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BackgroundIt 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.MethodsNon-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.FindingsParticipants 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.InterpretationAmubarvimab/romlusevimab treatment, while highly effective in preventing hospitalizations/deaths, did not reduce risk of Long COVID. Additional interventions are needed to prevent Long COVID.FundingNational Institute of Allergy and Infectious Diseases of the National Institutes of Health. Amubarvimab and romlusevimab supplied by Brii Biosciences.

Persistent multi-organ symptoms after coronavirus disease 2019 (COVID-19) have been termed "long COVID" or "post-acute sequelae of SARS-CoV-2 infection." The complexity of these clinical manifestations posed challenges early in the pandemic as different ambulatory models formed out of necessity to manage the influx of patients. Little is known about the characteristics and outcomes of patients seeking care at multidisciplinary post-COVID centers. We performed a retrospective cohort study of patients evaluated at our multidisciplinary comprehensive COVID-19 center in Chicago, Ill, between May 2020 and February 2022. We analyzed specialty clinic utilization and clinical test results according to severity of acute COVID-19. We evaluated 1802 patients a median of 8 months from acute COVID-19 onset, including 350 post-hospitalization and 1452 non-hospitalized patients. Patients were seen in 2361 initial visits in 12 specialty clinics, with 1151 (48.8%) in neurology, 591 (25%) in pulmonology, and 284 (12%) in cardiology. Among the patients tested, 742/916 (81%) reported decreased quality of life, 284/553 (51%) had cognitive impairment, 195/434 (44.9%) had alteration of lung function, 249/299 (83.3%) had abnormal computed tomography chest scans, and 14/116 (12.1%) had elevated heart rate on rhythm monitoring. Frequency of cognitive impairment and pulmonary dysfunction was associated with severity of acute COVID-19. Non-hospitalized patients with positive SARS-CoV-2 testing had findings similar to those with negative or no test results. The experience at our multidisciplinary comprehensive COVID-19 center shows common utilization of multiple specialists by long COVID patients, who harbor frequent neurologic, pulmonary, and cardiologic abnormalities. Differences in post-hospitalization and non-hospitalized groups suggest distinct pathogenic mechanisms of long COVID in these populations. • Multidisciplinary centers efficiently provide access to specialty care for the broad range of organ systems involved in long COVID. • Neurology, pulmonary, and cardiology are the most commonly utilized specialties in an established multidisciplinary center. • When long COVID patients receive appropriate specialty care, abnormal diagnostic test results are common, even among patients not hospitalized for acute infection. [ABSTRACT FROM AUTHOR]

Long COVID affects millions of people worldwide and has emerged as a major health consequence of the COVID-19 pandemic. While quantitative studies have helped paint a picture of ongoing symptomatology, there are very few longitudinal qualitative studies that present patients' perspectives about the significant and persistent impact Long COVID has on their daily lives. To address this gap, we conducted semi-structured qualitative interviews with nine Long COVID patients about 15 months after we performed an initial set of interviews with those patients who were seeking care at a Long COVID specialty clinic. Most patients that we re-interviewed reported having lingering symptoms that continue to impact their lives. Many described suffering with mental health issues, particularly depression and anxiety. Others described financial stress. Most reported not yet being unable to return to their pre-COVID level of health and well-being. Our work demonstrates the ongoing need to study Long COVID and provide robust social support, mental health resources, and healthcare focused on symptom relief. [ABSTRACT FROM AUTHOR]

Introduction: COVID-19 vaccinations reduce the severity and number of symptoms for acute SARS-CoV-2 infections and may reduce the risk of developing Long COVID, also known as post-acute sequelae of SARS-CoV-2 (PASC). Limited and heterogenous data exist on how these vaccinations received after COVID-19 infection might impact the symptoms and trajectory of PASC, once persistent symptoms have developed. Methods: We investigated the association of post-COVID-19 vaccination with any SARS-CoV-2 vaccine(s) on PASC symptoms in two independent cohorts: a retrospective chart review of self-reported data from patients (n = 128) with PASC seen in the Stanford PASC Clinic between May 2021 and May 2022 and a 2023 multinational survey assessment of individuals with PASC (n = 484). Findings: Within the PASC Clinic patient cohort (n = 128), 58.6% (n = 75) were female, and 41.4% (n = 53) were male; 50% (n = 64) were white, and 38.3% (n = 49) were non-white. A total of 60.2% (n = 77) of PASC Clinic patients reported no change in their PASC symptoms after vaccination, 17.2% (n = 22) reported improved symptoms, and 22.7% (n = 29) reported worsened symptoms. In the multinational survey cohort (n = 484), 380 were from the U.S., and 104 were from outside the U.S.; 88.4% (n = 428) were female, and 11.6% (n = 56) were male; and 88.8% (n = 430) were white, and 11.2% (n = 54) were non-white. The distribution of survey self-reported vaccine effects on PASC symptoms was 20.2% worsened (n = 98), 60.5% no effect (n = 293), and 19.2% improved (n = 93). In both cohorts, demographic features, including age, sex, and race/ethnicity, were not significantly associated with post-vaccination PASC symptom changes. There was also a non-significant difference in the median dates of COVID-19 infection among the different outcomes. BMI was significant for symptom improvement (p = 0.026) in the PASC Clinic cohort, while a history of booster doses was significant for symptom improvement (p < 0.001) in the survey cohort. Conclusions: Most individuals with PASC did not report significant changes in their overall PASC symptoms following COVID-19 vaccinations received after PASC onset. Further research is needed to better understand the relationship between COVID-19 vaccinations and PASC. [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.

Long COVID, a type of post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (PASC) defined by medically unexplained symptoms following infection with SARS-CoV-2, is a newly recognized infection-associated chronic condition that causes disability in some people. Substantial progress has been made in defining its epidemiology, biology, and pathophysiology. However, there is no cure for the tens of millions of people believed to be experiencing long COVID, and industry engagement in developing therapeutics has been limited. Here, we review the current state of knowledge regarding the biology and pathophysiology of long COVID, focusing on how the proposed mechanisms explain the physiology of the syndrome and how they provide a rationale for the implementation of a broad experimental medicine and clinical trials agenda. Progress toward preventing and curing long COVID and other infection-associated chronic conditions will require deep and sustained investment by funders and industry. Known under competing terms and definitions such as post-COVID-19 condition, post-COVID-19 conditions, post-acute sequelae of SARS-CoV-2 (PASC), post-COVID-19 syndrome, post-COVID-19, or long COVID, this review provides a framework for interpreting the literature and discusses how mechanistic studies are influencing the development of biomarkers, functional tests, and, ultimately, clinical interventions. [ABSTRACT FROM AUTHOR]

Introduction: Most healthy individuals recover from acute SARS-CoV-2 infection, whereas a remarkable number continues to suffer from unexplained symptoms, known as Long COVID or post-acute COVID-19 syndrome (PACS). It is therefore imperative that methods for preventing and treating the onset of PASC be investigated with the utmost urgency. Methods: A mathematical model of the immune response to vaccination and viral infection with SARS-CoV-2, incorporating immune memory cells, was developed. Results and discussion: Similar to our previous model, persistent infection was observed by the residual virus in the host, implying the possibility of chronic inflammation and delayed recovery from tissue injury. Pre-infectious vaccination and antiviral medication administered during onset can reduce the acute viral load; however, they show no beneficial effects in preventing persistent infection. Therefore, the impact of these treatments on the PASC, which has been clinically observed, is mainly attributed to their role in preventing severe tissue damage caused by acute viral infections. For PASC patients with persistent infection, vaccination was observed to cause an immediate rapid increase in viral load, followed by a temporary decrease over approximately one year. The former was effectively suppressed by the coadministration of antiviral medications, indicating that this combination is a promising treatment for PASC. [ABSTRACT FROM AUTHOR]

