The (apparent) antibody paradox in COVID-19

Abstract

Introduction: The immunological response to COVID-19 is only partly understood. It is increasingly clear that the virus triggers an inappropriate host inflammatory reaction in patients experiencing severe disease.

Areas covered: The role of antibodies in COVID-19 remains to be fully defined. There is evidence for both protection and harm in different clinical syndromes triggered by SARS-CoV-2. Many patients dying from COVID-19 had both high titers of antibodies to SARS-CoV-2 and elevated viral loads. The uncertain protective role of humoral immunity is mirrored by the lack of benefit of therapeutic convalescent plasma infusions in COVID-19. In contrast, there is increasing evidence that a vigorous T-cell response is protective. Delayed or low avidity T cell reactions were seen in patients suffering severe COVID-19.

Expert opinion: These observations suggest T cell responses to SARS-CoV-2 are the dominant long-term protective mechanism following either infection or vaccination. The magnitude and quality of the antibody response is likely to reflect underlying T cell immunity to SARS-CoV-2. Much of what has been learned about COVID-19 will need to be revised following the recent rapid emergence and dominance of the omicron variant of SARS-CoV-2.

Keywords: COVID-19; SARS-CoV-2; T cells; antibodies; monoclonal antibodies; vaccination.

Figure 1.

Factors determining the outcome of COVID-19. Both viral and host risk factors are important in progression from the nasal to the pulmonary and systemic phases. The omicron variant appears to produce milder pulmonary disease and may have a shorter nasal phase. New antiviral drugs such as molnupiravir (Merck) or paxlovid (Pfizer) are only likely to be effective early in disease. Later in disease, immunomodulatory drugs are more effective. Vaccines reduce the risk of aberrant immune responses, making the pulmonary and systemic phases less likely.