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A complete diagnostic autopsy is the gold-standard to gain insight into Coronavirus disease 2019 (COVID-19) pathogenesis. To delineate the in situ immune responses to SARS-CoV-2 viral infection, here we perform comprehensive high-dimensional transcriptional and spatial immune profiling in 22 COVID-19 decedents from Wuhan, China. We find TIM-3-mediated and PD-1-mediated immunosuppression as a hallmark of severe COVID-19, particularly in men, with PD-1+ cells being proximal rather than distal to TIM-3+ cells. Concurrently, lymphocytes are distal, while activated myeloid cells are proximal, to SARS-CoV-2 viral antigens, consistent with prevalent SARS-CoV-2 infection of myeloid cells in multiple organs. Finally, viral load positively correlates with specific immunosuppression and dendritic cell markers. In summary, our data show that SARS-CoV-2 viral infection induces lymphocyte suppression yet myeloid activation in severe COVID-19, so these two cell types likely have distinct functions in severe COVID-19 disease progression, and should be targeted differently for therapy. Postmortem analyses provide useful information for COVID-19 etiology. Here the authors profile 22 deceased severe COVID-19 patients with transcriptomic and histological approaches to find correlations between the presence of viral antigens with lymphocyte suppression yet myeloid activation, hinting distinct functions of these cells during pathogenesis. [ABSTRACT FROM AUTHOR]

Background: The emergence of COVID‐19 has become a global health emergency. The transmissibility of the disease is of great interest to healthcare workers and scientists alike. The primary route of transmission is via respiratory droplets, but viral RNA has also been found in feces and body fluids such as urine, serum, and semen. So far, there has been no report on whether SARS‐CoV‐2 is present in the exudates of cutaneous lesions. This study was designed to investigate whether SARS‐CoV‐2 can be found in the pressure injury exudates in patients with severe COVID‐19 infections. Methods: 46 critically ill COVID‐19 patients who were admitted to the ICU of the Sino‐French New City Branch of Tongji Hospital in Wuhan between February 4 and April 12 developed pressure injuries. 22 patients with pressure injuries had wound exudates. Wound and pharyngeal swabs of the 22 patients were collected and RT‐PCRs were conducted to detect SARS‐CoV‐2 viral RNA. Results: At the time of pressure injury, 5 patients still tested positive by pharyngeal swabs, the rest of the 17 patients tested negative. However, none of the wound exudate swabs from the participants tested positive for SARS‐CoV‐2 by RT‐PCR. Conclusion: Our study suggests that it is rather unlikely that COVID‐19 can be transmitted via pressure injury exudates, but we still recommend standardized personal protective equipment, face shield and an additional pair of gloves when treating pressure injuries. [ABSTRACT FROM AUTHOR]

Since the outbreak of COVID-19 in China at the end of 2019, the world has experienced a large-scale epidemic caused by the SARS-CoV-2. The epidemiological and clinical course of COVID-19 patients has been reported, but there have been few analyses about the characteristics, predictive risk factors, and outcomes of critical patients. In this single-center retrospective case–control study, 90 adult inpatients hospitalized at Tongji Hospital (Wuhan, China) were included. Demographic, clinical, laboratory tests, and treatment data were obtained and compared between critical and non-critical patients. We found that compared with non-critical patients, the critical patients had higher SOFA score and qSOFA scores. Critical patients had lower lymphocyte and platelet count, elevated D-dimer, decreased fibrinogen, and elevated high-sensitivity C-reactive protein (hsCRP), and interleukin-6(IL-6). More critical patients received treatment including antibiotics, anticoagulation, corticosteroid, and oxygen therapy than non-critical ones. Multivariable regression showed higher qSOFA score and elevation of IL-6 were related to critical patients. Antibiotic usage and anticoagulation were associated with decreased in-hospital mortality. And critical grouping contributed greatly to in-hospital death. Critical COVID-19 patients have a more severe clinical course. qSOFA score and elevation of IL-6 are risk factors for critical condition. Non-critical grouping, positive antibiotic application, and anticoagulation may be beneficial for patient survival. [ABSTRACT FROM AUTHOR]

OBJECTIVES Coronavirus disease 2019 (COVID-19) is a global pandemic. Critically ill patients often require prolonged intubation for mechanical ventilation to support breathing; thus, the artificial airway must be managed by tracheotomy. Therefore, studies exploring appropriate and safe methods for tracheotomy that minimize the risks of nosocomial transmission are important. Open in new tab Download slide Open in new tab Download slide METHODS A retrospective analysis of the clinical characteristics of 14 critically ill patients with COVID-19, who underwent bedside tracheotomy from March to April 2020 was conducted to summarize the indications for tracheotomy and key points related to personal protective equipment and surgical procedures. RESULTS All 14 patients were diagnosed with COVID-19 and were critically ill. All tracheotomies were performed in the late phase of the infection course. The interval between the infection and tracheotomy was 33 days, and the median interval between intubation and tracheotomy was 25.5 days. The reverse transcription-polymerase chain reaction results of secretions from the operative incision and inside the tracheotomy tube were negative. Twelve patients improved after tracheotomy, with SpO2 levels maintained above 96%. One patient died of progressive respiratory failure; another patient died of uncontrolled septic shock. No medical staff who participated in the tracheotomy was infected. CONCLUSIONS Tracheotomy in critically ill patients with COVID-19 who meet the indications for tracheotomy potentially represents a safer approach to manage the airway and help improve the treatment outcomes. A tracheotomy performed in the late phase of the disease has a relatively low risk of infection. Adherence to key steps in the tracheotomy procedure and donning adequate personal protection will help medical staff avoid infection. [ABSTRACT FROM AUTHOR]

