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YALE DAILY NEWS · FRIDAY, SEPTEMBER 17, 2021 · yaledailynews.com
SCIENCE AND TECHNOLOGY YSPH study examines high COVID-19 repeat positive test rates in nursing homes BY SYDNEY GRAY STAFF REPORTER In a Yale School of Public Health study, researchers found that rates of repeat positive tests among nursing home residents prior to widespread COVID-19 vaccine rollout were higher than in the general population and community-dwelling elderly. The study was conducted by doctoral student Jillian Armstrong GRD ’23, Head of Health Care-Associated Infections for the state of Connecticut Vivian Leung and associate professor of epidemiology Sunil Parikh. The research indicated that approximately 2.6 percent of elderly nursing home residents tested positive after an initial positive test 90 days prior, and that 13 percent of those individuals died within a few weeks of the repeat positive test. This study is one of many conducted in collaboration between the YSPH and the Connecticut Department of Public Health and was published in The Lancet Regional Health — Americas on Aug. 21. Study authors also commented on the reasons behind the higher rates of repeat positive tests. “Nearly 13% of [nursing home residents studied] died within a few weeks of the repeat positive test, suggesting that these repeat positive tests may be associated with severe outcomes,” Parikh wrote in an email to the News. “The implications are many. This data adds to a growing body of literature demonstrating the profoundly high risk of COVID-19 in nursing home residents.” The study made use of Connecticut’s testing program for SARS-CoV-2 and collaborated with multiple state laboratories that had been compiling reports of positive cases since the beginning of the pandemic, Parikh described. He wrote that researchers analyzed these results to identify nursing homes that were currently experiencing or at risk of experiencing outbreaks in their facilities. With increased testing around the state by the spring of 2020, researchers were able to test all nursing home residents on a weekly basis, with the goal of identifying and preventing outbreaks while also gathering useful data on COVID-19 among this vulnerable elderly population. “As the summer progressed, it became clear that many elderly in nursing homes were having multiple positive tests, often separated by weeks or months from one another,” Parikh described. “The question then became,
option is that these nursing home residents were indeed reinfected within the 90-day window. “It’s really hard to tease those three things out, and we still don’t know,” Ko said. Parikh also described some of the limitations of the study — namely, that researchers could not obtain patient samples for a process called comparative sequencing. This meant it was not possible to demonstrate if the viral genome that caused the initial reported infection in a nursing home resident was equivalent to the virus that caused a repeat positive test, Parikh said. “This just reflects the challenge and reality of doing research in the setting of a public health emergency,” Parikh wrote. “In these cases, one needs to explore other data that may further support whether these tests represent true reinfections.” He noted that they did find some evidence to support the possibility of reinfection. For instance, 80 percent of participants who died during the study had one or more negative intervening tests. But Parikh explained that while the researchers faced obstacles to collecting complete data, they do know that elderly individuals tend to be more medically frail and that living in highly congregated settings like nursing homes put them at greater risk of exposure to COVID-19. When one considers this information with the facts of biological “aging” of the immune system and the possibility that reinfections can occur as soon as three months after an initial infection, Parikh explained, it highlights the need to continue with COVID-19 testing in ZOE BERG/PHOTOGRAPHY EDITOR nursing homes. “We can’t assume that because COVID“Why would somebody have a positive test after the 19 has come through a facility, or that a resident has first test? We know that people can remain PCR positive already had COVID-19, that they are no longer at risk,” [for COVID-19] for longer than … other viral diseases,” Ko Parikh wrote. “Indeed, we are also seeing that the durasaid. “The median is about 18 days.” tion of protection after vaccination (in addition to after Ko said that there are three probable reasons that natural infection), is less in the elderly, than in younger the researchers were observing repeat positive tests in populations.” nursing homes. The first option was the case of “perOn Aug. 8, Gov. Ned Lamont issued an executive order sistent positives” — residents that were only infected that all long-term care facility staff in Connecticut must once but were still showing up as positive even 90 be vaccinated against COVID-19 and receive their first days after the initial infection — because of weakened dose of the vaccine no later than Sept. 7. Any long-term immune systems due to age. care facilities that do not comply with this rule are subject The second option, Ko described, was that more “per- to a $20,000 fine per day. sistent positives” were recorded in nursing home residents than the general population because these individContact SYDNEY GRAY at uals were getting tested more often. The third and final sydney.gray@yale.edu . ‘Are these actually reinfections, or are they just lingering cases, or false positives?’” He wrote that in the summer of 2020, the Centers for Disease Control and Prevention updated their recommendations, stating that any repeat positive tests within 90 days of an initial positive did not require a follow-up, as they “more likely represent[ed] persistent shedding of viral RNA than reinfection.” Raj and Indra Nooyi Professor of Public Health Albert Ko explained possible scenarios that would cause repeated positive tests when an individual has not actually been infected a second time.
