BACKGROUND: Postacute sequelae of COVID-19 (PASC) remain understudied in nonhospitalized patients. Digital wearables allow for a continuous collection of physiological parameters such as respiratory rate and oxygen saturation that have been predictive of disease trajectories in hospitalized patients.
OBJECTIVE: This protocol outlines the design and procedures of a prospective, longitudinal, observational study of PASC that aims to identify wearables-collected physiological parameters that are associated with PASC in patients with a positive diagnosis.
METHODS: This is a single-arm, prospective, observational study of a cohort of 550 patients, aged 18 to 65 years, male or female, who own a smartphone or a tablet that meets predetermined Bluetooth version and operating system requirements, speak English, and provide documentation of a positive COVID-19 test issued by a health care professional within 5 days before enrollment. The primary end point is long COVID-19, defined as ≥1 symptom at 3 weeks beyond the first symptom onset or positive diagnosis, whichever comes first. The secondary end point is chronic COVID-19, defined as ≥1 symptom at 12 weeks beyond the first symptom onset or positive diagnosis. Participants must be willing and able to consent to participate in the study and adhere to study procedures for 6 months.
RESULTS: The first patient was enrolled in October 2021. The estimated year for publishing the study results is 2025.
CONCLUSIONS: This is a fully decentralized study investigating PASC using wearable devices to collect physiological parameters and patient-reported outcomes. The study will shed light on the duration and symptom manifestation of PASC in nonhospitalized patient subgroups and is an exemplar of the use of wearables as population-level monitoring health tools for communicable diseases.
BACKGROUND: ClinicalTrials.gov NCT04927442; https://clinicaltrials.gov/study/NCT04927442.
UNASSIGNED: DERR1-10.2196/57382.

UNASSIGNED: Information on the quality of health of children and younger persons (CYPs) after SARS-COV-2 infection remains scarce, especially from Asia. In this study, we utilised an online survey to investigate Long COVID prevalence in CYPs in Singapore.
UNASSIGNED: The study was an anonymised online survey of physical and functional symptoms, made available from 14 October 2022 to 15 January 2023. Caregivers of CYPs aged 0 to 18 years were invited to complete the survey on behalf of their CYPs. Participants provided demographic information and their history of SARS-CoV-2 infection status to allow classification into cases and controls for analysis.
UNASSIGNED: A total of 640 completed responses were analysed, 471 (73.6%) were cases and 169 (26.4%) were controls. The prevalence of Long COVID ≥3 months post-infection was 16.8%. This decreased to 8.7% ≥6 months post-infection. Cases had higher odds of developing Long COVID (odds ratio [OR] 2.42, 95% confidence interval [CI] 1.31-4.74). The most common symptoms of Long COVID were persistent cough (7.4%), nasal congestion (7.6%) and fatigue (3.0%). Male gender was significantly associated with higher odds of Long COVID (adjusted OR 1.71 [1.04-2.83]). Vaccinated CYPs had lower odds of Long COVID but this was not statically significant (adjusted OR 0.65, 95% CI 0.34-1.25).
UNASSIGNED: About 1 in 6 CYPs in Singapore developed Long COVID with persistence of 1 or more symptoms ≥3 months post-infection, and approximately half will recover by 6 months. Male gender was associated with higher odds of Long COVID, and vaccination could potentially be protective against Long COVID in CYPs.

BACKGROUND: There have been over 772 million confirmed cases of COVID-19 worldwide. A significant portion of these infections will lead to long COVID (post-COVID-19 condition) and its attendant morbidities and costs. Numerous life-altering complications have already been associated with the development of long COVID, including chronic fatigue, brain fog, and dangerous heart rhythms.
OBJECTIVE: We aim to derive an actionable long COVID case definition consisting of significantly increased signs, symptoms, and diagnoses to support pandemic-related clinical, public health, research, and policy initiatives.
METHODS: This research employs a case-crossover population-based study using International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) data generated at Veterans Affairs medical centers nationwide between January 1, 2020, and August 18, 2022. In total, 367,148 individuals with ICD-10-CM data both before and after a positive COVID-19 test were selected for analysis. We compared ICD-10-CM codes assigned 1 to 7 months following each patient\'s positive test with those assigned up to 6 months prior. Further, 350,315 patients had novel codes assigned during this window of time. We defined signs, symptoms, and diagnoses as being associated with long COVID if they had a novel case frequency of ≥1:1000, and they significantly increased in our entire cohort after a positive test. We present odds ratios with CIs for long COVID signs, symptoms, and diagnoses, organized by ICD-10-CM functional groups and medical specialty. We used our definition to assess long COVID risk based on a patient\'s demographics, Elixhauser score, vaccination status, and COVID-19 disease severity.
RESULTS: We developed a long COVID definition consisting of 323 ICD-10-CM diagnosis codes grouped into 143 ICD-10-CM functional groups that were significantly increased in our 367,148 patient post-COVID-19 population. We defined 17 medical-specialty long COVID subtypes such as cardiology long COVID. Patients who were COVID-19-positive developed signs, symptoms, or diagnoses included in our long COVID definition at a proportion of at least 59.7% (268,320/449,450, based on a denominator of all patients who were COVID-19-positive). The long COVID cohort was 8 years older with more comorbidities (2-year Elixhauser score 7.97 in the patients with long COVID vs 4.21 in the patients with non-long COVID). Patients who had a more severe bout of COVID-19, as judged by their minimum oxygen saturation level, were also more likely to develop long COVID.
CONCLUSIONS: An actionable, data-driven definition of long COVID can help clinicians screen for and diagnose long COVID, allowing identified patients to be admitted into appropriate monitoring and treatment programs. This long COVID definition can also support public health, research, and policy initiatives. Patients with COVID-19 who are older or have low oxygen saturation levels during their bout of COVID-19, or those who have multiple comorbidities should be preferentially watched for the development of long COVID.

