Post-COVID-19 syndrome, low-grade inflammation and inflammatory markers: a cross-sectional study.

OBJECTIVE: Post-COVID syndrome (PCS) is a poorly known entity. An underlying chronic, low-grade inflammation (LGI) has been theorized as a pathophysiological mechanism. Available data on biomarkers in PCS show conflicting results. Our aim was to know whether subjects with PCS present higher levels of inflammatory markers, after a mild COVID-19. METHODS: Analytical cross-sectional study. Cases of mild COVID-19 in a community setting were included. We collected epidemiological data (age, sex, BMI, smoking, comorbidities), variables of the acute COVID-19 (duration, symptoms), and data at 3 months after the acute phase (symptoms and laboratory test). Serum C-reactive protein (CRP), neutrophil and lymphocyte counts, neutrophil/lymphocyte ratio (NLR), lactate dehydrogenase, ferritin, fibrinogen, and D-dimer levels were analysed. LGI was defined as CRP >0.3 and <1.0 mg/dL. A subject was classified as PCS + if presented signs and symptoms >12 weeks after an infection consistent with COVID-19. Five composite indices (C1-C5) were developed, combining the upper ranges of biomarkers distributions. Multivariate analyses were performed. RESULTS: We analysed 121 mild COVID-19 cases (mean age = 45.7 years, 56.2% women). Among the acute symptoms, women presented a higher frequency of fatigue (54.4% vs 30.2%; p = .008). PCS affected 35.8% of women and 20.8% of men (p = .07), and the most reported symptoms were fatigue (42.8%), anosmia (40%), ageusia (22.8%), dyspnea (17.1%) and myalgia (11.4%). Neutrophil count, NLR, CRP and fibrinogen showed the best correlations with PCS and were selected to develop the indices. In women PCS+, C1, C3 and C4 indices were more frequently met, while in men PCS+, C2, C5 and CRP were in the range of LGI. Anosmia, ageusia and fatigue were related to higher neutrophil counts, with sex differences. Fibrinogen levels were higher in persistent myalgia (510 ± 82 mg/dL vs 394 ± 87; p = .013). In multivariable analysis, a woman with a neutrophil count above the median, or with fibrinogen level or NLR in the highest tertile, had a 4-5-fold increased risk of prevalent PCS. A man with CRP in the range of LGI, or fibrinogen level or a neutrophil count in the highest tertile, had a 10-17-fold increased risk of prevalent PCS. CONCLUSIONS: The data obtained in the present cross-sectional study seems to demonstrate a consistent association between PCS and upper ranges of the neutrophil count, NLR, fibrinogen, and CRP in the LGI range. Furthermore, composite indices appear useful in detecting relationships between slight elevations of biomarkers and PCS, and our study identifies relevant sex differences in symptoms and markers regarding the PCS.

Methylprednisolone in adults hospitalized with COVID-19 pneumonia : An open-label randomized trial (GLUCOCOVID).

PURPOSE: To determine whether a 6-day course of methylprednisolone (MP) improves outcome in patients with severe SARS-CoV­2 (Corona Virus Disease 2019 [COVID-19]). METHODS: The study was a multicentric open-label trial of COVID-19 patients who were aged ≥ 18 years, receiving oxygen without mechanical ventilation, and with evidence of systemic inflammatory response who were assigned to standard of care (SOC) or SOC plus intravenous MP (40 mg bid for 3 days followed by 20 mg bid for 3 days). The primary outcome was a composite of death, admission to the intensive care unit, or requirement for noninvasive ventilation. Both intention-to-treat (ITT) and per protocol (PP) analyses were performed. RESULTS: A total of 91 patients were screened, and 64 were randomized (mean age70 ± 12 years). In the ITT analysis, 14 of 29 patients (48%) in the SOC group and 14 of 35 (40%) in the MP group suffered the composite endpoint (40% versus 20% in patients under 72 years and 67% versus 48% in those over 72 years; p = 0.25). In the PP analysis, patients on MP had a significantly lower risk of experiencing the composite endpoint (age-adjusted risk ratio 0.42; 95% confidence interval, CI 0.20-0.89; p = 0.043). CONCLUSION: The planned sample size was not achieved, and our results should therefore be interpreted with caution. The use of MP had no significant effect on the primary endpoint in ITT analysis; however, the PP analysis showed a beneficial effect due to MP, which consistent with other published trials support the use of glucocorticoids in severe cases of COVID-19.

Vitamin D Status in Hospitalized Patients with SARS-CoV-2 Infection.

BACKGROUND: The role of vitamin D status in COVID-19 patients is a matter of debate. OBJECTIVES: To assess serum 25-hydroxyvitamin D (25OHD) levels in hospitalized patients with COVID-19 and to analyze the possible influence of vitamin D status on disease severity. METHODS: Retrospective case-control study of 216 COVID-19 patients and 197 population-based controls. Serum 25OHD levels were measured in both groups. The association of serum 25OHD levels with COVID-19 severity (admission to the intensive care unit, requirements for mechanical ventilation, or mortality) was also evaluated. RESULTS: Of the 216 patients, 19 were on vitamin D supplements and were analyzed separately. In COVID-19 patients, mean ±â€…standard deviation 25OHD levels were 13.8 ±â€…7.2 ng/mL, compared with 20.9 ±â€…7.4 ng/mL in controls (P < .0001). 25OHD values were lower in men than in women. Vitamin D deficiency was found in 82.2% of COVID-19 cases and 47.2% of population-based controls (P < .0001). 25OHD inversely correlates with serum ferritin (P = .013) and D-dimer levels (P = .027). Vitamin D-deficient COVID-19 patients had a greater prevalence of hypertension and cardiovascular diseases, raised serum ferritin and troponin levels, as well as a longer length of hospital stay than those with serum 25OHD levels ≥20 ng/mL. No causal relationship was found between vitamin D deficiency and COVID-19 severity as a combined endpoint or as its separate components. CONCLUSIONS: 25OHD levels are lower in hospitalized COVID-19 patients than in population-based controls and these patients had a higher prevalence of deficiency. We did not find any relationship between vitamin D concentrations or vitamin deficiency and the severity of the disease.