Unraveling the Interplay of Omicron, Reinfections, and Long Covid

Authors:  Liz Szabo AUGUST 26, 2022 KHN

The latest covid-19 surge, caused by a shifting mix of quickly evolving omicron subvariants, appears to be waning, with cases and hospitalizations beginning to fall.

Like past covid waves, this one will leave a lingering imprint in the form of long covid, an ill-defined catchall term for a set of symptoms that can include debilitating fatigue, difficulty breathing, chest pain, and brain fog.

Although omicron infections are proving milder overall than those caused by last summer’s delta variant, omicron has also proved capable of triggering long-term symptoms and organ damage. But whether omicron causes long covid symptoms as often — and as severe — as previous variants is a matter of heated study.

Michael Osterholm, director of the University of Minnesota’s Center for Infectious Disease Research and Policy, is among the researchers who say the far greater number of omicron infections compared with earlier variants signals the need to prepare for a significant boost in people with long covid. The U.S. has recorded nearly 38 million covid infections so far this year, as omicron has blanketed the nation. That’s about 40% of all infections reported since the start of the pandemic, according to the Johns Hopkins University Coronavirus Research Center.

Long covid “is a parallel pandemic that most people aren’t even thinking about,” said Akiko Iwasaki, a professor of immunobiology at Yale University. “I suspect there will be millions of people who acquire long covid after omicron infection.”

Scientists have just begun to compare variants head to head, with varying results. While one recent study in The Lancet suggests that omicron is less likely to cause long covid, another found the same rate of neurological problems after omicron and delta infections.

Estimates of the proportion of patients affected by long covid also vary, from 4% to 5% in triple-vaccinated adults to as many as 50% among the unvaccinated, based on differences in the populations studied. One reason for that broad range is that long covid has been defined in widely varying ways in different studies, ranging from self-reported fogginess for a few months after infection to a dangerously impaired inability to regulate pulse and blood pressure that may last years.

Even at the low end of those estimates, the sheer number of omicron infections this year would swell long-covid caseloads. “That’s exactly what we did find in the UK,” said Claire Steves, a professor of aging and health at King’s College in London and author of the Lancet study, which found patients have been 24% to 50% less likely to develop long covid during the omicron wave than during the delta wave. “Even though the risk of long covid is lower, because so many people have caught omicron, the absolute numbers with long covid went up,” Steves said.

recent study analyzing a patient database from the Veterans Health Administration found that reinfections dramatically increased the risk of serious health issues, even in people with mild symptoms. The study of more than 5.4 million VA patients, including more than 560,000 women, found that people reinfected with covid were twice as likely to die or have a heart attack as people infected only once. And they were far more likely to experience health problems of all kinds as of six months later, including trouble with their lungs, kidneys, and digestive system.

“We’re not saying a second infection is going to feel worse; we’re saying it adds to your risk,” said Dr. Ziyad Al-Aly, chief of research and education service at the Veterans Affairs St. Louis Health Care System.

Researchers say the study, published online but not yet peer-reviewed, should be interpreted with caution. Some noted that VA patients have unique characteristics, and tend to be older men with high rates of chronic conditions that increase the risks for long covid. They warned that the study’s findings cannot be extrapolated to the general population, which is younger and healthier overall.

“We need to validate these findings with other studies,” said Dr. Harlan Krumholz, director of the Yale New Haven Hospital Center for Outcomes Research and Evaluation. Still, he added, the VA study has some “disturbing implications.”

With an estimated 82% of Americans having been infected at least once with the coronavirus as of mid-July, most new cases now are reinfections, said Justin Lessler, a professor of epidemiology at the University of North Carolina Gillings School of Global Public Health.

Of course, people’s risk of reinfection depends not just on their immune system, but also on the precautions they’re taking, such as masking, getting booster shots, and avoiding crowds.

New Jersey salon owner Tee Hundley, 43, has had covid three times, twice before vaccines were widely available and again this summer, after she was fully vaccinated. She is still suffering the consequences.

After her second infection, she returned to work as a cosmetologist at her Jersey City salon but struggled with illness and shortness of breath for the next eight months, often feeling like she was “breathing through a straw.”

She was exhausted, and sometimes slow to find her words. While waxing a client’s eyebrows, “I would literally forget which eyebrow I was waxing,” Hundley said. “My brain was so slow.”

