Post-acute sequelae of SARS-CoV-2 infection (PASC): a protocol for a multidisciplinary prospective observational evaluation of a cohort of patients surviving hospitalisation in Sao Paulo, Brazil

Abstract

IntroductionCOVID-19 may lead to persistent and potentially incapacitating clinical manifestations (post-acute sequelae of SARS-CoV-2 infection (PASC)). Using easy-to-apply questionnaires and scales (often by telephone interviewing), several studies evaluated samples of COVID-19 inpatients from 4 weeks to several months after discharge. However, studies conducting systematic multidisciplinary assessments of PASC manifestations are scarce, with thorough in-person objective evaluations restricted to modestly sized subsamples presenting greatest disease severity.Methods and analysesWe will conduct a prospective observational study of surviving individuals (above 18 years of age) from a cohort of over 3000 subjects with laboratory-confirmed COVID-19 who were treated as inpatients at the largest academic health centre in Sao Paulo, Brazil (Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo). All eligible subjects will be consecutively invited to undergo a 1–2-day series of multidisciplinary assessments at 2 time-points, respectively, at 6–9 months and 12–15 months after discharge. Assessment schedules will include detailed multidomain questionnaires applied by medical research staff, self-report scales, objective evaluations of cardiopulmonary functioning, physical functionality and olfactory status, standardised neurological, psychiatric and cognitive examinations, as well as diagnostic laboratory, muscle ultrasound and chest imaging exams. Remaining material from blood tests will be incorporated by a local biobank for use in future investigations on inflammatory markers, genomics, transcriptomics, peptidomics and metabolomics.Ethics and disseminationAll components of this programme have been approved by local research ethics committees. We aim to provide insights into the frequency and severity of chronic/post-COVID multiorgan symptoms, as well as their interrelationships and associations with acute disease features, sociodemographic variables and environmental exposures. Findings will be disseminated in peer-reviewed journals and at scientific meetings. Additionally, we aim to provide a data repository to allow future pathophysiological investigations relating clinical PASC features to biomarker data extracted from blood samples.Trial registration numberRBR-8z7v5wc; Pre-results.

Post-acute sequelae of SARS-CoV-2 infection: relationship of central nervous system manifestations with physical disability and systemic inflammation

“…Comorbid conditions prior to COVID-19 were identified using a database of information for all cases with suspected COVID-19 during their admission as inpatients at HCFMUSP (Busatto et al, 2021 ), and we excluded patients with a previous diagnosis of dementia or end-stage cancer. Additional exclusion criteria were nosocomial COVID-19 infection, subjects living in nursing homes or long-term care facilities, and insufficient physical mobility to leave home.…”

“…Online Supplementary material 1 (Methods S1) provides further details on the study period, procedures, and laboratory confirmation of COVID-19. A full description of general procedures for invitations and assessments was provided elsewhere (Busatto et al, 2021 ).…”

“…To assess symptoms of PTSD (Weathers, Litz, Herman, Huska, & Keane, 1993 ), anxiety and depression (Zigmond & Snalth, 1983 ), insomnia (Bastien, Vallières, & Morin, 2001 ), and subjective memory impairment (Vale, Balieiro, & Silva-Filho, 2012 ), multi-item scales were applied by specialized teams (Busatto et al, 2021 ). Validated cutoffs were used to generate categorical ‘yes-no’ variables (see online Supplementary Methods S2 and Table S1 for details).…”

“…fatigue, dyspnea, muscle/joint pain, and taste and/or olfaction changes) were also assessed using standardized scales (Bestall et al, 1999 ; Boonstra, Preuper, Balk, & Stewart, 2014 ; Brandão Neto et al, 2021 ; Webster, Cella, & Yost, et al, 2003 ) (see online Supplementary Table S1 for details). An adaptation of the WHO screening tool for neuroepidemiology investigations in low-and-middle-income countries (WHO, 1982 ) was applied by a team of neurologists (Busatto et al, 2021 ) to assess neurological manifestations including headache, weakness, gait problems, episodes of loss of consciousness, and paresthesia. Finally, subjects were inquired about the presence of 14 persistent post-COVID symptoms covering additional organ-system domains (Busatto et al, 2021 ) (see full list in online Supplementary Table S1).…”

Reabilitação ambulatorial da COVID longa: uma chamada à ação

“…The evaluation protocol for patients with long COVID is consistent with the institutional standards. 28 The sociodemographic and clinical information collected comprises age, gender, ethnic group, education, profession or occupation, origin, body mass index, date of hospital admission, and discharge for the treatment of acute infection. As part of the assessments, information on hospital stay and/or Intensive Care Unit, classification of the severity of SARS-CoV-2 infection by the WHO (Mild, Moderate, Severe and Critical), time since hospital discharge, presence of comorbidities (hypertension, diabetes, obesity, heart disease, vascular diseases, asthma, cancer, or others), time of rehabilitation in outpatient care, and rehabilitation status (objectives achieved, partially achieved or not achieved) were also retrieved.…”