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CNN — Covid-19 was never just another cold. We knew it was going to stick around and keep changing to try to get the upper hand on our immune systems. But we’ve changed, too. Our B cells and T cells, keepers of our immune memories, aren’t as blind to this virus as they were when we first encountered the novel coronavirus in 2020. The US Centers for Disease Control and Prevention has screened blood samples and estimates that 97% of people in the US have some immunity to Covid-19 through vaccination, infection or both. Then there’s science: We have updated vaccines and good antivirals to lean on when cases start to rise. Masks still work. Rapid tests are in stores. We now know to filter the air and to ventilate our spaces. Those strategies, plus our hard-won immunity, had helped bring our national numbers of infections, hospitalizations and deaths down to levels that felt almost forgettable. Almost. Now that Covid-19 infections have started to rise again, it feels like people all over the country are testing positive, and it’s hard to know how to react. The government has been dialing back its response since the end of the public health emergency in May. Good Covid-19 data is hard to come by and harder to interpret. So if people are less likely to be hospitalized or die from a Covid-19 infection now, has the danger passed? Is there still reason to worry if you do catch the infection for a second, third or fourth time? Experts say it’s less risky to catch Covid-19 than it used to be, but there are still good reasons not to treat it casually. “At this point, the risk is lower because of our prior immunity, whether for severe outcomes or for long Covid,” said Dr. Megan Ranney, an emergency physician and dean of the Yale School of Public Health. “Covid is still more dangerous than the flu, but its level of danger is becoming less,” she said, noting that we’re still very early in our human experience with the coronavirus, even four years in, and there are still things we don’t know. “But for it to behave like other respiratory viruses in terms of seasonality and surges is entirely expected,” she added. It would be “really weird” for Covid to disappear or for it not to cause illnesses, hospitalizations and deaths. “It is still a virus,” Ranney said. But a somewhat predictable waxing and waning of infections doesn’t make Covid-19 something to turn our backs on. Our immune systems are better at spotting danger After more than three grueling years, nearly all Americans have some immunity against Covid-19. That means our immune systems – as long as they’re healthy and working as they should – will remember most forms of the coronavirus when it next comes our way. That process takes some time to get going, however. That lag may give the virus enough of a window to get a foothold in our nasal passages or lungs, and we get sick. We may feel crummy for a few days, but then our B cells and T cells get their antibody production up and running. Eventually, they shut the virus down, and we get better. That’s what should happen. But for many, their immune system just doesn’t kick in as quickly or as vigorously as it should. Immune function drops off naturally with age. About 1 in 4 Americans is over the age of 60, according to census data. Then there are certain medications and health conditions that suppress immune function. About 3% of the U.S. population – 7 million people – is severely immunocompromised, according to the National Institutes of Health. This is a group taking medications to protect organ transplants or who are getting powerful drugs for cancer treatment, for example. Then there’s individual variability. Through genetic bad luck, some people may just be at higher risk of serious reactions to Covid-19 infections, and they probably wouldn’t know it. Taken together, that’s a sizeable pool of people who benefit greatly from having antibodies at the ready to take on the coronavirus as fast as possible. Vaccines get those antibodies in place and ready to work as soon as they’re needed. Sometimes, people are so immunocompromised that vaccines can’t help them much, either. They benefit from preventive shots containing Covid-fighting antibodies that are built to stick around the body for a few months. Until this year, there was such a preventive product available, Evusheld. But the virus has evolved so much that Evusheld lost its potency, and in January, the FDA revoked its authorization. Since then, people who have very low immune function haven’t had anything to protect them from infection or severe disease. But that could change. The government announced this week that it’s funding the development of a new preventive antibody through the drug company Regeneron. Trials of that drug are expected to start this fall, according to the US Department of Health and Human Services. While nearly all of us have immune systems that can recognize key parts of the virus now, even that memory to the infection fades over time. The longer it has been since you’ve been infected or vaccinated, the more forgetful your immune system becomes. Those B cells and T cells, “they’re going to be a little slower to respond. They’re not they’re not as primed and ready to go,” Ranney said. Your strongest immunity will be in the two weeks to two months after you get your vaccines. That means it’s smart to try to get your shots shortly before Covid is expected to be on the upswing. Just like for flu, experts expect the worst of Covid to hit in the fall and winter. CDC Director Dr. Mandy Cohen said that even though cases are going up now, most people will be better off waiting a few weeks to get the newly updated Covid-19 vaccines rather than trying to get one of the older bivalent

