Biological mechanisms underpinning the development of Long COVID

24 July 2023

There is a need to elucidate the pathobiological mechanisms underlying the clinical manifestations of Long Covid. 

In the review “Biological mechanisms underpinning the development of Long Covid” published in the journal iScience, a complete and well-characterized understanding of the biological mechanisms responsible for generating the diverse clinical phenotypes of Long Covid aims to underpin the development of diagnostic tests, biomarkers for risk-stratification, and therapeutic interventions.

The precise biological basis for the diverse range of problems that Long Covid patients develop is complex and likely multifactorial. In this review, Dr Rubeshan Perumal, Senior Scientist et al., provide an in-depth analysis of the evidence on potential mechanisms of Long Covid. The analysis shows a significant proportion of survivors experience a diversity of long-lasting clinical sequelae and have an increased risk for new morbidity and possibly mortality. 

This review identified several potential mechanisms supported by published evidence, including viral persistence, SARS-CoV-2 antigen persistence, micro clot formation, autoimmunity, reactivation of latent viruses, persistent systemic inflammation, dysbiosis, persistent central nervous system inflammation and metabolic dysfunction/bioenergetic failure. 

The analysis highlighted people living with HIV/AIDS (PLWHA) are at a higher risk of developing severe Covid-19 complications because of dysregulated inflammation and a functionally impaired immune system, especially in the setting of high-level HIV viremia.

There is an urgent need to further delineate the pathobiology underpinning the development of this major public health threat through well-characterized and deeply phenotyped clinical cohorts, and through clinical trials to also assess the effectiveness of candidate therapeutic options 
directed at key biological mechanisms in different populations, concluded the review. 

For further reading see: Perumal R, et al., Biological mechanisms underpinning the development of long COVID. Science.   2023;26(6):106935.\

Figure: “Putative biological mechanisms underpinning Long COVID