When she got a breakthrough infection in July, her symptoms were short-lived and milder: cough, runny nose, and fatigue. But the tightness in her chest remains.

“I feel like that’s something that will always be left over,” said Hundley, who warns friends with covid not to overexert. “You may not feel terrible, but inside of your body there is a war going on.”

Although each omicron subvariant has different mutations, they’re similar enough that people infected with one, such as BA.2, have relatively good protection against newer versions of omicron, such as BA.5. People sickened by earlier variants are far more vulnerable to BA.5.

Several studies have found that vaccination reduces the risk of long covid. But the measure of that protection varies by study, from as little as a 15% reduction in risk to a more than 50% decrease. A study published in July found the risk of long covid dropped with each dose people received.

For now, the only surefire way to prevent long covid is to avoid getting sick. That’s no easy task as the virus mutates and Americans have largely stopped masking in public places. Current vaccines are great at preventing severe illness but do not prevent the virus from jumping from one person to the next. Scientists are working on next-generation vaccines — “variant-proof” shots that would work on any version of the virus, as well as nasal sprays that might actually prevent spread. If they succeed, that could dramatically curb new cases of long covid.

“We need vaccines that reduce transmission,” Al-Aly said. “We need them yesterday.”

Diabetes may increase long COVID risk; COVID while pregnant linked to baby brain development issues

Authors: Nancy Lapid Thu, June 9, 2022,

The following is a summary of some recent studies on COVID-19. They include research that warrants further study to corroborate the findings and that has yet to be certified by peer review.

Diabetes may increase the risk of long COVID, new analyses of seven previous studies suggest.

Researchers reviewed studies that tracked people for at least four weeks after COVID-19 recovery to see which individuals developed persistent symptoms associated with long COVID such as brain fog, skin conditions, depression, and shortness of breath. In three of the studies, people with diabetes were up to four times more likely to develop long COVID compared to people without diabetes, according to a presentation https://eppro02.ativ.me/web/page.php?page=IntHtml&project=ADA22&id=1683 on Sunday at the annual Scientific Sessions of the American Diabetes Association. The researchers said diabetes appears to be “a potent risk factor” for long COVID but their findings are preliminary because the studies used different methods, definitions of long COVID, and follow-up times, and some looked at hospitalized patients while others focused on people with milder cases of COVID-19.

“More high-quality studies across multiple populations and settings are needed to determine if diabetes is indeed a risk factor” for long COVID, the researchers said. “In the meantime, careful monitoring of people with diabetes… may be advised” after COVID-19.

COVID-19 in pregnancy linked with babies’ learning skills

Babies born to mothers who had COVID-19 while pregnant may be at higher than average risk for problems with brain development involved in learning, focusing, remembering, and developing social skills, researchers have found.

They studied 7,772 infants delivered in Massachusetts between March and September 2020, tracking the babies until age 12 months. During that time, 14.4% of the babies born to the 222 women with a positive coronavirus test during pregnancy were diagnosed with a neurodevelopmental disorder, compared to 8.7% of babies whose mothers avoided the virus while pregnant. After accounting for other neurodevelopmental risk factors, including preterm delivery, SARS-CoV-2 infection during pregnancy was linked with an 86% higher risk of a neurodevelopmental disorder diagnosis in offspring, the researchers reported on Thursday in JAMA Network Open https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2793178. The risk was more than doubled when the infection occurred in the third trimester.

The researchers point out that their study was brief and cannot rule out the possibility that additional neurodevelopmental effects will become apparent as the children grow up. On the other hand, they note, larger and more rigorous studies are needed to rule out other potential causes and prove that the coronavirus is to blame.

The rare but life-threatening inflammatory syndrome seen in some children after a coronavirus infection has become even more rare with the Omicron variant causing most infections and more kids vaccinated, according to a new study.

Researchers looked at data from Denmark on more than half a million children and adolescents infected after Omicron became dominant, about half of whom experienced breakthrough infections after vaccination. Overall, only one vaccinated child and 11 unvaccinated children developed Multisystem Inflammatory Syndrome in Children (MIS-C), which causes inflammation in the heart, lungs, kidneys and brain after a mild or asymptomatic SARS-CoV-2 infection. That translates to rates of 34.9 MIS-C cases per million unvaccinated children with COVID-19 and 3.7 cases per million vaccinated young COVID-19 patients, the researchers said on Wednesday in JAMA Pediatrics https://jamanetwork.com/journals/jamapediatrics/fullarticle/2793024. By comparison, rates of MIS-C cases when Delta was predominant were 290.7 per million unvaccinated infected kids and 101.5 per million among the vaccinated who had COVID, they said.

