Herbal medicines for long COVID: A phase 2 pilot clinical study.

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.

Prevalence and determinant of long-term Post-COVID conditions among stroke survivors in the United States.

BACKGROUND: Persistent post-COVID conditions (PCCs) have become inevitable challenges for individuals who have survived COVID. The National Research Plan on Long COVID-19 underscores the priority of addressing post-COVID conditions (PCCs) within specific subgroups of the United States (US) population. This study aimed to investigate the prevalence and factors associated with PCCs among stroke survivors in the US. METHOD: In this retrospective cross-sectional study, we utilized the Behavioral Risk Factor Surveillance System (BRFSS) 2022 dataset. First, we identified respondents with a positive history of both COVID-19 and stroke. Subsequently, we categorized these respondents based on whether they experienced PCCs and conducted a comparative analysis of their characteristics. Additionally, our study included a comparison of our findings with those among individuals who have survived myocardial infarction (MI) and cancer. RESULTS: A total of 3999 stroke, 5406 MI, and 10551 cancer survivors were included. The estimated prevalence of PCCs among stroke survivors was 30.6 %, compared to 22.4 %, 29.2 %, and 24.6 % among non-stroke (p < 0.001), MI, and cancer survivors, respectively. Fatigue, dyspnea, and taste/smell loss were the most common primary symptoms. In multivariate regression analysis, female sex (adjusted odds ratio (aOR):1.62, 95 %CI:[1.17-2.24]), stroke-belt residence (aOR:1.67, 95 %CI: [1.13-2.46]), pulmonary disease (aOR:2.12, 95 %CI:[1.53-2.92]), and depression (aOR:1.55, 95 %CI: [1.1-2.2]) were independent factors associated with higher odds of PCCs among stroke survivors. Additionally, age above 64 years was associated with lower odds of PCCs (aOR:0.6, 95 %CI: [0.41-0.86]). CONCLUSION: Our study highlights a considerable prevalence of PCCs among stroke survivors, particularly among younger women and individuals with other chronic conditions.

Translation and cultural adaptation of the COVID-19 Yorkshire Rehabilitation Scale into German.

Background: Experts estimate that in up to 10% of the infected, SARS-CoV-2 would cause persistent symptoms, activity limitations and reduced quality of life. Referred to as long COVID, these conditions might, in the future, specifically impact German-speaking countries due to their higher rates of unvaccinated people compared to other Western countries. Accurate measurement of symptom burden and its consequences is needed to manage conditions such as long COVID, and several tools have been developed to do so. However, no patient-reported instrument existed in the German language at the time of writing. Objective: This study, therefore, aimed to develop a German version of the COVID-19 Yorkshire Rehabilitation Scale (C19-YRS). Methods: We conducted a translation and qualitative evaluation, including cultural adaptation, of the C19-YRS and assessed its face validity. After creating a preliminary version, 26 individuals (14 women [53%]) participated in cognitive interviews (January 2022 to March 2022). Using cognitive debriefing interviews, we ensured the content's comprehensibility. The matrix-framework method guided the qualitative data analysis. Results: Compared to the original English version, adaptations were necessary, resulting in changes to the introductory text, while the items for recording persistent symptoms were hardly changed. Conclusion: The German version of the C19-YRS is expected to support standardized long COVID care.

The Long Haul to Surgery: Long COVID Has Minimal Burden on Surgical Departments.

Many patients infected with the SARS-CoV-2 virus (COVID-19) continue to experience symptoms for weeks to years as sequelae of the initial infection, referred to as "Long COVID". Although many studies have described the incidence and symptomatology of Long COVID, there are little data reporting the potential burden of Long COVID on surgical departments. A previously constructed database of survey respondents who tested positive for COVID-19 was queried, identifying patients reporting experiencing symptoms consistent with Long COVID. Additional chart review determined whether respondents had a surgical or non-routine invasive procedure on or following the date of survey completion. Outcomes from surgeries on patients reporting Long COVID symptoms were compared to those from asymptomatic patients. A total of 17.4% of respondents had surgery or a non-routine invasive procedure in the study period. A total of 48.8% of these patients reported experiencing symptoms consistent with Long COVID. No statistically significant differences in surgical outcomes were found between groups. The results of this analysis demonstrate that Long COVID does not appear to have created a significant burden of surgical disease processes on the healthcare system despite the wide range of chronic symptoms and increased healthcare utilization by this population. This knowledge can help guide surgical operational resource allocation as a result of the pandemic and its longer-term sequelae.

Viral, Immunologic, and Laboratory Parameters in Patients With and Without Post-Acute Sequelae of SARS-CoV-2 Infection (PASC).

