Rampant C-to-U deamination accounts for the intrinsically high mutation rate in SARS-CoV-2 spike gene.

The high mutation rate of SARS-CoV-2 largely complicates our control of the pandemic. In particular, it is currently unclear why the spike (S) gene has an extraordinarily high mutation rate among all SARS-CoV-2 genes. By analyzing the occurrence of fixed synonymous mutations between SARS-CoV-2 and RaTG13, and profiling the DAF (derived allele frequency) of polymorphic synonymous sites among millions of worldwide SARS-CoV-2 strains, we found that both fixed and polymorphic mutations show higher mutation rates in the S gene than other genes. The majority of mutations are C-to-T, representing the APOBEC-mediated C-to-U deamination instead of the previously proposed A-to-I deamination. Both in silico and in vivo evidence indicated that the S gene is more likely to be single-stranded compared to other SARS-CoV-2 genes, agreeing with the APOBEC preference of ssRNA. We conclude that the single-stranded property of the S gene makes it a favorable target for C-to-U deamination, leading to its excessively high mutation rate compared to other non-S genes. In conclusion, APOBEC, rather than ADAR, is the "editor-in-chief" of SARS-CoV-2 RNAs. This work helps us to understand the molecular mechanism underlying the mutation and evolution of SARS-CoV-2, and we believe it will contribute to the control of the pandemic.

Development of septic shock and prognostic assessment in critically ill patients with coronavirus disease outside Wuhan, China.

BACKGROUND: The study aims to illustrate the clinical characteristics and development of septic shock in intensive care unit (ICU) patients confirmed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and to perform a comprehensive analysis of the association between septic shock and clinical outcomes in critically ill patients with coronavirus disease (COVID-19). METHODS: Patients confirmed with SARS-CoV-2 infection, who were admitted to the ICU of the Third People's Hospital of Shenzhen from January 1 to February 7, 2020, were enrolled. Clinical characteristics and outcomes were compared between patients with and without septic shock. RESULTS: In this study, 35 critically ill patients with COVID-19 were included. Among them, the median age was 64 years (interquartile range [IQR] 59-67 years), and 10 (28.4%) patients were female. The median ICU length of stay was 16 days (IQR 8-23 days). Three (8.6%) patients died during hospitalization. Nine (25.7%) patients developed septic shock in the ICU, and these patients had a significantly higher incidence of organ dysfunction and a worse prognosis than patients without septic shock. CONCLUSIONS: Septic shock is associated with a poor outcome in critically ill COVID-19 patients and is one of the hallmarks of the severity of patients receiving ICU care. A dysregulated immune response, uncontrolled inflammation, and coagulation disorders are strongly associated with the development and progression of COVID-19-related septic shock.

CT Manifestations of Coronavirus Disease 2019 and the Semi-Quantitative Evaluation of Its Clinical Classification

Purpose: To improve the understanding of the manifestations associated with computed tomography (CT) in the context of coronavirus disease 2019 (COVID-19). Methods: An analysis of a retrospective nature was carried out on clinically-based data as well as CT manifestations in 102 patients with a COVID-19 diagnosis who were admitted to our hospital between the 24th of January, 2020 and the 5th of February, 2020. Scoring of CT manifestations was accomplished, and the total score was used to determine the severity of lung injury. Results: Of the 102 patients, 10 had mild COVID-19, 72 had COVID-19 that was classed as moderate, 16 had COVID-19 that was severe, and 4 had COVID-19 that was critically severe. In all, 92 patients developed lung lesions, among whom 85 showed bilateral lung involvement. Superior lobe lesions and lesions in the middle-inner zone of the lung less frequently affected patients who developed moderate COVID-19 as compared to patients who developed severe/critically severe COVID-19 (all P < 0.05). The lesion manifestations included ground-glass opacity shadows (98.9%) and mixed-density shadows with consolidation (45.7%). Lamellar lesions and interlobular septal thickening less frequently affected patients with COVID-19 that was moderate than in patients with COVID-19 that was severe or critically severe (P < 0.05). In terms of COVID-19 that was moderate, severe or critically severe, the average scores associated with CT were 10.68 ± 6.32, 22.31 ± 8.07, and 30.75 ± 1.89 points respectively. A cumulative CT score of ≤ 20 points was the critical point for distinguishing moderate COVID-19 from severe/critically severe COVID-19. Conclusion: With regards to CT manifestations that were associated with COVID-19, certain characteristics were demonstrated and these varied in relation to different classifications of COVID-19. Cumulative CT score could be used to evaluate the clinical classification and degree of lung damage in patients who develop COVID-19.

