gms | German Medical Science

Introduction: Assessing infection/occurred transmission in studies of pathogens, which can cause asymptomatic or mild symptoms on one side but sometimes trigger immune response without infection, can be challenging. We aimed to compare definitions of infection based on serology with/without (rapid) test or symptoms only.

Methods: We used data from a prospective household transmission study conducted during the dominance of the Omicron variant of SARS-CoV-2. This study was embedded in the digital research platform DigiHero including persons from over 90,000 households from 13 federal states in Germany. We started the study in June 2022 by asking DigiHero participants to contact the study center when the first person in the household was tested positive for SARS-CoV-2. In this case, we asked the participants to obtain dry blood spots (DBS) from each household member in the beginning and 6-8 weeks later and fill in a symptoms diary for each household member. Systematic testing of family members was not part of the study, but when participants used the (rapid) tests, they could record them. DBS were analysed for anti-spike protein antibody and for anti-nucleocapsid protein antibody and quantitative titers were obtained (both titers were evaluated). We compared the following definitions of infection: seroconversion or 1.5-fold titer increase or a positive SARS-CoV-2 test (internal gold standard, L1), seroconversion or 1.5-fold titer increase (no test information, L2), seroconversion only (L3), common definition of acute respiratory infection (ARI) (S1), any respiratory symptoms or not meeting acute ARI threshold (S2). For each definition, we calculated the attack rate (i.e. proportion infected among all household members). For calculation of sensitivity and specificity of the other definitions, we used the L1 definition as reference.

Results: 457 households with 1191 household members participated, among them 662 persons from 262 households provided complete data and samples. Based on the applied definitions, we obtained attack rates of 58% (95%CI: 53-62%) for L1, 56% (51-61%) for Lab2, 32% (28-37%) for L3, 48% (43-53%) for S1, and 73% (69-77%) for S2. 13% (9-17%) of infections were asymptomatic, and in further 41% (36-46%) the symptoms were so mild that they did not meet the definition of ARI. 20% (16-24%) of individuals with ARI displayed no serologic indication of SARS-CoV-2 infection.

Sensitivity / specificity were 98%/100% for L2 vs. L1, 56%/100% L3 vs. L1, 66%/77% for S1 vs. L1, and 88%/46% S2 vs. L1. Children were on average less symptomatic (less often ARI and lower symptom scores): the sensitivity/specificity of S1 (compared to L1) was 70%/84% among adults and 43%/61% among children. In 96% (95% CI 92-99%) of household members with a positive test, there was a seroconversion or >1.5-fold increase of the titer. Conversely, in 63% (58-68%) of household members with seroconversion or >1.5-fold titer increase and who conducted the test, the test was positive.

Conclusion: Definitions based only on symptoms of ARI underestimated the attack rate by nearly 20% and likely included 20% of cases resulting from other infections. SARS-CoV-2 tests were not systematically applied in this study, but it also appears that when using serology, the benefit of additional testing for detection of infections was limited.

The authors declare that they have no competing interests.

The authors declare that a positive ethics committee vote has been obtained.