Heart-on-a-chip model of immune-induced cardiac dysfunction reveals the involvement of free mitochondrial DNA and therapeutic effects of endothelial exosomes (preprint)

Cardiovascular disease continues to take more human lives than all cancer combined, prompting the need for improved research models and treatment options. Despite a significant progress in development of mature heart-on-a-chip models of fibrosis and cardiomyopathies starting from induced pluripotent stem cells (iPSCs), human cell-based models of myocardial inflammation are lacking. Here, we bioengineered a vascularized heart-on-a-chip system with circulating immune cells to model SARS-CoV-2-induced acute myocarditis. Briefly, we observed hallmarks of COVID-19-induced myocardial inflammation in the heart-on-a-chip model, as the presence of immune cells augmented the expression levels of proinflammatory cytokines, triggered progressive impairment of contractile function and altered intracellular calcium transient activities. An elevation of circulating cell-free mitochondrial DNA (ccf-mtDNA) was measured first in the in vitro heart-on-a-chip model and then validated in COVID-19 patients with low left ventricular ejection fraction (LVEF), demonstrating that mitochondrial damage is an important pathophysiological hallmark of inflammation induced cardiac dysfunction. Leveraging this platform in the context of SARS-CoV-2 induced myocardial inflammation, we established that administration of human umbilical vein-derived EVs effectively rescued the contractile deficit, normalized intracellular calcium handling, elevated the contraction force and reduced the ccf- mtDNA and chemokine release via TLR-NF-kB signaling axis.

Lung ultrasound score as a predictor of failure to wean COVID-19 patients off mechanical ventilation: a prospective observational study (preprint)

Background The lung ultrasound score was developed for rapidly assessing the extent of lung ventilation, and it can predict failure to wean various types of patients off mechanical ventilation. Whether it is also effective for COVID-19 patients is unclear.Methods This single-center, prospective, observational study was conducted to assess the ability of the 12-region lung ultrasound score to predict failure to wean COVID-19 patients off ventilation. In parallel, we assessed whether right hemidiaphragmatic excursion or previously published predictors of weaning failure can apply to these patients. Predictive ability was assessed in terms of the area under the receiver operating characteristic curve (AUC).Results Among the 35 patients in the study, 12 patients (37%) could not be weaned off mechanical ventilation. The lung ultrasound score predicted these failures with an AUC of 0.885 (95% CI 0.770–0.999, p < 0.001), and a threshold score of 10 provided specificity of 72.7% and sensitivity of 92.3%. AUCs were lower for previously published predictors of weaning failure, and right hemidiaphragmatic excursion did not differ significantly between the two groups.Conclusions The lung ultrasound score can accurately predict failure to wean critically ill COVID-19 patients off mechanical ventilation, whereas assessment of right hemidiaphragmatic excursion does not appear helpful in this regard.Trial registration: https://clinicaltrials.gov/ct2/show/NCT05706441

Investigating the Intentions and Reasons of Senior High School Students in Registering for Nursing Education in China (preprint)

Background Shortage of qualified nurses and their low level of educational qualifications hinders the development of global health services. Researches have proved the role of nursing education in addressing these problems. However, no-related studies have focused on senior high school students before in China. This study aimed to explore senior high school students’ intention to learn nursing and identify the factors influencing their decision-making process.Methods An anonymous questionnaire was distributed to 8050 senior high school students. The questionnaire that included questions regarding their demographic characteristics, understanding of the nursing specialty, cognition of the nurse occupation and experiences during the pandemic. Descriptive calculation, the chi-square test and logistic regression were used for the analysis.Results Only 0.73% of the participants had a clear intention to study nursing. Academic performance and family support were significant predictor of students’ intentions to pursue nursing education. Students’ interest in nursing specialty were associated with their choice. There was a positive correlation between cognition of nursing occupation and students’ choice of nursing. Students’ experience of Covid-19 also have positive impact on their nursing career choice.Conclusion The shortage of nurses is a particularly daunting challenge in China. This study provided a new perspective for predictors of the nursing shortage and the potential interventions.

