Tag: risk factors

Risk of long COVID associated with delta versus omicron variants of SARS-CoV-2

The omicron variant of SARS-CoV-2 (PANGO B.1.1.529) spread rapidly across the world, out-competing former variants soon after it was first detected in November, 2021. According to the Our World in Data COVID-19 database, In Europe, the number of confirmed cases reported between December, 2021, and March, 2022 (omicron period) has exceeded all previously reported cases. Omicron appears to cause less severe acute illness than previous variants, at least in vaccinated populations. However, the potential for large numbers of people to experience long-term symptoms is a major concern, and health and workforce planners need information urgently to appropriately scale resource allocation.
In this case-control observational study, we set out to identify the relative odds of long-COVID (defined following the National Institute for Health and Care Excellence guidelines as having new or ongoing symptoms 4 weeks or more after the start of acute COVID-19) in the UK during the omicron period compared with the delta period. We used self-reported data from the COVID Symptom Study app. (King’s College London Research Ethics Management Application System number 18210, reference LRS-19/20-18210). Data were extracted and pre-processed using ExeTera13 (version 0.5.5).
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Source: Antonelli M, Pujol JC, Spector TD, Ourselin S, Steves CJ. Risk of long COVID associated with delta versus omicron variants of SARS-CoV-2. Lancet. 2022 Jun 18;399(10343):2263-2264. doi: 10.1016/S0140-6736(22)00941-2. PMID: 35717982; PMCID: PMC9212672. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)00941-2/fulltext (Full text)

Increased risks of cancer and autoimmune disease among the first-degree relatives of patients with myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS)

Background: Myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) is a disabling multi-system complex disorder with prevalence of 875 per 100,000 (up to 3.4 million people) in the United States. There are no known etiologic or risk factors and no approved treatments for ME/CFS. We conducted a molecular epidemiologic study to test the hypothesis that ME/CFS may be an autoimmune disease (AID) and explore the link between ME/CFS and cancer, specifically hematologic malignancies.Methods: Our clinic-based study involved carefully selected cases with confirmed diagnosis of ME/CFS (n=59) and healthy controls (n=54) frequency matched to cases on age, gender and ethnicity. During structured interviews, detailed multi-generation pedigrees, epidemiologic and medical questionnaires, and biospecimen were obtained on all subjects. Statistical analysis of pedigree data involved comparison of cases and controls with respect to the prevalence and cumulative incidence of AID and cancer among their first-degree relatives. For unadjusted analysis, risk ratios, 95% confidence intervals (CI), and p-values were calculated. For age-adjusted analyses, cumulative incidence estimates were compared using the log-rank test.

Results: The prevalence of AID was significantly higher among the first-degree relatives of cases compared to those of controls (OR=5.30; 95%CI: 1.83-15.38; p=0.001). The prevalence of AID among mothers was 14% for cases and 1.9% for controls (p=0.03). 11.2% of the first-degree relatives of cases had an AID compared to 3.1% of the relatives of controls (prevalence ratio=3.71; 95% CI: 1.74-7.88; p=0.0007). The cumulative incidence of AID among the first-degree relatives of ME/CFS cases was 9.4% compared to 2.7% for those of the controls (p=0.0025). First-degree relatives of ME/CFS cases had a significantly higher prevalence of any cancer compared to the relatives of unrelated controls (OR=4.06, 95%CI: 1.84-8.96, p=0.0005). Age-adjusted analysis revealed significantly higher (p=0.03) cumulative incidence of any cancer among the first-degree relatives of cases (20%) compared to the relatives of controls (15.4%). The cumulative incidence of hematologic cancers was also significantly higher among the relatives of cases (p<0.05).

Conclusions: We found statistically significant increased risks of AID and cancer among the first-degree relatives of ME/CFS cases. Our findings implicate immune dysregulation as an underlying mechanism, providing etiologic clues and leads for prevention. Given symptomatic similarities between ‘long COVID’ and ME/CFS, it is predicted that there will be a significant increase in incidence of ME/CFS as the result of COVID-19 pandemic. Our findings may enable defining a subset of COVID-19 patients who could be at risk of developing ME/CFS, and who may benefit from treatments used for certain AIDs.

