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The effects of Long COVID
Deutsches Ärzteblatt International publishes themed issue on Long COVID
Peer-Reviewed PublicationCOLOGNE: Three articles and an accompanying editorial provide information on the effects of Long COVID in the Deutsches Ärzteblatt International’s volume 10, a themed issue on the subject:
Christian Förster and coauthors report data on persistent symptoms after COVID-19 in their original article (Dtsch Arztebl Int 2022; 119: 167–74). In a population-based cohort study they collected data on the prevalence and on risk factors. The background for this study is the observation that after recovering from infection with COVID-19, many people complain of long-term symptoms. To date, the results of epidemiological studies of this observation vary enormously. The authors used a questionnaire to collect in three rural districts data on symptoms and clinical characteristics after COVID-19, with the focus on symptoms after 12 weeks. They evaluated data from 1450 patients. The prevalence of Post-COVID-19 was 72.6% in people admitted to hospital and 46.2% in those not admitted to hospital. The most common long-term symptoms were fatigue, physical exhaustion, difficulty concentrating, and loss of smell or taste. The patients with Post-COVID-19 perceived their quality of life as notably reduced. The strongest risk factors for Post-COVID-19 were female sex, overall severity of comorbidities, and severity of acute COVID-19. According to the researchers, non-hospitalized patients also often experienced continuing symptoms. In their view, the heterogeneity of the symptoms requires a multidisciplinary, stepwise approach to care. Identifying at-risk patients, they say, is crucial.
Another article on the prevalence of persistent symptoms after COVID-19 is presented by Korbinian Lackermair and colleagues (Dtsch Arztebl Int 2022; 119: 175–6). The authors undertook a cross sectional study of 896 patients treated exclusively on an outpatient basis. In addition to determining the prevalence, the researchers investigated the question whether less severe infection correspondingly causes fewer persistent symptoms. They collected their data from structured telephone interviews that were based on a standardized questionnaire. In the study period from March 2020 to February 2021, 1673 patients at Dachau medical center tested positive for COVID-19. For 896 patients, the complete follow-up questionnaire was available. The mean follow-up period was 6.9 months, patients’ mean age was 41.7 years. In about half of patients, comorbidities were present. 34% of patients reported persistent symptoms. The authors found that in addition to non-specific symptoms, such as fatigue or headache, typical COVID-19 symptoms—such as loss of smell or taste, or dyspnea—also often persisted. Patients with persistent symptoms were significantly older, more of them were women, and the acute phase was associated with more symptoms.
The case–control study of postacute sequelae of SARS-CoV-2 infection reported by Mandy Schulz and coauthors also studied patients treated on an outpatient basis (Dtsch Arztebl Int 2022; 119: 177– 8). The authors aimed to characterize patients with regard to risk factors and use of healthcare services. To this end they used nationwide billing data from statutory health insurance (SHI) providers. They included patients who in the second quarter of 2021 had been coded as ICD-10 U09.9!. This was the case for 160,663 patients. The control group was a random sample of all patients treated in the second quarter of 2021 (n=321,326), which matched in terms of age, sex, and place of residence, and for whom neither a post-COVID code had been issued in 2021 nor confirmed COVID-19 infection (ICD-Code U 07.1!) documented in 2020 and 2021. The group of cases included more women and middle-aged patients than the control group as well as a higher proportion of patients who had been treated by SHI-authorized physicians as early as 2020. Patients with COVID-19 accounted for almost double the number of treatment cases compared to the control group. At least one of the post-COVID-symptoms under study occurred in 61% of the cases and in 33% of the controls. Patients with comorbidities, such as back pain, obesity, adjustment disorders, and somatoform disorders had a greater age-dependent risk for post-COVID-19. In the Post-COVID-19 group, SHI-accredited services were more commonly sought, especially GP consultations, than in the control group.
Tobias Welte in an accompanying editorial (Dtsch Arztebl Int 2022; 119: 165–6) concludes that the post-COVID syndrome throws up more questions than it provides answers. He distinguishes between three groups of patients in post-COVID symptoms: patients who had been treated as inpatients, and partly in intensive care, for COVID-19; patients with many different symptoms who, however, were not severely impaired in their everyday lives; and patients who cannot manage their everyday lives independently because of massive exhaustion and inadequate resilience. The second group included the greatest number of patients. They presented predominantly with weariness and difficulty concentrating, together with the feeling of a lack of stamina. In Welte’s opinion, the challenge in treating these patients lies in differentiating between COVID-19 triggered medical impairments and pandemic-related psychosocial changes. The sequelae of COVID-19 can, he concludes, only be alleviated by reducing the number of infections and by changing attitudes. The pathogen is not likely to disappear in the foreseeable future, and SARS-CoV-2–related diseases will become part of our everyday lives, in the same way as other infectious diseases. For this reason, the options of prevention and therapies should be used, so as to learn to live with COVID-19.
