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The COVID-19 pandemic continues to constitute a public health emergency of international importance, although the state of emergency declaration has indeed been terminated worldwide, many people continue to be infected and present different symptoms associated with the illness. Undoubtedly, solutions based on divergent technologies such as machine learning have made great contributions to the understanding, identification, and treatment of the disease. Due to the sudden appearance of this virus, many works have been carried out by the scientific community to support the detection and treatment processes, which has generated numerous publications, making it difficult to identify the status of current research and future contributions that can continue to be generated around this problem that is still valid among us. To address this problem, this article shows the result of a scientometric analysis, which allows the identification of the various contributions that have been generated from the line of automatic learning for the monitoring and treatment of symptoms associated with this pathology. The methodology for the development of this analysis was carried out through the implementation of two phases: in the first phase, a scientometric analysis was carried out, where the countries, authors, and magazines with the greatest production associated with this subject can be identified, later in the second phase, the contributions based on the use of the Tree of Knowledge metaphor are identified. The main concepts identified in this review are related to symptoms, implemented algorithms, and the impact of applications. These results provide relevant information for researchers in the field in the search for new solutions or the application of existing ones for the treatment of still-existing symptoms of COVID-19. [ABSTRACT FROM AUTHOR]

This study sought to characterize cognitive functioning in patients with neurological post-acute sequelae of SARS-CoV-2 infection (Neuro-PASC) and investigate the association of subjective and objective functioning along with other relevant factors with prior hospitalization for COVID-19. Participants were 106 adult outpatients with Neuro-PASC referred for abbreviated neuropsychological assessment after scoring worse than one standard deviation below the mean on cognitive screening. Of these patients, 23 had been hospitalized and 83 had not been hospitalized for COVID-19. Subjective cognitive impairment was evaluated with the self-report cognition subscale from the Patient-Reported Outcome Measurement Information System. Objective cognitive performance was assessed using a composite score derived from multiple standardized cognitive measures. Other relevant factors, including fatigue and depression/mood symptoms, were assessed via the Patient-Reported Outcome Measurement Information System. Subjective cognitive impairment measures exceeded the minimal difficulties noted on objective tests and were associated with depression/mood symptoms as well as fatigue. However, fatigue independently explained the most variance (17.51%) in patients’ subjective cognitive ratings. When adjusting for fatigue and time since onset of COVID-19 symptoms, neither objective nor subjective impairment were associated with prior hospitalization for COVID-19. Findings suggest that abbreviated neuropsychological assessment may not reveal objective difficulties beyond initial cognitive screening in patients with NeuroPASC. However, subjective cognitive concerns may persist irrespective of hospitalization status, and are likely influenced by fatigue and depression/ mood symptoms. The impact of concomitant management of fatigue and mood in patients with Neuro-PASC who report cognitive concerns deserve further study. [ABSTRACT FROM AUTHOR]

This study sought to characterize cognitive functioning in patients with neurological post-acute sequelae of SARS-CoV-2 infection (Neuro-PASC) and investigate the association of subjective and objective functioning along with other relevant factors with prior hospitalization for COVID-19. Participants were 106 adult outpatients with Neuro-PASC referred for abbreviated neuropsychological assessment after scoring worse than one standard deviation below the mean on cognitive screening. Of these patients, 23 had been hospitalized and 83 had not been hospitalized for COVID-19. Subjective cognitive impairment was evaluated with the self-report cognition subscale from the Patient-Reported Outcome Measurement Information System. Objective cognitive performance was assessed using a composite score derived from multiple standardized cognitive measures. Other relevant factors, including fatigue and depression/mood symptoms, were assessed via the Patient-Reported Outcome Measurement Information System. Subjective cognitive impairment measures exceeded the minimal difficulties noted on objective tests and were associated with depression/mood symptoms as well as fatigue. However, fatigue independently explained the most variance (17.51%) in patients’ subjective cognitive ratings. When adjusting for fatigue and time since onset of COVID-19 symptoms, neither objective nor subjective impairment were associated with prior hospitalization for COVID-19. Findings suggest that abbreviated neuropsychological assessment may not reveal objective difficulties beyond initial cognitive screening in patients with Neuro-PASC. However, subjective cognitive concerns may persist irrespective of hospitalization status, and are likely influenced by fatigue and depression/mood symptoms. The impact of concomitant management of fatigue and mood in patients with Neuro-PASC who report cognitive concerns deserve further study.

Abstract Background Self-rated health (SRH) is widely recognized as a clinically significant predictor of subsequent mortality risk. Although COVID-19 may impair SRH, this relationship has not been extensively examined. The present study aimed to examine the correlation between habitual sleep duration, changes in sleep duration after infection, and SRH in subjects who have experienced SARS-CoV-2 infection. Methods Participants from 16 countries participated in the International COVID Sleep Study-II (ICOSS-II) online survey in 2021. A total of 10,794 of these participants were included in the analysis, including 1,509 COVID-19 individuals (who reported that they had tested positive for COVID-19). SRH was evaluated using a 0-100 linear visual analog scale. Habitual sleep durations of < 6 h and > 9 h were defined as short and long habitual sleep duration, respectively. Changes in habitual sleep duration after infection of ≤ -2 h and ≥ 1 h were defined as decreased or increased, respectively. Results Participants with COVID-19 had lower SRH scores than non-infected participants, and those with more severe COVID-19 had a tendency towards even lower SRH scores. In a multivariate regression analysis of participants who had experienced COVID-19, both decreased and increased habitual sleep duration after infection were significantly associated with lower SRH after controlling for sleep quality (β = −0.056 and −0.058, respectively, both p < 0.05); however, associations between current short or long habitual sleep duration and SRH were negligible. Multinomial logistic regression analysis showed that decreased habitual sleep duration was significantly related to increased fatigue (odds ratio [OR] = 1.824, p < 0.01), shortness of breath (OR = 1.725, p < 0.05), diarrhea/nausea/vomiting (OR = 2.636, p < 0.01), and hallucinations (OR = 5.091, p < 0.05), while increased habitual sleep duration was significantly related to increased fatigue (OR = 1.900, p < 0.01). Conclusions Changes in habitual sleep duration following SARS-CoV-2 infection were associated with lower SRH. Decreased or increased habitual sleep duration might have a bidirectional relation with post-COVID-19 symptoms. Further research is needed to better understand the mechanisms underlying these relationships for in order to improve SRH in individuals with COVID-19.

