Factors Associated With Long COVID Symptoms in an Online Cohort Study

Durstenfeld, Matthew S; Peluso, Michael J.; Peyser, Noah D.; Lin, Feng; Knight, Sara J.; Djibo, Audrey; Khatib, Rasha; Kitzman, Heather; O’Brien, Emily C.; Williams, Natasha; Isasi, Carmen R.; Kornak, John; Carton, Thomas; Olgin, Jeffrey E.; Pletcher, Mark J.; Marcus, Gregory M

doi:10.1093/ofid/ofad047

Cited by 61 publications

(51 citation statements)

References 34 publications

(41 reference statements)

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“…Investigation into mechanisms of PASC may benefit from proof-of-concept approaches to identify potential therapies. Although vaccination reduces the risk of PASC [57,58] and the newer circulating variants may be associated with lower risk of Long COVID [59], there is no data regarding whether anti-viral, anti-inflammatory, or anti-coagulant strategies improve exercise capacity in PASC. In chronotropic incompetence separate from COVID-19, chronic supervised exercise is the only intervention demonstrated to improve exercise capacity and surrogates of autonomic function [60][61][62].…”

Section: Implications For Therapymentioning

confidence: 99%

Reduced exercise capacity, chronotropic incompetence, and early systemic inflammation in cardiopulmonary phenotype Long COVID

Durstenfeld

Peluso

Kaveti

et al. 2022

Preprint

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BACKGROUNDMechanisms underlying persistent cardiopulmonary symptoms following SARS-CoV-2 infection (post-acute sequelae of COVID-19 “PASC” or “Long COVID”) remain unclear. The purpose of this study was to elucidate the pathophysiology of cardiopulmonary PASC using multimodality cardiovascular imaging including cardiopulmonary exercise testing (CPET), cardiac magnetic resonance imaging (CMR) and ambulatory rhythm monitoring.METHODSIn the Long-Term Impact of Infection with Novel Coronavirus (LIINC) Cohort, we performed CMR, CPET, and ambulatory rhythm monitoring among adults > 1 year after PCR-confirmed SARS-CoV-2 infection. We used logistic and linear regression to compare those with and without cardiopulmonary symptoms (dyspnea, chest pain, palpitations) adjusting for confounders.RESULTSOne hundred twenty individuals were studied, among whom 46 participants (unselected for symptom status) had at least one advanced test performed at median 17 months (IQR 15-18). Median age was 52 (IQR 42-61), 18 (39%) were female, and 6 (13%) were hospitalized for severe acute infection. On CMR (n=39), smaller RV volume and stroke volume and higher extracellular volume were present among those with symptoms, but no evidence of late-gadolinium enhancement or differences in T1 or T2 mapping were demonstrated. We did not find arrhythmias on ambulatory monitoring. In contrast, on CPET (n=39), 13/15 (87%) participants with reduced exercise capacity (<85% predicted) reported cardiopulmonary symptoms or fatigue (p=0.008). Adjusted peak VO2 was 2.7 ml/kg/min lower among those with cardiopulmonary symptoms (95%CI −6.9 to 1.5; p=0.20) or −11% predicted (95%CI −27 to 5, p=0.17). Including fatigue along with cardiopulmonary symptoms, the adjusted difference in peak VO2 was −5.9 ml/kg/min (−9.6 to −2.3; p=0.002) or −21% predicted (−35 to −7; p=0.006). Chronotropic incompetence was the primary abnormality among 9/15 with reduced peak VO2. Adjusted heart rate reserve <80% was associated with reduced exercise capacity (OR 15.6, 95%CI 1.30-187; p=0.03). Those with chronotropic incompetence had higher hsCRP, lower heart rate recovery, and lower heart rate variability suggestive of autonomic dysfunction.CONCLUSIONSReduced exercise capacity and reduced heart rate response to exercise, and hsCRP are associated with persistent cardiopulmonary symptoms more than 1 year following COVID-19. Chronic inflammation and autonomic dysfunction may underlie cardiopulmonary PASC.Clinical PerspectiveWhat is New?Impaired chronotropic response to exercise is associated with reduced exercise capacity and cardiopulmonary symptoms more than 1 year after SARS-CoV-2 infection.Findings on ambulatory rhythm monitoring point to perturbed autonomic function, while cardiac MRIfindings argue against myocardial dysfunction and myocarditis.Clinical ImplicationsCardiopulmonary testing to identify etiologies of persistent symptoms in post-acute sequalae of COVID-19 or “Long COVID” should be performed in a manner that allows for assessment of heart rate response to exercise.Therapeutic trials of antiviral, anti-inflammatory, and exercise strategies in PASC are urgently needed and should include assessment of symptoms and objective testing with cardiopulmonary exercise testing.

