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Patients with post-COVID/long-COVID symptoms need support, and health care professionals need to be able to provide evidence-based patient care. Digital interventions can meet these requirements, especially if personal contact is limited. We reviewed evidence-based digital interventions that are currently available to help manage physical and mental health in patients with post-COVID/long-COVID symptoms. A scoping review was carried out summarizing novel digital health interventions for treating post-COVID/long-COVID patients. Using the PICO (population, intervention, comparison, outcome) scheme, original studies were summarized, in which patients with post-COVID/long-COVID symptoms used digital interventions to help aid recovery. From all scanned articles, 8 original studies matched the inclusion criteria. Of the 8 studies, 3 were \"pretest\" studies, 3 described the implementation of a telerehabilitation program, 1 was a post-COVID/long-COVID program, and 1 described the results of qualitative interviews with patients who used an online peer-support group. Following the PICO scheme, we summarized previous studies. Studies varied in terms of participants (P), ranging from adults in different countries, such as former hospitalized patients with COVID-19, to individuals in disadvantaged communities in the United Kingdom, as well as health care workers. In addition, the studies included patients who had previously been infected with COVID-19 and who had ongoing symptoms. Some studies focused on individuals with specific symptoms, including those with either post-COVID-19 or long-term symptoms, while other studies included patients based on participation in online peer-support groups. The interventions (I) also varied. Most interventions used a combination of psychological and physical exercises, but they varied in duration, frequency, and social dimensions. The reviewed studies investigated the physical and mental health conditions of patients with post-COVID/long-COVID symptoms. Most studies had no control (C) group, and most studies reported outcomes (O) or improvements in physiological health perception, some physical conditions, fatigue, and some psychological aspects such as depression. However, some studies found no improvements in bowel or bladder problems, concentration, short-term memory, unpleasant dreams, physical ailments, perceived bodily pain, emotional ailments, and perceived mental health. More systematic research with larger sample sizes is required to overcome sampling bias and include health care professionals' perspectives, as well as help patients mobilize support from health care professionals and social network partners. The evidence so far suggests that patients should be provided with digital interventions to manage symptoms and reintegrate into everyday life, including work.

COVID-19 pandemic continues to challenge the world with a major public health problem, long COVID (LC), which is estimated to affect over 400 million people worldwide. Many unknowns remain regarding the mechanisms involved in LC. We investigated the impact of anti-SARS-CoV-2 antibody and IFN-γ responses on the development of LC and its various phenotypes. We studied a cohort of 137 convalescents following predominantly mild COVID-19 during the first pandemic wave (2020) and up to one-year post-infection. We found 45% of LC cases that were associated with a greater number and duration of acute-phase symptoms. Cardiovascular and/or gastrointestinal symptoms in the acute phase were associated to protection against LC development, while pulmonary, otorhinolaryngological, musculoskeletal and other symptoms were associated with increased risk of LC development. Regarding LC phenotypes, we observed risk associations and potentially deleterious effects of anti-SARS-CoV-2 antibodies for LC symptoms classified as general or other. In contrast, for vital organ-related LC symptoms, we found only protective associations, particularly for cardiovascular symptoms, which indeed had a low prevalence in LC (16%). Collectively, our data suggest that anti-SARS-CoV-2 antibodies play a protective role against vital organ-related LC symptoms, especially cardiovascular symptoms, but are insufficient in preventing or limiting other highly prevalent LC symptoms, such as neurological, psychiatric and pulmonary.

Introduction Long COVID is a multisystemic, fluctuating condition inducing a high burden on affected people. Despite the existence of some guidelines, its management remains complicated. We aimed to demonstrate that symptoms after a COVID-19 infection evolve following different trajectories from the initial infection until 24 months after, to identify the determinants of these trajectories, and the quality of life of people in these trajectories. Methods Study participants from the Predi-COVID cohort were digitally followed from their acute SARS-CoV-2 infection until a maximum of 24 months. Data from 10 common symptoms collected at study inclusion, and months 12, 15, and 24 awere used to create a total symptom score. Impact of symptoms on quality of life was assessed at month 24 using standardized questionnaires and ad-hoc questions. Latent classes mixed models were used to identify total score symptom trajectories and individual symptoms trajectories. Results We included 555 participants with at least 2 different time points available during follow-up (Baseline and at least one of the M12, M15 or M24 questionnaires). We identified 2 total symptom score trajectories: T1 “Mild symptoms, fast resolution” ( N  = 376; 67.7%), and T2 “Elevated and persisting symptoms” ( N  = 179; 32.3%). The main determinants of being in T2 were: older age (OR = 1.86; p  = 0.003), to be a woman (OR = 1.81; p  = 0.001)), elevated BMI (OR = 3.97; p  < 0.001), and the presence of multi comorbidities (OR = 2.67; p  = 0.005). Symptoms impacted the quality of life more in T2 than in T1 at 24 months (high fatigue level: 64.8% vs 19.5%, altered respiratory quality of life: 42.6% vs 4.6%, anxiety: 24.1% vs 4.6%, stress: 57.4% vs 35.6%, and bad sleep: 75.9% vs 51.1%). Conclusion A third of our study population was in the T2 “Elevated and persisting symptoms” trajectory, presenting high symptom frequencies up to 24 months after initial infection, with a significant impact on quality of life. This work underlined the urgent need to better identify individuals most vulnerable to long-term complications to develop tailored interventions for them. Trial registration Clinicaltrials.gov NCT04380987 (date of registration: 2020–05-07).

