Development of a Definition of Postacute Sequelae of SARS-CoV-2 Infection.

Importance: SARS-CoV-2 infection is associated with persistent, relapsing, or new symptoms or other health effects occurring after acute infection, termed postacute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID. Characterizing PASC requires analysis of prospectively and uniformly collected data from diverse uninfected and infected individuals. Objective: To develop a definition of PASC using self-reported symptoms and describe PASC frequencies across cohorts, vaccination status, and number of infections. Design, Setting, and Participants: Prospective observational cohort study of adults with and without SARS-CoV-2 infection at 85 enrolling sites (hospitals, health centers, community organizations) located in 33 states plus Washington, DC, and Puerto Rico. Participants who were enrolled in the RECOVER adult cohort before April 10, 2023, completed a symptom survey 6 months or more after acute symptom onset or test date. Selection included population-based, volunteer, and convenience sampling. Exposure: SARS-CoV-2 infection. Main Outcomes and Measures: PASC and 44 participant-reported symptoms (with severity thresholds). Results: A total of 9764 participants (89% SARS-CoV-2 infected; 71% female; 16% Hispanic/Latino; 15% non-Hispanic Black; median age, 47 years [IQR, 35-60]) met selection criteria. Adjusted odds ratios were 1.5 or greater (infected vs uninfected participants) for 37 symptoms. Symptoms contributing to PASC score included postexertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, palpitations, changes in sexual desire or capacity, loss of or change in smell or taste, thirst, chronic cough, chest pain, and abnormal movements. Among 2231 participants first infected on or after December 1, 2021, and enrolled within 30 days of infection, 224 (10% [95% CI, 8.8%-11%]) were PASC positive at 6 months. Conclusions and Relevance: A definition of PASC was developed based on symptoms in a prospective cohort study. As a first step to providing a framework for other investigations, iterative refinement that further incorporates other clinical features is needed to support actionable definitions of PASC.

Patient and stakeholder perspectives on impacts of the COVID-19 pandemic on HIV and mental health care delivery in South Africa.

BACKGROUND: The COVID-19 pandemic had a global impact on health systems and the delivery of health services, including for chronic conditions such as HIV. In South Africa, impacts on HIV services have widely been quantitatively described. Across different health settings, patients have also qualitatively described numerous negative impacts to their HIV care. However, patient perspectives on COVID-19 impacts to HIV care in South Africa, the largest HIV care system in the world, have been little explored to date. METHODS: We conducted 29 semi-structured individual interviews with people living with HIV (n = 24) and providers (n = 5) in Cape Town, South Africa. RESULTS: While most patient participants reported continued access to HIV treatment during the pandemic, many described perceiving that the quality of their care declined. Increased structural barriers were described as one contributing factor to this change. Additionally, patients described that reduced privacy in clinical interactions was a key factor negatively influencing their experience of receiving care. CONCLUSION: Findings underscore the importance of ensuring patient privacy for HIV services even during the rearrangement of services in emergencies. It is also important to continue developing models to integrate community mental health services within HIV care delivery in South Africa.

Distinguishing SARS-CoV-2 persistence and reinfection: A retrospective cohort study.

BACKGROUND: SARS-CoV-2 reinfection is poorly understood, partly because few studies have systematically applied genomic analysis to distinguish reinfection from persistent RNA detection related to initial infection. We aimed to evaluate the characteristics of SARS-CoV-2 reinfection and persistent RNA detection using independent genomic, clinical, and laboratory assessments. METHODS: All individuals at a large academic medical center who underwent a SARS-CoV-2 nucleic acid amplification test (NAAT) ≥ 45 days after an initial positive test, with both tests between March 14th and December 30th, 2020, were analyzed for potential reinfection. Inclusion criteria required having ≥2 positive NAATs collected ≥45 days apart with a cycle threshold (Ct) value <35 at repeat testing. For each included subject, likelihood of reinfection was assessed by viral genomic analysis of all available specimens with a Ct value <35, structured Ct trajectory criteria, and case-by-case review by infectious diseases physicians. RESULTS: Among 1,569 individuals with repeat SARS-CoV-2 testing ≥45 days after an initial positive NAAT, 65 (4%) met cohort inclusion criteria. Viral genomic analysis characterized mutations present, and was successful for 14/65 (22%) subjects. Six subjects had genomically-supported reinfection and eight subjects had genomically-supported persistent RNA detection. Compared to viral genomic analysis, clinical and laboratory assessments correctly distinguished reinfection from persistent RNA detection in 12/14 (86%) subjects but missed 2/6 (33%) genomically-supported reinfections. CONCLUSION: Despite good overall concordance with viral genomic analysis, clinical and Ct value-based assessments failed to identify 33% of genomically-supported reinfections. Scaling-up genomic analysis for clinical use would improve detection of SARS-CoV-2 reinfections.

