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Anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence is used to estimate the proportion of individuals within a population previously infected, to track viral transmission, and to monitor naturally and vaccine-induced immune protection. However, in sub-Saharan African settings, antibodies induced by higher exposure to pathogens may increase unspecific seroreactivity to SARS-CoV-2 antigens, resulting in false positive responses. To investigate the level and type of unspecific seroreactivitiy to SARS-CoV-2 in Africa, we measured immunoglobulin G (IgG), IgA, and IgM to a broad panel of antigens from different pathogens by Luminex in 602 plasma samples from African and European subjects differing in coronavirus disease 2019, malaria, and other exposures. Seroreactivity to SARS-CoV-2 antigens was higher in prepandemic African than in European samples and positively correlated with antibodies against human coronaviruses, helminths, protozoa, and especially Plasmodium falciparum. African subjects presented higher levels of autoantibodies, a surrogate of polyreactivity, which correlated with P. falciparum and SARS-CoV-2 antibodies. Finally, we found an improved sensitivity in the IgG assay in African samples when using urea as a chaotropic agent. In conclusion, our data suggest that polyreactive antibodies induced mostly by malaria are important mediators of the unspecific anti-SARS-CoV-2 responses, and that the use of dissociating agents in immunoassays could be useful for more accurate estimates of SARS-CoV-2 seroprevalence in African settings., (© 2024 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC.)

We evaluated the kinetics of antibody responses to Two years into the COVID-19 pandemic and 1 year after the start of vaccination rollout, the world faced a peak of cases associated with the highly contagious Omicron variant of concern (VoC) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) and nucleocapsid (N) antigens over five cross-sectional visits (January-November 2021), and the determinants of pre-booster immunoglobulin levels, in a prospective cohort of vaccinated primary health care workers in Catalonia, Spain. Antibodies against S antigens after a full primary vaccination course, mostly with BNT162b2, decreased steadily over time and were higher in pre-exposed (n = 247) than naïve (n = 200) individuals, but seropositivity was maintained at 100% (100% IgG, 95.5% IgA, 30.6% IgM) up to 319 days after the first dose. Antibody binding to variants of concern was highly maintained for IgG compared to wild type but significantly reduced for IgA and IgM, particularly for Beta and Gamma. Factors significantly associated with longer-term antibodies included age, sex, occupation, smoking, adverse reaction to vaccination, levels of pre-vaccination SARS-CoV-2 antibodies, interval between disease onset and vaccination, hospitalization, oxygen supply, post COVID and symptomatology. Earlier morning vaccination hours were associated with higher IgG responses in pre-exposed participants. Symptomatic breakthroughs occurred in 9/447 (2.01%) individuals, all among naïve (9/200, 4.5%) and generally boosted antibody responses. Additionally, an increase in IgA and/or IgM seropositivity to variants, and N seroconversion at later time points (6.54%), indicated asymptomatic breakthrough infections, even among pre-exposed. Seropositivity remained highly stable over almost a year after vaccination. However, gradually waning of anti-S IgGs that correlate with neutralizing activity, coupled to evidence of an increase in breakthrough infections during the Delta and Omicron predominance, provides a rationale for booster immunization., (© 2022 John Wiley & Sons Ltd.)

Antibodies to the nucleocapsid (N) antigen are suggested to be used to monitor infections after COVID-19 vaccination, as first generation subunit vaccines are based on the spike (S) protein. We used multiplex immunoassays to simultaneously measure antibody responses to different fragments of the SARS-CoV-2 S and N antigens for evaluating the immunogenicity of the mRNA-1273 (Spykevax) and the BNT162b2 (Comirnaty) vaccines in 445 health care workers. We report a >4-fold increase post-vaccination of IgG levels to the full length (N FL) and C-terminus of N (N CT) in 5.2% and 18.0% of individuals, respectively, and of IgA in 3.6% (N FL) and 9.0% (N CT) of them. The increase in IgG levels and avidity was more pronounced after Spykevax than Comirnaty vaccination (36.2% vs 13.1% for N CT, and 10.6% vs 3.7% for N FL). Data suggest the induction of cross-reactive antibodies against the N CT region after administering these S-based vaccines, and this should be taken into account when using N seropositivity to detect breakthroughs., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)