Background: Post-acute sequelae of SARS-CoV-2 infection (PASC) affects patients after recovering from acute coronavirus disease 2019 (COVID-19). This study investigates the impact of SARS-CoV-2 vaccination on PASC symptoms in children in Taiwan during the Omicron pandemic. Methods: We enrolled children under 18 years with PASC symptoms persisting for more than 4 weeks. Data collected included demographics, clinical information, vaccination status, and symptom persistence. We used logistic regression models to compare symptoms in the acute and post-COVID-19 phases and to assess the association between vaccination and these symptoms. Results: Among 500 PASC children, 292 (58.4%) were vaccinated, 282 (52.8%) were male, and the mean (SD) age was 7.6 (4.6) years. Vaccinated individuals exhibited higher odds of experiencing symptoms in the previous acute phase, such as cough (adjusted odds ratio [AOR] = 1.57; 95% confidence interval [CI]: 1.02–2.42), rhinorrhea/nasal congestion (AOR = 1.74; 95% CI: 1.13–2.67), sneezing (AOR = 1.68; 95% CI: 1.02–2.76), sputum production (AOR = 1.91; 95% CI: 1.15–3.19), headache/dizziness (AOR = 1.73; 95% CI: 1.04–2.87), and muscle soreness (AOR = 2.33; 95% CI: 1.13–4.80). In contrast, there were lower odds of experiencing abdominal pain (AOR = 0.49; 95% CI: 0.25–0.94) and diarrhea (AOR = 0.37; 95% CI: 0.17–0.78) in children who had received vaccination during the post-COVID-19 phase. Conclusions: This study revealed clinical features and vaccination effects in PASC children in Taiwan. Vaccination may reduce some gastrointestinal symptoms in the post-COVID-19 phase. [ABSTRACT FROM AUTHOR]

Abstract Background COVID-19 survivors may develop long-term symptoms of fatigue, dyspnea, mental health issues, and functional limitations: a condition termed post-acute sequelae of COVID-19 (PASC). Pulmonary rehabilitation (PR) is a recommended treatment for PASC; however, there is a lack of data regarding PR’s effect on multiple health indices and the factors that influence patient outcomes. The aim of our study is to evaluate the impact of pulmonary rehabilitation on functional and psychological parameters in patients diagnosed with Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), thereby offering insights into the efficacy of such interventions in improving the quality of life and clinical outcomes for these individuals. Methods We extracted patient demographic, comorbidity, and outcome data from Allegheny Health Network’s electronic medical records. Functionality test results were compared before and after PR, including 6-minute walk test (6MWT), chair rise repetitions (CR reps), timed up and go test (TUG), gait speed (Rehab gait), modified medical research council scale (MMRC), shortness of breath questionnaire (SOBQ), hospital anxiety and depression scale (HADS) and chronic obstructive pulmonary disease assessment test (CAT) scores. Multiple regression analysis was done to evaluate the effect of comorbidities and patient factors on patient responses to PR. Results The 55 patients included in this study had a mean time of 4 months between the initial COVID-19 diagnosis and the subsequent PASC diagnosis. Following pulmonary rehabilitation (PR), significant improvements were observed across various metrics. The distance covered in the 6-minute walk test (6MWT) increased markedly from a pre-rehabilitation average of 895 feet (SD 290) to 1,300 feet (SD 335) post-rehabilitation, with a mean change of 405 feet (95% CI [333, 477]). Chair rise repetitions (CR reps) saw an increase from 9 (SD 3) reps to 13 (SD 3) reps, with a change of 4 reps (95% CI [3.7, 4.9]). The timed up and go test (TUG) time decreased significantly from 13 s (SD 5) to 10 s (SD 2), reflecting a mean reduction of 3 s (95% CI [-4.5, -2.5]). Rehabilitation gait speed improved from 1.0 m/s to 1.3 m/s, changing by 0.3 m/s (95% CI [0.2, 0.3]). The Modified Medical Research Council (MMRC) dyspnea scale showed a notable decrease from a mean of 2 (SD 1) to 1 (SD 1), a change of -1 (95% CI [-1.5, -1]). The Shortness of Breath Questionnaire (SOBQ) scores reduced significantly from 51 (SD 21) to 22 (SD 18), with a change of -29 (95% CI [-34, -23]). The Hospital Anxiety and Depression Scale (HADS) scores decreased from 11 (SD 7) to 8 (SD 7), a reduction of -4 (95% CI [-5, -2]). Lastly, the Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) scores significantly dropped from 18 (SD 7) to 9 (SD 7), changing by -10 (95% CI [-11, -8]). However, the presence of hypertension, diabetes, chronic lung diseases, outpatient status, and receipt of specific pharmacologic treatments (decadron, decadron + remdesivir, and decadron + remdesivir + tocilizumab) were identified as factors associated with a poor response to PR. Conclusion Our study supports PR as an integrated model of care for PASC patients to improve several physical and mental health indices. The long-term effects of PR on patients’ functional status should be investigated in the future.

Abstract Background Post-acute sequelae of SARS-CoV-2 infection (PASC) symptoms have broad impact, and may affect individuals regardless of COVID-19 severity, socioeconomic status, race, ethnicity, or age. A prominent PASC symptom is cognitive dysfunction, colloquially referred to as “brain fog” and characterized by declines in short-term memory, attention, and concentration. Cognitive dysfunction can severely impair quality of life by impairing daily functional skills and preventing timely return to work. Methods RECOVER-NEURO is a prospective, multi-center, multi-arm, phase 2, randomized, active-comparator design investigating 3 interventions: (1) BrainHQ is an interactive, online cognitive training program; (2) PASC-Cognitive Recovery is a cognitive rehabilitation program specifically designed to target frequently reported challenges among individuals with brain fog; (3) transcranial direct current stimulation (tDCS) is a noninvasive form of mild electrical brain stimulation. The interventions will be combined to establish 5 arms: (1) BrainHQ; (2) BrainHQ + PASC-Cognitive Recovery; (3) BrainHQ + tDCS-active; (4) BrainHQ + tDCS-sham; and (5) Active Comparator. The interventions will occur for 10 weeks. Assessments will be completed at baseline and at the end of intervention and will include cognitive testing and patient-reported surveys. All study activities can be delivered in Spanish and English. Discussion This study is designed to test whether cognitive dysfunction symptoms can be alleviated by the use of pragmatic and established interventions with different mechanisms of action and with prior evidence of improving cognitive function in patients with neurocognitive disorder. If successful, results will provide beneficial treatments for PASC-related cognitive dysfunction. Trial registration ClinicalTrials.gov NCT05965739. Registered on July 25, 2023.

Long COVID (LC) is a condition in which patients do not fully recover from the initial SARS-CoV-2 infection but rather have persistent or new symptoms for months to years following the infection. Ongoing research efforts are investigating the pathophysiologic mechanisms of LC and exploring preventative and therapeutic treatment approaches for patients. As a burgeoning area of investigation, LC research can be structured to be more inclusive, innovative, and effective. In this perspective, we highlight opportunities for patient engagement and diverse research expertise, as well as the challenges of developing definitions and reproducible studies. Our intention is to provide a foundation for collaboration and progress in understanding the biomarkers and mechanisms driving LC. Long COVID (LC) has become a major public health concern, necessitating multi-pronged research efforts to understand the pathophysiologic mechanisms of this condition and aid in patient diagnosis and treatment. In this perspective, Hamlin and Blish review previous and ongoing studies, highlighting the challenges and opportunities in LC research. [ABSTRACT FROM AUTHOR]

Background: COVID-19 survivors may develop long-term symptoms of fatigue, dyspnea, mental health issues, and functional limitations: a condition termed post-acute sequelae of COVID-19 (PASC). Pulmonary rehabilitation (PR) is a recommended treatment for PASC; however, there is a lack of data regarding PR's effect on multiple health indices and the factors that influence patient outcomes. The aim of our study is to evaluate the impact of pulmonary rehabilitation on functional and psychological parameters in patients diagnosed with Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), thereby offering insights into the efficacy of such interventions in improving the quality of life and clinical outcomes for these individuals. Methods: We extracted patient demographic, comorbidity, and outcome data from Allegheny Health Network's electronic medical records. Functionality test results were compared before and after PR, including 6-minute walk test (6MWT), chair rise repetitions (CR reps), timed up and go test (TUG), gait speed (Rehab gait), modified medical research council scale (MMRC), shortness of breath questionnaire (SOBQ), hospital anxiety and depression scale (HADS) and chronic obstructive pulmonary disease assessment test (CAT) scores. Multiple regression analysis was done to evaluate the effect of comorbidities and patient factors on patient responses to PR. Results: The 55 patients included in this study had a mean time of 4 months between the initial COVID-19 diagnosis and the subsequent PASC diagnosis. Following pulmonary rehabilitation (PR), significant improvements were observed across various metrics. The distance covered in the 6-minute walk test (6MWT) increased markedly from a pre-rehabilitation average of 895 feet (SD 290) to 1,300 feet (SD 335) post-rehabilitation, with a mean change of 405 feet (95% CI [333, 477]). Chair rise repetitions (CR reps) saw an increase from 9 (SD 3) reps to 13 (SD 3) reps, with a change of 4 reps (95% CI [3.7, 4.9]). The timed up and go test (TUG) time decreased significantly from 13 s (SD 5) to 10 s (SD 2), reflecting a mean reduction of 3 s (95% CI [-4.5, -2.5]). Rehabilitation gait speed improved from 1.0 m/s to 1.3 m/s, changing by 0.3 m/s (95% CI [0.2, 0.3]). The Modified Medical Research Council (MMRC) dyspnea scale showed a notable decrease from a mean of 2 (SD 1) to 1 (SD 1), a change of -1 (95% CI [-1.5, -1]). The Shortness of Breath Questionnaire (SOBQ) scores reduced significantly from 51 (SD 21) to 22 (SD 18), with a change of -29 (95% CI [-34, -23]). The Hospital Anxiety and Depression Scale (HADS) scores decreased from 11 (SD 7) to 8 (SD 7), a reduction of -4 (95% CI [-5, -2]). Lastly, the Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) scores significantly dropped from 18 (SD 7) to 9 (SD 7), changing by -10 (95% CI [-11, -8]). However, the presence of hypertension, diabetes, chronic lung diseases, outpatient status, and receipt of specific pharmacologic treatments (decadron, decadron + remdesivir, and decadron + remdesivir + tocilizumab) were identified as factors associated with a poor response to PR. Conclusion: Our study supports PR as an integrated model of care for PASC patients to improve several physical and mental health indices. The long-term effects of PR on patients' functional status should be investigated in the future. [ABSTRACT FROM AUTHOR]

