NETosis, the process through which neutrophils release neutrophil extracellular traps (NETs), has emerged as a crucial mechanism in host defense and the pathogenesis of autoimmune responses. During the SARS-CoV-2 pandemic, this process received significant attention due to the central role of neutrophil recruitment and activation in infection control. However, elevated neutrophil levels and dysregulated NET formation have been linked to coagulopathy and endothelial damage, correlating with disease severity and poor prognosis in COVID-19. Moreover, it is known that SARS-CoV-2 can induce persistent low-grade systemic inflammation, known as long COVID, although the underlying causes remain unclear. It has been increasingly acknowledged that excessive NETosis and NET generation contribute to further pathophysiological abnormalities following SARS-CoV-2 infection. This review provides an updated overview of the role of NETosis in autoimmune diseases, but also the relationship between COVID-19 and long COVID with autoimmunity (e.g., latent and overt autoimmunity, molecular mimicry, epitope spreading) and NETosis (e.g., immune responses, NET markers). Finally, we discuss potential therapeutic strategies targeting dysregulated NETosis to mitigate the severe complications of COVID-19 and long COVID.

Tocilizumab, an IL-6 receptor antagonist, may prevent functional impairments in critically ill patients by attenuating the cytokine storm. This study investigated a potential effect of tocilizumab on preventing functional impairments in patients with severe coronavirus infection 2019 (COVID-19).

In a multicenter prospective observational study, patients with COVID-19 ≥ 20 years requiring mechanical ventilation admitted to the intensive care unit between April 2021 and September 2021 and discharged alive were followed for one year. A self-administered questionnaire on sequelae and functional impairments was mailed in August 2022, and data were collected. A multivariate logistic regression was used to assess the impact of tocilizumab on physical function, mental health, and Long COVID.

Of 157 analyzed patients, 41 received tocilizumab. The tocilizumab group had more severe illness, but a lower prevalence of physical impairment (17.1 % vs. 23.3 %, p = 0.41) and mental disorders (19.5 % vs. 39.7 %, p = 0.009) than the non-tocilizumab group. The prevalence of Long COVID was higher in the tocilizumab group (92.7 % vs. 80.2 %, p = 0.06), whereas fatigue/malaise was significantly lower (19.5 % vs. 37.1 %, p = 0.039). Adjusted odds ratios (95 % confidence interval) for physical impairment, mental disorders, and Long COVID with tocilizumab were 0.70 (0.2-2.1), 0.40 (0.16-1.01), and 2.94 (0.7-12.3), respectively, with no significant difference.

Tocilizumab was associated with a lower prevalence of physical impairment and mental disorders at 1 year in patients with severe COVID-19. Furthermore, Long COVID had a weaker impact on physical and cognitive functions.

Although there has been a steady decrease in morbidity and mortality from the SARS-CoV-2 virus since the 2020-2021 period, thousands of Americans are still infected with the virus daily. Some proportion of these infected individuals will go on to develop postacute sequelae from SARS-CoV-2 (PASC, or Long COVID), manifesting symptoms 4 weeks or more after recovery from COVID-19. PASC and its underlying pathophysiology are still poorly described and understood. Although hundreds of peer-reviewed, published investigations on Long COVID exist, few have focused on underserved urban patient populations. Most of the published research has involved reviews of diagnostic codes from electronic health records, or responses to questionnaires.

We sought to review Long COVID in an underserved population in Chicago, and to go beyond electronic health record reviews of diagnostic codes, utilizing in-depth chart reviews, gleaned via manual extraction, focusing on notations of care providers. We investigated which specific preexisting conditions, if any, might be associated with specific Long COVID symptomatology's, and if any preexisting conditions predicted Long COVID. Study participants included 204 Long COVID patients, 98 COVID-19-positive patients, and 104 healthy (no history of COVID-19 infection) patients from an inner-city health system caring for underserved communities, whose records were reviewed via manual data extraction from electronic health records, focusing on provider notes in patient charts.

Our Long COVID symptom frequencies were distinct compared to frequencies from other reviews that did not focus on underserved populations and done with medical records when only diagnostic codes are utilized. Preexisting medical conditions did not predict similar Long COVID symptomologies, save for the significant association between preexisting cough/dyspnea/pulmonary conditions and preexisting migraine/headache and their analogous Long COVID symptoms.

The odds of having Long COVID increased comparatively in subjects hospitalized with COVID-19, subjects with BMI >30, and female subjects.

Excess weight has been identified as a potential risk factor for post-COVID-19 condition (PCC). This systematic review and meta-analysis aimed to investigate whether excess weight is associated with the development or experience of neurological and neuropsychiatric symptoms in PCC.

We conducted a comprehensive search of eight databases (PubMed, Embase, Scopus, Web of Science, VHL, Google Scholar, ProQuest, and medRxiv) for studies published up to July 2023. Studies were included if they assessed PCC symptoms in relation to nutritional status, specifically the development of neurological and neuropsychiatric symptoms more than 12 weeks post-infection. The analysis compared exposure and controls groups (excess weight vs. normal weight; obesity vs. non-obesity). Data were synthesized using a random-effects model.

Of the 10,122 abstracts screened, 18 studies (n = 139,091 adults) were included. These studies included 79,050 individuals with excess weight vs 57,926 normal-weight individuals and 30,694 individuals with obesity vs 107,612 non-obese individuals. The presence of excess weight in PCC was significantly associated with persistent depression (RR = 1.21; 95% CI: 1.03-1.42), headache (OR = 1.23; 95% CI: 1.10-1.37), memory issues (RR = 1.43; 95% CI: 1.24-1.65), sleep disturbance (RR = 1.31; 95% CI: 1.16-1.48), and vertigo (RR = 1.21; 95% CI: 1.04-1.41). Obesity was significantly associated with persistent headache (OR = 1.45; 95% CI: 1.37-1.53), numbness (RR = 1.61; 95% CI: 1.46-1.78), smell disorder (OR = 1.16; 95% CI: 1.11-1.22), taste disorder (OR = 1.22; 95% CI: 1.08-1.38), and vertigo (RR = 1.44; 95% CI: 1.35-1.53).

Excess weight, including overweight and obesity, is associated with experiencing neuro-symptoms related to PCC. Individuals with these conditions urgently need enhanced personalized care management in current post-pandemic context.

Post-COVID-19 condition (PCC) has been studied extensively since the inception of the COVID-19 pandemic. In the population of long-term care (LTC) home residents, however, information about PCC and recovery after the acute phase of COVID-19 is lacking. This study contributes evidence about symptoms over time in 459 residents in nine Canadian LTC homes.

In a comprehensive retrospective chart review, we recorded medical symptoms in a 4-week period before contracting COVID-19 ("PRE-COVID") and during 24 weeks after contracting infection (a 4-week "ACUTE-COVID" period and five subsequent 4-week periods "POST1-5"). We investigated the number and type of symptoms over time, examined different "recovery trajectories", and compared the characteristics of residents across different trajectories.

