ImportanceSARS-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.ObjectiveTo develop a definition of PASC using self-reported symptoms and describe PASC frequencies across cohorts, vaccination status, and number of infections.Design, Setting, and ParticipantsProspective 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.ExposureSARS-CoV-2 infection.Main Outcomes and MeasuresPASC and 44 participant-reported symptoms (with severity thresholds).ResultsA 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 RelevanceA 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.

In a prospective cross-sectional study we quantified HIV viral load within the alveolar macrophage in a cohort of healthy HIV-infected subjects who did not have medical comorbidities or smoke cigarettes to determine if alveolar macrophage proviral DNA was associated with alveolar macrophage phagocytic immune dysfunction. We enrolled 23 subjects who underwent bronchoscopy and bronchoalveolar lavage. Alveolar macrophages were isolated and HIV-1 RNA was quantified in the cells using the Abbott RealTime HIV-1 Assay. Proviral DNA was qualitatively measured using a modified version of the HIV-1 RNA assay. Phagocytosis measured by incubating alveolar macrophages with FITC-labeled Staphylococcus aureus and determining fluorescence with a Zeiss inverted microscope. Phagocytic index was calculated as (% positive cells × mean channel fluorescence)/100. Sixteen subjects had (+) proviral DNA and seven had (-) proviral DNA in their alveolar macrophages. Of all subjects 100% in both groups were on highly active antiretroviral therapy (HAART). The median plasma viral load was 0 in both groups. HIV-1-infected subjects with (+) proviral DNA in their alveolar macrophages had a significantly lower median alveolar macrophage phagocytic index compared to those with (-) proviral DNA in their alveolar macrophages [11.8 (IQR 4.8-39.0) vs. 64.9 (IQR 14.0-166.0), p = 0.05]. Alveolar macrophages harbor HIV even in otherwise healthy subjects with undetectable plasma viral loads, representing a potential reservoir for the virus. In addition, HIV viral replication within the macrophage may impair phagocytosis and other immune functions in the lung, leading to an increased risk for lung infection.

Cytokine storm and hyperinflammation are associated with increased mortality in COVID-19. In this small uncontrolled cohort of patients with moderate-severe COVID-19, treatment with baricitinib plus hydroxychloroquine was associated with recovery in 11 of 15 patients. Baricitinib for the treatment of COVID-19 should be further investigated in randomized controlled clinical trials.

Despite anti-retroviral therapy (ART), human immunodeficiency virus-1 (HIV)-related pulmonary disease continues to be a major cause of morbidity and mortality for people living with HIV (PLWH). The spectrum of lung diseases has changed from acute opportunistic infections resulting in death to chronic lung diseases for those with access to ART. Chronic immune activation and suppression can result in impairment of innate immunity and progressive loss of T cell and B cell functionality with aberrant cytokine and chemokine responses systemically as well as in the lung. HIV can be detected in the lungs of PLWH and has profound effects on cellular immune functions. In addition, HIV-related lung injury and disease can occur secondary to a number of mechanisms including altered pulmonary and systemic inflammatory pathways, viral persistence in the lung, oxidative stress with additive effects of smoke exposure, microbial translocation, and alterations in the lung and gut microbiome. Although ART has had profound effects on systemic viral suppression in HIV, the impact of ART on lung immunology still needs to be fully elucidated. Understanding of the mechanisms by which HIV-related lung diseases continue to occur is critical to the development of new preventive and therapeutic strategies to improve lung health in PLWH.