There are limited data on the illness trajectory for individuals with long COVID. We prospectively followed 1,234 individuals with long COVID at 3 months post-SARS-CoV-2 infection to identify factors associated with persistence or recovery. At 6 months post-infection, 724 (58.7%) had persistent long COVID and 510 (41.3%) had fully recovered. In multivariable analyses, pre-existing health conditions at the time of initial SARS-CoV-2 infection and reporting fatigue, shortness of breath, and cough 3 months post-infection were independent predictors of persistent long COVID. Age, sex, and number of COVID vaccinations were not significantly associated with persistent long COVID. For persons with persistent long COVID, the median number of symptoms remained stable over follow-up, indicating that there had been little symptomatic improvement. A third of those with persistent long COVID reported seeking medical care for their symptoms and a third had ceased or reduced their hours of work/study. Our findings suggest that there may be distinct clinical trajectories for long COVID observed between 3- and 6-month follow-up, that is, persons who experience full recovery and those with minimal clinical improvement, and this may have implications for management of affected individuals.

The long-term symptoms of COVID-19 are the subject of public and scientific discussions. Understanding how those long COVID symptoms co-occur in clusters of syndromes may indicate the pathogenic mechanisms of long COVID. Our study objective was to cluster the different long COVID symptoms. We included persons who had a COVID-19 and assessed long-term symptoms (at least 4 weeks after first symptoms). Hierarchical clustering was applied to the symptoms as well as to the participants based on the Euclidean distance h of the log-values of the answers on symptom severity. The distribution of clusters within our cohort is shown in a heat map.From September 2021 to November 2023, 2371 persons with persisting long COVID symptoms participated in the study. Self-assessed long COVID symptoms were assigned to three symptom clusters. Cluster A unites rheumatological and neurological symptoms, cluster B includes neuro-psychological symptoms together with cardiorespiratory symptoms, and a third cluster C shows an association of general infection signs, dermatological and otology symptoms. A high proportion of the participants (n = 1424) showed symptoms of all three clusters. Clustering of long COVID symptoms reveals similarities to the symptomatology of already described syndromes such as the Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) or rheumatological autoinflammatory diseases. Further research may identify serological parameters or clinical risk factors associated with the shown clusters and might improve our understanding of long COVID as a systemic disease. Furthermore, multimodal treatments can be developed and scaled for symptom clusters and associated impairments.

Endothelial damage represents an essential pathogenic mechanism of respiratory and multiorgan dysfunction as seen in the post-acute phase of COVID-19. Biological differences between male and female sex, inflammation, and gut integrity may have an integral role in endothelial damage and explain the residual effects of COVID-19 infection in long COVID, yet evidence is limited. Confirmed COVID-19 negative participants were 1:1 propensity-score matched to COVID-19 positive participants. Symptoms occurring at least one-month following COVID-infection and lasting more than three-months was defined as long COVID. Measures of endothelial function included reactive hyperemic index (RHI ≥ 1.67 = normal endothelial function) and augmentation index (higher AIx = worse arterial elasticity). A total of 89 COVID-19 negative participants was matched to 89 COVID-19 positive participants. Among the COVID-19 survivors, the median age was 42.92 years, 46.07% were female sex, and 57 (64%) had long COVID. Higher levels of inflammation (TNF-RI and oxLDL) and gut integrity (zonulin and BDG) was associated ( P  < 0.05) with a two-fold increase in the odds of long COVID. Female sex, independent of COVID-19 status, was 4x more likely to have worse AIx ( P  < 0.0001) compared to male sex. Among female sex with long COVID, higher levels of inflammation (IL-6, VCAM, hsCRP) and gut integrity (zonulin) was independently associated ( P  < 0.05) with higher AIx. Female sex with long COVID symptoms had the worse inflammation, gut integrity, and arterial stiffness among COVID-19 survivors. This reinforces the importance of continued, long-term follow-up care following COVID-19 infection, with special attention needed for female sex who may be at a higher cardiovascular disease risk.

