Epigenetic reprograming in myalgic encephalomyelitis/chronic fatigue syndrome: A narrative of latent viruses.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic disease presenting with severe fatigue, post-exertional malaise, and cognitive disturbances-among a spectrum of symptoms-that collectively render the patient housebound or bedbound. Epigenetic studies in ME/CFS collectively confirm alterations and/or malfunctions in cellular and organismal physiology associated with immune responses, cellular metabolism, cell death and proliferation, and neuronal and endothelial cell function. The sudden onset of ME/CFS follows a major stress factor that, in approximately 70% of cases, involves viral infection, and ME/CFS symptoms overlap with those of long COVID. Viruses primarily linked to ME/CFS pathology are the symbiotic herpesviruses, which follow a bivalent latent-lytic lifecycle. The complex interaction between viruses and hosts involves strategies from both sides: immune evasion and persistence by the viruses, and immune activation and viral clearance by the host. This dynamic interaction is imperative for herpesviruses that facilitate their persistence through epigenetic regulation of their own and the host genome. In the current article, we provide an overview of the epigenetic signatures demonstrated in ME/CFS and focus on the potential strategies that latent viruses-particularly Epstein-Barr virus-may employ in long-term epigenetic reprograming in ME/CFS. Epigenetic studies could aid in elucidating relevant biological pathways impacted in ME/CFS and reflect the physiological variations among the patients that stem from environmental triggers, including exogenous viruses and/or altered viral activity.

Inclusion body myositis, viral infections, and TDP-43: a narrative review.

The ubiquitous RNA-processing molecule TDP-43 is involved in neuromuscular diseases such as inclusion body myositis, a late-onset acquired inflammatory myopathy. TDP-43 solubility and function are disrupted in certain viral infections. Certain viruses, high viremia, co-infections, reactivation of latent viruses, and post-acute expansion of cytotoxic T cells may all contribute to inclusion body myositis, mainly in an age-shaped immune landscape. The virally induced senescent, interferon gamma-producing cytotoxic CD8+ T cells with increased inflammatory, and cytotoxic features are involved in the occurrence of inclusion body myositis in most such cases, in a genetically predisposed host. We discuss the putative mechanisms linking inclusion body myositis, TDP-43, and viral infections untangling the links between viruses, interferon, and neuromuscular degeneration could shed a light on the pathogenesis of the inclusion body myositis and other TDP-43-related neuromuscular diseases, with possible therapeutic implications.

COVID-19 and Its Sequelae Masquerading as Gastrointestinal Ailments: A Report of Gastroesophageal Reflux Disease (GERD) and Review of Recent Cases.

Coronavirus disease 2019 (COVID-19) predominantly causes respiratory symptoms. However, a rare segment of patients recovering from COVID-19 may develop gastrointestinal (GI) symptoms. We describe a case of a female who presented with symptoms suggestive of refractory gastroesophageal reflux disease (GERD) for 18 months following COVID-19 infection. Her symptoms included epigastric and chest pain, coughing, and vomiting. Upper endoscopy and 24-hour pH monitoring were negative. Following hospital admission due to worsening symptoms, she was diagnosed with chronic pulmonary embolism (PE) presumed to be related to COVID-19. Her reflux symptoms resolved within two days of the initiation of anticoagulation. Our findings suggest that chronic PE should be considered in patients presenting with GERD refractory to treatment following COVID-19 infection. Generally, as COVID-19 and its sequelae may masquerade as GI conditions, they should be on the differential diagnosis, especially in the post-pandemic era when routine testing has significantly declined.

Characterization of Post-COVID-19 Definitions and Clinical Coding Practices: Longitudinal Study.