The fact that MIS-C risk was significantly lower in vaccinated children suggests the vaccine is helping to keep the immune system from causing the deadly inflammatory reaction that is an MIS-C hallmark, the researchers said.

Massive 23andMe survey reveals who may be at the highest risk for long COVID

Authors: Amy Graff, SFGATE May 31, 2022

It’s a question everyone wants answered: Who is more likely to develop long COVID-19, the debilitating symptoms that can linger for weeks, months or even longer, after an infection?

new unpublished study from 23andMe is part of a growing body of research shedding light on who experiences post-COVID conditions and why. The survey, which was voluntary and relied on people self-reporting symptoms, had several major findings, including that women were far more likely to experience long-term symptoms, as were people with a prior diagnosis of depression or anxiety. More than half of people who reported a diagnosis of long COVID had a history of cardiometabolic disease, such as heart attacks or diabetes.

The 23andMe survey included 100,000 people who reported a diagnosis of COVID. Of those, 26,000 described experiencing symptoms of COVID at least a month after being infected. In addition, more than 7,000 participants reported an official diagnosis of long COVID. Survey participants were asked about their symptoms at 3, 6 and 12 months. According to Centers for Disease Control and Prevention estimates, about 13.3% of people with COVID will experience symptoms for at least a month, and 2.5% of people will experience symptoms for longer than three months.

Dr. Stella Aslibekyan, a genetic epidemiologist for the consumer genetics company, which is based in South San Francisco, told SFGATE that the 23andMe study is unique because it’s so large and directly surveyed people about their symptoms. Many other studies into long-term symptoms are smaller, and based on data from medical records, as opposed to self-reported experiences. 

“We’re able to paint a more complete picture of the COVID experience than would be possible from just using medical records,” Aslibekyan said.

There are limitations to this approach, too. Participating in the study was voluntary, as opposed to a random sample of patients in a health system. The demographics and characteristics of people represented in these kinds of “self-selecting” studies are often skewed, based on who has enough time and interest to fill out the surveys.

The study, which has not been peer-reviewed or published in a medical journal, is part of an effort to solve the mystery of why so many people experience symptoms such as shortness of breath, cough, fever, fatigue, brain fog or chest pain for weeks to months after a COVID infection. Many of these symptoms align with the symptoms of chronic fatigue syndrome, a poorly understood condition that has often been linked to other viral infections, including flu and Epstein-Barr. 

“One hypothesis positions long COVID as an autoimmune condition, in which the immune system is attacking the body’s own tissues,” Aslibekyan said.

Many studies have found that long-term symptoms are much more likely to occur in the most severe COVID cases, but the U.S. Centers for Disease Control and Prevention says that “anyone who was infected with the virus can experience post-COVID conditions, even people who had mild illness or no symptoms from COVID-19.”

“Researchers found that individuals with COVID who required hospitalization had a more than ten-fold risk of being diagnosed with long COVID compared to those who were not hospitalized when controlling for age, sex, and ethnicity,” 23andMe said. 

Depression and anxiety also seem to be risk factors.

To Aslibekyan, one of the most illuminating findings in the survey was that people diagnosed with long COVID were twice as likely to report experiencing depression or anxiety before they were infected. 

There is extensive research into the relationship between depression and the immune system. People with diseases that cause over-activation of the immune system are more likely to be diagnosed with depression, and vice versa.

“When [depressed people] are hit with that acute COVID-19 infection, those long term symptoms also represent inappropriate malfunction of the immune system, so it makes sense that they’re more vulnerable to those long-term dysfunctions of the immune system,” Aslibekyan said.

Women are more likely than men to have long COVID

Researchers also found that people with two X chromosomes in each cell were more than twice as likely to report a long COVID diagnosis than those with only one. This finding is consistent with other studies that have found women are less likely to die from COVID, but more likely to develop long-term symptoms.

The X chromosome is home to many genes that control immune responses. While most men inherit just one copy from their mothers, women generally inherit two — one from each parent — and, therefore, two sets of those important immune-related genes. (In every individual cell, one or the other X chromosome is switched “on” at random.) That genetic diversity is often a good thing; women are better able to fight off many illnesses than men, for instance. But it’s also linked to a higher rate of autoimmune diseases among women, including multiple sclerosis and Sjogren’s syndrome, Aslibekyan said.

