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.

The incidence, risk factors and prognosis of acute kidney injury in severe and critically ill patients with COVID-19 in mainland China: a retrospective study (preprint)

Background: Since the clinical correlates, prognosis and determinants of AKI in patients with Covid-19 remain largely unclear, we perform a retrospective study to evaluate the incidence, risk factors and prognosis of AKI in severe and critically ill patients with Covid-19.Methods: We reviewed medical records of all adult patients (>18 years) with laboratory-confirmed Covid-19 who were admitted to the intensive care unit (ICU) between January 23rd 2020 and April 6th 2020 at Wuhan JinYinTan Hospital and The First Affiliated Hospital of Guangzhou Medical University. The clinical data, including patient demographics, clinical symptoms and signs, laboratory findings, treatment [including respiratory supports, use of medications and continuous renal replacement therapy (CRRT)] and clinical outcomes, were extracted from the electronic records, and we access the incidence of AKI and the use of CRRT, risk factors for AKI, the outcomes of renal diseases, and the impact of AKI on the clinical outcomes.Results: Among 210 subjects, 131 were males (62.4%). The median age was 64 years (IQR: 56-71). Of 92 (43.8%) patients who developed AKI during hospitalization, 13 (14.1%), 15 (16.3%) and 64 (69.6%) patients were classified as stage 1, 2 and 3, respectively. 54 cases (58.7%) received CRRT. Age, sepsis, Nephrotoxic drug, IMV and elevated baseline Scr were associated with AKI occurrence. The renal recover during hospitalization among 16 AKI patients (17.4%), who had a significantly shorter time from admission to AKI diagnosis, lower incidence of right heart failure and higher P/F ratio. Of 210 patients, 93 patients deceased within 28 days of ICU admission. AKI stage 3, critical disease, greater age and minimum P/F <150mmHg independently associated with it.Conclusions: Among patients with Covid-19, the incidence of AKI was high. age , sepsis, nephrotoxic drug, IMV and baseline Scr were strongly associated with the development of AKI. Time from admission to AKI diagnosis, right heart failure and P/F ratio were independently associated with the potential of renal recovery. Finally, AKI KIDGO stage 3 independently predicted the risk of death within 28 days of ICU admission.

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.

Clinical findings in critical ill patients infected with SARS-Cov-2 in Guangdong Province, China: a multi-center, retrospective, observational study (preprint)

Abstract Background In December 2019, human infection with a novel coronavirus, known as SARS-CoV-2, was identified in Wuhan, China. The mortality of critical illness was high in Wuhan. Information about critically ill patients with SARS-CoV-2 infection outside of Wuhan is scarce. We aimed to provide the clinical features, treatment, and prognosis of the critically ill patients with SARS-CoV-2 infection in Guangdong Province. Methods In this multi-centered, retrospective, observational study, we enrolled critically ill patients with SARS-CoV-2 pneumonia who were admitted to the intensive care unit (ICU) in Guangdong Province. Demographic data, symptoms, laboratory findings, comorbidities, treatments, and prognosis were collected. Data were compared between patients with and without intubation. Results Forty-five critically ill patients with SARS-CoV-2 pneumonia were identified in 7 ICUs in Guangdong Province. The mean age was 56.7 years, and 29 patients (64.4%) were men. The most common symptoms at the onset of illness were high fever and cough. Majority of patients presented with lymphopenia and elevated lactate dehydrogenase. Treatment with antiviral drugs was initiated in all the patients. Thirty-seven patients (82.2%) had developed acute respiratory distress syndrome, and 13 (28.9%) septic shock. A total of 20 (44.4%) patients required intubation and 9 (20%) required extracorporeal membrane oxygenation. As of February 28th 2020, only one patient (2.2%) had died and half of them had discharged of ICU. Conclusions Infection with SARS-CoV-2 in critical illness is characterized by fever, lymphopenia, acute respiratory failure and multiple organ dysfunction. Compared with critically ill patients infected with SARS-CoV-2 in Wuhan, the mortality of critically ill patients in Guangdong Province was relatively low. These data provide some general understandings and experience for the critical patients with SARS-CoV-2 outside of Wuhan.

The efficacy of convalescent plasma for the treatment of severe influenza (preprint)

Background. Administration of convalescent plasma may be of clinical benefit for treatment of severe acute viral respiratory infections. However, no clear evidence exists to support or oppose convalescent plasma use in clinical practice. We conducted a systematic review and meta-analysis to assess the evidence of randomized controlled trials (RCTs) in the convalescent plasma for the treatment of severe influenza. Methods. Healthcare databases were searched in February 2020. All records were screened against the eligibility criteria. Data extraction and risk of bias assessments were undertaken. The primary outcome was case fatality rates by influenza. Results. We identified 5 RCTs of severe influenza. The pooled analyses showed no evidence for a reduction in mortality (Odds Ratio (OR) 1.06; p = 0.87; I2 = 35%). We also found non significant reductions in days in ICU and hospital, and days on mechanical ventilation. There seemed to have a biological benefit of increasing HAI titer levels and decreasing influenza B virus loads and cytokines after convalescent plasma treatment. No serious adverse events was reported between two groups. Studies were commonly of low risk of bias with high quality. Conclusions. Convalescent plasma appears safe but may not reduce mortality in severe influenza. This therapy should be studied within the context of a well designed clinical trial for treatment of SARS Cov 2 infection.