Virus World

A new study analyzing nearly 2 million patient records in Israel concludes that for most people, the troubling symptoms that persist after a mild Covid infection fade away after about a year. Since long Covid emerged, how best to define it, predict it, and treat it has been up for debate, but perhaps the most urgent question for patients and providers alike has been how long it lasts. A new study analyzing nearly 2 million patient records in Israel concludes that for most people, the troubling symptoms that persist after a mild Covid infection fade away after about a year. Just as estimates of long Covid’s prevalence have varied widely, so have conclusions about a variety of symptoms. Covid infections reach into multiple organ systems, as does long Covid. Scientists have reported on some neuropsychiatric conditions lingering for two years, for example, but the team from the KI Research Institute wanted to paint a broader picture of long Covid’s duration. “When we started this study there was a lot of uncertainty regarding the long-term effects of the pandemic and there was a fear that a large proportion of infected individuals will have long-lasting symptoms and emergence of new morbidities,” the study’s senior author Maytal Bivas-Benita and lead author Barak Mizrahi said in a joint email to STAT. “As we analyzed the data, we were surprised to find only a small number of symptoms that were related to Covid and remained for a year post infection and the low number of people affected by them.” For their paper published Wednesday in BMJ, the researchers analyzed 1,913,234 patient records from Maccabi Healthcare Services, a large health maintenance organization in Israel whose members were tested for Covid-19 from March 2020 to October 2021, when the original virus and the Alpha and Delta variants were circulating. After compiling a list of 70 long Covid symptoms, they looked for them at different time points, comparing the nearly 300,000 patients who tested positive to comparable patients who tested negative for Covid-19, excluding anyone hospitalized for the illness. Studying non-hospitalized patients better reflects the vast majority of people who contract Covid, they said, also making it easier to tease out effects caused by the virus and not by intensive care treatments such as ventilators. “We wanted to truly understand what are the long-term effects of this infection on the majority of the population and whether we should expect a significant burden on healthcare providers,” Bivas-Benita and Mizrahi wrote.

Throughout the year of follow-up, patients with mild Covid-19 had an increased risk of problems including loss of smell and taste, concentration and memory impairment, breathing difficulties, weakness, palpitations, strep throat, and dizziness. Later in the year, health records showed more hair loss (particularly among women), chest pain, cough, muscle aches and pains, and respiratory disorders among Covid patients. But for most people, these problems also cleared up by the end of one year. Vaccinated people were at lower risk of developing breathing difficulties after breakthrough infections — the most common problem after mild infection, along with weakness — compared with unvaccinated people, but their risk was similar for other conditions. People from 41 to 60 years old had more health problems than people in other age groups, and shortness of breath continued to be a problem for those over 60. Children had fewer long Covid symptoms than adults, and most of those issues were gone after a year. “This is a reassuring large population medical record study,” Michael Absoud, honorary reader in the Department of Women & Children’s Health at King’s College London and not involved in the study, said. “It confirms that in children, of the small proportion who have prolonged persistent symptoms post SARS-CoV-2 infection, the vast majority show a very good recovery.” There were minor differences between men’s and women’s risk of outcomes, and findings remained consistent across the SARS-CoV-2 variants that emerged before Omicron. “The general message that symptoms improve over time is encouraging, but it may take a year or so for some symptoms to resolve,” Peter Openshaw, a professor of experimental medicine at Imperial College London, said. He was not involved in the research. “The study adds to the evidence that outcomes are improved by vaccination, even if vaccines don’t prevent viral transmission very well.” Ziyad Al-Aly, clinical epidemiologist at Washington University in St. Louis, isn’t so sure.