Researchers have discovered that the chikungunya virus can transmit directly from one cell to another through structures called intercellular long extensions (ILEs). This discovery may explain the virus’s resilience against antibodies and could pave the way for new treatments. The virus restructures infected cells to protect against antibody attacks. Scientists at the Albert Einstein College of Medicine have discovered that the <span class="glossaryLink" aria-describedby="tt" data-cmtooltip=" virus A virus is a tiny infectious agent that is not considered a living organism. It consists of genetic material, either DNA or RNA, that is surrounded by a protein coat called a capsid. Some viruses also have an outer envelope made up of lipids that surrounds the capsid. Viruses can infect a wide range of organisms, including humans, animals, plants, and even bacteria. They rely on host cells to replicate and multiply, hijacking the cell's machinery to make copies of themselves. This process can cause damage to the host cell and lead to various diseases, ranging from mild to severe. Common viral infections include the flu, colds, HIV, and COVID-19. Vaccines and antiviral medications can help prevent and treat viral infections. ” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]”>virus causing chikungunya fever can spread directly from cell to cell—perhaps solving the longstanding mystery of how the virus, now emerging as a major health threat, can manage to escape antibodies circulating in the bloodstream. The findings, recently published in the journal Nature Microbiology, suggest potential pathways for the creation of vaccines or treatments against chikungunya fever, a debilitating and increasingly common mosquito-borne disease. A Possible Explanation for Prolonged Infections “Previously, chikungunya virus was thought to spread in the body by infecting a cell, replicating within that cell, and then sending new copies of the virus into the bloodstream that then infect new cells,” said study leader Margaret Kielian, Ph.D., professor of cell biology and the Samuel H. Golding Chair in Microbiology at Einstein. “However, we’ve found that the virus can also hijack a host cell’s cytoskeleton—the proteins that support cells and maintain their shape. The virus causes the infected cell to send out long thin extensions that make contact with uninfected neighboring cells, enabling the virus to safely and efficiently travel from one cell to another.” Dr. Kielian and her colleagues have named these virus-induced structures intercellular long extensions, or ILEs. “This mode of viral transmission may not only shield some copies of the virus from the host’s immune response, but it may also explain why symptoms of chikungunya infection can persist for many months or years,” added first author Peiqi Yin, Ph.D., a postdoctoral fellow in Dr. Kielian’s lab. In addition to fever, chikungunya infections often lead to chronic and debilitating arthritis. The virus is spread to humans by the bite of infected mosquitoes, which become infected by feeding on people who already have the virus. Over the past 15 years, chikungunya virus has become an important and increasingly widespread human pathogen. Multiple outbreaks have caused millions of human infections in numerous areas including the Americas, Africa, Asia, Europe, and the Caribbean. The National Institute of Allergy and Infectious Diseases lists chikungunya virus as a Category B Pathogen, the second-highest priority for organisms posing threats to national security and public health. Confirming a Cell Structure’s Role Dr. Kielian and colleagues discovered the presence of ILEs in chikungunya-infected cells several years ago, but it wasn’t clear whether the structures facilitated cell-to-cell viral transmission. The study described in the Nature Microbiology paper was designed to answer that question. The first part of the study involved the use of cultured mouse cells. The researchers exposed the cells to chikungunya virus that expressed a fluorescent reporter protein, allowing them to observe that infectious virus particles were indeed being transmitted from cell to cell via ILEs. Cell-to-cell transmission occurred even in the presence of high quantities of neutralizing antibodies that were added to the culture medium. To confirm this mode of cell-to-cell transmission in living animals, the researchers studied chikungunya infection in mice. Mice that were first inoculated with neutralizing antibodies and were then directly injected with chikungunya virus did not become infected. However, antibody-treated mice that were then injected with virus-infected cells (rather than just the virus) did develop chikungunya infections that were resistant to the neutralizing antibodies. “Together, these studies show that ILEs shield chikungunya virus from neutralizing antibodies and promote intercellular virus transmission, both in vitro and in vivo,” said Dr. Yin. The mouse studies were conducted by Thomas E. Morrison, Ph.D., and his group at the University of Colorado School of Medicine in Aurora. Short-Circuiting the Connections In a final set of studies, the researchers determined that certain antiviral antibodies were able to block ILEs from forming and to prevent cell-to-cell transmission. “If we can generate the production of such antibodies in human patients, or develop other methods to stop ILE formation, that could be especially helpful in combatting the chronic symptoms of chikungunya infection,” said Dr. Kielian. “We’re currently studying different ways to do this.” Reference: “Chikungunya virus cell-to-cell transmission