In a new preproof study published in the latest issue of the International Journal of Infectious Diseases, a team of researchers explored the association between total immunoglobulin (IgM, IgA, and IgG) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and protective immunity.
Preliminary reports have demonstrated that the anti-SARS-CoV-2 antibody titers in SARS-CoV-2 -infected individuals decline within a year of contracting the infection. This decline in IgG antibody titers is common among males as compared to females and the younger population. Also, an individual’s comorbidity, immunosuppression, and genetic makeup, including blood type may influence this phenomenon.
However, studies have not exhaustively investigated why some relatively healthy individuals do not produce adequate anti-SARS-CoV-2 antibodies or become re-infected in spite of having adequate antibodies.
Several assays have evaluated the short-term persistence of some anti-SARS-CoV-2 antibodies, however, only a few studies have assessed the persistence of total immunoglobulin in SARS-CoV-2-infected individuals for the long term. Over 15 types of serological assays are currently available to demonstrate immune response against a previous SARS-CoV-2 infection or vaccination; however, the assays detecting total immunoglobulin assure maximum sensitivity, such as the Wantai enzyme-linked immunosorbent assay (ELISA).
About the study
In the present cohort study, the researchers, using SARS-CoV-2 Ab ELISA assay, screened blood samples of over 200,000 donors from all five regions in Denmark.
The researchers estimated total anti-SARS-CoV-2 immunoglobulins in the blood samples of all the participating donors and identified risk factors for undetectable antibodies. In addition, they calculated re-infection rates among seropositive and seronegative individuals.
A positive RT-PCR test report confirmed SARS-CoV-2 infection, and the researchers sourced this data from the Danish microbiological database (MiBa) and covered the earliest case in February 2020 until August 2021.
The Wantai assay sensitivity was assessed in a time frame of three months during which the researchers calculated assay sensitivity with 95% confidence intervals (CIs) by bootstrapping 106 times. They used binomial regression analysis to test time-dependent loss of sensitivity and risk factors for a negative Wantai test among RT-PCR-positives.
If any participant had two positive RT-PCR tests within three months, they were considered re-infected. The researchers used Poisson regression to calculate the rate of re-infection.
During the study period, between week 41, 2020, and week 26, 2021, 105,646 non-vaccinated participants were screened using Wantai assay, and 3,806 tested RT-PCR-positive before the blood donation. Among the RT-PCR positives, 3,587 tested antibody-positive with 94.2% sensitivity.
The analysis showed no correlation between positive antibody tests and days since infection. There was no difference in antibody detection during the first and the second wave of coronavirus disease 2019 (COVID-19) pandemic in Denmark, indicating that different SARS-CoV-2 strains did not significantly impact the development of detectable antibodies. Also, there was no association or impact of an individual’s sex, age, comorbidity, blood type, and susceptibility to SARS-CoV-2-infection.
Among the 1,218 sample donors who had taken two or more Wantai tests, nine seroconverted from negative to positive whereas six seroconverted from positive to negative. Re-infection occurred in 0.6% of our study participants and was associated with having a negative antibody test, suggesting that the results could in general be applied to any target population.
The observed re-infection rate with an incidence rate ratio (IRR) of 0.102 with 95% CI was 440/100,000 person-years for seropositives and 4,332/100,000 person-years for seronegatives. Contrastingly, the incidence rate of primary SARS-CoV-2 infection was 4,379/100,000 person-years for seronegatives which at an estimated PCR test specificity of 99.98% indicated that one out of seven re-infections were false RT-PCR-positives initially.
Notably, the analysis could not identify risk factors of a negative antibody test partly due to a large homogeneity in a blood donor population and lack of information on COVID-19 severity.
Over 90% of donors with a positive PCR test also had a positive antibody test and these antibodies did not decline below detectable levels for up to 15 months (long-term) after SARS-CoV-2 infection, thus indicating that the presence of antibodies does not equate to protective immunity.
Further, the risk of re-infection was more than nine times higher among individuals without antibodies when compared with individuals with antibodies. However, more than 60% of the re-infections occurred among individuals with detectable antibodies.
More importantly, study results showed that previously SARS-CoV-2-infected individuals having undetectable antibodies were at approximately the same risk of re-infection as individuals without prior SARS-CoV-2 exposure.