Background/Objectives: Millions of individuals worldwide continue to experience symptoms following SARS-CoV-2 infection. This study aimed to assess the prevalence and phenotype of multi-system symptoms attributed to Long COVID—including fatigue, pain, cognitive-emotional disturbances, headache, cardiopulmonary issues, and alterations in taste and smell—that have persisted for at least two years after acute infection, which we define as “persistent Long COVID”. Additionally, the study aimed to identify clinical features and blood biomarkers associated with persistent Long COVID symptoms. Methods: We sent a detailed long COVID symptoms questionnaire to an existing cohort of 1258 vaccinated adults (age 18–79 years) who had mild infection (e.g., non-hospitalized) SARS-CoV-2 Delta variant 2 years earlier. These individuals had comprehensive datasets, including blood samples, available for further analysis. We estimated prevalence of persistent long COVID two years post-infection using weighted adjustment (Horvitz–Thompson estimator) to overcome reporting bias. Multivariable logistic regression models were used to determine association of clinical features and blood biomarkers (pre-infection SARS-CoV-2 RBD-IgG, SARS-CoV-2 neutralizing antibodies, and pre-infection and post-infection neurofilament light) with prevalence of persistent long COVID. Results: N = 323 participants responded to the survey, of whom N = 74 (23%) reported at least one long COVID symptom that had persisted for two years after the acute infection. Weighted prevalence of persistent long COVID symptoms was 21.5% (95% CI = 16.7–26.3%). Female gender, smoking, and severity of acute COVID-19 infection were significantly associated with persistent Long COVID. The blood biomarkers assessed were not significantly associated with persistent Long COVID. Conclusions: Among vaccinated adults two years after mild infection with Delta variant SARS-CoV-2, persistent symptoms attributed to Long COVID are extremely common, certain subgroups are at higher risk, and further research into biological mechanisms and potential treatment targets is needed.

This cross-sectional study examines the functional limitations of Long COVID (LC) in a clinically confirmed cohort ( n = 220). We collected sociodemographic, clinical, and lifestyle data via a structured electronic form and assessed daily limitations using the Post-COVID-19 Functional Status (PCFS) scale. Linear models were used to evaluate the association between symptom burden and functional limitations and to identify symptom-specific predictors of impairment. Participants had a mean age of 44.8 years, and 80.5% were women. A dose–response pattern linked higher symptom counts with worse PCFS grades in the multivariable-adjusted model ( β = 0.17; 95% CI 0.10–0.25; p < 0.001). In hierarchical models, fatigue, dizziness, and memory loss were independent predictors of greater functional limitations (crude β : fatigue 1.56; 95% CI 1.22–1.90; dizziness 1.08; 95% CI 0.81–1.34; and memory loss 1.26; 95% CI 0.97–1.55), cumulatively explaining 51.3% of the variance in functional limitations. In contrast, other common LC symptoms did not retain independent associations after adjustment. These findings highlight the value of simple symptom counts and targeted symptom profiles for risk stratification in primary care and occupational health and for planning rehabilitation and work ability assessment. Prospective studies should validate these indicators over time and explore the mechanisms linking neurocognitive and fatigue phenotypes with persistent disability.

This article aims to present the overview of the situation during the coronavirus disease 2019 (COVID-19) pandemic about issues concerning the prevalence of mental disorders such as depression, anxiety, rate of suicide attempts, and long COVID (LC) infections in the general population during COVID-19 pandemic. Analysis of the literature (in English, Polish and Spanish language) on topics related to COVID-19, mental disorders (suicide attempts, depression, anxiety) and LC infection published during the 4 years (2020-2023) was done using Pubmed and PubMed Central search engine. Keywords such as \"COVID-19,\" \"mental disorders,\" \"long COVID infection,\" \"depression,\" \"anxiety,\" \"suicide attempts\" were used during the search. The conduct of this review/comment followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) protocol, which corresponds to a checklist of 27 items designed to facilitate the development and reporting of a robust protocol for systematic reviews or meta-analyses. Overall 35 studies were selected and analyzed in the review on topics: including among others LC (14 studies), suicide attempts (7 studies), mental disorders (depression, anxiety) (14 studies). The main issues raised in the articles were: higher risk of LC symptoms in women, fatigue and brain fog listed as frequently encountered patient's complaints together with anxiety, depression, loneliness, especially in younger age groups and in women. Issues regarding LC, mental disorders and suicide attempts requires further research as the results vary in different countries. Int J Occup Med Environ Health. 2024;37(3):360-80.