BACKGROUND: Post-COVID-19 condition (colloquially known as "long COVID-19") characterized as postacute sequelae of SARS-CoV-2 has no universal clinical case definition. Recent efforts have focused on understanding long COVID-19 symptoms, and electronic health record (EHR) data provide a unique resource for understanding this condition. The introduction of the International Classification of Diseases, Tenth Revision (ICD-10) code U09.9 for "Post COVID-19 condition, unspecified" to identify patients with long COVID-19 has provided a method of evaluating this condition in EHRs; however, the accuracy of this code is unclear. OBJECTIVE: This study aimed to characterize the utility and accuracy of the U09.9 code across 3 health care systems-the Veterans Health Administration, the Beth Israel Deaconess Medical Center, and the University of Pittsburgh Medical Center-against patients identified with long COVID-19 via a chart review by operationalizing the World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) definitions. METHODS: Patients who were COVID-19 positive with either a U07.1 ICD-10 code or positive polymerase chain reaction test within these health care systems were identified for chart review. Among this cohort, we sampled patients based on two approaches: (1) with a U09.9 code and (2) without a U09.9 code but with a new onset long COVID-19-related ICD-10 code, which allows us to assess the sensitivity of the U09.9 code. To operationalize the long COVID-19 definition based on health agency guidelines, symptoms were grouped into a "core" cluster of 11 commonly reported symptoms among patients with long COVID-19 and an extended cluster that captured all other symptoms by disease domain. Patients having ≥2 symptoms persisting for ≥60 days that were new onset after their COVID-19 infection, with ≥1 symptom in the core cluster, were labeled as having long COVID-19 per chart review. The code's performance was compared across 3 health care systems and across different time periods of the pandemic. RESULTS: Overall, 900 patient charts were reviewed across 3 health care systems. The prevalence of long COVID-19 among the cohort with the U09.9 ICD-10 code based on the operationalized WHO definition was between 23.2% and 62.4% across these health care systems. We also evaluated a less stringent version of the WHO definition and the CDC definition and observed an increase in the prevalence of long COVID-19 at all 3 health care systems. CONCLUSIONS: This is one of the first studies to evaluate the U09.9 code against a clinical case definition for long COVID-19, as well as the first to apply this definition to EHR data using a chart review approach on a nationwide cohort across multiple health care systems. This chart review approach can be implemented at other EHR systems to further evaluate the utility and performance of the U09.9 code.

Management of cognitive impairment associated with post-COVID-19 syndrome: recommendations for primary care.

Introduction: Although post-COVID-19 syndrome (PCS) with cognitive impairment is increasingly encountered in primary care, evidence-based recommendations for its appropriate management are lacking. Methods: A systematic literature search evaluating the diagnosis and treatment of cognitive impairment associated with PCS was conducted. Practical recommendations for the management of PCS-associated cognitive impairment in primary care are summarized, based on an evaluation of pharmacological plausibility and clinical applications. Results: Currently, the pathology of cognitive impairment associated with PCS remains unclear with no high-quality data to support targeted interventions. Existing treatment approaches are directed towards symptom relief where counseling on the chronicity of the disease and regular reassessments at 4- to 8-week intervals is considered reasonable. Patients should be informed and encouraged to adopt a healthy lifestyle that centers around balanced nutrition and appropriate physical activities. They may also benefit from the intake of vitamins, micronutrients, and probiotics. The administration of Ginkgo biloba extract could offer a safe and potentially beneficial treatment option. Other non-pharmacological measures include physiotherapy, digitally supported cognitive training, and, if indicated, ergotherapy or speech therapy. In most patients, symptoms improve within 8 weeks. If serious, ambiguous, or when new symptoms occur, specialized diagnostic measures such as comprehensive neurocognitive testing or neuroimaging should be initiated. Very few patients would require inpatient rehabilitation. Conclusion: PCS with cognitive impairment is a debilitating condition that could affect daily functioning and reduce work productivity. Management in primary care should adopt a multidisciplinary approach, centering around physical, cognitive, and pharmacological therapies.

Nonlinear EEG Analysis During Motor and Cognitive Tasks in Patients With Long COVID: A Dynamic Systems Approach.

