Secondary Infection in Severe and Critical COVID-19 Patients in China: A Multicenter Retrospective Study (preprint)

Background. Since 2020 COVID-19 pandemic became an emergent public sanitary incident. The epidemiology data and the impact on prognosis of secondary infection in severe and critical COVID-19 patients in China remained largely unclear.Methods. We retrospectively reviewed medical records of all adult patients with laboratory-confirmed COVID-19 who were admitted to ICUs from January 18th 2020 to April 26th 2020 at two hospitals in Wuhan, China and one hospital in Guangzhou, China. We measured the frequency of bacteria and fungi cultured from respiratory tract, blood and other body fluid specimens. The risk factors for and impact of secondary infection on clinical outcomes were also assessed. Results. Secondary infections were very common (86.6%) when patients were admitted to ICU for >72 hours. The majority of infections were respiratory, with the most common organisms being Klebsiella pneumoniae (24.5%), Acinetobacter baumannii (21.8%), Stenotrophomonas maltophilia (9.9%), Candida albicans (6.8%), and Pseudomonas spp. (4.8%). Furthermore, the proportions of multidrug resistant (MDR) bacteria and carbapenem resistant Enterobacteriaceae (CRE) were high. We also found that age ≥60 years and mechanical ventilation ≥13days independently increased the likelihood of secondary infection. Finally, patients with positive cultures had reduced ventilator free days in 28 days and patients with CRE and/or MDR bacteria positivity showed lower 28 day survival rate.Conclusions. In a retrospective cohort of severe and critical COVID-19 patients admitted to ICUs in China, the prevalence of secondary infection was high, especially with CRE and MDR bacteria, resulting in poor clinical outcomes.

Single-Cell Analysis Reveals Macrophage-Driven T Cell Dysfunction in Severe COVID-19 Patients (preprint)

The vastly spreading COVID-19 pneumonia is caused by SARS-CoV-2. Lymphopenia and cytokine levels are tightly associated with disease severity. However, virus-induced immune dysregulation at cellular and molecular levels remains largely undefined. Here, the leukocytes in the pleural effusion, sputum, and peripheral blood biopsies from severe and mild patients were analyzed at single-cell resolution. Drastic T cell hyperactivation accompanying elevated T cell exhaustion was observed, predominantly in pleural effusion. The mechanistic investigation identified a group of CD14+ monocytes and macrophages highly expressing CD163 and MRC1 in the biopsies from severe patients, suggesting M2 macrophage polarization. These M2-like cells exhibited up-regulated IL10, CCL18, APOE, CSF1 (M-CSF), and CCL2 signaling pathways. Further, SARS-CoV-2-specific T cells were observed in pleural effusion earlier than in peripheral blood. Together, our results suggest that severe SARS-CoV-2 infection causes immune dysregulation by inducing M2 polarization and subsequent T cell exhaustion. This study improves our understanding of COVID-19 pathogenesis.