He thinks the study’s message may be too optimistic, owing to its design. Comparing people who test positive to people who test negative may not account for the reason people are taking Covid tests. Someone with cancer might need to test before starting chemotherapy, he said, or someone else might need surgery for another reason. “Better designs would be needed to more confidently elevate our understanding, to actually deepen our understanding of the the toll and scale of the condition and the trajectory of the health performance of the individual affected with long Covid over the the ensuing year after that infection,” Al-Aly, who is also chief of research and development at the VA St. Louis Health Care System, told STAT. He was not part of the study. “It doesn’t mean that some people are not improving. We see a big improvement in some individuals …. I wish this was normally the case, but it’s really too rosy to be true.” In response, the study authors said it’s important to remember that PCR tests to detect Covid-19 were offered to all Israeli citizens free of charge, without needing a referral, throughout the entire study period. That meant 76% of Maccabi Healthcare Services’ members took at least one PCR test during the study period. And they say “chances are minimal” that those test-negative patients would be more likely to have symptoms like long Covid because any chronic conditions they had at baseline were matched to test-positive patients who also had them. And, they pointed out, infectious diseases other than Covid were rare during social distancing and lockdown in effect during the study period. The researchers acknowledged that not everyone recovers. And their results come from one country. “We are not claiming there are no patients who suffer from long Covid symptoms (like dyspnea, weakness, cognitive impairment etc.),” they wrote in a follow-up email. “This does not contradict evidence that a small number of patients do suffer from long lasting symptoms as seen in this analysis.” Next on their research agenda: evaluating the effects of the Omicron strain and assessing the prevalence and severity of outcomes following reinfections.

Study cited published in BMJ (Jan. 11, 2023):

 https://doi.org/10.1136/bmj-2022-072529 

A SARS-CoV-2 mutation that appeared in East Asia early in the pandemic is linked to symptoms milder than those caused by the unmutated version of the virus. In early 2020, researchers in Singapore identified a cluster of COVID-19 cases caused by a SARS-CoV-2 variant missing a chunk of DNA that spanned two genes, ORF7b and ORF8. To determine the consequences of this change, called a deletion, Lisa Ng at the Singapore Immunology Network and colleagues compared people infected with viruses carrying the deletion with those infected by normal viruses (B. E. Young et al. Lancet http://doi.org/d6x7; 2020).

None of the 29 people whose viruses had the mutation needed supplemental oxygen, but 26 of the 92 people whose viruses lacked the mutation did. Viruses carrying the deletion haven’t been detected since March — possibly owing to infection-control measures. The virus responsible for the 2002–04 outbreak of severe acute respiratory syndrome (SARS) acquired a similar deletion in the ORF8 gene, suggesting that this might be an important adaption to infecting humans, the authors say.

Study published in The Lancet (August 18, 2020):

https://doi.org/10.1016/S0140-6736(20)31757-8

Outcomes in COVID-19 patients may be better in those recently infected with endemic coronaviruses. There are four common cold coronaviruses that we all catch at some stage. We generate antibodies to them, but our immune memory of them fades over time, and we get re-infected.  Their names are all too easily forgotten—OC43, HKU1, 229E, and NL63—but our immune systems may nevertheless remember them for a time. There have been hints that exposure to these common coronaviruses might offer some protection from COVID-19, mostly by looking at signs of immune memory in blood samples taken from before the pandemic. A study in the Journal of Clinical Investigation reports the first clinical evidence linking recent endemic coronavirus infections to less severe COVID-19 and even a reduced death rate in patients.  The authors at Boston University School of Medicine found evidence for this by poring over the medical records of thousands of patients who had visited Boston Medical Center as inpatients or outpatients, most probably for respiratory illnesses, between 2015 and 2020. Each person had been assessed for infection using a PCR test that screens for bacteria and viruses, including the four endemic coronaviruses. 

