Effect of sampling positions in nucleic acid test on the test result: a report from 47 confirmed COVID-19 cases in Jinan City

Objective: To investigate the effect of sampling positions in nucleic acid test for COVID-19 on test results.

Research progress on potential drug interactions of anti-Coronavirus disease 2019 drugs

From the December 2019, coronavirus disease 2019 (COVID-19) was outbreak at home and abroad. Besides antiviral therapy, patients should be treated for complications, therefore a combination of drugs for treatment in Clinic need to be taken. Although recently published guidelines have repeatedly highlighted the drug interactions between the anti-COVID-l 9 medicines, it has not been detailed. The potential drug - drug interactions were reviewed 0f the anti-COVID-19 drugs, and in order to provide references for the clinical safety and rational use of the anti-COVID-19 drugs.

Government-led or Public-led? Chinese Policy Agenda Setting during the COVID-19 Pandemic (preprint)

This paper explores Chinese agenda setting during the COVID-19 pandemic to investigatewhether or not the pandemic enhances the government’s role in agenda setting, and to clarify therelationship between government-led and public-led agendas. Combining big data analysis and acase study, this paper finds an overall public-led agenda pattern in China, and a mixture ofgovernment-led and public-led agenda setting during the pandemic. In addition, it is also foundthat Chinese government bodies pay attention to, and are responsive to citizens’ emotionsexpressed through social media.

Transcriptomic Characteristics and Impaired Immune Function of Patients Who Retest Positive for SARS-CoV-2 RNA (preprint)

Background: The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has gradually become a global public health crisis. Some patients who have recovered from COVID-19 subsequently tested positive again for SARS-CoV-2 after discharge (retesting-positive, RTP). However, the underlying mechanism is unknown.Methods: Here, 30 RTP patients, 20 convalescent patients, and 20 healthy controls were enrolled for analysis of the immunological characteristics of their peripheral blood mononuclear cells (PBMCs). Furthermore, we sought to comprehensively characterize the transcriptional changes in the three groups by transcriptome sequencing.Findings: It was found that the absolute numbers of CD4+ T cells, CD8+ T cells, and NK cells were not decreased remarkably, while the expression of activation markers on these cells was significantly decreased in RTP patients. Furthermore, the percentage of granzyme B-producing T cells was also decreased in RTP patients compared with that in convalescent patients. Moreover, the high expression of inhibitor of differentiation-1 (ID1) and the low expression of IFITM10 may be associated with the insufficient activation of immune cells and RTP occurrence.Interpretation: Our findings provide insights into the impaired immune function and pathogenesis of RTP occurrence in COVID-19, which may contribute to the development of immunotherapy for RTP patients.Funding Statement: This work was supported by China National Center for Biotechnology Development (2020YFC0843800 and 2020YFC0846800), Ministry of Science and Technology of China (2020TFC0844100), and China Postdoctoral Science Foundation (2020T130112ZX).Declaration of Interests: The authors declare no potential conflict of interest.Ethics Approval Statement: The studies were approved by the Ethics Committee of the First Affiliated Hospital of the University of Science & Technology of China (2020-XG(H)-005) and Peking University First Hospital (2020-Research-112) for Emerging Infectious Diseases. Experiments were conducted in accordance with the ethical guidelines of the 1975 Declaration of Helsinki, the Principles of Good Clinical Practice, and the guidelines of China’s regulatory requirements.

Acute Pancreatitis may Occur in COVID-19 Patients with Clearance of SARS-CoV-2 in Lung: A Case Report (preprint)

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is mostly causes lung damages, but also lead to gastroenterology injury. SARS-CoV-2 - associated acute pancreatitis has been reported, however, clearance of SARS-CoV-2 and the pancreatitis was not clear.Case presentation: A 62 year old diabetic female patient suffer from coronavirus diseases (COVID-19) and detection of SARS-CoV-2 turned negative on day 11 and day 12 in sputum. Two days latter, the patient was diagnosed with acute pancreatitis. Through the support treatment, the patient got better and discharged from our hospital 18 days later.Conclusions: Our case provided an initial view of SARS-CoV-2 infection with acute pancreatitis and the acute pancreatitis may occur in COVID-19 patients with clearance of SARS-CoV-2 in lung.