BACKGROUND: The pathophysiological mechanisms underlying the post-acute sequelae of severe acute respiratory syndrome coronavirus 2 infection (PASC) are not well understood. Our study aimed to investigate various aspects of theses mechanisms, including viral persistence, immunological responses, and laboratory parameters in patients with and without PASC. METHODS: We prospectively enrolled adults aged ≥ 18 years diagnosed with coronavirus disease 2019 (COVID-19) between August 2022 and July 2023. Blood samples were collected at three time-points: within one month of diagnosis (acute phase) and at 1 month, and 3 months post-diagnosis. Following a recent well-designed definition of PASC, PASC patients were defined as those with a questionnaire-based PASC score ≥ 12 persisting for at least 4 weeks after the initial COVID-19 diagnosis. RESULTS: Of 57 eligible COVID-19 patients, 29 (51%) had PASC, and 28 (49%) did not. The PASC group had significantly higher nucleocapsid protein (NP) antigenemia 3 months after COVID-19 diagnosis (P = 0.022). Furthermore, several cytokines, including IL-2, IL-17A, VEGF, RANTES, sCD40L, IP-10, I-TAC, and granzyme A, were markedly elevated in the PASC group 1 and/or 3 month(s) after COVID-19 diagnosis. In contrast, the median values of several serological markers, including thyroid markers, autoimmune indicators, and stress-related hormones, were within the normal range. CONCLUSION: Levels of NP antigen and of various cytokines involved in immune responses become significantly elevated over time after COVID-19 diagnosis in PASC patients compared to non-PASC patients. This suggests that PASC is associated with prolonged immune dysregulation resulting from heightened antigenic stimulation.

Mechanisms of long COVID and the path toward therapeutics.

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.

Sleep and long COVID: preexisting sleep issues and the risk of PASC in a large general population using 3 different model definitions.

STUDY OBJECTIVES: Insomnia, poor sleep quality and extremes of sleep duration are associated with COVID-19 infection. This study assessed whether these factors are related to Post-Acute Sequelae of SARS-CoV-2 infection (PASC). METHODS: Cross-sectional survey of a general population of 24,803 U.S. adults to determine the association of insomnia, poor sleep quality and sleep duration with PASC. Three definitions of PASC were used based on post COVID-19 clinical features: COPE (≥3), NICE (≥1), and RECOVER (scoring algorithm). RESULTS: Prevalence rates of PASC were 21.9%, 38.9%, 15.5% for COPE, NICE and RECOVER PASC definitions, respectively. PASC was associated with insomnia in all 3 models after full adjustment with odds ratios (aORs) and 95% confidence intervals (CI) ranging from 1.30 (95% CI: 1.11-1.52, p≤0.05, PASC Score) to 1.52 (95% CI: 1.34-1.71, p≤0.001, (NICE). Poor sleep quality was related to PASC in all models with aORs ranging from 1.77 (95% CI: 1.60-1.97, p≤0.001, NICE) to 2.00 (95% CI: 1.77-2.26, p≤0.001, COPE). Sleep <6 hours was associated with PASC with aORs between 1.59 (95% CI: 1.40-1.80, p≤0.001, PASC Score) to 1.70 (95% CI: 1.53-1.89, p≤0.001, COPE). Sleep ≥ 9 hours was not associated with PASC in any model. Although vaccination with COVID-19 booster decreased the likelihood of developing PASC, it did not attenuate associations between insomnia, poor sleep quality and short sleep duration with PASC in any of the models. CONCLUSIONS: Insomnia, poor sleep quality and short sleep duration are cross-sectionally associated with PASC and may be potential risk factors. Further longitudinal studies should be conducted.

The Omicron Variant Is Associated with a Reduced Risk of the Post COVID-19 Condition and Its Main Phenotypes Compared to the Wild-Type Virus: Results from the EuCARE-POSTCOVID-19 Study.

Post COVID-19 condition (PCC) is defined as ongoing symptoms at ≥1 month after acute COVID-19. We investigated the risk of PCC in an international cohort according to viral variants. We included 7699 hospitalized patients in six centers (January 2020-June 2023); a subset of participants with ≥1 visit over the year after clinical recovery were analyzed. Variants were observed or estimated using Global Data Science Initiative (GISAID) data. Because patients returning for a post COVID-19 visit may have a higher PCC risk, and because the variant could be associated with the probability of returning, we used weighted logistic regressions. We estimated the proportion of the effect of wild-type (WT) virus vs. Omicron on PCC, which was mediated by Intensive Care Unit (ICU) admission, through a mediation analysis. In total, 1317 patients returned for a post COVID visit at a median of 2.6 (IQR 1.84-3.97) months after clinical recovery. WT was present in 69.6% of participants, followed by the Alpha (14.4%), Delta (8.9%), Gamma (3.9%) and Omicron strains (3.3%). Among patients with PCC, the most common manifestations were fatigue (51.7%), brain fog (32.7%) and respiratory symptoms (37.2%). Omicron vs. WT was associated with a reduced risk of PCC and PCC clusters; conversely, we observed a higher risk with the Delta and Alpha variants vs. WT. In total, 42% of the WT effect vs. Omicron on PCC risk appeared to be mediated by ICU admission. A reduced PCC risk was observed after Omicron infection, suggesting a possible reduction in the PCC burden over time. A non-negligible proportion of the variant effect on PCC risk seems mediated by increased disease severity during the acute disease.