Knowledge, Attitude, and Practices (KAP) regarding recent advances in RT-PCR test for the diagnosis of COVID-19 among technicians in China (preprint)

Since the 2019 COVID-19 virus outbreak, real-Time RT-PCR become the gold standard detection for COVID-19. We aimed to analyze the RT-PCR technicians’ knowledge, attitudes, and practices regarding to recent advances in RT-PCR tests for COVID-19. This is a cross-sectional study, that was conducted from 10 Nov 2022 to 20 Nov 2022, and included a total of 531 participants from China. To measure the difference in the mean scores, and analyze the factors related to knowledge, attitude, and practice toward RT-PCR by using univariate, non-parametric, and regression analysis. Of this survey, the mean knowledge, attitude, and practice scores about recent advances in RT-PCR tests for the diagnosis of COVID-19 were 13.23 (SD = 0.85, range: 13–16), 13.16 (SD = 1.71, range: 5–12), and 6.14 (SD = 1.85, range: 1–8), respectively, indicated good KAP. However, some significant predictors including education level and work status, influence knowledge. Age, marital status, and yearly income influence attitudes and practices. Our investigation can further understand the characteristics of RT-PCR technicians for the diagnosis of COVID-19, and be targeted to improve their overall ability.

Effectiveness of Xiaoyao capsule on sleep disorders and mood disturbance in patients in recovery from coronavirus disease 2019: a randomized controlled trial.

OBJECTIVE: To study the efficacy of Xiaoyao capsule in improving the clinical symptoms of sleep and mood disorders during recovery from coronavirus disease 2019 (COVID-19). METHODS: The study cohort comprised 200 patients with sleep and mood disorders during recovery from COVID-19. Patients were randomized into the control group and the experimental group in a 1:1 ratio by blocked randomization. The patients received either Xiaoyao capsule (experimental group) or a placebo Xiaoyao capsule (control group) for 2 weeks. The improvements in the Traditional Chinese Medicine (TCM) syndrome scales, total effective rates, and disappearance rates of irritability, anxiety, and poor sleep were compared between the two groups. RESULTS: The TCM syndrome pattern scales, total effective rates, and disappearance rates of irritability, anxiety, and poor sleep did not significantly differ between the experimental group versus the control group in the full analysis set and the per protocol set after 1 and 2 weeks of treatment ( > 0.05). CONCLUSIONS: Xiaoyao capsule do not significantly improve the clinical symptoms of sleep and mood disorders in patients in recovery from COVID-19.

Protective effect of plasma neutralization from prior SARS-CoV-2 Omicron infection against BA.5 subvariant symptomatic reinfection (preprint)

From December 2022 to January 2023, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections caused by BA.5 and BF.7 subvariants of B.1.1.529 (Omicron) swept across mainland China. It is crucial to estimate the protective effect of the neutralizing antibodies generated by such mass infections against the next potential SARS-CoV-2 reinfection wave, especially if driven by CH.1.1 or XBB.1.5. Previously, we recruited and continuously followed a cohort of individuals that experienced Omicron BA.1, BA.2, and BA.5 breakthrough infections, as well as a control cohort with no history of SARS-CoV-2 infection. In the previously uninfected cohort, the total symptomatic infection rate surveyed during the outbreak was 91.6%, while the symptomatic reinfection rate was 32.9%, 10.5%, and 2.8% among individuals with prior Omicron BA.1, BA.2 and BA.5 infection, respectively, with median intervals between infections of 335, 225 and 94 days. Pseudovirus neutralization assays were performed in plasma samples collected from previously Omicron BA.1-infected individuals approximately 3 months before the outbreak. Results indicate a robust correlation between the plasma neutralizing antibody titers and the protective effect against symptomatic reinfection. The geometric mean of the 50% neutralizing titers (NT50) against D614G, BA.5, and BF.7 were 2.0, 2.5, and 2.3-fold higher in individuals without symptomatic reinfection than in those with symptomatic reinfection (p < 0.01). Low plasma neutralizing antibody titer (below the geometric mean of NT50) was associated with an enhanced cumulative risk of symptomatic reinfection, with a hazard ratio (HR) of 23.55 (95% CI: 9.23-60.06) against BF.7 subvariant. Importantly, neutralizing antibodies titers post one month after BF.7/BA.5 breakthrough infections against CH.1.1 and XBB.1.5 are similar to that against BF.7 from individuals with prior BA.1 infection while not experiencing a symptomatic BF.7/BA.5 reinfection (plasma collected 3 months before the outbreak), suggesting that the humoral immunity generated by the current BF.7/BA.5 breakthrough infection may provide protection against CH.1.1 and XBB.1.5 symptomatic reinfection wave for 4 months. Of note, the higher hACE2 binding of XBB.1.5 may reduce the protection period since the potential increase of infectivity.