Source: Roxana Moslehi, Anil Kumar, Amiran Dzutsev. Increased risks of cancer and autoimmune disease among the first-degree relatives of patients with myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 34. https://aacrjournals.org/cancerres/article/82/12_Supplement/34/700144

 

Post-COVID Condition in Adults and Children Living in the Same Household in Italy: A Prospective Cohort Study Using the ISARIC Global Follow-Up Protocol

Abstract:

Background: Emerging evidence shows that both adults and children may develop post-acute sequelae of SARS-CoV-2 infection (PASC). The aim of this study is to characterise and compare long-term post-SARS-CoV-2 infection outcomes in adults and children in a defined region in Italy.

Methods: A prospective cohort study including children (≤18 years old) with PCR-confirmed SARS-CoV-2 infection and their household members. Participants were assessed via telephone and face-to-face visits up to 12 months post-SARS-CoV-2 diagnosis of household index case, using the ISARIC COVID-19 follow-up survey.

Results: Of 507 participants from 201 households, 56.4% (286/507) were children, 43.6% (221/507) adults. SARS-CoV-2 positivity was 87% (249/286) in children, and 78% (172/221) in adults. The mean age of PCR positive children was 10.4 (SD = 4.5) and of PCR positive adults was 44.5 years (SD = 9.5), similar to the PCR negative control groups [children 10.5 years (SD = 3.24), adults 42.3 years (SD = 9.06)]. Median follow-up post-SARS-CoV-2 diagnosis was 77 days (IQR 47-169). A significantly higher proportion of adults compared to children reported at least one persistent symptom (67%, 68/101 vs. 32%, 57/179, p < 0.001) at the first follow up. Adults had more frequently coexistence of several symptom categories at both follow-up time-points. Female gender was identified as a risk factor for PASC in adults (p 0.02 at 1-3 months and p 0.01 at 6-9 months follow up), but not in children. We found no significant correlation between adults and children symptoms. In the paediatric group, there was a significant difference in persisting symptoms between those with confirmed SARS-CoV-2 infection compared to controls at 1-3 months follow up, but not at 6-9 months. Conversely, positive adults had a higher frequency of persisting symptoms at both follow-up assessments.

Conclusion: Our data highlights that children can experience persistent multisystemic symptoms months after diagnosis of mild acute SARS-CoV-2 infection, although less frequently and less severely than co-habitant adults. There was no correlation between symptoms experienced by adults and children living in the same household. Our data highlights an urgent need for studies to characterise PASC in whole populations and the wider impact on families.

Source: Buonsenso D, Munblit D, Pazukhina E, Ricchiuto A, Sinatti D, Zona M, De Matteis A, D’Ilario F, Gentili C, Lanni R, Rongai T, Del Balzo P, Fonte MT, Valente M, Zampino G, De Rose C, Sigfrid L, Valentini P; FIMP-Roma. Post-COVID Condition in Adults and Children Living in the Same Household in Italy: A Prospective Cohort Study Using the ISARIC Global Follow-Up Protocol. Front Pediatr. 2022 Apr 21;10:834875. doi: 10.3389/fped.2022.834875. PMID: 35529336; PMCID: PMC9070551.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9070551/ (Full text)

Persistent COVID-19 symptoms at least one month after diagnosis: A national survey

Abstract:

Background: Post-acute COVID-19 syndrome (PACS) is an important healthcare burden. We examined persistent symptoms in COVID-19 patients at least four weeks after the onset of infection, participants’ return to pre-COVID-19 health status and associated risk factors.

Methods: Cross-sectional study was conducted (December 2020 to January 2021). A validated online questionnaire was sent to randomly selected individuals aged more than 14 years from a total of 1397,386 people confirmed to have COVID-19 at least 4 weeks prior to the start of this survey. This sample was drawn from the Saudi ministry of health COVID-19 testing registry system.