In the sample overall, the number of different symptoms increased from PRE-COVID to ACUTE-COVID (mean difference of 3 symptoms, p<.001), returning to the PRE-COVID level within the first two months post-infection. An individual-level examination revealed that after ACUTE-COVID about a quarter of residents did not return to their symptom baseline. There was no statistically significant difference in demographic characteristics or PRE-COVID comorbidities across different recovery trajectories. Comparing the group of residents that did not return to their symptom baseline and the group that did, the risk for not returning to baseline increased with the number of symptoms in ACUTE-COVID (adjusted for age, sex, and PRE-COVID comorbidities, exp[B]=1.15, 95% CI [1.05;1.25], p=.002). Additionally, there was a greater increase in the number of symptoms from PRE-COVID to ACUTE-COVID in the former group (significant interaction effect, p<.001). We present symptom types in each time-period.

Group-level results indicated that the number of symptoms after contracting COVID-19 fell to the pre-COVID level within the first two months post-infection. An examination of individual-level symptom trajectories contributed a more granular picture of recovery after infection and characteristics of residents across different trajectories.

Post-COVID syndrome affects at least 10% of individuals recovering from COVID-19. Currently, there is no causal treatment. This retrospective cohort study aimed to evaluate the potential of traditional Chinese medicine (TCM) in treating post-COVID symptoms. TCM physicians in Germany and Austria completed online questionnaires to retrospectively record symptoms, treatment approaches, and outcomes for patients diagnosed with post-COVID. Nine physicians collected data from 79 patients (65% female, 47 ± 16 SD). The most common TCM treatments for post-COVID were acupuncture (n = 66; 85%), Chinese pharmacological therapy (n = 61; 77%), and Chinese dietary counseling (n = 32; 41%). After an average of 7 ± 4 TCM consultations, physicians rated global symptom improvement as 62% ± 29%. Significant alleviation from the start of TCM treatment was observed in major symptoms, such as fatigue (P < .001), impaired physical performance (P < .001), and exertional dyspnea (P < .001). TCM treatment was associated with significant improvements in post-COVID symptoms, warranting further evaluation through randomized controlled studies.

Long COVID remains a public health challenge, impacting over 65 million people globally and manifesting as persistent, multisystemic symptoms that complicate both diagnosis and treatment. To address the need for a standardized, patient-centered assessment tool, this study introduces the Memorial Symptom Assessment Scale-Long COVID (MSAS-LC), which evaluates symptom prevalence, frequency, severity, and distress. The MSAS-LC was developed by modifying the Memorial Symptom Assessment Scale to include 45 prevalent Long COVID symptoms. A cross-sectional survey of 261 U.S. adults (129 with Long COVID and 131 without) assessed validity and group differences. Symptom prevalence was analyzed using logistic regression, while symptom burden (frequency, severity, and distress) was compared using generalized linear models. Participants with Long COVID reported significantly higher symptom prevalence and burden across all systems. Memory problems (73.4% vs. 30.5%; OR = 6.29, p < 0.001) and post-exertional fatigue (OR = 8.55, p < 0.001) were among the most burdensome symptoms. These findings offer preliminary evidence supporting the potential utility of MSAS-LC and underscore the continued public health relevance of individual and collective symptom presentations. The findings suggest the distinct symptom burden, emphasizing the importance of future research to inform diagnostic and treatment strategies. With continued validation, the MSAS-LC may contribute to improved symptom monitoring and care planning in clinical and public health settings.

The acute and post-acute sequelae of SARS-CoV-2 infection have been of great clinical interest since the inception of the COVID-19 pandemic. Despite a high prevalence of individuals with persistent symptoms, a wholistic view of the effects of SARS-CoV-2 on special sensory systems is lacking. Considering the significant impact of normal sensory function on quality of life, the goal of this review is to highlight unresolved issues related to SARS-CoV-2-associated insults to the sensory nervous system.

In this narrative review, we discuss the epidemiology of SARS-CoV-2-induced sensory perturbations, underlying pathological mechanisms, and possible therapeutic strategies across the olfactory, gustatory, somatosensory, visual, and auditory systems. Examined literature included studies with human biospecimens, human-derived cell lines, and naturally susceptible animal models, which highlighted evidence of persistent functional disruption in all sensory systems. SARS-CoV-2 infection was associated with persistent inflammation in the olfactory epithelium/bulb, somatosensory ganglia, and gustatory systems, long-term transcriptional perturbations in the sensory central nervous system and peripheral nervous system, and detectable degeneration/apoptosis in the gustatory and visual systems. Few studies have proposed evidence-based therapeutic strategies for attenuating specific sensory abnormalities after SARS-CoV-2 infection.

While the olfactory system, and to some extent the visual and somatosensory systems, have been more thoroughly investigated from symptomatology, behavioral and molecular perspectives, there is still an unmet need for the development of therapeutics to treat COVID-induced impairment of these systems. Further, additional attention must be placed on COVID-associated impairment of the gustatory, visual, and auditory systems, which lack detailed mechanistic investigations into their pathogenesis.

'Brain fog' is commonly reported in more than a dozen chronic diseases, but what is it? We review research across conditions which has characterised brain fog and evaluate its definitions and objective correlates. Brain fog has been used to refer to a variable set of overlapping symptoms implicating cognition, fatigue, and affect. It has been defined as a distinct symptom, a syndrome, or a nonspecific term. We consider the evidence that brain fog is a transdiagnostic entity with a common phenomenology and profile of objective cognitive deficits. We discuss where these commonalities arise and argue that linguistic ambiguity, shared cognitive impairments, and noncognitive factors are more likely than shared neurobiology. We suggest how future research might apply existing tools to disambiguate the phenomena that brain fog conflates.

SARS-CoV-2 infection has resulted in more than 700 million cases and nearly 7 million deaths worldwide. Although vaccination efforts have effectively reduced mortality and transmission rates, a significant proportion of recovered patients-up to 40%-develop long COVID syndrome (LC) or post-acute sequelae of COVID-19 infection (PASC). LC is characterized by the persistence or emergence of new symptoms following initial SARS-CoV-2 infection, affecting the cardiovascular, neurological, respiratory, gastrointestinal, reproductive, and immune systems. Despite the broad range of clinical symptoms that have been described, the risk factors and pathogenic mechanisms behind LC remain unclear. This review, the first of a two-part series, is distinguished by the discussion of the role of the SARS-CoV-2 spike protein in the primary mechanisms underlying the pathophysiology of LC.

This study aimed to evaluate brain glymphatic function in COVID-19 recovered patients using the non-invasive Diffusion Tensor Imaging-Analysis Along the Perivascular Space (DTI-ALPS) technique. The DTI-ALPS technique was employed to investigate changes in brain glymphatic function in these patients and explore correlations with cognitive function and fatigue.

Follow-up assessments were conducted at 1, 3, and 12 months post-recovery. A total of 31 patients completed follow-ups at all three time points, with 30 healthy controls (HCs) for comparison.

