The Apoprotein E4 isotype does not affect the severity of COVID-19 infection and other flu-like syndromes

<b>Introduction.</b> Apolipoprotein E (ApoE), especially the ApoE4 isotype, is suggested to influence the severity of respiratory viral infections; however, this association is still unclear.<b>Hypothesis.</b> The presence of allele ε4 impacts the development of flu-like syndromes.<b>Aim.</b> This study aimed to evaluate the impact of the Apo E4 isoform on the severity and duration of flu-like syndromes, including the coronavirus disease COVID-19.<b>Methodology.</b> This study comprised 280 individuals presenting flu-like symptoms, all genotyped for ApoE isoforms. Data were collected on clinical course, comorbidities, nutritional status, biochemical and inflammatory markers, SARS-CoV-2 reverse transcription PCR results and disease severity (mild, moderate or severe) according to the World Health Organization criteria. The individuals were analysed as a whole and within subgroups based on the SARS-CoV-2-positive (COVID-19 group) or SARS-CoV-2-negative (flu-like syndrome group) test.<b>Results.</b> The frequency of the ε4 allele was similar across the whole population and in both the COVID-19 and flu-like syndrome subgroups (17 and 18%, respectively). No differences were seen in sex, age range, self-reported skin colour, body mass index (BMI), number of comorbidities, vaccination status, biochemical, cytokine and lipid profiles (except for total cholesterol) in the flu-like group when ε4 allele carriers and non-carriers were compared. In the COVID-19 group, the ε4 allele did not correlate with disease severity or duration, number of comorbidities or inflammatory biomarkers. While gender distribution was equal in the overall COVID-19 population, male gender strongly correlated with COVID-19 severity. Multivariate analysis showed that older individuals, male gender, higher BMI and the presence of comorbidities were linked to increased chances of developing moderate and severe disease. IL-4 was the only factor found to reduce the risk of severe COVID-19.<b>Conclusion.</b> The presence of one ɛ4 allele showed no association with the duration and severity of flu-like syndromes, including COVID-19. Nonetheless, SARS-CoV-2-positive individuals tend to be older men with a higher BMI and a tendency to be overweight or with obesity. Regarding COVID-19 severity, BMI, male sex and the number of associated comorbidities were the factors that increased the chance of developing a more severe form of COVID-19.