Association of SARS-CoV-2 Seropositivity With Myalgic Encephalomyelitis and/or Chronic Fatigue Syndrome Among Children and Adolescents in Germany

Abstract:

Importance: During the COVID-19 pandemic, a reduction in quality of life and physical and mental health among children and adolescents has been reported that may be associated with SARS-CoV-2 infection and/or containment measures.

Objective: To assess the association of SARS-CoV-2 seropositivity with symptoms that may be related to myalgic encephalomyelitis and/or chronic fatigue syndrome (ME/CFS) among children and adolescents.

Design, setting, and participants: This substudy of the cross-sectional SARS-CoV-2 seroprevalence surveys in Germany (SARS-CoV-2 KIDS) was performed in 9 pediatric hospitals from May 1 to October 31, 2021. Pediatric patients were recruited during an inpatient or outpatient visit regardless of the purpose of the visit. Parental questionnaires and serum samples were collected during clinically indicated blood draws. The parental questionnaire on demographic and clinical information was extended by items according to the DePaul Symptom Questionnaire, a pediatric screening tool for ME/CFS in epidemiological studies in patients aged 5 to 17 years.

Exposures: Seropositivity was determined by SARS-CoV-2 IgG antibodies in serum samples using enzyme-linked immunosorbent assays.

Main outcomes and measures: Key symptoms of ME/CFS were evaluated separately or as clustered ME/CFS symptoms according to the DePaul Symptom Questionnaire, including fatigue.

Results: Among 634 participants (294 male [46.4%] and 340 female [53.6%]; median age, 11.5 [IQR, 8-14] years), 198 (31.2%) reported clustered ME/CFS symptoms, including 40 of 100 SARS-CoV-2-seropositive (40.0%) and 158 of 534 SARS-CoV-2-seronegative (29.6%) children and adolescents. After adjustment for sex, age group, and preexisting disease, the risk ratio for reporting clustered ME/CFS symptoms decreased from 1.35 (95% CI, 1.03-1.78) to 1.18 (95% CI, 0.90-1.53) and for substantial fatigue from 2.45 (95% CI, 1.24-4.84) to 2.08 (95% CI, 1.05-4.13). Confinement to children and adolescents with unknown previous SARS-CoV-2 infection status (n = 610) yielded lower adjusted risks for all symptoms except joint pain ME/CFS-related symptoms. The adjusted risk ratio was 1.08 (95% CI, 0.80-1.46) for reporting clustered ME/CFS symptoms and 1.43 (95% CI, 0.63-3.23) for fatigue.

Conclusions and relevance: These findings suggest that the risk of ME/CFS in children and adolescents owing to SARS-CoV-2 infection may be very small. Recall bias may contribute to risk estimates of long COVID-19 symptoms in children. Extensive lockdowns must be considered as an alternative explanation for complex unspecific symptoms during the COVID-19 pandemic.

Source: Sorg AL, Becht S, Jank M, Armann J, von Both U, Hufnagel M, Lander F, Liese JG, Niehues T, Verjans E, Wetzke M, Stojanov S, Behrends U, Drosten C, Schroten H, von Kries R. Association of SARS-CoV-2 Seropositivity With Myalgic Encephalomyelitis and/or Chronic Fatigue Syndrome Among Children and Adolescents in Germany. JAMA Netw Open. 2022 Sep 1;5(9):e2233454. doi: 10.1001/jamanetworkopen.2022.33454. PMID: 36166227.  https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2796733 (Full text)

Long COVID Risk and Pre-COVID Vaccination: An EHR-Based Cohort Study from the RECOVER Program

Abstract:

Importance: Characterizing the effect of vaccination on long COVID allows for better healthcare recommendations. Objective: To determine if, and to what degree, vaccination prior to COVID-19 is associated with eventual long COVID onset, among those a documented COVID-19 infection.

Design, Settings, and Participants: Retrospective cohort study of adults with evidence of COVID-19 between August 1, 2021 and January 31, 2022 based on electronic health records from eleven healthcare institutions taking part in the NIH Researching COVID to Enhance Recovery (RECOVER) Initiative, a project of the National Covid Cohort Collaborative (N3C). Exposures: Pre-COVID-19 receipt of a complete vaccine series versus no pre-COVID-19 vaccination.