Compared to HCs, COVID-19 recovered patients showed a significant decline in MoCA scores at 3 months post-recovery (p < 0.05), which returned to near-normal levels by 12 months. Mental fatigue, measured by the Fatigue Assessment Scale (FAS), was significantly higher in COVID-19 patients at all follow-up points compared to HCs (p < 0.05). The DTI-ALPS index in both hemispheres showed significant differences at 3 months post-recovery compared to HCs (p < 0.001), indicating increased glymphatic activity. Longitudinal analysis revealed a peak in the DTI-ALPS index at 3 months post-recovery, which then decreased by 12 months. Correlation analysis showed a significant negative correlation between the Bilateral brain hemisphere DTI-ALPS index and MoCA scores (right side: r = -0.373, p = 0.003; left side: r = -0.255, p = 0.047), and a positive correlation with mental fatigue (right side: r = 0.275, p = 0.032; left side: r = 0.317, p = 0.013).

This study demonstrates dynamic changes in brain glymphatic function in COVID-19 recovered patients, with a peak in activity at 3 months post-recovery. These changes are associated with cognitive function and mental fatigue, suggesting potential targets for addressing neurological symptoms of long COVID. The non-invasive DTI-ALPS technique proves to be a valuable tool for assessing brain glymphatic function in this population.

Individuals living with long COVID experience a range of symptoms that affect their ability to carry out daily activities or participate in social and community life. This study aimed to analyze association between functional disability and the occurrence of long COVID symptoms, as well as to analyze the effect of symptom persistence time on functional disability.

This is a cross-sectional study using data from the SulCovid-19 study, which interviewed individuals who had COVID-19 between December 2020 and March 2021. The functional disability outcome was assessed using the Basic Activities of Daily Living (BADL) and Instrumental Activities of Daily Living (IADL) scales, while the exposures were the symptoms of long COVID. Adjusted analyses between outcomes and exposures, stratified by time after the acute phase of infection, were performed using Poisson regression with robust variance adjustment.

The prevalence of BADL disability was 4.8% (95%CI 4.0;5.6), and for IADL disability, it was 8.4% (95%CI 7.4;9.4). The main symptoms associated with BADL disability were dyspnea, dry cough and sore throat, while for IADL, they were joint pain, muscle pain, loss of sensation, nasal congestion, sore throat and runny nose. When stratified by tertiles of time after the acute phase of infection, a relationship was found between BADL disability and dyspnea, ageusia and, nasal congestion in the 3rd tertile, while only ageusia was found to be related to IADL disability in the 3rd tertile.

Long COVID symptoms were associated wiht limitations in the functional capacity of adults and the seniors. The findings can be used to guide the care and rehabilitation of individuals with disabilities who have had COVID-19, particularly for referral to appropriate health professionals.

The COVID-19 pandemic represented a healthcare challenge of unparalleled magnitude worldwide. As patients recovered from the acute infection, a new challenge emerged, i.e., the development of post-acute symptoms. The main goal of this study was to evaluate the trajectory of cognitive symptoms since the acute phase of COVID-19 among patients followed through a telehealth program in Brazil.

A retrospective cohort study was conducted with confirmed COVID-19 patients followed by a Brazilian telehealth program who presented cognitive symptoms in the acute phase of infection. The objective of the current analysis was to assess the persistence or remission of cognitive symptoms at 24 weeks after the onset of acute COVID-19 symptoms, as well as the factors associated with such manifestations. The study used chi-square tests and multivariate logistic regression models to assess the association between patients' parameters and the presence of cognitive symptoms. A backward stepwise method was applied to define significant characteristics, which were then evaluated using odds ratios and 95% confidence intervals.

Among 319 patients who had cognitive symptoms during acute COVID-19, 89 (27.9%) reported persistence of cognitive symptoms for more than 24 weeks from the acute onset of the infection. Female sex (OR 2.33 [95% CI 1.23-4.43]) and having been infected during the second wave of COVID-19 (OR 2.30 [95% CI 1.34-3.96]) were associated with the persistence of symptoms beyond 24 weeks.

Approximately one-third of patients with COVID-19, mainly women and people infected during the second wave of infection, experienced persistent cognitive symptoms.

The infection rates with SARS-CoV 2 virus, known since 2019, are currently significantly weakened in their dynamics. Nevertheless, COVID 19 is still a common disease, which in most cases is overcome quite well and can be treated by the general practitioner. Despite an initially uncomplicated disease progression, the long-term consequences can be considerable. Symptoms persisting over a period of more than 12 weeks after infection are summarized as Post-COVID (PC) syndrome. The aim of this study is to document the symptom expression in PC patients in the outpatient setting, with a major focus on limitations in daily life and consequences for mental health.

This survey is part of a prospective European collaborative study with the German cohort having been slightly extended and evaluated separately. Data collection was performed by telephone interviews of adult SARS CoV 2 positive patients using standardized questionnaires (38 open and 6 closed questions). After an inclusion interview, follow-up interviews were conducted every 4 weeks over a period of 6 months. Participants were recruited in collaboration with the local health department (Wuerzburg, Germany).

Sixty participants were recruited in April and May 2021. After 12 weeks (PC cutoff), 48.3% still reported symptoms related to SARS-CoV-2 infection. The most commonly reported symptoms were fatigue/tiredness (33.3%), reduced concentration (26.7%), and shortness of breath (23.3%). One-quarter of respondents reported impaired functioning, with the most common daily limitations being sports (28.3%), work (25.0%), and social life (15.0%). At 6 months, 21.6% of respondents experienced anxiety and 11.6% reported depressive symptoms. Overall, 40.0% of respondents were concerned that their health would deteriorate again or not fully normalize because of COVID-19. Over two-thirds (70.0%) visited a physician during the course of the study because of COVID-19, 73.8% of whom visited their general practitioner.

PC in outpatient care appears to be a complex and multifaceted condition that not only presents with physical symptoms, but also has a significant impact on mental health and daily life. Although the complexity of the condition is not yet fully understood, our findings suggest that it presents long-term challenges, particularly in outpatient care. Further research, particularly in larger and more diverse cohorts, is needed to confirm these observations. Routine screening for psychosocial comorbidities could be a valuable approach to identify supportive interventions that may help to reduce the risk of chronification and/or somatization.

Elucidating the factors that mitigate the effects of COVID-19 on cognitive function offers important insights for public health policy and intervention. This systematic review and individual participant data (IPD) meta-analysis assesses cognitive reserve (CR) as a potential moderator of post-COVID-19 cognitive dysfunction (PCCD). Under PRISMA-IPD guidelines, data searches were conducted via PubMed, PsycINFO, Scopus, and Embase, up to January 2023. Eligible studies included at least one cognitive assessment, CR proxy, and disease severity indicator. Of 5604 studies, 87 were eligible (10,950 COVID-19 cases; 78,305 controls), and IPD was obtained for 29 datasets (3919 COVID-19 cases; 8267 controls). Three-level random-effects meta-analyses indicated that CR had a moderate positive association (rsp =.29), and COVID-19 severity had a small negative association (rsp = -.07) with cognitive outcomes. These effects were moderated by a significant within-study interaction. Cognitive deficits following COVID-19 were 33 % smaller among high CR individuals, and 33 % greater among low CR individuals, relative to those with average CR. Population-based initiatives promoting reserve-building behaviors may alleviate the PCCD-related public health burden. REVIEW REGISTRATION: PROSPERO registration number: CRD42022360670.