The SARS-CoV-2 RNA with mild pulmonary consolidation lasts longer in non-severe COVID-19 patients: an observational study (preprint)

Background: Since December 2019, COVID-19 has rapidly swept the world. It is particularly important to understand the dynamic changes of the whole disease course of non-severe patients from the onset to the follow-up after discharge.Methods: On February 1, 2020, 18 cases of non-severe COVID-19 appeared in a hospital in Beijing. All patients were SARS-CoV-2 RNA positive by RT-PCR for pharyngeal swabs. We recorded the clinical information and viral dynamics of these patients from the onset of the disease to 2 months after discharge. According to the severity of lung consolidation, 18 patients were divided into two groups (mild pulmonary consolidation group [imaging score ≤10]; severe pulmonary consolidation group [imaging score >10]).Results: Eighteen patients (median age 43) were included, including 14 females. Fever (11/18) and cough (8/18) were the most common symptoms. The duration of SARS-CoV-2 RNA positive in mild pulmonary consolidation group was significantly longer than severe pulmonary consolidation group (the median time was 30 days and 13 days, respectively, P= 0.0031). Two months after discharge, almost all patients were followed up for IgM antibody disappearance and IgG antibody production.Conclusion: In non-severe COVID-19 patients, the positive duration of the SARS-CoV-2 RNA in patients with mild pulmonary consolidation was longer than the severe pulmonary consolidation. However, it is necessary for a large sample to verify our conclusions.

Thyroid function abnormalities in COVID-19 patients (preprint)

Background: The novel coronavirus COVID-19, has caused a worldwide pandemic, impairing several human organs and systems. Whether COVID-19 affects human thyroid function remains unknown. Methods: 84 hospitalized COVID-19 patients in the First Affiliated Hospital, Zhejiang University School of Medicine (Hangzhou, China) were respectively enrolled in this study. In addition, 73 other patients with pneumonia and 819 healthy subjects were included as controls. Results: We found that the levels of TT3 and TSH were lower in COVID-19 patients than control groups (p<0.001). Within the group of COVID-19 patients, 61.9% patients (52/84) presented with thyroid function abnormalities. We found a larger proportion of patients in severe condition exhibited thyroid dysfunction than mild/moderate cases (90.4% vs. 50.0%, p < 0.001). Patients with thyroid dysfunction tended to have increased interval time for negative conversion of viral nucleic acid (14.1 {+/-} 9.4 vs. 10.6 {+/-} 8.3 days, p = 0.088). To note, thyroid dysfunction was also associated with decreased lymphocytes (p < 0.001) and increased CRP (p = 0.002). In 7 patients with dynamic changes of thyroid function, we observed the levels of TT3 and TSH gradually increased and reached normal range without thyroid hormone replacement at Day 30 post-admission. The correlation between TT3 and TSH level seemed to be positive rather than negative in the early stage, and gradually turned to be negatively related over time. Conclusions: Thyroid function abnormalities are common in COVID-19 patients, especially in severe cases. This might be caused by virus attack and damage to the thyroid-pituitary axis. Therefore, more attention should be paid to thyroid function during treatment of COVID-19, and close follow-up is also needed after discharge.