Main Outcomes and Measures: Two approaches to the identification of long COVID were used. In the clinical diagnosis cohort (n=47,752), ICD-10 diagnosis codes or evidence of a healthcare encounter at a long COVID clinic were used. In the model-based cohort (n=199,498), a computable phenotype was used. The association between pre-COVID vaccination and long COVID was estimated using IPTW-adjusted logistic regression and Cox proportional hazards.

Results: In both cohorts, when adjusting for demographics and medical history, pre-COVID vaccination was associated with a reduced risk of long COVID (clinic-based cohort: HR, 0.66; 95% CI, 0.55-0.80; OR, 0.69; 95% CI, 0.59-0.82; model-based cohort: HR, 0.62; 95% CI, 0.56-0.69; OR, 0.70; 95% CI, 0.65-0.75).

Conclusions and Relevance: Long COVID has become a central concern for public health experts. Prior studies have considered the effect of vaccination on the prevalence of future long COVID symptoms, but ours is the first to thoroughly characterize the association between vaccination and clinically diagnosed or computationally derived long COVID. Our results bolster the growing consensus that vaccines retain protective effects against long COVID even in breakthrough infections.

Source: M Daniel BrannockRobert F ChewAlexander J PreissEmily C HadleyJulie A McMurryPeter J LeeseAndrew T GirvinMiles CrosskeyAndrea G ZhouRichard A MoffittMichele Jonsson FunkEmily PfaffMelissa HaendelChristopher G ChuteN3C ConsortiumRECOVER Consortium. Long COVID Risk and Pre-COVID Vaccination: An EHR-Based Cohort Study from the RECOVER Program.

Long COVID symptoms in a population-based sample of persons discharged home from hospital

Abstract:

Objectives: The impact of long COVID among persons hospitalized and discharged home is unknown. We aimed to (1) report the prevalence of long COVID in persons hospitalized for COVID-19 and discharged home; (2) estimate the prevalence of physical, sensory, and psychological/mental health impairments; and (3) explore associated factors.

Methods: We conducted a telephone survey of adult residents in Laval, Quebec, who were discharged home ≥ 2 months post-hospitalization for COVID-19. Participants responded to a standard questionnaire regarding persistent symptoms. We calculated the prevalence of long COVID and of persistent types of symptoms and evaluated associated factors using bivariate analysis and multivariable logistic regression.

Results: In our sample (n = 398), 70% reported physical symptoms, 58% psychological problems, and 16% sensory impairments. 31.5% reported being troubled by persistent symptoms (long COVID). Factors associated with long COVID were a greater number of symptoms (odds ratio (OR) = 1.97, 95% confidence interval (CI) = 1.69-2.28) and increased hospital stay (OR = 1.03, 95% CI = 1.01-1.06). Other factors associated with physical and psychological symptoms were female sex (OR = 2.17, 95% CI = 1.27-3.71 and OR = 2.06, 95% CI = 1.25-3.39; respectively), higher education level (OR = 2.10, 95% CI = 1.20-3.68 and OR = 2.43, 95% CI = 1.44-4.14; respectively), and obesity (OR = 1.95, 95% CI = 1.15-3.34 and OR = 1.70, 95% CI = 1.05-2.77; respectively).

Conclusion: In this population-based study of persons hospitalized for COVID-19 and discharged home, nearly one third were troubled by symptoms for 2 months or more post-discharge. There was a high proportion with persistent physical and psychological/mental health symptoms. Further research will assess the specific needs of these patients to inform health policy makers on service requirements for these persons.

Source: Feldman DE, Boudrias MH, Mazer B. Long COVID symptoms in a population-based sample of persons discharged home from hospital. Can J Public Health. 2022 Sep 21:1–10. doi: 10.17269/s41997-022-00695-9. Epub ahead of print. PMID: 36131218; PMCID: PMC9491248. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9491248/ (Full text)

Post-COVID myalgic encephalomyelitis in chronic heart disease patient: A case series

Abstract

Purpose of Study: Myalgic encephalomyelitis (ME), also called chronic fatigue syndrome, is a condition characterized by severe fatigue that impairs a patient’s ability to perform common daily activities.