Introduction. Nonlinear EEG provides information about dynamic properties of the brain. This study aimed to compare nonlinear EEG parameters estimated from patients with Long COVID in different cognitive and motor tasks. Materials and Methods. This 12-month prospective cohort study included 83 patients with Long COVID: 53 symptomatic and 30 asymptomatic. Brain electrical activity was evaluated by EEG in 4 situations: (1) at rest, (2) during the Trail Making Test Part A (TMT-A), (3) during the TMT Part B (TMT-B), and (4) during a coordination task: the Box and Blocks Test (BBT). Nonlinear EEG parameters were estimated in the time domain (activity and complexity). Assessments were made at 0 to 3, 3 to 6, and 6 to 12 months after inclusion. Results. There was a decrease in activity and complexity during the TMT-A and TMT-B, and an increase of these parameters during the BBT in both groups. There was an increase in activity at rest and during the TMT-A in the COVID-19 group at 0 to 3 months compared to the control, an increase in activity in the TMT-B in the COVID-19 group at 3 to 6 months compared to the control, and reduced activity and complexity at rest and during the TMT-A at 6 to 12 months compared to the control. Conclusion. The tasks followed a pattern of increased activity and complexity in cognitive tasks, which decreased during the coordination task. It was also observed that an increase in activity at rest and during cognitive tasks in the early stages, and reduced activity and complexity at rest and during cognitive tasks in the late phases of Long COVID.

Impact of long COVID on health-related quality-of-life: an OpenSAFELY population cohort study using patient-reported outcome measures (OpenPROMPT).

Background: Long COVID is a major problem affecting patient health, the health service, and the workforce. To optimise the design of future interventions against COVID-19, and to better plan and allocate health resources, it is critical to quantify the health and economic burden of this novel condition. We aimed to evaluate and estimate the differences in health impacts of long COVID across sociodemographic categories and quantify this in Quality-Adjusted Life-Years (QALYs), widely used measures across health systems. Methods: With the approval of NHS England, we utilised OpenPROMPT, a UK cohort study measuring the impact of long COVID on health-related quality-of-life (HRQoL). OpenPROMPT invited responses to Patient Reported Outcome Measures (PROMs) using a smartphone application and recruited between November 2022 and October 2023. We used the validated EuroQol EQ-5D questionnaire with the UK Value Set to develop disutility scores (1-utility) for respondents with and without Long COVID using linear mixed models, and we calculated subsequent Quality-Adjusted Life-Months (QALMs) for long COVID. Findings: The total OpenPROMPT cohort consisted of 7575 individuals who consented to data collection, with which we used data from 6070 participants who completed a baseline research questionnaire where 24.6% self-reported long COVID. In multivariable regressions, long COVID had a consistent impact on HRQoL, showing a higher likelihood or odds of reporting loss in quality-of-life (Odds Ratio (OR): 4.7, 95% CI: 3.72-5.93) compared with people who did not report long COVID. Reporting a disability was the largest predictor of losses of HRQoL (OR: 17.7, 95% CI: 10.37-30.33) across survey responses. Self-reported long COVID was associated with an 0.37 QALM loss. Interpretation: We found substantial impacts on quality-of-life due to long COVID, representing a major burden on patients and the health service. We highlight the need for continued support and research for long COVID, as HRQoL scores compared unfavourably to patients with conditions such as multiple sclerosis, heart failure, and renal disease. Funding: This research was supported by the National Institute for Health and Care Research (NIHR) (OpenPROMPT: COV-LT2-0073).

Proposal to apply a "Positive Emotion, Engagement, Relationships, Meaning, and Accomplishment (PERMA)" based approach to manage the COVID-19-related mental health problems in the era of long COVID.

Long COVID (LC)-related health problems are highly concerned. Many patients seem to have "recovered" from an acute SARS-CoV-2 infection, however, they might experience various symptoms, almost involving all organs and systems. Of those, neuropsychiatric symptoms like depression, anxiety, and post-traumatic stress disorder (PTSD) are not rare. These problems significantly impact the quality of life (QOL) of patients, family, and caregivers, even lead a tragic suicide outcome. Other than the conventional psychological and medical approaches, here, we proposal a positive emotion, engagement, relationships, meaning, and accomplishment (PERMA)-based approach to fight against these COVID-19-related mental health problems (CRMHPs). This approach is characterized by positive psychological interventions and self-achievements, which has been proved to be a powerful tool against mood disorders in common people. Nowadays, abolishment of certain prophylactic measures (such as isolation, lockdown, compulsorily wearing a mask and maintaining social distance, measures to avoid crowding) enables us to have more opportunities to contact patients and implement the PERMA-based approach to the patients with CRMHPs. We believe that application of PERMA-based approach is conducive to alleviate the influence of the CRMHPs and improve their QOL.