Cross-lagged analysis of the relationship between risk perception, physical activity, and adolescent mental health (preprint)

Background Anxiety symptoms were prevalent in teenagers during the new coronavirus pandemic at 31% and depression symptoms were at 34%, both significantly higher than they were before the pandemic, according to research on global adolescent mood disorders during the epidemic. It is unclear, nevertheless, if physical activity still promotes mental health given the perceived danger of sickness, even though it has been demonstrated to be useful in reducing teenage mental health issues. Therefore, this study looked into the relationship between teenage mental health, risk perception, and physical activity. Methods In December 2022 and January 2023, two surveys were given to the same pupils in five high schools. During the New Crown pandemic, the risk perception scores, physical activity levels, and mental health of adolescents were examined in the study N=344. Results For adolescents' risk perceptions, there were significant gender differences (P＜0.01), with gender difference effects of 0.255 (d = 0.416) and 0.195 (d = 0.402) for the two measurements, respectively. For mental health, there were gender differences, with gender difference effects of 0.159 (d = 0.262) and 0.179 (d = 0.278) for the two measurements. The levels of risk perception, physical activity, and teenage mental health met persistent connections across months with contemporaneous correlations, however gender differences in physical activity levels were not significant (p > 0.05); Contrarily, in the cross-lagged study, males had higher levels of physical activity and mental health than females, and teenagers' risk perception was higher. Physical activity and mental health were both predicted by T1 ( values of 0.28, 0.19, and P＜0.01, respectively). Risk perception T1 physical exercise T2 mental health T2 (mediating value impact of 0.012, the Z value of 0.112), as well as the indirect effect of Bootstrap, were all able to predict mental health T2 (β= 0.33, P ＜0.01). Indicating a substantial mediating role for physical activity between risk perception and mental health is the 95% CI, not the 0 value from this pathway. Conclusion Raising awareness of physical activity among adolescents according to gender is important for improving mental health and there is a longitudinal causal relationship between perceived risk of disease, physical activity, and mental health among adolescents, suggesting that physical activity still has a role in mental health in the presence of risk perception.

Network distribution and sentiment interaction: Information diffusion mechanisms between social bots and human users on social media

When public health emergencies occur, a large amount of low-credibility information is widely disseminated by social bots, and public sentiment is easily manipulated by social bots, which may pose a potential threat to the public opinion ecology of social media. Therefore, exploring how social bots affect the mechanism of information diffusion in social networks is a key strategy for network governance. This study combines machine learning methods and causal regression methods to explore how social bots influence information diffusion in social networks with theoretical support. Specifically, combining stakeholder perspective and emotional contagion theory, we proposed several questions and hypotheses to investigate the influence of social bots. Then, the study obtained 144,314 pieces of public opinion data related to COVID-19 in J city from March 1, 2022, to April 18, 2022, on Weibo, and selected 185,782 pieces of data related to the outbreak of COVID-19 in X city from December 9, 2021, to January 10, 2022, as supplement and verification. A comparative analysis of different data sets revealed the following findings. Firstly, through the STM topic model, it is found that some topics posted by social bots are significantly different from those posted by humans, and social bots play an important role in certain topics. Secondly, based on regression analysis, the study found that social bots tend to transmit information with negative sentiments more than positive sentiments. Thirdly, the study verifies the specific distribution of social bots in sentimental transmission through network analysis and finds that social bots are weaker than human users in the ability to spread negative sentiments. Finally, the Granger causality test is used to confirm that the sentiments of humans and bots can predict each other in time series. The results provide practical suggestions for emergency management under sudden public opinion and provide a useful reference for the identification and analysis of social bots, which is conducive to the maintenance of network security and the stability of social order.

