Newswise — Much of what we know about viral respiratory infections like COVID-19 and influenza comes from studies of symptomatic patients. Now, a new longitudinal study by Columbia University researchers of symptomatic, asymptomatic, and mild infections sheds light on how our bodies respond to these infections on a molecular level. They report the discovery of a gene expression signature capable of differentiating both between symptomatic and asymptomatic infections and between positive asymptomatic individuals and negative individuals.

The study presents a complex picture of how several common respiratory viruses interact with the human body, and with each other, as well as with common respiratory bacteria. The results are available as an interactive web tool(link is external and opens in a new window) for scientists to generate and test new hypotheses, and are described in a new peer-reviewed article in the journal PLOS Biology

Over 19 months, 214 volunteers enrolled in the Virome of Manhattan study provided nasal swab samples, which were analyzed by molecular testing (RNA-seq and qPCR) along with daily individual reports of symptoms and demographic information. The majority of the infections were caused by rhinoviruses and coronaviruses. Only 8 percent of positive samples contained evidence of multiple viral coinfections (one case was positive for five different viruses). The study found that influenza leads to greater changes in gene expression than other viruses, such as coronavirus or rhinovirus. Their findings were also suggestive of a possible link between repeat exposure to pathogens and host responses.

“The repeated emergences of influenza and coronavirus pandemic outbreaks have emphasized the need for a better understanding of host-pathogen interactions in respiratory infections,” says study co-first author Marta Galanti, PhD, an associate research scientist in environmental health sciences at Columbia University Mailman School of Public Health. 

“Identifying the main biological pathways by which viruses interact with our bodies is key for developing therapeutic tools, such as antivirals or vaccines, as well as for better identifying individuals at risk, both for seasonal respiratory viruses and emerging pandemic threats,” says study co-senior author Jeffrey Shaman, PhD, professor of environmental health sciences at Columbia Mailman and Interim Dean of the Columbia Climate School.  

An earlier study using data from the same cohort found that reinfections with endemic coronaviruses are not uncommon, even within a year of prior infection. The study found that when reinfection occurred, it was not associated with less severe symptoms. Instead, genetic factors may be a greater determinant of the severity of an infection.

Study co-authors include Haruka Morita, Mariam Youssef, Devon Comito, Chanel Ligon, Benjamin Lane, Nelsa Matienzo, Sadiat Ibrahim, Eudosie Tagne, and Atinuke Shittu of Columbia Mailman; and Juan Angel Patiño-Galindo (co-first author), Ioan Filip (co-first author), Angelica Galianese, Oliver Elliott, Tomin Perea-Chamblee, Sanjay Natesan, Daniel Scholes Rosenbloom, and Raul Rabadan (co-senior author)of the Department of Systems Biology, Columbia University Irving Medical Center. 

The study was supported by the Defense Advanced Research Projects Agency (contracts W911NF-16-2-0035, R01GM117591). 

The authors have the following competing interests: Rabadan is a member of the SAB of Diatech Pharmacogenetics and Flahy and a founder of Genotwin. Shaman and Columbia University disclose partial ownership of SK Analytics. Shaman discloses consulting for BNI.  Rosenbloom is now an employee of Merck & Co. and may hold stock. Filip is now employee of Illumina. Elliott is currently an employee of Genowin. All other authors have no competing interests.

Journal Link: PLoS Biology