Background: Coronavirus disease 2019 (COVID-19) can lead to persistent and debilitating symptoms referred to as Post-Acute sequelae of SARS-CoV-2 infection (PASC) This broad symptomatology lasts for months after the acute infection and impacts physical and mental health and everyday functioning. In the present study, we aimed to evaluate the prevalence and predictors of long-term impairment of working ability in non-elderly people hospitalised for COVID-19. Methods: This cross-sectional study involved 322 subjects hospitalised for COVID-19 from 1 March 2020 to 31 December 2022 in the University Hospital of Bari, Apulia, Italy, enrolled at the time of their hospital discharge and followed-up at a median of 731 days since hospitalization (IQR 466–884). Subjects reporting comparable working ability and those reporting impaired working ability were compared using the Mann-Whitney test (continuous data) and Fisher's test or Chi-Square test (categorical data). Multivariable analysis of impaired working ability was performed using a logistic regression model. Results: Among the 322 subjects who were interviewed, 184 reported comparable working ability (57.1%) and 134 reported impaired working ability (41.6%) compared to the pre-COVID-19 period. Multivariable analysis identified age at hospital admission (OR 1.02, 95% CI 0.99 to 1.04), female sex (OR 1.90, 95% CI 1.18 to 3.08), diabetes (OR 3.73, 95% CI 1.57 to 9.65), receiving oxygen during hospital stay (OR 1.76, 95% CI 1.01 to 3.06), and severe disease (OR 0.51, 95% CI 0.26 to 1.01) as independent predictors of long-term impaired working ability after being hospitalised for COVID-19. Conclusions: Our findings suggest that PASC promotes conditions that could result in decreased working ability and unemployment. These results highlight the significant impact of this syndrome on public health and the global economy, and the need to develop clinical pathways and guidelines for long-term care with specific focus on working impairment. [ABSTRACT FROM AUTHOR]

Background: Infections of Coronavirus Disease-2019 (COVID-19) can cause long-term effects known as long COVID. This pilot study aimed to evaluate the feasibility of a clinical study as well as the efficacy and safety of traditional East Asian herbal medicines in alleviating fatigue and cognitive dysfunction in patients with long COVID. Methods: This prospective pilot study investigated the use of three types of herbal medicines, Bojungikgi-tang (BIT), Kyungok-go (KOG), and Cheonwangbosim-dan (CBD), for a 12-week period as potential treatments for fatigue and cognitive dysfunction in patients with long COVID. Forty-five patients with long COVID were recruited, and one of three drugs was given based on the patient's symptoms and pattern identification. The effect of herbal medications on fatigue and cognitive function outcomes was assessed over a 36-week period, with patient adherence closely monitored. Results: After 12 weeks of herbal drug administration, fatigue symptoms improved significantly across all groups, with treatment success rates of 80 %, 53.33 %, and 46.67 % in the BIT, KOG, and CBD groups, respectively. However, cognitive dysfunction symptoms showed less improvement, with treatment success rates of 40 %, 46.67 %, and 13.33 % in the BIT, KOG, and CBD groups, respectively. All adverse events reported were mild and unrelated to the medication. The study design was found to be feasible with high medication adherence. Conclusions: This study demonstrated the feasibility of conducting a clinical trial with three herbal medicines to treat long COVID symptoms like fatigue and cognitive dysfunction.

Introduction: Post-acute sequelae of SARS-CoV-2 infection (PASC) presents a spectrum of symptoms following acute COVID-19, with exercise intolerance being a prevalent manifestation likely linked to disrupted oxygen metabolism and mitochondrial function. This study aims to assess maximal fat oxidation (MFO) and exercise intensity at MFO (FATmax) in distinct PASC subject groups and compare these findings with normative data. Methods: Eight male subjects with PASC were involved in this study. The participants were divided into two groups: "endurance-trained" subjects (VO2max > 55mL/min/kg) and "recreationally active" subjects (VO2max < 55 mL/min/kg). Each subject performed a graded exercise test until maximal oxygen consumption (VO2max) to measure fat oxidation. Subsequently, MFO was assessed, and FATmax was calculated as the ratio between VO2 at MFO and VO2 max. Results: The MFO and FATmax of "endurance-trained" subjects were 0.85, 0.89, 0.71, and 0.42 and 68%, 69%, 64%, and 53%, respectively. Three out of four subjects showed both MFO and FATmax values placed over the 80th percentile of normative data. The MFO and FATmax of "recreationally active" subjects were 0.34, 0.27, 0.35, and 0.38 and 47%, 39%, 43%, and 41%, respectively. All MFO and FATmax values of those subjects placed below the 20th percentile or between the 20th and 40th percentile. Discussion: Significant differences in MFO and FATmax values between 'endurance-trained' and "recreationally active" subjects suggest that specific endurance training, rather than simply an active lifestyle, may provide protective effects against alterations in mitochondrial function during exercise in subjects with PASC. [ABSTRACT FROM AUTHOR]

Long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC), can manifest as long-term symptoms in multiple organ systems, including respiratory, cardiovascular, neurological, and metabolic systems. In patients with severe COVID-19, immune dysregulation is significant, and the relationship between metabolic regulation and immune response is of great interest in determining the pathophysiological mechanisms. We aimed to characterize the metabolomic footprint of recovering severe COVID-19 patients at three consecutive timepoints and compare metabolite levels to controls. Our findings add proof of dysregulated amino acid metabolism in the acute phase and dyslipidemia, glycoprotein level alterations, and energy metabolism disturbances in severe COVID-19 patients 3–4 months post-hospitalization. [ABSTRACT FROM AUTHOR]

Background: Long COVID, also known as post-acute sequelae of COVID-19 (PASC), is characterized by persistent clinical symptoms following COVID-19. Objective: To correlate biomarkers of endothelial dysfunction with persistent clinical symptoms and pulmonary function defects at distance from COVID-19. Methods: Consecutive patients with long COVID-19 suspicion were enrolled. A panel of endothelial biomarkers was measured in each patient during clinical evaluation and pulmonary function test (PFT). Results: The study included 137 PASC patients, mostly male (68%), with a median age of 55 years. A total of 194 PFTs were performed between months 3 and 24 after an episode of SARS-CoV-2 infection. We compared biomarkers evaluated in PASC patients with 20 healthy volunteers (HVs) and acute hospitalized COVID-19 patients (n = 88). The study found that angiogenesis-related biomarkers and von Willebrand factor (VWF) levels were increased in PASC patients compared to HVs without increased inflammatory or platelet activation markers. Moreover, VEGF-A and VWF were associated with persistent lung CT scan lesions and impaired diffusing capacity of the lungs for carbon monoxide (DLCO) measurement. By employing a Cox proportional hazards model adjusted for age, sex, and body mass index, we further confirmed the accuracy of VEGF-A and VWF. Following adjustment, VEGF-A emerged as the most significant predictive factor associated with persistent lung CT scan lesions and impaired DLCO measurement. Conclusion: VEGF-A is a relevant predictive factor for DLCO impairment and radiological sequelae in PASC. Beyond being a biomarker, we hypothesize that the persistence of angiogenic disorders may contribute to long COVID symptoms. [ABSTRACT FROM AUTHOR]

