SARS-CoV-2 spike antigen-specific B cell and antibody responses in pre-vaccination period COVID-19 convalescent males and females with or without post-covid condition

Abstract

BackgroundFollowing SARS-CoV-2 infection a significant proportion of convalescent individuals develop the post-COVID condition (PCC) that is characterized by wide spectrum of symptoms encompassing various organs. Even though the underlying pathophysiology of PCC is not known, detection of viral transcripts and antigens in tissues other than lungs raise the possibility that PCC may be a consequence of aberrant immune response to the viral antigens. To test this hypothesis, we evaluated B cell and antibody responses to the SARS-CoV-2 antigens in PCC patients who experienced mild COVID-19 disease during the pre-vaccination period of COVID-19 pandemic.MethodsThe study subjects included unvaccinated male and female subjects who developed PCC or not (No-PCC) after clearing RT-PCR confirmed mild COVID-19 infection. SARS-CoV-2 D614G and omicron RBD specific B cell subsets in peripheral circulation were assessed by flow cytometry. IgG, IgG3 and IgA antibody titers toward RBD, spike and nucleocapsid antigens in the plasma were evaluated by ELISA.ResultsThe frequency of the B cells specific to D614G-RBD were comparable in convalescent groups with and without PCC in both males and females. Notably, in females with PCC, the anti-D614G RBD specific double negative (IgD-CD27-) B cells showed significant correlation with the number of symptoms at acute of infection. Anti-spike antibody responses were also higher at 3 months post-infection in females who developed PCC, but not in the male PCC group. On the other hand, the male PCC group also showed consistently high anti-RBD IgG responses compared to all other groups.ConclusionsThe antibody responses to the spike protein, but not the anti-RBD B cell responses diverge between convalescent males and females who develop PCC. Our findings also suggest that sex-related factors may also be involved in the development of PCC via modulating antibody responses to the SARS-CoV-2 antigens.

Anti-Nucleocapsid and Anti-Spike Antibody Trajectories in People with Post-Covid Condition versus Acute-Only Infections: Results from the Virus Watch Prospective Cohort Study

“…Our findings broadly corroborate smaller community-based serological studies of early pandemic infections, which found evidence of stronger antibody responses in people with PCC compared to those with acute infections only (11,12), (13). The elevated, persistent anti-N response in people with PCC is suggestive of a stronger response to the acute infection, which could be driven by higher viral loads, a pro-inflammatory state and/or persistent viral antigens prompting the continued production of these antibodies (11).…”

“…Two-year postinfection follow-up of 31 people with PCC and 31 acute-only controls found that markers of inflammation and anti-S and anti-N antibodies were elevated in people with PCC, but normalised to the levels of the acute-only group after 12-24 months (11); participants were infected prior to the availability of COVID-19 vaccines, but later post-vaccination antibody responses appeared to be similar between groups. Similarly, a cohort of people with mild SARS-CoV-2 infections who were unvaccinated at the time of infection found that anti-S levels were higher at three months in women with PCC compared to those with acute infections only, and that levels of anti-N antibody were similar between both groups (12). A further cohort of 51 community cases followed-up twice for 5-6 months post-infection found persistently elevated anti-S and anti-N antibody levels in people with greater post-infectious symptomatology (13).…”