Clinical characteristics and etiology of children with bronchiolitis before and during the COVID-19 pandemic in Suzhou, China

Objective We sought to compare the clinical characteristics and etiology of children with bronchiolitis in Suzhou before the pandemic of coronavirus disease 2019 (COVID-19) with those during the pandemic. Methods Children who were hospitalized with bronchiolitis in the Department of Respiratory Disease, Children's Hospital of Soochow University were retrospectively enrolled over 3 consecutive years (2019, 2020, and 2021) from February 1 to January 31. Medical records were reviewed for etiology, clinical manifestations, and laboratory examination results. Results The pathogen detection rate and the positive respiratory syncytial virus (RSV) detection rate were lowest in 2020 and highest in 2021. The rate of human rhinovirus detection in 2021 was higher than that in 2019 but similar to that in 2020. The RSV-positive rate differences among the 3 years varied by age group. Regarding the monthly distribution of RSV-positive cases over the 3-year study, all age groups showed a significant increase in the number of cases during the winter of 2021, and this increase started as early as October. With regard to clinical manifestations, the proportion of children presenting with stuffy nose rhinorrhea in 2021 [73.33% (165/225)] was greater than that in 2019 [48.61% (122/251)] and 2020 [57.06% (97/170)], while the proportion of children with gastrointestinal symptoms in 2021 [11.56% (26/225)] was smaller than that in 2019 [25.50% (64/251)] but similar to that in 2020 [17.06% (29/170)]. Conclusions After the implementation of COVID-19 pandemic-related interventions, significantly lower pathogen detection and RSV-positive rates were observed in children with bronchiolitis in 2020. An upward trend in these rates was observed in 2021, coinciding with the relaxation of COVID-19 prevention measures. Strengthening infection control and surveillance systems is extremely important for future work.

Research on the Influence of Socially Regulated Learning on Online Collaborative Knowledge Building in the Post COVID-19 Period

Online teaching has become an important initiative to maintain normal educational order in the post COVID-19 period. However, learners face multiple challenges in the online learning process, which cannot be successfully carried out without the support of socially regulated learning (SoRL). This study designed SoRL intervention strategies from the perspective of shared metacognitive scripts. A total of 77 undergraduate students participated in this study and were randomly assigned into experimental and control groups. The students in the experimental group received an SoRL intervention, and the students in the control group learned with the traditional online collaborative learning approach. The results showed that there was variability in the supply of SoRL intervention scripts and the actual selection status of the learners. The regulation foci activated in this study were time management, content monitoring, and atmosphere activation. Atmosphere activation drove collaborative learning activities to continue. Time management and content monitoring drove collaborative knowledge building (CKB) to a deeper level. This study is of great significance in revealing the impact mechanism of SoRL on CKB.

The effect of COVID-19 restrictions on atmospheric new particle formation in Beijing

During the COVID-19 lockdown, the dramatic reduction of anthropogenic emissions provided a unique opportunity to investigate the effects of reduced anthropogenic activity and primary emissions on atmospheric chemical processes and the consequent formation of secondary pollutants. Here, we utilize comprehensive observations to examine the response of atmospheric new particle formation (NPF) to the changes in the atmospheric chemical cocktail. We find that the main clustering process was unaffected by the drastically reduced traffic emissions, and the formation rate of 1.5 nm particles remained unaltered. However, particle survival probability was enhanced due to an increased particle growth rate (GR) during the lockdown period, explaining the enhanced NPF activity in earlier studies. For GR at 1.5–3 nm, sulfuric acid (SA) was the main contributor at high temperatures, whilst there were unaccounted contributing vapors at low temperatures. For GR at 3–7 and 7–15 nm, oxygenated organic molecules (OOMs) played a major role. Surprisingly, OOM composition and volatility were insensitive to the large change of atmospheric NOx concentration;instead the associated high particle growth rates and high OOM concentration during the lockdown period were mostly caused by the enhanced atmospheric oxidative capacity. Overall, our findings suggest a limited role of traffic emissions in NPF.