OBJECTIVE: Many individuals with rheumatic disease are at higher risk for severe acute coronavirus disease 2019 (COVID-19). We aimed to evaluate risk factors for postacute sequelae of COVID-19 (PASC) using an electronic health record (EHR)-based definition.
METHODS: We identified patients with prevalent rheumatic diseases and COVID-19 within the Mass General Brigham healthcare system. PASC was defined by the International Classification of Diseases, 10th revision (ICD-10) codes, relevant labs, vital signs, and medications at least 30 days following the first COVID-19 infection. Patients were followed until the earliest of incident PASC, repeat COVID-19 infection, 1 year of follow-up, death, or February 19, 2023. We used multivariable Cox regression to estimate the association of baseline characteristics with PASC risk.
RESULTS: Among 2459 patients (76.37% female, mean age 57.4 years), the most common incident PASC manifestations were cough (14.56%), dyspnea (12.36%), constipation (11.39%), and fatigue (10.70%). Serious manifestations including acute coronary disease (4.43%), thromboembolism (3.09%), hypoxemia (3.09%), stroke (1.75%), and myocarditis (0.12%) were rare. The Delta wave (adjusted hazard ratio [aHR] 0.63, 95% CI 0.49-0.82) and Omicron era (aHR 0.50, 95% CI 0.41-0.62) were associated with lower risk of PASC than the early pandemic period (March 2020-June 2021). Age, obesity, comorbidity burden, race, and hospitalization for acute COVID-19 infection were associated with greater risk of PASC. Glucocorticoid (GC) use (aHR 1.19, 95% CI 1.05-1.34 compared to no use) was associated with greater risk of PASC.
CONCLUSIONS: Among patients with rheumatic diseases, following their first COVID-19 infection, we found a decreased risk of PASC over calendar time using an EHR-based definition. Aside from GCs, no specific immunomodulatory medications were associated with increased risk, and risk factors were otherwise similar to those seen in the general population.

BACKGROUND: The postacute sequelae of COVID-19 (PASC) is a syndrome characterized by persistent COVID-19 symptoms or the onset of new symptoms following recovery from the initial or acute phase of the illness. Such symptoms often occur 4 or more weeks after being diagnosed with COVID-19. Although a lot of work has gone into understanding the long-term mental health effects of PASC, many questions related to the etiology and risk of this condition remain.
OBJECTIVE: This protocol is for a systematic review assessing the association between PASC and adverse psychiatric outcomes and whether people with PASC are at greater risk of developing an adverse psychiatric outcome than those without PASC.
METHODS: Various medical literature databases (eg, PubMed and EMBASE) will be searched for eligible articles, using predefined search criteria. Gray literature will also be explored. Epidemiological observational studies and secondary analyses of randomized controlled trials that report a quantitative relationship between PASC and at least one adverse psychiatric outcome will be included. The Population, Exposure of interest, Comparator, and Outcome framework will be used as a standardized framework for the inclusion criteria. The Joanna Briggs Institute critical appraisal tools will be used to assess methodological quality and critically appraise the risk of bias in included studies. A random-effects meta-analysis will be conducted if possible. A formal narrative synthesis will be performed if a meta-analysis is impossible due to substantial heterogeneity across studies. The Grading of Recommendations Assessment, Development and Evaluation approach will be used to rate the cumulative certainty of the evidence for all outcomes. Ethical approval is not required. The study results will be published in a peer-reviewed journal.
RESULTS: This study documents and addresses etiology, risk factors, and long-term symptoms of COVID-19 among people with PASC. It focuses on a key priority area for new evidence syntheses on the clinical management of COVID-19 and pandemic-related conditions. It will include evidence on nonhospitalized and hospitalized patients with a history of PASC.
CONCLUSIONS: Substantial heterogeneity across studies may limit the ability to perform a meta-analysis. Findings will inform disease prevention, decision-making, health care policy, and clinical research (Reviewed by the Plan P #PeerRef Community).
BACKGROUND: PROSPERO CRD42022308737; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=308737.