Pre-exposure Prophylaxis Persistence at a Diverse Sexual Health Clinic: Comparison of the pre-COVID-19 era to the COVID-19 era.

The COVID-19 pandemic interrupted health care delivery and exacerbated disparities. Many sexual health clinics transitioned to telemedicine, including for pre-exposure prophylaxis (PrEP). We conducted a retrospective cohort study of patients at an urban sexual health clinic to assess the likelihood and predictors of PrEP persistence in the year following PrEP initiation. We compared patients starting PrEP in the four months preceding the first COVID surge to those starting PrEP one year prior. We found lower PrEP persistence in the COVID cohort compared to the pre-COVID cohort (50.8% vs. 68.9%, respectively). In both cohorts, most care was provided through in-person visits and telemedicine was rare. In the pre-COVID cohort, older patients and those identifying as non-Hispanic White were more likely to persist on PrEP. In the COVID cohort, these disparities in PrEP persistence were not observed. Flexible models of care may facilitate equitable care engagement and re-engagement.

Discharge to post-acute care and other predictors of prolonged length of stay during the initial COVID-19 surge: a single site analysis.

BACKGROUND: During the initial surge of coronavirus disease 2019 (COVID-19), health-care utilization fluctuated dramatically, straining acute hospital capacity across the USA and potentially contributing to excess mortality. METHODS: This was an observational retrospective study of patients with COVID-19 admitted to a large US urban academic medical center during a 12-week COVID-19 surge in the Spring of 2020. We describe patterns in length of stay (LOS) over time. Our outcome of interest was prolonged LOS (PLOS), which we defined as 7 or more days. We performed univariate analyses of patient characteristics, clinical outcomes and discharge disposition to evaluate the association of each variable with PLOS and developed a final multivariate model via backward elimination, wherein all variables with a P-value above 0.05 were eliminated in a stepwise fashion. RESULTS: The cohort included 1366 patients, of whom 13% died and 29% were readmitted within 30 days. The LOS (mean: 12.6) fell over time (P < 0.0001). Predictors of PLOS included discharge to a post-acute care (PAC) facility (odds ratio [OR]: 11.9, 95% confidence interval [CI] 2.6-54.0), uninsured status (OR 3.2, CI 1.1-9.1) and requiring intensive care and intubation (OR 18.4, CI 11.5-29.6). Patients had a higher readmission rate if discharged to PAC facilities (40%) or home with home health agency (HHA) services (38%) as compared to patients discharged home without HHA services (26%) (P < 0.0001). CONCLUSION: Patients hospitalized with COVID-19 during a US COVID-19 surge had a PLOS and high readmission rate. Lack of insurance, an intensive care unit stay and a decision to discharge to a PAC facility were associated with a PLOS. Efforts to decrease LOS and optimize hospital capacity during COVID-19 surges may benefit from focusing on increasing PAC and HHA capacity and resources.

Pediatric biorepository participation during the COVID-19 pandemic: predictors of enrollment and biospecimen donation.

