The body's first encounter with SARS-CoV-2, the virus behind Covid-19, happens in the nose and throat, or nasopharynx, thus it may help determine who will develop severe Covid disease and who will get through with mild or no illness, according to a study.The study, led by a team of researchers at the Massachusetts Institute of Technology, Boston Children's Hospital (BCH); and the Universities of Mississippi and Harvard found that people who develop severe Covid-19 have markedly blunted antiviral responses in the nasopharynx."Why some people get more sick than others has been one of the most puzzling aspects of this virus from the beginning," said researchers, including Jose Ordovas-Montanes, of Boston Children's Hospital."Many studies looking for risk predictors have looked for signatures in the blood, but blood may not really be the right place to look," Ordovas-Montanes added.For the study, published in the journal Cell, the team comprehensively mapped SARS-CoV-2 infection in the nasopharynx. They obtained samples from the nasal swabs of 35 adults with Covid-19 from April to September 2020, ranging from mildly symptomatic to critically ill.
They also got swabs from 17 control subjects and six patients who were intubated but did not have Covid-19.When the team compared nasopharyngeal swabs from people with different severity of Covid-19 illness, they found that in people with mild or moderate Covid-19, epithelial cells showed increased activation of genes involved with antiviral responses, especially genes stimulated by type I interferon, a very early alarm that rallies the broader immune system.Further, in people who developed severe Covid-19, requiring mechanical ventilation, antiviral responses were markedly blunted.In particular, their epithelial cells had a muted response to interferon, despite harbouring high amounts of virus. At the same time, their swabs had increased numbers of macrophages and other immune cells that boost inflammatory responses."Everyone with severe Covid-19 had a blunted interferon response early on in their epithelial cells, and were never able to ramp up a defense," said Ordovas-Montanes."Having the right amount of interferon at the right time could be at the crux of dealing with SARS-CoV-2 and other viruses."