Post-acute COVID-19 outcomes including participant-reported long COVID: amubarvimab/romlusevimab versus placebo in the ACTIV-2 trial.

Background: It is unknown if early COVID-19 monoclonal antibody (mAb) therapy can reduce risk of Long COVID. The mAbs amubarvimab/romlusevimab were previously demonstrated to reduce risk of hospitalization/death by 79%. This study assessed the impact of amubarvimab/romlusevimab on late outcomes, including Long COVID. Methods: Non-hospitalized high-risk adults within 10 days of COVID-19 symptom onset enrolled in a randomized, double-blind, placebo-controlled phase 2/3 trial of amubarvimab/romlusevimab for COVID-19 treatment. Late symptoms, assessed using a participant-completed symptom diary, were a pre-specified exploratory endpoint. The primary outcome for this analysis was the composite of Long COVID by participant self-report (presence of COVID-19 symptoms as recorded in the diary at week 36) or hospitalization or death by week 36. Inverse probability weighting (IPW) was used to address incomplete outcome ascertainment, giving weighted risk ratios (wRR) comparing amubarvimab/romlusevimab to placebo. Findings: Participants received amubarvimab/romlusevimab (n = 390) or placebo (n = 390) between January and July 2021. Median age was 49 years, 52% were female, 18% Black/African American, 49% Hispanic/Latino, and 9% COVID-19-vaccinated at entry. At week 36, 103 (13%) had incomplete outcome ascertainment, and 66 (17%) on amubarvimab/romlusevimab and 92 (24%) on placebo met the primary outcome (wRR = 0.70, 95% confidence interval (CI) 0.53-0.93). The difference was driven by fewer hospitalizations/deaths with amubarvimab/romlusevimab (4%) than placebo (13%). Among 652 participants with available diary responses, 53 (16%) on amubarvimab/romlusevimab and 44 (14%) on placebo reported presence of Long COVID. Interpretation: Amubarvimab/romlusevimab treatment, while highly effective in preventing hospitalizations/deaths, did not reduce risk of Long COVID. Additional interventions are needed to prevent Long COVID. Funding: National Institute of Allergy and Infectious Diseases of the National Institutes of Health. Amubarvimab and romlusevimab supplied by Brii Biosciences.

Defining long COVID using a population-based SARS-CoV-2 survey in California.

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.

Prevalence and risk factors of post-acute sequelae of SARS-CoV-2 (PASC) among veterans in the airborne hazards and open burn pit registry: a prospective, observational, nested study.

BACKGROUND: Veterans have unique military risk factors and exposures during deployment that may augment their risk of post-acute sequelae of SARS-CoV-2 (PASC). The purpose of this study is to identify potential risk factors for PASC among Veterans in the national Airborne Hazards and Open Burn Pit Registry (AHOBPR). METHODS: This prospective observational study consisted of a semi-structured interview conducted via phone or videoconference from November 2021 to December 2022 among a stratified random sample of deployed Veterans nested within the national AHOBPR with laboratory-confirmed SARS-CoV-2 infection. PASC was defined as persistent new-onset symptoms lasting more than 2 months after initial SARS-CoV-2 infection. Deployment history, airborne hazards exposure and symptoms were obtained from the AHOBPR self-assessment questionnaire completed prior to SARS-CoV-2 infection (past). Post-infection symptoms and health behaviors obtained at study interview (present) were used to test the hypothesis that deployment experience and exposure increases the risk for PASC. RESULTS: From a sample of 212 Veterans, 149 (70%) met criteria for PASC with a mean age of 47 ± 8.7 years; 73 (49%) were women and 76 (51%) were men, and 129 (82.6%) continued to experience persistent symptoms of SARS-CoV-2 (596.8 ± 160.4 days since initial infection). Neither exposure to airborne hazards (OR 0.97, CI 0.92-1.03) or to burn pits (OR 1.00, CI 0.99-1.00) augmented risk for PASC. CONCLUSIONS: PASC is highly common among Veterans enrolled in the AHOBPR, but we did not observe any unique military risk factors (e.g., airborne hazards exposure) that augmented the risk of PASC. Our findings may provide guidance to clinicians in the VHA network to administer appropriate care for Veterans experiencing PASC.

Vaccine and antiviral drug promise for preventing post-acute sequelae of COVID-19, and their combination for its treatment.

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.

Clinical Features and Vaccination Effects among Children with Post-Acute Sequelae of COVID-19 in Taiwan.