Vulnerable or resilient? The response of informal settlements to COVID-19: The case of urban village communities in Beijing

The COVID-19 pandemic has brought topics of the impact, response and adaptation of cities in emergencies to the forefront. When compared with formal settlements, the problems faced by informal settlements are more prominent. We propose the framework of an actor-network theory, substantiated by an empirical study of three typical informal settlements in Haidian District, Beijing, in which the process, characteristics and internal mechanism of the spatial reconstruction of the informal settlements in response to COVID-19 are closely scrutinised. Human actors such as local governments, community volunteers, landlords, tenants and non-human actors all participated in the response to COVID-19 according to their goal vision and political logic, with the local government as the core driving force, forming an integrated actor network. Rooted in the special locality of informal settlements, the actor network was both hierarchical and flexible, and its inherent dynamism has proven to be efficient during COVID-19, resulting in social adaptation and spatial reconstruction. This study contributes to the cautiously optimistic estimate of similar urban community resilience in terms of global epidemics and enriches the understanding of their interlacing dynamics from the perspective of spatial reconstruction.

Dual‐Functional Anti‐Pathogen Coatings

A dual-functional anti-pathogenic coating with controllable repelling and capturing/inactivation of pathogens, which make it capable of eliminating a broad range of pathogenic bacteria and viruses, including SARS-CoV-2, is reported. The reversible switch between repelling and capturing/inactivation is readily made via its CO2-responsive wettability. In its superhydrophobic state, the coating enables a SARS-CoV-2 repellent efficacy of 99.9997%. In its superhydrophilic state, the coating has a virucidal efficacy of up to 99.9897%, which is comparable to the inactivation rate of chemical disinfectants. The coating is highly flexible with anti-corrosive and anti-frosting properties, which works for repelling essentially all pathogens and potentially could be applied into various daily used products and materials. The coating has the potential to set a new prevention standard in fighting the current pandemic and preventing future ones via especially intercepting the transmission of pathogens through contaminated surfaces.

Management model of mass vaccination of COVID-19 vaccine

OBJECTIVE: To explore the role of systematic vaccination management model in mass vaccination of COVID-19 vaccine. METHODS: According to the mass vaccination plan formulated by the Day Clinic of the Fifth Medical Center of Chinese PLA General Hospital, the vaccination work was fully deployed before vaccination;and the temporary specification of mass vaccination sites were set up according to the requirements of the temporary vaccination site for the new coronavirus vaccine in Beijing;the vaccine management systems was strictly implemented, the doctor group, nursing group and guarantee group performed the responsibilities of their own to ensure smooth and orderly vaccination work. RESULTS: The medical center has participated in more than 30 mass vaccinations of COVID-19, no vaccination error-related reactions and psychogenic reactions occurred at the vaccination site, and no adverse events that were caused by problems in the process link occurred. CONCLUSION: The detailed work plan for mass vaccination may facilitate the safe and orderly mass vaccination, and the vaccination work is unanimously recognized by the recipients.

Case Report: Subacute thyroiditis after receiving inactivated SARS-CoV-2 vaccine (BBIBP-CorV)

Background Subacute thyroiditis, an inflammatory disease, has been reported caused by vaccines in rare cases. In the context of the coronavirus disease 19 pandemic, various SARS-CoV-2 vaccines have been developed and may be potential triggers for subacute thyroiditis. Case presentation We report a case of subacute thyroiditis 3 days after receiving the second dose of inactivated SARS-CoV-2 vaccine (BBIBP-CorV). The patient did not report a previous history of thyroid disease, upper respiratory tract infection, or COVID-19. Physical examination, laboratory testing, ultrasonography, and radioactive iodine uptake were consistent with subacute thyroiditis. During follow-up, the patient recovered from symptoms and signs, and imaging changes except for hypothyroidism, requiring an ongoing thyroxine replacement. Conclusions Inactivated SARS-CoV-2 vaccine may be a causal trigger leading to subacute thyroiditis. Clinicians should be aware of subacute thyroiditis as a possible thyroid-related side effect of an inactivated SARS-CoV-2 vaccine.