https://www.aerzteblatt.de/int/archive/issue?heftid=6821
Welte T: Post-COVID syndrome—more questions than answers. Dtsch Arztebl Int 2022; 119: 165–6. DOI: 10.3238/arztebl.m2022.0154
Förster C, Colombo MG, Wetzel AJ, Martus P, Joos S: Persisting symptoms after COVID-19—prevalence and risk factors in a population-based cohort.Dtsch Arztebl Int 2022; 119: 167–74. DOI: 10.3238/arztebl.m2022.0147
Lackermair K, Wilhelm K, William F, Grzanna N, Lehmann E, Sams L, Fichtner S, Kellnar A, Estner H: The prevalence of persistent symptoms after COVID-19 disease—a cross-sectional study of 896 patients treated on an outpatient basis.Dtsch Arztebl Int 2022; 119: 175–6. DOI: 10.3238/arztebl.m2022.0125
Schulz M, Mangiapane S, Scherer M, Karagiannidis C, Czihal T: Post-acute sequelae of SARS-CoV-2 infection—characterization of community-treated patients in a case–control study based on nationwide claims data. Dtsch Arztebl Int 2022; 119: 177– 8. DOI: 10.3238/arztebl.m2022.0134
JOURNAL
Deutsches Ärzteblatt international
METHOD OF RESEARCH
Survey
SUBJECT OF RESEARCH
People
ARTICLE TITLE
Persisting symptoms after COVID-19—prevalence and risk factors in a population-based cohort
COI STATEMENT
All authors declare that no conflict of interest exists.
Females far likelier to suffer with Long COVID, a new review of studies shows, underscoring a critical need for sex-disaggregated research
The odds of females developing Long COVID syndrome is 22% higher than males, researchers find
Peer-Reviewed PublicationA new study published today in the peer-reviewed journal Current Medical Research and Opinion, reveals that females are “significantly” more likely to suffer from Long COVID than males and will experience substantially different symptoms.
Long COVID is a syndrome in which complications persist more than four weeks after the initial infection of COVID-19, sometimes for many months.
Researchers from the Johnson & Johnson Office of the Chief Medical Officer Health of Women Team, who carried out the analysis of data from around 1.3 million patients, observed females with Long COVID are presenting with a variety of symptoms including ear, nose, and throat issues; mood, neurological, skin, gastrointestinal and rheumatological disorders; as well as fatigue.
Male patients, however, were more likely to experience endocrine disorders such as diabetes and kidney disorders.
“Knowledge about fundamental sex differences underpinning the clinical manifestations, disease progression, and health outcomes of COVID-19 is crucial for the identification and rational design of effective therapies and public health interventions that are inclusive of and sensitive to the potential differential treatment needs of both sexes,” the authors explain.
“Differences in immune system function between females and males could be an important driver of sex differences in Long COVID syndrome. Females mount more rapid and robust innate and adaptive immune responses, which can protect them from initial infection and severity. However, this same difference can render females more vulnerable to prolonged autoimmune-related diseases.”
As part of the review, researchers restricted their search of academic papers to those published between December 2019–August 2020 for COVID-19 and to January 2020–June 2021 for Long COVID syndrome. The total sample size spanning articles reviewed amounted to 1,393,355 unique individuals.
While the number of participants sounds large, only 35 of the 640,634 total articles in the literature provided sex disaggregated data in sufficient details about symptoms and sequalae of COVID-19 disease to understand how females and males experience the disease differently.
When looking at the early onset of COVID-19, findings show that female patients were far more likely to experience mood disorders such as depression, ear, nose, and throat symptoms, musculoskeletal pain, and respiratory symptoms. Male patients, on the other hand, were more likely to suffer from renal disorders—those that affect the kidneys.
The authors note that this synthesis of the available literature is among the few to break down the specific health conditions that occur as a result of COVID-related illness by sex. Plenty of studies have examined sex differences in hospitalization, ICU admission, ventilation support, and mortality. But the research on the specific conditions that are caused by the virus, and its long-term damage to the body, have been understudied when it comes to sex.
“Sex differences in outcomes have been reported during previous coronavirus outbreaks,” authors add. “Therefore, differences in outcomes between females and males infected with SARS-CoV-2 could have been anticipated. Unfortunately, most studies did not evaluate or report granular data by sex, which limited sex-specific clinical insights that may be impacting treatment.” Ideally, sex disaggregated data should be made available even if it was not the researcher’s primary objective, so other interested researchers can use the data to explore important differences between the sexes.
The paper also notes complicating factors worthy of additional study. Notably, women may be at greater risk of exposure to the virus in certain professions, such as nursing and education. Further, “there may be disparities in access to care based on gender that could affect the natural history of the disease, leading to more complications and sequela.”
The latter serves as a rallying cry: availability of sex disaggregated data and intentional analysis is imperative if we are to ensure that disparate outcomes in disease course are addressed. No research is complete unless the data is made available to people who want to answer the question: does sex and gender matter?