Analysis of differences in lymphocyte subsets and CD4+ T cells immune activation between re-detectable positive and non-re-detectable positive COVID-19 convalescent patients (preprint)

Background: Recently many literature were reported on the re-detectable positive phenomenon of COVID-19 patients during recovery, but there were few studies on the lymphocyte subsets and T-lymphocyte activation indicators between the RP (re-detectable positive) and NRP (non-re-detectable positive) patients. The aim of this study was to analyze immunological characteristics of RP and NRP patients among convalescent patients from post-discharge COVID-19 patients. Methods: Anticoagulated whole blood samples were collected from 11HCs (healthy controls) and 66 COVID-19 convalescent patients, then the percentage of lymphocyte subsets and CD4+CD38+/HLA-DR+ T cells were tested with flow cytometry, SARS-CoV-2 S RBD-IgG antibody ( anti-spike protein receptor-binding domain IgG antibody) was detected by chemiluminescence. Results: B cells (%) in RP group was significantly lower than that in HC group (P=0.005), and B cells (%) decreased successively in HC, NRP and RP group, with significant differences among the three groups (P=0.016). CD3+ and CD8+T cells (%) in RP group were noticeably higher than that in NRP group (P=0.004,0.019, respectively), but there was no difference in CD4+T cells (%) and NK cells (%) among the three groups. The CD4+CD38+ and CD4+HLA-DR+T cells (%) in RP group were noticeably higher than that in HC group (P=0.025,0.018). ANOVA (Analysis of variance) of the three groups showed that CD4+CD38+ and HLA-DR+T cells (%) were also significant difference (P=0.037, 0.029), and CD4+HLA-DR+T cells (%) in the three groups increased in turn. Meanwhile, there was a substantial positive correlation between RBD-IgG titer and CD4+HLA-DR+(%) (P=0.003, r=0.517), and the RBD-IgG titer of HLA-DR + high group was obviously higher than that of HLA-DR + Low group (P=0.005). Conclusions: In this work, we analyzed the immunological characteristics of re-detectable positive COVID-19 convalescent patients through lymphocyte subsets, suggesting that the low B cells (%) and the increased CD4+HLA-DR+T cells (%) in the convalescent patients of COVID-19 may be related to re-detectable positive phenomenon. 

Epidemiological Characteristics of Traumatic Spinal Cord Injuries in Multi-Center Retrospective Study in Northwest China, 2017-2020. (preprint)

Introduction: Traumatic spinal cord injuries (TSCI) are worldwide public health problems. There has been a lack of extensive multi-center study of TSCI epidemiology in Northwest China in pre- and post-pandemic period of COVID-19. Materials: and Methods: A multi-center retrospective study of 14 hospitals of Northwest China was conducted on patients with TSCI between 2017 and 2020. Variables assessed included patient demographics, etiology, segmental distribution, treatment, waiting time for treatment and outcomes. Results: : The number of patients with TSCI showed an increasing trend from 2017 to 2019 while there were fewer patients in 2020 than in 2019. The male-to-female ratio was 3.67:1 and the mean age was 48±14.9. The major cause of TSCI was high fall (38.8%), low fall (27.7%), traffic accidents (23.9%), sports (2.6%) and others (7.0%). The segmental distribution showed a bimodal pattern, peak segments were C6 and Tl1, L1(14.7%) was the most frequently injured segments. Incomplete injury (72.8%) occurred more often than complete injury (27.2%). ASIA scale of most patients did not change before and after treatment both in operational or conservative group. 975 patients from urban and 1646 patients from rural areas were conducted, most urban residents could rush to get treatment after injured immediately (<1 h), whereas most rural patients get treatment spend several hours since injured. The rough annual incidence from 2017-2020 are 112.4, 143.4,152.2 and 132.6 per million people calculated by the population-coverage-rate. Conclusion: The incidence of TSCI in Northwest China is high and growing. However, under the pandemic policy reasons, it has decreased in 2020. The promotion of online work may be an effective primary prevention measures for trauma. Also, due to the distance from the hospitals with proper conditions, rural patients need to spend long time to there, the timely treatment of them should be paid attention.

