‘Viral reservoir’ of spike protein may explain long-term symptoms

‘Viral reservoir’ of spike protein may explain long-term symptoms

A blurry close-up of a man wearing a face mask against COVID-19 as unmasked people go about their days behind him in the streetShare on Pinterest
Scientists may have identified a potential biomarker for long COVID. Hollie Adams/Bloomberg via Getty Images
  • Researchers investigated the antigens of SARS-CoV-2—the virus that causes COVID-19—present in blood plasma samples collected from individuals with long COVID and typical COVID-19 infection.
  • They found that one particular SARS-CoV-2 antigen—the spike protein—was present in the blood of a majority of long COVID patients, up to a year after they were first diagnosed with COVID-19.
  • In patients with typical COVID-19 infection, however, 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 it continues to release spike protein and trigger inflammation.

Current data from the World Health Organization (WHO) indicates that around 1 in 4 individuals with COVID-19 continue to experience symptoms 4–5 weeks after diagnosis, and approximately 1 in 10 have continuing symptoms after 12 weeks.

Individuals with post-acute sequelae of COVID-19 (PASC), or long COVID, have reported a range of symptoms, including, but not limited to, fatigue, anosmia (loss of the sense of smell), memory loss, gastrointestinal distress, and shortness of breath.

The underlying mechanism of long COVID is complicated. Identifying a blood biomarker for long COVID, or in other words, a biological molecule that appears in the blood of most long COVID patients, could contribute to a better understanding of the biology of long COVID.

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

A preprint of the study was published on medRxiv.

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

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

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

The researchers found that the spike protein, S1 subunit, or nucleocapsid were present in the blood of 65{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809} of the long COVID patients they tested, up to 12 months after their initial COVID-19 infection.

Out of the three SARS-CoV-2 antigens, the spike protein was the most common, having been detected in 60{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809}—or 3 out of 5—of long COVID patients.

In contrast, the researchers did not detect spike protein in any of the patients with 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 dropped 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 a persistent infection somewhere in the body,” Dr. John P. Moore, professor of microbiology and immunology at Weill Cornell Medicine, who was not involved in the study, told Medical News Today.

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

Dr. David R. Walt, one of the study’s authors, told The Guardian that the presence of the spike protein indicated such a reservoir as the half-life of this antigen is “pretty short” in the body.

Dr. Andrew Pekosz, professor of molecular microbiology and immunology at the 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 potentially explain the symptoms of long 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 COVID. This kind of persistent infection is seen with some viruses but has not been clearly demonstrated with SARS-CoV-2.”
– Dr. Andrew Pekosz

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

Dr. Akiko Iwasaki, sterling professor of immunobiology and molecular, cellular and developmental biology at Yale University, who was not involved in the study, told MNT:

“Evidence for persistent virus and viral antigen/RNA reservoirs [is] becoming more and more prevalent […] The presence of the spike protein in circulation in long haulers is adding to this emerging evidence.”

Studies have pointed to the gut as a possible reservoir.

At Stanford University in California, Dr. Ami S. Bhatt and colleagues found that about 4{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809} of individuals (or 1 out of 25) with mild to moderate COVID-19 continued shedding viral RNA in their stools seven months after COVID-19 diagnosis.

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

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

However, before coming to solid conclusions, researchers will need to conduct further studies to confirm.

One question to answer is why 35-40{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809} of the long COVID patients did not have measurable spike protein in their blood.

“Does this mean that their symptoms arise from something other than long COVID or does it mean that long COVID results from a multiplicity of causes? From our studies, we can’t answer that question,” Walt told MNT.

Dr. Pekosz described the study as “intriguing” but cautioned that more investigation is required to truly understand its implication.

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

Hypertension and diet: Protein variety may matter

Hypertension and diet: Protein variety may matter

  • Just about 50 percent of older people in the United States have high blood pressure, or hypertension.
  • Latest evidence indicates that dietary modifications can reduce blood pressure, but extra investigation is needed.
  • A latest examine in China displays that eating a well balanced diet plan together with protein from a wide variety of resources may perhaps assist grown ups decrease their chance of producing superior blood force.

Hypertension can guide to cardiovascular disorder, stroke, and ailments that affect the kidneys and the mind.

