A Common Cold Virus Could Stifle COVID

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There might be an unexpected benefit to the rhinovirus, or the most frequent cause of the common cold — protection against COVID, according to a study at Yale University.

Around 200 viruses cause the common cold, of which rhinovirus is the most common. Researchers found that the rhinovirus kick-starts interferon-stimulated gene activity. Within airway tissues infected with the rhinovirus, this also can halt replication of the SARS-CoV-2 virus.

Setting off these defences early in the course of COVID infection might prevent or treat the infection, said Ellen Foxman, assistant professor of laboratory medicine and immunobiology at the Yale School of Medicine and senior author of the study. One method is treating patients with interferons, an immune system protein which is also available as a drug.

“But it all depends upon the timing,” Prof Foxman clarified.

In later stages of COVID, high interferon levels correlate with worse disease and may fuel overactive immune responses, according to previous research. But recent genetic studies show that interferon-stimulated genes may actually also be protective in cases of COVID infection.

Prof Foxman’s lab wanted to study this defence system early in the course of COVID infection.

Earlier studies by the lab had shown that common cold viruses may protect against influenza, so they decided to find out whether rhinoviruses would have the same beneficial impact against the COVID virus. The researchers infected lab-grown human airway tissue with SARS-CoV-2 and found that for the first three days, viral load in the tissue doubled about every six hours. However, replication of the coronavirus was completely halted in tissue which had been exposed to rhinovirus. When antiviral defences were blocked, the SARS-CoV-2 could replicate in airway tissue previously exposed to rhinovirus.

The same defences slowed down SARS-CoV-2 infection even without rhinovirus, but only with a low infectious dose, suggesting that the viral load at the time of exposure affects whether the body can effectively fight the infection.

The researchers also studied nasal swab samples from patients diagnosed close to the start of infection. They found evidence of rapid growth of SARS-CoV-2 in the first few days of infection, followed by activation of the body’s defenses. According to their findings, the virus typically increased rapidly for the first few days of infection, before host defenses kicked in, doubling about every six hours; in some patients the virus grew even faster.

“There appears to be a viral sweet spot at the beginning of COVID, during which the virus replicates exponentially before it triggers a strong defence response,” Foxman said.

Interferon treatment is promising but could be tricky, she said, because it would be mostly effective in the days immediately after infection, when many people are asymptomatic. In theory, interferon treatment could be used prophylactically in people at high risk who have been in close contact with others diagnosed with COVID. Interferon is being trialled in COVID, and there appears to be a benefit when given early, but not late.

The study helps explain why influenza infections are lowered at times of the year when the common cold is prevalent, Prof Foxman said. The easing of social distancing measures could cause the common cold and flu viruses, which have been suppressed, to spring back with greater force. Respiratory viruses interference with each other could be a mitigating factor, creating an ‘upper limit’ on the degree to which respiratory viruses circulate together, she said.

“There are hidden interactions between viruses that we don’t quite understand, and these findings are a piece of the puzzle we are just now looking at,” Prof Foxman said.

Source: Yale University

Journal information: Cheemarla, N.R., et al. (2021) Dynamic innate immune response determines susceptibility to SARS-CoV-2 infection and early replication kinetics. Journal of Experimental Medicine.doi.org/10.1084/jem.20210583.