In total, 15,928 patients had at least one such PCR test. Of them, 875 tested positive for an endemic coronavirus (this group was called eCoV+), while the remaining 15,053 people never had a documented coronavirus infection (termed eCoV-).  Of the entire cohort, a total of 1,812 (11.4 percent) later returned for a SARS-CoV-2 test during the initial COVID-19 surge in Boston between March 12 and June 12. “Our study is the first to examine people with known endemic coronavirus infections, and compare them to people who, as far as we know, don’t have any recent documented coronavirus infections,” says Manish Sagar, the lead author of the study and a virologist at Boston Medical Center.  The infection rate for SARS-CoV-2 was no different between those who had a recently recorded endemic coronavirus infection (eCoV+) and those who did not have a positive test (eCoV-). This led the authors to conclude that a recent infection with endemic coronaviruses did not keep SARS-CoV-2 at bay—both groups were just as likely to become infected with the pandemic virus. When the researchers peered closer at the data, they observed an important difference between the two groups. “The COVID-19 disease is actually much less severe in those patients who had documented endemic coronavirus infections,” says Sagar. The odds of intensive care unit (ICU) admission were significantly lower in eCoV+ than in eCoV- patients, and there was “a trend towards lower odds of mechanical ventilation,” the authors write in their report. The data also show that among hospitalized patients who had previous positive test results for endemic coronavirus, 4.8 percent of them died compared with 17.7 percent among those in the group without such a test result.

Local immune memory may help explain these results. Such “heterotypic immunity,” says immunologist Joseph Mizgerd, director of the pulmonary center at Boston University School of Medicine, occurs when immune memory is etched into the lungs and/or nose. It’s common after other types of respiratory infections and might offer protection against SARS-CoV-2 if elicited by endemic coronaviruses. Although the Boston group did not measure this type of immunity in patients, they now hypothesize that local immunity gained from endemic coronaviruses helps limit lung injury during COVID-19. “We are testing that in ongoing experiments,” Mizgerd says by email. He adds that such cross-reactive immunity is often mediated by memory T cells, which can localize in the lung, and he notes that lung-localized heterotypic T cells can prevent severe lung infection during pneumonias caused by other types of respiratory pathogens. If indeed prior infection does ramp up protection against SARS-CoV-2, the study could not answer how long it takes for any such benefit to taper off. Nor did the work shed light on which of the four endemic coronaviruses in particular might be offering protection against the pandemic virus. The scientists are seeking funding to expand their research and include data from other institutions....

Study cited available in J. Clinical Investigation:

https://doi.org/10.1172/JCI143380

Early reports from hospitals document a spike in large vessel blockages, especially among people in their 30s and 40s who tested positive for the coronavirus. Several hospitals in the US have observed strokes in a number of patients being treating for coronavirus, leading to concern that the infection may be causing devastating blockages in the brain. For at least two facilities, these events account for a spike in stroke cases among middle-aged patients.

“Our report shows a seven-fold increase in incidence of sudden stroke in young patients during the past two weeks,” Thomas Oxley, a neurosurgeon at Mount Sinai Health System in New York who describes five of his patients in an upcoming paper in the New England Journal of Medicine, tells CNN. “Most of these patients have no past medical history and were at home with either mild symptoms (or in two cases, no symptoms) of Covid.” Although the numbers of stroke incidents among coronavirus patients remains low, The Washington Post notes that three medical centers in the US will be publishing reports on dozens of COVID-19 patients who experienced strokes. And these appear to be the most serious kind of stroke, called a large vessel occlusion, which might account for the surge in the number of people who have died at home during the pandemic, but this cannot be confirmed.  

Thomas Jefferson University Hospitals and NYU Langone Health found that 40 percent of the 12 people treated for large vessel blockage who also tested positive for SARS-CoV-2 were under age 50, according to the Post. “We are used to thinking of 60 as a young patient when it comes to large vessel occlusions,” Eytan Raz of NYU Langone tells the newspaper. “We have never seen so many in their 50s, 40s and late 30s.” Oxley tells Medscape Medical News that the virus may be causing inflammation in blood vessels, leading to blood clots. Raz speculates that perhaps because younger people don’t suffer the respiratory issues that take a toll on older COVID-19 patients, they survive long enough for the virus to cause damage elsewhere.

Original Study to be published in New England J. Med.  (April 29, 2020)