Severe COVID-19 is a T cell immune dysregulatory disorder triggered by SARS-CoV-2

ABSTRACT

Introduction

COVID-19 has had a calamitous impact on the global community. Apart from at least 6 M deaths, hundreds of millions have been infected and a much greater number have been plunged into poverty. Vaccines have been effective but financial and logistical challenges have hampered their rapid global deployment. Vaccine disparities have allowed the emergence of new SARS-CoV-2 variants including delta and omicron, perpetuating the pandemic.

Areas covered

The immunological response to SARS-CoV-2 is now better understood. Many of the clinical manifestations of severe disease are a consequence of immune dysregulation triggered by the virus. This may explain the lack of efficacy of antiviral treatments, such as convalescent plasma infusions, given later in the disease.

Expert opinion

T cells play a crucial role in both the outcome of COVID-19 as well as the protective response to vaccines. Vaccines do not prevent infection but reduce the risk of a chaotic and destructive cellular immune response to the virus. Severe COVID-19 should be considered a virus-induced secondary immune dysregulatory disorder of cellular immunity, with broad host susceptibility. This perspective of COVID-19 will lead to better diagnostic tests, vaccines, and therapeutic strategies in the future.

KEYWORDS:

• COVID-19
• SARS-CoV2
• plasma therapy
• Omicron
• immunodeficiency
• Vaccines

Article highlights

• SARS-CoV-2, the agent responsible for COVID-19, has caused calamitous global consequences

• The immune system plays a critical role in the outcome of infection

• Defects of innate immunity and cellular immunity are associated with severe outcomes

• An effective early T cell response is associated with mild disease

• Effective T cell responses following COVID-19 or vaccination, confer protection against SARS-CoV-2

• The primary role of vaccines is to prevent a chaotic destructive cellular immune response to SARS-CoV-2

• Severe COVID-19 should be considered a T cell immune dysregulatory disorder associated with inappropriate overactivation of the innate immune system, triggered by SARS-CoV-2

• Anti-viral treatments will be effective early, while immunomodulatory treatments will be more helpful later in the disease

Acknowledgments

NZ has long-standing experience in ISO accredited diagnostic T cell assays. A SARS-CoV-2 T cell assay has not been validated and implemented in any diagnostic laboratory in NZ.

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.

Additional information

Funding

This paper was not funded.