Background: Self-rated health (SRH) is widely recognized as a clinically significant predictor of subsequent mortality risk. Although COVID-19 may impair SRH, this relationship has not been extensively examined. The present study aimed to examine the correlation between habitual sleep duration, changes in sleep duration after infection, and SRH in subjects who have experienced SARS-CoV-2 infection. Methods: Participants from 16 countries participated in the International COVID Sleep Study-II (ICOSS-II) online survey in 2021. A total of 10,794 of these participants were included in the analysis, including 1,509 COVID-19 individuals (who reported that they had tested positive for COVID-19). SRH was evaluated using a 0-100 linear visual analog scale. Habitual sleep durations of < 6 h and > 9 h were defined as short and long habitual sleep duration, respectively. Changes in habitual sleep duration after infection of ≤ -2 h and ≥ 1 h were defined as decreased or increased, respectively. Results: Participants with COVID-19 had lower SRH scores than non-infected participants, and those with more severe COVID-19 had a tendency towards even lower SRH scores. In a multivariate regression analysis of participants who had experienced COVID-19, both decreased and increased habitual sleep duration after infection were significantly associated with lower SRH after controlling for sleep quality (β = −0.056 and −0.058, respectively, both p < 0.05); however, associations between current short or long habitual sleep duration and SRH were negligible. Multinomial logistic regression analysis showed that decreased habitual sleep duration was significantly related to increased fatigue (odds ratio [OR] = 1.824, p < 0.01), shortness of breath (OR = 1.725, p < 0.05), diarrhea/nausea/vomiting (OR = 2.636, p < 0.01), and hallucinations (OR = 5.091, p < 0.05), while increased habitual sleep duration was significantly related to increased fatigue (OR = 1.900, p < 0.01). Conclusions: Changes in habitual sleep duration following SARS-CoV-2 infection were associated with lower SRH. Decreased or increased habitual sleep duration might have a bidirectional relation with post-COVID-19 symptoms. Further research is needed to better understand the mechanisms underlying these relationships for in order to improve SRH in individuals with COVID-19. [ABSTRACT FROM AUTHOR]

The associations between longitudinal dynamics and the breadth of SARS‐CoV‐2 neutralizing antibody (nAb) response with various Long COVID phenotypes before vaccination are not known. The capacity of antibodies to cross‐neutralize a variety of viral variants may be associated with ongoing pathology and persistent symptoms. We measured longitudinal neutralizing and cross‐neutralizing antibody responses to pre‐ and post‐SARS‐CoV‐2 Omicron variants in participants infected early in the COVID‐19 pandemic, before widespread rollout of SARS‐CoV‐2 vaccines. Cross‐sectional regression models adjusted for clinical covariates and longitudinal mixed‐effects models were used to determine the impact of the breadth and rate of decay of neutralizing responses on the development of Long COVID symptoms, as well as Long COVID phenotypes. We identified several novel relationships between SARS‐CoV‐2 antibody neutralization and the presence of Long COVID symptoms. Specifically, we show that, although nAb responses to the original, infecting strain of SARS‐CoV‐2 were not associated with Long COVID in cross‐sectional analyses, cross‐neutralization ID50 levels to the Omicron BA.5 variant approximately 4 months following acute infection was independently and significantly associated with greater odds of Long COVID and with persistent gastrointestinal and neurological symptoms. Longitudinal modeling demonstrated significant associations in the overall levels and rates of decay of neutralization capacity with Long COVID phenotypes. A higher proportion of participants had antibodies capable of neutralizing Omicron BA.5 compared with BA.1 or XBB.1.5 variants. Our findings suggest that relationships between various immune responses and Long COVID are likely complex but may involve the breadth of antibody neutralization responses. Summary: SARS‐CoV‐2‐specific antibody neutralization of Omicron BA.5 variant approximately 4 months following acute infection with wild‐type virus before vaccination was independently and significantly associated with greater odds of distinct Long COVID phenotypes. [ABSTRACT FROM AUTHOR]

This dataset was created with the primary objective of elucidating the intricate relationship between the incidence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) re-infections and the pre-illness vaccination profile and types concerning alterations in sports-related physical activity (PA) after SARS-CoV-2 infection among adults. A secondary objective encompassed a comprehensive statistical analysis to explore the influence of three key factors—namely, Vaccination profile, Vaccination types, and Incidence of SARS-CoV-2 re-infections—on changes in PA related to exercise and sports, recorded at two distinct time points: one to two weeks prior to infection and one month after the last SARS-CoV-2 infection.The sample population (n = 5829), drawn from Hellenic territory, adhered to self-inclusion and exclusion criteria. Data collection spanned from February to March 2023 (a two-month period), involving the utilization of the Active-Q (an online, interactive questionnaire) to automatically assess weekly habitual sports-related PA among adults both before and after their last SARS-CoV-2 infection. The questionnaire also captured participant characteristics, pre-illness vaccination statuses (i.e., unvaccinated, partially vaccinated, fully vaccinated, and vaccine types), and occurrences of SARS-CoV-2 re-infections.The dataset sheds light on two noteworthy phenomena: (i) the intricate interplay between post-acute SARS-CoV-2 infection and a decline in sports-related physical activity (−27.6 ± 0.6%, 95%CI: -26.1 – −29.1), influenced by the pre-illness vaccination profile factor (p = 0.040); and (ii) the divergence in sports-related physical activity decline between partially vaccinated (−38.2 ± 0.7%, 95%CI: -35.3 – −41.1, p = 0.031) and fully vaccinated respondents (−19.2 ± 0.5%, 95%CI: −17.2 – −21.2).These phenomena underscore the imperative for tailored interventions and further investigation to promote the resumption of physical activity and mitigate long-term repercussions. Furthermore, this dataset enriches our understanding of the dynamics of sports-related physical activity and provides valuable insights for public health initiatives aiming to address the consequences of COVID-19 on sports-related physical activity levels. Consequently, this cross-sectional dataset is amenable to a diverse array of analytical methodologies, including univariate and multivariate analyses, and holds potential relevance for researchers, leaders in the sports and medical sectors, and policymakers, all of whom share a vested interest in fostering initiatives directed at reinstating physical activity and mitigating the enduring ramifications of post-acute SARS-CoV-2 infection.