Results: Out of the 9507 COVID-19 patients who responded to the survey, 5946 (62.5%) of them adequately completed it. 2895 patients (48.7%) were aged 35-44 years, 64.4% were males, and 91.5% were Middle Eastern or North African. 79.4% experienced unresolved symptoms for at least 4 weeks after the disease onset. 9.3% were hospitalized with 42.7% visiting healthcare facility after discharge and 14.3% requiring readmission. The rates of main reported persistent symptoms in descending order were fatigue 53.5%, muscle and body ache 38.2%, loss of smell 35.0%, joint pain 30.5%, and loss of taste 29.1%. There was moderate correlation between the number of symptoms at the onset and post-four weeks of COVID-19 infection. Female sex, pre-existing comorbidities, increased number of baseline symptoms, longer hospital-stay, and hospital readmission were predictors of delayed return to baseline health state (p < 0.05).

Conclusion: The symptoms of PACS are prevalent after contracting COVID-19 disease. Several risk factors could predict delayed return to baseline health state.

Source: Tleyjeh IM, Kashour T, Riaz M, Amer SA, AlSwaidan N, Almutairi L, Halwani R, Assiri A. Persistent COVID-19 symptoms at least one month after diagnosis: A national survey. J Infect Public Health. 2022 May;15(5):578-585. doi: 10.1016/j.jiph.2022.04.006. Epub 2022 Apr 20. PMID: 35477145; PMCID: PMC9020835. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9020835/ (Full text)

Frailty assessment for COVID-19 follow-up: a prospective cohort study

Abstract:

Background: The Clinical Frailty Scale (CFS) is increasingly used for clinical decision making in acute care but little is known about frailty after COVID-19.

Objectives: To investigate frailty and the CFS for post-COVID-19 follow-up.

Methods: This prospective multicentre cohort study included COVID-19 survivors aged ≥50 years presenting for a follow-up visit ≥3 months after the acute illness. Nine centres retrospectively collected pre-COVID-19 CFS and prospectively CFS at follow-up. Three centres completed the Frailty Index (FI), the short physical performance battery (SPPB), 30 s sit-to-stand test and handgrip strength measurements. Mixed effect logistic regression models accounting for repeated measurements and potential confounders were used to investigate factors associated with post-COVID-19 CFS. Criterion and construct validity were determined by correlating the CFS to other concurrently assessed frailty measurements and measures of respiratory impairment, respectively.

Results: Of the 288 participants 65% were men, mean (SD) age was 65.1 (9) years. Median (IQR) CFS at follow-up was 3 (2-3), 21% were vulnerable or frail (CFS ≥4). The CFS was responsive to change, correlated with the FI (r=0.69, p<0.001), the SPPB score (r=-0.48, p<0.001) (criterion validity) and with the St George’s Respiratory Questionnaire score (r=0.59, p<0.001), forced vital capacity %-predicted (r=-0.25, p<0.001), 6 min walk distance (r=-0.39, p<0.001) and modified Medical Research Council (mMRC) (r=0.59, p<0.001). Dyspnoea was significantly associated with a higher odds for vulnerability/frailty (per one mMRC adjusted OR 2.01 (95% CI 1.13 to 3.58), p=0.02).

Conclusions: The CFS significantly increases with COVID-19, and dyspnoea is an important risk factor for post-COVID-19 frailty and should be addressed thoroughly.