BACKGROUND: Patient-level predictors of enrollment in pediatric biorepositories are poorly described. Especially in pandemic settings, understanding who is likely to enroll in a biorepository is critical to interpreting analyses conducted on biospecimens. We describe predictors of pediatric COVID-19 biorepository enrollment and biospecimen donation to identify gaps in COVID-19 research on pediatric biospecimens. METHODS: We compared data from enrollees and non-enrollees aged 0-25 years with suspected or confirmed COVID-19 infection who were approached for enrollment in the Massachusetts General Hospital pediatric COVID-19 biorepository between April 12, 2020, and May 28, 2020, from community or academic outpatient or inpatient settings. Demographic and clinical data at presentation to care were from automatic and manual chart extractions. Predictors of enrollment and biospecimen donation were assessed with Poisson regression models. RESULTS: Among 457 individuals approached, 214 (47%) enrolled in the biorepository. A COVID-19 epidemiologic risk factor was recorded for 53%, and 15% lived in a US Centers for Disease Control and Prevention-defined COVID-19 hotspot. Individuals living in a COVID-19 hotspot (relative risk (RR) 2.4 [95% confidence interval (CI): 1.8-3.2]), with symptoms at presentation (RR 1.8 [95% CI: 1.2-2.7]), or admitted to hospital (RR 1.8 [95% CI: 1.2-2.8]) were more likely to enroll. Seventy-nine percent of enrollees donated any biospecimen, including 97 nasopharyngeal swabs, 119 oropharyngeal swabs, and 105 blood, 16 urine, and 16 stool specimens, respectively. Age, sex, race, ethnicity, and neighborhood-level socioeconomic status based on zip code did not predict enrollment or biospecimen donation. CONCLUSIONS: While fewer than half of individuals approached consented to participate in the pediatric biorepository, enrollment appeared to be representative of children affected by the pandemic. Living in a COVID-19 hotspot, symptoms at presentation to care and hospital admission predicted biorepository enrollment. Once enrolled, most individuals donated a biospecimen.

Experiences of participants in a decentralized antiretroviral therapy program in South Africa during the COVID-19 pandemic.

The COVID-19 pandemic and associated restrictions could adversely affect long-term HIV care. We evaluated the experiences of people receiving antiretroviral therapy (ART) through a decentralized delivery program in South Africa during the COVID-19 pandemic. We telephoned a random subsample of participants enrolled in a prospective cohort study in KwaZulu-Natal in April and May 2020 and administered a semi-structured telephone interview to consenting participants. We completed interviews with 303 of 638 contacted participants (47%); 66% were female, with median age 36y. The most common concerns regarding the COVID-19 pandemic were food running out (121, 40%), fear of becoming infected with COVID-19 (103, 34%), and being unable to work/losing employment or income (102, 34%). Twenty-five (8%) participants had delayed ART pick-up due to the pandemic, while 212 (70%) had new concerns about ART access going forward. Mental health scores were worse during the pandemic compared to baseline (median score 65.0 vs 80.0, p < 0.001). Decentralized ART distribution systems have the potential to support patients outside of health facilities during the COVID-19 pandemic, but economic concerns and mental health impacts related to the pandemic must also be recognized and addressed.

Willingness to accept COVID-19 vaccination among people living with HIV in a high HIV prevalence community.

