Dynamic Zero-Covid strategy curtails mutagenesis and emergence of new variants of the SARS-CoV-2 (preprint)

Within the local outbreak period of SARS-CoV-2 Delta variant in Nanjing and Yangzhou, China, we analyzed the mutation process of the Delta variants in 520 cases, as well as the production, spread and elimination of new mutant strains under the non-pharmaceutical interventions (NPI) strategy. The investigation on distribution of COVID-19 cases and phylogenetic analysis of SARS-CoV-2 genome sequences attributed to tracking the transmission chains, transmission chains were terminated by the isolation of the COVID-19 patients and quarantine of close-contracts, suggesting the importance of NPI in prompting some mutations to disappear and stopping the transmission of new variants. Dynamic zero-Covid strategy has been implemented successfully to against the second-largest local epidemic caused by an imported COVID-19 case in China.

Increased Incidence of Adult Complicated Appendicitis in One Resource-Competent Community during the Coronavirus Disease 2019 Pandemic: Time to Improve Health-Seeking Behaviors (preprint)

Background: The impact of the coronavirus disease 2019 (COVID-19) pandemic on medical services is overwhelming due to limited medical resources. During its initial surge in 2020, Taiwan’s government rapidly established diverse public actions, which helped maintain the medical supply without travel restrictions. However, whether the fear of being infected with COVID-19 interfered with health-seeking behavior (HSB) remains unclear. Therefore, this study aimed to elucidate whether acute complicated appendicitis (ACA) rates in adults were affected by the COVID-19 pandemic. Methods: A retrospective analysis of acute appendicitis in adults was performed between January 1 and June 30, 2020 (COVID-19 period). The control period was collected from the first two quarters for the preceding 3 years. Outcome measures were ACA and length of hospital stays. Results: A total of 145 patients with acute appendicitis presented to our institution during the COVID-19 era. Compared to a 3-year control cohort of 320 patients, the COVID-19 pandemic was associated with a higher rate of symptom duration until their presentation to the emergency room within >48 h (17.2% vs 9.1%, P = 0.011), a higher incidence of ACA (29.7% vs 19.4%, P = 0.014), and a longer length of hospital stays (5.0 days vs 4.0 days, P = 0.043) were observed. In the adjusted regression analysis, the COVID-19 period was significantly associated with a higher rate of ACA (odds ratio [OR] = 1.87; 95% confidence interval [CI]: 1.23–2.52; P = 0.008) and longer length of hospital stay (OR= 2.10; 95% CI: 0.92 to 3.31; P < 0.001). Conclusions: The COVID-19 pandemic was significantly associated with increased ACA rates in one community with a normal medical supply. The fear of being infected with COVID-19 may prohibit patients from seeking medical needs. To improve HSB during the pandemic, a surgical community should attempt to provide scientific information to the public and maintain surgical services under the coverage of workplace safety.

Epidemiological characteristics of 147 patients infected with SARS-CoV-2 in Chengdu

Objective: Analysis of the epidemiological characteristics and trend of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were conducted in Chengdu.

Clinical characteristics comparative analysis of imported and local cases with COVID-19 in Hainan

Objective: To observe the epidemiology, clinical features, auxiliary examinations and prognosis of 69 cases with COVID-19 in Hainan province.

Risk Factors for Mortality in Critically Ill Patients with COVID-19: A Multicenter Retrospective Case-Control Study (preprint)

Background Coronavirus disease 2019 (COVID-19) has spread around the world and caused many deaths, but little is known about the risk factors for death in critically patients.Methods we collected demographic and clinical data on all severe inpatients with COVID-19 .We used univariable and multivariable Cox regression methods to determine the independent risk factors related to likelihood of 28-day and 60-day survival, performing survival curve analysis.Results Of 325 patients enrolled in the study, Multi-factor Cox analysis showed increasing odds of in-hospital death associated with basic illness (hazard ratio [HR] 6.455, 95% Confidence Interval [CI] 1.658–25.139, P = 0.007), lymphopenia (HR 0.373, 95% CI 0.148–0.944, P = 0.037), higher Sequential Organ Failure Assessment (SOFA) score on admission (HR 1.171, 95% CI 1.013–1.354, P = 0.033) and being critically ill (HR 0.191, 95% CI 0.053–0.687, P = 0.011). Increasing 28-day and 60-day mortality, declining survival time and more serious inflammation and organ failure were associated with lymphocyte count ≤ 0.8 × 109/L, SOFA score > 3, Acute Physiology and Chronic Health Evaluation II (APACHE II) score > 7, PaO2/FiO2 ≤ 200 mmHg, IL-6 > 120 pg/ml, and CRP > 52 mg/L.Conclusions Being critically ill and lymphocyte count, SOFA score, APACHE II score, PaO2/FiO2, IL-6, and CRP on admission were associated with poor prognosis in COVID-19 patients.