With just about half of adults in the U.S. residing with hypertension, researchers are seeking for ways to decrease the risk of establishing the issue.

Scientists feel that hypertension takes place thanks to a mixture of environmental and way of life components. Existing information is that eating much more healthily can decrease superior blood tension.

These days, there has been a rising desire in the function of protein as a achievable tactic to avoiding hypertension.

The current study, led by Dr. Xianhui Qin, M.D., at the Southern Clinical College in Guangzhou, China, investigated the backlink amongst the assortment and amount of protein in the eating plan and new-onset hypertension.

The examine authors discovered that eating protein from a variety of resources could help reduce the possibility of high blood pressure. Their results appear in the journal Hypertension.

Tracy Parker, senior dietitian at the British Coronary heart Foundation, explained to Healthcare Information These days, “This examine adds to the evidence that taking in a reasonable amount of money of protein from a range of food items is an vital part of a wholesome food plan.”

“Although this analyze was observational, it indicates that having a range of both of those plant- and animal-centered proteins in your diet program can help manage your blood force and advantage your coronary heart. More investigate is now necessary to assist comprehend this, including in unique populace teams with distinctive dietary intakes.”

The crew took facts from the China Well being and Diet Survey, a collaborative job in between the College of North Carolina at Chapel Hill and the Chinese Center for Disease Regulate and Avoidance (CCDC).

The study collected knowledge between 1989 and 2015 and covered a lot more than 47{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809} of the Chinese populace. The selection of knowledge took spot in waves each individual 2–4 a long time. In the 2009 wave, researchers gathered blood samples.

The present research employed knowledge gathered from 1997 to 2015, excluding contributors who already experienced a hypertension diagnosis, who experienced not completed two rounds of the study, or whose nutritional details have been insufficient.

Trained nutritionists gathered info about meals consumption through deal with-to-deal with interviews. This entailed 24-hour nutritional recalls around 3 days of the exact same week, together with a residence meals stock. From this data, the researchers then calculated the nutrient ingestion.

The staff appeared at the selection and amount of protein ingestion from eight major meals resources: total and refined grains, processed and unprocessed red meat, poultry, fish, eggs, and legumes. They then created protein scores based mostly on the variety of protein resources a particular person consumed, awarding just one point for each source.

In excess of an typical adhere to-up of 6.1 decades, the researchers captured information about new hypertension diagnoses. The closing evaluation incorporated a overall of 12,177 participants.

The common age of the participants was 41, and about 53{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809} had been female. During the analyze, just above 35{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809} of the members formulated hypertension.

The scientists observed that the individuals with the finest assortment of protein in their eating plan experienced much less than 50 {cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809} the rate of new-onset hypertension than individuals with a protein wide range score of a lot less than 2.

The complete quantity of protein showed a U-shaped curve in relation to hypertension onset. This usually means that people with the least variety and the most protein consumption had the greatest chance of new-onset hypertension.

For each individual variety of protein, the researchers identified specific concentrations the place the chance of hypertension is decreased.

Dr. Qin informed MNT that he was not stunned by the benefits. “We speculated that consuming better range of proteins in proper amount could assurance the ingestion of distinctive crucial amino acids, which may possibly correlate with superior dietary standing, microbiota richness, and range.”

“The coronary heart overall health concept is that consuming a balanced eating plan with proteins from a variety of, distinctive resources, instead than focusing on a solitary supply of dietary protein, may assist stop the enhancement of large blood pressure,” Dr. Qin says.

Dr. Qin explained to MNT that long run function must involve contributors of other ethnicities and from other locations. “Randomized trials are desired to further more analyze the associations among the variety and quantity of protein consumption from distinctive food items resources and the risks of hypertension and other wellbeing outcomes.”

“Moreover, we ought to even further determine the appropriate sum of the consumption of each protein in various populations.”

Parker additional: “To preserve your heart healthful, you must emphasis on eating more fruit, vegetables, fish, pulses, and entire grains and slicing down on food items high in salt, sugar, and saturated unwanted fat, like cake, biscuits, and sweets. Lifestyle elements, this kind of as performing exercises on a regular basis, quitting smoking cigarettes, and sustaining a healthful pounds, are also critical means to lessen your danger of coronary heart and circulatory conditions.”