BACKGROUND: People living with HIV (PLWH) may have a poorer prognosis with COVID-19 infection and are an important population for COVID-19 vaccination. We assessed the willingness and reasons for COVID-19 vaccine acceptance or hesitancy among PLWH in South Africa. METHODS: We conducted a cross-sectional study consisting of telephone interviews with a randomly selected subset of participants enrolled in a prospective observational cohort study evaluating a decentralized antiretroviral therapy (ART) delivery program in South Africa. Questions assessed willingness to accept a future COVID-19 vaccine, concerns regarding COVID-19 vaccination, and overall vaccine confidence. Interviews were conducted between September 2020 and January 2021. We evaluated participant demographics, sources of COVID-19 information, stigma and medical mistrust, uptake of non-pharmaceutical interventions, and socioeconomic impacts of the COVID-19 pandemic as potential covariates of willingness to accept vaccination. RESULTS: We completed interviews with 213 participants; 153 (72%) were female, median age 35y, and 100 (47%) had completed secondary school. Among the participants, 121 (57%) were willing to accept future vaccination, 46 (22%) were unsure, and 45 (21%) stated they did not intend to be vaccinated. Fear of side effects, reported by 42 (20%), was the most common concern about COVID-19 vaccination. Older age was associated with willingness to accept vaccination (aOR 1.75 for every 10-year increase in age, 95% CI 1.10-2.78, p = 0.02), while higher medical mistrust related to COVID-19 (aOR 0.21, 95% CI 0.093-0.45, p < 0.001) and use of social media for COVID-19 information (aOR 0.30, 95% CI 0.11-0.84, p = 0.02) were associated with lower willingness to accept vaccination. CONCLUSIONS: In this cohort of PLWH in South Africa, over half were willing to accept COVID-19 vaccination, although a substantial proportion remained unsure or were not willing to be vaccinated. Public health messaging should emphasize the safety and efficacy of COVID-19 vaccination and address misinformation and medical mistrust among PLWH. Ongoing efforts to ensure access to COVID-19 vaccines for vulnerable populations are crucial.

Dermatology on the global stage: The role of dermatologists in international health advocacy and COVID-19 research.

BACKGROUND: Over the last decade, there has been a surge in interest and funding for global health dermatology. Skin conditions are now recognized as the fourth leading cause of nonfatal disease burden worldwide in disability-adjusted life years. Dermatologists are uniquely positioned within global health because skin conditions are often the presenting sign of severe illnesses, such as neglected tropical diseases and COVID-19. METHODS: We review four major areas of work by dermatologists within global health: i) characterization of global burden of skin disease, ii) advocacy for dermatologic therapies on the World Health Organization's Model List of Essential Medicines, iii) advancements in global programming for skin-related tropical diseases, and iv) the role of dermatologists during the COVID-19 pandemic. For each area of work, the significance and impact on the health of women and girls is briefly highlighted. RESULTS: Dermatologists have led the efforts to quantify and evaluate the global burden of skin disease, the burden of which is disproportionately shared by women. The dermatology community has also championed global efforts to eliminate skin-related neglected tropical diseases, such as scabies. Through national and international policy advocacy, dermatologists have pushed for more dermatologic therapies in the World Health Organization's Model List of Essential Medicines, helping to secure better care for patients with skin disease throughout the world. Since 2020, the dermatology community has worked collaboratively in the fight against COVID-19, establishing a worldwide registry for cutaneous manifestations of SARS-CoV-2 and pursuing research that has allowed colleagues in the house of medicine to better understand this landmark disease. CONCLUSION: Through the study and promotion of global health, dermatologists have an important role in the house of medicine.

Understanding the Link Between Obesity and Severe COVID-19 Outcomes: Causal Mediation by Systemic Inflammatory Response.

BACKGROUND: Obesity is an established risk factor for severe COVID-19 outcomes. The mechanistic underpinnings of this association are not well-understood. OBJECTIVE: To evaluate the mediating role of systemic inflammation in obesity-associated COVID-19 outcomes. METHODS: This hospital-based, observational study included 3828 SARS-CoV-2-infected patients who were hospitalized February to May 2020 at Massachusetts General Hospital (MGH) or Columbia University Irving Medical Center/New York Presbyterian Hospital (CUIMC/NYP). We use mediation analysis to evaluate whether peak inflammatory biomarkers (C-reactive protein [CRP], erythrocyte sedimentation rate [ESR], D-dimer, ferritin, white blood cell count and interleukin-6) are in the causal pathway between obesity (BMI ≥ 30) and mechanical ventilation or death within 28 days of presentation to care. RESULTS: In the MGH cohort (n = 1202), obesity was associated with greater likelihood of ventilation or death (OR = 1.73; 95% CI = [1.25, 2.41]; P = 0.001) and higher peak CRP (P < 0.001) compared with nonobese patients. The estimated proportion of the association between obesity and ventilation or death mediated by CRP was 0.49 (P < 0.001). Evidence of mediation was more pronounced in patients < 65 years (proportion mediated = 0.52 [P < 0.001] vs 0.44 [P = 0.180]). Findings were more moderate but consistent for peak ESR. Mediation by other inflammatory markers was not supported. Results were replicated in CUIMC/NYP cohort (n = 2626). CONCLUSION: Findings support systemic inflammatory pathways in obesity-associated severe COVID-19 disease, particularly in patients < 65 years, captured by CRP and ESR. Contextualized in clinical trial findings, these results reveal therapeutic opportunity to target systemic inflammatory pathways and monitor interventions in high-risk subgroups and particularly obese patients.