Persistent Lymphopenia After Diagnosis of COVID-19 Predicts Acute Respiratory Distress Syndrome: A Retrospective Cohort Study (preprint)

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a main characterized by severe Coronavirus disease-2019(COVID-19). Lymphopenia is a marker of immunosuppression following infection. This study was designed to establish whether persistent lymphopenia on the seventh day following the diagnosis of COVID-19 predicts ARDS. METHODS: A retrospective cohort study of 125 patients with COVID-19 admitted to government-designated treatment center between January 14, 2020, and March 20, 2020. All complete blood cell counts during the day 0th, 3rd, and 7th following the diagnosis of COVID-19 were recorded. Patients were grouped based on the depression of the lymphocyte cell count, their return, or their failure to normal. The primary outcome was ARDS, and Secondary outcomes included the development of vital organ dysfunction and hospital lengths of stay. RESULTS: 17.6% (22/125) patients developed ARDS. The lymphocyte counts with ARDS and non-ARDS were 0.94×109/L, 1.20×109/L at admission, respectively (P=0.02). At 3rd and 7th day, the median of lymphocyte count in ARDS was significantly lower compared with that of non-ARDS, Multivariable logistic regression adjusting for potentially confounding factors (including age, comorbidities, APACH II score) showed persistent lymphopenia within 7th day was found to be independently associated with ARDS (OR, 3.94 [95%CI, 1.26-12.33, P=0.018); Further, patients with persistent lymphopenia had longer hospital lengths of stay (p<0.001). CONCLUSION: The results showed persistent lymphopenia on the seventh day following the confirmed COVID-19 predicts ARDS，and it may be a target for immunostimulation for COVID-19 associated ARDS.

Early warning signs for severe patients with Coronavirus Disease 2019 and its epidemical significance (preprint)

Background Since December 2019 coronavirus disease 2019 (COVID-19) emerged in Wuhan city and rapidly spread throughout China. However, early warning signs for severe patients with COVID-19 were not fully known.Methods Information on admission was collected through a standard questionnaire. We described the epidemiological characteristics of the patients with COVID-19, analyzed the risk factors associated with severe illness, and estimated the key epidemiologic time-delay distributions.Results A total of 631 patients with laboratory-confirmed COVID-19 were identified. The proportion of severe cases was 8.4%. The epidemic of COVID-19 experienced four stages: sporadic phase, exponential growth phase, peak plateau phase, and declining phase. The proportion of severe cases was significantly different in four stages and 13 municipal prefectures (P < 0.001). Factors including elderly more than 65years(yrs) old, underlying medical conditions, fever patient whose highest temperature beyond 39.0℃, dyspnea, and lymphocytopenia(< 1.0 × 109/L) could possibly become the early warning signs for severe patients of COVID-19. In contrast, earlier visit to the clinic could reduce the severe risk. Besides, the viral load may be a potentially useful marker associated with disease severity of COVID-19 infection.Conclusions The epidemic experienced four stages with obviously areas difference. People aged beyond 65 yrs or underlying medical conditions once appear symptoms like fever beyond 39.0℃ and/or dyspnea should immediately visit health care.

Remdesivir inhibits renal fibrosis in obstructed kidneys (preprint)

Aim Kidney impairment is observed in patients with COVID-19. We aimed to demonstrate the effect of anti-COVID-19 agent remdesivir on renal fibrosis. Methods Remdesivir and its active nucleoside metabolite GS-441524 were used to treat TGF-β stimulated renal fibroblasts (NRK-49F) and human renal epithelial cells (HK2). Cell viability was determined by CCK8 assay, and fibrotic markers were measured by Western blotting. Vehicle or remdesivir were given by intraperitoneal injection or renal injection through the left ureter in unilateral ureteral obstruction (UUO) mice. Serum and kidneys were harvested. The concentrations of remdesivir and GS-441524 were measured using LC-MS/MS. Renal and liver function were assessed. Renal fibrosis was evaluated by Masson’s trichrome staining and Western blotting. Results Remdesivir and GS-441524 inhibited cell proliferation and the expression of fibrotic markers (fibronectin, pSmad3, and aSMA) in NRK-49F and HK2 cells. Intraperitoneal injection or renal injection of remdesivir attenuated renal fibrosis of UUO kidneys. Renal and liver function were not changed in remdesivir treated UUO mice. Remdesivir can not be detected, but two remdesivir metabolites were detected after injection. Conclusion Remdesivir inhibits renal fibrosis in obstructed kidneys.

