Published on Thu Jul 08 2021

POST-COVID-19 SYNDROME, INFLAMMATORY MARKERS AND SEX DIFFERENCES

MAAMAR, M., ARTIME, A., PARIENTE RODRIGO, E., FIERRO, P., RUIZ, Y., GUTIERREZ, S., GONZALEZ SANTAMARIA, R., BUSTAMANTE, E., PINEDO, G., RODRIGUEZ, B., PENA IRUN, A., GOMEZ GUTIERREZ, M. A., URARTE, C., PEREZ-PAJARES, I., TOBALINA, M., SECADA, C., DIAZ-SALAZAR, S., PINI VALDIVIESO, S., RAMOS BARRON, C., OLMOS MARTINEZ, J. M., HERNANDEZ HERNANDEZ, J. L.

Post-COVID syndrome (PCS) is a poorly-known entity. Underlying low-grade inflammation has been theorized as one of its pathophysiological mechanisms. We aimed to investigate a possible relationship between PCS and an increase in inflammation markers, in a sex-stratified analysis. We analyzed 121 subjects with mild COVID-19 (56.2% women; mean age 46 years) The most common symptom in the acute episode was fever (60.3%), while it was fatigue in PCS (42.8%)

9
11
18
Abstract

INTRODUCTION AND OBJECTIVE Post-COVID syndrome (PCS) is a poorly-known entity. Underlying low-grade inflammation (LGI) has been theorized as one of its pathophysiological mechanisms. We aimed to investigate a possible relationship between PCS and an increase in inflammation markers, in a sex-stratified analysis. PARTICIPANTS AND METHODS Mild cases of COVID-19 according to the WHO classification followed-up in a Primary Care Center, were included. We collected epidemiological data (age, sex, body mass index -BMI-, smoking, and comorbidities -Charlson index-), variables of the acute COVID-19 episode, and data at 3 months of follow-up (clinical manifestations and inflammatory markers). Serum C-reactive protein (CRP), neutrophil and lymphocyte counts, neutrophil/lymphocyte ratio (NLR), lactate dehydrogenase (LDH), ferritin, fibrinogen, and D-dimer levels were analyzed. Low-grade inflammation (LGI) was defined as serum CRP between >0.3 and <1.0 mg/dL. Five composite indices were built combining the upper ranges of 4 markers. Bivariate and multivariate analyses (logistic regression and general linear models) were performed, stratified by sex. RESULTS We analyzed 121 subjects with mild COVID-19 (56.2% women; mean age 46 years). The most common symptom in the acute episode was fever (60.3%), while it was fatigue in PCS (42.8%). Prevalence of PCS was 35.8% in women and 20.8% in men (p = 0.07). In women, after controlling for age, BMI, smoking, and comorbidities, the D1, D3, and D4 indices were consistently associated with PCS, with ORs of 5.14 (95% CI, 1.6-16.4), 4.20 (95% CI, 1.3- 13.3), and 4.12 (95% CI, 1.3-13.1), respectively; in patients with post-COVID anosmia and ageusia, neutrophils were significantly elevated (3.43 {+/-} 0.3 vs 2.58 {+/-} 0.1; p = 0.014, and 3.89 {+/-}0.3 vs 2.59 {+/-} 0.1; p = 0.002, respectively), after adjusting for confounders. In men, the D2 and D5 indices were associated with PCS, with adjusted ORs of 10.1 (95% CI, 1.2- 85) and 17.5 (95% CI, 2-153), respectively; furthermore, serum CRP in the LGI range was associated with PCS [adjusted OR=12.9 (95% CI, 1.3-121)], and in post-COVID persistent fatigue, the neutrophil count was significantly elevated (4.68 {+/-} 0.6 vs 3.37 {+/-} 0.1; p = 0.041), after controlling for confounders. CONCLUSIONS Consistent associations among PCS, anosmia, ageusia, and fatigue, with slight -but significant- elevated levels of inflammatory markers, have been observed. The neutrophil count was the most frequently involved marker. Sex-stratified analyses showed relevant differences between women and men concerning PCS and serum inflammatory markers.