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
• antibodies
• monoclonal antibodies
• vaccination
• T cells

Article highlights

• SARS-CoV-2 the agent responsible for COVID-19 has caused calamitous social, economic and health consequences globally

• The virus is able to evade the innate immune system and is also able to subvert the adaptive immune system in those who are severely affected

• The role of antibodies in protection against the infection is incompletely understood. In some circumstances, the humoral immune response appears to be protective, while in other situations it may be aggravating the inflammatory response

• At this time, it is not possible to predict specific protective antibody levels that prevent breakthrough infections in patients who have been vaccinated

• The antibody response may be best viewed as a biomarker of either infection or vaccination.

• It is becoming increasingly clear that cellular immunity is the most critical part of the response to either the virus or immunization, which allows long-term protection.

• In the future, it is possible measurement of T cell responses will predict protective responses to vaccines in vulnerable individuals

• This article seeks to provide an overview of the current status of knowledge on the role of antibodies in COVID-19

• What is currently understood about COVID-19 may need to be revised with the rapid emergence and dominance of the omicron variant of SARS-CoV-2.

• Omicron appears to be fundamentally different to previous SARS-CoV-2 variants and may need to be considered a new infection

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Further information

Neither the diagnostic T cell assay for SARS-CoV-2 nor the NZACE2-Pātari project has received support at this time.

Additional information

Funding

This paper was not funded.