七例2019冠状病毒病(COVID-19)普通型患者出院后病毒核酸随访结果 Follow-up testing of viral nucleic acid in discharged patients with moderate type of COVID-19

目的 随访研究2019冠状病毒病（COVID-19）患者在达到出院标准后病毒核酸检测结果，为医疗机构对出院患者随访管理提供决策依据。 方法 对浙江大学医学院附属第四医院经治疗后已符合出院标准的COVID-19患者采取院内继续隔离观察7 d，再居家隔离4周，期间记录患者每日临床体征，定期送检痰液行病毒核酸检测，评估患者病情变化。 结果 已符合现有出院标准的7例患者中有3例在5~7 d后再次出现痰液病毒核酸检测阳性，持续阳性2~6 d后再次转阴；复查患者血常规、C反应蛋白、血生化以及胸部CT结果均无明显异常，也无明显临床症状。其余4例患者随访4周，痰液病毒核酸检测均为阴性，未出现COVID-19相关临床症状，实验室和影像学检查结果无异常。 结论 COVID-19患者按现有标准出院后复阳的比例较高，建议有条件的医疗机构对满足现行出院标准的患者继续院内隔离观察7 d并进行连续的病毒核酸监测。

Spatiotemporal Variation and Driving Factors of Embodied Carbon in China-G7 Trade

China and G7 countries contribute 70% global GDP and 55% global carbon emissions. The carbon leakage between China and G7 is a crucial issue in achieving the synergetic emission abatement globally. The motivation of this study is to evaluate the embodied carbon transfer between China and G7 in the trade between 2000 and 2014, and investigate the driving factors that impact the embodied carbon trend. A multiregional input–output (MRIO) model based on the WIOD database is constructed, and a structural decomposition analysis (SDA) is employed. The results indicate that China plays the role of net exporter of embodied carbon in trade with G7, which mainly flows to the US (5825.67 Mt), Japan (3170.36 Mt) and Germany (1409.93 Mt). However, China’s embodied carbon exports to the G7 show an inverted U-shaped trend with a turning point after financial crisis, while the G7’s embodied carbon exports to China continue to rise. The conclusion is that to achieve the climate goal of carbon neutrality, it is not enough to rely solely on the low-carbon transition on the production side, the demand side should also be adjusted.

Opportunities and Challenges for mRNA Delivery Nanoplatforms.

With the global outbreak of SARS-CoV-2, mRNA vaccines became the first type of COVID-19 vaccines to enter clinical trials because of their facile production, low cost, and relative safety, which initiated great advances in mRNA therapeutic techniques. However, the development of mRNA therapeutic techniques still confronts some challenges. First, in vitro transcribed mRNA molecules can be easily degraded by ribonuclease (RNase), resulting in their low stability. Next, the negative charge of mRNA molecules prevents them from direct cell entry. Therefore, finding efficient and safe delivery technology could be the key issue to improve mRNA therapeutic techniques. In this Perspective, we mainly discuss the problems of the existing mRNA-based delivery nanoplatforms, including safety evaluation, administration routes, and preparation technology. Moreover, we also propose some views on strategies to further improve mRNA delivery technology.

Immune checkpoint blocking impact and nomogram prediction of COVID-19 inactivated vaccine seroconversion in patients with cancer: a propensity-score matched analysis.

BACKGROUND: Patients with cancer on active immune checkpoint inhibitors therapy were recommended to seek prophylaxis from COVID-19 by vaccination. There have been few reports to date to discuss the impact of progression cell death-1 blockers (PD-1B) on immune or vaccine-related outcomes, and what risk factors that contribute to the serological status remains to be elucidated. The study aims to find the impact of PD-1B on vaccination outcome and investigate other potential risk factors associated with the risk of seroconversion failure. METHODS: Patients with active cancer treatment were retrospectively enrolled to investigate the interaction effects between PD-1B and vaccination. Through propensity score matching of demographic and clinical features, the seroconversion rates and immune/vaccination-related adverse events (irAE and vrAE) were compared in a head-to-head manner. Then, a nomogram predicting the failure risk was developed with variables significant in multivariate regression analysis and validated in an independent cohort. RESULTS: Patients (n=454) receiving either PD-1B or COVID-19 vaccination, or both, were matched into three cohorts (vac+/PD-1B+, vac+/PD-1B-, and vac-/PD-1B+, respectively), with a non-concer control group of 206 participants. 68.1% (94/138), 71.3% (117/164), and 80.5% (166/206) were seropositive in vac+/PD-1B+cohort, vac+/PD-1B- cohort, and non-cancer control group, respectively. None of irAE or vrAE was observed to be escalated in PD-1B treatment except for low-grade rash.The vaccinated patients with cancer had a significantly lower rate of seroconversion rates than healthy control. A nomogram was thus built that encompassed age, pathology, and chemotherapy status to predict the seroconversion failure risk, which was validated in an independent cancer cohort of 196 patients. CONCLUSION: Although patients with cancer had a generally decreased rate of seroconversion as compared with the healthy population, the COVID-19 vaccine was generally well tolerated, and seroconversion was not affected in patients receiving PD-1B. A nomogram predicting failure risk was developed, including age, chemotherapy status, pathology types, and rheumatic comorbidity.

