ABSTRACT
Background: Muscle and fat mass loss as a consequence of protein catabolism and prolonged immobilization is frequent in critically ill patients. Post-COVID acute sarcopenia may be due also to inflammaging for the strong inflammatory reaction. The study aims were to describe changes in chest CT body composition parameters from baseline to follow-up CT scan in severe COVID-19 survivors, and to evaluate the impact of COVID-19 inflammatory burden on these changes. Methods: Baseline (t0), 2-3 months (t1) and 6-7 months (t2) follow-up CT scan of severe COVID-19 pneumonia survivors were retrospectively reviewed to measure pectoralis muscle area (PMA) and density (PMD), liver-to-spleen ratio (LSR), and total, visceral, and intermuscular adipose tissue areas (TAT, VAT and IMAT) at T7-T8 vertebrae. C-reactive protein (CRP) curve integral was used to describe COVID-19 inflammatory burden, and its impact on body composition changes was evaluated in multivariable linear regression models adjusted for age, sex, and baseline TAT (index of general adiposity). Results: At follow-up a decrease in mean PMA and in all mean body fat areas was registered, faster from t0 to t1, and slower from t1 to t2, with the exception of PMD, which increased (i.e. intramuscular fat decreased) only from t1 to t2 (Table). Mean VAT decrease was more conspicuous than mean TAT decrease. In models adjusted for age, sex, and baseline TAT, increasing CRP integral was significantly associated with higher PMA reduction (p=0,017 for delta t2-t0) and lower PMD increase (p=0.01 for delta t2-t0), higher LSR increase (i.e. higher steatosis decrease) (p<0.0001 for delta t1-t0, n.s. for delta t2-t0), and higher VAT decrease (p=0.035 for delta t2-t0), but not with TAT decrease. These associations were stronger in patients with higher VAT and lower LSR at baseline. Conclusion: Muscle and fat loss after COVID-19 is faster in the first months, but slowly continues till 6-7 months. Fat loss is more apparent in visceral compartments. Inflammatory burden is associated with the degree of muscle and visceral/liver fat loss.
ABSTRACT
Objective: Chloroquine (CLQ)/hydroxychloroquine (HCQ) are two of the most studied drugs for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. There are very limited data on the effect of treatment of patients affected by rheumatic diseases with HCQ/CLQ and other conventional disease-modifying anti-rheumatic drugs (cDMARDs) on COVID-19. The aim of this study is to investigate the hypothesis that treatment of rheumatic diseases with hydroxychloroquine (HCQ)/chloroquine (CLQ) as compared to other conventional disease-modifying anti-rheumatic drugs (cDMARDs) might decrease the COVID-19-related risk of hospitalization and mortality. Methods: This large-scale case-control study nested within a cohort of cDMARD users was conducted in the Lombardy, Veneto, Tuscany and Lazio regions and Reggio Emilia (Emilia Romagna) Local Health Unit, covering a total of 25.1 million inhabitants. Claims databases were linked to loco-regional COVID-19 surveillance registries from the same catchment area through unique fully-anonymized patient identifiers. Risk of COVID-19-related outcomes was estimated as odds ratios (ORs) along with 95% confidence intervals (CIs), using a multivariate conditional logistic regression analysis, by comparing HCQ/CLQ vs methotrexate (primary comparator) and other cDMARDs (secondary comparator). In addition, the same risk for HCQ/CLQ, methotrexate and other cDMARDs separately vs nonuse of these drugs as well as for presence of rheumatic diseases vs. absence in a non-nested population was investigated. Results: From the cohort of cDMARD users, 1275 cases who were hospitalized due to COVID-19 were identified and matched to 12,734 controls. When compared to recent use of methotrexate, no statistically significant association between recent HCQ/CLQ monotherapy with COVID-19 hospitalization (OR 0.83 [95% CI, 0.69 to 1.00]) or mortality (OR 1.19 [95% CI, 0.85 to 1.67]) was observed. A statistically significant lower risk was found when comparing recent use of HCQ/CLQ to treatment with other cDMARDs and glucocorticoids concomitantly. In the sensitivity analysis in the non-nested population, HCQ/CLQ was not associated with COVID-19 hospitalization as compared with non-use, whereas a mild statistically significant increased risk for recent use of both methotrexate as monotherapy (OR 1.19 [95% CI, 1.05 to 1.34]) or other cDMARDs (OR 1.21 [95% CI, 1.08 to 1.36]) vs non-use was found. Finally, the presence of rheumatoid arthritis or systemic lupus erythematosus was not associated with COVID-19 hospitalization (OR 0.98 [95% CI, 0.89 to 1.07]) or mortality (OR 0.88 [95% CI, 0.74 to 1.05]). Conclusion: Prior exposure to HCQ/CLQ in rheumatic patients was not associated with a protective effect against COVID-19-related hospitalization and mortality. On the contrary, an increased risk in patients receiving other cDMARDs was observed when compared to non-use, especially in those patients concomitantly treated with glucocorticoids. This is likely attributable to a synergistic immunosuppressive effect, leading to increased risk of severe SARS-CoV-2 infection.