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To understand the roles of acute-phase viral dynamics and host immune responses in post-acute sequelae of SARS-CoV-2 infection (PASC), we enrolled 136 participants within 5 days of their first positive SARS-CoV-2 real-time PCR test. Participants self-collected up to 21 nasal specimens within the first 28 days post-symptom onset; interviewer-administered questionnaires and blood samples were collected at enrollment, days 9, 14, 21, 28, and month 4 and 8 post-symptom onset. Defining PASC as the presence of any COVID-associated symptom at their 4-month visit, we compared viral markers (quantity and duration of nasal viral RNA load, infectious viral load, and plasma N-antigen level) and host immune markers (IL-6, IL-10, TNF-α, IFN-α, IFN-γ, MCP, IP-10, and Spike IgG) over the acute period. Compared to those who fully recovered, those reporting PASC demonstrated significantly higher maximum levels of SARS-CoV-2 RNA and N-antigen, burden of RNA and infectious viral shedding, and lower Spike-specific IgG levels within 9 days post-illness onset. No significant differences were identified among a panel of host immune markers. Our results suggest early viral dynamics and the associated host immune responses play a role in the pathogenesis of PASC, highlighting the importance of understanding early biological markers in the natural history of PASC.

Acute COVID-19 infection can be followed by diverse clinical manifestations referred to as Post Acute Sequelae of SARS-CoV2 Infection (PASC). Studies have shown an increased risk of being diagnosed with new-onset psychiatric disease following a diagnosis of acute COVID-19. However, it was unclear whether non-psychiatric PASC-associated manifestations (PASC-AMs) are associated with an increased risk of new-onset psychiatric disease following COVID-19. A retrospective electronic health record (EHR) cohort study of 2,391,006 individuals with acute COVID-19 was performed to evaluate whether non-psychiatric PASC-AMs are associated with new-onset psychiatric disease. Data were obtained from the National COVID Cohort Collaborative (N3C), which has EHR data from 76 clinical organizations. EHR codes were mapped to 151 non-psychiatric PASC-AMs recorded 28-120 days following SARS-CoV-2 diagnosis and before diagnosis of new-onset psychiatric disease. Association of newly diagnosed psychiatric disease with age, sex, race, pre-existing comorbidities, and PASC-AMs in seven categories was assessed by logistic regression. There were significant associations between a diagnosis of any psychiatric disease and five categories of PASC-AMs with odds ratios highest for neurological, cardiovascular, and constitutional PASC-AMs with odds ratios of 1.31, 1.29, and 1.23 respectively. Secondary analysis revealed that the proportions of 50 individual clinical features significantly differed between patients diagnosed with different psychiatric diseases. Our study provides evidence for association between non-psychiatric PASC-AMs and the incidence of newly diagnosed psychiatric disease. Significant associations were found for features related to multiple organ systems. This information could prove useful in understanding risk stratification for new-onset psychiatric disease following COVID-19. Prospective studies are needed to corroborate these findings.

BACKGROUND: The economic and health burden of COVID-19 has transformed the healthcare system in the US. Hospitals have adapted to the heterogeneity in long COVID symptoms, and the sheer number of people affected by this condition, by building long COVID centers and programs. OBJECTIVE: We sought to describe characteristics, services, and clinical trials of long COVID centers at top US hospitals. DESIGN: Cross-sectional analysis. PARTICIPANTS: Long COVID treatment programs or centers at top US hospitals. EXPOSURES: Frequency of long COVID centers, eligibility for being treated, the services they provide, specialist to whom the patients may be referred, and the long COVID clinical trials in which these hospitals participate. FINDINGS: Most top hospitals in the US (n = 43/50; 86%) offer long COVID services. 65% (28/43) did not describe the services provided. 12 (28%) required a referral from a primary care physician. The most common services were meeting with a team member (n = 20; 47%), ordering lab and/or radiology services (n = 8; 18.6%), and administering a physical exam (n = 7; 16%). 7 (16%) centers/programs treated only adults; 5 (12%) treated both adults and children, and 31 (72%) did not specify. The most common specialists described were psychology (n = 25; 58%), neurology (n = 25; 58%), and pulmonary (n = 24; 56%). Sixty-three trials (of 134 long COVID clinical trials) had at least one top hospital listed as a study site. The median number of clinical trials that each hospital sponsored or was a study site was 2 (interquartile range: 1, 3). CONCLUSIONS AND RELEVANCE: We find that services offered at long COVID clinics at top hospitals in the US often include meeting with a team member and referrals to a wide range of specialists. The diversity in long COVID services offered parallels the diversity in long COVID symptoms, suggesting a need for better consensus in developing and delivering treatment.

Long COVID, or post-acute sequelae of COVID-19 (PASC), represents a complex condition with persistent symptoms following SARS-Cov-2 infection. The symptoms include fatigue, dyspnoea, cognitive impairment, decreased quality of life in variable levels of severity. Potential mechanisms behind long COVID include vascular damage, immune dysregulation and viral persistence. Diagnosing long COVID involves medical evaluation by multidisciplinary team and assessment of persistent symptoms with scoring systems in development. Treatment strategies are symptom-focused, encompassing multidisciplinary care, rehabilitation and tailored exercise programmes. Pulmonary rehabilitation, an effective and critical component of long COVID management, has shown promise, particularly for patients with respiratory symptoms such as dyspnoea. These programmes, which combine exercise, breathing techniques, education and psychological support, improve symptoms, quality of life and overall recovery. Innovative technologies, such as telemedicine, wearable devices, telerehabilitation, are transforming long COVID management. Telemedicine facilitates consultations and interventions, eliminating healthcare access barriers. Wearable devices enable remote and continuous monitoring of patients during their rehabilitation activities. Telerehabilitation has proven to be safe and feasible and to have high potential for COVID-19 recovery. This review provides a concise overview of long COVID, encompassing its definition, prevalence, mechanisms, clinical manifestations, diagnosis and management approaches. It emphasizes the significance of multidisciplinary approach in diagnosis and treatment of long COVID, with focus on pulmonary rehabilitation and innovative technology advances to effectively address the management of long COVID.

The risk of developing medium- and long-term sequelae after recovery from COVID-19 is validated. Long-COVID burden represents a major health care issue, thus paving the way to effective prevention and/or treatment measures. Physical activity prevents many human pathologies, including COVID-19. Being physically active before and immediately after a severe acute respiratory syndrome coronavirus 2 infection substantially lowers the risk of developing long-COVID. In addition, long-COVID is an important cause of physical inactivity. Physically inactive individuals are at increased risk of developing long-COVID, while patients with long-COVID are more likely to reduce their physical activity levels after recovering from the acute infection, with the risk of generating a continuous loop. This harmful interaction needs to be recognized by public health institutions, and the adoption of physical activity as a routine clinical practice in all individuals after a severe acute respiratory syndrome coronavirus 2 infection needs to be proactively promoted. [ABSTRACT FROM AUTHOR]