While the risk of concurrent influenza and Covid-19 epidemics this winter bothers doctors, some virologists are worried about another scenario: the possible emergence of a "frankenvirus".
Sars-CoV-2, the virus that causes Covid-19, most likely results from the hybridization of two different coronaviruses. Details remain unclear, but after the genome of the virus was sequenced, this mixing would have occurred in a bat about ten years ago. The animal was reportedly infected with two closely related coronaviruses simultaneously, which merged to form a new one.
Such recombination is not unusual in coronaviruses. "If you look in the coronavirus family tree, you see that there are recombinations everywhere," says virologist Samuel Díaz-Muñoz of the University of California, Davis.
Co-infection and hybridization possible
There are two reasons for this. First, coronaviruses tolerate co-infection: unlike many other viruses, they accept to coexist with other viruses within the same organism.
Second, the way coronaviruses replicate their genomes makes hybridization not only possible but probable. They are RNA viruses, which normally have a very high mutation rate (the highest rate of all known biological entities) because the enzymes that copy their RNA lack a proofreading function. A high mutation rate allows a virus to quickly develop resistance to the immune response of its host.
But coronaviruses are the exception to the rule, as their replicating enzymes [replicases] have a replay function.
A respiratory panel virus turned up in 3.3% (15 of 459) of the specimens that also tested positive for SARS-CoV-2 by RT-PCR at University of Chicago Medicine from March 12 through April 15, 2020.
The most common co-infections were with rhinovirus/enterovirus (eight cases, 1.7%), influenza A (three cases, 0.7%), adenovirus (two cases, 0.4%), and human metapneumovirus (two cases, 0.4%), Aniruddha Hazra, MD, of the University of Chicago, and colleagues reported in Infection Control & Hospital Epidemiology.
The findings fit more with the data from January in Wuhan, China, where no cases of respiratory virus co-infection were found, than with the 20.7% co-infection rate reported from the San Francisco area about two weeks prior to the Chicago data (March 3-25).
While the co-infection rate will likely shift with prevalence of respiratory virus prevalence, declining in the summer and rising in the fall, Hazra noted that there are important implications for testing protocols.
"A lot of folks are concerned about the upcoming respiratory viral season and what that will mean in terms of a stress on diagnostics and potentially treatment as well," he told MedPage Today.
If a single negative swab was sufficient to rule out COVID-19 for patients under investigation who test positive for another pathogen on the panel, it would conserve resources in such a situation -- if the co-infection rate was negligible, he noted.
With these results, though, that's probably not optimal, commented Michael Stevens, MD, MPH, of Virginia Commonwealth University in Richmond and a spokesperson for the Society for Healthcare Epidemiology of America.
While the pretest probability of COVID-19 will shift with season and locality, "it's for sure not optimal to say three times out of 100 I'm going to miss COVID-19 because I identified another virus, especially among people who are admitted to the hospital, because that has implications for personal protective equipment and for not providing optimal therapy for those patients," he said. "We need to be able to test for both viruses."
The researchers used the BioFire FilmArray Respiratory Panel 2 along with in-house, real-time PCR testing for SARS-CoV-2, which doesn't have cross-reactivity.
During the study period, 2,535 specimens were simultaneously tested for 2,458 symptomatic patients. Among them, 18.1% were positive for SARS-CoV-2 and 14.4% were positive for at least one respiratory pathogen. Most of the specimens were collected in the emergency department (47.9%) or on inpatients (40.1%).
As expected from other viruses, coinfection was seen in significantly younger populations than in COVID-19-only cases (median 39 vs 58 years, P=0.02).
Social distancing and mask wearing should help across the board with respiratory infection rates, Hazra noted. Heavy emphasis on the flu vaccine this fall will hopefully help reduce co-infections with COVID-19 as well, he suggested.
However, "from a practical standpoint, we can anticipate we are going to have community spread for the immediate future until we have a vaccine or we have enough people infected to have herd immunity, which we are nowhere close to that," Stevens concluded.
"What we should be advocating for from a pragmatic standpoint is widespread availability of testing," he said. "Nationally in the United States there are many places that are suffering from inability to access testing, with long turnaround times, which very much negatively impacts health systems and patient care."