Efficacy and Safety of Leflunomide for Refractory COVID-19: A Pilot Study.

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may persist in patients with coronavirus disease 2019 (COVID-19) despite receiving standard care. Methods: In this pilot study of hospitalized adult patients (≥18 years of age), with radiologically confirmed pneumonia who were SARS-CoV-2 positive for more than 28 days despite standard care, were assigned to receive standard of care (SOC, grp I) or leflunomide + SOC (grp 2). After 2 weeks, grp 1 and grp 2 patients who continued to be SARS-CoV-2-positive received leflunomide for 14 days while continuing SOC. The primary outcomes were the rate of and time to SARS-CoV-2 clearance and the 14-day and 30-day hospital discharge rate. Results: 12 patients were enrolled in grp 1 and 15 patients were in grp 2. The 14 days SARS-CoV-2 viral clearance rate was 80.0% (12/15) for grp 2 patients receiving leflunomide vs. 16.7% for grp 1 patients (2/12) (p = 0.002). By day 14, the median time to SARS-CoV-2 clearance was 6.0 days (range 1-12, IQR 1-12) for grp 2 patients. In grp 1, two patients converted to viral negative on days 1 and 6 (p = 0.002). The 14-day discharge rate was 73.3% (11/15) for the grp 2 vs. 8.3% (1/12) for grp 1 (p = 0.001). The 30 days discharge rate was 100% (15/15) for the grp 2 vs. 66.7% (8/12) for grp 1. No severe adverse events or deaths were reported. Conclusion: Leflunomide may improve the SARS-CoV-2 clearance rate and discharge rate in patients with refractory COVID-19. The tolerability of the 14-28 days course of treatment with leflunomide is acceptable. These preliminary observations need to be verified by a large sample size and randomized controlled trial.

Depressive State in the Emergency Department During COVID-19: A National Cross-Sectional Survey in China.

Chinese emergency department (ED) staff encountered significant mental stress while fighting the coronavirus disease 2019 (COVID-19) pandemic. We sought to investigate the prevalence and associated factors for depressive symptoms among ED staff (including physicians, nurses, allied health, and auxiliary ED staff). A cross-sectional national survey of ED staff who were on duty and participated in combating the COVID-19 pandemic was conducted March 1-15, 2020. A total of 6,588 emergency medical personnel from 1,060 hospitals responded to this survey. A majority of respondents scored above 10 points on the PHQ-9 standardized test, which is associated with depressive symptoms. Those aged 31-45, those working in the COVID-19 isolation unit, and those with relatives ≤ 16 or ≥70 years old at home all had statistically significant associations with scoring >10 points. Depressive symptoms among Chinese emergency medical staff were likely quite common during the response to the COVID-19 pandemic and reinforce the importance of targeted ED staff support during future outbreaks.

Clinical characteristics, cause analysis and infectivity of COVID-19 nucleic acid repositive patients: A literature review.

Coronavirus disease 2019 (COVID-19) poses a serious threat to human health and lives. The virus is still spreading throughout the world, and the cumulative number of confirmed cases is increasing. After patients with COVID-19 are treated and discharged, some have repeated clinical symptoms and become positive for nucleic acid tests a second time. Through analysis and review of the existing literature, the proportion of repositive patients in the discharged patient population and their clinical characteristics were systematically described for the first time. Furthermore, an in-depth analysis of the causes of repositive nucleic acid tests and the potential transmission of the disease provides the basis for the management and protection of discharged patients with COVID-19.

Positive result of Sars-Cov-2 in faeces and sputum from discharged patients with COVID-19 in Yiwu, China.

BACKGROUND: With the effective prevention and control of COVID-19 in China, the number of cured cases has increased significantly. Further monitoring of the disease prognosis and effective control of the "relapse" of the epidemic has become the next focus of work. This study analysed the clinical prognosis of discharged COVID-19 patients by monitoring their SAR-CoV-2 nucleic acid status, which provided a theoretical basis for medical institutions to formulate discharge standards and follow-up management for COVID-19 patients. METHODS: We included 13 discharged COVID-19 patients who were quarantined for 4 weeks at home. The patient's daily clinical signs were recorded and sputum and faecal specimens were regularly sent for detection of SARS-CoV-2 nucleic acid. RESULTS: The time between initial symptoms and meeting discharge criteria was 18 to 44 days with an average of 25 ± 6 days. The faecal samples of two patients still tested positive after meeting the discharge criteria and the sputum samples of four patients returned positive 5 to 14 days after discharge. The rate of the recurring positive test result in samples from the respiratory system was 31% (4/13). CONCLUSION: Under the present discharge criteria, the high presence of SARS-CoV-2 nucleic acid in faecal and respiratory samples of discharged COVID-19 patients indicates potential infectivity. Therefore, we suggest that faecal virus nucleic acid should be tested as a routine monitoring index for COVID-19 and a negative result be added to the criteria. Simultaneously, we should strengthen the regular follow-up of discharged patients with continuous monitoring of the recurrence of viral nucleic acid.

