Respiratory virus researcher Masfique Mehedi tackles RSV, COVID, and influenza at the UND School of Medicine & Health Sciences<\/p>\n
As with many papers in the sciences, a series of seemingly benign phrases belied a more significant result: \u201cWe confirmed RSV infects primarily ciliated cells by detecting RSV [nucleoprotein] mRNA in the infected ciliated but not in the goblet or basal cells,\u201d wrote Masfique Mehedi, Ph.D., and his research team in a paper published in Virus Research<\/a> early in 2023.<\/p>\n Translation: we now know what\u2019s happening at the cellular level that makes respiratory syncytial virus (RSV) dangerous for infants in particular \u2013 and it\u2019s not systemic in nature.<\/p>\n This is all good news, said Mehedi, an assistant professor in the UND School of Medicine & Health Sciences (SMHS) Department of Biomedical Sciences<\/a> specializing in RSV, in so far as knowing better the pathology of the virus allows researchers to focus on better treatments for the disease.<\/p>\n This knowledge also, somewhat fortuitously, helps researchers understand just a bit more about that other high-profile lung infection: SARS-CoV-2, the coronavirus behind the COVID-19 pandemic.<\/p>\n <\/p>\n RSV and\/or bronchiolitis?<\/strong><\/p>\n But first RSV.<\/p>\n Identified in 1956, RSV is a common viral infection of the lower airway. It takes its name from the fact that infected cells fuse to produce multi-nucleus cells, or syncytia, in the airway\u2019s outermost cell wall, or epithelium. These infected cells become inflamed and expand into the airway, narrowing the host\u2019s bronchioles (those branches within the human lung that end in the alveoli where oxygen is absorbed) and complicating respiration in a condition known as bronchiolitis.<\/p>\n While the infection is usually unremarkable in healthy adults and children ages two and up, it can be serious for infants in particular because the inflammation of babies\u2019 already tiny airways can obstruct breathing very quickly.<\/p>\n But the specific mechanism of that inflammation, which is key to how the virus functions, has been less well-known, said Mehedi.<\/p>\n \u201cIn our bronchial model, upper-layer cells are infected by RSV and the infection is limited to that specific cell type \u2013 it does not infect other cell types,\u201d explained Mehedi to North Dakota Medicine<\/em><\/a> from his second-floor office in the SMHS. \u201cAs a result, [RSV] does not damage the epithelium. This means that over a period of time the infection resolves on its own. It may recapitulate \u2013 some of us may get RSV often \u2013 but most adults have no problem.\u201d<\/p>\n More specifically, Mehedi\u2019s team found that the bronchiolitis experienced by RSV patients was occurring because the cytoskeletons of infected airway cells \u2013 the complex network of interlocking proteins in cells\u2019 cytoplasm \u2013 was swelling, in some cases to double the size of uninfected cells. Despite this swelling, RSV left the cells\u2019 membrane or \u201cskin\u201d intact, resulting in an undamaged cell wall after the inflammation had subsided, almost as if there had never been an infection in the first place.<\/p>\n \u201cRSV is diagnosed as \u2018bronchiolitis\u2019 99% of the time, so physicians previously didn\u2019t even test for it,\u201d continued Mehedi, speaking of the pre-COVID adult population, which is typically given nothing by way of treatment other than the tried-and-true prescriptions of bedrest, fluids, and anti-inflammatory medications \u2013 with the occasional bronchodilator. \u201cThey know that bronchiolitis is RSV, so what\u2019s happening is that adults are generally okay during and after infection.\u201d<\/p>\n A baby\u2019s airway is much thinner, though, which is why providers tend to see \u201csevere pathophysiology\u201d in that population. So it is that finding novel treatments for the infection feels especially important this year, Mehedi added, given the high rate of RSV infection among children that providers have seen of late.<\/p>\n As Mehedi put it, the United States experienced a surprisingly early and notably severe surge in cases of RSV in late-2022. Pointing to one Centers for Disease Control and Prevention<\/a> (CDC) report, Mehedi noted too that after a few years of reduced prevalence of the virus \u2013 due likely to the infection control protocols brought on by the pandemic \u2013 the rate of RSV hospitalizations jumped by a factor of ten in Nov. 2022, relative to Nov. 2019.<\/p>\n \u201cBecause we don\u2019t have a vaccine for people under age 60, or therapeutics to treat RSV, the virus still causes 34 million acute lower respiratory infections globally,\u201d he said. \u201cPre-term babies, infants, and young children are the most vulnerable to getting a severe disease from RSV infection, so we need to find better ways of helping this population.\u201d<\/p>\n <\/p>\n Wherefore vaccines? <\/strong><\/p>\n All of this begs two questions: why the surge now and what is the status of an RSV vaccine, for children in particular?<\/p>\n This is where the conversation gets thorny, admitted Mehedi, who, after working with former National Institute of Allergy and Infectious Diseases (NIAID)<\/a> principal investigator and RSV specialist Dr. Peter L. Collins, has been managing his own lab at UND since 2017.<\/p>\n On the surge question, it\u2019s likely that the increased incidence of RSV is due not only to a relaxing of pandemic protocols but the more frequent testing of children for the virus, Mehedi said, which is another result of COVID-19.<\/p>\n \u201cGenerally, clinicians confidently identified RSV as the cause of bronchiolitis without generic RSV testing, since RSV is known to cause bronchiolitis,\u201d he said. \u201cHowever, since 2022, RSV has been included in the diagnostic panel with COVID testing. Therefore, RSV has been detected in higher numbers than usual.\u201d<\/p>\n Concerning the vaccine, Mehedi, who is very much in favor of vaccination generally, admits that the necessity of an RSV vaccine for a large majority of the population and for infants remains an open question in the field. Citing the distinction between the variety of potential RSV vaccines currently undergoing clinical trial, Mehedi suggests that the \u201clive attenuated\u201d vaccines \u2013 which utilize a reduced form of the virus in question to induce the immune system to produce antibodies against that virus \u2013 seem to be the safest and most effective option for the infant population.<\/p>\n But not all vaccines being reviewed are live attenuated. And recently, the FDA approved an adjuvanted RSV vaccine for patients age 60 and older only.<\/p>\n \u201cFor kids, the vaccine platform should be live attenuated,\u201d Mehedi insisted, referencing one paper authored by Collins that notes how the \u201clive-attenuated approach continues to offer a number of advantages for development of an RSV vaccine for RSV-na\u00efve infants and young children.\u201d \u201cThat is the best way of vaccination for those under two years old.\u201d<\/p>\n <\/p>\n RSV vs COVID <\/strong><\/p>\n And given his interest in infections of the airway, Mehedi was obviously primed to study SARS-CoV-2 as soon as it emerged in 2019. Since 2020 his team has contributed to five published papers on coronavirus, helping researchers and physicians understand the differences between SARS-CoV-2 and RSV.<\/p>\n \u201cBoth viruses use a similar droplet or airway transmission, but they differ in their pathophysiology,\u201d explained Mehedi, adding that while both viruses contact the bronchial wall, only RSV sticks. \u201cWhat I mean by that is that RSV always causes bronchiolitis, and only in rare cases pneumonia. But SARS-CoV-2 never causes bronchiolitis. It very often causes pneumonia \u2013 and almost anything you can name \u2013 because it becomes a systemic infection.\u201d<\/p>\n This ability to move past the epithelium and, thus, enter the bloodstream is what has made SARS-CoV-2 so serious, he added.<\/p>\n