Over the past year, scientists keep seeing a COVID-19 oddity showing up in New York Cityxe2x80x99s sewer system: bits and pieces of virus in the wastewater that suggest therexe2x80x99s a mysterious new variant in the city. Thankfully, therexe2x80x99s no evidence that itxe2x80x99s particularly infectious or deadly. But scientists arenxe2x80x99t sure where the xe2x80x9ccryptic lineages,xe2x80x9d as researchers call the fragments, are coming from. One theory is that the virus is coming from people whose strains have yet to be sequenced. But another is totally and utterly alarming: that this variant could be courtesy of the cityxe2x80x99s rats.

A new paper about the mystery was published in Nature Communications last week. Curbed spoke with four of the co-authors xe2x80x94 John Dennehy, a virologist at Queens College; Monica Trujillo, a microbiologist at Queensborough Community College; Marc Johnson, a virologist at the University of Missouri; and Davida Smyth, a microbiologist at Texas A&M University xe2x80x94 about whether or not New Yorkers should be bracing themselves for a rat-COVID wave.

Whatxe2x80x99s the argument that this variant is coming from rats?

Marc Johnson: One of the amino-acid changes that wexe2x80x99re seeing in the virus has not been seen in patients. Ever. But this amino-acid change has been seen in rodent-adapted virus, which really says something to me. In immunocompromised patients, you see a lot of similar mutations, but this one particular mutation right at the receptor binding site has just not been found. If these lineages are coming from an immunocompromised patient, it is probably that, a single patient, and itxe2x80x99s really hard to believe that this much signal could come from one person.

How could rats even catch COVID?xc2xa0

Johnson: Alpha, Beta, and Gamma have gained the ability to infect rodents, but the original strain of COVID could not.

John Dennehy: Theyxe2x80x99re probably drinking sewer water, and I heard they eat feces, so if therexe2x80x99s any clumps of material in the wastewater, Ixe2x80x99m sure they might try to consume it. Wexe2x80x99ve never detected live virus in the wastewater. But given the volume of wastewater and the number of rats, itxe2x80x99s certainly possible that theyxe2x80x99ve gotten infected that way.

What points toward rats over other animals?

Johnson: There was a figure in the paper where we actually show that these lineages have all gained the ability to utilize the rat receptor. It was this suspicion that led us to do the experiment that confirmed this: I was like, xe2x80x9cWell, probably not rats, but if it is rats, then it should have gained the ability to infect rat cells,xe2x80x9d and sure enough, the virus did.

Based on that hunch, you tested for signs of the virus in city rats. What does that entail?xc2xa0

Johnson: So John would go wandering around dark alleys at night and collect rat feces for me and hexe2x80x99d put them in Ziploc bags, label them, and send them to me. My brave undergraduates would plug their noses and extract the RNA from them the same we do with wastewater, and screened them for SARS-CoV-2 RNA. None of those came back positive. In the case of APHIS [the Animal and Plant Health Inspection Service in the U.S. Department of Agriculture, which was a research partner], they would collect blood from rats and send them to us and we would check to see if they had antibodies against SARS-CoV-2, which would tell us if theyxe2x80x99ve been previously infected, and none had clear antibodies.

Dennehy: Itxe2x80x99s estimated that there are at least a couple million rats. We only tested, what, almost 100? Itxe2x80x99s quite possible we didnxe2x80x99t collect the right animals.

Is there any evidence that COVID-19 is widely circulating in rats?

Johnson: Not that we know of. Itxe2x80x99s kind of haunting, but itxe2x80x99s coming from somewhere.

Monica Trujillo: I think the important thing to keep in mind here is that every time the virus replicates, it has a possibility to mutate. So if there is a population where you are not aware where the virus is replicating, that is worrisome. That is why itxe2x80x99s important to know where these cryptic sequences are coming from.

But have new variants developed in animal hosts? Has that been documented?

Dennehy: Not that we know of. Omicron is possibly hypothesized to come from animals in Africa, but thatxe2x80x99s not proven. There are some instances where other animals have gotten infected and then spread it back to humans. I think mink is an example.

Johnson: The one that jumped into mink mutated a little bit, but nothing like what wexe2x80x99re seeing.

What does that say to you? Could rats, if infected, possibly reinfect humans with a new strain?

Johnson: We donxe2x80x99t know where Omicron came from. So we donxe2x80x99t know where Pi [an as yet nonexistent variant] is going to come from xe2x80x94 but these animals sure look like likely candidates.

So xe2x80xa6 could rats potentially spread the virus in the city?

Dennehy: Yes and no. I think rodents tend to inhabit the same spaces as we do. I think probably there are often more interactions with humans and rats than we realize, not necessarily physical contact, but touching the same surfaces, that sort of stuff. Perhaps rats could exhale the virus into the air in certain areas xe2x80x94 the subways.

Johnson: It doesnxe2x80x99t mean itxe2x80x99s an immediate, imminent threat. Itxe2x80x99s worth paying attention to, but itxe2x80x99s not worth panicking over. Itxe2x80x99s theoretically possible, but wexe2x80x99ve been following these lineages for over a year now and we havenxe2x80x99t seen it happen yet.

Davida Smyth: Rats are known to be vectors. They do transmit things, but itxe2x80x99s very rare. So one of the major things we see, for example, is leptospirosis. Thatxe2x80x99s something that does pop up from time to time. Itxe2x80x99s associated with the urine of a rat, but itxe2x80x99s very, very rare. So in order for you to be infected by a rat, youxe2x80x99d have to be living in very close quarters with the rats.

Whatxe2x80x99s the worst-case scenario here? The best-case one?

Johnson: If it is in rats, it could be that it can only infect rats and loses the ability to infect humans altogether. Thatxe2x80x99s fully possible. Worse-case scenario is it spills back into humans and itxe2x80x99s Pi. Best-case scenario is it takes care of your rat problem. Problem solved.

This interview has been edited and condensed for clarity.