Abstract Background Defining patterns of symptoms in long COVID is necessary to advance therapies for this heterogeneous condition. Here we aimed to describe clusters of symptoms in individuals with long COVID and explore the impact of the emergence of variants of concern (VOCs) and vaccination on these clusters. Methods In a prospective, multi centre cohort study, individuals with symptoms persisting > 4 weeks from acute COVID-19 were divided into two groups based on timing of acute infection; pre-Alpha VOC, denoted wild type (WT) group and post-Alpha VOC (incorporating alpha and delta dominant periods) denoted VOC group. We used multiple correspondence analysis (MCA) and hierarchical clustering in the WT and VOC groups to identify symptom clusters. We then used logistic regression to explore factors associated with individual symptoms. Results A total of 417 individuals were included in the analysis, 268 in WT and 149 in VOC groups respectively. In both groups MCA identified three similar clusters; a musculoskeletal (MSK) cluster characterised by joint pain and myalgia, a cardiorespiratory cluster and a less symptomatic cluster. Differences in characteristic symptoms were only seen in the cardiorespiratory cluster where a decrease in the frequency of palpitations (10% vs 34% p = 0.008) and an increase in cough (63% vs 17% p

Background: Post-acute sequelae of SARS-CoV-2 infection (PASC) affects patients after recovering from acute coronavirus disease 2019 (COVID-19). This study investigates the impact of SARS-CoV-2 vaccination on PASC symptoms in children in Taiwan during the Omicron pandemic. Methods: We enrolled children under 18 years with PASC symptoms persisting for more than 4 weeks. Data collected included demographics, clinical information, vaccination status, and symptom persistence. We used logistic regression models to compare symptoms in the acute and post-COVID-19 phases and to assess the association between vaccination and these symptoms. Results: Among 500 PASC children, 292 (58.4%) were vaccinated, 282 (52.8%) were male, and the mean (SD) age was 7.6 (4.6) years. Vaccinated individuals exhibited higher odds of experiencing symptoms in the previous acute phase, such as cough (adjusted odds ratio [AOR] = 1.57; 95% confidence interval [CI]: 1.02–2.42), rhinorrhea/nasal congestion (AOR = 1.74; 95% CI: 1.13–2.67), sneezing (AOR = 1.68; 95% CI: 1.02–2.76), sputum production (AOR = 1.91; 95% CI: 1.15–3.19), headache/dizziness (AOR = 1.73; 95% CI: 1.04–2.87), and muscle soreness (AOR = 2.33; 95% CI: 1.13–4.80). In contrast, there were lower odds of experiencing abdominal pain (AOR = 0.49; 95% CI: 0.25–0.94) and diarrhea (AOR = 0.37; 95% CI: 0.17–0.78) in children who had received vaccination during the post-COVID-19 phase. Conclusions: This study revealed clinical features and vaccination effects in PASC children in Taiwan. Vaccination may reduce some gastrointestinal symptoms in the post-COVID-19 phase.

Abstract Headache is one of the most common neurological manifestations of COVID-19, but it is unclear whether chronic headache as a symptom of Post-COVID-19 is associated with ongoing CNS damage. We compared cerebrospinal fluid (CSF) levels of markers of CNS damage and inflammation in Post-COVID-19 patients with persistent headache to hospitalized acute COVID-19 patients with neurological symptoms and to non-COVID-19 disease-controls. CSF levels of neurofilament light chain, Ubiquitin carboxyl-terminal hydrolase L1 and Tau were similar in patients with persistent headache in post-COVID-19 compared to acute COVID-19 patients and all control groups. Levels of glial fibrillary astrocytic protein were lower in patients with persistent headache in post-COVID-19 compared to some control groups of patients with neurological disease. Therefore, our pilot study of CSF markers indicates that persistent post-COVID-19 headache is not a sign of underlying neuronal damage or glial activation.

IntroductionPost-COVID-19 condition (PCC) is characterised by a plethora of symptoms, with fatigue appearing as the most frequently reported. The alterations that drive both the persistent and post-acute disease newly acquired symptoms are not yet fully described. Given the lack of robust knowledge regarding the mechanisms of PCC we have examined the impact of inflammation in PCC, by evaluating serum cytokine profile and its potential involvement in inducing the different symptoms reported.MethodsIn this cross-sectional study, we recruited 227 participants who were hospitalised with acute COVID-19 in 2020 and came back for a follow-up assessment 6–12 months after hospital discharge. The participants were enrolled in two symptomatic groups: Self-Reported Symptoms group (SR, n = 96), who did not present major organ lesions, yet reported several debilitating symptoms such as fatigue, muscle weakness, and persistent loss of sense of smell and taste; and the Self-Reported Symptoms and decreased Pulmonary Function group (SRPF, n = 54), composed by individuals with the same symptoms described by SR, plus diagnosed pulmonary lesions. A Control group (n = 77), with participants with minor complaints following acute COVID-19, was also included in the study. Serum cytokine levels, symptom questionnaires, physical performance tests and general clinical data were obtained in the follow-up assessment.ResultsSRPF presented lower IL-4 concentration compared with Control (q = 0.0018) and with SR (q = 0.030), and lower IFN-α2 serum content compared with Control (q = 0.007). In addition, SRPF presented higher MIP-1β serum concentration compared with SR (q = 0.029). SR presented lower CCL11 (q = 0.012 and q = 0.001, respectively) and MCP-1 levels (q = 0.052 for both) compared with Control and SRPF. SRPF presented lower G-CSF compared to Control (q = 0.014). Female participants in SR showed lower handgrip strength in relation to SRPF (q = 0.0082). Male participants in SR and SRPF needed more time to complete the timed up-and-go test, as compared with men in the Control group (q = 0.0302 and q = 0.0078, respectively). Our results indicate that different PCC symptom profiles are accompanied by distinct inflammatory markers in the circulation. Of particular concern are the lower muscle function findings, with likely long-lasting consequences for health and quality of life, found for both PCC phenotypes.

Background: Information on cerebrospinal fluid (CSF) findings in patients with neurological manifestations in post-COVID-19 syndrome is scarce. Methods: Retrospective evaluation of 84 CSF samples in patients fulfilling post-COVID-19 criteria in two neurological post-COVID-19 outpatient clinics. Results: In 68% of samples, all CSF parameters were normal. The most frequent pathological CSF finding was elevation of total protein (median total protein 33.3 mg/dl [total range 18.5–116.2]) in 20 of 83 (24%) samples. The second most prevalent pathological finding was a blood–CSF barrier dysfunction as measured by elevation of QAlb (median QAlb 4.65 [2.4–13.2]) in 11/84 (13%). Pleocytosis was found in only 5/84 (6%) samples and was mild in all of them. CSF-restricted oligoclonal bands were found in 5/83 (6%) samples. Anti-neuronal autoantibodies in CSF were negative in most cases, whilst 12/68 (18%) samples were positive for anti-myelin autoantibodies in serum. PCR for herpesviridae (HSV-1/-2, VZV, EBV, CMV, HHV6) showed, if at all, only weakly positive results in CSF or EDTA whole blood/plasma. Conclusions: The majority of samples did not show any pathologies. The most frequent findings were elevation of total protein and blood–CSF barrier dysfunction with no signs of intrathecal inflammation. CSF analysis still keeps its value for exclusion of differential diagnoses. [ABSTRACT FROM AUTHOR]

Background: Single studies support the presence of several post‐COVID‐19 symptoms; however, there is no evidence for the synthesis of symptoms. Objective: We attempt to provide an overview of the persistent symptoms that post‐COVID‐19 patients encounter, as well as the duration of these symptoms to help them plan their rehabilitation. Design: Systematic review and meta‐analysis. Participants: A total of 16 studies involving 8756 patients post‐COVID‐19 were included. Methods: The CINAHL, PubMed, EMBASE, Scopus, and Web of Science databases were searched from 2019 to August 2021. Observational studies that reported data on post‐COVID‐19 symptoms were included. The methodological quality of the studies was assessed using the Joanna Briggs Institute Critical Appraisal for Observational Studies. We included medium‐ to high‐quality studies. We used a random‐effects model for the meta‐analytical pooled prevalence of each post‐COVID‐19 symptom, and I2 statistics for heterogeneity. Results: From the 2481 studies identified, 16 met the inclusion criteria. The sample included 7623 hospitalised and 1133 non‐hospitalised patients. We found the most prevalent symptoms were fatigue and dyspnea with a pooled prevalence ranging from 42% (27%–58%). Other post‐COVID‐19 symptoms included sleep disturbance 28% (14%–45%), cough 25% (10%–44%), anosmia/ageusia 24% (7%–47%), fever 21% (4%–47%), myalgia 17% (2%–41%), chest pain 11% (5%–20%), and headache 9% (2%–20%). In addition to physical symptoms, anxiety/depression was also prevalent 27% (8%–53%). Conclusions: Fatigue and dyspnea were the most prevalent post‐COVID‐19 symptoms and experienced up to 12 months. Relevance to clinical practice: Multiple persistent symptoms are still experienced until 12 months of post‐Covid 19. This meta‐analysis should provide some awareness to nurses to highlights the unmet healthcare needs of post‐COVID‐19 patients. Long‐term monitoring for the evaluation and treatment of symptoms and conditions and rehabilitation programs should be conducted. [ABSTRACT FROM AUTHOR]