The most common symptom reported by patients after recovery from coronavirus disease 2019 (COVID-19) is fatigue. However, robust clinical evidence supporting the effectiveness of treatments and interventions for fatigue in COVID-19 survivors is lacking. This pilot clinical trial aims to assess the safety and efficacy of Kyungok-go, a herbal preparation targeting fatigue, in patients after recovering from COVID-19. The study will include 100 participants with persistent fatigue for more than 12 weeks after COVID-19 recovery. They will be randomly allocated into two groups: the Kyungok-go group (n =  50) and the placebo group (n =  50). Kyungok-go or placebo will be administered twice daily for 12 weeks, and the participants will be assessed at 4-week intervals. The primary outcome will be the change in the Fatigue Severity Scale score. Secondary outcomes will include cognitive function, physical function, quality of life, depression, sleep quality, medication adherence, and feasibility. This study is the first attempt to investigate the safety and efficacy of Kyungok-go for relieving fatigue related to long COVID. The results are expected to contribute to the establishment of a knowledge base and reveal the potential of herbal medicine prescriptions for managing and recovering from the most common sequelae of COVID-19. Trial registration number: KCT0008789.

To investigate the association between symptoms of long-term effects of coronavirus disease 2019 (long COVID) and sleep problems in a sample population from southern Brazil. This cross-sectional study used data from the SULcovid-19 survey, developed in the municipality of Rio Grande, RS, Brazil. The outcome, long COVID, was investigated through the presence of 18 symptoms, and the exposure variable was sleep problems. Poisson regression with robust adjustment for variance was used to estimate crude and adjusted prevalence ratios for the outcome-exposure relationship. Odds ratio was calculated through multinomial regression of the relationship between the number of symptoms of long COVID and sleep problems. Analyses were adjusted for sex, age, marital status, income, body mass index, smoking status, comorbidities, and hospital admission. A total of 2919 adults and older adults were interviewed. The prevalence of long COVID was 48.3% (95% confidence interval [CI] 46.5-50.1%) and sleep problems were reported by 41.2% of the sample (95% CI 39.4-43.0%). Individuals with sleep problems were more likely to exhibit altered sensitivity (prevalence ratio [PR] 3.27; 95% CI 1.96-5.45), nasal congestion (PR 2.75; 95% CI 1.53-4.94), musculoskeletal symptoms (PR 1.75; 95% CI 1.48-2.06), respiratory issues (PR 1.58; 95% CI 1.24-2.01), and one or more symptom of long COVID (PR 1.27; 95% CI 1.15-1.39). Approximately one-half of the population analysed had long COVID, and four of 10 reported experiencing sleep problems. In addition, the sample tended to have experienced a greater number of symptoms compared with those who reported to sleep well.

Increasing long-term observations suggest that coronavirus disease 2019 (COVID-19) vasculopathy may persist even 1.5 years after the acute phase, potentially accelerating the development of atherosclerotic cardiovascular diseases. This study systematically reviewed the variability of brachial flow-mediated dilation (FMD) and carotid-femoral pulse wave velocity (cfPWV) from the acute phase of COVID-19 through 16 months of follow-up (F/U). Databases including PubMed, Web of Science, MEDLINE, and Embase were screened for a meta-analysis without language or date restrictions (PROSPERO reference CRD42025642888, last search conducted on 1 February 2025). The quality of the included studies was assessed using the Newcastle-Ottawa Quality Scale. We considered all studies (interventional pre-post studies, prospective observational studies, prospective randomized, and non-randomized trials) that assessed FMD or cfPWV in adults (aged ≥ 18 years) with or after laboratory-confirmed COVID-19 compared with non-COVID-19 controls or that assessed changes in these parameters during the F/U. Twenty-one studies reported differences in FMD, and 18 studies examined cfPWV between COVID-19 patients and control groups during various stages: acute/subacute COVID-19 (≤30 days from disease onset), early (>30-90 days), mid-term (>90-180 days), late (>180-270 days), and very late (>270 days) post-COVID-19 recovery. Six studies assessed variability in FMD, while nine did so for cfPWV during the F/U. Data from 14 FMD studies (627 cases and 694 controls) and 15 cfPWV studies (578 cases and 703 controls) were included in our meta-analysis. FMD showed a significant decrease compared to controls during the acute/subacute phase (standardized mean difference [SMD]= -2.02, p < 0.001), with partial improvements noted from the acute/subacute phase to early recovery (SMD = 0.95, p < 0.001) and from early to mid-term recovery (SMD = 0.92, p = 0.006). Normalization compared to controls was observed in late recovery (SMD = 0.12, p = 0.69). In contrast, cfPWV values, which were higher than controls in the acute/subacute phase (SMD = 1.27, p < 0.001), remained elevated throughout the F/U, with no significant changes except for a decrease from mid-term to very late recovery (SMD= -0.39, p < 0.001). In the very late recovery, cfPWV values remained higher than those of controls (SMD = 0.45, p = 0.010). In the manuscript, we discuss how various factors, including the severity of acute COVID-19, the persistence of long-term COVID-19 syndrome, and the patient's initial vascular age, depending on metrics age and cardiovascular risk factors, influenced the time and degree of FMD and cfPWV improvement.

COVID-19 survivors may experience complex, distressing and persistent symptoms, referred to as long COVID, lasting months or years after diagnosis. More evidence is needed for effective long COVID screening and management.

To explore the clinical profile of long COVID and factors associated with its development.

A multicentre correlational study using a cross-sectional design.

Adults diagnosed with COVID-19 6-9 months earlier were recruited via social media and referrals from three facilities. Participants provided demographic data and assessed their symptoms and functional status using validated questionnaires. Data were analysed using descriptive statistics and binomial logistic regression.

Among 102 participants, 13%-30% reported significant impairments in cognitive, emotional and physical functioning. Over 10% experienced symptoms such as diarrhoea, sleep problems, dyspnoea, nausea, fatigue and pain. These impairments and symptoms were associated with acute symptom severity, chronic disease, overweight status, regular exercise and living without partners.

This study adds to the literature by examining long-term functional status and symptoms in omicron survivors using comprehensive, validated tools. The findings highlight the prevalence and clinical significance of long COVID symptoms, aiding in the identification of functional impairments requiring medical and nursing interventions.

Nurses should recognise these symptoms and educate survivors about potential challenges. Policies addressing long-term issues, including research, health services and education, are essential.

This study follows the STROBE guideline (Table S1).

Patients self-reported symptoms for this study.

ClinicalTrials.gov (NCT05303103).