Brain fog was the most commonly self-reported symptom

The symptom most commonly reported by people responding to the survey was brain fog, a term for sluggish thinking, followed by fatigue, shortness of breath and loss of smell. Among people who received long COVID diagnoses, about 19% reported brain fog a year after infection. 

Among participants who received vaccines after catching COVID, more than half (55%) reported no change in their symptoms, 25% reported an improvement in symptoms, and about 13% reported that their symptoms got worse. The rest did not know, weren’t sure or didn’t answer.

23andMe began collecting data in April 2020. That means many of the people in the survey contracted COVID-19 before the vaccine was available. 

“So what does that tell us?” Aslibekyan said. “The vaccine may not be a cure for long COVID. Now what we do know is that the vaccine is very good at preventing both initial infection and hospitalization, yes. And hospitalization was associated with a tenfold increase in risk of long COVID. So the vaccine is great for prevention.”

Risk of blood clots in lung doubled for Covid survivors

Authors: FMT May 25, 2022

Coronavirus survivors have twice the risk of developing dangerous blood clots that travel to their lungs compared to people who weren’t infected, as well double the chance of respiratory symptoms, a large new study said Tuesday.

The research by the Centers for Disease Control and Prevention found that as many as one in five adults aged 18-64 years and one in four of those over 65 went on to experience health conditions that could be related to their bout of Covid — a finding consistent with other research.

Among all conditions, the risk of developing acute pulmonary embolism — a clot in an artery of the lung — increased the most, by a factor of two in both adults younger and older than 65, as did respiratory symptoms like chronic cough or shortness of breath.

Pulmonary embolisms usually travel to the lungs from a deep vein in the legs, and can cause serious problems, including lung damage, low oxygen levels and death.

The study was based on more than 350,000 patient records of people who had Covid-19 from March 2020 – November 2021, paired with 1.6 million people in a “control” group who had sought medical attention in the same month as a corresponding “case” patient but weren’t diagnosed with Covid.

The team assessed the records for the occurrence of 26 clinical conditions previously associated with long Covid.

Patients were followed one month out from the time they were first seen until they developed a subsequent condition, or until a year had passed, whichever came first.

The most common conditions in both age groups were respiratory symptoms and musculoskeletal pain.

In patients under 65, risks after Covid elevated for most types of conditions, but no significant differences were observed for cerebrovascular disease, mental health conditions, or substance-related disorders.

“Covid-19 severity and illness duration can affect patients’ health care needs and economic well-being,” the authors wrote.

“The occurrence of incident conditions following infection might also affect a patient’s ability to contribute to the workforce and might have economic consequences for survivors and their dependents,” as well as placing added strain on health systems.

Limitations of the study included the fact that data on sex, race, and geographic region were not considered, nor was vaccination status. Because of the time period, the study also didn’t factor in newer variants.

Different SARS-CoV-2 variants may give rise to different long COVID symptoms, study suggests

Italian study of long-COVID patients suggests those infected with the Alpha variant experienced different neurological and emotional symptoms compared to those who contracted the original form of SARS-CoV-2

Authors: EUROPEAN SOCIETY OF CLINICAL MICROBIOLOGY AND INFECTIOUS DISEASES

24-MAR-2022

New research to be presented at this year’s European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) in Lisbon, Portugal (23-26 April), suggests that the symptoms connected to long COVID could be different in people who are infected with different variants. The study is by Dr Michele Spinicci and colleagues from the University of Florence and Careggi University Hospital in Italy.

Estimates suggest that over half of survivors of SARS-CoV-2 infection experience post-acute sequelae of COVID-19 (PASC), more commonly known as ‘long COVID’ [1]. The condition can affect anyone—old and young, otherwise healthy, and those with underlying conditions. It has been seen in people who were hospitalised with COVID-19 and those with mild symptoms. But despite an increasing body of literature, long COVID remains poorly understood.

In this study, researchers did a retrospective observational study of 428 patients—254 (59%) men and 174 (41%) women—treated at the Careggi University Hospital’s post-COVID outpatient service between June 2020 and June 2021, when the original form of SARS-CoV-2 and the Alpha variant were circulating in the population. The patients had been hospitalised with COVID-19 and discharged 4-12 weeks before attending a clinical visit at the outpatient service and completing a questionnaire on persistent symptoms (an average [median] of 53 days after hospital discharge). In addition, data on medical history, microbiological and clinical COVID-19 course, and patient demographics were obtained from electronic medical records.