Compared to healthy volunteers, participants with post‐acute sequelae of SARS‐CoV‐2 infection (PASC) demonstrated increased plasma levels of the prothrombotic protein NEDD9, which associated inversely with indices of pulmonary vascular function. This suggests persistent pulmonary vascular dysfunction may play a role in the pathobiology of PASC. [ABSTRACT FROM AUTHOR]

The post-acute sequelae of SARS-CoV-2 (PASC) pose a threat to patients' health-related quality of life (HRQOL). Here, the impact of COVID-19 on HRQOL and the clinical factors associated with impaired HRQOL were examined. Discharged COVID-19 patients were assessed at 3 and 6 months after disease onset. The patients completed a medical examination and the SF-36 questionnaire at these two time points and underwent pulmonary function testing at 6 months after disease onset. All had undergone computed tomography (CT) imaging upon hospital admission. Of the 74 included patients, 38% reported respiratory symptoms at 3 months, and 26% reported respiratory symptoms at 6 months after disease onset. The aggregated SF-36 scores declined in the role/social component summary (RCS), a category related to social activity. Patients with lower RCS tended to have respiratory sequelae or a relatively lower forced vital capacity. The CT score that reflected the extent of COVID-19 pneumonia was inversely correlated with the RCS score (3 months, p = 0.0024; 6 months, p = 0.0464). A high CT score (≥10 points) predicted a low RCS score at 6 months (p = 0.013). This study highlights the impairment of RCS and its associations with respiratory sequelae. The study also emphasizes the importance of radiological findings in predicting long-term HRQOL outcomes after COVID-19. [ABSTRACT FROM AUTHOR]

Background: Post-Acute Sequelae of COVID-19 (PASC) have emerged as a global public health and healthcare challenge. This study aimed to uncover predictive factors for PASC from multi-modal data to develop a predictive model for PASC diagnoses. Methods: We analyzed electronic health records from 92,301 COVID-19 patients, covering medical phenotypes, medications, and lab results. We used a Super Learner-based prediction approach to identify predictive factors. We integrated the model outputs into individual and composite risk scores and evaluated their predictive performance. Results: Our analysis identified several factors predictive of diagnoses of PASC, including being overweight/obese and the use of HMG CoA reductase inhibitors prior to COVID-19 infection, and respiratory system symptoms during COVID-19 infection. We developed a composite risk score with a moderate discriminatory ability for PASC (covariate-adjusted AUC (95% confidence interval): 0.66 (0.63, 0.69)) by combining the risk scores based on phenotype and medication records. The combined risk score could identify 10% of individuals with a 2.2-fold increased risk for PASC. Conclusions: We identified several factors predictive of diagnoses of PASC and integrated the information into a composite risk score for PASC prediction, which could contribute to the identification of individuals at higher risk for PASC and inform preventive efforts. [ABSTRACT FROM AUTHOR]

Background: Defining patterns of symptoms in long COVID is necessary to advance therapies for this heterogeneous condition. Here we aimed to describe clusters of symptoms in individuals with long COVID and explore the impact of the emergence of variants of concern (VOCs) and vaccination on these clusters. Methods: In a prospective, multi centre cohort study, individuals with symptoms persisting > 4 weeks from acute COVID-19 were divided into two groups based on timing of acute infection; pre-Alpha VOC, denoted wild type (WT) group and post-Alpha VOC (incorporating alpha and delta dominant periods) denoted VOC group. We used multiple correspondence analysis (MCA) and hierarchical clustering in the WT and VOC groups to identify symptom clusters. We then used logistic regression to explore factors associated with individual symptoms. Results: A total of 417 individuals were included in the analysis, 268 in WT and 149 in VOC groups respectively. In both groups MCA identified three similar clusters; a musculoskeletal (MSK) cluster characterised by joint pain and myalgia, a cardiorespiratory cluster and a less symptomatic cluster. Differences in characteristic symptoms were only seen in the cardiorespiratory cluster where a decrease in the frequency of palpitations (10% vs 34% p = 0.008) and an increase in cough (63% vs 17% p < 0.001) in the VOC compared to WT groups was observed. Analysis of the frequency of individual symptoms showed significantly lower frequency of both chest pain (25% vs 39% p = 0.004) and palpitations (12% vs 32% p < 0.001) in the VOC group compared to the WT group. In adjusted analysis being in the VOC group was significantly associated with a lower odds of both chest pain and palpitations, but vaccination was not associated with these symptoms. Conclusion: This study suggests changes in long COVID phenotype in individuals infected later in the pandemic, with less palpitations and chest pain reported. Adjusted analyses suggest that these effects are mediated through introduction of variants rather than an effect from vaccination. [ABSTRACT FROM AUTHOR]

• Neuro-PASC patients show plasma proteomic alterations 3–9 months post infection. • Plasma proteome differences are identified based on PASC symptoms. • Proteomic differences suggest inflammation and mitochondrial involvement in Neuro-PASC. Persistent symptoms of COVID-19 survivors constitute long COVID syndrome, also called post-acute sequelae of SARS-CoV-2 infection (PASC). Neurologic manifestations of PASC (Neuro-PASC) are particularly debilitating, long lasting, and poorly understood. To gain insight into the pathogenesis of PASC, we leveraged a well-characterized group of Neuro-PASC (NP) patients seen at our Neuro-COVID-19 clinic who had mild acute COVID-19 and never required hospitalization to investigate their plasma proteome. Using the SomaLogic platform, SomaScan, the plasma concentration of >7000 proteins was measured from 92 unvaccinated individuals, including 48 NP patients, 20 COVID-19 convalescents (CC) without lingering symptoms, and 24 unexposed healthy controls (HC) to interrogate underlying pathobiology and potential biomarkers of PASC. We analyzed the plasma proteome based on post-COVID-19 status, neurologic and non-neurologic symptoms, as well as subjective and objective standardized tests for changes in quality-of-life (QoL) and cognition associated with Neuro-PASC. The plasma proteome of NP patients differed from CC and HC subjects more substantially than post-COVID-19 groups (NP and CC combined) differed from HC. Proteomic differences in NP patients 3–9 months following acute COVID-19 showed alterations in inflammatory proteins and pathways relative to CC and HC subjects. Proteomic associations with Neuro-PASC symptoms of brain fog and fatigue included changes in markers of DNA repair, oxidative stress, and neutrophil degranulation. Furthermore, we discovered a correlation between NP patients lower subjective impression of recovery to pre-COVID-19 baseline with an increase in the concentration of the oxidative phosphorylation protein COX7A1, which was also associated with neurologic symptoms and fatigue, as well as impairment in QoL and cognitive dysfunction. Finally, we identified other oxidative phosphorylation-associated proteins correlating with central nervous system symptoms. Our results suggest ongoing inflammatory changes and mitochondrial involvement in Neuro-PASC and pave the way for biomarker validation for use in monitoring and development of therapeutic intervention for this debilitating condition. [ABSTRACT FROM AUTHOR]

We describe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cell responses, soluble markers of inflammation, and antibody levels and neutralization capacity longitudinally in 70 individuals with PCR-confirmed SARS-CoV-2 infection. Participants represent a spectrum of illness and recovery, including some with persistent viral shedding in saliva and many experiencing post-acute sequelae of SARS-CoV-2 infection (PASC). T cell responses remain stable for up to 9 months. Whereas the magnitude of early CD4+ T cell immune responses correlates with severity of initial infection, pre-existing lung disease is independently associated with higher long-term SARS-CoV-2-specific CD8+ T cell responses. Among participants with PASC 4 months following coronavirus disease 2019 (COVID-19) symptom onset, we observe a lower frequency of CD8+ T cells expressing CD107a, a marker of degranulation, in response to Nucleocapsid (N) peptide pool stimulation, and a more rapid decline in the frequency of N-specific interferon-γ-producing CD8+ T cells. Neutralizing antibody levels strongly correlate with SARS-CoV-2-specific CD4+ T cell responses.