Since 2020, several specialized follow-up outpatient clinics have been established across Germany to address the complex needs of patients with Long COVID/ Post-COVID-19 Condition (PCC). This article reviews the current landscape of these specialized clinics in Germany and critically evaluates their diagnostic and treatment algorithms.

This study employed a mixed-method approach, combining publicly available information on post-COVID-19 outpatient clinics with an observational cross-sectional online survey among lead doctors of PCC follow-up outpatient clinics in Germany. The survey was conducted from November 2023 to January 2024. Descriptive statistics and t-tests for group-comparisons were employed, with statistical significance set at p < 0.05.

At the time of the survey, 112 specialized PCC outpatient clinics were identified in Germany through publicly available information. Forty-five PCC outpatient clinic lead doctors (40.2%) responded to our survey. Treatment of PCC patients is personalized and symptom-oriented rather than standardized. Patient characteristics of the two identified main treatment domains, focusing on respiratory and neurocognitive symptoms, differed only in sex distribution. A higher proportion of females (63.9%) presented with pulmonary symptoms compared to patients with neurocognitive impairments (50.2%, p < 0.05). The level of distress among patients is generally perceived as high and outpatient clinic lead doctors are convinced that their outpatient counseling services offer significant benefits.

As the demand for PCC follow-up outpatient clinics persists, the establishment of new services continues, particularly to address the growing need for neurocognitive care services. PCC outpatient care is currently personalized and symptom-orientated, leading to high variability across clinics. Further standardization of treatment protocols and diagnostic algorithms could improve patient care and facilitate professional exchange.

Over 65 million people have long COVID. Evidence for using Chinese herbal medicine (CHM) to treat long COVID is growing. A systematic review of evidence for guiding clinical decision is warranted.

To examine the effects and safety of CHM in alleviating the severity of dyspnea, fatigue, exercise intolerance, depression, anxiety and insomnia in long COVID adults based on registered randomized clinical trials (RCT).

World Health Organization International Clinical Trials Registry Platform and Chinese Clinical Trial Registry were searched for registered trial protocols from database inception to February 10, 2023. English (PubMed, Embase, AMED and CINAHL) and Chinese databases (CNKI, Wanfang Data and CQVIP) were then searched to identify relevant publications from December 2019 through April 6, 2023.

Registered RCTs that compared the effects of Chinese herbal medicines or Chinese herbal formulas against a control treatment (i.e., the placebo or usual care) in adults with persistent symptoms of long COVID. The primary outcome of dyspnea, and secondary outcomes of fatigue, exercise intolerance, depression, anxiety and insomnia were measured using validated tools at the end of the treatment.

Data were extracted, and eligible RCTs were evaluated using version 2 of the Cochrane risk-of-bias tool for randomized trials and Grading of Recommendations, Assessment, Development and Evaluations independently by two researchers. Effect sizes were estimated by random-effects modelling and mean difference (MD). Heterogeneity between trials was quantified by I2.

Among the 38 registered clinical trials we identified, seven RCTs (1,519 patients) were included in the systematic review. One RCT had a low overall risk of bias. Compared to the control, CHM reduces dyspnea on the Borg Dyspnea Scale score (MD = -0.2, 95% confidence interval [CI] = -0.65 to 0.25) with moderate certainty, and reduces fatigue on the Borg Scale (MD = -0.48, 95% CI = -0.74 to -0.22) with low certainty. CHM clinically reduces depression on Hamilton Depression Rating Scale score (MD = -6.00, 95% CI = -7.56 to -4.44) and anxiety on Hamilton Anxiety Rating Scale score (MD = -6.10, 95% CI = -7.67 to -4.53), and reduces insomnia on the Insomnia Severity Index (MD = -4.86, 95% CI = -12.50 to 2.79) with moderate certainty. Meta-analysis of two RCTs (517 patients) showed that CHM clinically improves exercise intolerance by increasing 6-minute walking distance (MD = -15.92, 95% CI = -10.20 to 42.05) with substantial heterogeneity (I2 = 68%) and low certainty.

CHM is associated with a post-treatment clinical reduction in depression and anxiety in long COVID adults, compared to the control, but it does not have a strong treatment effect on dyspnea and insomnia. Effects of CHM on exercise intolerance and fatigue are uncertain, and the safety of using CHM remains questionable. Please cite this article as: Tsang MS, Zhou IW, Zhang AL, Xue CC. Chinese herbal medicine for dyspnea and persistent symptoms of long COVID: A systematic review and meta-analysis of randomized controlled trials. J Integr Med. 2025; 23(2): 126-137.

We investigated the prevalence of new or persistent manifestations experienced by COVID-19 survivors at 3 or more months after their initial infection, collectively known as post-COVID-19 condition (PCC).

We searched four electronic databases and major grey literature resources for prospective studies, systematic reviews, authoritative reports and population surveys. A random-effects meta-analysis pooled the prevalence data of 22 symptoms and outcomes. The GRADE approach was used to assess the certainty of evidence. PROSPERO CRD42021231476.

Of 20 731 identified references, 194 met our inclusion criteria. These studies followed 483 531 individuals with confirmed COVID-19 diagnosis over periods of up to 2 years. Most focused on adults, nearly two-thirds were conducted in Europe and 63% were of high or moderate quality. The supplementary search identified 17 systematic reviews, five authoritative reports and four population surveys that reported on PCC prevalence. Our analysis revealed that more than half of COVID-19 survivors experienced one or more symptoms more than a year after their initial infection. The most common symptoms were fatiguedyspneamemory, sleep or concentration disturbances; depressionand pain. Limitation in returning to work was the most common outcome. Prevalence tended to be higher among females, individuals hospitalized during their initial infection and those who experienced severe COVID-19 illness.

PCC presents a significant health burden, affecting some groups more than others. This information will help inform health care system policies and services for people living with PCC and those caring for them.

The symptom burden for patients with Long COVID-associated dysautonomia is high, yet there are currently no effective treatments. Mindfulness programs reduce psychological and physical symptoms as well as inflammatory gene expression in a variety of medical conditions. The study aim was to evaluate the effect of a six-week mindfulness program in women with Long COVID dysautonomia symptoms.

Using a single arm, pre- and posttest design, women aged 18-54 years with Long COVID and orthostatic intolerance suggestive of dysautonomia were recruited from a single center. Participants attended a standardized, six-week, virtual mindfulness program. An active stand test and 6-min walk test (6MWT) were performed at baseline and post-intervention. Self-reported measures of physical and mental health symptoms collected at baseline, post-intervention and 4 week follow up included the composite autonomic symptom score (COMPASS-31), perceived stress (PSS), anxiety (GAD7), depression (PHQ8), COVID-19 event specific distress (IES-R), fatigue (FSI), sleep (ISI), well-being (MHC-SF), resilience (CD-RISC 10), and quality of life (SF-20). The effects on conserved transcriptional response to adversity (CTRA) were examined by next-generation sequencing of dried whole blood samples.