This study investigated changes in physical activity (PA) after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection while considering age, PA level, underlying medical conditions (UMCs), vaccination profiles/types, re-infections, disease severity, and treatment. Data were collected from 5829 respondents by using a validated web-based questionnaire. The findings showed that there was a significant overall decrease in PA (−16.2%), including in daily occupation (−11.9%), transportation (−13.5%), leisure-time (−16.4%), and sporting (−27.6%) activities. Age, PA level, UMCs, vaccination profiles/types, disease severity, and treatment played a role in determining PA in individuals' post-acute SARS-CoV-2 infections. Re-infections did not impact the decline in PA. Unvaccinated individuals experienced a significant decline in PA (−13.7%). Younger (−22.4%) and older adults (−22.5%), those with higher PA levels (−20.6%), those with 2–5 UMCs (−23.1%), those who were vaccinated (−16.9%) or partially vaccinated (−19.1%), those with mRNA-type vaccines only (−17.1%), those with recurrent (−19.4%)-to-persistent (−54.2%) symptoms, and those that required hospital (−51.8%) or intensive care unit (−67.0%) admission during their infections had more pronounced declines in PA. These findings emphasize the complex relationship between post-acute SARS-CoV-2 infection and PA and highlight the need for targeted interventions, further research, and multidisciplinary care to promote PA resumption and mitigate long-term effects on global public health. [ABSTRACT FROM AUTHOR]

We are reviewing the current state of knowledge on the virological and immunological correlates of long COVID, focusing on recent evidence for the possible association between the increasing number of SARS-CoV-2 reinfections and the parallel pandemic of long COVID. The severity of reinfections largely depends on the severity of the initial episode; in turn, this is determined both by a combination of genetic factors, particularly related to the innate immune response, and by the pathogenicity of the specific variant, especially its ability to infect and induce syncytia formation at the lower respiratory tract. The cumulative risk of long COVID as well as of various cardiac, pulmonary, or neurological complications increases proportionally to the number of SARS-CoV-2 infections, primarily in the elderly. Therefore, the number of long COVID cases is expected to remain high in the future. Reinfections apparently increase the likelihood of long COVID, but less so if they are mild or asymptomatic as in children and adolescents. Strategies to prevent SARS-CoV-2 reinfections are urgently needed, primarily among older adults who have a higher burden of comorbidities. Follow-up studies using an established case definition and precise diagnostic criteria of long COVID in people with or without reinfection may further elucidate the contribution of SARS-CoV-2 reinfections to the long COVID burden. Although accumulating evidence supports vaccination, both before and after the SARS-CoV-2 infection, as a preventive strategy to reduce the risk of long COVID, more robust comparative observational studies, including randomized trials, are needed to provide conclusive evidence of the effectiveness of vaccination in preventing or mitigating long COVID in all age groups. Thankfully, answers not only on the prevention, but also on treatment options and rates of recovery from long COVID are gradually starting to emerge. [ABSTRACT FROM AUTHOR]

Plain English summary The World Health Organisation defines Long COVID as a condition which impacts people 3 months after they first had COVID-19. Some of the symptoms that characterise Long COVID symptoms include fatigue, breathlessness and brain fog. These symptoms have a major impact on people’s health and quality of life. Today, over 2 million people in the United Kingdom suffer from Long COVID and there is a lack of drugs and non-drugs treatment. However, some non-drugs treatments which aim to manage fatigue in other conditions, such as pacing, could be used with people with Long COVID. In this paper, we report how we co-produced a study which tested whether or not it is feasible for people who have Long COVID to use a pacing resource and report their symptoms using an electronic platform. After a meeting to review existing non-drugs treatments, the research team and a group of patient partners agreed on co-developing a clinical trial platform to test different pacing resources. The research team then met with the patient partners twice a week to co-design the study during which people with Long COVID will use the pacing resources and report their symptoms. They also co-designed the study documents and how to report its results. Co-producing a study with patient partners was effective and influenced important aspects of the study.

Summary: Background: Long-COVID (LC) encompasses diverse symptoms lasting months after the initial SARS-CoV-2 infection. Symptoms can be debilitating and affect the quality of life of individuals with LC and their families. Although the symptoms of LC are well described, the aetiology of LC remains unclear, and consequently, patients may be underdiagnosed. Identification of LC specific biomarkers is therefore paramount for the diagnosis and clinical management of the syndrome. This scoping review describes the molecular and cellular biomarkers that have been identified to date with potential use for diagnosis or prediction of LC. Methods: This review was conducted using the Joanna Briggs Institute (JBI) Methodology for Scoping Reviews. A search was executed in the MEDLINE and EMBASE databases, as well as in the grey literature for original studies, published until October 5th, 2022, reporting biomarkers identified in participants with LC symptoms (from all ages, ethnicities, and sex), with a previous infection of SARS-CoV-2. Non-English studies, cross-sectional studies, studies without a control group, and pre-prints were excluded. Two reviewers independently evaluated the studies, extracted population data and associated biomarkers. Findings: 23 cohort studies were identified, involving 2163 LC patients [median age 51.8 years, predominantly female sex (61.10%), white (75%), and non-vaccinated (99%)]. A total of 239 candidate biomarkers were identified, consisting mainly of immune cells, immunoglobulins, cytokines, and other plasma proteins. 19 of the 239 candidate biomarkers identified were evaluated by the authors, by means of receiver operating characteristic (ROC) curves. Interpretation: Diverse cellular and molecular biomarkers for LC have been proposed. Validation of candidate biomarkers in independent samples should be prioritized. Modest reported performance (particularly in larger studies) suggests LC may encompass many distinct aetiologies, which should be explored e.g., by stratifying by symptom clusters and/or sex. Funding: Dr. Tebbutt has received funding from the Canadian Institutes of Health Research (177747) to conduct this work. The funding source was not involved in this scoping review, or in the decision to submit this manuscript for publication.