Sex Differences in Students’ Performance in VR-based Learning of Gross Anatomical Education (preprint)

Background: Studying anatomy has always challenged medical students. The coronavirus disease 2019 pandemic has transformed medical education worldwide, and virtual reality (VR) has recently emerged as a useful learning tool to promote memorization through understanding and visualization. With a remarkable rise in the use of remote learning methods during the pandemic, more schools are adopting distance learning through VR for anatomy. However, scholars have yet to explore the potential sex differences among students who use VR-based anatomical learning. Thus, we investigated the effects of teaching strategies on learners’ experiences with and performance in an anatomy course using VR-based learning. Method: Fifty first-year medical students enrolled in a human anatomy course were provided with VR devices for anatomical learning. They received a questionnaire comprising four determinants of experience: demographic background, discomfort symptoms, satisfaction levels, and opinions about the VR-based learning experience after their final examination. Student performance was then compared to previous performances over three-semester years when traditional teaching methods were used. A three-way mixed-model ANOVA was used to test the effects of sex, examination, and teaching methods on the examination scores. Results: VR-based learning resulted in better exam scores when compared to the traditional learning method. Female students experienced significantly higher disorientation symptoms compared with male students, and male students showed significant improvement in laboratory examination performance. Results showed that VR-based teaching can facilitate gross anatomical learning among first-year medical students and improve the laboratory performance of male students. Conclusion: Medical schools can use VR to teach anatomy effectively; however, faculty should be prepared to support inexperienced users when learning to use a VR system. Future research should further explore sex differences for reliability.

Epidemiological Study and Clinical Characterization of COVID-19 Cases in Xuzhou, China

In this paper, an epidemiological study was performed by focusing on all confirmed patients with COVID-19 in Xuzhou, a prefecture-level city, and a transportation hub with 10.44 million population in the east region of China. The median age of the patients is 42-year-old and 45.57% are male;25 cases (31.65%) are imported. 23 cases (29.11%) were confirmed between January 26 to 31, 2020 while 56 cases (70.89%) were from February 1 to 16, 2020. Among the ten administrative divisions of Xuzhou city, Suining county (n=31) and Pizhou City (n=15) have the most cases while Tongshan district has none. A representative familial cluster with 6 cases was analyzed in detail in order to get a better understanding of the transmission routes of the virus. Furthermore, we performed a retrospective, single-centre study of 41 COVID-19 patients at Xuzhou Infectious Diseases Hospital in terms of clinical findings, which provided an insightful understanding of the disease.

AAAN: Anomaly Alignment in Attributed Networks

Anomaly subgraph detection is an important problem that has been well researched in various applications, ranging from cyberattacks in computer networks to malicious activities in social networks. Most existing approaches detect anomaly subgraphs in attributed networks with sufficient features. However, multitudinous industry data with insufficient anomalous attributes are the main challenge for traditional anomaly subgraph detection algorithms. In particular, none of the literature focuses on connected anomaly subgraph detection with insufficient anomalous features. To address this problem, we propose Anomaly Alignment in Attributed Networks (AAAN), which first detects connected anomaly subgraphs by aligning anomalies in two attributed networks (one with insufficient anomalous features and the other with sufficient anomalous features). Extensive experiments on three real-world datasets (the Weibo, Baidu migration network, and COVID-19 pandemic datasets) show the effectiveness and efficiency of our algorithm. We can identify the crime hotspots in terms of city blocks from urban traffic networks, which are aligned with the criminal events reported on social networks. The results also demonstrate how AAAN outperforms competitive approaches in the COVID-19 outbreak anomaly subgraph detection and urban crime hotspot detection tasks.

