Virus World

Four seasonal coronaviruses—2 of which are betacoronaviruses, like SARS-CoV-2—cause about 30% of common colds. Instead of helping to fight off COVID-19, antibodies to these pathogens may interfere with the SARS-CoV-2 immune response, a recent study of health care workers suggests. Although these preexisting antibodies are ubiquitous, individuals’ varying levels of them might factor into the broad spectrum of responses to the novel coronavirus, which range from immunity against infection all the way to severe respiratory distress and death.

T cell reactivity against SARS-CoV-2 was observed in unexposed people; however, the source and clinical relevance of the reactivity remains unknown. It is speculated that this reflects T cell memory to circulating ‘common cold’ coronaviruses.

It will be important to define specificities of these T cells and assess their association with COVID-19 disease severity and vaccine responses. Recent studies have shown T cell reactivity to SARS-CoV-2 in 20–50% of unexposed individuals; it is speculated that this is due to T cell memory to common cold coronaviruses. Here, Crotty and Sette discuss the potential implications of these findings for disease severity, herd immunity and vaccine development....

Original review Published in Nature (July 7, 2020):

https://doi.org/10.1038/s41577-020-0389-z

Outcomes in COVID-19 patients may be better in those recently infected with endemic coronaviruses. There are four common cold coronaviruses that we all catch at some stage. We generate antibodies to them, but our immune memory of them fades over time, and we get re-infected.  Their names are all too easily forgotten—OC43, HKU1, 229E, and NL63—but our immune systems may nevertheless remember them for a time. There have been hints that exposure to these common coronaviruses might offer some protection from COVID-19, mostly by looking at signs of immune memory in blood samples taken from before the pandemic. A study in the Journal of Clinical Investigation reports the first clinical evidence linking recent endemic coronavirus infections to less severe COVID-19 and even a reduced death rate in patients.  The authors at Boston University School of Medicine found evidence for this by poring over the medical records of thousands of patients who had visited Boston Medical Center as inpatients or outpatients, most probably for respiratory illnesses, between 2015 and 2020. Each person had been assessed for infection using a PCR test that screens for bacteria and viruses, including the four endemic coronaviruses. 

In total, 15,928 patients had at least one such PCR test. Of them, 875 tested positive for an endemic coronavirus (this group was called eCoV+), while the remaining 15,053 people never had a documented coronavirus infection (termed eCoV-).  Of the entire cohort, a total of 1,812 (11.4 percent) later returned for a SARS-CoV-2 test during the initial COVID-19 surge in Boston between March 12 and June 12. “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.  The infection rate for SARS-CoV-2 was no different between those who had a recently recorded endemic coronavirus infection (eCoV+) and those who did not have a positive test (eCoV-). This led the authors to conclude that a recent infection with endemic coronaviruses did not keep SARS-CoV-2 at bay—both groups were just as likely to become infected with the pandemic virus. When the researchers peered closer at the data, they observed an important difference between the two groups. “The COVID-19 disease is actually much less severe in those patients who had documented endemic coronavirus infections,” says Sagar. The odds of intensive care unit (ICU) admission were significantly lower in eCoV+ than in eCoV- patients, and there was “a trend towards lower odds of mechanical ventilation,” the authors write in their report. The data also show that among hospitalized patients who had previous positive test results for endemic coronavirus, 4.8 percent of them died compared with 17.7 percent among those in the group without such a test result.

Local immune memory may help explain these results. Such “heterotypic immunity,” says immunologist Joseph Mizgerd, director of the pulmonary center at Boston University School of Medicine, occurs when immune memory is etched into the lungs and/or nose. It’s common after other types of respiratory infections and might offer protection against SARS-CoV-2 if elicited by endemic coronaviruses. Although the Boston group did not measure this type of immunity in patients, they now hypothesize that local immunity gained from endemic coronaviruses helps limit lung injury during COVID-19. “We are testing that in ongoing experiments,” Mizgerd says by email. He adds that such cross-reactive immunity is often mediated by memory T cells, which can localize in the lung, and he notes that lung-localized heterotypic T cells can prevent severe lung infection during pneumonias caused by other types of respiratory pathogens. If indeed prior infection does ramp up protection against SARS-CoV-2, the study could not answer how long it takes for any such benefit to taper off. Nor did the work shed light on which of the four endemic coronaviruses in particular might be offering protection against the pandemic virus. The scientists are seeking funding to expand their research and include data from other institutions....

Study cited available in J. Clinical Investigation:

https://doi.org/10.1172/JCI143380