Criteria for ME include 6 months of fatigue-limited daily activities, unrefreshing sleep, and symptom exacerbation following physical or mental strain, and orthostatic intolerance.

New reports indicate that ME incidence may be higher in specific patient populations. This study was designed to investigate the association between ME and Cardiovascular disease in patients recovering from COVID-19 infection.

Methods: Used The patient population used for this study includes 19 patients that were referred to the Amarillo Heart Group in Amarillo, TX who also tested positive for Covid-19 at least 6 months prior to September 1, 2021.

The patients that fit this timeline were asked a series of standardized questions and rate the severity of their symptoms on a scale of 0 to 5, with 0 being the absence of symptoms and 5 being the most severe. Two sets of questions were created and named Life Spheres Criteria (4 questions) and Symptoms Criteria (3 questions) based on the 2015 IOM Diagnostic Criteria for CFS. Rating more than 1 Life Spheres question as a 3 or higher or rating all 3 Symptoms Criteria questions as a 3 or higher indicated Chronic Fatigue Syndrome. Information from the survey, including time since infection, demographics, and question scores, were analyzed.

Summary of Results: Our study included 10 women and 10 men, with the average amount of time since Covid-19 infection being 328.17 ± 41.36 days. Worsening of symptoms with mild exertion was the most commonly endorsed criteria (3.58 ± 1.64) and the least common criterion was fatigue reducing activity in school (2.00 ± 1.94).

Women scored higher in every category except reduced activity in school when compared to men. However, there was no significant difference in symptom scores between the two groups with the Combined Fatigue Score being 2.89 ± 1.47 for women and 2.67 ± 1.59 for men.

Nearly all symptom scores significantly positively correlated with one another, meaning if one category was high it was likely for other categories to be high as well.

Ultimately, when looking at the Cumulative Pearson Correlation Scores, reduced social life, difficulty concentrating, and symptoms worsening with mild exertion were found to be most predictive of a high Combined Fatigue Score.

Conclusions: In this case series, over 80% of patients met the criteria for Post-COVID Myalgic Encephalomyelitis. While the link between ME and both COVID-19 and cardiovascular disease has been established, little is known about the severity of ME in patients who have a history of both cardiovascular disease and COVID-19 infection.

To our knowledge, this is the first study to examine ME in patients with both of these predisposing conditions. A high degree of clinical suspicion for ME should be used when screening and treating cardiac patients who have been infected with COVID-19.

Source: Holder, K. G.; Vemulapalli, V.; Daines, B.; Kankam, A.; Galvan, B.; Nambiar, R. Post-COVID myalgic encephalomyelitis in chronic heart disease patient: A case series. Journal of Investigative Medicine ; 70(2):475, 2022. https://pesquisa.bvsalud.org/global-literature-on-novel-coronavirus-2019-ncov/resource/pt/covidwho-1705710

Impact of cross-coronavirus immunity in post-acute sequelae of COVID-19

Abstract:

Beyond the unpredictable acute illness caused by SARS-CoV-2, one-fifth of infections unpredictably result in long-term persistence of symptoms despite the apparent clearance of infection. Insights into the mechanisms that underlie post-acute sequelae of COVID-19 (PASC) will be critical for the prevention and clinical management of long-term complications of COVID-19. Several hypotheses have been proposed that may account for the development of PASC, including persistence of virus or the dysregulation of immunity. Among the immunological changes noted in PASC, alterations in humoral immunity have been observed in some patient subsets.

To begin to determine whether SARS-CoV-2 or other pathogen specific humoral immune responses evolve uniquely in PASC, we performed comprehensive antibody profiling against SARS-CoV-2 and a panel of endemic pathogens or routine vaccine antigens using Systems Serology in a cohort of patients with pre-existing rheumatic disease who either developed or did not develop PASC.

A distinct humoral immune response was observed in individuals with PASC. Specifically, individuals with PASC harbored less inflamed and weaker Fcγ receptor binding anti-SARS-CoV-2 antibodies and a significantly expanded and more inflamed antibody response against endemic Coronavirus OC43. Individuals with PASC, further, generated more avid IgM responses and developed an expanded inflammatory OC43 S2-specific Fc-receptor binding response, linked to cross reactivity across SARS-CoV-2 and common coronaviruses. These findings implicate previous common Coronavirus imprinting as a marker for the development of PASC.