Epidemiological Characteristics of COVID-19 Deaths In China: An Analysis of Environmental Factors (preprint)

Background: As of April 2020, most of the confirmed cases outside Hubei province have been cured or confirmed dead in China. We aimed to understand environmental factors leading to COVID-19-related mortality in non-Hubei region. Methods: : We collected spatial-temporal and environmental data of 99 cases of COVID-19-related deaths outside of Hubei province in Mainland China between January 22, 2020 and April 6, 2020. A descriptive analysis, including a spatial-temporal distribution of daily reported diagnosed cases and related deaths, was conducted. We analyzed the possible environmental factors that affect the provincial-level case fatality rate (CFR) of COVID-19 outside Hubei, China. Results: Among the 99 reported deaths, 59 (59.6%) were male and 40 (40.4%) were female. The mean age at death was 71.30 (SD 12.98) years and 74 deaths were among those 65 years or older. The CFR was negatively correlated with temperature (r=-0.679, P <0.001) and humidity (r=-0.607, P =0.002), while latitude was positively correlated with the CFR (r=0.636, P =0.001). There were no statistically significant associations between CFR and the social environment factors. Conclusion: Higher CFR of COVID-19 was associated with lower temperature, lower humidity, and higher latitude. Continual analysis of daily reported diagnoses and mortality data can help healthcare professionals and policy makers understand the trends within a country in order to better prepare nationwide prevention and care guidelines, along with adequately appropriate funds accordingly.

Sustainable Development of University EFL Learners’ Engagement, Satisfaction, and Self-Efficacy in Online Learning Environments: Chinese Experiences

This study investigated the sustainable development of university EFL learners regarding their engagement, satisfaction, and self-efficacy in online learning environments during the outbreak of COVID-19. In a questionnaire survey with a sample of 428 Chinese undergraduate EFL learners, the students reported a favorable view of online learning environments and subjective learning outcomes. Behavioral engagement was positively related to involvement. Emotional engagement was positively related to student cohesiveness and negatively related to teacher support. Satisfaction was not related to any of the learning environment factors. Self-efficacy mediated the effect of student cohesiveness and student involvement on behavioral engagement, emotional engagement, and satisfaction. These results of the study have implications for creating a sustainable online learning environment and promoting EFL learners’ sustainable development.

Associations Between the Use of Non-Steroidal Anti-Inflammatory Drugs and Adverse Outcomes Among Patients with COVID-19: A Systematic Review and Meta-Analysis (preprint)

Background: There are concerns that the use of non-steroidal anti-inflammatory drugs (NSAIDs) may increase the risk of adverse outcomes in COVID-19 patients. Therefore, this study aimed to synthesize the existing evidence on associations between the use of NSAIDs and adverse outcomes among patients with COVID-19.Methods: Systematic search of WHO COVID-19 Database, Medline, The Cochrane Library, Web of Science, Embase, China Biology Medicine disc, China National Knowledge Infrastructure, and Wanfang Database for all articles published from January 1, 2020, to August 10, 2021, as well as a supplementary search of Google Scholar. We included comparative observational studies and randomized controlled trials that enrolled patients with COVID-19 who took NSAIDs before or after diagnosis of COVID-19. Data extraction and quality assessment of methodology of included studies were completed by two reviewers independently. We conducted a meta-anlysis on the main outcomes, as well as selected subgroup analyses stratified by the type of NSAID.Fingings: Fifteen non-randomized studies evaluating 24700 adult COVID-19 patients were identified. The use of NSAIDs in patients with COVID-19, compared with no use of NSAIDs, was not significantly associated with an elevated mortality (odds ratio [OR]=0.94, 95% confidence interval [CI]: 0.87 to 1.02), or an increased probability of ICU admission (OR=1.35, 95% CI: 0.73 to 2.49), requiring mechanical ventilation (OR=1.23, 95% CI: 0.71 to 2.13), or administration of supplemental oxygen (OR=0.99, 95% CI: 0.91 to 1.08). The subgroup analyses revealed that the use of ibuprofen (OR=1.22, 95% CI: 0.32 to 4.60), etoricoxib (OR=0.36, 95% CI: 0.02 to 6.49) or celecoxib (zero deaths in both groups) were not associated with an increased risk of death in COVID-19 patients, compared with not using any NSAID.Interpretation: Fever is one of the main clinical symptoms of COVID-19. According to our findings, NSAIDs such as ibuprofen can be used to treat fever in COVID-19 patients safely.Funding: None to declare. Declaration of Interest: None to declare.