Twenty participants were enrolled with a mean age of 39.9 years (range 21-52 years). No significant changes were observed for the active stand test or 6MWT. A significant reduction in insomnia severity (ISI: 16.6 vs. 13.6; p = 0.001) was observed post-intervention, but scores reverted toward baseline levels at 4-week follow-up. No significant improvements were seen in autonomic symptoms, anxiety, perceived stress, depression, well-being, or COVID-19 related distress. Pro-inflammatory CTRA gene expression decreased significantly from pre-to post-intervention (p = 0.004). Declines in CTRA gene expression were most significant among those with 3 COVID-19 positive events (p = 0.01), followed by 2 events (p = 0.04) and 1 event (p = 0.05). Declines in CTRA gene expression did not vary significantly as a function of recent illness, COVID-19 hospitalization, demographic characteristics, or general medical history.

A virtual, six-week mindfulness program may improve sleep quality in women with Long COVID dysautonomia. While no objective improvement in dysautonomia symptoms were observed, our findings suggest a favorable effect of the mindfulness intervention on inflammatory and antiviral biology with a decrease in CTRA gene expression. Nonetheless, the symptom burden in this population is very high, and more attention is needed to provide effective multi-modal clinical therapies to this population.

Approximately 10-20% of individuals suffering from COVID-19 develop prolonged symptoms known as long COVID or post-COVID condition (LC). This review aimed to assess healthcare resource use (HCRU) and healthcare costs associated with LC. Because LC is not clearly defined and often remains undiagnosed, studies reporting on long-term follow-up of individuals with a COVID-19 diagnosis were also included. Among the 41 publications included, 36 reported on HCRU and 16 on costs. Individuals with LC had significantly elevated HCRU and healthcare costs vs. controls without a COVID-19 diagnosis over ≥15 months, with a 7.6-13.1% increase in total healthcare costs per person per month as assessed by difference-in-difference analysis. Among studies that did not specifically refer to LC, having a COVID-19 diagnosis was associated with a significant 4-10% increase in long-term total HCRU over 6-8 months and a 1.3- to 2.9-fold relative increase in total healthcare costs over 6 months. Due to the heterogeneity of the included studies, high-quality evidence is needed to better understand the economic burden of LC. In the absence of effective treatments, prioritizing the prevention of acute COVID-19, e.g., through vaccination, may be crucial for preventing LC and the associated long-term HCRU and medical spending.

With the outbreak of COVID-19 in China, a large number of COVID-19 patients are at risk of long COVID after recovery. The purpose of our research is to systematically review the existing clinical studies to understand the current prevalence and related risk factors of long COVID in COVID-19 patients in China.

The protocol of this systematic review was registered on PROSPERO (CRD42024519375). We searched six electronic databases from 1st January 2020-1st March 2024. Literature screening, data extraction, and risk bias assessment were independently carried out by two reviewers. Quality of the included studies was evaluated by AHRQ and NOS. The meta-analysis was performed by R software 4.2.3 to derive the prevalence of long COVID and risk factors.

Overall, 50 studies with 65880 participants were included. The results showed that the prevalence of long COVID (with at least one symptom) among the COVID-19 patients was approximately 50 % (95 %Confidence Interval (CI) 42-58 %) in China. Although we conducted meta-regression and subgroup analysis, the heterogeneity of the study was high. But the Omicron BA.2 variant had a statistically significant effect on the prevalence of long COVID (P = 0.0004). The three most common symptoms of long COVID were fatigue (0.33, 95 %CI 0.28-0.39), cognitive decline (0.30, 95 %CI 0.14-0.46) and shortness of breath (0.29, 95 %CI 0.15-0.43). Patients with severe acute phase of COVID-19 (Odds Ratio (OR) 1.57, 95 % CI 1.39-1.77), combined 2 comorbidities (OR 1.80, 95 % CI 1.40-2.32), combined 3 comorbidities (OR 2.13, 95 % CI 1.64-2.77), advanced age (OR 1.02, 95 % CI 1.01-1.04), female (OR 1.58, 95 % CI 1.44-1.73) were the risk factors for long COVID prevalence.

Current systematic review found that nearly half of COVID-19 patients may suffering from long COVID in China. Establishing a long COVID recovery-support platform and regular follow-up would help to long-term monitor and manage the patients, especially those high-risk population.

We investigated the presence of impaired endothelial function in individuals with post-acute sequelae of coronavirus disease-2019 (PASC) compared to healthy individuals and explored the efficacy of combined exercise training in restoring or improving endothelial function in those with PASC.

Study I was a cross-sectional study which compared endothelial function between individuals with PASC (n = 29, mean age 22.9 ± 3.9 year) and healthy individuals (n = 42, mean age 21.7 ± 2.0 year). Study II, an intervention design, explored if combined exercise training (n = 14) could reverse the decline in endothelial function associated with PASC compared to controls (n = 14). The combined exercise program included aerobic, resistance, and inspiratory muscle training administered for 8 weeks. We measured endothelial function using flow-mediated dilation of the brachial artery and assessed peak oxygen uptake (VO2peak), dyspnea, and fatigue before and after the intervention.

Individuals with PASC exhibited significantly lower endothelial function compared to healthy controls (4.95 ± 2.0% vs 8.00 ± 2.4%, P < .001). The exercise group showed a significant increase in endothelial function (4.73 ± 1.5% to 7.98 ± 2.4%) as opposed to the control group (5.31 ± 2.5% to 6.30 ± 2.5%) (interaction effect: P = .008), reaching levels similar to those in healthy individuals. Additionally, the exercise group demonstrated improvement in VO2peak (38.3 ± 6.4 ml/min/kg to 42.8 ± 7.3 ml/min/kg, P < .001) and a reduction in dyspnea and fatigue compared to the control group (P < .001).

Having PASC is associated with impaired endothelial function, but combined exercise training effectively restores it, making it a promising lifestyle intervention for vascular function in PASC.

Most long coronavirus disease (long COVID) studies rely on traditional surveillance methods that miss underserved populations who use emergency departments (EDs) as their primary health care source. In medically underserved ED populations, we sought to determine (1) whether there are gaps in awareness and self-declared understanding about long COVID illness, and (2) the prevalence, impact on school/work attendance, and receipt of care for long COVID symptoms.

This study was a cross-sectional, convenience sample survey study of adult patients at 11 geographically representative US EDs from December 2022 to October 2023. Awareness and self-declared understanding about long COVID illness were measured. Prevalence, impact on school/work attendance, and receipt of care for long COVID symptoms were also assessed.

Of 1,618 eligible patients, 1455 (89.9%) agreed to participate, including 33.4% African Americans and 30.9% Latino/a. Of the patients, 17.1% lacked primary care. In total, 33.2% had persistent COVID-19 symptoms lasting >1 month, and 20.3% had symptoms >3 months. Moreover, 49.8% with long COVID symptoms missed work/school because of symptoms; 30.3% of all participants and 33.5% of participants who had long COVID symptoms had prior awareness and self-declared understanding of long COVID. Characteristics associated with poor understanding of long COVID were African American race (adjusted odds ratio [aOR] 3.68, 95% confidence interval [CI] 2.66 to 5.09) and Latino/a ethnicity (aOR 3.16, 95% CI 2.15 to 4.64). Participants lacking primary care were less likely to have received long COVID care (24.6% versus 51.2%; difference 26.6%; 95% CI 13.7% to 36.9%).