Background: The high incidence of COVID-19 globally has led to a large prevalence of Long COVID but there is a lack of evidence-based treatments. There is a need to evaluate existing treatments for symptoms associated with Long COVID. However, there is first a need to evaluate the feasibility of undertaking randomised controlled trials of interventions for the condition. We aimed to co-produce a feasibility study of non-pharmacological interventions to support people with Long COVID. Methods: A consensus workshop on research prioritisation was conducted with patients and other stakeholders. This was followed by the co-production of the feasibility trial with a group of patient partners, which included the design of the study, the selection of interventions, and the production of dissemination strategies. Results: The consensus workshop was attended by 23 stakeholders, including six patients. The consensus from the workshop was to develop a clinical trial platform that focused on testing different pacing interventions and resources. For the co-production of the feasibility trial, patient partners selected three pacing resources to evaluate (video, mobile application, and book) and co-designed feasibility study processes, study materials and undertook usability testing of the digital trial platform. Conclusion: In conclusion, this paper reports the principles and process used to co-produce a feasibility study of pacing interventions for Long COVID. Co-production was effective and influenced important aspects of the study. Plain English summary: The World Health Organisation defines Long COVID as a condition which impacts people 3 months after they first had COVID-19. Some of the symptoms that characterise Long COVID symptoms include fatigue, breathlessness and brain fog. These symptoms have a major impact on people's health and quality of life. Today, over 2 million people in the United Kingdom suffer from Long COVID and there is a lack of drugs and non-drugs treatment. However, some non-drugs treatments which aim to manage fatigue in other conditions, such as pacing, could be used with people with Long COVID. In this paper, we report how we co-produced a study which tested whether or not it is feasible for people who have Long COVID to use a pacing resource and report their symptoms using an electronic platform. After a meeting to review existing non-drugs treatments, the research team and a group of patient partners agreed on co-developing a clinical trial platform to test different pacing resources. The research team then met with the patient partners twice a week to co-design the study during which people with Long COVID will use the pacing resources and report their symptoms. They also co-designed the study documents and how to report its results. Co-producing a study with patient partners was effective and influenced important aspects of the study. [ABSTRACT FROM AUTHOR]

Post-Acute Sequelae of SARS-CoV-2 infection (PASC), commonly known as Long COVID, represents a significant and complex health challenge with a wide range of symptoms affecting multiple organ systems. This review examines the emerging evidence suggesting a critical role of the gut and gut-brain axis in the pathophysiology of Long COVID. It explores how changes in the gut microbiome, disruption of gut barrier integrity, and the persistence of SARS-CoV-2 antigens within the gastrointestinal tract may contribute to the prolonged and varied symptoms seen in Long COVID, including chronic inflammation and neuropsychiatric disturbances. The review also summarizes key insights gained about Long COVID, highlighting its multifactorial nature, which involves immune dysregulation, microvascular damage, and autonomic nervous system dysfunction, with the gut playing a central role in these processes. While progress has been made in understanding these mechanisms, current evidence remains inconclusive. The challenges of establishing causality, standardizing research methodologies, and addressing individual variations in the microbiome are discussed, emphasizing the need for further longitudinal studies and more comprehensive approaches to enhance our understanding of these complex interactions. This review underscores the importance of personalized approaches in developing effective diagnostic and therapeutic strategies for Long COVID, while also acknowledging the significant gaps in our current understanding. Future research should aim to further unravel the complex interplay between the gut and Long COVID, ultimately improving outcomes for those affected by this condition., (Copyright ©2024, Yale Journal of Biology and Medicine.)

Abstract Background Coronavirus disease 2019 (COVID-19) results in debilitating long-term symptoms, often referred to as Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), in a substantial subgroup of patients. One of the most prevalent symptoms following COVID-19 is severe fatigue. Prompt delivery of cognitive behavioural therapy (CBT), an evidence-based treatment that has shown benefit in reducing severe fatigue in other conditions, may reduce post-COVID-19 fatigue. Based on an existing CBT protocol, a blended intervention of 17 weeks, Fit after COVID, was developed to treat severe fatigue after the acute phase of infection with SARS-CoV-2. Method The ReCOVer study is a multicentre 2-arm randomised controlled trial (RCT) to test the efficacy of Fit after COVID on severe post-infectious fatigue. Participants are eligible if they report severe fatigue 3 up to and including 12 months following COVID-19. One hundred and fourteen participants will be randomised to either Fit after COVID or care as usual (ratio 1:1). The primary outcome, the fatigue severity subscale of the Checklist Individual Strength (CIS-fatigue), is assessed in both groups before randomisation (T0), directly post CBT or following care as usual (T1), and at follow-up 6 months after the second assessment (T2). In addition, a long-term follow-up (T3), 12 months after the second assessment, is performed in the CBT group only. The primary objective is to investigate whether CBT will lead to a significantly lower mean fatigue severity score measured with the CIS-fatigue across the first two follow-up assessments (T1 and T2) as compared to care as usual. Secondary objectives are to determine the proportion of participants no longer being severely fatigued (operationalised in different ways) at T1 and T2 and to investigate changes in physical and social functioning, in the number and severity of somatic symptoms and in problems concentrating across T1 and T2. Discussion This is the first trial testing a cognitive behavioural intervention targeting severe fatigue after COVID-19. If Fit after COVID is effective in reducing fatigue severity following COVID-19, this intervention could contribute to alleviating the long-term health consequences of COVID-19 by relieving one of its most prevalent and distressing long-term symptoms. Trial registration Netherlands Trial Register NL8947 . Registered on 14 October 2020.

