The coronavirus disease 2019 (COVID-19) is still in a global pandemic state. Some studies have reported that COVID-19 vaccines had a protective effect against long COVID. However, the conclusions of the studies on the effect of COVID-19 vaccines on long COVID were not consistent. This study aimed to systematically review relevant studies in the real world, and performed a meta-analysis to explore the relationship between vaccination and long COVID. We systematically searched PubMed, Embase, Web of science, and ScienceDirect from inception to 19 September 2022. The PICO (P: patients; I: intervention; C: comparison; O: outcome) was as follows: patients diagnosed with COVID-19 (P); vaccination with COVID-19 vaccines (I); the patients were divided into vaccinated and unvaccinated groups (C); the outcomes were the occurrence of long COVID, as well as the various symptoms of long COVID (O). A fixed-effect model and random-effects model were chosen based on the heterogeneity between studies in order to pool the effect value. The results showed that the vaccinated group had a 29% lower risk of developing long COVID compared with the unvaccinated group (RR = 0.71, 95% CI: 0.58–0.87, p < 0.01). Compared with patients who were not vaccinated, vaccination showed its protective effect in patients vaccinated with two doses (RR = 0.83, 95% CI: 0.74–0.94, p < 0.01), but not one dose (RR = 0.83, 95% CI: 0.65–1.07, p = 0.14). In addition, vaccination was effective against long COVD in patients either vaccinated before SARS-CoV-2 infection/COVID-19 (RR = 0.82, 95% CI: 0.74–0.91, p < 0.01) or vaccinated after SARS-CoV-2 infection/COVID-19 (RR = 0.83, 95% CI: 0.74–0.92, p < 0.01). For long COVID symptoms, vaccination reduced the risk of cognitive dysfunction/symptoms, kidney diseases/problems, myalgia, and sleeping disorders/problems sleeping. Our study shows that COVID-19 vaccines had an effect on reducing the risk of long COVID in patients vaccinated before or after SARS-CoV-2 infection/COVID-19. We suggest that the vaccination rate should be improved as soon as possible, especially for a complete vaccination course. There should be more studies to explore the basic mechanisms of the protective effect of COVID-19 vaccines on long COVID in the future.

/pdf/effect-of-covid-19-vaccines-on-reducing-the-risk-of-long-1mu92anr.pdf

Effect of COVID-19 Vaccines on Reducing the Risk of Long COVID in the Real World: A Systematic Review and Meta-Analysis

Background Long-term health sequelae of the Coronavirus Disease 2019 (COVID-19) are a major public health concern. However, evidence on post-acute COVID-19 syndrome (post-COVID-19) is still limited, particularly for children and adolescents. Utilizing comprehensive healthcare data on approximately 46% of the German population, we investigated post-COVID-19-associated morbidity in children/adolescents and adults. Methods and findings We used routine data from German statutory health insurance organizations covering the period between January 1, 2019 and December 31, 2020. The base population included all individuals insured for at least 1 day in 2020. Based on documented diagnoses, we identified individuals with polymerase chain reaction (PCR)-confirmed COVID-19 through June 30, 2020. A control cohort was assigned using 1:5 exact matching on age and sex, and propensity score matching on preexisting medical conditions. The date of COVID-19 diagnosis was used as index date for both cohorts, which were followed for incident morbidity outcomes documented in the second quarter after index date or later.Overall, 96 prespecified outcomes were aggregated into 13 diagnosis/symptom complexes and 3 domains (physical health, mental health, and physical/mental overlap domain). We used Poisson regression to estimate incidence rate ratios (IRRs) with 95% confidence intervals (95% CIs). The study population included 11,950 children/adolescents (48.1% female, 67.2% aged between 0 and 11 years) and 145,184 adults (60.2% female, 51.1% aged between 18 and 49 years). The mean follow-up time was 236 days (standard deviation (SD) = 44 days, range = 121 to 339 days) in children/adolescents and 254 days (SD = 36 days, range = 93 to 340 days) in adults. COVID-19 and control cohort were well balanced regarding covariates. The specific outcomes with the highest IRR and an incidence rate (IR) of at least 1/100 person-years in the COVID-19 cohort in children and adolescents were malaise/fatigue/exhaustion (IRR: 2.28, 95% CI: 1.71 to 3.06, p < 0.01, IR COVID-19: 12.58, IR Control: 5.51), cough (IRR: 1.74, 95% CI: 1.48 to 2.04, p < 0.01, IR COVID-19: 36.56, IR Control: 21.06), and throat/chest pain (IRR: 1.72, 95% CI: 1.39 to 2.12, p < 0.01, IR COVID-19: 20.01, IR Control: 11.66). In adults, these included disturbances of smell and taste (IRR: 6.69, 95% CI: 5.88 to 7.60, p < 0.01, IR COVID-19: 12.42, IR Control: 1.86), fever (IRR: 3.33, 95% CI: 3.01 to 3.68, p < 0.01, IR COVID-19: 11.53, IR Control: 3.46), and dyspnea (IRR: 2.88, 95% CI: 2.74 to 3.02, p < 0.01, IR COVID-19: 43.91, IR Control: 15.27). For all health outcomes combined, IRs per 1,000 person-years in the COVID-19 cohort were significantly higher than those in the control cohort in both children/adolescents (IRR: 1.30, 95% CI: 1.25 to 1.35, p < 0.01, IR COVID-19: 436.91, IR Control: 335.98) and adults (IRR: 1.33, 95% CI: 1.31 to 1.34, p < 0.01, IR COVID-19: 615.82, IR Control: 464.15). The relative magnitude of increased documented morbidity was similar for the physical, mental, and physical/mental overlap domain. In the COVID-19 cohort, IRs were significantly higher in all 13 diagnosis/symptom complexes in adults and in 10 diagnosis/symptom complexes in children/adolescents. IRR estimates were similar for age groups 0 to 11 and 12 to 17. IRs in children/adolescents were consistently lower than those in adults. Limitations of our study include potentially unmeasured confounding and detection bias. Conclusions In this retrospective matched cohort study, we observed significant new onset morbidity in children, adolescents, and adults across 13 prespecified diagnosis/symptom complexes, following COVID-19 infection. These findings expand the existing available evidence on post-COVID-19 conditions in younger age groups and confirm previous findings in adults. Trial registration ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT05074953.

