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ImportanceProlonged symptoms following SARS-CoV-2 infection, or Long COVID, is common, but few prospective studies of Long COVID risk factors have been conducted. ObjectiveTo determine whether sociodemographic factors, lifestyle, or medical history preceding COVID-19 or characteristics of acute SARS-CoV-2 infection are associated with Long COVID. DesignCohort study with longitudinal assessment of symptoms before, during, and after SARS-CoV-2 infection, and cross-sectional assessment of Long COVID symptoms using data from the COVID-19 Citizen Science (CCS) study. SettingCCS is an online cohort study that began enrolling March 26, 2020. We included data collected between March 26, 2020, and May 18, 2022. ParticipantsAdult CCS participants who reported a positive SARS-CoV-2 test result (PCR, Antigen, or Antibody) more than 30 days prior to May 4, 2022, were surveyed. ExposuresAge, sex, race/ethnicity, education, employment, socioeconomic status/financial insecurity, self-reported medical history, vaccination status, time of infection (variant wave), number of acute symptoms, pre-COVID depression, anxiety, alcohol and drug use, sleep, exercise. Main OutcomePresence of at least 1 Long COVID symptom greater than 1 month after acute infection. Sensitivity analyses were performed considering only symptoms beyond 3 months and only severe symptoms. Results13,305 participants reported a SARS-CoV-2 positive test more than 30 days prior, 1480 (11.1% of eligible) responded to a survey about Long COVID symptoms, and 476 (32.2% of respondents) reported Long COVID symptoms (median 360 days after infection). Respondents mean age was 53 and 1017 (69%) were female. Common Long COVID symptoms included fatigue, reported by 230/476 (48.3%), shortness of breath (109, 22.9%), confusion/brain fog (108, 22.7%), headache (103, 21.6%), and altered taste or smell (98, 20.6%). In multivariable models, number of acute COVID-19 symptoms (OR 1.30 per symptom, 95%CI 1.20-1.40), lower socioeconomic status/financial insecurity (OR 1.62, 95%CI 1.02-2.63), pre-infection depression (OR 1.08, 95%CI 1.01-1.16), and earlier variants (OR 0.37 for Omicron compared to ancestral strain, 95%CI 0.15-0.90) were associated with Long COVID symptoms. Conclusions and RelevanceVariant wave, severity of acute infection, lower socioeconomic status and pre-existing depression are associated with Long COVID symptoms. Key PointsO_ST_ABSQuestionC_ST_ABSWhat are the patterns of symptoms and risk factors for Long COVID among SARS-CoV-2 infected individuals? FindingsPersistent symptoms were highly prevalent, especially fatigue, shortness of breath, headache, brain fog/confusion, and altered taste/smell, which persisted beyond 1 year among 56% of participants with symptoms; a minority of participants reported severe Long COVID symptoms. Number of acute symptoms during acute SARS-CoV-2 infection, financial insecurity, pre-existing depression, and infection with earlier variants are associated with prevalent Long COVID symptoms independent of vaccination, medical history, and other factors. MeaningSeverity of acute infection, SARS-CoV-2 variant, and financial insecurity and depression are associated with Long COVID symptoms.
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BACKGROUNDShortness of breath, chest pain, and palpitations occur as post-acute sequelae of COVID-19 (PASC), but whether symptoms are associated with echocardiographic abnormalities, cardiac biomarkers, or markers of systemic inflammation remains unknown. METHODSIn a cross-sectional analysis, we assessed symptoms, performed echocardiograms, and measured biomarkers among adults >8 weeks after PCR-confirmed SARS-CoV-2 infection. We modeled associations between symptoms and baseline characteristics, echocardiographic findings, and biomarkers using logistic regression. RESULTSWe enrolled 102 participants at a median 7.2 months (IQR 4.1-9.1) following COVID-19 onset; 47 individuals reported dyspnea, chest pain, or palpitations. Median age was 52 years (range 24-86) and 41% were women. Female sex (OR 2.55, 95%CI 1.13-5.74) and hospitalization during acute infection (OR 3.25, 95%CI 1.08-9.82) were associated with symptoms. IgG antibody to SARS-CoV-2 receptor binding domain (OR 1.38 per doubling, 95%CI 1.38-1.84) and high-sensitivity C-reactive protein (OR 1.31 per doubling, 95%CI 1.00-1.71) were associated with symptoms. Regarding echocardiographic findings, 4/47 (9%) with symptoms had pericardial effusions compared to 0/55 without symptoms (p=0.038); those with pericardial effusions had a median 4 symptoms compared to 1 without (p<0.001). There was no strong evidence for a relationship between symptoms and echocardiographic functional parameters (including left ventricular ejection fraction and strain, right ventricular strain, pulmonary artery pressure) or high-sensitivity troponin, NT-pro-BNP, interleukin-10, interferon-gamma, or tumor necrosis factor-alpha. CONCLUSIONSAmong adults in the post-acute phase of SARS-CoV-2 infection, SARS-CoV-2 RBD antibodies, markers of inflammation and, possibly, pericardial effusions are associated with cardiopulmonary symptoms. Investigation into inflammation as a mechanism underlying PASC is warranted. FUNDINGThis work was supported by the UCSF Division of Cardiology at Zuckerberg San Francisco General, and the National Institutes of Health/National Heart Lung Blood Institute and National Institute of Allergy and Infectious Diseases. MSD is supported by NIH 5K12HL143961. MJP is supported on NIH T32 AI60530-12. JDK is supported by NIH K23AI135037. TJH is supported by NIH/NIAID 3R01A1141003-03S1. PYH is supported by NIH/NAID 2K24AI112393-06. This publication was supported by the National Center for Advancing Translational Sciences, National Institutes of Health, through UCSF-CTSI Grant Number UL1TR001872. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=169 HEIGHT=200 SRC="FIGDIR/small/21266834v1_ufig1.gif" ALT="Figure 1"> View larger version (42K): org.highwire.dtl.DTLVardef@7b2424org.highwire.dtl.DTLVardef@81d995org.highwire.dtl.DTLVardef@f3d6e5org.highwire.dtl.DTLVardef@a19373_HPS_FORMAT_FIGEXP M_FIG C_FIG