Physical Distancing, Face Masks, and Eye Protection to Prevent Person-Person COVID-19 Transmission: A Systematic Review and Meta-Analysis (preprint)

Background: Coronavirus disease 2019 (COVID-19) is spread person to person by virus through close contact. The optimal person-person distance and use of facemasks and/or eye protection to prevent disease transmission in healthcare and non-healthcare settings is debated.Methods: We systematically reviewed the impact of distance, masks, and eye protection on transmission of COVID-19, SARS, or MERS from 21 standard, World Health Organization (WHO)-specific and COVID-19-specific data sources from inception to April 15, 2020 for studies of any design and language 1) comparing different distances between those infected and the people close to them, mask use, or eye protection, or 2) contextual factors of acceptability, feasibility, resource use, and equity of these interventions. We screened studies, extracted data, and assessed risk of bias in duplicate. Frequentist and Bayesian meta-analyses and meta-regression for the main outcome of viral transmission were by random effects. Secondary outcomes were contextual factors. We rated certainty of evidence rating per GRADE. PROSPERO: 177047.Findings: We identified 0 RCTs and 164 relevant observational studies in healthcare and non-healthcare (community) settings from 16 countries across 6 continents. A physical distance of one metre or more compared to less than one metre from those infected was associated with 1) a lower risk of viral transmission (n=7782, 5.3% vs 15.5%; RD -10.2% [95%CI -11.5% to -7.5%], pooled adjusted odds ratio [aOR] 0.18 [95%CI 0.09-0.38], moderate certainty) and 2) incremental benefits with increasing distance, change in relative risk (RR) per metre 1.57 (moderate certainty). Facemask use was associated with less infection (n=2647, 2.7% vs 17.4%; RD -14.% [95% credible interval [CrI] -15.9% to -10.7%]; aOR 0.15 [95%CrI 0.07-0.34], low certainty), with stronger associations with N95 or similar (including powered) respirators compared to disposable surgical or similar (e.g. reusable 12-16-layer cotton) masks, p interaction =0.090; posterior probabilities for RR<1 of N95 vs surgical masks were >95% despite minimally informative priors; moderate certainty). Eye protection was associated with quantitatively similar lower risk of infection in 2 adjusted and 15 unadjusted studies (n=3751, 5.4% vs 16.0%; RD -10.6 [95%CI -12.5% to -7.7%]; RR 0.34 [95%CI 0.22-0.52]; aOR 0.22 [95%CI 0.12-0.39], low certainty).Interpretation: This meta-analysis supports physical distancing by more than one metre and provides quantitative estimates for models and contact tracing to inform policy. Although direct evidence is limited, the optimal use of masks, in particular N95 or similar respirators, may depend on risk assessment and contextual factors. Eye protection may provide significant additional benefits. Globally collaborative, well-conducted studies on preventative and therapeutic strategies are required but are challenging to achieve immediately and, thus, recommendations in the interim to curtail the COVID-19 pandemic should be informed by this systematic appraisal of current evidence.Funding Statement: Commissioned by the World Health Organization as a rapid review on March 25, 2020. The funders of the study helped with defining the scope of the question, but otherwise had no role in study design, data collection, data analysis, data interpretation, writing of the report, or the decision to submit it.Declaration of Interests: ML is an investigator of an ongoing clinical trial on medical masks versus N95 respirators for COVID-19 (NCT04296643). All other authors declare no competing interests. Ethics Approval Statement: The authors prospectively submitted the systematic review protocol for registration on PROSPERO (submission number 177047). This study followed PRISMA and MOOSE reporting guidelines.

Risk factors and clinical features of deterioration in COVID-19 patients in Zhejiang, China: a single- centre, retrospective study (preprint)