• Significant negative correlation between IL-6 and platelet parameters was discovered. • Correlation between multiple cytokines and coagulation indicators was found. • Pro-inflammatory factors were found to be more associated to coagulation parameters. • Cytokines play an important role in the pathogenesis and evaluation of the condition of COVID-19. The novel SARS-CoV-2 caused a large number of infections and deaths worldwide. Thus, new ideas for an appropriated assessment of patients' condition and clinical treatment are of utmost importance. Therefore, in this study, the laboratory parameters of patients with coronavirus disease 2019 (COVID-19) were evaluated to identify the correlation between cytokine expression and other laboratory parameters. A retrospective and single-center study was performed in Wuhan, involving 83 severe or critical COVID-19 patients admitted to the intensive care unit (ICU). Laboratory parameters in ICU patients with laboratory-confirmed infection of SARS-CoV2 were collected. The association between parameters was assessed by Spearman's rank correlation. Patients' median age was 66 years (IQR, 57–73), and 55 (66%) were men. Among the 83 patients, 61 (73%) had 1 or more coexisting medical condition. The median concentration of IL-2R, IL-6, IL8, IL10, and TNFα were above the normal range, without IL-1β. A significant negative correlation between IL-6 and platelet count was discovered (r2 = −0.448, P < 0.001) as well as a significant correlation between IL-6 and other platelet parameters. Finally, a correlation between multiple cytokines and coagulation indicators was found, pro-inflammatory factors were found to be more associated to coagulation parameters, with the highest correlation between IL-6 and the International normalized ratio (INR) (r2 = 0.444, P < 0.001). Our results suggested that cytokines play an important role in the pathogenesis of COVID-19. In addition, IL-6 seems more relevant in the evaluation of the condition of COVID-19 patients. [ABSTRACT FROM AUTHOR]

Background: COVID-19 is a viral respiratory disease caused by the severe acute respiratory syndrome-Coronavirus type 2 (SARS-CoV-2). Patients with this disease may be more prone to venous or arterial thrombosis because of the activation of many factors involved in it, including inflammation, platelet activation and endothelial dysfunction. Interferon gamma inducible protein-10 (IP-10), monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein 1-alpha (MIP1α) are cytokines related to thrombosis. Therefore, this study focused on these three indicators in COVID-19, with the hope to find biomarkers that are associated with patients' outcome. Methods: This is a retrospective single-center study involving 74 severe and critically ill COVID-19 patients recruited from the ICU department of the Tongji Hospital in Wuhan, China. The patients were divided into two groups: severe patients and critically ill patients. The serum IP-10, MCP-1 and MIP1α level in both groups was detected using the enzyme-linked immunosorbent assay (ELISA) kit. The clinical symptoms, laboratory test results, and the outcome of COVID-19 patients were retrospectively analyzed. Results: The serum IP-10 and MCP-1 level in critically ill patients was significantly higher than that in severe patients (P < 0.001). However, no statistical difference in MIP1α between the two groups was found. The analysis of dynamic changes showed that these indicators remarkably increased in patients with poor prognosis. Since the selected patients were severe or critically ill, no significant difference was observed between survival and death. Conclusions: IP-10 and MCP-1 are biomarkers associated with the severity of COVID-19 disease and can be related to the risk of death in COVID-19 patients. [ABSTRACT FROM AUTHOR]

The pandemic outbreak of coronavirus disease 2019 (COVID-19) is rapidly spreading all over the world. Reports from China showed that about 20% of patients developed severe disease, resulting in a fatality of 4%. In the past two months, we clinical immunologists participated in multi-rounds of MDT (multidiscipline team) discussion on the anti-inflammation management of critical COVID-19 patients, with our colleagues dispatched from Chinese leading PUMC Hospital to Wuhan to admit and treat the most severe patients. Here, from the perspective of clinical immunologists, we will discuss the clinical and immunological characteristics of severe patients, and summarize the current evidence and share our experience in anti-inflammation treatment, including glucocorticoids, IL-6 antagonist, JAK inhibitors and choloroquine/hydrocholoroquine, of patients with severe COVID-19 that may have an impaired immune system. • The epidemic outbreak of coronavirus disease 2019 (COVID-19) has rapidly spread all over the world. • Inflammatory cytokine storm was common in patients with severe COVID-19. • The immune system was impaired in critical COVID-19 patients • A timely anti-inflammation treatment at the right window time is of pivotal importance. [ABSTRACT FROM AUTHOR]