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.

Lessons learnt from broad-spectrum coronavirus antiviral drug discovery.

INTRODUCTION: Highly pathogenic coronaviruses (CoVs), such as severe acute respiratory syndrome CoV (SARS-CoV), Middle East respiratory syndrome CoV (MERS-CoV), and the most recent SARS-CoV-2 responsible for the COVID-19 pandemic, pose significant threats to human populations over the past two decades. These CoVs have caused a broad spectrum of clinical manifestations ranging from asymptomatic to severe distress syndromes (ARDS), resulting in high morbidity and mortality. AREAS COVERED: The accelerated advancements in antiviral drug discovery, spurred by the COVID-19 pandemic, have shed new light on the imperative to develop treatments effective against a broad spectrum of CoVs. This perspective discusses strategies and lessons learnt in targeting viral non-structural proteins, structural proteins, drug repurposing, and combinational approaches for the development of antivirals against CoVs. EXPERT OPINION: Drawing lessons from the pandemic, it becomes evident that the absence of efficient broad-spectrum antiviral drugs increases the vulnerability of public health systems to the potential onslaught by highly pathogenic CoVs. The rapid and sustained spread of novel CoVs can have devastating consequences without effective and specifically targeted treatments. Prioritizing the effective development of broad-spectrum antivirals is imperative for bolstering the resilience of public health systems and mitigating the potential impact of future highly pathogenic CoVs.

Post-Acute Sequelae of SARS-CoV-2 Infection and Its Impact on Adolescents and Young Adults.

This review discusses the varying definitions for post-acute sequelae of SARS CoV-2 infection (PASC) in adolescents and young adults (AYAs), symptom profiles of AYAs with PASC, and assessment and management strategies when AYAs present with symptoms concerning for PASC. Additionally, it reviews the impact that PASC can have on AYAs and includes strategies for providers to support AYAs with PASC. Finally, it concludes with a discussion around equity in the care of AYAs with possible PASC.

Sleep and long COVID: Preexisting sleep issues and the risk of PASC in a large general population using 3 different model definitions.

Study Objectives: Insomnia, poor sleep quality and extremes of sleep duration are associated with COVID-19 infection. This study assessed whether these factors are related to Post-Acute Sequelae of SARS-CoV-2 infection (PASC). Methods: Cross-sectional survey of a general population of 24,803 U.S. adults to determine the association of insomnia, poor sleep quality and sleep duration with PASC. Results: Prevalence rates of PASC among previously COVID-19 infected participants for three definitions of PASC were COPE (21.9%), NICE (38.9%) and RECOVER PASC Score (15.3%). PASC was associated with insomnia in all 3 models in fully adjusted models with adjusted odds ratios (aORs) and 95% confidence intervals (CI) ranging from 1.30 (95% CI: 1.11-1.52, p≤0.05, PASC Score) to 1.52 (95% CI: 1.34-1.71, p≤0.001, (NICE). Poor sleep quality was related to PASC in all models with aORs ranging from 1.77 (95% CI: 1.60-1.97, p≤0.001, NICE) to 2.00 (95% CI: 1.77-2.26, p≤0.001, COPE). Sleep <6 hours was associated with PASC with aORs between 1.59 (95% CI: 1.40-1.80, p≤0.001, PASC Score) to 1.70 (95% CI: 1.53-1.89, p≤0.001, COPE). Sleep ≥ 9 hours was not associated with PASC in any model. Although vaccination with COVID-19 booster decreased the likelihood of developing PASC, it did not attenuate associations between insomnia, poor sleep quality and short sleep duration with PASC in any of the models. Conclusions: Insomnia, poor sleep quality and short sleep duration are potential risk factors for PASC. Interventions to improve sleep may decrease the development of PASC.

Cognitive functioning in patients with neuro-PASC: the role of fatigue, mood, and hospitalization status.

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

Long COVID management: a mini review of current recommendations and underutilized modalities.

Long COVID is a condition that develops in a subset of patients after COVID-19 infection comprising of symptoms of varying severity encompassing multiple organ systems. Currently, long COVID is without consensus on a formal definition, identifiable biomarkers, and validated treatment. Long COVID is expected to be a long-term chronic condition for a subset of patients and is associated with suffering and incapacity. There is an urgent need for clear management guidelines for the primary care provider, who is essential in bridging the gap with more specialized care to improve quality of life and functionality in their patients living with long COVID. The purpose of this mini review is to provide primary care providers with the latest highlights from existing literature regarding the most common long COVID symptoms and current management recommendations. This review also highlights the underutilized interventions of stellate ganglion blocks and low-dose naltrexone, both with well-established safety profiles demonstrated to improve quality of life and functionality for patients suffering with some symptoms of long COVID, and encourages prompt referral to interventional pain management.

Challenges and opportunities in long COVID research.

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.