Common cold coronaviruses linked to less severe COVID-19 cases

The common cold isn’t caused by one specific virus. Over 200 viruses are known to cause cold-like symptoms, and of them, four are coronaviruses — part of the same family as SARS-CoV-2. A new study suggests that while these so-called endemic coronaviruses don’t protect against SARS-CoV-2 infection, they seem linked to milder infections.

Their names are easy to forget (OC43, HKU1, 229E, and NL63), but your immune system has a good memory. It remembers the fight against these viruses for a while and uses it in the fight against other, similar viruses. At least that was the assumption of a team of researchers at Boston University School of Medicine. They combed medical records of thousands of patients that had visited Boston Medical Center. Each person had been assessed for infection using a PCR test that screens for bacteria and viruses, including the four endemic coronaviruses. They ended up with a list of 15,928 patients that had done at least one such PCR test.

Out of these participants, 875 tested positive for one of the four endemic coronaviruses. Also, 1,812 later returned for a SARS-CoV-2 test between March and June 2020. The researchers hoped to see some kind of connection.

“Our study is the first to examine people with known endemic coronavirus infections, and compare them to people who, as far as we know, don’t have any recent documented coronavirus infections,” says Manish Sagar, the lead author of the study and a virologist at Boston Medical Center.

At first, it didn’t seem to pan out. People who had a previous coronavirus infection seemed to become infected at the same rate as those who hadn’t. But when they looked closer, they did find something.

“The COVID-19 disease is actually much less severe in those patients who had documented endemic coronavirus infections,” says Sagar.

Patients who had tested positive for one of the endemic coronaviruses had a significantly higher survival rate than those who hadn’t (95.2% vs 82.3%).

The difference may be caused by something called “heterotypic immunity”, a form of imperfect immunity caused by a different type of virus. It’s common for respiratory viruses to offer some protection to other viruses, and this could be the case for SARS-CoV-2.

“Importantly, the patients with a previously detected eCoV had less severe coronavirus disease-2019 (COVID-19) illness,” the study reads. “Our observations suggest that pre-existing immune responses against endemic human coronaviruses can mitigate disease manifestations from SARS-CoV-2 infection.”

This has been suggested before, but evidence is not clear-cut. In September, a preprint on bioRxiv, presented results on serum antibodies and antibody-producing B cells from 36 donors to see whether those antibodies reacted with the spike protein from the new pandemic virus. Most of them didn’t, but one particular antibody did seem to neutralize SARS-CoV-2. In another study in Nature, researchers in Singapore found evidence of memory T cells in patients who had recovered from SARS back in 2003 — T cells that were reactive to proteins from SARS-CoV-2. Another recent study published in Science found that 5% of 302 adults and 43% of 48 children had antibodies that worked against SARS-CoV-2 — presumably also due to some form of heterotypic immunity. This makes sense since children are more prone to common cold infections, perhaps also explaining why they tend to suffer less severe COVID-19 symptoms.

While much of this is circumstantial, it seems to suggest that some kind of cross-immunity is at play. Much of the evidence comes from small-scale studies, so more research is still needed to confirm this hypothesis.

There’s also no telling how strong this is or how long it lasts, even if it exists, so Sagar and colleagues are currently seeking funding to expand the research and include data from other institutions to assess this phenomenon.

The study ‘Recent endemic coronavirus infection is associated with less severe COVID-19’ has been published in the Journal of Clinical Investigation.

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