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Section: Implications For Therapymentioning

confidence: 99%

Reduced exercise capacity, chronotropic incompetence, and early systemic inflammation in cardiopulmonary phenotype Long COVID

Durstenfeld

Peluso

Kaveti

et al. 2022

Preprint

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“…Others have demonstrated faster viral clearance with nirmatrelvir/ritonavir [24, 25]; as higher viral loads and prolonged viral shedding have been previously associated with risk of Long COVID [3, 4], there is a strong rationale for the hypothesis that treatment with nirmatrelvir/ritonavir may lower the risk of Long COVID. Secondly, in this cohort, we have previously shown that the number of symptoms during acute infection is associated with Long COVID symptoms independent of vaccination and variant wave [15], but whether reducing acute symptoms with antiviral therapy reduces risk of Long COVID has not been demonstrated.…”

Section: Discussionmentioning

confidence: 93%

“…The primary outcome was ≥1 self-reported Long COVID symptom more than 90 days after first SARS-CoV-2 positive test on a cross-sectional survey distributed in November 2022 that asked about presence, duration, and severity of Long COVID symptoms using a non-validated instrument as we have previously published [15]. Symptoms queried included fatigue, shortness of breath, confusion, headache, altered taste and smell, joint pain, muscle aches, cough, chest pain, scratchy throat, nausea, vomiting, diarrhea, fever, chills, red or painful eyes, sore throat, and other.…”

Section: Methodsmentioning

confidence: 99%

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Association of Nirmatrelvir/Ritonavir Treatment with Long COVID Symptoms in an Online Cohort of Non-Hospitalized Individuals Experiencing Breakthrough SARS-CoV-2 Infection in the Omicron Era

Durstenfeld

Peluso²,

Lin³

et al. 2023

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BackgroundOral nirmatrelvir/ritonavir is a treatment for COVID-19, but whether treatment during the acute phase reduces the risk of developing Long COVID is unknown.MethodsUsing the Covid Citizen Science (CCS) online cohort, we surveyed individuals who reported their first SARS-CoV-2 positive test between March and August 2022 regarding Long COVID symptoms. We excluded those who were pregnant, unvaccinated, hospitalized for COVID-19, or received other antiviral therapy. The primary exposure was oral nirmatrelvir/ritonavir. The primary outcome was the presence of any Long COVID symptoms reported on cross-sectional surveys in November and December 2022. We used propensity-score models and inverse probability of treatment weighting to adjust for differences in treatment propensity. Our secondary question was whether symptom or test positivity rebound were associated with Long COVID.Results4684 individuals met the eligibility criteria, of whom 988 (21.1%) were treated and 3696 (78.9%) were untreated; 353/988 (35.7%) treated and 1258/3696 (34.0%) untreated responded to the survey. Median age was 55 years and 66% were female. We did not identify an association between nirmatrelvir/ritonavir treatment and Long COVID symptoms (OR 1.15; 95%CI 0.80-1.64). Among n=666 treated with nirmatrelvir/ritonavir who responded who responded to questions about rebound, rebound symptoms or test positivity were not associated with Long COVID symptoms (OR 1.34; 95%CI 0.74-2.41; p=0.33).ConclusionsWithin this cohort, treatment with nirmatrelvir/ritonavir among vaccinated, non-hospitalized individuals was not associated with lower prevalence of Long COVID symptoms or severity of Long COVID. Experiencing rebound symptoms or test positivity is not strongly associated with developing Long COVID.

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“…Through impacting physical and mental functioning (3), long COVID can contribute to mental health disorders including anxiety and depression (4). Yet only a handful of US population-based studies have explored sociodemographic and socioeconomic predictors of long COVID and economic and health sequelae, and such studies remain limited to relatively small samples (5)(6)(7)(8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

Who Gets Long COVID and Suffers its Mental Health and Socioeconomic Consequences in the United States? Preliminary Findings from a Large Nationwide Study

Kim¹

2023

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As the coronavirus (COVID-19) pandemic approaches the three-year mark and the number of confirmed COVID-19 cases now exceeds 100 million cases in the United States and continues to climb, there have been increasing concerns raised over the future public health and economic burden of long COVID including disability and concomitant declines in labor force participation. Only a handful of US studies have explored sociodemographic and socioeconomic characteristics that may put people at risk of long COVID or have investigated the possible mental health and socioeconomic sequelae of long COVID. In this paper, I report findings from the largest multivariable analysis to date using US nationally-representative population-based data on 152,812 adults including 19,871 adults with long COVID to explore key predictors and sequelae of long COVID. An estimated 14.0% of US adults aged 18-84 years (34.55 million adults; 95% CI = 33.63 to 35.47 million adults) and 15.4% of US working-aged adults aged 18-64 years (31.14 million adults; 95% CI = 30.26 to 32.02 million adults) had developed long COVID by November 2022. I identify several sociodemographic and socioeconomic factors as predictors of long COVID including lower household income levels, being Hispanic, female, gay/lesbian or bisexual, and divorced or separated. Even after accounting for such factors, having long COVID was linked to higher risks of recent unemployment, financial hardship, and anxiety and depressive symptomatology, with evidence of dose-response relationships. Overall, an estimated 27.3 million US adults with long COVID were at risk of adverse socioeconomic and health outcomes including anxiety and depression. These preliminary estimates highlight the substantial public health and economic implications of long COVID among Americans and should prompt further inquiry and intervention.

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Factors Associated With Long COVID Symptoms in an Online Cohort Study

Cited by 61 publications

References 34 publications

Reduced exercise capacity, chronotropic incompetence, and early systemic inflammation in cardiopulmonary phenotype Long COVID

Reduced exercise capacity, chronotropic incompetence, and early systemic inflammation in cardiopulmonary phenotype Long COVID

Association of Nirmatrelvir/Ritonavir Treatment with Long COVID Symptoms in an Online Cohort of Non-Hospitalized Individuals Experiencing Breakthrough SARS-CoV-2 Infection in the Omicron Era

Who Gets Long COVID and Suffers its Mental Health and Socioeconomic Consequences in the United States? Preliminary Findings from a Large Nationwide Study

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