At least three-quarters 325/428 (76%) of patients reported at least one persistent symptom. The most common reported symptoms were shortness of breath (157/428; 37%) and chronic fatigue (156/428; 36%) followed by sleep problems (68/428; 16%), visual problems (55/428; 13%), and brain fog (54/428; 13%).

Analyses suggest that people with more severe forms, who required immunosuppressant drugs such as tocilizumab, were six times as likely to report long COVID symptoms, while those who received high flow oxygen support were 40% more likely to experience ongoing problems. Women were almost twice as likely to report symptoms of long COVID compared with men. However, patients with type 2 diabetes seemed to have a lower risk of developing long COVID symptoms. The authors say that further studies are needed to better understand this unexpected finding.

Researchers performed a more detailed evaluation comparing the symptoms reported by patients infected between March and December 2020 (when the original SARS-COV-2 was dominant) with those reported by patients infected between January and April 2021 (when Alpha was the dominant variant) and discovered a substantial change in the pattern of neurological and cognitive/emotional problems.

They found that when the Alpha variant was the dominant strain, the prevalence of myalgia (muscle aches and pain), insomnia, brain fog and anxiety/depression significantly increased, while anosmia (loss of smell), dysgeusia (difficulty in swallowing), ad impaired hearing were less common (figure 2 in notes to editors).

“Many of the symptoms reported in this study have been measured, but this is the first time they have been linked to different COVID-19 variants”, says Dr Spinicci. “The long duration and broad range of symptoms reminds us that the problem is not going away, and we need to do more to support and protect these patients in the long term. Future research should focus on the potential impacts of variants of concern and vaccination status on ongoing symptoms.”

The authors acknowledge that the study was observational and does not prove cause and effect, and they could not confirm which variant of the virus caused the infection in different patients—which may limit the conclusions that can be drawn.

Long COVID Could Be Linked to the Effects of SARS-CoV-2 on the Vagus Nerve

SciTechDaily

Authors: EUROPEAN SOCIETY OF CLINICAL MICROBIOLOGY AND INFECTIOUS DISEASES FEBRUARY 11, 2022

New research to be presented at this year’s European Congress of Clinical Microbiology and Infectious Diseases (ECCMID 2022, Lisbon, April 23-26) suggests that many of the symptoms connected to post-COVID syndrome (PCC, also known as long COVID) could be linked to the effect of the virus on the vagus nerve – one of the most important multi-functional nerves in the body. The study is by Dr. Gemma Lladós and Dr. Lourdes Mateu, University Hospital Germans Trias i Pujol, Badalona, Spain, and colleagues.

The vagus nerve extends from the brain down into the torso and into the heart, lungs, and intestines, as well as several muscles including those involved in swallowing. As such, this nerve is responsible for a wide variety of bodily functions including controlling heart rate, speech, the gag reflex, transferring food from the mouth to the stomach, moving food through the intestines, sweating, and many others.

Long COVID is a potentially disabling syndrome affecting an estimated 10-15% of subjects who survive COVID-19. The authors propose that SARS-CoV-2-mediated vagus nerve dysfunction (VND) could explain some long COVID symptoms, including dysphonia (persistent voice problems), dysphagia (difficulty in swallowing), dizziness, tachycardia (abnormally high heart rate), orthostatic hypotension (low blood pressure) and diarrhea.

The authors performed a pilot, extensive morphological and functional evaluation of the vagus nerve, using imaging and functional tests in a prospective observational cohort of long COVID subjects with symptoms suggestive of VND. In their total cohort of 348 patients, 228 (66%) had at least one symptom suggestive of VND. The current evaluation was performed in the first 22 subjects with VND symptoms (10% of the total) seen in the Long COVID Clinic of University Hospital Germans Trias i Pujol between March and June 2021. The study is ongoing and continues to recruit patients.

Of the 22 subjects analyzed, 20 (91%) were women with a median age of 44 years. The most frequent VND-related symptoms were: diarrhea (73%), tachycardia (59%), dizziness, dysphagia and dysphonia (45% each), and orthostatic hypotension (14%). Almost all (19 subjects, 86%) had at least 3 VND-related symptoms. The median prior duration of symptoms was 14 months. Six of 22 patients (27%) displayed alteration of the vagus nerve in the neck shown by ultrasound – including both thickening of the nerve and increased ‘echogenicity’ which indicates mild inflammatory reactive changes.

