In this cross-sectional study we investigated a large, heterogenous population of affected individuals following a school COVID-19 outbreak, with the aim of assessing the potential correlation between various clinical characteristics and the long-term persistence of SARS nCoV-2 IgG.
Our findings confirmed previous reports indicating the relationship between the degree of IgG- positivity and PCR-positivity10. Our results indicate high sensitivity of 80% at 7 months following the outbreak, adding to current data of up to 100% sensitivity when taken after 20 days11 and roughly 4.5 months12 after symptom onset.
Interestingly, we found that the titer of IgG also correlated with PCR results. The small percentage of PCR-positive and serology-negative individuals may reflect a low virion inoculum, which also markedly reduced the development of a humoral response. In patients with positive serology, the inoculum probably increased after PCR testing, thereby allowing the immune system to mount a humoral response.
Age was unequivocally correlated with IgG titers: children and adolescents’ mean IgG levels were 150% higher than of adults > 18 years on average. Young age was once again correlated with IgG levels in a multi-variant linear regression model (ß=-0.12). Though age-dependency has been already suggested by Yang et al13, our data’s significance is due to its ability to take into consideration other clinical variables that may confound this correlation, including symptoms which is lower in younger population. This may be the reason that the correlation found in our study was milder than in Yang’s study (r=-0.45 up to 18 years and r = 0.24 in adults).
Previous studies14 demonstrated more robust humoral response (higher IgG titers) at up to 6 months in severe symptomatic cases, findings confirmed by our study. We’ve also shown, for the first time, correlations of specific symptoms with IgG levels; mainly fever, but also weakness and rash. Interestingly, diabetes and immune deficiency were also positively correlated with high titers, a fact which requires further investigation.
Interestingly, the main difference between seropositive and seronegative individuals (with PCR-positivity) was their exposure to another sick individual at the household. The only other clinical parameter differed between the groups was fever, a fact that may suggest it as potential marker for immune response, and complements previous data indicating overall symptoms as associated with humoral response15.
As portrayed in our study, the outbreak was much more prominent in students’ households than the staff’s (43.9–53% of affected individual/s at home vs 27.3–38.3%, respectively), a phenomenon that is probably under-expressed due to the lower proportion of affected students among study population, compared to staff members. This finding is well correlated with previous data from a large-scale South-Korean tracing-study indicating highest infection rates in households with index patients aged 10–19 years16. This phenomenon may be explained by the high rate of asymptomatic infection among young people17 that may lead to lower suspicion and lesser measures of isolation kept in school and/or households prior to testing.
Our study has several strengths; mainly its relative large size that enabled enough power to evaluate discrete clinical characteristics’ influence on IgG titers. Secondly, the fact that the majority of confirmed PCR-positive cases in this outbreak were included in this study enabled a more accurate epidemiological view after a long period of time. The fact that PCR-positive cases unrelated to this concrete eruption have been excluded, has assisted in evaluation of temporal links between symptoms and humoral response, with reduced effect of confounders.
This trial holds several limitations; the main one is its retrospective and self-reporting manner that can result in recall bias. Others are lacking in objective data such as RT-PCR cycle-times and medical documentation including physical examination by a doctor, vitals and other lab work.