PANoptosis: A Cell Death Characterized by Pyroptosis, Apoptosis, and Necroptosis.

PANoptosis is a new cell death proposed by Malireddi et al in 2019, which is characterized by pyroptosis, apoptosis and necroptosis, but cannot be explained by any of them alone. The interaction between pyroptosis, apoptosis and necroptosis is involved in PANoptosis. In this review, from the perspective of PANoptosis, we focus on the relationship between pyroptosis, apoptosis and necroptosis, the key molecules in the process of PANoptosis and the formation of PANoptosome, as well as the role of PANoptosis in diseases. We aim to understand the mechanism of PANoptosis and provide a basis for targeted intervention of PANoptosis-related molecules to treat human diseases.

Hypertension as a sequela in patients of SARS-CoV-2 infection.

BACKGROUND: COVID-19 is a respiratory infectious disease caused by SARS-CoV-2, and cardiovascular damage is commonly observed in affected patients. We sought to investigate the effect of SARS-CoV-2 infection on cardiac injury and hypertension during the current coronavirus pandemic. STUDY DESIGN AND METHODS: The clinical data of 366 hospitalized COVID-19-confirmed patients were analyzed. The clinical signs and laboratory findings were extracted from electronic medical records. Two independent, experienced clinicians reviewed and analyzed the data. RESULTS: Cardiac injury was found in 11.19% (30/268) of enrolled patients. 93.33% (28/30) of cardiac injury cases were in the severe group. The laboratory findings indicated that white blood cells, neutrophils, procalcitonin, C-reactive protein, lactate, and lactic dehydrogenase were positively associated with cardiac injury marker. Compared with healthy controls, the 190 patients without prior hypertension have higher AngⅡ level, of which 16 (8.42%) patients had a rise in blood pressure to the diagnostic criteria of hypertension during hospitalization, with a significantly increased level of the cTnI, procalcitonin, angiotensin-II (AngⅡ) than those normal blood pressure ones. Multivariate analysis indicated that elevated age, cTnI, the history of hypertension, and diabetes were independent predictors for illness severity. The predictive model, based on the four parameters and gender, has a good ability to identify the clinical severity of COVID-19 in hospitalized patients (area under the curve: 0.932, sensitivity: 98.67%, specificity: 75.68%). CONCLUSION: Hypertension, sometimes accompanied by elevated cTnI, may occur in COVID-19 patients and become a sequela. Enhancing Ang II signaling, driven by SARS-CoV-2 infection, might play an important role in the renin-angiotensin system, and consequently lead to the development of hypertension in COVID-19.

Clinical characteristics of 25 death cases with COVID-19: a retrospective review of medical records in a single medical center, Wuhan, China. (Coronavirus (COVID-19) collection.)

Objectives: This study aims to summarize the clinical characteristics of death cases with COVID-19 and to identify critically ill patients of COVID-19 early and reduce their mortality. Methods The clinical records, laboratory findings and radiological assessments included chest X-ray or computed tomography were extracted from electronic medical records of 25 died patients with COVID-19 in Renmin Hospital of Wuhan University from Jan 14 to Feb 13, 2020. Two experienced clinicians reviewed and abstracted the data. Results The age and underlying diseases (hypertension, diabetes, etc.) were the most important risk factors for death of COVID-19 pneumonia. Bacterial infections may play an important role in promoting the death of patients. Malnutrition was common to severe patients. Multiple organ dysfunction can be observed, the most common organ damage was lung, followed by heart, kidney and liver. The rising of neutrophils, SAA, PCT, CRP, cTnI, D-dimer, LDH and lactate levels can be used as indicators of disease progression, as well as the decline of lymphocytes counts. Conclusions The clinical characteristics of 25 death cases with COVID-19 we summarized, which would be helpful to identify critically ill patients of COVID-19 early and reduce their mortality.

Resolution of Coronavirus Disease 2019 Infection and Pulmonary Pathology With Nebulized DAS181: A Pilot Study.

