Low awareness of past SARS-CoV-2 infection in healthy adults

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic challenges governments worldwide to balance appropriate virus control measures and their societal and economic consequences. These control measures include the identification, isolation and testing of potentially infected individuals. As this relies on an individuals awareness of infection, we investigated the extent to which healthy adults suspected having had COVID-19, and how COVID-19 suspicion and symptoms relate to antibodies indicative of a past infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods and findingsFor this cross-sectional study, individuals donating plasma anywhere in the Netherlands between May 11th and 18th were screened for total SARS-CoV-2 antibodies using ELISA and invited to participate in an online questionnaire about COVID-19-related symptoms and awareness. Antibody and questionnaire data were complete for 3,676 individuals, including 239 (6.5%) that tested positive for SARS-CoV-2 antibodies. Here, we show that a 38% of the individuals that tested positive for SARS-CoV-2 antibodies reported having had no or only very mild symptoms at any time during the peak of the epidemic. The loss of taste and/or smell in particular was significantly associated with seropositivity, independent of age and sex. Forty-eight percent of antibody-positive persons did not suspect having had COVID-19, in spite of most of them reporting symptoms. ConclusionsAwareness of infection was low among individuals that tested positive for SARS-CoV-2 antibodies, even at the peak of the epidemic. Improved awareness and recognition of COVID-19 symptoms and tracing of asymptomatic contacts is crucial to halting SARS-CoV-2 transmission.

Afucosylated immunoglobulin G responses are a hallmark of enveloped virus infections and show an exacerbated phenotype in COVID-19

IgG antibodies are crucial for protection against invading pathogens. A highly conserved N-linked glycan within the IgG-Fc-tail, essential for IgG function, shows variable composition in humans. Afucosylated IgG variants are already used in anti-cancer therapeutic antibodies for their elevated binding and killing activity through Fc receptors (Fc{gamma}RIIIa). Here, we report that afucosylated IgG which are of minor abundance in humans ([~]6% of total IgG) are specifically formed against surface epitopes of enveloped viruses after natural infections or immunization with attenuated viruses, while protein subunit immunization does not elicit this low fucose response. This can give beneficial strong responses, but can also go awry, resulting in a cytokine-storm and immune-mediated pathologies. In the case of COVID-19, the critically ill show aggravated afucosylated-IgG responses against the viral spike protein. In contrast, those clearing the infection unaided show higher fucosylation levels of the anti-spike protein IgG. Our findings indicate antibody glycosylation as a potential factor in inflammation and protection in enveloped virus infections including COVID-19.