Completed absorption of coronavirus disease 2019 (COVID-19) pneumonia lesions: a preliminary study.

Background: Complete absorption of coronavirus disease 2019 (COVID-19) pneumonia in a short term was not detailedly reported. We aimed to investigate the clinical and imaging characteristics of COVID-19 patients with complete absorption of pulmonary lesions. Methods: Retrospectively collected the clinical and chest CT data of 224 patients with COVID-19 in one regional medical center. Currently, pulmonary lesions in 37 patients were completely absorbed. The clinical manifestations, laboratory examinations, and CT findings of lesions for these patients were summarized. Results: Among the 37 patients (age, 39.0 ± 12.4 [14-63] years, 20 males), disease in 36 (97.3%) was mild and in 1 (2.7%) was from severe to mild. The most common symptoms were cough (24/37, 64.9%) and fever (23/37, 62.2%). Their laboratory indicators at admission were usually normal, while the white blood cell and neutrophil count significantly increased at discharge (p = 0.004, p = 0.006). On initial CT images, all patients had various pulmonary lesions (mean involved lobes: 2.8 ± 1.5, range: 1-5; mean involved segments: 6.6 ± 4.3, range: 1-16), which mainly manifested as multiple patchy and or spherical ground glass opacities (GGOs) (30/37, 81.1%) with fibrous strips (19/30, 63.3%) or consolidation (11/30, 36.7%). After treatment, lesions in most (33/37, 89.2%) patients were continuously absorbed. At discharge, previous lesions were mostly absorbed in 11 patients (11/37, 29.7%), the main residues were GGOs (24/37, 64.9%), followed by fibrous strips (13/37, 35.1%). On the latest CT, all the pulmonary lesions were completely absorbed, the duration of lesions was 31.6 ± 11.4 days (range: 5-50 days). Conclusion: The pulmonary lesions in some mild COVID-19 patients (generally with normal laboratory indicators at admission, GGOs as the main manifestation on initial CT, and representation of continuous absorption after treatment) could be completely absorbed with a mean duration of 31.6 days.

The Clinical Features and Prognostic Assessment of SARS-CoV-2 Infection-Induced Sepsis Among COVID-19 Patients in Shenzhen, China.

Background: The outbreak of the novel coronavirus disease (COVID-19) that began in December 2019 has posed a great threat to human health and caused a significant loss of life. In Shenzhen, 465 patients were confirmed to have COVID-19 as of August 31, 2020. In the present study, we aimed to describe the clinical characteristics of COVID-19 patients in Shenzhen and identify risk factors for the development of viral sepsis. Methods: In this retrospective study, patients who were confirmed to have a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and were admitted to the Third People's Hospital of Shenzhen from January 11 to April 27, 2020 were included in the cohort. Clinical data were extracted and followed up to May 10, 2020, by using predesigned data collection forms. Results: A total of 422 hospitalized COVID-19 patients were enrolled in this study, including 97 (23%) patients with viral sepsis at hospital admission and 325 (77%) non-septic patients. Patients with sepsis were much older than those without sepsis (57 vs. 43 years, P < 0.001) and presented with more comorbidities. Septic patients showed multiple organ dysfunction and significant abnormalities in immune- and inflammation-related biomarkers, and had poorer outcomes when compared to those without sepsis. Increased levels of interleukin-6, blood urea nitrogen, and creatine kinase were associated with the development of SARS-CoV-2-induced sepsis, and an elevated production of interleukin-6 was found to be an independent risk factor for the progression to critical illness among septic COVID-19 patients. Conclusions: SARS-CoV-2 infection-induced sepsis is critically involved in the severity and prognosis of COVID-19 patients by characterizing both aberrant immune response and uncontrolled inflammation. The development of sepsis might contribute to multiple organ dysfunction and poor outcomes in COVID-19 patients during hospitalization.

Sustainable Designed Pavement Materials.

This Special Issue "Sustainable Designed Pavement Materials" has been proposed and organized as a means to present recent developments in the field of environmentally-friendly designed pavement materials. For this reason, articles included in this special issue relate to different aspects of pavement materials, from industry solid waste recycling to pavement materials recycling, from pavement materials modification to asphalt performance characterization, from pavement defect detection to pavement maintenance, and from asphalt pavement to cement concrete pavement, as highlighted in this editorial.