is mediated by intercellular extensions in vitro and in vivo” by Peiqi Yin, Bennett J. Davenport, Judy J. Wan, Arthur S. Kim, Michael S. Diamond, Brian C. Ware, Karen Tong, Thérèse Couderc, Marc Lecuit, Jonathan R. Lai, Thomas E. Morrison and Margaret Kielian, 17 August 2023, Nature Microbiology.DOI: 10.1038/s41564-023-01449-0 The research was supported by grants from the <span class="glossaryLink" aria-describedby="tt" data-cmtooltip=" National Institutes of Health The National Institutes of Health (NIH) is the primary agency of the United States government responsible for biomedical and public health research. Founded in 1887, it is a part of the U.S. Department of Health and Human Services. The NIH conducts its own scientific research through its Intramural Research Program (IRP) and provides major biomedical research funding to non-NIH research facilities through its Extramural Research Program. With 27 different institutes and centers under its umbrella, the NIH covers a broad spectrum of health-related research, including specific diseases, population health, clinical research, and fundamental biological processes. Its mission is to seek fundamental knowledge about

Hospitalizations are still low but are on the rise in recent weeks, according to the Centers for Disease Control and Prevention. A late-summer wave of coronavirus infections has touched schools, workplaces and local government, as experts warned the public to brace for even more Covid-19 spread this fall and winter. Hospitalizations have increased 24 percent in a two-week period ending Aug. 12, according to the most recent data from the Centers for Disease Control and Prevention. Wastewater monitoring suggests a recent rise in Covid infections in the West and Northeast. In communities across the United States, outbreaks have occurred in recent weeks at preschools, summer camps and office buildings. Public health officials said that the latest increase in Covid hospitalizations is still relatively small and the vast majority of the sick are experiencing mild symptoms that are comparable to a cold or the flu. And most Americans, more than three months after the Biden administration allowed the 2020 declaration calling the coronavirus a public health emergency to expire, have shown little willingness to return to the days of frequent testing, mask wearing and isolation. But for Americans who have become accustomed to feeling the nation has moved beyond Covid, the current wave could be a rude reminder that the emerging New Normal is not a world without the virus. “We’re in almost the best place we’ve been in the pandemic since it began,” said Michael T. Osterholm, the director of the Center for Infectious Disease Research and Policy at the University of Minnesota. “But we are caught in the very uncomfortable area of having left the fog of the pandemic war and trying to understand what the sunrise on a normal post-Covid world looks like.” In cities across the country, the remnants of coronavirus restrictions still remain, even if they are no longer observed. Retail stores may have signs in the windows requesting that patrons wear masks, but no one inside is wearing them. Years-old stickers asking customers to stand six feet apart in line are faded, worn and ignored. The occasional storefronts in major cities advertise free Covid-19 testing, though the spaces inside are empty. And the virus is still disrupting work, school and politics: A Covid outbreak tied to a City Council meeting in Nashville this month left more than a dozen people infected, including council members, city employees and at least one reporter. One of the people who tested positive for Covid, Freddie O’Connell, a City Council member who is in a Sept. 14 runoff election for mayor, said it was a stark reminder that the virus had once again taken hold in the community. “All year long, there have been many Covid spikes in my personal network, but it hasn’t felt like this, where all of a sudden we’re back to events that we used to hear about in 2020, where suddenly dozens of people in one fell swoop all get it,” Mr. O’Connell said in an interview from his home, where he had been marooned for a five-day quarantine. “I haven’t really had to think about the phrase ‘superspreader event’ in a long time.” A patient’s Covid-19 and flu tests being prepped in Oregon City, Ore.Mason Trinca for The New York Times As students have returned to school in recent days, most administrators have signaled that they are not planning to return to stricter rules surrounding masks and testing, typically only asking parents to keep their children home when they are sick. In Chicago, where Covid-related hospitalizations are still extremely low but have crept up in recent weeks, the public school district promised to provide free rapid Covid tests to students and staff but did not intend to resume testing in schools. Even in the face of rising Covid infections, there is a balance that should be struck in schools now, said Hedy N. Chang, the executive director of Attendance Works, a national group that promotes solutions to chronic absenteeism. “We got trained to stay home for every sign of illness during the pandemic,” she said. “We actually have to shift norms again, to being judicious and thoughtful about when we keep kids home, and only keeping them home if we think it’s truly a problem.” Dr. John M. Coleman, a pulmonary and critical care doctor at Northwestern Memorial Hospital, said he expected Covid infections to continue to increase this fall and winter, but he noted that the most recent strains of the virus were less severe than those that circulated early in the pandemic. People who are hospitalized for