptomatic persons. The first, the test-negative case-control design (TND) is the easiest to implement ; it only demands collecting information about potential risk factors for COVID-19 from the tested symptomatic persons . The second, standard case-control studies (CC) with population controls, requires the collection of data on one or more population controls for each person who is tested in the test facilities, so that test-positives and test-negatives can each be compared with population controls . We first summarize the TND and explain how to add it to large-scale testing of symptomatic persons . The TND will detect differences in risk factors between symptomatic persons who have COVID-19 (test-positives) and those who have other respiratory infections (test-negatives). However, risk factors with effect sizes of equal magnitude for both COVID-19 and other respiratory infections will not be identified by the TND. Second, we discuss how to add population controls to compare with the test-positives and the test-negatives separately, yielding two additional case-control studies. We describe two different types of population control groups: one composed of accompanying persons to the test facilities , the other drawn from existing country-wide health care databases. We also describe other types of population controls that may be most suitable in other situations. Combining the test-negative design with population controls yields a triangulation approach that distinguishes between exposures that are risk factors for both COVID-19 and other respiratory infections, and exposures that are risk factors for just COVID-19 .
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