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Multi-organ impairment in low-risk individuals with long COVID

Our take —

This cross-sectional study, available as a preprint and thus not yet peer reviewed, described symptoms and evidence of organ impairment up to four and a half months from acute SARS-CoV-2 infection or a clinical diagnosis of COVID-19 among relatively low-risk participants at two healthcare centers in England. They documented multi-organ MRI changes (lung, heart, pancreas, kidney, liver, and spleen) in up to ⅔ of patients, adding to the growing literature that symptoms and organ abnormalities can linger several months after initial COVID-19 diagnosis. While these findings may have implications for patient management, the lack of pre-diagnosis data means they do not establish a causal relationship between SARS-CoV-2 infection and long-term organ impairment.

Study design

Cross-Sectional

Study population and setting

This cross-sectional pre-print reports the residual impact of COVID-19 in 201 adults (mean age 44 years, 70% female) in southern England at a median follow up of 140 days from their initial symptoms at the baseline visit of an ongoing prospective cohort study. Participants were recruited from clinics in Oxford and London, England between April and August 2020 if they had a history of a positive SARS-CoV-2 PCR (n=62), a positive antibody test (n=63), or a clinical diagnosis of COVID-19 from two independent physicians (n=73) and were excluded if they had current COVID-19 symptoms, a COVID-19 hospitalization in the last 7 days, and/or contraindications to magnetic resonance imaging (MRI) at the time of enrollment. The authors assessed lung, heart, kidney, liver, pancreas and spleen function at follow up using validated symptom assessment scales, fasting laboratory values, and MRI. They compared participants by hospitalization status while symptomatic using Wilcoxon tests, Fisher exact tests, or Spearman correlation as appropriate and created a multivariable model to assess risk factors of a previous hospitalization among participants.

Summary of Main Findings

Of the 201 participants, 20% and 18% of whom reported pre-existing obesity and asthma respectively, 99% were experiencing more than three and 42% were experiencing more than nine COVID-19 symptoms at study enrollment, which occurred a median of 140 days (interquartile range (IQR) 105-160) from participants’ initial COVID-19 symptoms. The most common reported symptoms included fatigue (98%), muscle ache (88%), shortness of breath (87%), and headache (83%), and 52% of participants reported persistent problems resuming usual activities. Participants who were hospitalized with COVID-19 were more likely to have abnormal triglycerides, cholesterol, LDL-cholesterol, and transferrin saturation than those who were not. Organ dysfunction on MRI was also more common among participants who were hospitalized, with evidence of lung (33% of all participants), heart (32%), pancreas (17%), kidney (12%), liver (10%), and spleen (6%) dysfunction on MRI in 66% of participants. Multivariable logistic regression suggested that increasing age (OR=1.06, 95% Confidence Interval (95% CI) 1.02-1.10), liver volume (OR=1.18, 95% CI 1.06-1.30), and multiorgan impairment on MRI (OR=2.75, 95% CI 1.22-6.22) were associated with prior hospitalization adjusted for sex and BMI.

Study Strengths

This study includes a moderate number of participants with few comorbidities and describes well-measured symptom, laboratory, and MRI evidence of the persistent impacts of COVID-19 a median of four and a half months after initial symptoms.

Limitations

It is unclear how participants were approached for inclusion in this study, which could select for individuals still experiencing COVID-19 symptoms who are likely different from those who have recovered without lingering symptoms. This selection bias would likely artificially amplify the prevalence of the reported findings. Furthermore, we cannot conclude that the virus caused the laboratory and/or imaging findings without data from before participants were infected with SARS-CoV-2. Additionally, it is impossible to contextualize the abnormal laboratory and imaging findings without a control group of similar adults who were not exposed to SARS-CoV-2. Finally, it is difficult if not impossible to interpret a model that predicts an outcome (previous hospitalization) that occured before the recorded covariates.

Value added

This is one of the first studies to document the presence of symptoms and organ impairment about four and a half months after initial confirmation of SARS-CoV-2 infection or clinical diagnosis of COVID-19.

This review was posted on: 2 November 2020