Successful management of seven cases of critical COVID-19 with early noninvasive-invasive sequential ventilation algorithm and bundle pharmacotherapy.

We report the clinical and laboratory findings and successful management of seven patients with critical coronavirus disease 2019 (COVID-19) requiring mechanical ventilation (MV). The patients were diagnosed based on epidemiological history, clinical manifestations, and nucleic acid testing. Upon diagnosis with COVID-19 of critical severity, the patients were admitted to the intensive care unit, where they received early noninvasive-invasive sequential ventilation, early prone positioning, and bundle pharmacotherapy regimen, which consists of antiviral, anti-inflammation, immune-enhancing, and complication-prophylaxis medicines. The patients presented fever (n = 7, 100%), dry cough (n = 3, 42.9%), weakness (n = 2, 28.6%), chest tightness (n = 1, 14.3%), and/or muscle pain (n = 1, 14.3%). All patients had normal or lower than normal white blood cell count/lymphocyte count, and chest computed tomography scans showed bilateral patchy shadows or ground glass opacity in the lungs. Nucleic acid testing confirmed COVID-19 in all seven patients. The median MV duration and intensive care unit stay were 9.9 days (interquartile range, 6.5-14.6 days; range, 5-17 days) and 12.9 days (interquartile range, 9.7-17.6 days; range, 7-19 days), respectively. All seven patients were extubated, weaned off MV, transferred to the common ward, and discharged as of the writing of this report. Thus, we concluded that good outcomes for patients with critical COVID-19 can be achieved with early noninvasive-invasive sequential ventilation and bundle pharmacotherapy.

Coronavirus disease 2019 (COVID-19) associated coagulopathy and its impact on outcomes in Shenzhen, China: A retrospective cohort study.

BACKGROUND: Early detection of suspected critical patients infected with coronavirus disease 2019 (COVID-19) is very important for the treatment of patients. This study aimed to investigate the role of COVID-19 associated coagulopathy (CAC) to preview and triage. METHODS AND RESULTS: A cohort study was designed from government designated COVID-19 treatment center. CAC was defined as International Society on Thrombosis and Haemostasis (ISTH) score ≥2. Data from 117 patients COVID-19 were reviewed on admission. The primary and secondary outcomes were admission to Intensive Care Unit (ICU), the use of mechanical ventilation, vital organ dysfunction, discharges of days 14, 21 and 28 from admission and hospital mortality. Among them, admission to ICU was increased progressively from 16.1% in patients with non-CAC to 42.6% in patients with CAC (P < 0.01). Likely, invasive ventilation and noninvasive ventilation were increased from 1.8%, 21.4% in patients with non-CAC to 21.3%, 52.5% in patients with CAC, respectively (P < 0.01). The incidences of acute hepatic injury and acute respiratory distress syndrome in non-CAC and CAC were 28.6% vs. 62.3%, 8.9% vs. 27.9%, respectively (P < 0.01). The discharges of days 14, 21 and 28 from admission were more in non-CAC than those of CAC (P < 0.05). Multiple logistic regression results showed that ISTH score ≥2 was obviously associated with the admission to ICU (OR 4.07, 95% CI 1.47-11.25 P = 0.007) and the use of mechanical ventilation (OR 5.54, 95% CI 2.01-15.28 P = 0.001) in patients with COVID-19. CONCLUSION: All results show ISTH score ≥2 is an important indicator to preview and triage for COVID-19 patients.

Importance of respiratory airway management as well as psychological and rehabilitative treatments to COVID-19 patients.

The clinical therapy for severe 2019 coronavirus disease (i.e., COVID-19) sufferers is relatively challenging. Herein, the processes involving salvage of a critical COVID-19 patient were retrospectively analyzed. The condition of an obese female critical COVID-19 sufferer progressively worsened in the initial period after admission. According to her symptoms and examination reports, endotracheal intubation and mechanical ventilation were timely conducted and meanwhile high-dose sedatives and analgesics were administrated. In the later therapeutic phase, however, sedative and analgesic dosages were gradually reduced, and psychological and rehabilitative therapies were conducted, concomitantly with enhancement of airway care to facilitate sputum expectoration. Eventually, the endotracheal tube was feasibly removed after intubation for 18 days and subsequently replaced with noninvasive ventilation and a high-flow nasal cannula oxygen therapy. Intensive airway care alongside psychological and rehabilitative therapies can shorten the mechanical ventilation time and improve the prognosis of COVID-19 sufferers.