Mechanisms underlying persistent cardiopulmonary symptoms after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (postacute sequelae of coronavirus disease 2019 [COVID-19; PASC] or \"long COVID\") remain unclear. This study sought to elucidate mechanisms of cardiopulmonary symptoms and reduced exercise capacity.
We conducted cardiopulmonary exercise testing (CPET), cardiac magnetic resonance imaging (CMR) and ambulatory rhythm monitoring among adults >1 year after SARS-CoV-2 infection, compared those with and those without symptoms, and correlated findings with previously measured biomarkers.
Sixty participants (median age, 53 years; 42% female; 87% nonhospitalized; median 17.6 months after infection) were studied. At CPET, 18/37 (49%) with symptoms had reduced exercise capacity (<85% predicted), compared with 3/19 (16%) without symptoms (P = .02). The adjusted peak oxygen consumption (VO2) was 5.2 mL/kg/min lower (95% confidence interval, 2.1-8.3; P = .001) or 16.9% lower percent predicted (4.3%-29.6%; P = .02) among those with symptoms. Chronotropic incompetence was common. Inflammatory markers and antibody levels early in PASC were negatively correlated with peak VO2. Late-gadolinium enhancement on CMR and arrhythmias were absent.
Cardiopulmonary symptoms >1 year after COVID-19 were associated with reduced exercise capacity, which was associated with earlier inflammatory markers. Chronotropic incompetence may explain exercise intolerance among some with \"long COVID.\"

The pandemics of coronavirus disease 2019 (COVID-19) and non-alcoholic fatty liver disease (NAFLD) coexist. Elevated liver function tests are frequent in COVID-19 and may influence liver damage in NAFLD, while preexisting liver damage from NAFLD may influence the course of COVID-19. However, the prognostic relevance of this interaction, though, is unclear. Obesity is a risk factor for the presence of NAFLD as well as a severe course of COVID-19. Cohort studies reveal conflicting results regarding the influence of NAFLD presence on COVID-19 illness severity. Striking molecular similarities of cytokine pathways in both diseases, including postacute sequelae of COVID-19, suggest common pathways for chronic low-activity inflammation. This review will summarize existing data regarding the interaction of both diseases and discuss possible mechanisms of the influence of one disease on the other.

The multifaceted long-term impairments resulting from critical illness and COVID-19 require interdisciplinary management approaches in the recovery phase of illness. Operational insights into the structure and process of recovery clinics (RCs) from heterogeneous health systems are needed. This study describes the structure and process characteristics of existing and newly implemented ICU-RCs and COVID-RCs in a subset of large health systems in the United States.
METHODS: Cross-sectional survey.
METHODS: Thirty-nine RCs, representing a combined 156 hospitals within 29 health systems participated.
METHODS: None.
METHODS: None.
RESULTS: RC demographics, referral criteria, and operating characteristics were collected, including measures used to assess physical, psychologic, and cognitive recoveries. Thirty-nine RC surveys were completed (94% response rate). ICU-RC teams included physicians, pharmacists, social workers, physical therapists, and advanced practice providers. Funding sources for ICU-RCs included clinical billing (n = 20, 77%), volunteer staff support (n = 15, 58%), institutional staff/space support (n = 13, 46%), and grant or foundation funding (n = 3, 12%). Forty-six percent of RCs report patient visit durations of 1 hour or longer. ICU-RC teams reported use of validated scales to assess psychologic recovery (93%), physical recovery (89%), and cognitive recovery (86%) more often in standard visits compared with COVID-RC teams (psychologic, 54%; physical, 69%; and cognitive, 46%).
CONCLUSIONS: Operating structures of RCs vary, though almost all describe modest capacity and reliance on volunteerism and discretionary institutional support. ICU- and COVID-RCs in the United States employ varied funding sources and endorse different assessment measures during visits to guide care coordination. Common features include integration of ICU clinicians, interdisciplinary approach, and focus on severe critical illness. The heterogeneity in RC structures and processes contributes to future research on the optimal structure and process to achieve the best postintensive care syndrome and postacute sequelae of COVID outcomes.

We studied risk factors, antibodies, and symptoms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in a diverse, ambulatory population.
A prospective cohort (n = 831) previously undiagnosed with SARS-CoV-2 infection underwent serial testing (SARS-CoV-2 polymerase chain reaction, immunoglobulin G [IgG]) for 6 months.
Ninety-three participants (11.2%) tested SARS-CoV-2-positive: 14 (15.1%) asymptomatic, 24 (25.8%) severely symptomatic. Healthcare workers (n = 548) were more likely to become infected (14.2% vs 5.3%; adjusted odds ratio, 2.1; 95% confidence interval, 1.4-3.3) and severely symptomatic (29.5% vs 6.7%). IgG antibodies were detected after 79% of asymptomatic infections, 89% with mild-moderate symptoms, and 96% with severe symptoms. IgG trajectories after asymptomatic infections (slow increases) differed from symptomatic infections (early peaks within 2 months). Most participants (92%) had persistent IgG responses (median 171 days). In multivariable models, IgG titers were positively associated with symptom severity, certain comorbidities, and hospital work. Dyspnea and neurologic changes (including altered smell/taste) lasted ≥ 120 days in ≥ 10% of affected participants. Prolonged symptoms (frequently more severe) corresponded to higher antibody levels.
In a prospective, ethnically diverse cohort, symptom severity correlated with the magnitude and trajectory of IgG production. Symptoms frequently persisted for many months after infection.Clinical Trials Registration. NCT04336215.