The Frequency of Hand-to-Eye/Nose Contact can Increase the Risk of Ocular Symptoms in SARS-CoV-2-Infected Patients (preprint)

Purpose: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has the capacity to use the eye for transocular entry. The characteristics of lacrimal drainage remind us to pay attention to the transmission route passing through the nasolacrimal ducts and then into the respiratory tract. The aim of this study was to assess ocular symptoms and hand-to-eye/nose contact behaviour in SARS-CoV-2-infected patients. Methods: A questionnaire was designed by brain storing method according to practical requirements, then the survey of ocular symptoms and hand-to-eye/nose contact behaviour in SARS-CoV-2-infected patients was administered in person. The patients answered the items under the guidance of a nurse. The data of ocular symptoms and basic information was collected analysed. The correlation between ocular symptoms and hand-to-eye/nose contact behaviour was evaluated. Results: The most common ocular symptoms were increased discharge (in 53.19% of patients), foreign body sensation (44.68%), tearing (44.68%), conjunctival congestion (40.43%) and mild eye pain (40.43%). In total, 61.7% of patients had nasal obstruction and running. A total of 40.4% of patients blew their nose more frequently than usual because of nasal symptoms. A total of 63.8% of patients rubbed their eyes with their hands 1-5 times per day. Only 44.68% of patients washed their hands immediately when arriving at home more than 6 days per week. Increased frequencies of blowing noses (p=0.032), washing hands (p=0.025), and rubbing eyes (p=0.005) can affect ocular symptoms. The frequency and the way of face washing had no correlation with ocular symptoms. Conclusions: Ocular symptoms in SARS-CoV-2-infected patients are much more common than currently reported but nonspecific. This prompt us pay more attention to the true incidence of conjunctivitis in SARS-CoV-2-infected patients. The frequency of hand-to-eye/nose contact can increase the risk of presenting ocular symptoms. However, hand washing can decrease the risk. These results provide direct evidence of behaviour change and smooth the concerns for many people.

How Information Diffuse in a Nomination Network (preprint)

During the special period of the COVID-19 outbreak, this project investigated the driving factors in different information diffusion modes (i.e. broadcasting mode, contagion mode) based on the nomination relations in a social welfare campaign on Weibo. Specifically, we mapped a nomination social network and tracked the core communicators in both modes. Besides, we also observed the network from perspectives such as relationships between core communicators and modularity of the whole network. We extracted 6 homophily factors and tested them on 2 representative communities within the largest component of the network. We found that some core communicators distributed in a co-dependent way. At last, we supposed several explanations to the phenomenon which can be explored in further research.

Working conditions and health status of 6,317 front line public health workers across five provinces in China during the COVID-19 epidemic: a cross-sectional study (preprint)

