Increasing the Efficiency of a National Laboratory Response to COVID-19: a Nationwide Multicenter Evaluation of 47 Commercial SARS-CoV-2 Immunoassays by 41 Laboratories.

In response to the worldwide pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the subsequent antibody tests that flooded the market, a nationwide collaborative approach in the Netherlands was employed. Forty-one Dutch laboratories joined forces and shared their evaluation data to allow for the evaluation of a quantity of serological assays for SARS-CoV-2 that exceeds the capacity of each individual laboratory. As of April 2020, these performance data had been aggregated and shared in regularly updated reports with other laboratories, Dutch government, public health organizations, and the public. This frequently updated overview of assay performance increased the efficiency of our national laboratory response, supporting laboratories in their choice and implementation of assays. Aggregated performance data for 47 immunoassays for SARS-CoV-2 showed that none of the evaluated immunoassays that detect only IgM or IgA met the diagnostic criteria, indicating that they are not suitable for diagnosing acute infections. For the detection of IgG, only the Biozek Corona virus COVID rapid test, Euroimmun SARS-CoV-2 IgG, and Wantai SARS-CoV-2 antibody (Ab) ELISA met predefined performance criteria in hospitalized patients where samples were collected 14 days post-onset of symptoms (DPO), while for patients with mild or asymptomatic infections, only the Wantai SARS-CoV-2 Ab ELISA met the predefined performance criteria if samples were collected 14 days postonset. Here, we describe this unique nationwide collaboration during the onset of the COVID-19 pandemic; the collected data and their results are an example of what can be accomplished when forces are joined during a public health crisis.

Convalescent Plasma in a Patient with Protracted COVID-19 and Secondary Hypogammaglobulinemia Due to Chronic Lymphocytic Leukemia: Buying Time to Develop Immunity?

It is not exactly clear yet which type of immune response prevails to accomplish viral clearance in coronavirus disease 2019 (COVID-19). Studying a patient with chronic lymphocytic leukemia and hypogammaglobulinemia who suffered from COVID-19 provided insight in the immunological responses after treatment with COVID-19 convalescent plasma (CCP). Treatment consisted of oxygen, repeated glucocorticosteroids and multiple dosages of CCP guided by antibody levels. Retrospectively performed humoral and cellular immunity analysis made clear that not every serological test for COVID-19 is appropriate for follow-up of sufficient neutralizing antibodies after CCP. In retrospect, we think that CCP merely bought time for this patient to develop an adequate cellular immune response which led to viral clearance and ultimately clinical recovery.

Dynamics of antibodies to SARS-CoV-2 in convalescent plasma donors.

OBJECTIVES: Characterisation of the human antibody response to SARS-CoV-2 infection is vital for serosurveillance purposes and for treatment options such as transfusion with convalescent plasma or immunoglobulin products derived from convalescent plasma. In this study, we longitudinally and quantitatively analysed antibody responses in RT-PCR-positive SARS-CoV-2 convalescent adults during the first 250 days after onset of symptoms. METHODS: We measured antibody responses to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein and the nucleocapsid protein in 844 longitudinal samples from 151 RT-PCR-positive SARS-CoV-2 convalescent adults. With a median of 5 (range 2-18) samples per individual, this allowed quantitative analysis of individual longitudinal antibody profiles. Kinetic profiles were analysed by mixed-effects modelling. RESULTS: All donors were seropositive at the first sampling moment, and only one donor seroreverted during follow-up analysis. Anti-RBD IgG and anti-nucleocapsid IgG levels declined with median half-lives of 62 and 59 days, respectively, 2-5 months after symptom onset, and several-fold variation in half-lives of individuals was observed. The rate of decline of antibody levels diminished during extended follow-up, which points towards long-term immunological memory. The magnitude of the anti-RBD IgG response correlated well with neutralisation capacity measured in a classic plaque reduction assay and in an in-house developed competitive assay. CONCLUSION: The result of this study gives valuable insight into the long-term longitudinal response of antibodies to SARS-CoV-2.

Low awareness of past SARS-CoV-2 infection in healthy plasma donors.

Awareness of infection with SARS-CoV-2 is crucial for the effectiveness of COVID-19 control measures. Here, we investigate awareness of infection and symptoms in relation to antibodies against SARS-CoV-2 in healthy plasma donors. We asked individuals donating plasma across the Netherlands between May 11th and 18th 2020 to report COVID-19-related symptoms, and we tested for antibodies indicative of a past infection with SARS-CoV-2. Among 3,676 with antibodies, and from questionnaire data, 239 (6.5%) are positive for SARS-CoV-2 antibodies. Of those, 48% suspect no COVID-19, despite the majority reporting symptoms; 11% of seropositive individuals report no symptoms and 27% very mild symptoms at any time during the first peak of the epidemic. Anosmia/ageusia and fever are most strongly associated with seropositivity. Almost half of seropositive individuals do not suspect SARS-CoV-2 infection. Improved recognition of COVID-19 symptoms, in particular, anosmia/ageusia and fever, is needed to reduce widespread SARS-CoV-2 transmission.

Afucosylated IgG characterizes enveloped viral responses and correlates with COVID-19 severity.

Immunoglobulin G (IgG) antibodies are crucial for protection against invading pathogens. A highly conserved N-linked glycan within the IgG-Fc tail, which is essential for IgG function, shows variable composition in humans. Afucosylated IgG variants are already used in anticancer therapeutic antibodies for their increased activity through Fc receptors (FcγRIIIa). Here, we report that afucosylated IgG (approximately 6% of total IgG in humans) are specifically formed against enveloped viruses but generally not against other antigens. This mediates stronger FcγRIIIa responses but also amplifies brewing cytokine storms and immune-mediated pathologies. Critically ill COVID-19 patients, but not those with mild symptoms, had high concentrations of afucosylated IgG antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), amplifying proinflammatory cytokine release and acute phase responses. Thus, antibody glycosylation plays a critical role in immune responses to enveloped viruses, including COVID-19.

Low SARS-CoV-2 seroprevalence in blood donors in the early COVID-19 epidemic in the Netherlands.

The world is combating an ongoing COVID-19 pandemic with health-care systems, society and economies impacted in an unprecedented way. It is unclear how many people have contracted the causative coronavirus (SARS-CoV-2) unknowingly and are asymptomatic. Therefore, reported COVID-19 cases do not reflect the true scale of outbreak. Here we present the prevalence and distribution of antibodies to SARS-CoV-2 in a healthy adult population of the Netherlands, which is a highly affected country, using a high-performance immunoassay. Our results indicate that one month into the outbreak (i) the seroprevalence in the Netherlands was 2.7% with substantial regional variation, (ii) the hardest-hit areas showed a seroprevalence of up to 9.5%, (iii) the seroprevalence was sex-independent throughout age groups (18-72 years), and (iv) antibodies were significantly more often present in younger people (18-30 years). Our study provides vital information on the extent of exposure to SARS-CoV-2 in a country where social distancing is in place.