OBJECTIVES: Severe acute respiratory syndrome coronavirus 2 infections commonly lead to respiratory failure and potentially fatal systemic inflammation and organ failure. Nebulized DAS181, a host-directed biologics with sialidase activity, is an investigational drug with antiviral activities on parainfluenza and influenza under phase 3 and phase 2 development. The objective of this study (NCT04324489) is to investigate the safety and effects of nebulized DAS181 on hypoxic coronavirus disease 2019 patients. DESIGN: Single-center, prospective, open-label, compassionate use. SETTING: Renmin Hospital of Wuhan University, Department of Respiratory and Critical Care Medicine and Department of Infectious Diseases. SUBJECTS: Patients 18 to 70 years old who met Chinese criteria for severe coronavirus disease 2019 pneumonia and required supplemental oxygen but not on mechanical ventilator at screening. INTERVENTIONS: Nebulized DAS181 (4.5 mg) twice a day for 10 days. MEASUREMENTS AND MAIN RESULTS: Three male coronavirus disease 2019 hypoxic patients with bilateral lung involvement completed DAS181 treatment for 10 days. By day 14, all achieved return to room air (primary endpoint) and their nasopharyngeal swabs were negative for severe acute respiratory syndrome coronavirus 2. Clinical severity improved from severe coronavirus disease 2019 at baseline to moderate or mild disease by day 5, consistent with rapid reduction of inflammatory cytokines by days 2-3 and radiologic improvement by days 5-10. No DAS181-related adverse events were reported. CONCLUSIONS: Inhalation of DAS181 was well tolerated and potential clinical benefit of DAS181 on hypoxic coronavirus disease 2019 is the reduction of supplemental oxygen need. Efficacy and safety, including pharmacokinetics and viral studies of DAS181 in severe, hypoxic coronavirus disease 2019, should be examined by a double-blind, randomized controlled study.

Clinical Challenges in an Outbreak of COVID-19 in Wuhan, China: Concerns from Frontiers.

PURPOSE OF REVIEW: In December 2019, outbreaks of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected pneumonia patients were discovered in Wuhan City, Hubei Province, China. With the spread of the epidemic, new cases have been found in other regions of China and abroad. This review summarizes the current coronavirus disease 2019 (COVID-19) transmission pathways, high-risk factors, diagnostic points, pathogenesis, and therapeutic drugs to provide the prevention and treatment theories for COVID-19. RECENT FINDINGS: COVID-19 is highly contagious and is transmitted mainly through the respiratory tract. Most patients with SARS-CoV-2 infection have milder symptoms. Some patients will have mild disease in the early stage, suddenly exacerbate later, and eventually die of multiple organ failure caused by cytokine storm. The basis for clinical diagnosis of COVID-19 is not just the detection of viral nucleic acids as the gold standard. The diagnostic accuracy improves when viral nucleic acid test is combined with clinical symptoms, CT results, and biochemical tests. For the treatment of COVID-19, the specific antiviral agents have not been developed, except for symptomatic supportive treatments. SUMMARY: The methods for detecting SARS-CoV-2 infection have become increasingly mature, but specific antiviral drugs for the treatment of COVID-19 have not yet been developed. Treatment must pay attention to the cytokine storm that leads to the seriousness of COVID-19.

Coronavirus Disease 19 Infection Does Not Result in Acute Kidney Injury: An Analysis of 116 Hospitalized Patients from Wuhan, China.

BACKGROUND: Whether the patients with coronavirus disease 19 (COVID-19) infected by severe acute respiratory syndrome (SARS)-CoV-2 would commonly develop acute kidney injury (AKI) is an important issue worthy of clinical attention. This study aimed to explore the effects of SARS-CoV-2 infection on renal function through analyzing the clinical data of 116 hospitalized COVID-19-confirmed patients. METHODS: One hundred sixteen COVID-19-confirmed patients enrolled in this study were hospitalized in the Department of Infectious Diseases, Renmin Hospital of Wuhan University from January 14 to February 13, 2020. The recorded information includes demographic data, medical history, contact history, potential comorbidities, symptoms, signs, laboratory test results, chest computer tomography scans, and treatment measures. SARS-CoV-2 RNA in 53 urine sediments of enrolled patients was detected by real-time reverse transcription-polymerase chain reaction. RESULTS: Twelve (10.8%) patients showed mild increase of blood urea nitrogen or creatinine (<26 µmol/L within 48 h), and 8 (7.2%) patients showed trace or 1+ albuminuria in 111 COVID-19-confirmed patients without chronic kidney disease (CKD). All these patients did not meet the diagnostic criteria of AKI. In addition, 5 patients with CKD who were undergone regular continuous renal replacement therapy (CRRT) before admission were confirmed infection of SARS-CoV-2 and diagnosed as COVID-19. In addition to therapy for COVID-19, CRRT was also applied 3 times weekly during hospitalization for these 5 patients with CKD. In the course of treatment, the renal function indicators showed stable state in all 5 patients with CKD, without exacerbation of CKD, and pulmonary inflammation was gradually absorbed. All 5 patients with CKD were survived. Moreover, SARS-CoV-2 RNA in urine sediments was positive only in 3 patients from 48 cases without CKD, and 1 patient had a positive for SARS-CoV-2 open reading frame 1ab from 5 cases with CKD. CONCLUSION: AKI was uncommon in COVID-19. SARS-CoV-2 infection does not result in AKI, or aggravate CKD in the COVID-19 patients.