Background: Public health workers at the Chinese Centre for Disease Control and Prevention (China CDC) and primary health care institutes (PHIs) were among the main workers who implemented prevention, control, and containment measures. However, their efforts and health status have not been well documented. We aimed to investigate the working conditions and health status of front line public health workers in China during the COVID-19 epidemic. Methods: : Between 18 February and 1 March 2020, we conducted an online cross-sectional survey of 2,313 CDC workers and 4,004 PHI workers in five provinces across China experiencing different scales of COVID-19 epidemic. We surveyed all participants about their work conditions, roles, burdens, perceptions, mental health, and self-rated health using a self-constructed questionnaire and standardised measurements (i.e., Patient Health Questionnaire and General Anxiety Disorder scale). To examine the independent associations between working conditions and health outcomes, we used multivariate regression models controlling for potential confounders. Results: : The prevalence of depression, anxiety, and poor self-rated health was 21.3%, 19.0%, and 9.8%, respectively, among public health workers (27.1%, 20.6%, and 15.0% among CDC workers and 17.5%, 17.9%, and 6.8% among PHI workers). The majority (71.6%) made immense efforts in both field and non-field work. Nearly 20.0% have worked all night for more than 3 days, and 45.3% had worked throughout the Chinese New Year holiday. Three risk factors and two protective factors were found to be independently associated with all three health outcomes in our final multivariate models: working all night for >3 days (multivariate odds ratio [ORm]=1.67~1.75, p <0.001), concerns about infection at work (ORm=1.46~1.89, p <0.001), perceived troubles at work (ORm=1.10~1.28, p <0.001), initiating COVID-19 prevention work after January 23 (ORm=0.78~0.82, p =0.002~0.008), and ability to persist for > 1 month at the current work intensity (ORm=0.44~0.55, p <0.001). Conclusions: : Chinese public health workers made immense efforts and personal sacrifices to control the COVID-19 epidemic and faced the risk of mental health problems. Efforts are needed to improve the working conditions and health status of public health workers and thus maintain their morale and effectiveness during the fight against COVID-19.

Difficulties of Prevention and Control Staff in COVID-19 Outbreak: A Cross-sectional Study Based on Five Provinces (preprint)

Objectives: The aim of this study is to address the difficulties encountered by epidemic control staff in the early and middle stages of their efforts to combat COVID-19, compare the gaps among different types of institutions, and identify shortcomings in epidemic control. Methods: Using multi-stage sampling, a survey of primary (“primary-urban” and “primary-rural”) and non-primary (“CDC”) public health workers involved in the prevention and control of COVID-19 in five provinces, including Hubei, Guangdong, Sichuan, Jiangsu and Gansu, was conducted from 18 February to 1 March 2020 through a self-administered questionnaire.Results: A total of 9475 outbreak prevention and control workers were surveyed, of which 40.0% were from the primary-rural, 27.0% were from the primary-urban and 33.0% were CDC. Resources shortage was reported at 27.9%, with the primary-rural being the worst affected (OR=1.201, 95%CI: 1.073-1.345). Difficulties in data processing were reported at 31.5%, with no significant differences among institutions. Communication and coordination difficulties were reported at 29.8%, with the CDC being the most serious (the rural primary: OR=0.520, 95%CI: 0.446-0.606; the primary-urban: OR=0.533, 95%CI: 0.454-0.625). Work object difficulties were reported at 20.2%, with the primary-urban being the worst (OR=1.368, 95%CI: 1.199-1.560). Psychological distress was reported at 48.8%, with no significant differences among institutions.Conclusions: Psychological distress is the most serious problem in the prevention and control of COVID-19, and the resources shortage in primary-rural, communication and coordination difficulties in CDC, and difficulties in working with the target population in the primary-urban deserve attention. This study will provide a scientific basis for improving the national public health emergency management system, especially for reducing the urban-rural differences in emergency response capacity.

Rapid evaluation of neutralizing antibodies in COVID-19 patients (preprint)

The ongoing coronavirus disease 2019 (COVID-19) pandemic calls for a method to rapidly and conveniently evaluate neutralizing antibody (NAb) activity in patients. Here, an up-conversion phosphor technology-based point-of-care testing (UPT-POCT) and a microneutralization assay were employed to detect total antibodies against the receptor-binding domain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein and NAb activity in COVID-19 patients' sera, respectively, in order to determine if UPT-POCT could be used as a surrogate method for rapid evaluation of serum NAb activity in COVID-19 patients. In total, 519 serum samples from 213 recovered and 99 polymerase chain reaction re-positive (RP) COVID-19 patients were used in this report. We found that UPT-POCT reporting values correlated highly with NAb titers from 1:4 to 1:1024, with a correlation coefficient r = 0.9654 (P < 0.001), as well as protection rate against RP (r = 0.9886, P < 0.0001). As a significant point for reducing re-positive rate, UPT-POCT values of 4.380, corresponding to NAb titer of 1:64, may be appropriate as an indicator for evaluating high efficiency of protection. This study demonstrates that the quantitative lateral flow based UPT-POCT, could be used to rapidly evaluate NAb titer, which is of importance for assessing vaccine immunization efficacy, herd immunity, and screening patient plasma for high NAbs.

