Reservoirs of SARS-CoV-2 and their potential role in Long COVID

A review article in Nature Immunology summarizes what is currently known about the persistence of SARS-CoV-2 virus in the body after COVID-19. Theorized as a possible cause of Long COVID, the ongoing presence of the virus could trigger immune responses that account for most or all the sequelae of COVID-19. For the virus to persist, a “reservoir”—that is, a particular tissue that is host to either viral genetic material or ongoing viral replication—must exist.

Some of the most prevalent symptoms of Long COVID

The authors noted that viruses similar to SARS-CoV-2 persist in the body after infection and cause chronic illnesses as a direct result. The genetic material of the SARS-CoV-2 virus is RNA, and in particular it is single-stranded RNA or “ssRNA” for short. Several other ssRNA viruses—including Zika virus, Ebola virus, enteroviruses, and the measles virus—are known to persist in tissues for months to years after initial infection. 

The persistence of these other ssRNA viruses often results in chronic disorders including heart, eye, neurological, and musculoskeletal syndromes. Therefore it is a reasonable hypothesis that SARS-CoV-2 exhibits similar behavior that is responsible for at least a significant proportion of cases of Long COVID. It should also be noted that reservoirs of these viruses have been associated with viral mutations while the virus replicates for long periods of time in the body as well as ongoing transmission of the virus—often silent given that individuals are often months past acute infection.

The purpose of the review article was to assess what science currently has discovered about reservoirs of SARS-CoV-2 and their association with Long COVID. Also, the authors reviewed the possible biological mechanisms by which viral reservoirs might result in the broad array of sequelae seen in Long COVID patients.

The answer is that dozens of tissues are documented reservoirs of SARS-CoV-2 for periods up to 676 days (nearly two years). Viral RNA and associated proteins have been found in brain, nerve, gastrointestinal tract, lymph node, lung and breast tissue, among others. Viral RNA and proteins, including the spike protein, have been found circulating in blood plasma for over a year post-infection.

The reason why so many tissues serve as reservoir of the virus is still a subject for future study. One leading hypothesis is that most human tissues are dense with Angiotensin Converting Enzyme 2 (ACE2) receptors, and ACE2 receptors are the primary way the SARS-CoV-2 virus binds cells in order to enter them. Notably, ACE2 receptors are particularly abundant in the tissues of the gastrointestinal tract, brain, lung, heart and blood vessels.

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