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection swept through Wuhan and spread across China and overseas beginning in December 2019. To identify predictors associated with disease progression, we evaluated clinical risk factors for exacerbation of SARS-CoV-2 infection.MethodsA retrospective analysis was used for PCR-confirmed COVID-19 (coronavirus disease 2019)-diagnosed hospitalized cases between January 19, 2020, and February 19, 2020, in Zhejiang, China. We systematically analysed the clinical characteristics of the patients and predictors of clinical deterioration.ResultsOne hundred patients with COVID-19, with a median age of 54 years, were included. Among them, 49 patients (49%) had severe and critical disease. Age ([36-58] vs [51-70], P=0.0001); sex (49% vs 77.6%, P=0.0031); Body Mass Index (BMI ) ([21.53-25.51] vs [23.28-27.01], P=0.0339); hypertension (17.6% vs 57.1%, P<0.0001); IL-6 ([6.42-30.46] vs [16.2-81.71], P=0.0001); IL-10 ([2.16-5.82] vs [4.35-9.63], P<0.0001); T lymphocyte count ([305- 1178] vs [167.5-440], P=0.0001); B lymphocyte count ([91-213] vs [54.5-163.5], P=0.0001); white blood cell count ([3.9-7.6] vs [5.5-13.6], P=0.0002); D2 dimer ([172-836] vs [408-953], P=0.005), PCT ([0.03-0.07] vs [0.04-0.15], P=0.0039); CRP ([3.8-27.9] vs [17.3-58.9], P<0.0001); AST ([16, 29] vs [18, 42], P=0.0484); artificial liver therapy (2% vs 16.3%, P=0.0148); and glucocorticoid therapy (64.7% vs 98%, P<0.0001) were associated with the severity of the disease. Age and weight were independent risk factors for disease severity.ConclusionDeterioration among COVID-19-infected patients occurred rapidly after hospital admission. In our cohort, we found that multiple factors were associated with the severity of COVID19. Early detection and monitoring of these indicators may reduce the progression of the disease. Removing these factors may halt the progression of the disease. In addition, Oxygen support, early treatment with low doses of glucocorticoids and liver therapy, when necessary, may help reduce mortality in critically ill patients.

Pattern of liver injury in adult patients with COVID-19: a retrospective analysis of 105 patients (preprint)

【Background】Recent studies reported that patients with coronavirus disease-2019 (COVID-19) might have liver injury. However, few data on the combined analysis and change patterns of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBil) have been shown.【Methods】 This is a single-center retrospective study. A total of 105 adult patients hospitalized for confirmed COVID-19 in Beijing Ditan Hospital between January 12, and March 17, 2020 were included, and divided into mild and severe groups. We compared liver functional test results between the two groups. Category of ALT change during the disease course was also examined.【Results】 56.2% of the patients had unnormal ALT, AST, or total TBil throughout the course of the disease, but in 91.4% cases the level of ALT, AST or TBil ≤ 3 fold of the upper normal range. The overall distribution of ALT, AST, and TBil were all significantly difference between mild and severe group (p<0.05).The percentage of the patients with both elevated ALT and AST was 12.7% in mild cases vs. 46.2% in severe cases (p = 0.001). 34.6% severe group patients started to have abnormal ALT after admission，and 73.4% of all patients had normal ALT before discharge.【Conclusion】Elevated liver function index is very common in patients with COVID-19 infection, and the level were less than 3 × ULN，but most are reversible. The abnormality of 2 or more indexes is low in the patients with COVID-19, but it is more likely to occur in the severe group.

Retrospective study of low-to-moderate dose glucocorticoids on viral clearance in patients with novel coronavirus pneumonia / 中华临床感染病杂志

Objective@#To study the effect of low-to-moderate dose glucocorticoid therapy on viral clearance time in patients with COVID-19.@*Methods@#A total of 72 patients diagnosed with COVID-19 from January 19 to February 17, 2020 at the First Affiliated Hospital, School of Medicine, Zhejiang University were recruited. All patients received oral abidol and/or combined lopinavir/ritonavir, darunavir antiviral, and symptomatic supportive care. Among them, 51 patients received methylprednisolone (0.75-1.50 mg·kg-1·d-1) (glucocorticoid treatment group), and 21 patients who did not use glucocorticoid were the control group. The time of stable virologic conversion insputumand the time of radiologic recovery in lungsince onset were compared between the two groups and among the normal patients.The Kruskal-Wallis test or Fisher exact test was used to compare the difference between groups.@*Results@#The median ages of the glucocorticoid group and the control group were 52 [interquartile range (IQR):45, 62] years and 46 (IQR: 32, 56)years, and the differences were significant (P<0.05). The clinical conditions at hospital admission were different between the two groups (P<0.01). There were 52.0% critical ill patients in the glucocorticoid treatment group, compared to that of 71.4% normal patients in the control group. The median times from the onset tostable virologic conversion to negative in the two groups were 15 (IQR:13,20) days and 14 (IQR:12,20) days (P>0.05), and the difference was no statistically significant. The median times from onset to radiologic recovery were 13 (IQR: 11,15) days and 13 (IQR:12,17) days in the two groups, and there was no difference (P>0.05). In ordinary patients, the median timesfrom the onset tostable virologic conversion insputum were no difference (P>0.05), with 13 (IQR:11,18) days in the glucocorticoid group and 13 (IQR:12,15) days in the control group; The median times from onset to radiologic recovery in lungwere also no difference (P>0.05), with 12 (IQR: 10,15)days in the glucocorticoid group and 13 (IQR: 12,17) days inthe control group.@*Conclusions@#Low-to-moderate glucocorticoid treatment has no effect on the time of virus clearance in patients with different clinical types of COVID-19. The glucocorticoid is not recommended since no effectiveness on accelerating the improvement of radiologic recovery in lung has been observed.