Viral RNA level, serum antibody responses, and transmission risk in discharged COVID-19 patients with recurrent positive SARS-CoV-2 RNA test results: a population-based observational cohort study (preprint)

SummaryO_ST_ABSBackgroundC_ST_ABSManaging discharged COVID-19 (DC) patients with recurrent positive (RP) SARS-CoV-2 RNA test results is challenging. We aimed to comprehensively characterize the viral RNA level and serum antibody responses in RP-DC patients and evaluate their viral transmission risk. MethodsA population-based observational cohort study was performed on 479 DC patients discharged from February 1 to May 5, 2020 in Shenzhen, China. We conducted RT-qPCR, antibody assays, neutralisation assays, virus isolation, whole genome sequencing (WGS), and epidemiological investigation of close contacts. FindingsOf 479 DC patients, the 93 (19%) RP individuals, including 36 with multiple RP results, were characterised by young age (median age: 34 years, 95% confidence interval [CI]: 29-38 years). The median discharge-to-RP length was 8 days (95% CI: 7-14 days; maximum: 90 days). After readmission, RP-DC patients exhibited mild (28%) or absent (72%) symptoms, with no disease progression. The viral RNA level in RP-DC patients ranged from 1{middle dot}9-5{middle dot}7 log10 copies/mL (median: 3{middle dot}2, 95% CI: 3{middle dot}1-3{middle dot}5). At RP detection, the IgM, IgG, IgA, total antibody, and neutralising antibody (NAb) seropositivity rates in RP-DC patients were 38% (18/48), 98% (47/48), 63% (30/48), 100% (48/48), and 91% (39/43), respectively. Regarding antibody levels, there was no significant difference between RP-DC and non-RP-DC patients. The antibody level remained constant in RP-DC patients pre- and post-RP detection. Virus isolation of nine representative specimens returned negative results. WGS of six specimens yielded only genomic fragments. No clinical symptoms were exhibited by 96 close contacts of 23 RP-DC patients; their viral RNA (96/96) and antibody (20/20) test results were negative. After full recovery, 60% of patients (n=162, 78 no longer RP RP-DC and 84 non-RP-DC) had NAb titres of [≥]1:32. InterpretationRP may occur in DC patients following intermittent and non-stable excretion of low viral RNA levels. RP-DC patients pose a low risk of transmitting SARS-CoV-2. An NAb titre of [≥] 1:32 may provide a reference indicator for evaluating humoral responses in COVID-19 vaccine clinical trials. FundingSanming Project of Medicine in Shenzhen, China National Science and Technology Major Projects Foundation, Special Foundation of Science and Technology Innovation Strategy of Guangdong Province of China, and Shenzhen Committee of Scientific and Technical Innovation grants.

Clinical Features of Hemodialysis (HD) patients confirmed with Coronavirus Disease 2019 (COVID-19): a Retrospective Case-Control Study (preprint)

