Are SARS-CoV-2 Specific Antibodies a Correlate for Protection?
Condition: SARS-CoV2; COVID-19
Study type: Interventional

Summary: 
      The objectives of this study are (1) to determine the ex vivo neutralizing capacity and the
      longevity of SARS-CoV-2-specific Ab responses and (2) to measure the memory B-cell responses
      in a cohort of health care workers (HCW) recovering from severe, mild or asymptomatic
      infection. By focusing on HCW, a population that is at risk for re-infection during a second
      epidemic wave, the correlation between nAb levels and protection is investigated.
    

Detailed description: 
      SARS-CoV-2 has spread at an unprecedented speed and scale since January 2020. Since then,
      Belgium has been confronted with >60.000 diagnosed cases and likely many more undiagnosed
      with mild or no symptoms. The true seroprevalence of SARS-CoV-2 in the Belgian population is
      not known, yet increasing confidence about the performance of several serological assays
      paves the way to large-scale serosurveys. These studies will be crucial in assessing
      population immunity and evaluating the risk of re-infection. The first, smaller-scaled,
      antibody surveys report a range of seroprevalences, i.e. Germany (14%), The Netherlands (4%),
      USA (2.49-4.16%) and Belgium (4.7-6.9%). These studies suffer from conceptual and technical
      flaws yet are used for easing lockdown measures. A major limitation is that antibody (Ab)
      capture assays measure exposure to SARS-CoV-2, rather than subsequent protection, which
      requires assessment of the quality of the Abs including their capacity to neutralize the
      virus. Also the Ab levels required for protection and their duration are yet unknown. The
      proposed project aims to address these pertinent questions in a population at risk of
      re-infection during a second epidemic wave. Sero-neutralisation assays are regarded the gold
      standard method to measure ex vivo Ab neutralising activity against viruses, including
      SARS-CoV-2. A recent Chinese study, using a pseudovirus neutralisation assay, found that nAbs
      are detected from day 10-15 after onset of disease and that younger patients typically have
      lower levels of nAbs compared to middle-aged and elderly patients. Importantly, in about 1
      out of 3 patients the nAb titers were low and in 10 young patients nAbs were absent. A
      pseudovirus is an imperfect model for SARS-CoV-2 because of the non-natural embedding of
      Spike protein in the pseudovirions and differences in glycosylation. In this study, a whole
      virus neutralisation assay will be used that was recently validated using a panel of
      SARS-CoV-2 convalescent sera in the lab of the Principal Investigator. Preliminary results of
      the study team show a rapid decline in nAb titer within 15-36d after diagnosis in 4/11
      patients, while IgG and IgA remain steady and high in ELISA. Older studies with SARS-CoV-1
      showed declining IgM and IgA antibody titers within 6 months, declining IgG titers after 1y,
      and a complete lack of antigen-specific peripheral memory B-cell (MBC) responses after
      recovery. Measuring only circulating Abs can be misleading as it excludes the detection of
      the MBC pool, which can exist in the absence of detectable serum Ab levels and is a
      pre-requisite to maintain protective immunity in the long term. Upon re-encounter with the
      antigen, MBC can rapidly differentiate to produce Abs. So far, little is known about humoral
      immune responses against SARS-CoV-2 and their contribution to protection.
    

Intervention name(s): Assessing antibody responses, neutralizing capacity and memory B-cell function
Intervention type(s): Diagnostic Test
Intervention description(s): Assessing antibody responses, neutralizing capacity and memory B-cell function and their contribution to protection against re-infection
Intervention MeSH terms: Antibodies
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science