Medical Mistrust and Stigma Associated with COVID-19 Among People Living with HIV in South Africa.

We evaluated COVID-19 stigma and medical mistrust among people living with HIV in South Africa. We conducted telephone interviews with participants in a prospective study of a decentralized antiretroviral therapy program. Scales assessing medical mistrust, conspiracy beliefs, anticipated and internalized stigma, and stereotypes specific to COVID-19 were adapted primarily from the HIV literature, with higher scores indicating more stigma or mistrust. Among 303 participants, the median stigma summary score was 4 [interquartile range (IQR) 0-8; possible range 0-24] and 6 (IQR 2-9) for mistrust (possible range 0-28). A substantial proportion of participants agreed or strongly agreed with at least one item assessing stigma (54%) or mistrust (43%). Higher COVID-19 stigma was associated with female gender and antecedent HIV stigma, and lower stigma with reporting television as a source of information on COVID-19. Further efforts should focus on effects of stigma and mistrust on protective health behaviors and vaccine hesitancy.

Sex differences in inflammatory markers in patients hospitalized with COVID-19 infection: Insights from the MGH COVID-19 patient registry.

BACKGROUND: Men are at higher risk for serious complications related to COVID-19 infection than women. More robust immune activation in women has been proposed to contribute to decreased disease severity, although systemic inflammation has been associated with worse outcomes in COVID-19 infection. Whether systemic inflammation contributes to sex differences in COVID-19 infection is not known. STUDY DESIGN AND METHODS: We examined sex differences in inflammatory markers among 453 men (mean age 61) and 328 women (mean age 62) hospitalized with COVID-19 infection at the Massachusetts General Hospital from March 8 to April 27, 2020. Multivariable linear regression models were used to examine the association of sex with initial and peak inflammatory markers. Exploratory analyses examined the association of sex and inflammatory markers with 28-day clinical outcomes using multivariable logistic regression. RESULTS: Initial and peak CRP were higher in men compared with women after adjustment for baseline differences (initial CRP: ß 0.29, SE 0.07, p = 0.0001; peak CRP: ß 0.31, SE 0.07, p<0.0001) with similar findings for IL-6, PCT, and ferritin (p<0.05 for all). Men had greater than 1.5-greater odds of dying compared with women (OR 1.71, 95% CI 1.04-2.80, p = 0.03). Sex modified the association of peak CRP with both death and ICU admission, with stronger associations observed in men compared with women (death: OR 9.19, 95% CI 4.29-19.7, p <0.0001 in men vs OR 2.81, 95% CI 1.52-5.18, p = 0.009 in women, Pinteraction = 0.02). CONCLUSIONS: In a sample of 781 men and women hospitalized with COVID-19 infection, men exhibited more robust inflammatory activation as evidenced by higher initial and peak inflammatory markers, as well as worse clinical outcomes. Better understanding of sex differences in immune responses to COVID-19 infection may shed light on the pathophysiology of COVID-19 infection.

CoVA: An Acuity Score for Outpatient Screening that Predicts Coronavirus Disease 2019 Prognosis.