Source: Jonathan D. HermanCaroline AtyeoYonatan ZurClaire E. CookNaomi J. PatelKathleen M. VanniEmily N. KowalskiGrace QianNancy A. ShadickDouglas LaffenburgerZachary S. WallaceJeffrey A. SparksGalit Alter. Impact of cross-coronavirus immunity in post-acute sequelae of COVID-19.

Higher rates of long covid symptoms in patients with mild covid-19

Abstract:

BACKGROUND: The Coronavirus Disease 2019 (COVID-19) pandemic has affected over 61 million U.S. citizens, and up to 30-80% of COVID-19 survivors may go on to develop post-acute sequelae of SARS-CoV-2 (PASC). These sequelae can be debilitating and often impair quality of life and daily function. Although it has been suggested that severity of acute COVID-19 infection is directly related to PASC development, this association remains unclear.

METHODS: This prospective cohort study was conducted through consecutive recruitment of confirmed and probable COVID-19 patients with persistent symptoms lasting ≥3 weeks from disease onset or positive SARS-CoV-2 test from academic PASC clinics at Emory University and Grady Memorial Hospital in Atlanta, GA during January-December 2021. Sociodemographic, comorbidity, and acute COVID-19 data were collected. Severe acute COVID- 19 was defined as requiring hospitalization, and critical acute COVID-19 required intensive care. New or worsening symptoms persisting ≥3 weeks from COVID-19 onset were collected using a standardized review of systems, and confirmed by clinician interview. Differences in PASC symptom type were assessed by calculating risk ratios (RR) and 95% confidence intervals (CI) using the Taylor series, and difference in PASC duration was assessed using student’s t-test. Two-tailed p-values ≤0.05 were considered significant.

RESULTS: Of 269 enrollees, median age was 52 years (range 18-93) and there were more women (74%) than men (26%). There were 152 (57%) African American, 76 (28%) White, and 21 (8%) Hispanic. Among PASC patients, the most common symptoms were dyspnea (68%), fatigue (63%), brain fog (48%), dizziness (27%), chest pain (25%), cough (23%) and headache (23%) with a median PASC duration of 132 days (range 21-523). Acute COVID-19 severity was asymptomatic in one participant, mild in 149 (55%), severe in 95 (35%), and critical in 23 (9%). Asymptomatic- mild acute COVID-19 patients had more persistent dyspnea (RR 1.33, 95%, CI 1.09- 1.61), fatigue (RR 1.53, 95%CI 1.22-1.91), brain fog (RR 2.00, 95%CI 1.44-2.67), dizziness (RR 2.03, 95%CI 1.27-3.25), and headache (RR 2.07, 95%CI 1.22-3.48) compared with severe-critical acute disease, who had a non-significant trend towards more cough and chest pain. Asymptomatic-mild participants were further from incident infection (153 days) compared to severe-critical participants (110 days) (p=0.04).

CONCLUSIONS: Contrary to previous observations, COVID-19 survivors who experienced asymptomatic-mild infections may develop higher rates of prevalent PASC symptoms compared to those with severe- critical antecedent infections. These findings are not attributable to PASC duration, as longer PASC duration has been previously associated with fewer symptoms. To ensure early identification and linkage to specialized care, clinicians should be aware of PASC in patients with antecedent asymptomatic-mild acute COVID-19 infections.

Source: Walker, T.; Truong, A.; Summers, A.; Dixit, A.; Goldstein, F.; Hajjar, I.; Echols, M.; Cook, S.; Lee, E.; Tekwani, S.; Carroll, K.; Sanz, I.; Lee, E. H.; Han, J. Higher rates of long covid symptoms in patients with mild covid-19. Journal of General Internal Medicine ; 37:S280, 2022. Article in English | EMBASE | ID: covidwho-1995854 https://pesquisa.bvsalud.org/global-literature-on-novel-coronavirus-2019-ncov/resource/pt/covidwho-1995854?lang=en

Differences in Long-COVID Symptoms between Vaccinated and Non-Vaccinated (BNT162b2 Vaccine) Hospitalized COVID-19 Survivors Infected with the Delta Variant