Sinus Tachycardia Following COVID-19 and Its Implications.

Background Within the cardiovascular system, sinus tachycardia has been a noted finding in patients with post-COVID-19 syndrome (symptoms persisting beyond 12 weeks post-infection). To better understand post-COVID-19 tachycardia, we examined the prevalence of sinus tachycardia 12-16 weeks after diagnosis of SARS-COV-2 infection and its correlation with intensive care utilization, ventilator use, and mortality in vaccinated and unvaccinated patients. Methods We identified adult patients in the TriNetX COVID-19 Research Network with confirmed SARS-COV-2 diagnosis from January 20th, 2020, to February 14th, 2022, and sinus tachycardia 12-16 weeks after diagnosis. Two cohorts were created: patients who developed tachycardia 12 weeks after initial diagnosis and patients without tachycardia. The tachycardia cohort was divided further based on vaccination status. Results Of 1,363,907 patients included, 30,705 (2.2%) developed tachycardia. The patients with tachycardia had more comorbidities. Using propensity score matching (PSM), two cohorts of 30,702 were created. The SARS-COV-2 tachycardic cohort had higher mortality (5.1% vs 2.1%, p<0.001), critical care utilization (5.8% vs 2.2%, p<0.001), and ventilator use (1.8% vs 0.5%, p<0.001). Out of 22,878 patients with persistent tachycardia and recorded vaccination status, 14,840 (65%) were not vaccinated. Mortality (5.9% vs 2.3%, p<0.001), critical care utilization (8.3% vs 3.6%, p<0.001), and ventilator use (3.8% vs 0.6%, p<0.001) were higher in the non-vaccinated patients compared with the vaccinated patients after PSM.  Conclusion The prevalence of persistent tachycardia after SARS-COV-2 infection is notable at 2.2%. Patients with persistent tachycardia have higher mortality rates and demonstrate greater healthcare utilization at one year compared to patients without persistent tachycardia, particularly if unvaccinated.

Favorable Antiviral Effect of Metformin on Severe Acute Respiratory Syndrome Coronavirus 2 Viral Load in a Randomized, Placebo-Controlled Clinical Trial of Coronavirus Disease 2019.

BACKGROUND: Metformin has antiviral activity against RNA viruses including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The mechanism appears to be suppression of protein translation via targeting the host mechanistic target of rapamycin pathway. In the COVID-OUT randomized trial for outpatient coronavirus disease 2019 (COVID-19), metformin reduced the odds of hospitalizations/death through 28 days by 58%, of emergency department visits/hospitalizations/death through 14 days by 42%, and of long COVID through 10 months by 42%. METHODS: COVID-OUT was a 2 × 3 randomized, placebo-controlled, double-blind trial that assessed metformin, fluvoxamine, and ivermectin; 999 participants self-collected anterior nasal swabs on day 1 (n = 945), day 5 (n = 871), and day 10 (n = 775). Viral load was quantified using reverse-transcription quantitative polymerase chain reaction. RESULTS: The mean SARS-CoV-2 viral load was reduced 3.6-fold with metformin relative to placebo (-0.56 log10 copies/mL; 95% confidence interval [CI], -1.05 to -.06; P = .027). Those who received metformin were less likely to have a detectable viral load than placebo at day 5 or day 10 (odds ratio [OR], 0.72; 95% CI, .55 to .94). Viral rebound, defined as a higher viral load at day 10 than day 5, was less frequent with metformin (3.28%) than placebo (5.95%; OR, 0.68; 95% CI, .36 to 1.29). The metformin effect was consistent across subgroups and increased over time. Neither ivermectin nor fluvoxamine showed effect over placebo. CONCLUSIONS: In this randomized, placebo-controlled trial of outpatient treatment of SARS-CoV-2, metformin significantly reduced SARS-CoV-2 viral load, which may explain the clinical benefits in this trial. Metformin is pleiotropic with other actions that are relevant to COVID-19 pathophysiology. CLINICAL TRIALS REGISTRATION: NCT04510194.

Characteristics of brain lesions found using MRI imaging in patients with post-COVID with signs of cognitive decline.