Despite high prevalence and impact on school/work attendance of long COVID symptoms, most of this ED population had limited awareness and self-declared understanding of long COVID, and many had not received care. EDs should consider the development of protocols for diagnosis, education, and treatment of long COVID illness.

Neurological symptoms often prominent in post-acute sequelae of COVID-19 (PASC) necessitate deeper understanding. Our objective was to investigate brain metabolism in PASC and examine correlations with neurological symptoms during both the acute and chronic stages.

Eighty-seven adults experiencing PASC with neurocognitive symptoms were recruited in the PERSICOR prospective study and examined using brain [ 18 F]FDG PET/CT. Comprehensive clinical variables including neurocognitive symptoms were evaluated. PET images were compared voxel-wise with SPM12 software ( P < 0.05, false discovery rate corrected) and volume-of-interest basis (BrainVisa software) with those of 55 healthy controls recruited before COVID-19 pandemic. We also investigated differences in brain metabolism according to the time interval after acute COVID-19. The correlation between brain metabolism and neurocognitive symptoms was assessed.

Frequently reported neurological symptoms included concentration difficulties (79%) and immediate/working memory impairments (66%). Significant hypometabolism was identified in regions previously identified in PASC: left fusiform gyrus (33% of patients), amygdala (23% on left, 28% on right), parahippocampal area (25% left, 24% right), and vermis (22%). The most substantial metabolism decreases were observed in the pons (5.5% decrease in the whole patient group vs controls) and right amygdala (-4.2%). Concentration and memory impairments correlated with decreased metabolism in prefrontal and mesial/inferior temporal areas, respectively ( P < 0.01 for both). A shorter interval between PET imaging and the acute phase of COVID-19 correlated with reduced glucose metabolism in the brainstem, thalamus, mesiotemporal lobe, frontobasal cortex, and olfactory bulb ( P < 10 -3 ).

This study underscores the links between neurological symptoms and cerebral hypometabolism in specific regions in PASC. These findings illuminate the complex neuropathophysiological mechanisms of PASC and pave the way for potential therapeutic interventions.

This study investigated the prevalence of temporomandibular disorders (TMD) in patients with malocclusion through a systematic review and meta-analysis.

A comprehensive literature search was conducted up to November 15, 2024. Cross-sectional studies providing data on TMD prevalence among malocclusion patients were included. Study quality was assessed using the Joanna Briggs Institute (JBI) checklist. A random-effects model was used for meta-analysis, with subgroup and meta-regression analyses to explore heterogeneity. Sensitivity analyses were performed to evaluate result robustness.

Thirty-two studies were included, showing an overall TMD prevalence of 43% (95% CI: 35%-50%; I2 = 97.9%). Prevalence was higher in females (44%) than males (33%) and in adults (42%) than adolescents (39%). Among malocclusion types, Class II (40%) and posterior unilateral crossbite (59%) had the highest TMD prevalence. Sensitivity analysis confirmed the robustness of findings, though diagnostic criteria variations contributed to heterogeneity.

The prevalence of TMD in malocclusion patients was 43%, with higher rates in females, adults, and specific malocclusion types such as Class II, open bite, overjet, and crossbite. Variations in diagnostic criteria and malocclusion classification contributed to heterogeneity, emphasizing the need to consider individual patient characteristics when assessing TMD risk. Standardized diagnostic criteria, representative sampling, and multilingual search strategies are essential for future research to minimize bias and improve data reliability.

Although it is true that the coronavirus disease 2019 (COVID-19) situation has improved significantly around the world, especially after the implementation of mass vaccination campaigns, there is still a lack of consensus both in the literature and among health authorities and other stakeholders about the current epidemiological situation. This, in turn, has been intensified after the World Health Organization declared the end of the public health emergency of international concern related to COVID-19. In this context, worrying questions have arisen, including a rampant dissemination of scientific misinformation coupled with increased resistance to the implementation and/or revocation of appropriate public health measures. In response to these challenges and hoping to contribute to their mitigation, this article addresses current aspects about the epidemiological situation of COVID-19, discusses long COVID and its controversies, the intensification of scientific misinformation as well as considerations on related health surveillance, and recommendations for improving the existing situation.

Anxiety and stress are major challenges for public health and represent significant symptoms in long COVID. Despite the repercussions on quality of life and mental health, their impacts have not been systematically consolidated in the Brazilian population. Our objective was to analyze the indicators and predictors of anxiety and perceived stress in people who have experienced long COVID in different regional contexts in Brazil. This cross-sectional survey was carried out in the five regions of Brazil and included 4239 adult individuals who had at least one diagnosis of COVID-19. Participants responded to questions on the Depression, Anxiety, and Stress Scale (DASS-21). The GAMLSS class of regression models estimated the predictors associated with the outcomes investigated. The results showed a predominance of participants with a single diagnosis of COVID-19 (65.4%), mild clinical conditions (89.5%), and high adherence to immunization strategies (98.4%). Overall, 48.5% of participants had residual symptoms that started between 4 and 12 weeks after the acute phase of COVID-19 infection. Positive screening for anxiety and perceived stress was associated with female gender, diagnosis of chronic diseases, presence of physical symptoms, moderate or severe clinical condition in the acute phase of the infection, and the need for hospitalization. Through this study, we confirmed that anxiety and stress, developed or exacerbated during the post-COVID-19 phase, represent significant challenges in the Brazilian population. Sociodemographic, clinical, and care conditions were predictors of the outcomes assessed. Knowing these repercussions can allow for personalizing mental health care and help structure evidence-based public policies.

Since its emergence in 2019, COVID-19 has continued to pose significant threats to both the physical and mental health of the global population, as well as to healthcare systems worldwide (Raman et al., Eur Heart J 43:1157-1172, 2022). Emerging evidence indicates that COVID-19 may lead to post-acute COVID-19 syndrome (PACS) with cardiovascular implications, potentially driven by factors such as ACE2 interaction with viruses, systemic inflammation, and endothelial dysfunction. However, there remains a limited amount of research on the cardiovascular manifestations of PACS, which may delay the development of optimal treatment strategies for affected patients. Therefore, it is crucial to investigate the prevalence of cardiovascular sequelae in COVID-19 patients and to determine whether COVID-19 infection acts as an independent risk factor for these outcomes.

This meta-analysis adhered to PRISMA guidelines and was registered in PROSPERO (CRD42024524290). A systematic search of PubMed, Embase, and the Cochrane Library was conducted up to March 17, 2024. The primary outcomes included hypertension, palpitations, and chest pain, with pooled effect estimate reported as proportions and odds ratios (ORs) with 95% confidence intervals (CIs). Sensitivity and subgroup analysis were performed to assess the robustness of the results and to identify sources of heterogeneity.