Abstract Compared to healthy volunteers, participants with post‐acute sequelae of SARS‐CoV‐2 infection (PASC) demonstrated increased plasma levels of the prothrombotic protein NEDD9, which associated inversely with indices of pulmonary vascular function. This suggests persistent pulmonary vascular dysfunction may play a role in the pathobiology of PASC.

Introduction: Post-acute sequelae of SARS-CoV-2 infection (PASC) presents a spectrum of symptoms following acute COVID-19, with exercise intolerance being a prevalent manifestation likely linked to disrupted oxygen metabolism and mitochondrial function. This study aims to assess maximal fat oxidation (MFO) and exercise intensity at MFO (FATmax) in distinct PASC subject groups and compare these findings with normative data.Methods: Eight male subjects with PASC were involved in this study. The participants were divided into two groups: “endurance-trained” subjects (V˙O2max > 55 mL/min/kg) and “recreationally active” subjects (V˙O2max < 55 mL/min/kg). Each subject performed a graded exercise test until maximal oxygen consumption (V˙O2max) to measure fat oxidation. Subsequently, MFO was assessed, and FATmax was calculated as the ratio between V˙O2 at MFO and V˙O2 max.Results: The MFO and FATmax of “endurance-trained” subjects were 0.85, 0.89, 0.71, and 0.42 and 68%, 69%, 64%, and 53%, respectively. Three out of four subjects showed both MFO and FATmax values placed over the 80th percentile of normative data. The MFO and FATmax of “recreationally active” subjects were 0.34, 0.27, 0.35, and 0.38 and 47%, 39%, 43%, and 41%, respectively. All MFO and FATmax values of those subjects placed below the 20th percentile or between the 20th and 40th percentile.Discussion: Significant differences in MFO and FATmax values between ‘endurance-trained’ and “recreationally active” subjects suggest that specific endurance training, rather than simply an active lifestyle, may provide protective effects against alterations in mitochondrial function during exercise in subjects with PASC.

Headache is one of the most common neurological manifestations of COVID-19, but it is unclear whether chronic headache as a symptom of Post-COVID-19 is associated with ongoing CNS damage. We compared cerebrospinal fluid (CSF) levels of markers of CNS damage and inflammation in Post-COVID-19 patients with persistent headache to hospitalized acute COVID-19 patients with neurological symptoms and to non-COVID-19 disease-controls. CSF levels of neurofilament light chain, Ubiquitin carboxyl-terminal hydrolase L1 and Tau were similar in patients with persistent headache in post-COVID-19 compared to acute COVID-19 patients and all control groups. Levels of glial fibrillary astrocytic protein were lower in patients with persistent headache in post-COVID-19 compared to some control groups of patients with neurological disease. Therefore, our pilot study of CSF markers indicates that persistent post-COVID-19 headache is not a sign of underlying neuronal damage or glial activation. [ABSTRACT FROM AUTHOR]

Kamilah Thomas-Purcell,1,&ast; Rosemary Davenport,2,&ast; Victoria Ayala,2,&ast; Donrie Purcell,3,&ast; Raymond L Ownby2,&ast; 1Department of Health Science, Nova Southeastern University, Ft. Lauderdale, FL, USA; 2Department of Psychiatry, Nova Southeastern University, Ft. Lauderdale, FL, USA; 3Satcher Health Leadership Institute, Morehouse School of Medicine, Atlanta, GA, USA&ast;These authors contributed equally to this workCorrespondence: Raymond L Ownby, Nova Southeastern University, Center for Collaborative Research Suite 430, 3301 College Avenue, Ft. Lauderdale, FL, 33314, USA, Tel +1-954-608-4846, Email ro71@nova.eduIntroduction: Approximately 20– 30% of individuals who contract acute coronavirus disease (COVID-19) infection develop longer term complications of their initial infection, referred to as Post-Acute Sequelae of SARS-CoV-2 infection (PASC). PASC is characterized by chronic, varying symptomatology.Methods: Using a mixed methods study design, we aimed to gain insight into individuals’ experience with PASC, including cognitive issues, fatigue, and sleep disturbances. We explored whether our previously developed application (app), aimed at improving self-management skills among individuals with chronic diseases, is relevant for individuals with PASC and gained information to adapt the app for individuals with PASC. The study included 19 individuals, aged 40 years and older, recruited from our research participant database, Nova Southeastern University clinics, and community locations. We included this age range because older adults are more likely to have comorbid conditions, allowing us to better understand the impact of COVID-19 infection in these individuals. Participants completed seven standardized self-report questionnaires online, and an individual semi-structured interview via videoconferencing. Quantitative data were assessed using descriptive statistics and calculating individuals’ scores in relation to norms. Qualitative data were analyzed using a thematic analysis approach. Triangulation of the data was accomplished by calculating correlations between participants’ responses on self-report scales and themes found in semi-structured interviews.Results: Themes included disruption of everyday life, diverse physical symptoms, and cognitive problems including brain fog, fatigue, coping, and emotional upset. Quantitative analysis demonstrated that participants experienced high levels of fatigue, negative mood, cognitive problems, and overall reduction in health-related quality of life (HRQOL). Correlation analyses revealed that individual interview responses were related to participants’ self-report of symptoms on standard questionnaires.Discussion: Findings indicate that self-report questionnaires may reflect the experience of individuals with PASC and its impact. Additionally, further efforts to expand our prior mobile app are warranted among individuals with PASC.Keywords: post-acute sequelae of SARS-CoV-2 infection, COVID-19, long COVID, SARS-CoV-2 cognitive issues, health-related quality of life, self-report questionnaires, qualitative analysis

Background: The aim of the study was to longitudinally evaluate the association between MMP-2, MMP-9, TIMP-1 and chest radiological findings in COVID-19 patients. Methods: COVID-19 patients were evaluated based on their hospital admission (baseline) and three months after hospital discharge (T post) and were stratified into ARDS and non-ARDS groups. As a control group, healthy donors (HD) were enrolled. Results: At the baseline, compared to HD (n = 53), COVID-19 patients (n = 129) showed higher plasma levels of MMP-9 (p < 0.0001) and TIMP-1 (p < 0.0001) and the higher plasma activity of MMP-2 (p < 0.0001) and MMP-9 (p < 0.0001). In the ARDS group, higher plasma levels of MMP-9 (p = 0.0339) and TIMP-1 (p = 0.0044) and the plasma activity of MMP-2 (p = 0.0258) and MMP-9 (p = 0.0021) compared to non-ARDS was observed. A positive correlation between the plasma levels of TIMP-1 and chest computed tomography (CT) score (ρ = 0.2302, p = 0.0160) was observed. At the T post, a reduction in plasma levels of TIMP-1 (p < 0.0001), whereas an increase in the plasma levels of MMP-9 was observed (p = 0.0088). Conclusions: The positive correlation between TIMP-1 with chest CT scores highlights its potential use as a marker of fibrotic burden. At T post, the increase in plasma levels of MMP-9 and the reduction in plasma levels of TIMP-1 suggested that inflammation and fibrosis resolution were still ongoing. [ABSTRACT FROM AUTHOR]