OBJECTIVE: Aim: To describe and evaluate abnormalities of the brain in post-COVID patients with neurologic symptoms and cognitive deficits using MRI imaging of the brain. PATIENTS AND METHODS: Materials and Methods: We included 21 patients with a previous positive PCR testing for SARS-CoV-2 and one or more of the following symptoms: memory and cognitive decline, dizziness, anxiety, depression, chronic headaches. All patients had MRI imaging done at onset of symptoms, but after at least 1 year after positive testing for COVID-19 based on the patient's previous medical history. RESULTS: Results: All of the patients complained of lack of concentration, forgetfulness, hard to process information. 15 patients suffered from confusion, 10 from anxiety. Of the 21 patients 14 had isolated chronic headaches, 3 had isolated dizziness, 4 patients had both symptoms upon inclusion. All patients underwent MRI imaging as a part of the diagnostic workup and had varying degrees of neurodegeneration. CONCLUSION: Conclusions: Our data correlates with existing research and shows tendency for cognitive decline in post-COVID patients. This provides groundwork for further research to determine correlation between acceleration of neurodegeneration and post-COVID.

Pathology of COVID-19 Lung Disease.

The pathology of severe COVID-19 lung injury is predominantly diffuse alveolar damage, with other reported patterns including acute fibrinous organizing pneumonia, organizing pneumonia, and bronchiolitis. Lung injury was caused by primary viral injury, exaggerated immune responses, and superinfection with bacteria and fungi. Although fatality rates have decreased from the early phases of the pandemic, persistent pulmonary dysfunction occurs and its pathogenesis remains to be fully elucidated.

Chronic Chest CT Findings following COVID-19 pneumonia.

Respiratory symptoms are a frequent manifestation of patients with post-acute sequela of SARS-CoV-2 (PASC), also known as long-COVID. Many cohorts of predominantly hospitalized patients have shown that a significant subset may have persistent chest CT findings for more than 12 months after the acute infection. Proper understanding of the evolving long-term imaging findings and terminology is crucial for accurate imaging interpretation and patient care. The goal of this article is to review the chronic chest CT findings of patients with PASC and common pitfalls.

Post-Covid-19 condition (Long Covid) in children and young people 12 months after infection or reinfection with the Omicron variant: a prospective observational study.

Our previous study in children and young people (CYP) at 3- and 6-months post-infection showed that 12-16% of those infected with the Omicron (B.1.1.529) variant of SARS-CoV-2 met the research definition of Long Covid, with no differences between first-positive and reinfected CYP. The primary objective of the current study is to explore the impact of the Omicron variant of SARS-CoV-2 infection on young people 12 months post infection. 345 CYP aged 11-17 years with a first laboratory-confirmed infection with the Omicron variant and 360 CYP reinfected with the Omicron variant completed an online questionnaire assessing demographics, symptoms, and their impact shortly after testing and again at 3-, 6-and 12-months post-testing. Vaccination status was determined from information held at UKHSA. Comparisons between groups were made using chi-squared, Mann-Whitney U, and Kruskal-Wallis tests. The most common symptoms in first-positive and reinfected CYP 12-months post-testing were tiredness (35.7 and 33.6% respectively) and sleeping difficulties (27.5 and 28.3% respectively). Symptom profiles, severity and impact were similar in the two infection status groups. Overall, by 12-months, 17.4% of first-positives and 21.9% of reinfected CYP fulfilled the research consensus Long Covid definition (p = 0.13). 12-months post Omicron infection, there is little difference between first-positive and reinfected CYP with respect to symptom profiles and impact. Clinicians may not therefore need to consider number of infections and type of variant when developing treatment plans. Further studies are needed to assess causality of reported symptoms up to 12-months after SARS-CoV-2 infection.

Clinical effectiveness of nirmatrelvir plus ritonavir on the short- and long-term outcome in high-risk children with COVID-19.