Covid now tend to have pre-existing conditions or suppressed immune systems that make them more susceptible to severe symptoms, he said. “Moving forward, we have to learn to live cohesively with Covid,” Dr. Coleman said. “Covid is always going to be around.” Particularly for people who already have health risks, he said, it is crucial to receive the new booster this fall, wash hands frequently and wear a mask if feeling unwell. Throughout the summer, public health officials have stressed prevention and treatment in the face of an increase in cases. The Cambridge, Mass., health department said in a statement this month that it saw outbreaks at nursing homes in the city and urged the public to stay up-to-date on vaccinations. But some institutions have responded to the recent increase in Covid infections by reinstating pandemic-era rules. In keeping with an order from the health department in Los Angeles County, the movie studio Lionsgate recently sent a memo to staff members informing them that because of a Covid outbreak among employees, they would be required to wear masks in the office again. (The health department notified the studio on Friday that because it had reported no new cases, the requirement was lifted.) Morris Brown College, a small private school in Atlanta, announced this month that it would require face masks on campus again. The school banned parties and large gatherings on campus for two weeks and said that temperature checks would be administered to

Patients with an infection before liver transplant had excellent survival outcomes despite requiring more complex post-transplant care. “The risk of poor outcomes because of the persistence/recurrence of infections after liver transplant (LT) is a main barrier in the decision to proceed or not to LT in patients with cirrhosis and infections,” Salvatore Piano, MD, PhD, and colleagues wrote. “In fact, infections increase morbidity and mortality in the early post-transplant period, and use of immunosuppression may limit the ability of the host to counteract the pathogens. For these reasons, international guidelines state that active infections should be adequately treated before LT. However, the optimal timing of LT in patients surviving an episode of infection as well as their prioritization on LT waiting list is still to be established.” Further, studies that examined post-LT outcomes among patients who survived an infection have conflicting results, according to Dr. Piano and colleagues. While some studies demonstrate no difference in survival for patients with versus without pre-LT infections, others indicate a higher risk for sepsis-related mortality in those with pre-LT infections, particularly if complicated by septic shock. For a study published in JHEP Reports, the researchers examined the influence of bacterial infections within the 3 months preceding LT on post-transplant outcomes and the impact of time from infection improvement/resolution to LT on post-transplant outcomes. The single-center study, conducted from 2012 to 2018, categorized patients undergoing an LT into two groups: (1) patients surviving a bacterial infection in the 3 months prior to LT (study group) and (2) patients with no infection preceding LT (control group). Dr. Piano and colleagues obtained data on post-LT outcomes, including complications, new infections, and survival. LT Survival Comparable With or Without Infection The study included 466 LT recipients, most of whom (n=358) who were in the control group rather than the study group (n=108). Median age was comparable in the control group versus the study group (58 vs 56). More than 70% of patients in each group were men. Hepatocellular carcinoma occurred more often in the control group compared with the study group. The most common cirrhosis etiology was hepatitis C virus for the control group and alcohol for the study group. Following LT, there were higher incidences in the study group of new bacterial (57% vs 20%; P<0.001) and fungal infections (14% vs 5%; P=0.001) and septic shock (8% vs 2%; P=0.004) than in the control group. Several factors served as independent predictors of post-LT infections, including the Model for End-stage Liver Disease (MELD) score (P=0.002), alcohol-related cirrhosis (P=0.011), and bacterial infection before LT (P<0.001). Survival rates were comparable between the study group and control group at 1 year (88% vs 89%) and 5 years (76% vs 75%; Figure). In our series, patients surviving an infectious episode within 3 months before LT had a higher incidence of new infections, both bacterial and fungal, a higher incidence of septic shock, and required longer ICU and in-hospital care,” Dr. Piano and colleagues wrote. “Therefore, although survival is excellent, post-transplant care is more complex in patients undergoing LT after a bacterial infection.” Determining LT Timing After Infection Historically, it has been unclear how long clinicians should wait before proceeding with LT among those with infections, Dr. Piano and colleagues note. “An important finding of our study is that, in patients with pre-LT infection, time elapsed from infection improvement/resolution to transplantation did not affect patient outcome. Patients who underwent LT within 7 days [of] infection improvement/resolution had rates of post-operative complications comparable with those of patients who underwent LT beyond 7 days from infection improvement/resolution.” This finding has direct implications for clinicians, they continue. “As soon as bacterial infection is controlled, it is safe to proceed with LT. This is a novel finding, as no previous study assessed a safe time interval from infection improvement/resolution to LT.”