Pneumomediastinum in COVID-19: Risk factors and outcomes from a multicentre case-control study.

BACKGROUND: An increased incidence of pneumomediastinum has been observed among patients hospitalized with coronavirus disease 2019 (COVID-19) pneumonia. The study aimed to identify risk factors for COVID-19-associated pneumomediastinum and investigate the impact of pneumomediastinum on clinical outcomes. METHODS: In this multicentre retrospective case-control study, we included consecutive patients with COVID-19 pneumonia and pneumomediastinum hospitalized from March 2020 to July 2020 at ten centres; then, we identified a similarly sized control group of consecutive patients hospitalized with COVID-19 pneumonia and respiratory failure who did not develop pneumomediastinum during the same period. Clinical, laboratory, and radiological characteristics, as well as respiratory support and outcomes, were collected and compared between the two groups. Risk factors of pneumomediastinum were assessed by multivariable logistic analysis. RESULTS: Overall 139 patients with pneumomediastinum and 153 without pneumomediastinum were analysed. Lung involvement ≥75 %, consolidations, body mass index (BMI) < 22 kg/m2, C-reactive protein (CRP) > 150 mg/L, D-dimer >3000 ng/mL FEUs, and smoking exposure >20 pack-year were all independently correlated with the occurrence of pneumomediastinum. Patients with pneumomediastinum had a longer hospital stay (mean ± SD 31.2 ± 20.2 days vs 19.6 ± 14.2, p < 0.001), higher intubation rate (73/139, 52.5 % vs 27/153, 17.6 %, p < 0.001), and in-hospital mortality (68/139, 48.9 % vs 36/153, 23.5 %, p < 0.001) compared to controls. CONCLUSIONS: Extensive lung parenchyma involvement, consolidations, low BMI, high inflammatory markers, and tobacco exposure are associated with a greater risk of pneumomediastinum in COVID-19 pneumonia. This complication significantly worsens the outcomes.

Prolonged higher dose methylprednisolone versus conventional dexamethasone in COVID-19 pneumonia: a randomised controlled trial (MEDEAS).

BACKGROUND: Dysregulated systemic inflammation is the primary driver of mortality in severe coronavirus disease 2019 (COVID-19) pneumonia. Current guidelines favour a 7-10-day course of any glucocorticoid equivalent to dexamethasone 6 mg daily. A comparative randomised controlled trial (RCT) with a higher dose and a longer duration of intervention was lacking. METHODS: We conducted a multicentre, open-label RCT to investigate methylprednisolone 80 mg as a continuous daily infusion for 8 days followed by slow tapering versus dexamethasone 6 mg once daily for up to 10 days in adult patients with COVID-19 pneumonia requiring oxygen or noninvasive respiratory support. The primary outcome was reduction in 28-day mortality. Secondary outcomes were mechanical ventilation-free days at 28 days, need for intensive care unit (ICU) referral, length of hospitalisation, need for tracheostomy, and changes in C-reactive protein (CRP) levels, arterial oxygen tension/inspiratory oxygen fraction (P aO2 /F IO2 ) ratio and World Health Organization Clinical Progression Scale at days 3, 7 and 14. RESULTS: 677 randomised patients were included. Findings are reported as methylprednisolone (n=337) versus dexamethasone (n=340). By day 28, there were no significant differences in mortality (35 (10.4%) versus 41 (12.1%); p=0.49) nor in median mechanical ventilation-free days (median (interquartile range (IQR)) 23 (14) versus 24 (16) days; p=0.49). ICU referral was necessary in 41 (12.2%) versus 45 (13.2%) (p=0.68) and tracheostomy in 8 (2.4%) versus 9 (2.6%) (p=0.82). Survivors in the methylprednisolone group required a longer median (IQR) hospitalisation (15 (11) versus 14 (11) days; p=0.005) and experienced an improvement in CRP levels, but not in P aO2 /F IO2 ratio, at days 7 and 14. There were no differences in disease progression at the prespecified time-points. CONCLUSION: Prolonged, higher dose methylprednisolone did not reduce mortality at 28 days compared with conventional dexamethasone in COVID-19 pneumonia.

Prolonged Low-Dose Methylprednisolone in Patients With Severe COVID-19 Pneumonia.

BACKGROUND: In hospitalized patients with coronavirus disease 2019 (COVID-19) pneumonia, progression to acute respiratory failure requiring invasive mechanical ventilation (MV) is associated with significant morbidity and mortality. Severe dysregulated systemic inflammation is the putative mechanism. We hypothesize that early prolonged methylprednisolone (MP) treatment could accelerate disease resolution, decreasing the need for intensive care unit (ICU) admission and mortality. METHODS: We conducted a multicenter observational study to explore the association between exposure to prolonged, low-dose MP treatment and need for ICU referral, intubation, or death within 28 days (composite primary end point) in patients with severe COVID-19 pneumonia admitted to Italian respiratory high-dependency units. Secondary outcomes were invasive MV-free days and changes in C-reactive protein (CRP) levels. RESULTS: Findings are reported as MP (n = 83) vs control (n = 90). The composite primary end point was met by 19 vs 40 (adjusted hazard ratio [aHR], 0.41; 95% CI, 0.24-0.72). Transfer to ICU and invasive MV were necessary in 15 vs 27 (P = .07) and 14 vs 26 (P = .10), respectively. By day 28, the MP group had fewer deaths (6 vs 21; aHR, 0.29; 95% CI, 0.12-0.73) and more days off invasive MV (24.0 ±â€…9.0 vs 17.5 ±â€…12.8; P = .001). Study treatment was associated with rapid improvement in PaO2:FiO2 and CRP levels. The complication rate was similar for the 2 groups (P = .84). CONCLUSION: In patients with severe COVID-19 pneumonia, early administration of prolonged MP treatment was associated with a significantly lower hazard of death (71%) and decreased ventilator dependence. Treatment was safe and did not impact viral clearance. A large randomized controlled trial (RECOVERY trial) has been performed that validates these findings. Clinical trial registration. ClinicalTrials.gov NCT04323592.