In this study, we investigated whether treatment with palmitoylethanolamide and luteolin (PEA-LUT) leads to improvement in the quantitative or qualitative measures of olfactory dysfunction or relief from mental clouding in patients affected by long COVID. Patients with long COVID olfactory dysfunction were allocated to different groups based on the presence ("previously treated") or absence ("naïve") of prior exposure to olfactory training. Patients were then randomized to receive PEA-LUT alone or in combination with olfactory training. Olfactory function and memory were assessed at monthly intervals using self-report measures and quantitative thresholds. A total of 69 patients (43 women, 26 men) with an age average of 40.6 + 10.5 were recruited. PEA-LUT therapy was associated with a significant improvement in validated odor identification scores at the baseline versus each subsequent month; assessment at 3 months showed an average improvement of 10.7 + 2.6, CI 95%: 6–14 (p < 0.0001). The overall prevalence of parosmia was 79.7% (55 patients), with a significant improvement from the baseline to 3 months (p < 0.0001), namely in 31 patients from the Naïve 1 group (72%), 15 from the Naïve 2 group (93.7%), and 9 from the remaining group (90%). Overall, mental clouding was detected in 37.7% (26 subjects) of the cases, with a reduction in severity from the baseline to three months (p = 0.02), namely in 15 patients from the Naïve 1 group (34.8%), 7 from the Naïve 2 group (43.7%), and 4 from the remaining group (40%). Conclusions. In patients with long COVID and chronic olfactory loss, a regimen including oral PEA-LUT and olfactory training ameliorated olfactory dysfunction and memory. Further investigations are necessary to discern biomarkers, mechanisms, and long-term outcomes. [ABSTRACT FROM AUTHOR]

The SARS-CoV-2 pandemic has left millions of individuals with a host of post-viral symptoms that can be debilitating and persist indefinitely. To date there are no definitive tests or treatments for the collection of symptoms known as "Long COVID" or Post-acute sequelae of COVID-19 (PASC). Following our initial case report detailing improvement of Long COVID symptoms after sequential bilateral stellate ganglion blockade (SGB), we performed a retrospective chart analysis study on individuals treated with the same protocol over the course of six months (2021−2022) in our clinic. Patients self-reported symptoms on a 10-point scale as part of optional patient follow-up using an online survey. After one month or more following treatment, patients reported striking reductions in Fatigue, Worsening of Symptoms following Mental and Physical Activity, Memory Problems, Problems Concentrating, Sleep Problems, Anxiety, and Depression. Loss of Taste and Loss of Smell in some individuals did not respond to treatment, likely indicating structural damage following infection. This study suggests that neuromodulation may provide relief of Long COVID symptoms for at least a subset of individuals, and provides support for prospective studies of this potential treatment. • SARS-CoV-2 infection can cause a long-standing complex constellation of symptoms (Long COVID) • Stellate Ganglion Block can improve symptoms of Long COVID • The mechanism by which SGB improves Long COVID symptoms remains unknown • SGB may correct neuroimmune and/or brain-body axis dysfunction in Long COVID [ABSTRACT FROM AUTHOR]

BackgroundSome patients with acute COVID-19 are left with persistent, debilitating fatigue, cognitive impairment (“brain fog”), orthostatic intolerance (OI) and other symptoms (“Long COVID”). Many of the symptoms are like those of other post-infectious fatigue syndromes and may meet criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Common diagnostic laboratory tests are often unrevealing.MethodsWe evaluated whether a simple, standardized, office-based test of OI, the 10-min NASA Lean Test (NLT), would aggravate symptoms and produce objective hemodynamic and cognitive abnormalities, the latter being evaluated by a simple smart phone-based app.ParticipantsPeople with Long COVID (N = 42), ME/CFS (N = 26) and healthy control subjects (N = 20) were studied just before, during, immediately after, 2 and 7 days following completion of the NLT.ResultsThe NLT provoked a worsening of symptoms in the two patient groups but not in healthy control subjects, and the severity of all symptoms was similar and significantly worse in the two patient groups than in the control subjects (p < 0.001). In the two patient groups, particularly those with Long COVID, the NLT provoked a marked and progressive narrowing in the pulse pressure. All three cognitive measures of reaction time worsened in the two patient groups immediately following the NLT, compared to the healthy control subjects, particularly in the Procedural Reaction Time (p < 0.01).ConclusionsA test of orthostatic stress easily performed in an office setting reveals different symptomatic, hemodynamic and cognitive abnormalities in people with Long COVID and ME/CFS, compared to healthy control subjects. Thus, an orthostatic challenge easily performed in an office setting, and the use of a smart phone app to assess cognition, can provide objective confirmation of the orthostatic intolerance and brain fog reported by patients with Long COVID and ME/CFS.