JOURNAL
Current Medical Research and Opinion
METHOD OF RESEARCH
Literature review
SUBJECT OF RESEARCH
People
ARTICLE TITLE
Sex differences in sequelae from COVID-19 infection and in long COVID syndrome: a review
International study identifies risks
for Long COVID in children
Study finds age, hospitalization and number of symptoms are key factors
Peer-Reviewed PublicationIMAGE: DR. STEPHEN FREEDMAN, MD view more
CREDIT: UCALGARY/RILEY BRANDT
Nearly 6 percent of children who presented to the Emergency Department (ED) with COVID-19 reported symptoms of long COVID 90 days later, according to a study conducted in eight countries and published in JAMA Network Open. Initial hospitalization of 48 or more hours, four or more symptoms at the initial ED visit, and age 14 years or older were associated with long COVID.
“We found that in some children, illness with COVID-19 is associated with reporting persistent symptoms after 3 months,” said Principal Investigator Stephen Freedman, MDCM, MSc, with the Cumming School of Medicine at University of Calgary, and Alberta Health Services. “Our results suggest that appropriate guidance and follow-up are needed, especially for children at high risk for long COVID.”
The study included 1,884 children with COVID-19 who had 90-day follow-up. Long COVID was found in nearly 10 percent of hospitalized children and 5 percent in children discharged from the ED.
“Reported rates of long COVID in adults are substantially higher than what we found in children,” said Co-Principal Investigator Nathan Kuppermann, MD, MPH, from University of California, Davis School of Medicine, Sacramento. “Our findings can inform public health policy decisions regarding COVID-19 mitigation strategies for children and screening approaches for long COVID among those with severe infections.”
The most reported persistent symptoms in children were fatigue or weakness, cough, difficulty breathing or shortness of breath.
“Our finding that children who had multiple COVID-19 symptoms initially were at higher risk for long COVID is consistent with studies in adults,” said Co-Principal Investigator Todd Florin, MD, MSCE, from Ann & Robert H. Lurie Children’s Hospital of Chicago and Northwestern University Feinberg School of Medicine. “Unfortunately, there are no known therapies for long COVID in children and more research is needed in this area. However, if symptoms are significant, treatment targeting the symptoms is most important. Multidisciplinary care is warranted if symptoms are impacting quality of life.”
About the Cumming School of Medicine
The University of Calgary’s Cumming School of Medicine (CSM) is driven to create the future of health. We are a proud leader with seven world-class research institutes and 2,900 students, as well as faculty and staff, working to advance education and research in precision medicine and precision public health, improving lives in our community and around the world. Visit cumming.ucalgary.ca and follow us @UCalgaryMed.
About University of California, Davis School of Medicine
The UC Davis School of Medicine is among the nation's leading medical schools, recognized for its research and primary-care programs. The school offers fully accredited master's degree programs in public health and in informatics, and its combined M.D.-Ph.D. program is training the next generation of physician-scientists to conduct high-impact research and translate discoveries into better clinical care. Along with being a recognized leader in medical research, the school is committed to serving underserved communities and advancing rural health. For more information, visit UC Davis School of Medicine at medschool.ucdavis.edu.
About Ann & Robert H. Lurie Children’s Hospital of Chicago
Research at Ann & Robert H. Lurie Children’s Hospital of Chicago is conducted through Stanley Manne Children’s Research Institute. The Manne Research Institute is focused on improving child health, transforming pediatric medicine and ensuring healthier futures through the relentless pursuit of knowledge. Lurie Children’s is ranked as one of the nation’s top children’s hospitals by U.S. News & World Report. It is the pediatric training ground for Northwestern University Feinberg School of Medicine. Emergency medicine-focused research at Lurie Children’s is conducted through the Grainger Research Program in Pediatric Emergency Medicine.
JOURNAL
JAMA Network Open
METHOD OF RESEARCH
Observational study
SUBJECT OF RESEARCH
People
ARTICLE TITLE
Post–COVID-19 Conditions Among Children 90 Days After SARS-CoV-2 Infection
ARTICLE PUBLICATION DATE
22-Jul-2022
COI STATEMENT
Dr Kuppermann reported receiving grants from University of Califonia, Davis during the conduct of the study. Dr Florin reported receiving grants from Cincinnati Children’s Hospital Medical Center Division of Emergency Medicine Small Grant Program during the conduct of the study. Dr Tancredi reported receiving personal fees from International Flavors & Fragrances Inc for statistical consulting outside the submitted work. Dr Ambroggio reported receiving grants from Pfizer Inc outside the submitted work. Dr Morris reported having a patent pending for therapies for the treatment of coronoviruses. Dr Freedman reported receiving grants from the Canadian Institutes of Health Research, the Alberta Health Services–University of Calgary, the Alberta Children’s Hospital Research Institute, and the Alberta Children’s Hospital Foundation during the conduct of the study. No other disclosures were reported.
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