Background: Since December 2019, Coronavirus Disease 2019(COVID-19) occurred in wuhan, China, and outbreaked rapidly into a global pandemic. This current poses great challenges to hemodialysis (HD) patients. Objective: To make a comprehensive evaluation and comparison between HD patients confirmed with COVID-19 and the general HD patients. Methods: HD patients confirmed with COVID-19 in Wuhan No.5 Hospital were admitted as confirmed group from Jan 10 to Mar 15, 2020. And HD patients not infected in our dialysis center were chosen as control group. General characteristics, laboratory indicators were retrospectively collected, analyzed and compared. Results: A total of 142 cases were admitted, including 43 cases in confirmed group and 99 in control group. Body mass index (BMI) was slightly lower in confirmed group than that in control group (P=0.011). The proportion of one or less underlying disease in confirmed group(51.16%) was higher than that in control group(14.14%)(P< 0.001), and the proportion of three or more underlying diseases in confirmed group(11.63%) was lower than that in control group(52.53%)(P< 0.001). Patients in confirmed group exhibited significantly lower hemoglobin, lymphocyte count, and lymphocyte percentage, but higher neutrophil percentage, neutrophil-to-lymphocyte ratio (NLR), C-reactive protein, aspartate transaminase, and alkaline phosphatase. There was no significant difference in age, gender, dialysis age, primary disease, the using of ACEI/ARB, platelet-to-lymphocyte ratio (PLR) , and other indicators between the two groups. Conclusions: Faced with Severe Acute Respiratory Syndrome-CoV-2 (SARS-CoV-2), HD patients with lower BMI and hemoglobin were more susceptible to be infected, which might be related to malnutrition. Once confirmed with COVID-19, HD patients expressed obviously disregulated in inflammation and immune.

A Novel Amplification-free SARS-CoV-2 Point-of-care Nucleic Acid Detection System based on Hybrid Capture Fluorescence Immunoassay (preprint)

Herein we presented a novel, rapid and amplification-free SARS-CoV-2 nucleic acid detection system based on hybrid capture fluorescence immunoassay (HC-FIA) technology. The usage of the monoclonal antibody S9.6 in recognizing DNA-RNA double-stranded hybrids enabled the conversion of nucleic acid testing into immunofluorescence carrying on a simple lateral flow dipstick. The established HC-FIA also exhibited satisfactory sensitivity, specificity and great robustness. The clinical evaluation of HC-FIA kit and fluorescence reading device are further processed in three hospitals independently. The results of 734 samples from 670 subjects indicated high consistency between our HC-FIA and quantitative polymerase chain reaction based commercially available kit or clinical diagnosis according to Kappa statistics. Altogether, HC-FIA related method and commercial test kit show unparalleled advantages as time saving, amplification-free, high throughput and portable POCT molecular diagnosis, which facilitates its application as on-site Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid detection in epidemic prevention and control worldwide, especially during the outbreak.

The production of antibodies for SARS-CoV-2 and its clinical implication (preprint)

Background: Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), a novel betacoronavirus, has caused an outburst of pneumonia cases in Wuhan, China. We report the production of specific IgM and IgG antibodies after the infection of SARS-CoV-2 and its implication for the diagnosis, pathology and the course of the disease as well as the recurrence of positive nucleic acid tests after discharge. Methods: Test results for SARS-CoV-2 IgM and IgG antibodies of 221 confirmed COVID-19 patients were retrospectively examined, and their clinical data were collected and analyzed based on various subgroups. SARS-CoV-2 IgM and IgG antibodies were determined with the chemiluminescence method. Findings: The concentration (S/CO) of SARS-CoV-2 IgM and IgG antibodies peaked on day 19-21 after symptom onset, with a median of 17.38 (IQR 4.39-36.4) for IgM and 5.59 (IQR 0.73-13.65) for IgG. Detection rates reached highest on day 16-18 and day 19-21 for IgM and IgG, which were 73.6% and 98.6%, respectively, with significantly higher concentration of IgG in critically ill patients than in those with mild to moderate disease (P=0.027). The concentration of the antibodies on day 16-21 is not correlated with the course or outcome of the disease (Spearman r < 0.20, P > 0.05). Nasopharyngeal swabs revealed positive SARS-CoV-2 RNA in up to 52.7% of recovered patients after discharge, whose IgG proved to be significantly lower than that of those with negative RNA results (P = 0.009). IgG and IgM were tested twice within 14 days after discharge with a 7-day interval, and the second testing of these antibodies displayed a decrease in concentration of 21.2% (IQR, 11.2%34.48%) for IgG and 23.05% (IQR, -27.96%46.13%) for IgM, without statistical significance between the patients with re-detectable positive RNA results and those with negative RNA results after discharge. However, those with positive results experienced a count decrease in lymphocyte subsets. Interpretation: The concentration of SARS-CoV-2 IgM and IgG antibodies peaked on day 19-21 after symptom onset, and antibody testing on day 16-21 is associated with increased detection rates, but the antibody concentration does not affect the course and outcome of the infection. Recovering patients with re-detectable positive SARS-CoV-2 RNA displayed lower concentration of IgG, but the downward trend of IgG during recovery indicated its limited duration of protection, and the protective effect of IgG remains to be investigated.