This study investigated the clinical effectiveness of nirmatrelvir plus ritonavir (NMV-r) on short-term outcome and the risk of postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) among pediatric patients with coronavirus disease 2019 (COVID-19). This retrospective cohort study used the TriNetX research network to identify pediatric patients between 12 and 18 years with COVID-19 between January 1, 2022 and August 31, 2023. The propensity score matching (PSM) method was used to match patients receiving NMV-r (NMV-r group) with those who did not receive NMV-r (control group). Two cohorts comprising 633 patients each (NMV-r and control groups), with balanced baseline characteristics, were identified using the PSM method. During the initial 30 days, the NMV-r group showed a lower incidence of all-cause hospitalization, mortality, or ED visits (hazard ratio [HR] = 0.546, 95% confidence interval [CI]: 0.372-0.799, p = 0.002). Additionally, the NMV-r group had a significantly lower risk of all-cause hospitalization compared with the control group (HR = 0.463, 95% CI: 0.269-0.798), with no deaths occurring in either group. In the 30-180-day follow-up period, the NMV-r group exhibited a non-significantly lower incidence of post-acute sequelae of SARS-CoV-2 infection (PASC), encompassing symptoms such as fatigue, cardiopulmonary symptoms, pain, cognitive impairments, headache, dizziness, sleep disorders, anxiety, and depression, compared to the control group. This study underscores the potential effectiveness of NMV-r in treating high-risk pediatric patients with COVID-19, demonstrating significant reductions in short-term adverse outcomes such as emergency department visits, hospitalization, or mortality within the initial 30-day period. Additionally, NMV-r shows promise in potentially preventing the development of PASC.

Determination of COVID-19 Late Disorders as Possible Long-COVID and/or Vaccination Consequences.

In this era in which the vast majority of the global population have developed COVID-19 infection and/or got vaccinated against it, identification of the late disorders as the vaccines' side effect or long-COVID manifestation seems essential. This study included the vaccinated individuals of 4 different vaccine regimens including inactivated virus-based, subunit protein, and adenovirus-based vaccines in a follow-up schedule 6-month post the booster shot. All the documented vaccine adverse events were thoroughly assessed considering the cases' medical history by Adverse Events Committee of Pasteur Institute of Iran. Totally 329 individuals who got 3 doses of vaccination were followed 6 months after the booster shots among whom 41 (12.4%) cases with the mean age of 40.9 ± 10.48 years had a type of disorder. Gynecological and osteoarticular involvements were the most common recorded disorders of which 73.1% were possibly linked to vaccination outcomes and the rest were affected by both long-COVID-19 and vaccination. Notably, the average time of symptoms persistence was 155 ± 10.4 days. This study has the advantage of long-term follow-up which presents various forms of late events in each episode of COVID-19 infection and vaccination. About 26.8% of people with persistent complications suffered from both long-COVOD/ vaccination in whom the differentiation between the vaccine side effect and long-COVID manifestation was quite challenging. Long-term follow-up studies in large population seems essential to outline the role of long-COVID and vaccination regarding persistent complications.

Association between Physical Activity Amount and Cardiorespiratory Fitness, Sleep Quality, and Health-related Quality of Life in Patients with Long COVID: A Cross-Sectional Study.

OBJECTIVE: To investigate the association between physical activity (PA) amount and gender differences on cardiorespiratory fitness (CRF), sleep quality, and health-related quality of life (HRQoL) in individuals with long COVID. DESIGN: Cross-sectional study. SETTING: An integrated outpatient clinic for post-COVID-19 at a medical center. PARTICIPANTS: Convenience sample of patients (N=264) diagnosed with long COVID. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: PA amounts, sleep quality, and HRQoL were measured by the International Physical Activity Questionnaire, Pittsburgh Sleep Quality Index, and the World Health Organization Questionnaire on Quality of Life: Short Form, respectively. CRF was evaluated through graded exercise testing. RESULTS: The participants had a mean age of 42.5±13.5 years and a mean duration of post-COVID-19 symptoms of 12.7±6.8 weeks. More than half (n=149, 56.5%) were female patients. Female participants had significantly lower CRF compared to male participants (P<.05). Older age and higher body mass index were associated with worse CRF and HRQoL (P<.05). Less sitting behavior and greater amounts of vigorous-intensity physical activity (VPA) or total PA were associated with better CRF (P<.05). In addition, greater total PA and moderate-intensity physical activity (MPA) were associated with better sleep quality and HRQoL (P<.05), respectively. CONCLUSIONS: Gender differences were found in CRF among patients with long COVID. Greater self-reported VPA or total PA was associated with better CRF, while greater total PA and MPA were associated with better sleep quality and HRQoL, respectively, in patients with long COVID. Further research is needed to explore these associations in longitudinal studies.

