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medrxiv; 2020.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2020.08.10.20171561


Background The 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 individual's 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 findings 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. Conclusions Awareness 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.

medrxiv; 2020.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2020.06.17.20133793


SARS-CoV-2 infections often cause only mild disease that may evoke relatively low antibody titers compared to patients admitted to hospitals. Generally, total antibody bridging assays combine good sensitivity with high selectivity. Therefore, we developed sensitive total antibody bridging assays for detection of SARS-CoV-2 antibodies to the receptor-binding domain (RBD) and nucleocapsid protein (NP), in addition to conventional isotype-specific assays. Antibody kinetics was assessed in PCR-confirmed hospitalized COVID-19 patients (n=41) and three populations of patients with COVID-19 symptoms not requiring hospital admission: PCR-confirmed convalescent plasmapheresis donors (n=182), PCR-confirmed hospital care workers (n=47), and a group of longitudinally sampled symptomatic individuals highly suspect of COVID-19 (n=14). In non-hospitalized patients, the antibody response to RBD is weaker but follows similar kinetics as has been observed in hospitalized patients. Across populations, the RBD bridging assay identified most patients correctly as seropositive. In 11/14 of the COVID-19-suspect cases, seroconversion in the RBD bridging assay could be demonstrated before day 12; NP antibodies emerged less consistently. Furthermore, we demonstrated the feasibility of finger prick sampling for antibody detection against SARS-CoV-2 using these assays. In conclusion, the developed bridging assays reliably detect SARS-CoV-2 antibodies in hospitalized and non-hospitalized patients, and are therefore well-suited to conduct seroprevalence studies.

biorxiv; 2020.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2020.06.18.159202


Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the current coronavirus disease 2019 (COVID-19) pandemic. Understanding both the immunological processes providing specific immunity and potential immunopathology underlying the pathogenesis of this disease may provide valuable insights for potential therapeutic interventions. Here, we quantified SARS-CoV-2 specific immune responses in patients with different clinical courses. Compared to individuals with a mild clinical presentation, CD4+ T cell responses were qualitatively impaired in critically ill patients. Strikingly, however, in these patients the specific IgG antibody response was remarkably strong. The observed disparate T and B cell responses could be indicative of a deregulated immune response in critically ill COVID-19 patients.