Predicting the local COVID-19 outbreak around the world with meteorological conditions: a model-based qualitative study.

OBJECTIVES: This study aims to investigate the relationship between daily weather and transmission rate of SARS-CoV-2, and to develop a generalised model for future prediction of the COVID-19 spreading rate for a certain area with meteorological factors. DESIGN: A retrospective, qualitative study. METHODS AND ANALYSIS: We collected 382 596 records of weather data with four meteorological factors, namely, average temperature, relative humidity, wind speed, and air visibility, and 15 192 records of epidemic data with daily new confirmed case counts (1 587 209 confirmed cases in total) in nearly 500 areas worldwide from 20 January 2020 to 9 April 2020. Epidemic data were modelled against weather data to find a model that could best predict the future outbreak. RESULTS: Significant correlation of the daily new confirmed case count with the weather 3 to 7 days ago were found. SARS-CoV-2 is easy to spread under weather conditions of average temperature at 5 to 15°C, relative humidity at 70% to 80%, wind speed at 1.5 to 4.5 m/s and air visibility less than 10 statute miles. A short-term model with these four meteorological variables was derived to predict the daily increase in COVID-19 cases; and a long-term model using temperature to predict the pandemic in the next week to month was derived. Taken China as a discovery dataset, it was well validated with worldwide data. According to this model, there are five viral transmission patterns, 'restricted', 'controlled', 'natural', 'tropical' and 'southern'. This model's prediction performance correlates with actual observations best (over 0.9 correlation coefficient) under natural spread mode of SARS-CoV-2 when there is not much human interference such as epidemic control. CONCLUSIONS: This model can be used for prediction of the future outbreak, and illustrating the effect of epidemic control for a certain area.

Breastfed 13 month-old infant of a mother with COVID-19 pneumonia: a case report.

BACKGROUND: In China, mothers with confirmed or suspected COVID-19 pneumonia are recommended to stop breastfeeding. However, the evidence to support this guidance is lacking. There have been relatively few cases reported about direct breastfeeding an infant by a mother with SARS-CoV-2 pneumonia. Therefore, it is necessary to assess the safety of breastfeeding and the possible protective effects of breast milk on infants. CASE PRESENTATION: This report analyzes the case of a mother who continued breastfeeding her 13 month-old child when both were diagnosed with confirmed COVID-19 pneumonia. We describe the clinical presentation, diagnosis, treatment, and outcome. The presence of SARS-CoV-2 nucleic acid was determined in maternal serum, breast milk, nasopharyngeal (NP) swabs and feces, and in infant serum, NP swabs and feces. IgM and IgG antibodies against SARS-CoV-2 were assessed in maternal serum and breast milk and in infant serum. SARS-CoV-2 nucleic acid was not detected in the breast milk, and antibodies against SARS-CoV-2 were detected in the mother's serum and milk. CONCLUSIONS: The present case further confirms that the possibility of mother-to-child transmission about SARS-CoV-2 via breast milk alone was very small, and breast milk is safe for direct feeding of infants.

Clinical course and predictors of 60-day mortality in 239 critically ill patients with COVID-19: a multicenter retrospective study from Wuhan, China.

BACKGROUND: The global numbers of confirmed cases and deceased critically ill patients with COVID-19 are increasing. However, the clinical course, and the 60-day mortality and its predictors in critically ill patients have not been fully elucidated. The aim of this study is to identify the clinical course, and 60-day mortality and its predictors in critically ill patients with COVID-19. METHODS: Critically ill adult patients admitted to intensive care units (ICUs) from 3 hospitals in Wuhan, China, were included. Data on demographic information, preexisting comorbidities, laboratory findings at ICU admission, treatments, clinical outcomes, and results of SARS-CoV-2 RNA tests and of serum SARS-CoV-2 IgM were collected including the duration between symptom onset and negative conversion of SARS-CoV-2 RNA. RESULTS: Of 1748 patients with COVID-19, 239 (13.7%) critically ill patients were included. Complications included acute respiratory distress syndrome (ARDS) in 164 (68.6%) patients, coagulopathy in 150 (62.7%) patients, acute cardiac injury in 103 (43.1%) patients, and acute kidney injury (AKI) in 119 (49.8%) patients, which occurred 15.5 days, 17 days, 18.5 days, and 19 days after the symptom onset, respectively. The median duration of the negative conversion of SARS-CoV-2 RNA was 30 (range 6-81) days in 49 critically ill survivors that were identified. A total of 147 (61.5%) patients deceased by 60 days after ICU admission. The median duration between ICU admission and decease was 12 (range 3-36). Cox proportional-hazards regression analysis revealed that age older than 65 years, thrombocytopenia at ICU admission, ARDS, and AKI independently predicted the 60-day mortality. CONCLUSIONS: Severe complications are common and the 60-day mortality of critically ill patients with COVID-19 is considerably high. The duration of the negative conversion of SARS-CoV-2 RNA and its association with the severity of critically ill patients with COVID-19 should be seriously considered and further studied.