This study compared differences in the presence of post-COVID symptoms among vaccinated and non-vaccinated COVID-19 survivors requiring hospitalization due to the Delta (B.1.617.2) variant. This cohort study included hospitalized subjects who had survived SARS-CoV-2 infection (Delta variant) from July to August 2021 in an urban hospital in Madrid, Spain. Individuals were classified as vaccinated if they received full administration (i.e., two doses) of BNT162b2 (“Pfizer-BioNTech”) vaccines. Other vaccines were excluded. Those with just one dose of the BNT162b2 vaccine were considered as non-vaccinated.
Patients were scheduled for a telephone interview at a follow-up around six months after infection for assessing the presence of post-COVID symptoms with particular attention to those symptoms starting after acute infection and hospitalization. Anxiety/depressive levels and sleep quality were likely assessed. Hospitalization and clinical data were collected from medical records. A total comprising 109 vaccinated and 92 non-vaccinated COVID-19 survivors was included.
Vaccinated patients were older and presented a higher number of medical comorbidities, particular cardiorespiratory conditions, than non-vaccinated patients. No differences in COVID-19 onset symptoms at hospitalization and post-COVID symptoms six months after hospital discharge were found between vaccinated and non-vaccinated groups. No specific risk factor for any post-COVID symptom was identified in either group.
This study observed that COVID-19 onset-associated symptoms and post-COVID symptoms six-months after hospitalization were similar between previously hospitalized COVID-19 survivors vaccinated and those non-vaccinated. Current data can be applied to the Delta variant and those vaccinated with BNT162b2 (Pfizer-BioNTech) vaccine.
Source: Fernández-de-las-Peñas C, Ortega-Santiago R, Fuensalida-Novo S, Martín-Guerrero JD, Pellicer-Valero OJ, Torres-Macho J. Differences in Long-COVID Symptoms between Vaccinated and Non-Vaccinated (BNT162b2 Vaccine) Hospitalized COVID-19 Survivors Infected with the Delta Variant. Vaccines. 2022; 10(9):1481. https://doi.org/10.3390/vaccines10091481 https://www.mdpi.com/2076-393X/10/9/1481/htm (Full text)

Risk of Long Covid in people infected with SARS-CoV-2 after two doses of a COVID-19 vaccine: community-based, matched cohort study

Abstract:

We investigated Long Covid incidence by vaccination status in a random sample of UK adults from April 2020 to November 2021. Persistent symptoms were reported by 9.5% of 3,090 breakthrough SARS-CoV-2 infections and 14.6% of unvaccinated controls (adjusted odds ratio 0.59, 95% CI: 0.50-0.69), emphasising the need for public health initiatives to increase population-level vaccine uptake.

Source: Daniel Ayoubkhani, Matthew L Bosworth, Sasha King, Koen B Pouwels, Myer Glickman, Vahé Nafilyan, Francesco Zaccardi, Kamlesh Khunti, Nisreen A Alwan, A Sarah Walker, Risk of Long Covid in people infected with SARS-CoV-2 after two doses of a COVID-19 vaccine: community-based, matched cohort study, Open Forum Infectious Diseases, 2022;, ofac464, https://doi.org/10.1093/ofid/ofac464 (Full text available as PDF file)

Predictors of Long COVID in Patients without Comorbidities: Data from the Polish Long-COVID Cardiovascular (PoLoCOV-CVD) Study

Abstract:

Background: The SARS-CoV-2 pandemic has become an enormous worldwide challenge over the last two years. However, little is still known about the risk of Long COVID (LC) in patients without comorbidities. Thus, we aimed to assess the predictors of LC in patients without comorbidities.

Methods: Patients’ information, the course of the disease with symptoms, and post-COVID-19 complaints were collected within 4-12 weeks after COVID-19 recovery. Next, the patients were followed for at least 3 months. ECG, 24-h ECG monitoring, 24-h blood pressure (BP) monitoring, echocardiography, and selected biochemical tests were performed. LC was recognized based on the WHO definition.