/pdf/post-covid-19-associated-morbidity-in-children-adolescents-2uq6a792.pdf

Post-COVID-19-associated morbidity in children, adolescents, and adults: A matched cohort study including more than 157,000 individuals with COVID-19 in Germany

Post-COVID-19 conditions, also known as ‘Long-COVID-19’, describe a longer and more complex course of illness than acute COVID-19 with no widely accepted uniform case definition. We aimed to map the available evidence on persistent symptoms and sequelae following SARS-CoV-2 in children and adults. We searched the Cochrane COVID-19 Study Register and the WHO COVID-19 Global literature on coronavirus disease database on 5 November 2021. We included longitudinal and cross-sectional studies and we extracted their characteristics, including the type of core outcomes for post-COVID-19 conditions. We included 565 studies (657 records). Most studies were uncontrolled cohort studies. The median follow-up time was 13 weeks (IQR 9 to 24). Only 72% of studies were conducted in high-income countries, 93% included unvaccinated adults with mild-to-critical disease, only 10% included children and adolescents, and less than 5% included children under the age of five. While most studies focused on health symptoms, including respiratory symptoms (71%), neurological symptoms (57%), fatigue (54%), pain (50%), mental functioning (43%), cardiovascular functioning (40%), and post-exertion symptoms (28%), cognitive function (26%), fewer studies assessed other symptoms such as overall recovery (24%), the need for rehabilitation (18%), health-related quality of life (16%), changes in work/occupation and study (10%), or survival related to long-COVID-19 (4%). There is a need for controlled cohort studies with long-term follow-up and a focus on overall recovery, health-related quality of life, and the ability to perform daily tasks. Studies need to be extended to later phases of the pandemic and countries with low resources.

/pdf/long-term-health-symptoms-and-sequelae-following-sars-cov-2-3afyij2j.pdf

Long-Term Health Symptoms and Sequelae Following SARS-CoV-2 Infection: An Evidence Map

The aim of this study was to assess the impact of the COVID-19 pandemic on the mental wellbeing of children 8–18 years old with chronic conditions, by comparing pandemic data with pre-pandemic data and with healthy peers. Data were obtained from two ongoing longitudinal cohorts: the PROactive cohort study following children with a chronic condition, and the WHISTLER population cohort. Mental wellbeing was assessed by three indicators: life satisfaction, internalising symptoms, and psychosomatic health. The stringency of the COVID-19-related lockdown was considered a moderating factor. Data on chronic patients were recorded before (n = 934, 65% girls) and during (n = 503, 61% girls) the pandemic, and compared to healthy peers during the pandemic (n = 166, 61% girls). Children with a chronic condition reported lower life satisfaction, but no clinically relevant changes in internalising symptoms or psychosomatic health, during the pandemic compared to before. In comparison to healthy peers, children with a chronic condition experienced decreased life satisfaction and psychosomatic health, but internalising symptoms did not differ between groups during the COVID-19 pandemic. The lockdown stringency was negatively associated with all indicators of mental wellbeing—worse life satisfaction, more internalising symptoms, and more psychosomatic symptoms.