The clinical manifestation study of post-acute sequelae of SARS-CoV-2 infection (PASC) has shown a lack of knowledge regarding its morphology and pathogenesis. The aim of this research was to investigate morphological manifestations of PASC in the myocardium. Materials and Methods: The study included 38 patients requiring endomyocardial biopsy (EMB) during the post-acute phase of coronavirus infection and a control group including patients requiring EMB prior to the SARS-CoV-2 pandemic. The patients' clinical and laboratory data were analyzed. Histological examination and immunohistochemistry (IHC) of the myocardial tissue was conducted with antibodies to CD3, CD68, HLA-DR, MHC1, C1q, VP1 enteroviruses, spike protein SARS-CoV-2, Ang1, von Willebrand factor (VWF), and VEGF. The morphometric analysis included counting the mean number of inflammatory infiltrate cells per mm2 and evaluating the expression of SARS-CoV-2 spike protein, HLA-DR, MHC1, C1q, Ang1, VWF, and VEGF using a scoring system. If the expression of SARS-CoV-2 spike protein was >3 points, an additional IHC test with antibodies to ACE2, CD16 as well as RT-PCR testing of the myocardial tissue were performed. For two patients, immunofluorescence tests of the myocardial tissue were performed using antibody cocktails to SARS-CoV-2 spike protein/CD16, SARS-CoV-2 spike protein/CD68, CD80/CD163. The statistical data analysis was carried out using the Python programming language and libraries such as NumPy, SciPy, Pandas, and Matplotlib. Results: The study demonstrated a significant increase in the number of CD68+ macrophages in the myocardium of PASC patients compared to patients who did not have a history of COVID-19 (p = 0.014 and p = 0.007 for patients with and without myocarditis, respectively), predominantly due to M2 macrophages. An increase in the number of CD68+ macrophages was more frequently observed in patients with shorter intervals between the most recent positive SARS-CoV-2 PCR test and the time of performing the EMB (r = −0.33 and r = −0.61 for patients with and without myocarditis, respectively). The expression scores of Ang1, VEGF, VWF, and C1q in PASC patients did not significantly differ from those in EMB samples taken before 2019. Conclusion: The myocardium of PASC patients demonstrated a significant increase in the number of CD68+ macrophages and a decrease in the expression of markers associated with angiopathy. No evidence of coronavirus-associated myocarditis was observed in any PASC patient. [ABSTRACT FROM AUTHOR]

Persistent or recurrent cardiovascular symptoms have been identified as one of the hallmarks of long-COVID or post-acute sequelae of SARS-CoV-2 infection (PASC). The purpose of this study was to determine the prevalence and extent of cardiac abnormalities in patients referred for cardiac MRI due to clinical evidence of PASC. To investigate this, two tertiary care hospitals identified all patients who were referred for cardiac MRI under the suspicion of PASC in a 2-year period and retrospectively included them in this study. Patients with previously known cardiac diseases were excluded. This resulted in a total cohort of 129 patients (63, 51% female; age 41 ± 16 years). The majority of patients (57%) showed normal cardiac results. No patient had active myocarditis or an acute myocardial infarction. However, 30% of patients had evidence of non-ischemic myocardial fibrosis, which exceeds the prevalence in the normal adult population and suggests that a possible history of myocarditis might explain persistent symptoms in the PASC setting. [ABSTRACT FROM AUTHOR]

Background: Anxiety and post-traumatic stress symptoms have been reported in association with acute and post-acute sequelae of COVID-19 (PASC). Purpose: This study aimed to document the cross-sectional prevalence, characteristics and clinical correlates of anxiety and post-traumatic stress in a study of neuropsychiatric sequelae of COVID-19. Method: 75 participants recruited from a post-COVID-19 recovery program and the community were assessed for sociodemographic, medical, psychiatric, and neurocognitive symptoms and performance. The generalized anxiety questionnaire-7 (GAD-7) and post-traumatic stress disorder questionnaire for DSM5 (PCL5) were utilized to measure anxiety and PTSD symptoms. Established cutoff scoring for the GAD-7 and algorithm-based scoring of the PCL5 were utilized to determine clinically significant anxiety symptoms and PTSD, respectively. Results: The cohort was 71% female, 36% ethnic minority, with the main age of 43.5 years, 80% employment, 40% with the prior psychiatric treatment history and 2/3 seeking post-COVID care for PASC. Clinically significant anxiety symptoms were found in 31% and PTSD was found in 29% of the cohort. Nervousness and excessive worry were the most prominent anxiety symptoms, while changes in mood/cognition and avoidance were most frequent in PTSD. There was a high degree of comorbidity between clinically significant anxiety symptoms, PTSD, depression and fatigue. In logistic regression, acute COVID illness severity, prior psychiatric history, and memory complaints (but not objective neuropsychological performance) predicted clinically significant anxiety symptoms and/or PTSD. Conclusion: Clinically significant anxiety and PTSD are found in approximately 1 of 3 individuals after COVID-19 infection. They are highly comorbid with each other as well as with depression and fatigue. All patients seeking care for PASC should be screened for these neuropsychiatric complications. Symptoms of worry, nervousness, subjective changes in mood, and cognition as well as behavioral avoidance are particularly important targets of clinical intervention. [ABSTRACT FROM AUTHOR]

The long-term consequences of COVID-19 survivors care and post-coronavirus infection are not yet well understood. The review aims to see whether homoeopathy can help COVID-19 survivors recover from its consequences and improve their quality of life. A systematic search of published articles for post-COVID sequelae and the impact of Homoeopathy were conducted. For the literature search, the major electronic bio-medical database PubMed/MEDLINE was used. In addition, supplementary searches were conducted through the references of those published articles. A total of 113 records were identified of which 61 studies included for this review. Homoeopathy is effective in the treatment of mental disorders including anxiety and depressive disorder (ADD), some research studies have found, although systematic reviews disagree. Likewise, some medical societies denounce homoeopathy for pain management; other literature shows that it can be used to treat pain effectively. Homoeopathy can aid in the treatment of cardiovascular diseases, as Crataegus, a homoeopathic medication, was found to be just as effective as a standard angiotensin-converting enzyme (ACE) inhibitor and diuretic treatment for minor cardiac insufficiency. The outcomes for Chronic Fatigue Syndrome (CFS), Influenza, and Acute Respiratory Tract Infections (ARTIs) are also promising. Based on the results of homoeopathy in non-COVID conditions, it can be thought of in the management of post-COVID-19 outcomes. Consequently, we propose that while investigating post-COVID-19 patient rehabilitation, homoeopathic management may be included as part of the follow-up route and as much data as possible in the context of homoeopathy should be collected, so that in future, the role of homoeopathy in dealing with it can be better demonstrated. – The long-term consequences of post coronavirus infections are poorly understood. –The Aim of this review is to understand how Homoeopathy may aid COVID 19 survivors in regaining function and improving their quality of life. – Based on non-COVID conditions, Homoeopathy has the potential to play an important role in the treatment of post-COVID 19 survivor complaints such as psychiatric illness, pain management, fatigue syndrome, and cardiovascular complications. [ABSTRACT FROM AUTHOR]

Background: Coronavirus disease 2019 (COVID-19) can lead to persistent and debilitating symptoms referred to as Post-Acute sequelae of SARS-CoV-2 infection (PASC) This broad symptomatology lasts for months after the acute infection and impacts physical and mental health and everyday functioning. In the present study, we aimed to evaluate the prevalence and predictors of long-term impairment of working ability in non-elderly people hospitalised for COVID-19. Methods: This cross-sectional study involved 322 subjects hospitalised for COVID-19 from 1 March 2020 to 31 December 2022 in the University Hospital of Bari, Apulia, Italy, enrolled at the time of their hospital discharge and followed-up at a median of 731 days since hospitalization (IQR 466–884). Subjects reporting comparable working ability and those reporting impaired working ability were compared using the Mann-Whitney test (continuous data) and Fisher’s test or Chi-Square test (categorical data). Multivariable analysis of impaired working ability was performed using a logistic regression model. Results: Among the 322 subjects who were interviewed, 184 reported comparable working ability (57.1%) and 134 reported impaired working ability (41.6%) compared to the pre-COVID-19 period. Multivariable analysis identified age at hospital admission (OR 1.02, 95% CI 0.99 to 1.04), female sex (OR 1.90, 95% CI 1.18 to 3.08), diabetes (OR 3.73, 95% CI 1.57 to 9.65), receiving oxygen during hospital stay (OR 1.76, 95% CI 1.01 to 3.06), and severe disease (OR 0.51, 95% CI 0.26 to 1.01) as independent predictors of long-term impaired working ability after being hospitalised for COVID-19. Conclusions: Our findings suggest that PASC promotes conditions that could result in decreased working ability and unemployment. These results highlight the significant impact of this syndrome on public health and the global economy, and the need to develop clinical pathways and guidelines for long-term care with specific focus on working impairment.

Abstract Recent studies have indicated that long-term neurological sequelae after COVID-19 are not accompanied by an increase of canonical biomarkers of central nervous system injury in blood, but subgroup stratifications are lacking. This is a particular concern in chronic headache, which can be a leading symptom of Post-COVID diseases associated with neuronal damage such as vasculitis or autoimmune encephalitis. We here compared patients with mild Post-COVID-19 syndrome and persistent headache (persistent Post-COVID-19 headache) lasting longer than 12 weeks after the initial serological diagnosis, to patients with mild and severe COVID-19 and COVID-19-negative controls. Levels of neurofilament light chain and glial fibrillary astrocytic protein, i.e. markers of neuronal damage and reactive astrogliosis, were lower in blood from patients with persistent Post-COVID-19 headache compared to patients with severe COVID-19. Hence, our pilot serological study indicates that long-term Post-COVID-19 headache may not be a sign of underlying neuronal damage or neuroinflammation.

