Predictors of Nonseroconversion after SARS-CoV-2 Infection

Abstract

C oronavirus disease (COVID-19) is typically diagnosed by reverse transcription PCR (RT-PCR) amplifi cation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA from nasopharyngeal fl uids (1). RT-PCR yields cycle threshold (C t ) values that are inversely correlated with viral loads (2) and thus provide an estimate of the number of SARS-CoV-2 RNA copies in the sample. Serologic assays complement COVID-19 diagnosis by documenting past infections. In most persons, binding and neutralizing antibodies develop within 1-3 weeks after onset of symptoms (3), and titers correlate with disease severity (4).Initial serosurveys identifi ed antibodies in nearly 100% of persons with RT-PCR-confi rmed SARS-CoV-2 infection (5). However, more recent studies have shown that seroconversion rates are surprisingly variable (6-10). For example, a multicenter study from Israel reported that 5% of participants remained seronegative despite a positive test result on a nasal swab specimen (6). In contrast, a seroprevalence study from New York found that 20% of persons with a positive RT-PCR test result did not seroconvert (8). Another study from Germany reported that 85% of confi rmed infected COVID-19 contacts failed to develop antibodies (9). To examine the reasons for these differences, we investigated the relationship between seroconversion and demographic, clinical, and laboratory data in a convenience sample of convalescent persons recruited at the University of Alabama at Birmingham (Birmingham, Alabama, USA) in 2020. The StudyWe studied 72 persons, all of whom had a previous positive RT-PCR test but were symptom-free for >3 weeks before blood was collected for testing (Table ). Only 2 persons (3%) reported no symptoms, whereas 13 (18%) persons reported mild disease, 48 (67%) reported moderate disease, and 9 (12%) reported severe disease (Appendix Table 1, https://wwwnc.cdc.gov/ EID/article/27/9/21-1024-App1.pdf).We tested plasma samples (n = 144) collected at enrollment and follow-up visits for antibodies to the spike protein by using a validated ELISA (Appendix). Only 46 of the 72 participants had detectable IgG responses, IgA responses, or both (Table ); reciprocal endpoint titers ranged from 182 to >312,500 (Appendix Table 2). Analysis of the same samples for receptor-binding domain (RBD) and nucleocapsid (N)

COVID-19 Incidence and hospitalization during the delta surge were inversely related to vaccination coverage among the most populous U.S. Counties

“…While there is evidence that as many as one-third of COVID-19 survivors have no detectable antibodies against SARS-CoV-2, [26] it is likely that those who experienced a sufficiently high viral load during their illness have acquired some degree of natural immunity. In that case, we would expect to observe a protective effect of higher rates of past infection on COVID-19 incidence and hospitalizations, even taking vaccination coverage into account.…”

Immunological and Genetic Investigation of SARS-CoV-2 Reinfection in an Otherwise Healthy, Young Marine Recruit

“…The participant did not develop a detectable humoral response upon the first infection, which explains the negative IgM and IgG response before days 49 and 91, respectively. While this scenario is not common, several reports have shown various percentages of lack of seroconversion after SARS-CoV-2 infection in healthy immunocompetent adults [8][9][10]. Younger age among adults and high Ct values, consistent with the participant's age and the high Ct values at the day 7 infection, has been associated with a higher probability of not developing SARS-CoV-2 antibodies [9].…”

“…While this scenario is not common, several reports have shown various percentages of lack of seroconversion after SARS-CoV-2 infection in healthy immunocompetent adults [8][9][10]. Younger age among adults and high Ct values, consistent with the participant's age and the high Ct values at the day 7 infection, has been associated with a higher probability of not developing SARS-CoV-2 antibodies [9]. A robust humoral immune response was developed after the second infection (day 46), which was characterized by higher viral load and presence of symptoms.…”

COVID-19 Incidence and Hospitalization During the Delta Surge Were Inversely Related to Vaccination Coverage Among the Most Populous U.S. Counties

“…While there is evidence that as many as one-third of COVID-19 suffers have no detectable antibodies against SARS-CoV-2, 26 it is likely that those who experienced a sufficiently high viral load during their illness have acquired some degree of natural immunity. In that case, we would expect to observe a protective effect of higher rates of past infection on COVID-19 incidence and hospitalizations, even taking vaccination coverage into account.…”