A total of 37 studies, encompassing 2,965,467 patients, were included in the analysis. Pooled results from case-control studies revealed that, compared to the control group, the ORs of chest pain in the COVID-19 group was 4.0 (95% CI: 1.6, 10.0). The ORs for palpitation and hypertension were 3.4 (95% CI: 1.1, 10.2) and 1.7 (95% CI: 1.6, 1.8), respectively. The proportions of PACS patients experiencing chest pain, palpitation, and hypertension as sequelae were 22% (95% CI: 14%, 33%), 18% (95% CI: 13%, 24%), and 19% (95% CI: 12%, 31%), respectively.

Our findings indicate that 15% of COVID-19 patients experience cardiovascular sequelae. Furthermore, COVID-19 infection significantly increases the likelihood of developing these sequelae compared to uninfected individuals. Future research should prioritize investigating the underlying pathological mechanisms and developing targeted preventive and management strategies.

CRD42024524290.

Maximal oxygen uptake (V.O2max) assesses athletic performance; however, its values are inconsistent in post-COVID-19 athletes. This study aimed to analyze the dynamics of V.O2max in post-COVID-19 athletes. Observational studies were identified by screening the PubMed database published up to 17 July 2023. The initial electronic search found 320 studies. Of these, 26 employing the cardiopulmonary exercise test (CPET) to assess aerobic fitness were selected. Of the 2625 pooled athletes, 1464 were infected and considered as the post-COVID-19 group, either asymptomatic or symptomatic, while the remaining 1161, who were uninfected or had V.O2max results prior to infection, were defined as the infection-free group. Age and V.O2max were differently distributed between post-COVID-19 athletes and those without infection (p = 0.03 in both). Persistent symptoms athletes had 8 mL/Kg/min lower V.O2max than those without infection (p = 0.04). In addition, post-infected athletes who underwent CPET after 12 weeks showed a significant reduction of 2.9 mL/Kg/min in V.O2max according to the increase in body mass index (BMI). The pooled analysis showed that aerobic fitness was reduced in athletes post-COVID-19. V.O2max was negatively correlated with BMI in those who underwent CPET at 12 weeks, suggesting that symptoms persist beyond 12 weeks, affecting return-to-play.

Long COVID is a common complication of infection with severe acute respiratory syndrome coronavirus 2, but the prevalence and predictors of the condition remain poorly characterized.

We prospectively studied adults (≥18 years) with acute coronavirus disease 2019 (COVID-19) presenting to an urban safety net hospital and associated clinics between July 2020 and December 2022. Logistic regression models were used to evaluate the association between baseline demographic, clinical, and laboratory characteristics with long COVID status, defined as symptoms persisting at least 9 months after acute disease. Among unrecovered participants, we describe the prevalence of individual symptoms.

We enrolled 222 participants, 162 (73%) of whom had known recovery status by 9 months. Median age was 54 years, half (55%) were female, and the majority of participants (78%) had at least 1 comorbidity at the time of COVID-19 diagnosis. Based on acute illness characteristics, the adjusted odds ratio for long COVID was 3.0 (95% confidence interval [CI], 1.1-8.0) among those with detectable nucleocapsid antigen and 3.6 (95% CI, 1.2-11) for those who required supplemental oxygen. Of the 41% of participants with symptoms persisting at least 9 months, central nervous system and psychological symptoms were most commonly reported, with 57% reporting functional limitations due to their persistent symptoms.

The strong association with initial disease suggests a decreasing prevalence of long COVID as acute illnesses become milder. However, many contemporary patients still experience high viral burden with extended viral replication, even after vaccination. Our findings highlight the importance of properly characterizing long COVID as viral evolution shifts acute disease presentation.

This review aims to describe the neurologic post-COVID-19 conditions (PCC, also known as "long COVID"), a complex array of diagnoses that can occur following recovery from acute COVID-19. The review also includes clinical considerations for the recognition, diagnosis and management of neurologic manifestations of PCC. Cognitive impairment ("Brain Fog"), headaches, and neuropathies are specifically reviewed.

Long COVID, as currently defined by the World Health Organization (WHO) and other authorities, is a symptomatic condition that has been shown to affect an estimated 10 %-30 % of non-hospitalized patients after one infection. However, COVID-19 can also cause organ damage in individuals without symptoms, who would not fall under the current definition of Long COVID. This organ damage, whether symptomatic or not, can lead to various health impacts such as heart attacks and strokes. Given these observations, it is necessary to either expand the definition of Long COVID to include organ damage or recognize COVID-19-induced organ damage as a distinct condition affecting many symptomatic and asymptomatic individuals after COVID-19 infections. It is important to consider that many known adverse health outcomes, including heart conditions and cancers, can be asymptomatic until harm thresholds are reached. Many more medical conditions can be identified by testing than those that are recognized through reported symptoms. It is therefore important to similarly recognize that while Long COVID symptoms are associated with organ damage, there are many individuals that have organ damage without displaying recognized symptoms and to include this harm in the characterization of COVID-19 and in the monitoring of individuals after COVID-19 infections.

•Fatigue was highly prevalent one year after ICU admission in ICU survivors with COVID-19.•Younger age, pain/discomfort, dyspnoea, and mental health symptoms were associated with reports of fatigue.•COVID-19 ICU survivors should be assessed with comprehensive symptom screening during follow-up care.

COVID-19 has led to reports of fatigue and sleep problems. Brain function changes underlying sleep problems (SP) post-COVID-19 are unclear.

This study investigated SP-related brain functional connectivity (FC) alterations.

Fifty-five COVID-19 survivors with SP (COVID_SP) and 33 without SP (COVID_NSP), matched for demographics, completed PSQI and underwent rs-fMRI at baseline and 2-month follow-up. Correlations between FC and clinical data were analyzed by Pearson correlation analysis with Gaussian random field (GRF) correction. The repeated-measures analysis of variance (R-M ANOVA) was completed to explore the interaction with time.

At baseline, COVID_SP exhibited elevated FC: right precentral gyrus (PrG) with left lateral occipital cortex (LOcC)/right PrG, left inferior parietal lobule (IPL) with right superior frontal gyrus (SFG), left hippocampus with right inferior frontal gyrus (IFG). Higher FC between left hippocampus and right SFG correlated with PSQI scores. At 2-month follow-up, decreased FC implicated in emotion regulation, executive function, and memory; increased FC in semantics, attention, and auditory-visual processing. The changes in these regions are correlated with the scores of PSQI, GAD, and PHQ. The Repeated-Measures Analysis of Variance (R-M ANOVA) revealed a significant time interaction effect between sleep and various emotion scales. Moreover, the analysis of the functional connectivity between the right PrG and the right PrG as well as that between the left IPL and the right SFG also discovered a significant time interaction effect.

This study provides insight into the changes in brain function associated with SP after COVID-19. These changes may partially explain the development of SP, and they also changed over time.