Abstract Background Although the coronavirus disease 19 (COVID-19) pandemic has now impacted the world for over two years, the persistent secondary neuropsychiatric effects are still not fully understood. These “long COVID” symptoms, also referred to as post-acute sequelae of SARS-CoV-2 infection (PASC), can persist for months after infection without any effective treatments. Long COVID involves a complex heterogenous symptomology and can lead to disability and limit work. Long COVID symptoms may be due to sustained inflammatory responses and prolonged immune response after infection. Interestingly, vagus nerve stimulation (VNS) may have anti-inflammatory effects, however, until recently, VNS could not be self-administered, at-home, noninvasively. Methods We created a double-blind, noninvasive transcutaneous auricular VNS (taVNS) system that can be self-administered at home with simultaneous remote monitoring of physiological biomarkers and video supervision by study staff. Subsequently, we carried out a pilot (n = 13) randomized, sham-controlled, trial with this system for four weeks to treat nine predefined long covid symptoms (anxiety, depression, vertigo, anosmia, ageusia, headaches, fatigue, irritability, brain fog). No in-person patient contact was needed, with informed consent, trainings, ratings, and all procedures being conducted remotely during the pandemic (2020–2021) and equipment being shipped to individuals’ homes. This trial was registered on ClinicalTrials.gov under the identifier: NCT04638673 registered November 20, 2020. Results Four-weeks of at-home self-administered taVNS (two, one-hour sessions daily, delivered at suprathreshold intensities) was feasible and safe. Although our trial was not powered to determine efficacy as an intervention in a heterogenous population, the trends in the data suggest taVNS may have a mild to moderate effect in reducing mental fatigue symptoms in a subset of individuals. Conclusions This innovative study demonstrates the safety and feasibility of supervised self-administered taVNS under a fully contactless protocol and suggests that future studies can safely investigate this novel form of brain stimulation at-home for a variety of neuropsychiatric and motor recovery applications.

Some patients remain unwell for months after “recovering” from acute COVID-19. They develop persistent fatigue, cognitive problems, headaches, disrupted sleep, myalgias and arthralgias, post-exertional malaise, orthostatic intolerance and other symptoms that greatly interfere with their ability to function and that can leave some people housebound and disabled. The illness (Long COVID) is similar to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) as well as to persisting illnesses that can follow a wide variety of other infectious agents and following major traumatic injury. Together, these illnesses are projected to cost the U.S. trillions of dollars. In this review, we first compare the symptoms of ME/CFS and Long COVID, noting the considerable similarities and the few differences. We then compare in extensive detail the underlying pathophysiology of these two conditions, focusing on abnormalities of the central and autonomic nervous system, lungs, heart, vasculature, immune system, gut microbiome, energy metabolism and redox balance. This comparison highlights how strong the evidence is for each abnormality, in each illness, and helps to set priorities for future investigation. The review provides a current road map to the extensive literature on the underlying biology of both illnesses.

BackgroundAnxiety and post-traumatic stress symptoms have been reported in association with acute and post-acute sequelae of COVID-19 (PASC).PurposeThis study aimed to document the cross-sectional prevalence, characteristics and clinical correlates of anxiety and post-traumatic stress in a study of neuropsychiatric sequelae of COVID-19.Method75 participants recruited from a post-COVID-19 recovery program and the community were assessed for sociodemographic, medical, psychiatric, and neurocognitive symptoms and performance. The generalized anxiety questionnaire-7 (GAD-7) and post-traumatic stress disorder questionnaire for DSM5 (PCL5) were utilized to measure anxiety and PTSD symptoms. Established cutoff scoring for the GAD-7 and algorithm-based scoring of the PCL5 were utilized to determine clinically significant anxiety symptoms and PTSD, respectively.ResultsThe cohort was 71% female, 36% ethnic minority, with the main age of 43.5 years, 80% employment, 40% with the prior psychiatric treatment history and 2/3 seeking post-COVID care for PASC. Clinically significant anxiety symptoms were found in 31% and PTSD was found in 29% of the cohort. Nervousness and excessive worry were the most prominent anxiety symptoms, while changes in mood/cognition and avoidance were most frequent in PTSD. There was a high degree of comorbidity between clinically significant anxiety symptoms, PTSD, depression and fatigue. In logistic regression, acute COVID illness severity, prior psychiatric history, and memory complaints (but not objective neuropsychological performance) predicted clinically significant anxiety symptoms and/or PTSD.ConclusionClinically significant anxiety and PTSD are found in approximately 1 of 3 individuals after COVID-19 infection. They are highly comorbid with each other as well as with depression and fatigue. All patients seeking care for PASC should be screened for these neuropsychiatric complications. Symptoms of worry, nervousness, subjective changes in mood, and cognition as well as behavioral avoidance are particularly important targets of clinical intervention.

Abstract Background Previous studies assessing the prevalence of COVID-19 sequelae in adults and children were performed in the absence of an agreed definition. We investigated prevalence of post-COVID-19 condition (PCC) (WHO definition), at 6- and 12-months follow-up, amongst previously hospitalised adults and children and assessed risk factors. Methods Prospective cohort study of children and adults with confirmed COVID-19 in Moscow, hospitalised between April and August, 2020. Two follow-up telephone interviews, using the International Severe Acute Respiratory and Emerging Infection Consortium survey, were performed at 6 and 12 months after discharge. Results One thousand thirteen of 2509 (40%) of adults and 360 of 849 (42%) of children discharged participated in both the 6- and 12-month follow-ups. PCC prevalence was 50% (95% CI 47–53) in adults and 20% (95% CI 16–24) in children at 6 months, with decline to 34% (95% CI 31–37) and 11% (95% CI 8–14), respectively, at 12 months. In adults, female sex was associated with PCC at 6- and 12-month follow-up (OR 2.04, 95% CI 1.57 to 2.65) and (OR 2.04, 1.54 to 2.69), respectively. Pre-existing hypertension (OR 1.42, 1.04 to 1.94) was associated with post-COVID-19 condition at 12 months. In children, neurological comorbidities were associated with PCC both at 6 months (OR 4.38, 1.36 to 15.67) and 12 months (OR 8.96, 2.55 to 34.82) while allergic respiratory diseases were associated at 12 months (OR 2.66, 1.04 to 6.47). Conclusions Although prevalence of PCC declined one year after discharge, one in three adults and one in ten children experienced ongoing sequelae. In adults, females and persons with pre-existing hypertension, and in children, persons with neurological comorbidities or allergic respiratory diseases are at higher risk of PCC.

Background : More than four years after the start of the COVID-19 pandemic, understanding of SARS-CoV-2 burden and post-acute sequela of COVID (PASC), or long COVID, continues to evolve. However, prevalence estimates are disparate and uncertain. Leveraging survey responses from a large serosurveillance study, we assess prevalence estimates using five different long COVID definitions among California residents. Methods : The California Department of Public Health (CDPH) conducted a cross-sectional survey that included questions about acute COVID-19 infection and recovery. A random selection of California households was invited to participate in a survey that included demographic information, clinical symptoms, and COVID-19 vaccination history. We assessed prevalence and predictors of long COVID among those previously testing positive for SARS-CoV-2 across different definitions using logistic regression. Findings : A total of 2883 participants were included in this analysis; the majority identified as female (62.5 %), and the median age was 39 years (interquartile range: 17–55 years). We found a significant difference in long COVID prevalence across definitions with the highest prevalence observed when participants were asked about incomplete recovery (20.9 %, 95 % confidence interval [CI]: 19.4–22.5) and the lowest prevalence was associated with severe long COVID affecting an estimated 4.9 % (95 % CI 4.1–5.7) of the participant population. Individuals that completed the primary vaccination series had significantly lower prevalence of long COVID compared to those that did not receive COVID vaccination. Interpretation : There were significant differences in the estimated prevalence of long COVID across different definitions. People who experience a severe initial COVID-19 infection should be considered at a higher probability for developing long COVID. Funding : Centers for Disease Control and Prevention - Epidemiology and Laboratory Capacity. • Analysis of responses from a randomized household survey across California finds significant differences in estimated prevalence of long COVID by different definitions. Severe initial COVID-19 infection was a strong predictor of long COVID while COVID-19 vaccination was found to be protective. [ABSTRACT FROM AUTHOR]