Results: We identified 701 consecutive patients, 488 of whom completed a 3-month follow-up (63% women). Comparisons were made between the LC group (n = 218) and patients without any symptoms after SARS-CoV-2 recovery (non-LC group) (n = 270). Patients with a severe course of acute-phase COVID-19 developed LC complications more often (34% vs. 19%, p < 0.0001). The persistent symptoms were observed in 45% of LC patients. The LC group also had significantly more symptoms during the acute phase of COVID-19, and they suffered significantly more often from dyspnoea (48 vs. 33%), fatigue (72 vs. 63%), chest pain (50 vs. 36%), leg muscle pain (41 vs. 32%), headache (66 vs. 52%), arthralgia (44 vs. 25%), and chills (34 vs. 25%). In LC patients, significant differences regarding sex and body mass index were observed-woman: 69% vs. 56% (p = 0.003), and BMI: 28 [24-31] vs. 26 kg/m2 [23-30] (p < 0.001), respectively. The number of symptoms in the acute phase was significantly greater in the LC group than in the control group (5 [2-8] vs. 2 [1-5], p = 0.0001). The LC group also had a higher 24-h heart rate (77 [72-83] vs. 75 [70-81], p = 0.021) at admission to the outpatient clinic. Multivariate regression analysis showed that LC patients had a higher BMI (odds ratio (OR): 1.06, 95% confidence intervals [CI]: 1.02-1.10, p = 0.007), almost twice as often had a severe course of COVID-19 (OR: 1.74, CI: 1.07-2.81, p = 0.025), and presented with joint pain in the acute phase (OR: 1.90, CI: 1.23-2.95, p = 0.004).

Conclusions: A severe course of COVID-19, BMI, and arthralgia are independently associated with the risk of Long COVID in healthy individuals.

Source: Chudzik M, Lewek J, Kapusta J, Banach M, Jankowski P, Bielecka-Dabrowa A. Predictors of Long COVID in Patients without Comorbidities: Data from the Polish Long-COVID Cardiovascular (PoLoCOV-CVD) Study. J Clin Med. 2022 Aug 25;11(17):4980. doi: 10.3390/jcm11174980. PMID: 36078910. https://www.mdpi.com/2077-0383/11/17/4980/htm (Full text)

The prevalence of SARS-CoV-2 infection and long COVID in US adults during the BA.5 surge, June-July 2022

Abstract:

Due to changes in SARS-CoV-2 testing practices, passive case-based surveillance may be an increasingly unreliable indicator for monitoring the burden of SARS-CoV-2, especially during surges. We conducted a cross-sectional survey of a population-representative sample of 3,042 U.S. adults between June 30 and July 2, 2022, during the Omicron BA.5 surge. Respondents were asked about SARS-CoV-2 testing and outcomes, COVID-like symptoms, contact with cases, and experience with prolonged COVID-19 symptoms following prior infection.

We estimated the weighted age and sex-standardized SARS-CoV-2 prevalence, during the 14-day period preceding the interview. We estimated age and gender adjusted prevalence ratios (aPR) for current SARS-CoV-2 infection using a log-binomial regression model.

An estimated 17.3% (95% CI 14.9, 19.8) of respondents had SARS-CoV-2 infection during the two-week study period, equating to 44 million cases as compared to 1.8 million per the CDC during the same time period. SARS-CoV-2 prevalence was higher among those 18-24 years old (aPR 2.2, 95% CI 1.8, 2.7) and among non-Hispanic Black (aPR 1.7, 95% CI 1.4 ,2.2) and Hispanic (aPR 2.4, 95% CI 2.0 , 2.9). SARS-CoV-2 prevalence was also higher among those with lower income (aPR 1.9, 95% CI 1.5, 2.3), lower education (aPR 3.7 95% CI 3.0,4.7), and those with comorbidities (aPR 1.6, 95% CI 1.4, 2.0). An estimated 21.5% (95% CI 18.2, 24.7) of respondents with a SARS-CoV-2 infection more than 4 weeks prior reported long COVID symptoms.

The inequitable distribution of SARS-CoV-2 prevalence during the BA.5 surge will likely drive inequities in the future burden of long COVID.

Source: Saba Qasmieh, McKaylee Robertson, Chloe A Teasdale, Sarah Kulkarni, Heidi E Jones, Margaret McNairy, Luisa N Borrell, Denis Nash. The prevalence of SARS-CoV-2 infection and long COVID in US adults during the BA.5 surge, June-July 2022. medRxiv 2022.09.04.22279588; doi: https://doi.org/10.1101/2022.09.04.22279588 (Full text available as PDF file)