Chest Computed Tomography for the Diagnosis of Patients with Coronavirus Disease 2019 (COVID-19): A Rapid Review and Meta-Analysis (preprint)

Background: The outbreak of the coronavirus disease 2019 (COVID-19) has had a massive impact on the whole world. Computed tomography (CT) has been widely used in the diagnosis of this novel pneumonia. This study aims to understand the role of CT for the diagnosis and the main imaging manifestations of patients with COVID-19. Methods: We conducted a rapid review and meta-analysis on studies about the use of chest CT for the diagnosis of COVID-19. We comprehensively searched databases and preprint servers on chest CT for patients with COVID-19 between 1 January 2020 and 31 March 2020. The primary outcome was the sensitivity of chest CT imaging. We also conducted subgroup analyses and evaluated the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results: A total of 104 studies with 5694 patients were included. Using RT-PCR results as reference, a meta-analysis based on 64 studies estimated the sensitivity of chest CT imaging in COVID-19 was 99% (95% CI, 0.97-1.00). If case reports were excluded, the sensitivity in case series was 96% (95% CI, 0.93-0.99). The sensitivity of CT scan in confirmed patients under 18 years old was only 66% (95% CI, 0.11-1.00). The most common imaging manifestation was ground-glass opacities (GGO) which was found in 75% (95% CI, 0.68-0.82) of the patients. The pooled probability of bilateral involvement was 84% (95% CI, 0.81-0.88). The most commonly involved lobes were the right lower lobe (84%, 95% CI, 0.78-0.90) and left lower lobe (81%, 95% CI, 0.74-0.87). The quality of evidence was low across all outcomes. Conclusions: In conclusion, this meta-analysis indicated that chest CT scan had a high sensitivity in diagnosis of patients with COVID-19. Therefore, CT can potentially be used to assist in the diagnosis of COVID-19.

Supportive Care for Patient with Respiratory Diseases: An Umbrella Review (preprint)

Abstract Background: Supportive treatment is an important and effective part of the management for patients with life-threatening diseases. This study aims to identify and evaluate the forms of supportive care for patients with respiratory diseases. Methods: An umbrella review of supportive care for patient respiratory diseases was undertaken. We comprehensively searched the following databases: Medline, EMBASE, Web of Science, CNKI (China National Knowledge Infrastructure), Wanfang Data and CBM (SinoMed) from their inception to 31 March 2020, and other sources to identify systematic reviews and meta-analyses related to supportive treatments for patient with respiratory diseases including COVID-19, SARS, MERS and influenza. We assessed the methodological quality using the AMSTAR score and the quality of the evidence for the primary outcomes of each included systematic review and meta-analysis. Results: We included 18 systematic reviews and meta-analyses in this study. Most studies focused on the respiratory and circulatory support. Ten studies were of high methodological quality, five studies of medium quality, and three studies of low quality. According to four studies extracorporeal membrane oxygenation did not reduce mortality in adults (OR/RR ranging from 0.71 to 1.28), but two studies reported significantly lower mortality in patients receiving venovenous extracorporeal membrane oxygenation than in the control group (OR/RR ranging from 0.38 to 0.73). Besides, monitoring of vital signs and increasing the number of medical staff may also reduce the mortality in patients with respiratory diseases. Conclusions: Our overview suggests that supportive care may reduce the mortality of patients with respiratory diseases to some extent. However, the quality of evidence for the primary outcomes in the included studies was low to moderate. Further systematic reviews and meta-analyses are needed to address the evidence gap regarding the supportive care for SARS, MERS and COVID-19.