Background: The pathophysiological mechanisms underlying the post-acute sequelae of severe acute respiratory syndrome coronavirus 2 infection (PASC) are not well understood. Our study aimed to investigate various aspects of theses mechanisms, including viral persistence, immunological responses, and laboratory parameters in patients with and without PASC., Methods: We prospectively enrolled adults aged ≥ 18 years diagnosed with coronavirus disease 2019 (COVID-19) between August 2022 and July 2023. Blood samples were collected at three time-points: within one month of diagnosis (acute phase) and at 1 month, and 3 months post-diagnosis. Following a recent well-designed definition of PASC, PASC patients were defined as those with a questionnaire-based PASC score ≥ 12 persisting for at least 4 weeks after the initial COVID-19 diagnosis., Results: Of 57 eligible COVID-19 patients, 29 (51%) had PASC, and 28 (49%) did not. The PASC group had significantly higher nucleocapsid protein (NP) antigenemia 3 months after COVID-19 diagnosis ( P = 0.022). Furthermore, several cytokines, including IL-2, IL-17A, VEGF, RANTES, sCD40L, IP-10, I-TAC, and granzyme A, were markedly elevated in the PASC group 1 and/or 3 month(s) after COVID-19 diagnosis. In contrast, the median values of several serological markers, including thyroid markers, autoimmune indicators, and stress-related hormones, were within the normal range., Conclusion: Levels of NP antigen and of various cytokines involved in immune responses become significantly elevated over time after COVID-19 diagnosis in PASC patients compared to non-PASC patients. This suggests that PASC is associated with prolonged immune dysregulation resulting from heightened antigenic stimulation., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Background: It is unknown if early COVID-19 monoclonal antibody (mAb) therapy can reduce risk of Long COVID. The mAbs amubarvimab/romlusevimab were previously demonstrated to reduce risk of hospitalization/death by 79%. This study assessed the impact of amubarvimab/romlusevimab on late outcomes, including Long COVID., Methods: Non-hospitalized high-risk adults within 10 days of COVID-19 symptom onset enrolled in a randomized, double-blind, placebo-controlled phase 2/3 trial of amubarvimab/romlusevimab for COVID-19 treatment. Late symptoms, assessed using a participant-completed symptom diary, were a pre-specified exploratory endpoint. The primary outcome for this analysis was the composite of Long COVID by participant self-report (presence of COVID-19 symptoms as recorded in the diary at week 36) or hospitalization or death by week 36. Inverse probability weighting (IPW) was used to address incomplete outcome ascertainment, giving weighted risk ratios (wRR) comparing amubarvimab/romlusevimab to placebo., Findings: Participants received amubarvimab/romlusevimab (n = 390) or placebo (n = 390) between January and July 2021. Median age was 49 years, 52% were female, 18% Black/African American, 49% Hispanic/Latino, and 9% COVID-19-vaccinated at entry. At week 36, 103 (13%) had incomplete outcome ascertainment, and 66 (17%) on amubarvimab/romlusevimab and 92 (24%) on placebo met the primary outcome (wRR = 0.70, 95% confidence interval (CI) 0.53-0.93). The difference was driven by fewer hospitalizations/deaths with amubarvimab/romlusevimab (4%) than placebo (13%). Among 652 participants with available diary responses, 53 (16%) on amubarvimab/romlusevimab and 44 (14%) on placebo reported presence of Long COVID., Interpretation: Amubarvimab/romlusevimab treatment, while highly effective in preventing hospitalizations/deaths, did not reduce risk of Long COVID. Additional interventions are needed to prevent Long COVID., Funding: National Institute of Allergy and Infectious Diseases of the National Institutes of Health. Amubarvimab and romlusevimab supplied by Brii Biosciences., Competing Interests: Dr. Evering reports other from AIDS Clinical Trials Group (ACTG), during the conduct of the study; personal fees from Tonix Pharmaceuticals, outside the submitted work. Dr. Moser reports grants from NIH/NIAID, grants from NIH/NIAID, during the conduct of the study. Dr. Jilg reports other from AIDS Clinical Trials Group (ACTG), during the conduct of the study; grants from National Institutes of Health (NIH), grants from Harvard University Center for AIDS Research (HU-CFAR), other from Sagent Pharmaceuticals, outside the submitted work. Mr. Ritz reports grants from NIH/NIAID, grants from NIH/NIAID, during the conduct of the study. Dr. Wohl reports grants and personal fees from Gilead Sciences, grants and personal fees from ViiV Healthcare, grants and personal fees from Merck & Co, personal fees from Janssen Pharmaceuticals, personal fees from BMS, personal fees from Theratechnologies, personal fees from EMD Serono, personal fees from Regeneron, outside the submitted work. Dr. Margolis reports other from BRII Biosciences, outside the submitted work. Dr. Eron reports grants from National Institutes of Health, during the conduct of the study; personal fees from Merck & Co, grants and personal fees from Gilead Sciences, other from Invivyd, outside the submitted work. Dr. Currier reports personal fees from Merck, outside the submitted work. Dr. Daar reports grants from NIH, during the conduct of the study; grants and personal fees from Gilead, grants and personal fees from ViiV, personal fees from Theratechnologies, outside the submitted work. Dr. Smith reports grants from NIH, during the conduct of the study; personal fees from Model Medicines, personal fees from Bayer, personal fees from Gilead, personal fees from Lucira, personal fees from VXBiosciences, personal fees from Linear Therapies, personal fees from Red Queen Therapeutics, other from A2 Bio, personal fees from Pharma Holdings, personal fees from Evidera, personal fees from Hyundai, outside the submitted work. Dr. Hughes reports grants from United States National Institutes of Health, during the conduct of the study. Dr. Chew reports grants from NIH/NIAID, grants from NIH/NCATS, during the conduct of the study; personal fees from Pardes Biosciences, outside the submitted work. The remaining authors have no competing interests to disclose., (© 2024 Published by Elsevier Ltd.)

