Prevalence and determinants of persistent symptoms after infection with SARS-CoV-2: protocol for an observational cohort study (LongCOVID-study)

Abstract

IntroductionA substantial proportion of individuals infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), report persisting symptoms weeks and months following acute infection. Estimates on prevalence vary due to differences in study designs, populations, heterogeneity of symptoms and the way symptoms are measured. Common symptoms include fatigue, cognitive impairment and dyspnoea. However, knowledge regarding the nature and risk factors for developing persisting symptoms is still limited. Hence, in this study, we aim to determine the prevalence, severity, risk factors and impact on quality of life of persisting symptoms in the first year following acute SARS-CoV-2 infection.Methods and analysisThe LongCOVID-study is both a prospective and retrospective cohort study being conducted in the Netherlands, with a one year follow-up. Participants aged 5 years and above, with self-reported positive or negative tests for SARS-CoV-2 will be included in the study. The primary outcome is the prevalence and severity of persistent symptoms in participants that tested positive for SARS-CoV-2 compared with controls. Symptom severity will be assessed for fatigue (Checklist Individual Strength (CIS subscale fatigue severity)), pain (Rand-36/SF-36 subscale bodily pain), dyspnoea (Medical Research Council (mMRC)) and cognitive impairment (Cognitive Failure Questionnaire (CFQ)). Secondary outcomes include effect of vaccination prior to infection on persistent symptoms, loss of health-related quality of life (HRQoL) and risk factors for persisting symptoms following infection with SARS-CoV-2.Ethics and disseminationThe Utrecht Medical Ethics Committee (METC) declared in February 2021 that the Medical Research Involving Human Subjects Act (WMO) does not apply to this study (METC protocol number 21-124/C). Informed consent is required prior to participation in the study. Results of this study will be submitted for publication in a peer-reviewed journal.

STIMULATE-ICP: A pragmatic, multi-centre, cluster randomised trial of an integrated care pathway with a nested, Phase III, open label, adaptive platform randomised drug trial in individuals with Long COVID: a structured protocol

“…Cognitive Failure Questionnaire (CFQ) if an individual scores 3 or more on PDQ5 (individuals receive an email to complete this questionnaire online via a secure password and patient ID number)(31,32)…”

Prevalence and severity of symptoms 3 months after infection with SARS-CoV-2 compared to test-negative and population controls in the Netherlands

“…Details on the study design are described in the study protocol (in preprint). 12 In this paper we report on COVID-19 cases aged 18 or older three months after a positive SARS-CoV-2 test who joined the study between May 19 th 2021 and December 13th 2021. Cases (included within seven days after a positive polymerase chain reaction (PCR) or rapid lateral flow (antigen) SARS-COV-2-test) were recruited from three sources as defined in the study protocol (accepted for publication) 12 To control for background prevalence of long-term symptoms in individuals without suspected or confirmed COVID-19, two control groups were included.…”

“…12 In this paper we report on COVID-19 cases aged 18 or older three months after a positive SARS-CoV-2 test who joined the study between May 19 th 2021 and December 13th 2021. Cases (included within seven days after a positive polymerase chain reaction (PCR) or rapid lateral flow (antigen) SARS-COV-2-test) were recruited from three sources as defined in the study protocol (accepted for publication) 12 To control for background prevalence of long-term symptoms in individuals without suspected or confirmed COVID-19, two control groups were included. One group consisted of test-negative adults, who were included within seven days after a negative SARS-CoV-2 test and indicated the presence of symptoms as reason to perform the test (test-negative controls); the other control group consisted of adults randomly invited by direct mail from the Dutch population (population controls).…”

“…including only participants that completed both T0 and T3 surveys, without any missing data points as discussed in the study protocol (accepted for publication)). 12 As a sensitivity analysis, we used four additional scenarios to substitute missing data at T3, and included the symptoms significantly elevated in the primary analysis to assess alternative prevalence of at least one of these symptoms in cases and controls (specified in supplement ).…”

“…Statistical procedures were predefined in a published study protocol (accepted for publication)). 12 Descriptive statistics were used for participant characteristics, vaccination status and describing acute disease. The prevalence of all symptoms and the severity of fatigue, cognitive impairment, pain and dyspnoea was analysed at T0 and T3, and compared between cases and the two control groups.…”