Biosound Therapy as a treatment for long COVID patients: A pre-post pilot study.

BACKGROUND: 43 % of people who are diagnosed with COVID-19 will experience persistent symptoms, also known as "long COVID," which lasts past the recovery of the acute infection. Long COVID symptoms overlap with symptoms that the Biosound Therapy System (BTS) has been shown to improve. The BTS is a multimodal treatment that includes biofeedback, vibroacoustic therapy synchronized with music that plays binaural beats, and video content. This study aimed to determine feasibility for a future full-scale Randomized Controlled Trial (RCT) and explore the impact of the BTS on long COVID symptoms. METHODS: This pre-post pilot study was conducted in an outpatient mental health clinic. Adults aged 20-65 years old with persistent COVID-19 symptoms were screened and randomly assigned to the intervention or control group. The intervention group was given 8 Biosound Therapy sessions during a period of 4 weeks. All participants were assessed at baseline and at post-intervention using the Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder 7-item scale (GAD-7), Cambridge Brain Sciences (CBS) tasks, and the COVID-19 Persistent Symptom Questionnaire. The feasibility outcomes were recruitment rates, retention rates, and open-ended questions about participants' experiences. RESULTS: 15 participants enrolled in the study and 13 completed the study (9 intervention, 4 control). Trial recruitment ended prematurely due to the emergence of the Omicron variant of COVID-19. Participants responded to open-ended questions with only positive remarks and made no comments on the study not being feasible. A Wilcoxon signed-rank test indicated that compared to baseline, participants in the intervention group had significant improvement in their GAD-7 score, PHQ9 score, 2 Cambridge Brain Science tasks ("Odd" and "Double Trouble"), fatigue, and difficulties in concentrating or remembering (p < 0.05; 95 % CI). CONCLUSION: The intervention group showed promising improvement without reported side effects. A full-scale RCT is feasible as long as the recruitment setting is changed to a location that allows access to more patients with long COVID. Results were limited due to the small sample size; therefore, a full-scale trial is needed.

Long-term symptoms after SARS-CoV-2 infection in a cohort of people living with HIV.

BACKGROUND: Our Hospital in Northern Italy assists 3817 people living with HIV (PLWH) and has faced the impact of COVID-19. Little is known about the impact of HIV infection on the risk of post-COVID-19 conditions (PCCs) onset. We aim to assess the incidence of PCC in PLWH and the factors associated with its occurrence. METHODS: We performed a retrospective, observational study including all PLWH > 18 years registered in the Brescia Health Protection Agency database, assessing SARS-CoV-2 burden, vaccination status, socio-demographic, and viro-immunological parameters from February 2020 until May 2022. Persistence of self-reported symptoms (clustered into gastrointestinal, respiratory, osteo-muscular, and neuro-behavioral symptoms) was evaluated after 3 months by a telephone-administered questionnaire. We estimated the associations between all variables and outcomes through univariate and multivariable logistic models. RESULTS: In the study period, 653 PLWH were diagnosed with SARS-CoV-2 infection (17.1%). We observed 19 (2.9%) reinfections, 71 (10.9%) hospitalizations, and 3 (0.5%) deaths. We interviewed 510/653 PLWH (78%), and 178 (PCCs prevalence 34.9%; CI 95% 30.7-39.2) reported persistent symptoms. Asthenia/fatigue was the most reported symptom (60/178), followed by muscular pain (54/178). In the multivariate regression model, there was a lower risk of PCCs in males respect to females (adjusted OR = 0.64; CI 95% 0.99-3.66), while hospitalization during acute infection was associated with an increased the risk of PCCs (adjusted OR = 1.9; CI 95% 0.99-3.66). Notably, no viro-immunological variable modified the PCCs risk onset. CONCLUSIONS: Our study highlights a substantial prevalence of PCCs among PLWH, three months post-SARS-CoV-2 infection, independent of viro-immunological features or vaccination status.