Long COVID syndrome: a case-control study
Authors: Xuereb R A , Gatt A , Vella K , Xuereb R G , Barbara C J , Fava S , Magri C J 
Published: October 2022

Abstract

Background
Cardiovascular complications are rapidly emerging as a major threat in COVID-19 infection. Nonetheless, the mechanisms underlying the disproportionate effect of SARS-CoV-2 infection on patients with cardiovascular comorbidities remain incompletely understood.

Purpose
To assess whether COVID-19 infection has an adverse clinical outcome at medium-term follow-up.

Methods
A case-control study was performed. Cases were subjects who were diagnosed with COVID-19 infection following nasopharyhngeal swabbing. Controls were age- and gender-matched subjects who were not found to be infected with COVID-19 following swabbing and were negative on testing for COVID-19 IgG antibodies. All participants were submitted a standardised questionnaire regarding past medical history. Baseline blood investigations were taken including N-terminal pro–B-type natriuretic peptide (NT-proBNP) and troponin levels. High-sensitivity C-reactive protein (hsCRP) was taken as marker of inflammation and von Willebrand factor (vWF) was taken as marker of endothelial dysfunction.

Results
270 subjects were recruited, comprising 174 cases and 96 controls. Of the latter, 21 were found to be COVID-19 IgG positive and were excluded from the analysis. Hence, the study cohort comprised 174 cases and 75 controls. The mean age of the participants was 46.1±13.8 years. The median follow-up was of 173.5 days (IQR 129–193.25 days). There was no statistically significant difference in the baseline demographics between cases and controls with regards age, gender as well as cardiovascular risk factors and underlying medical conditions. Regarding symptomatology at follow-up, there was a statistically significant difference between the groups in deterioration in general condition (p&lt;0.001), shortness of breath (SOB) (p=0.008), fatigue (p=0.044), arthralgia (p&lt;0.001), abnormal taste (p&lt;0.001) and anosmia (p&lt;0.001), all being more frequent in subjects with prior COVID-19 infection. At follow-up, the blood investigations showed that only hsCRP was statistically significantly higher in the cases as compared to the controls (p=0.03, Figure 1). Correlation analysis consequently revealed a negative correlation in both troponin (p=0.013, r=−0.19) and vWF levels (p=0.026, r=−0.169) with time. Finally, the association between the cases experiencing dyspnoea and the blood investigations at follow-up was assessed. Multivariate analysis revealed that COVID-19 positive cases experiencing dyspnoea have significantly higher white cell count (WCC) (OR 1.22, 95% CI 1.02–1.46, p=0.029) and troponin levels (OR 1.15, 95% CI 1.02–1.29, p=0.015) and lower haemoglobin levels at follow-up (OR 0.66, 95% CI 0.5–0.86, p&lt;0.002), Figure 2.

Conclusion
Patients previously infected with COVID-19 have persistent symptomatology at medium-term follow-up. The role of troponin, together with markers of inflammation and endothelial dysfunction at long-term follow-up merit further investigation.

Funding Acknowledgement
Type of funding sources: None.