A thoracic ultrasound showed flattened ‘diaphragmatic curves’ in 10 out of 22 (46%) subjects (which translates a decrease in diaphragmatic mobility during breathing, or more simply abnormal breathing). A total of 10 of 16 (63%) assessed individuals showed reduced maximum inspiration pressures, showing weakness of breathing muscles.

Eating and digestive function was also affected in some patients, with 13 of 18 assessed (72%) having a positive screen for self-perceived oropharyngeal dysphagia (trouble swallowing). An assessment of gastric and bowel function performed in 19 patients revealed 8 (42%) had their ability to deliver food to the stomach (via the esophagus) impaired, with 2 of these 8 (25%) reporting difficulty in swallowing. Gastroesophageal reflux (acid reflux) was observed in 9 of 19 (47%) individuals; with 4 of these 9 (44%) again having difficulty delivering food to the stomach and 3 of these 9 (33%) with hiatal hernia – which occurs when the upper part of the stomach bulges through the diaphragm into the chest cavity.

A Voice Handicap Index 30 test (a standard way to measure voice function) was abnormal in 8/17 (47%) cases, with 7 of these 8 cases (88%) suffering dysphonia.

The authors say: “In this pilot evaluation, most long COVID subjects with vagus nerve dysfunction symptoms had a range of significant, clinically-relevant, structural and/or functional alterations in their vagus nerve, including nerve thickening, trouble swallowing, and symptoms of impaired breathing. Our findings so far thus point at vagus nerve dysfunction as a central pathophysiological feature of long COVID.”

Meeting: The European Congress of Clinical Microbiology & Infectious Diseases (ECCMID 2022)

Assessment of the Frequency and Variety of Persistent Symptoms Among Patients With COVID-19A Systematic Review

Authors: Tahmina Nasserie, MPH1Michael Hittle, BS1Steven N. Goodman, MD, MHS, PhD1 JAMA Netw Open. 2021;4(5):e2111417. doi:10.1001/jamanetworkopen.2021.11417 May 26, 2021

Key Points

Question  What are the frequency and variety of persistent symptoms after COVID-19 infection?

Findings  In this systematic review of 45 studies including 9751 participants with COVID-19, the median proportion of individuals who experienced at least 1 persistent symptom was 73%; symptoms occurring most frequently included shortness of breath or dyspnea, fatigue or exhaustion, and sleep disorders or insomnia. However, the studies were highly heterogeneous and needed longer follow-up and more standardized designs.

Meaning  This systematic review found that COVID-19 symptoms commonly persisted beyond the acute phase of infection, with implications for health-associated functioning and quality of life; however, methodological improvements are needed to reliably quantify these risks.Abstract

Importance  Infection with COVID-19 has been associated with long-term symptoms, but the frequency, variety, and severity of these complications are not well understood. Many published commentaries have proposed plans for pandemic control that are primarily based on mortality rates among older individuals without considering long-term morbidity among individuals of all ages. Reliable estimates of such morbidity are important for patient care, prognosis, and development of public health policy.

Objective  To conduct a systematic review of studies examining the frequency and variety of persistent symptoms after COVID-19 infection.

Evidence Review  A search of PubMed and Web of Science was conducted to identify studies published from January 1, 2020, to March 11, 2021, that examined persistent symptoms after COVID-19 infection. Persistent symptoms were defined as those persisting for at least 60 days after diagnosis, symptom onset, or hospitalization or at least 30 days after recovery from the acute illness or hospital discharge. Search terms included COVID-19SARS-CoV-2coronavirus2019-nCoVlong-termafter recoverylong-haulpersistentoutcomesymptomfollow-up, and longitudinal. All English-language articles that presented primary data from cohort studies that reported the prevalence of persistent symptoms among individuals with SARS-CoV-2 infection and that had clearly defined and sufficient follow-up were included. Case reports, case series, and studies that described symptoms only at the time of infection and/or hospitalization were excluded. A structured framework was applied to appraise study quality.