Source: Müller I, Mancinetti M, Renner A, Bridevaux PO, Brutsche MH, Clarenbach C, Garzoni C, Lenoir A, Naccini B, Ott S, Piquilloud L, Prella M, Que YA, Soccal PM, von Garnier C, Geiser TK, Funke-Chambour M, Guler S. Frailty assessment for COVID-19 follow-up: a prospective cohort study. BMJ Open Respir Res. 2022 Apr;9(1):e001227. doi: 10.1136/bmjresp-2022-001227. PMID: 35459694. https://bmjopenrespres.bmj.com/content/9/1/e001227.long (Full text)

COVCOG 1: Factors Predicting Physical, Neurological and Cognitive Symptoms in Long COVID in a Community Sample. A First Publication From the COVID and Cognition Study

Abstract:

Since its first emergence in December 2019, coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has evolved into a global pandemic. Whilst often considered a respiratory disease, a large proportion of COVID-19 patients report neurological symptoms, and there is accumulating evidence for neural damage in some individuals, with recent studies suggesting loss of gray matter in multiple regions, particularly in the left hemisphere.

There are a number of mechanisms by which COVID-19 infection may lead to neurological symptoms and structural and functional changes in the brain, and it is reasonable to expect that many of these may translate into cognitive problems. Indeed, cognitive problems are one of the most commonly reported symptoms in those experiencing “Long COVID”-the chronic illness following COVID-19 infection that affects between 10 and 25% of patients. The COVID and Cognition Study is a part cross-sectional, part longitudinal, study documenting and aiming to understand the cognitive problems in Long COVID. In this first paper from the study, we document the characteristics of our sample of 181 individuals who had experienced COVID-19 infection, and 185 who had not.

We explore which factors may be predictive of ongoing symptoms and their severity, as well as conducting an in-depth analysis of symptom profiles. Finally, we explore which factors predict the presence and severity of cognitive symptoms, both throughout the ongoing illness and at the time of testing. The main finding from this first analysis is that that severity of initial illness is a significant predictor of the presence and severity of ongoing symptoms, and that some symptoms during the initial illness-particularly limb weakness-may be more common in those that have more severe ongoing symptoms. Symptom profiles can be well described in terms of 5 or 6 factors, reflecting the variety of this highly heterogenous condition experienced by the individual. Specifically, we found that neurological/psychiatric and fatigue/mixed symptoms during the initial illness, and that neurological, gastrointestinal, and cardiopulmonary/fatigue symptoms during the ongoing illness, predicted experience of cognitive symptoms.

Source: Guo P, Benito Ballesteros A, Yeung SP, Liu R, Saha A, Curtis L, Kaser M, Haggard MP, Cheke LG. COVCOG 1: Factors Predicting Physical, Neurological and Cognitive Symptoms in Long COVID in a Community Sample. A First Publication From the COVID and Cognition Study. Front Aging Neurosci. 2022 Mar 17;14:804922. doi: 10.3389/fnagi.2022.804922. PMID: 35370617; PMCID: PMC8968323. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8968323/ (Full text)

Obesity and lipid metabolism disorders determine the risk for development of long COVID syndrome: a cross-sectional study from 50,402 COVID-19 patients

Abstract:

Purpose: Metabolic disorders have been identified as major risk factors for severe acute courses of COVID-19. With decreasing numbers of infections in many countries, the long COVID syndrome (LCS) represents the next major challenge in pandemic management, warranting the precise definition of risk factors for LCS development.

Methods: We identified 50,402 COVID-19 patients in the Disease Analyzer database (IQVIA) featuring data from 1056 general practices in Germany. Multivariate logistic regression analysis was used to identify risk factors for the development of LCS.

Results: Of the 50,402 COVID-19 patients included into this analysis, 1,708 (3.4%) were diagnosed with LCS. In a multivariate regression analysis, we identified lipid metabolism disorders (OR 1.46, 95% CI 1.28-1.65, p < 0.001) and obesity (OR 1.25, 95% CI 1.08-1.44, p = 0.003) as strong risk factors for the development of LCS. Besides these metabolic factors, patients’ age between 46 and 60 years (compared to age ≤ 30, (OR 1.81 95% CI 1.54-2.13, p < 0.001), female sex (OR 1.33, 95% CI 1.20-1.47, p < 0.001) as well as pre-existing asthma (OR 1.67, 95% CI 1.39-2.00, p < 0.001) and depression (OR 1.27, 95% CI 1.09-1.47, p = < 0.002) in women, and cancer (OR 1.4, 95% CI 1.09-1.95, p = < 0.012) in men were associated with an increased likelihood of developing LCS.