/pdf/the-impact-of-the-covid-19-outbreak-on-mental-wellbeing-in-2tvjchoa.pdf

The Impact of the COVID-19 Outbreak on Mental Wellbeing in Children with a Chronic Condition Compared to Healthy Peers

/pdf/neurocognitive-and-psychosocial-characteristics-of-pediatric-1kllhxs2.pdf

Neurocognitive and Psychosocial Characteristics of Pediatric Patients With Post-Acute/Long-COVID: A Retrospective Clinical Case Series

The majority of coronavirus disease 2019 (COVID-19) symptom presentations in adults and children appear to run their course within a couple of weeks. However, a subgroup of adults has started to emerge with effects lasting several months or more after initial infection, which raises questions about the long-term physical, mental and social health effects of COVID-19 in the pediatric population. The purpose of this review was to determine these impacts well into the second year of the pandemic.A search was conducted using PubMed, Web of Science, Science Direct, and Cochrane between 11/1/2019 and 9/1/2021. Search inclusion criteria were as follows: (1) COVID-19 illness and symptoms in children; (2) severe acute respiratory syndrome coronavirus 2 in children; (3) English language; and (4) human studies only.The few studies that have documented long-term physical symptoms in children show that fatigue, difficulty in concentrating (brain fog), sleep disturbances, and sensory problems are the most reported outcomes. Most studies examining the impact of COVID-19 in pediatric populations have focused on initial clinical presentation, and symptoms, which are similar to those in adult populations. In addition, COVID-19 has had a moderate impact on children and adolescents' social environment, which may exacerbate current and future physiological, psychological, behavioral, and academic outcomes.There are limited studies reporting long physical symptoms of COVID-19 in the pediatric population. However, pediatric COVID-19 cases are underreported due to low rates of testing and symptomatic infection, which calls for more longitudinal studies. Children who have experienced COVID-19 illness should be monitored for long physiological, psychological, behavioral, and academic outcomes. 

/pdf/long-term-physical-mental-and-social-health-effects-of-covid-3foh5zmp.pdf

Long-term physical, mental and social health effects of COVID-19 in the pediatric population: a scoping review

The prevalence of long-term symptoms of coronavirus disease 2019 (COVID-19) in nonhospitalized pediatric populations in the United States is not well described. The objective of this analysis was to examine the presence of persistent COVID symptoms in children by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody status.Data were collected between October 2020 and May 2022 from the Texas Coronavirus Antibody REsponse Survey, a statewide prospective population-based survey among 5-90 years old. Serostatus was assessed by the Roche Elecsys Anti-SARS-CoV-2 Immunoassay for detection of antibodies to the SARS-CoV-2 nucleocapsid protein. Self-reported antigen/polymerase chain reaction COVID-19 test results and persistent COVID symptom status/type/duration were collected simultaneously. Risk ratios for persistent COVID symptoms were calculated versus adults and by age group, antibody status, symptom presence/severity, variant, body mass index and vaccine status.A total of 82 (4.5% of the total sample [n = 1813], 8.0% pre-Delta, 3.4% Delta and beyond) participants reported persistent COVID symptoms (n = 27 [1.5%] 4-12 weeks, n = 58 [3.3%] >12 weeks). Compared with adults, all pediatric age groups had a lower risk for persistent COVID symptoms regardless of length of symptoms reported. Additional increased risk for persistent COVID symptoms >12 weeks included severe symptoms with initial infection, not being vaccinated and having unhealthy weight (body mass index ≥85th percentile for age and sex).These findings highlight the existence of nonhospitalized youth who may also experience persistent COVID symptoms. Children and adolescents are less likely to experience persistent COVID symptoms than adults and more likely to be symptomatic, experience severe symptoms and have unhealthy weight compared with children/adolescents without persistent COVID symptoms. 

R. T. Pardasani

Papers

Long-term physical, mental and social health effects of COVID-19 in the pediatric population: a scoping review

Comparison of Persistent Symptoms Following SARS-CoV-2 Infection by Antibody Status in Nonhospitalized Children and Adolescents