BACKGROUND: We sought to develop an automatable score to predict hospitalization, critical illness, or death for patients at risk for coronavirus disease 2019 (COVID-19) presenting for urgent care. METHODS: We developed the COVID-19 Acuity Score (CoVA) based on a single-center study of adult outpatients seen in respiratory illness clinics or the emergency department. Data were extracted from the Partners Enterprise Data Warehouse, and split into development (n = 9381, 7 March-2 May) and prospective (n = 2205, 3-14 May) cohorts. Outcomes were hospitalization, critical illness (intensive care unit or ventilation), or death within 7 days. Calibration was assessed using the expected-to-observed event ratio (E/O). Discrimination was assessed by area under the receiver operating curve (AUC). RESULTS: In the prospective cohort, 26.1%, 6.3%, and 0.5% of patients experienced hospitalization, critical illness, or death, respectively. CoVA showed excellent performance in prospective validation for hospitalization (expected-to-observed ratio [E/O]: 1.01; AUC: 0.76), for critical illness (E/O: 1.03; AUC: 0.79), and for death (E/O: 1.63; AUC: 0.93). Among 30 predictors, the top 5 were age, diastolic blood pressure, blood oxygen saturation, COVID-19 testing status, and respiratory rate. CONCLUSIONS: CoVA is a prospectively validated automatable score for the outpatient setting to predict adverse events related to COVID-19 infection.

Massachusetts general hospital Covid-19 registry reveals two distinct populations of hospitalized patients by race and ethnicity.

OBJECTIVE: To evaluate differences by race/ethnicity in clinical characteristics and outcomes among hospitalized patients with Covid-19 at Massachusetts General Hospital (MGH). METHODS: The MGH Covid-19 Registry includes confirmed SARS-CoV-2-infected patients hospitalized at MGH and is based on manual chart reviews and data extraction from electronic health records (EHRs). We evaluated differences between White/Non-Hispanic and Hispanic patients in demographics, complications and 14-day outcomes among the N = 866 patients hospitalized with Covid-19 from March 11, 2020-May 4, 2020. RESULTS: Overall, 43% of patients hospitalized with Covid-19 were women, median age was 60.4 [IQR = (48.2, 75)], 11.3% were Black/non-Hispanic and 35.2% were Hispanic. Hispanic patients, representing 35.2% of patients, were younger than White/non-Hispanic patients [median age 51y; IQR = (40.6, 61.6) versus 72y; (58.0, 81.7) (p<0.001)]. Hispanic patients were symptomatic longer before presenting to care (median 5 vs 3d, p = 0.039) but were more likely to be sent home with self-quarantine than be admitted to hospital (29% vs 16%, p<0.001). Hispanic patients had fewer comorbidities yet comparable rates of ICU or death (34% vs 36%). Nonetheless, a greater proportion of Hispanic patients recovered by 14 days after presentation (62% vs 45%, p<0.001; OR = 1.99, p = 0.011 in multivariable adjusted model) and fewer died (2% versus 18%, p<0.001). CONCLUSIONS: Hospitalized Hispanic patients were younger and had fewer comorbidities compared to White/non-Hispanic patients; despite comparable rates of ICU care or death, a greater proportion recovered. These results have implications for public health policy and the design and conduct of clinical trials.

The role of obesity in inflammatory markers in COVID-19 patients.

Obesity has emerged as a significant risk factor for severe COVID-19 worldwide. Given both COVID-19 infection and obesity have been associated with increased systemic inflammation, we evaluated inflammatory markers in obese and non-obese individuals hospitalized for COVID-19 at Massachusetts General Hospital. We hypothesized that obese patients would have a more exuberant inflammatory response as evidenced by higher initial and peak inflammatory markers along with worse clinical outcomes. Of the 781 patients, 349 were obese (45%). Obese individuals had higher initial and peak levels of CRP and ESR as well as higher peak d-dimer (P < 0.01 for all) in comparison to non-obese individuals, while. IL-6 and ferritin were similar. In addition, obese individuals had a higher odds of requiring vasopressor use (OR 1.54, 95% CI 1.00-2.38, P = 0.05), developing hypoxemic respiratory failure (OR 1.58, 95% CI 1.04-2.40, P = 0.03) and death (OR 2.20, 95% CI 1.31-3.70, P = 0.003) within 28 days of presentation to care. Finally, higher baseline levels of CRP and D-dimer were associated with worse clinical outcomes even after adjustment for BMI. Our findings suggest greater disease severity in obese individuals is characterized by more exuberant inflammation.