Findings  A total of 1974 records were identified; of those, 1247 article titles and abstracts were screened. After removal of duplicates and exclusions, 92 full-text articles were assessed for eligibility; 47 studies were deemed eligible, and 45 studies reporting 84 clinical signs or symptoms were included in the systematic review. Of 9751 total participants, 5266 (54.0%) were male; 30 of 45 studies reported mean or median ages younger than 60 years. Among 16 studies, most of which comprised participants who were previously hospitalized, the median proportion of individuals experiencing at least 1 persistent symptom was 72.5% (interquartile range [IQR], 55.0%-80.0%). Individual symptoms occurring most frequently included shortness of breath or dyspnea (26 studies; median frequency, 36.0%; IQR, 27.6%-50.0%), fatigue or exhaustion (25 studies; median frequency, 40.0%; IQR, 31.0%-57.0%), and sleep disorders or insomnia (8 studies; median 29.4%, IQR, 24.4%-33.0%). There were wide variations in the design and quality of the studies, which had implications for interpretation and often limited direct comparability and combinability. Major design differences included patient populations, definitions of time zero (ie, the beginning of the follow-up interval), follow-up lengths, and outcome definitions, including definitions of illness severity.

Conclusions and Relevance  This systematic review found that COVID-19 symptoms commonly persisted beyond the acute phase of infection, with implications for health-associated functioning and quality of life. Current studies of symptom persistence are highly heterogeneous, and future studies need longer follow-up, improved quality, and more standardized designs to reliably quantify risks.

For More Information: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2780376

COVID-19 vaccines and thrombosis with thrombocytopenia syndrome

Authors: Chih-Cheng Lai 1Wen-Chien Ko 2Chih-Jung Chen 3Po-Yen Chen 4Yhu-Chering Huang 3Ping-Ing Lee 5Po-Ren Hsueh 6 7

Abstract

Introduction: To combat COVID-19, scientists all over the world have expedited the process of vaccine development. Although interim analyses of clinical trials have demonstrated the efficacy and safety of COVID-19 vaccines, a serious but rare adverse event, thrombosis with thrombocytopenia syndrome (TTS), has been reported following COVID-19 vaccination.

Areas covered: This review, using data from both peer-reviewed and non-peer-reviewed studies, aimed to provide updated information about the critical issue of COVID-19 vaccine-related TTS.

Expert opinion: : The exact epidemiological characteristics and possible pathogenesis of this adverse event remain unclear. Most cases of TTS developed in women within 2 weeks of the first dose of vaccine on the receipt of the ChAdOx1 nCoV-19 and Ad26.COV2.S vaccines. In countries with mass vaccination against COVID-19, clinicians should be aware of the relevant clinical features of this rare adverse event and perform related laboratory and imaging studies for early diagnosis. Non-heparin anticoagulants, such as fondaparinux, argatroban, or a direct oral anticoagulant (e.g. apixaban or rivaroxaban) and intravenous immunoglobulins are recommended for the treatment of TTS. However, further studies are required to explore the underlying mechanisms of this rare clinical entity.

Plain language summary: What is the context? Thrombosis with thrombocytopenia syndrome (TTS) usually develops within 2 weeks of the first doses of the ChAdOx1 nCoV-19 and Ad26.COV2.S COVID-19 vaccines. TTS mainly occurs in patients aged < 55 years and is associated with high morbidity and mortality. What is new? TTS mimics autoimmune heparin-induced thrombocytopenia and can be mediated by platelet-activating antibodies against platelet factor 4. Non-heparin anticoagulants, such as fondaparinux, argatroban, or a direct oral anticoagulant (e.g. apixaban or rivaroxaban) should be considered as the treatment of choice if the platelet count is > 50 × 109/L and there is no serious bleeding. Intravenous immunoglobulins and glucocorticoids may help increase the platelet count within days and reduce the risk of hemorrhagic transformation when anticoagulation is initiated. What is the impact? TTS should be a serious concern during the implementation of mass COVID-19 vaccination, and patients should be educated about this complication along with its symptoms such as severe headache, blurred vision, seizure, severe and persistent abdominal pain, painful swelling of the lower leg, and chest pain or dyspnea. The incidence of TTS is low; therefore, maintenance of high vaccination coverage against COVID-19 should be continued.