Conclusion: Lipid metabolism disorders and obesity represent age-independent risk factors for the development of LCS, suggesting that metabolic alterations determine the risk for unfavorable disease courses along all phases of COVID-19.

Source: Loosen SH, Jensen BO, Tanislav C, Luedde T, Roderburg C, Kostev K. Obesity and lipid metabolism disorders determine the risk for development of long COVID syndrome: a cross-sectional study from 50,402 COVID-19 patients. Infection. 2022 Mar 30:1–6. doi: 10.1007/s15010-022-01784-0. Epub ahead of print. PMID: 35355237; PMCID: PMC8966865. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8966865/ (Full text)

Lowered oxygen saturation and increased body temperature in acute COVID-19 largely predict chronic fatigue syndrome and affective symptoms due to LONG COVID: a precision nomothetic approach

Abstract:

Background: Long coronavirus disease 2019 (LC) is a chronic sequel of acute COVID-19. The exact pathophysiology of the affective, chronic fatigue and physiosomatic symptoms labeled as physio-affective phenome of LC has remained elusive. Objective: The current study aims to delineate the effects of oxygen saturation (SpO2) and body temperature during the acute phase on the physio-affective phenome of LC.

Method: We recruited 120 LC patients and 36 controls. For all participants, we assessed the lowest SpO2 and peak body temperature during acute COVID-19, and the Hamilton Depression and Anxiety Rating Scale (HAMD/HAMA) and Fibro Fatigue (FF) scales 3 to 4 months later.

Results: Lowered SpO2 and increased body temperature during the acute phase and female sex predict 60.7% of the variance in the physio-affective phenome of LC. Using unsupervised learning techniques we were able to delineate a new endophenotype class, which comprises around 26.7% of the LC patients and is characterized by very low SpO2 and very high body temperature, and depression, anxiety, chronic fatigue, and autonomic and gastro-intestinal symptoms scores. Single latent vectors could be extracted from both biomarkers, depression, anxiety and FF symptoms or from both biomarkers, insomnia, chronic fatigue, gastro-intestinal and autonomic symptoms.

Conclusion: The newly constructed endophenotype class and pathway phenotypes indicate that the physio-affective phenome of LC is at least in part the consequence of the pathophysiology of acute COVID-19, namely the combined effects of lowered SpO2, increased body temperature and the associated immune-inflammatory processes and lung lesions.

Source: Dhurgham Shihab Al-Hadrawi, Haneen Tahseen Al-Rubaye, Abbas F. Almulla, Hussein Kadhem Al-Hakeim, Michael F. Maes. Lowered oxygen saturation and increased body temperature in acute COVID-19 largely predict chronic fatigue syndrome and affective symptoms due to LONG COVID: a precision nomothetic approach. medRxiv 2022.04.10.22273660; doi: https://doi.org/10.1101/2022.04.10.22273660 https://www.medrxiv.org/content/10.1101/2022.04.10.22273660v1 (Full text as PDF file)

Patient-Reported Symptoms and Sequelae 12 Months After COVID-19 in Hospitalized Adults: A Multicenter Long-Term Follow-Up Study

Abstract:

Objective: Our knowledge on the long-term consequences of COVID-19 is still scarce despite the clinical relevance of persisting syndrome. The aim of this study was to analyze patient-reported outcomes, including assessment by specific questionnaires of health impairment and symptoms.

Methods: This is a prospective, observational and multicenter cohort study coordinated by Fondazione IRCSS Ca’ Granda Ospedale Maggiore Policlinico di Milano and Istituto di Ricerche Farmacologiche Mario Negri IRCCS including eight hospitals located in North and Central Italy. A telephone interview to assess rehospitalization, access to health care resources, general health status subjective evaluation, and symptoms was performed at 12 months after the discharge in patients admitted to hospital because of COVID-19 from February 2020 to the end of May 2020.

