Background Bacterial and fungal superinfections may complicate the course of hospitalized patients with COVID-19. Objectives To identify predictors of superinfections in COVID-19. Methods Prospective, observational study including patients with COVID-19 consecutively admitted to the University Hospital of Pisa, Italy, between 4 March and 30 April 2020. Clinical data and outcomes were registered. Superinfection was defined as a bacterial or fungal infection that occurred ≥48 h after hospital admission. A multivariate analysis was performed to identify factors independently associated with superinfections. Results Overall, 315 patients with COVID-19 were hospitalized and 109 episodes of superinfections were documented in 69 (21.9%) patients. The median time from admission to superinfection was 19 days (range 11–29.75). Superinfections were caused by Enterobacterales (44.9%), non-fermenting Gram-negative bacilli (15.6%), Gram-positive bacteria (15.6%) and fungi (5.5%). Polymicrobial infections accounted for 18.3%. Predictors of superinfections were: intestinal colonization by carbapenem-resistant Enterobacterales (OR 16.03, 95% CI 6.5–39.5, P < 0.001); invasive mechanical ventilation (OR 5.6, 95% CI 2.4–13.1, P < 0.001); immunomodulatory agents (tocilizumab/baricitinib) (OR 5.09, 95% CI 2.2–11.8, P < 0.001); C-reactive protein on admission >7 mg/dl (OR 3.59, 95% CI 1.7–7.7, P = 0.001); and previous treatment with piperacillin/tazobactam (OR 2.85, 95% CI 1.1–7.2, P = 0.028). Length of hospital stay was longer in patients who developed superinfections ompared with those who did not (30 versus 11 days, P < 0.001), while mortality rates were similar (18.8% versus 23.2%, P = 0.445). Conclusions The risk of bacterial and fungal superinfections in COVID-19 is consistent. Patients who need empiric broad-spectrum antibiotics and immunomodulant drugs should be carefully selected. Infection control rules must be reinforced.

Objectives To evaluate the impact of low molecular weight heparin (LMWH) on the outcome of patients with SARS-CoV-2 pneumonia. Methods Prospective observational study including consecutive patients with laboratory confirmed SARS-CoV-2 pneumonia admitted to the University Hospital of Pisa (4th March-30th April 2020). Demographic, clinical, and outcome data were collected. The primary endpoint was 30-day mortality. The secondary endpoint was a composite of death or severe ARDS. LMWH, hydroxychloroquine, doxycycline, macrolides, antiretrovirals, remdesivir, baricitinib, tocilizumab, and steroids were evaluated as treatment exposures of interest. First, a Cox-regression analysis, in which treatments were introduced as time-dependent variables, was performed to evaluate the association of exposures and outcomes. Then, a time-dependent Propensity-score (PS) was calculated and a PS-matching performed for each treatment variable. Results Among 315 patients with SARS-CoV-2 pneumonia, 70 (22.2%) died during hospital stay. The composite endpoint was achieved by 114 (36.2%) patients. Overall, 244 (77.5%) patients received LMWH, 238 (75.5%) hydroxychloroquine, 201 (63.8%) proteases inhibitors, 150 (47.6%) doxycycline, 141 (44.8%) steroids, 42 (13.3%) macrolides, 40 (12.7%) baricitinib, 13 (4.1%) tocilizumab, and 13 (4.1%) remdesivir. At multivariate analysis, LMWH was associated with a reduced risk of 30-day mortality (HR 0.36 [95% CI 0.21-0.6], p<0.001) and composite endpoint (HR 0.61 [95% CI 0.39-0.95], p=0.029). The PS-matched cohort of 55 couples confirmed the same results for both primary and secondary endpoint. Conclusions This study suggests that LMWH might reduce the risk of in-hospital mortality and severe ARDS in Covid-19. Randomized controlled trials are warranted to confirm these preliminary findings.

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