High school students working in the lab of Florian Krammer, PhD, as part of the New York City Virus Hunters program. Image credit: Christine Marizzi, PhD, BioBus.

The H5N1 bird flu virus was detected for the first time in cows in March, and in May, a third person tested positive for bird flu, presumably from exposure to infected dairy cattle. With viral fragments detected in dairy, the Food and Drug Administration tested and announced that pasteurized milk was safe to drink, and the Centers for Disease Control and Prevention (CDC) has been working with city and state health authorities and institutions nationwide to monitor any new spread of the pathogen.

Were the bovine cases of bird flu expected and detected quickly?

Dr. Krammer: It took a while before H5N1 avian influenza was detected in cows for several reasons. Typically, cows do not get infected with influenza A virus. So nobody’s looking at cows, because why would you look if it has historically not been there? Compared to the poultry industry, where there is a good system in place for rapid detection of any outbreaks. Also, in cows, the H5N1 avian influenza is a slow disease. In avian species, when they get infected, they tend to die quickly. Other mammals, like bears, raccoons, or foxes that get infected with H5N1 via ingestion of infected birds, they often get neurological symptoms and die quickly too. It is different with the cows.

Are there adequate systems to prevent and protect against unexpected pathogenic outbreaks?

Dr. Krammer: From a scientific perspective, we have very good capabilities for detecting pathogens quickly. But preventing outbreaks is a complex task that takes more than just good science. Take the cases of avian influenza in dairy cattle, for example: When the outbreak occurred, there were no legal grounds for initial testing, or even for restricting movement of cows across state borders—there was not much the government could do. Academic networks like the Centers of Excellence for Influenza Research and Response, funded by the National Institute of Allergy and Infectious Diseases, produced the first reports of the recent cases, and are much more flexible and can respond quicker. These networks work very closely with government agencies to provide needed recommendations to handle unexpected outbreaks. One of these centers is located at Mount Sinai and we have also been very active with H5N1 surveillance and research.

Dr. Simon: Besides global and national surveillance networks, local efforts are important, too, especially for a large metropolitan city such as New York City. We have known for a long time that because New York is a very popular place for tourists to visit, that makes it a very likely entry point for any virus or pathogen. The city and state have various surveillance programs, and Mount Sinai also has a pathogen surveillance program that is more than 10 years old. This program is co-directed by Harm van Bakel, PhD; Emilia Sordillo, MD, PhD; and myself. We have been tracking nosocomial infections—picked up while in a hospital—and gaining information about circulating pathogens, including influenza virus strains, bacteria, and fungi. Our Pathogen Surveillance Program has resulted in Mount Sinai being the only site in the United States that is part of the Global Hospital Influenza Surveillance Network, which works to provide a unified protocol on covering hospitalized cases of severe influenza at a global level.

Are there any particular pathogens these networks are keeping an eye out for?

Dr. Simon: Some pathogens that the Mount Sinai Pathogen Surveillance Program is watching include bacteria like Staphylococcus aureus, Enterococci and Clostridioides difficile; viruses like influenza, RSV, SARS-CoV-2, and hantavirus; as well as fungi such as Candida auris.

What are some research questions these surveillance networks are trying to answer?

Dr. Simon: Some major questions include how influenza strains change in humans—their escape from the human immune system or their change of glycosylation (the process where sugar molecules attach to lipids, proteins, or other organic molecules); how to improve vaccines; and ensuring our diagnostics are able to pick up all the strains that can cause disease in humans.

Dr. Krammer: The tracking of the changes is not a problem. The World Health Organization does that on a regular basis, and we can do that too at Mount Sinai. A bigger challenge might be: can we catch up with seasonal viruses with our vaccines, or are we always a step behind? One way to tackle that is trying to design a vaccine that gives us broad protection, no matter if the viruses change, or if the strain is an H5N1 or an H1N1. Mount Sinai is very active in working on a vaccine that would work against any type of influenza—a universal influenza virus vaccine. As for diagnostics, there are so many subtypes of influenza viruses, but you never know which one presents a risk. We’re trying to find out what are the pathogenicity markers that make a strain dangerous for humans and make it transmit well. Or, what determines the risk of avian influenza jumping to humans? That’s why we have a program that looks at not only human influenza, but also avian influenza in animals in an urban space in New York City.

What does it take for such surveillance networks to succeed?

Dr. Krammer: You have to consider the fact that influenza viruses were not human viruses originally—they were bird viruses—and to tackle the vast topic of “One Health,” an approach that seeks to address the health of people, animals, plants, and the environment interconnectedly, you might need a wide range of expertise. This includes epidemiologists, immunologists, molecular virologists, structural biologists, doctors of veterinary medicine, and medical doctors. And that’s the nice thing about health systems like Mount Sinai, where we have a lot of those experts and they are able to come together to tackle this issue.