Results: Among the 776 patients discharged alive, 44 (5.7%) died, 456 subjects (58.8%) completed the questionnaire and 276 (35.6%) were not reachable or refused to join the telephone interview. The mean age of the study population was 59.4 years (SD 14.1), 69.8% of individuals needed oxygen support during hospitalization and 10.4% were admitted to ICU. Overall, 91.7% of participants reported at least one symptom/sequela at 12 months. Exertional dyspnea (71.7%), fatigue (54.6%), and gastrointestinal symptoms (32.8%) were the most reported ones. Health issues after discharge including hospitalization or access to emergency room were described by 19.4% of subjects. Female and presence of comorbidities were independent predictors of health impairment and presence of ≥2 symptoms/sequelae after 12 months from hospitalization for COVID-19.

Conclusions: Patient-reported symptoms and sequelae, principally dyspnea and fatigue, are found in most individuals even 12 months from COVID-19 hospitalization. Long-term follow-up based on patient-centered outcome can contribute to plan tailored interventions.

Source: Comelli A, Viero G, Bettini G, Nobili A, Tettamanti M, Galbussera AA, Muscatello A, Mantero M, Canetta C, Martinelli Boneschi F, Arighi A, Brambilla P, Vecchi M, Lampertico P, Bonfanti P, Contoli M, Blasi F, Gori A, Bandera A. Patient-Reported Symptoms and Sequelae 12 Months After COVID-19 in Hospitalized Adults: A Multicenter Long-Term Follow-Up Study. Front Med (Lausanne). 2022 Mar 22;9:834354. doi: 10.3389/fmed.2022.834354. PMID: 35391879; PMCID: PMC8981315. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8981315/ (Full study)

Sex-Related Differences in Long-COVID-19 Syndrome

Abstract:

Background: Sex differences have been demonstrated in the acute phase of COVID-19. Women (F) were found to be less prone to develop a severe disease than men (M), but few studies have assessed sex-differences in Long-COVID-19 syndrome.

Methods: The aim of this prospective/retrospective study was to characterize the long-term consequences of this infection based on sex. For this purpose, we enrolled 223 patients (89 F and 134 M) who were infected by SARS-CoV-2. In the acute phase of the illness, F reported the following symptoms more frequently than M: weakness, dysgeusia, anosmia, thoracic pain, palpitations, diarrhea, and myalgia-all without significant differences in breathlessness, cough, and sleep disturbance.

Results: After a mean follow-up time of 5 months after the acute phase, F were significantly more likely than M to report dyspnea, weakness, thoracic pain, palpitations, and sleep disturbance but not myalgia and cough. At the multivariate logistic regression, women were statistically significantly likely to experience persistent symptoms such as dyspnea, fatigue, chest pain, and palpitations. On the contrary, myalgia, cough, and sleep disturbance were not influenced by sex.

Conclusion: We demonstrated that F were more symptomatic than M not only in the acute phase but also at follow-up. Sex was found to be an important determinant of Long-COVID-19 syndrome because it is a significant predictor of persistent symptoms in F, such as dyspnea, fatigue, chest pain, and palpitations. Our results suggest the need for long-term follow-up of these patients from a sex perspective to implement early preventive and personalized therapeutic strategies.

Source: Pelà G, Goldoni M, Solinas E, Cavalli C, Tagliaferri S, Ranzieri S, Frizzelli A, Marchi L, Mori PA, Majori M, Aiello M, Corradi M, Chetta A. Sex-Related Differences in Long-COVID-19 Syndrome. J Womens Health (Larchmt). 2022 Mar 25. doi: 10.1089/jwh.2021.0411. Epub ahead of print. PMID: 35333613. https://www.liebertpub.com/doi/10.1089/jwh.2021.0411 (Full text)