Long COVID: ‘viral reservoir’ of spike protein may explain long-term symptoms

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Scientists may have identified a potential biomarker for long-term COVID. Hollie Adams/Bloomberg via Getty Images
  • Researchers examined the antigens of SARS-CoV-2 – the virus that causes COVID-19 – present in blood plasma samples collected from individuals with long-term COVID-19 infection and a typical COVID-19 infection.
  • They found that one specific SARS-CoV-2 antigen — the spike protein — was present in the blood of a majority of long-term COVID patients for up to a year after they were first diagnosed with COVID-19.
  • However, in patients with a typical COVID-19 infection, the spike protein was not detected.
  • This finding provides evidence for the hypothesis that SARS-CoV-2 can persist in the body through viral reservoirs, where the spike protein continues to release spike protein and cause inflammation.

Current dates of the World Health Organization (WHO) indicates that about 1 in 4 people with COVID-19 still experience symptoms 4-5 weeks after diagnosis, and about 1 in 10 have persistent symptoms after 12 weeks.

Individuals with post-acute effects of COVID-19 (PASC), or long-term COVID, have reported a range of symptoms including, but not limited to, fatigue, anosmia (loss of the sense of smell), amnesiagastrointestinal complaintsand shortness of breath

The underlying mechanism of long-term COVID is complicated. Identifying a blood biomarker for long-term COVID, or in other words, a biomolecule found in the blood of most long-term COVID patients, could contribute to a better understanding of the biology of long-term COVID.

A new study finds evidence of a biomarker that could indicate an active viral reservoir in the body, particularly in the gut after initial SARS-CoV-2 infection.

A preprint of the research has been published on: medRxiv

To identify a blood biomarker for long-term COVID, researchers from Harvard Medical School and the Ragon Institute of MGH, MIT and Harvard analyzed blood plasma samples collected from patients with long-term COVID-19 infection and typical COVID-19 infection. over a period of 12 months.

They tried to determine the levels of three SARS-CoV-2 antigens:

  • Spike protein – spike-like molecules protruding from the surface of the SARS-CoV-2 virus
  • S1 subunit of spike protein – one of the two subunits that make up the spike protein
  • Nucleocapsid – nucleic acid (genetic material) and surrounding capsid (protein layer) of the virus

The researchers found that the spike protein, S1 subunit or nucleocapsid was present in the blood of 65% of the tall COVID patients they tested for up to 12 months after their first COVID-19 infection.

Of the three SARS-CoV-2 antigens, the spike protein was the most common, as it was detected in 60% — or 3 out of 5 — long-term COVID patients.

In contrast, the researchers found no spike protein in any of the patients with a typical COVID-19 infection. The S1 subunit and nucleocapsid were detected in the blood of COVID-19 patients immediately after the COVID-19 diagnosis, but the levels of these antigens quickly fell below the limit of detection.

“The most logical interpretation [of the data presented in the pre-print] is that spike protein in serum is a surrogate marker for an ongoing infection somewhere in the body,” dr. John P. Mooreprofessor of microbiology and immunology at Weill Cornell Medicine, who was not involved in the study, said: Medical news today

The researchers believe that the presence of SARS-CoV-2 spike protein in a majority of long-term COVID patients up to 12 months after diagnosis suggests the presence of an active persistent SARS-CoV-2 viral reservoir.

dr. David R. Walttold one of the study’s authors: the guard that the presence of the spike protein indicated such a reservoir, since the half-life of this antigen is “quite short” in the body.

dr. Andrew Pekoszoprofessor of molecular microbiology and immunology at Johns Hopkins University Bloomberg School of Public Health, who was not involved in the study, told MNT that the existence of reservoirs of SARS-CoV-2 in organs such as the gut could possibly explain the symptoms of long-term COVID.

“The presence of virus-infected cells at low levels […] would be the “trigger” for continued activation of the immune system. Finding these viral proteins in the blood could also explain why multiple organs can be affected by long-term COVID. This kind of persistent infection is seen in some viruses, but has not been clearly demonstrated in SARS-CoV-2.”
– dr. Andrew Pekosz

Other researchers have also found evidence of viral persistence (the persistent presence of the virus) in patients with long-term COVID symptoms.

dr. Akiko Iwasakitold sterling professor of immunobiology and molecular, cellular and developmental biology at Yale University, who was not involved in the study, MNT

“Evidence for Persistent Virus and Viral Antigen/RNA Reservoirs” [is] increasingly common […] The presence of the spike protein in circulation at long transporters adds to this emerging evidence.”

Studies have pointed to the gut as a possible reservoir.

At Stanford University in California, dr. Ami S. Bhatto and colleagues found that about 4% of subjects (or 1 in 25) with mild to moderate COVID-19 continued to release viral RNA in their stool seven months after diagnosis of COVID-19.

Individuals with detectable viral RNA in their stool also reported persistent gastrointestinal symptoms such as abdominal pain, nausea and vomiting.

In addition to providing compelling evidence for the viral reservoir hypothesis of long-term COVID, the presence of spike protein in the majority of long-term COVID patients suggests that spike protein could potentially be used as a biomarker for long-term COVID. Enabling doctors to diagnose long-term COVID through a blood plasma test is a step toward more effective treatment.

However, before researchers come to any solid conclusions, they need to conduct further research to confirm this.

One question that needs to be answered is why 35-40% of tall COVID patients had no measurable spike protein in their blood.

“Does this mean their symptoms stem from something other than long-term COVID or does long-term COVID result from a multitude of causes? Based on our studies, we can’t answer that question,” Walt said MNT

dr. Pekosz described the study as “intriguing,” but cautioned that more research is needed to really understand its implications.

“The big questions are really, is this enough? [spike] protein to trigger [long COVID] symptoms? Would treatments such as antivirals or booster vaccinations eliminate and thus alleviate these sources of viral protein? [long COVID] symptoms? Where are the infected cells and how do the virus proteins get into the blood?” he said.

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