Background: Coronavirus disease 2019 (COVID-19) results in debilitating long-term symptoms, often referred to as Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), in a substantial subgroup of patients. One of the most prevalent symptoms following COVID-19 is severe fatigue. Prompt delivery of cognitive behavioural therapy (CBT), an evidence-based treatment that has shown benefit in reducing severe fatigue in other conditions, may reduce post-COVID-19 fatigue. Based on an existing CBT protocol, a blended intervention of 17 weeks, Fit after COVID, was developed to treat severe fatigue after the acute phase of infection with SARS-CoV-2.Method: The ReCOVer study is a multicentre 2-arm randomised controlled trial (RCT) to test the efficacy of Fit after COVID on severe post-infectious fatigue. Participants are eligible if they report severe fatigue 3 up to and including 12 months following COVID-19. One hundred and fourteen participants will be randomised to either Fit after COVID or care as usual (ratio 1:1). The primary outcome, the fatigue severity subscale of the Checklist Individual Strength (CIS-fatigue), is assessed in both groups before randomisation (T0), directly post CBT or following care as usual (T1), and at follow-up 6 months after the second assessment (T2). In addition, a long-term follow-up (T3), 12 months after the second assessment, is performed in the CBT group only. The primary objective is to investigate whether CBT will lead to a significantly lower mean fatigue severity score measured with the CIS-fatigue across the first two follow-up assessments (T1 and T2) as compared to care as usual. Secondary objectives are to determine the proportion of participants no longer being severely fatigued (operationalised in different ways) at T1 and T2 and to investigate changes in physical and social functioning, in the number and severity of somatic symptoms and in problems concentrating across T1 and T2.Discussion: This is the first trial testing a cognitive behavioural intervention targeting severe fatigue after COVID-19. If Fit after COVID is effective in reducing fatigue severity following COVID-19, this intervention could contribute to alleviating the long-term health consequences of COVID-19 by relieving one of its most prevalent and distressing long-term symptoms.Trial Registration: Netherlands Trial Register NL8947 . Registered on 14 October 2020. [ABSTRACT FROM AUTHOR]

During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, providing safe in-person schooling has been a dynamic process balancing evolving community disease burden, scientific information, and local regulatory requirements with the mandate for education. Considerations include the health risks of SARS-CoV-2 infection and its post-acute sequelae, the impact of remote learning or periods of quarantine on education and well-being of children, and the contribution of schools to viral circulation in the community. The risk for infections that may occur within schools is related to the incidence of SARS-CoV-2 infections within the local community. Thus, persistent suppression of viral circulation in the community through effective public health measures including vaccination is critical to in-person schooling. Evidence suggests that the likelihood of transmission of SARS-CoV-2 within schools can be minimized if mitigation strategies are rationally combined. This article reviews evidence-based approaches and practices for the continual operation of in-person schooling.

The autonomic nervous system (ANS) is a complex network of nerves originating in the brain, brain stem, spinal cord, heart and extracardiac organs that regulates neural and physiological responses to internal and external environments and conditions. A common observation among patients with the 2019 Coronavirus (CoV) (SARS-severe acute respiratory syndrome CoV-2) (SARS-CoV-2) or COVID-19 [CO for corona, VI for virus, D for disease and 19 for when the outbreak was first identified (31 December 2019)] in the acute and chronic phases of the disease is tachycardia, labile blood pressure, muscular fatigue and shortness of breath. Because abnormalities in the ANS can contribute to each of these symptoms, herein a review of autonomic dysfunction in SARS-COV-2 infection is provided to guide diagnostic testing, patient care and research initiatives. The autonomic nervous system is a complex network of nerves originating in the brain, brain stem, spinal cord, heart and extracardiac organs that regulates neural and physiological responses to internal and external environments and conditions. A common collection of signs and symptoms among patients with the 2019 Coronavirus (CoV) (SARS-severe acute respiratory syndrome CoV-2) (SARS-CoV-2) or COVID-19 [CO for corona, VI for virus, D for disease and 19 for when the outbreak was first identified (31 December 2019)] is tachycardia, labile blood pressure, muscular fatigue and shortness of breath. Abnormalities in the autonomic nervous system (ANS) can contribute to each of these identifiers, potentially offering a unifying pathobiology for acute, subacute and the long-term sequelae of SARS-CoV-2 infection (PASC) and a target for intervention. [ABSTRACT FROM AUTHOR]

To describe the rheumatic and musculoskeletal symptoms at hospitalization as well as their persistence/severity after discharge with coronavirus disease 2019 (COVID-19) and to identify whether age, sex, body mass index (BMI), and length of hospital stay are associated with persistence of these symptoms. In this single-center cohort study, comprising 300 participants, two phone interviews were conducted (2-week and 1-month after hospitalization) and symptoms were queried with a standardized form. This form included musculoskeletal symptoms and other COVID-19 symptoms. Considering all symptoms (musculoskeletal and other), 100.0%, 86.7%, and 72.0% of patients reported one or more symptoms, at hospitalization, 2-week, and 1-month, respectively. Considering only musculoskeletal symptoms, 92.3%, 72.7%, and 56.3% of patients reported any musculoskeletal symptom at hospitalization, 2-week, and 1-month, respectively. The musculoskeletal symptoms were fatigue (44.3% of patients reported), back pain (22.7%), arthralgia (22.0%), myalgia (21.0%), low back pain (16.3%), and neck pain (10.3%); the other symptoms were shortness of breath (26.3%), loss of taste (15.0%), cough (14.0%), loss of smell (12.3%), loss of appetite (10.3%), headache (8.7%), sore throat (3.0%), diarrhea (1.3%), dizziness (1.3%), and fever (0.3%) at 1-month. Increasing BMI was associated with higher odds of persistence of fatigue (OR: 1.08, 1.03 to 1.13), myalgia (OR: 1.08, 1.01 to 1.14), and arthralgia (OR: 1.07, 1.02 to 1.14, p = 0.012) at 1-month. Nearly three-quarters reported one or more symptoms, with more than half of patients reported any musculoskeletal symptom at 1 month. The most common musculoskeletal symptom was fatigue, followed by back pain, arthralgia, myalgia, low back pain, and neck pain. The persistence of fatigue, myalgia, and arthralgia was related to BMI. The study results increase our understanding of the spectrum of COVID-19, which, in turn, may lead to more efficient and better care for COVID-19 survivors. [ABSTRACT FROM AUTHOR]