The multicenter study of Chest HRCT imaging characteristics of 2019 Novel Coronavirus (COVID-19) Pneumonia (preprint)

Background: In December 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China. A novel coronavirus was detected, capable of infecting humans, on 6 January 2020 and termed COVID-19. By 16 February 2020, there were 51857 confirmed cases with 2019-nCoV (COVID-19) pneumonia in 25 countries. COVID-19 can also lead to acute respiratory distress syndrome (ARDS).Methods: 149 patients with 2019 Novel Coronavirus (COVID-19)pneumonia(68 males, 81 females, ages 1-89)from 6 research centers in China were diagnosed with positive 2019 Novel Coronavirus(COVID-19)nucleic acids antibodies. And their high-resolution computed tomography(HRCT) imaging datas were evaluated.Results: 136/149(91.3%)patients had a clear history of exposure to Wuhan. Fever (122/149, 81.9%)and cough(83/149, 55.7%)were the most common symptoms. The main imaging characteristics within 4 days of onset included 30(20.13%) cases of pure ground glass opacities (P<0.05), 38(25.50%) cases of GGO with reticulation(P<0.01), 12(8.05%) cases of consolidation(P<0.01). In the 5-8 days group, the main imaging features included 71(47.65%) cases of pGGO(P<0.05), 69(46.31%) cases of GGO with reticulation(P<0.01). In the 9-12 days group, the main feature was 85(57.04%) cases with GGO with reticulation(P<0.01). In the group of 13-16 days group, the main imaging characteristics included 48(32.21%) cases of GGO with reticulation(P < 0.01), 34(22.82%) cases of consolidation(P<0.01).Conclusion: Patients infected with COVID-19 pneumonia show more chest CT characteristics within 5-8 days after the onset of disease. The main manifestations included pGGO, GGO with reticulation, consolidation and GGO with consolidation.

Caution on Kidney Dysfunctions of 2019-nCoV Patients (preprint)

Summary Background: To date, large amounts of epidemiological and case study data have been available for the Coronavirus Disease 2019 (COVID-19), which suggested that the mortality was related to not just respiratory complications. Here, we specifically analyzed kidney functions in COVID-19 patients and their relations to mortality. Methods: In this multi-centered, retrospective, observational study, we included 193 adult patients with laboratory-confirmed COVID-19 from 2 hospitals in Wuhan, 1 hospital in Huangshi (Hubei province, 83 km from Wuhan) and 1 hospital in Chongqing (754 km from Wuhan). Demographic data, symptoms, laboratory values, comorbidities, treatments, and clinical outcomes were all collected, including data regarding to kidney functions. Data were compared among three groups: non-severe COVID-19 patients (128), severe COVID-19 patients (65) and a control group of other pneumonia (28). For the data from computed tomographic (CT) scans, we also included a control group of healthy subjects (110 cases, without abnormalities in the lung and without kidney diseases). The primary outcome was a common presence of kidney dysfunctions in COVID-19 patients and the occurrence of acute kidney injury (AKI) in a fraction of COVID-19 patients. Secondary outcomes included a survival analysis of COVID-19 patients in conditions of AKI or comorbid chronic illnesses. Findings: We included 193 COVID-19 patients (128 non-severe, 65 severe (including 32 non-survivors), between January 6th and February 21th,2020; the final date of follow-up was March 4th, 2020) and 28 patients of other pneumonia (15 of viral pneumonia, 13 of mycoplasma pneumonia) before the COVID-19 outbreak. On hospital admission, a remarkable fraction of patients had signs of kidney dysfunctions, including 59% with proteinuria, 44% with hematuria, 14% with increased levels of blood urea nitrogen, and 10% with increased levels of serum creatinine, although mild but worse than that in cases with other pneumonia. While these kidney dysfunctions might not be readily diagnosed as AKI at admission, over the progress during hospitalization they could be gradually worsened and diagnosed as AKI. A univariate Cox regression analysis showed that proteinuria, hematuria, and elevated levels of blood urea nitrogen, serum creatinine, uric acid as well as D-dimer were significantly associated with the death of COVID-19 patients respectively. Importantly, the Cox regression analysis also suggested that COVID-19 patients that developed AKI had a ~5.3-times mortality risk of those without AKI, much higher than that of comorbid chronic illnesses (~1.5 times risk of those without comorbid chronic illnesses). Interpretation: To prevent fatality in such conditions, we suggested a high degree of caution in monitoring the kidney functions of severe COVID-19 patients regardless of the past disease history. In addition, upon day-by-day monitoring, clinicians should consider any potential interventions to protect kidney functions at the early stage of the disease and renal replacement therapies in severely ill patients, particularly for those with strong inflammatory reactions or a cytokine storm. Funding: None.