Host susceptibility to severe COVID-19: a retrospective analysis of 487 case outside Wuhan (preprint)

Background: The recent outbreak of SARS-CoV-2 infection results in a considerable morbidity and mortality, mainly in China. The study is to investigate the intrinstic features of infected patients that associated with severe type of this disease. Method: A total of 487 laboratory-confirmed COVID-19 patients were included in analysis. The demographic and epidemiological of patients representing as mild and severe at admission were compared. A step-wise multivariate logistic regression analysis were performed to identify significant risk factors associated with severe COVID-19 . A score systemc incorporating risk factors was established for risk stratification and validated in a small cohort during in-hospital follow-up. Results: Of all patients, 49 (10.1%) cases are severe at admission. Severe cases are elder [56(17) vs. 45(19), P<0.001), with more male (73.5% vs. 50.9%, P=0.003). They have a higher incidence of hypertension (53.1% vs. 16.7%, P<0.001), diabetes (14.3% vs. 5.0%, P=0.009), cardiovascular diseases (8.2% vs. 1.6%, P=0.003) and malignancy (4.1% vs. 0.7%, P=0.025), and less exposure to epidemic area (49.0% vs. 65.1%, P=0.027), but more infected familiy members(P=0.031). On multivariate analysis, elder age, male and presence of hypertension are independently associated with severe disease at admission. A host risk score, incorporating age, sex and hypertension history, clearly stratifies risk of developing severe type of COVID-19 both in patients at admission and during in-hospital follow-up. Conclusions: Elder age, male and presence of hypertension are associated with host susceptibility to developing severe COVID-19. The host risk score may be a useful tool to identify high risk indiviuals but requires validation.

Deep Learning System to Screen Coronavirus Disease 2019 Pneumonia (preprint)

We found that the real time reverse transcription-polymerase chain reaction (RT-PCR) detection of viral RNA from sputum or nasopharyngeal swab has a relatively low positive rate in the early stage to determine COVID-19 (named by the World Health Organization). The manifestations of computed tomography (CT) imaging of COVID-19 had their own characteristics, which are different from other types of viral pneumonia, such as Influenza-A viral pneumonia. Therefore, clinical doctors call for another early diagnostic criteria for this new type of pneumonia as soon as possible.This study aimed to establish an early screening model to distinguish COVID-19 pneumonia from Influenza-A viral pneumonia and healthy cases with pulmonary CT images using deep learning techniques. The candidate infection regions were first segmented out using a 3-dimensional deep learning model from pulmonary CT image set. These separated images were then categorized into COVID-19, Influenza-A viral pneumonia and irrelevant to infection groups, together with the corresponding confidence scores using a location-attention classification model. Finally the infection type and total confidence score of this CT case were calculated with Noisy-or Bayesian function.The experiments result of benchmark dataset showed that the overall accuracy was 86.7 % from the perspective of CT cases as a whole.The deep learning models established in this study were effective for the early screening of COVID-19 patients and demonstrated to be a promising supplementary diagnostic method for frontline clinical doctors.