For More Information: https://pubmed.ncbi.nlm.nih.gov/34176415/

Predictors of COVID-19 severity: A literature review

Authors: Benjamin Gallo Marin,1Ghazal Aghagoli,1Katya Lavine,1Lanbo Yang,1Emily J. Siff,2Silvia S. Chiang,3,4Thais P. Salazar-Mather,1,5Luba Dumenco,1,5Michael C Savaria,1Su N. Aung,6Timothy Flanigan,6 and Ian C. Michelow3,4

Summary

The coronavirus disease 2019 (COVID-19) pandemic is a rapidly evolving global emergency that continues to strain healthcare systems. Emerging research describes a plethora of patient factors—including demographic, clinical, immunologic, hematological, biochemical, and radiographic findings—that may be of utility to clinicians to predict COVID-19 severity and mortality. We present a synthesis of the current literature pertaining to factors predictive of COVID-19 clinical course and outcomes. Findings associated with increased disease severity and/or mortality include age > 55 years, multiple pre-existing comorbidities, hypoxia, specific computed tomography findings indicative of extensive lung involvement, diverse laboratory test abnormalities, and biomarkers of end-organ dysfunction. Hypothesis-driven research is critical to identify the key evidence-based prognostic factors that will inform the design of intervention studies to improve the outcomes of patients with COVID-19 and to appropriately allocate scarce resources.

1. INTRODUCTION

The newly described coronavirus disease (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has strained healthcare systems around the world. The viral spread has been amplified not only by the occurrence of asymptomatic infections but also by limited widespread testing and personal protective equipment (PPE) for healthcare providers across the world.1 The overwhelming influx of COVID19-infected patients to many hospitals presents a need to thoroughly understand the clinical, radiological, and laboratory findings associated with greater disease severity and mortality. Here, we synthesize the current literature to describe early demographic, clinical, virologic, immunologic, hematological, biochemical, and radiographic factors that may correlate with COVID-19 disease severity. In this paper, we will use the World Health Organization’s (WHO) definition of severe pneumonia to categorize severe disease. As of 27 May 2020, the WHO’s most recent clinical guidelines define “severe disease” as adults with clinical signs of pneumonia (fever, dyspnea, cough, and fast breathing) accompanied by one of the following: respiratory rate > 30 breaths/min; severe respiratory distress; or oxygen saturation (SpO2) ≤ 90% on room air.2 The precise determinants of severe disease are not known, but it appears that primarily host factors rather than viral genetic mutations drive the pathogenesis.3 However, emerging data from a non-peer-reviewed paper suggest that a D614G mutation in the viral spike (S) protein of strains from Europe and the United States, but not China, is associated with more efficient transmission.4 Identification of potential risk factors that predict the disease course may be of great utility for healthcare professionals to efficiently triage patients, personalize treatment, monitor clinical progress, and allocate proper resources at all levels of care to mitigate morbidity and mortality. Here, we present a review of the current literature on patient factors that have been proposed as predictors for COVID-19 severity and mortality.

For More Information: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855377/

Long-Term Neurologic Symptoms Emerge in COVID-19

— Hospitalized patients show deficits including cognitive impairment 6 months later

Authors: by Judy George, Senior Staff Writer, MedPage Today January 7, 2021share to facebookshare to twittershare to linkedinemail article

Long-term neurologic manifestations were seen in more than a third of patients hospitalized with SARS-CoV-2 infection, a prospective study in Italy showed.

In a group of hospitalized COVID-19 patients with no prior neurologic disease, 37.4% showed abnormalities on neurologic exam 6 months later — most commonly cognitive deficits, hyposmia, and postural tremor — according to Alessandro Padovani, MD, PhD, of the University of Brescia, and co-authors. The findings were reported in a medRxiv preprint and have not undergone peer review.

Patients also noted fatigue, memory impairment, and sleep disorders, Padovani said. “The severity of SARS-CoV-2 infection was an important predictor, together with age and premorbid condition, of long-term neurological symptoms and features in the cohort.”

The findings are important for long-term management of COVID-19 patients, he told MedPage Today. “They showed that the severity of SARS-CoV-2 infection may impact on neurological sequelae, but also that the symptoms reported do not always reflect neurological features at examination.”

The study is one of the first to look specifically for new long-term neurologic manifestations in COVID-19 patients who were hospitalized. Earlier research showed that 87% of patients hospitalized with COVID-19 reported persistence of at least one lingering symptom, notably fatigue and dyspnea, 60 days after discharge. Fatigue and dyspnea also were the most prevalent symptoms reported during infection and at 3-month follow-up in an analysis of both hospitalized and non-hospitalized COVID-19 patients.

For More Information: https://www.medpagetoday.com/infectiousdisease/covid19/90587