Yale study examines effect of COVID-19 antibodies BY RAHMA AHMED CONTRIBUTING REPORTER A new study from researchers at Yale School of Medicine’s Iwasaki Lab analyzed the protective capacity of antibodies generated by both the COVID-19 vaccine and natural infection. The researchers examined the role of T-cells and B-cells in COVID-19 infections and differences in protection produced by vaccines and natural infection. When infected with COVID19 for the first time, both T-cells and B-cells play a role in combating the infection. However, the researchers found that when mice that had been vaccinated or had recovered from a natural infection became sick again later, they were still protected from infection — even if the scientists had selectively removed the T-cell part of their immune response. This indicates that antibodies alone, produced by B-cells, could protect against reinfection.The study was published in the journal Science Immunology on Sept. 2. “We saw that antibodies [generated from both vaccine and natural infection] were also sufficient to protect against the … Beta variant. That’s the variant that — at least until this point — had been shown to be the most evasive of antibody responses,” said Benjamin Goldman-Israelow, lead author of the study and a postdoctoral researcher at the Iwasaki Lab. “Even more so than the Delta variant.” The results show that, despite the Beta variant’s ability to evade adaptive immune responses, there is still a large enough antibody response to protect against significant disease. These results are similar to those seen in humans who get reinfected or who contract COVID-19 after being vaccinated, according to Goldman-Israelow. Their infections are often less severe and the likelihood of their hospitalization or death is low. The Delta variant is not as immune evasive as the Beta variant, as the variant has not altered
to evade adaptive immune responses as well, according to Goldman-Israelow. However, the Delta variant does seem to be able to transmit from individual to individual much faster than the Beta type. According to Goldman-Israelow, Delta has quickly become the predominant variant around the world. “There has been some data that is starting to come out … that shows that you have a higher likelihood of getting infected from Delta the further out you are from your second dose of the vaccine, which would suggest there is some weaning of immunity,” Goldman-Israelow said. It seems that vaccinated people are able to transmit the Delta variant because it has efficiently adapted to become highly transmissible, according to Goldman-Israelow. Providing booster shots might be able to further reduce transmission within the population. Such a move could potentially help protect those who are unable to get vaccinated or are immunocompromised. One of the unique aspects of mRNA vaccines is that they are easily modifiable, according to Jon Klein, a graduate student at the Iwasaki Lab. Although mRNA vaccines are a relatively new technology, they have proven to be highly effective in prevention. “A booster shot will likely be important in helping us [build] stronger immune protection against SARS-CoV2 and this will especially be required in the face of highly transmissible and potentially immune-evasive viral variants,” said Tianyang Mao, second author of the study and 5th year graduate student in the Iwasaki Lab. “One of the defining features of...immune memory, is [that] the quality … and the speed of the immune response is much stronger during reinfection. Now we actually remember what the pathogen looks like and we are
much more equipped to actually fight against these pathogens.” Although those who contract COVID-19 naturally generate antibodies that can protect against reinfection, the vaccine standardizes this protection, according to Klein. Medical histories, genetics and other factors can all play a role in the quality of antibodies that people can produce through natural infection. Some immune systems do not really make great antibodies while others do, according to Klein. “I think my personal opinion is that the vaccine generates really high quality antibodies almost universally,” Klein said. “In terms of booster shots, viruses naturally evolve over time. So in theory, booster shots may be required in the future. What we’ve seen now is that the vaccine produces pretty durable immunity.” According to the Centers for Disease Control and Prevention, 53.4 percent of the total U.S. population has been fully vaccinated against the virus. Contact RAHMA AHMED at rahma.ahmed@yale.edu .
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