A recent meta-analysis from 15 studies encompassing 47,910 patients showed that 80% of patients develop at least one symptom during follow-up times ranging from 2 weeks to 4 months post viral infection ([2]). The current opinion article will discuss the current state of knowledge on the development of long COVID symptoms with a special focus on post-COVID fatigue being the most common symptom. Keywords: anxiety; chronic COVID; depression; functional; long covid; post-infectious; psychosomatic; post-acute sequelae of SARS-CoV-2 infection (PASC) EN anxiety chronic COVID depression functional long covid post-infectious psychosomatic post-acute sequelae of SARS-CoV-2 infection (PASC) 1 3 3 05/25/21 20210521 NES 210521 Introduction Since the start of the pandemic until now (end of February 2021), more than 113 million people worldwide have been infected (encompassing people with and without symptoms) with SARS-CoV-2, with 89 million of those (78.8%) being classified as recovered ([1]). [Extracted from the article]

Background: The associations between longitudinal dynamics and the breadth of SARS-CoV-2 neutralizing antibody response with various Long COVID (LC) phenotypes prior to vaccination are not known. The capacity of antibodies to cross neutralize a variety of viral variants may be associated with ongoing pathology and persistent symptoms., Methods: We measured longitudinal neutralizing and cross-neutralizing antibody responses to pre- and post-SARS-CoV-2 Omicron variants in participants infected during the early waves of the COVID-19 pandemic, prior to wide-spread rollout of SARS-CoV-2 vaccines. Cross sectional regression models adjusted for various clinical covariates and longitudinal mixed effects models were used to determine the impact of the breadth and rate of decay of neutralizing responses on the development of Long COVID symptoms in general, as well as LC phenotypes., Results: We identified several novel relationships between SARS-CoV-2 antibody neutralization and the presence of LC symptoms. Specifically, we show that, although neutralizing antibody responses to the original, infecting strain of SARS-CoV-2 were not associated with LC in cross-sectional analyses, cross-neutralization ID50 levels to the Omicron BA.5 variant approximately 4 months following acute infection was independently and significantly associated with greater odds of LC and with persistent gastrointestinal and neurological symptoms. Longitudinal modeling demonstrated significant associations in the overall levels and rates of decay of neutralization capacity with LC phenotypes. A higher proportion of participants had antibodies capable of neutralizing Omicron BA.5 compared with BA.1 or XBB.1.5 variants., Conclusions: Our findings suggest that relationships between various immune responses and LC are likely complex but may involve the breadth of antibody neutralization responses., Competing Interests: MJP reports consulting fees for Gilead Sciences and AstraZeneca, outside the submitted work. TJH receives grant support from Merck and Co. and has consulted for Roche and Regeneron.

Background: Post-viral syndromes (PVS), including Long COVID, are symptoms sustained from weeks to years following an acute viral infection. Non-pharmacological treatments for these symptoms are poorly understood. This review summarises the evidence for the effectiveness of non-pharmacological treatments for PVS., Methods: We conducted a systematic review to evaluate the effectiveness of non-pharmacological interventions for PVS, as compared to either standard care, alternative non-pharmacological therapy, or placebo. The outcomes of interest were changes in symptoms, exercise capacity, quality of life (including mental health and wellbeing), and work capability. We searched five databases (Embase, MEDLINE, PsycINFO, CINAHL, MedRxiv) for randomised controlled trials (RCTs) published between 1 January 2001 to 29 October 2021. The relevant outcome data were extracted, the study quality was appraised using the Cochrane risk-of-bias tool, and the findings were synthesised narratively., Findings: Overall, five studies of five different interventions (Pilates, music therapy, telerehabilitation, resistance exercise, neuromodulation) met the inclusion criteria. Aside from music-based intervention, all other selected interventions demonstrated some support in the management of PVS in some patients., Interpretation: In this study, we observed a lack of robust evidence evaluating the non-pharmacological treatments for PVS, including Long COVID. Considering the prevalence of prolonged symptoms following acute viral infections, there is an urgent need for clinical trials evaluating the effectiveness and cost-effectiveness of non-pharmacological treatments for patients with PVS., Registration: The study protocol was registered with PROSPERO [CRD42021282074] in October 2021 and published in BMJ Open in 2022.

Studies reported post-COVID-19 fatigue in the general population, but not among pregnant women. Our objectives were to determine prevalence, duration, and risk factors of post-viral fatigue among pregnant women with SARS-CoV-2. This study involved 588 pregnant women with SARS-CoV-2 during pregnancy or delivery in Brazil. Three groups were investigated: G1 ( n = 259, symptomatic infection during pregnancy); G2 ( n = 131, positive serology at delivery); G3 ( n = 198, negative serology at delivery). We applied questionnaires investigating fatigue at determined timepoints after infection for G1, and after delivery for all groups; fatigue prevalence was then determined. Cox regression was used to estimate hazard ratio (HR) and 95% CI of the risk of remaining with fatigue in G1. Overall fatigue prevalence in G1 at six weeks, three months and six months were 40.6%, 33.6%, and 27.8%, respectively. Cumulative risk of remaining with fatigue increased over time, with HR of 1.69 (95% CI: 0.89-3.20) and 2.43 (95% CI: 1.49-3.95) for women with moderate and severe symptoms, respectively. Multivariate analysis showed cough and myalgia as independent risk factors in G1. Fatigue prevalence was significantly higher in G1 compared to G2 and G3. Post-viral fatigue prevalence is higher in women infected during pregnancy; fatigue's risk and duration increased with the severity of infection.

The coronavirus disease (COVID-19), caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection, is leading to unknown and unusual health conditions that are challenging to manage. Post-COVID-19 syndrome is one of those challenges, having become increasingly common as the pandemic evolves. The latest estimates suggest that 10 to 20% of the SARS-CoV-2 patients who undergo an acute symptomatic phase are experiencing effects of the disease beyond 12 weeks after diagnosis. Although research is beginning to examine this new condition, there are still serious concerns about the diagnostic identification, which limits the best therapeutic approach. Exercise programs and physical activity levels are well-known modulators of the clinical manifestations and prognosis in many chronic diseases. This narrative review summarizes the up-to-date evidence on post-COVID-19 syndrome to contribute to a better knowledge of the disease and explains how regular exercise may improve many of these symptoms and could reduce the long-term effects of COVID-19.