N-Acetylcysteine Treatment Accelerates Patient-Reported Outcomes Improvement in Patients With COVID-19 A Prospective Study (preprint)

Background: Since its outbreak in late December 2019, the coronavirus disease 2019 (COVID-19) has culminated in a global pandemic, and its causative virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has continued to mutate, with increasing rates of transmission and pathogenicity, having a serious worldwide impact. This study aims to assess the benefits of the health-related quality of life of using N-acetylcysteine(NAC).Methods: In this prospective observational research, 63 confirmed COVID-19 patients who were treated between the ends of January and March 2020 were divided into patients treated with NAC-treatment (32 cases) and non-NAC-treatment groups (31 cases). Patients were followed up at discharge and at 1, 3, and 6 months after discharge. The clinical treatment effects of the two groups were compared, and the St. George’s Respiratory Questionnaire (SGRQ) evaluated patient-reported outcomes.Results: There were strong correlations between SGRQ component scores (0.728, 0.749, 0.850; P < 0.001 for all items) as well as between each SGRQ component score and the total patient score (0.822, 0.958, 0.957; P < 0.001 for all items). In the univariate analysis, the change differences of one month after discharge compared with discharge between two groups patients were statistically significant in the impacts and total scores (753.000, P < 0.001; 644.000, P = 0.042); the change differences of three months after discharge compared with discharge were also significant in the activity, impacts, and total scores (660.500, P = 0.022; 800.000, P < 0.001; 707.000, P = 0.004). In the multivariate analysis, the factors that have statistically significant influence on the unit value of SGRQ total score difference (UVDSGRQ) is NAC treatment (β = 1.954, P < 0.001), disease severity (β = 3.179, P < 0.001), follow-up duration (β = -0.232, P = 0.001), as well as NAC treatment and follow-up duration interaction item (β = -0.436, P = 0.004).Conclusion: Our study shows as the follow-up time increases, the SGRQ total scores of patients treated with NAC decreases significantly faster than those who were treated without NAC. In the treatment of COVID-19 patients, increasing the use of NAC has clinical significance.

Real-world study of the effectiveness of BBIBP-CorV (Sinopharm) COVID-19 vaccine in the Kingdom of Morocco (preprint)

The Kingdom of Morocco approved BBIBP-CorV (Sinopharm) COVID-19 vaccine for emergency use on 22 January 2021 in a two-dose, three-to-four-week interval schedule. We conducted a case-control study to determine real-world BBIBP-CorV vaccine effectiveness (VE) against serious or critical hospitalization of individuals RT-PCR-positive for SARS-CoV-2 during the first five months of BBIBP-CorV use in Morocco. The study was conducted among adults 18-99 years old who were tested by RT-PCR for SARS-CoV-2 infection between 1 February and 30 June 2021. RT-PCR results were individually linked with outcomes from the COVID-19 severe or critical hospitalization dataset and with vaccination histories from the national vaccination registration system. Individuals with partial vaccination (<2 weeks after dose two) or in receipt of any other COVID-19 vaccine were excluded. Unadjusted and adjusted VE estimates against hospitalization for serious or critical illness were made by comparing two-dose vaccinated and unvaccinated individuals in logistic regression models, calculated as (1-odds ratio) * 100%. There were 348,190 individuals able to be matched across the three databases. Among these, 140,892 were fully vaccinated, 206,149 were unvaccinated, and 1,149 received homologous BBIBP-CorV booster doses. Unadjusted, full-series, unboosted BBIBP-CorV VE against hospitalization for serious or critical illness was 90.2% (95%CI: 87.8% - 92.0%). Full-series, unboosted VE, adjusted for age, sex, and calendar day of RT-PCR test, was 88.5% (95%CI: 85.8% - 90.7%). Calendar day- and sex-adjusted VE ranged from 93.9% to 100% for individuals <60 years, and was 53.3% for individuals 60 years and older. There were no serious or critical illnesses among BBIBP-CorV-boosted individuals. Effectiveness of Sinopharm's BBIBP-CorV was consistent with phase III clinical trial results. Two doses of BBIBP-CorV was highly protective against COVID-19-associated serious or critical hospitalization in working-age adults under real-world conditions and moderately effective in older adults. Booster dose VE should be evaluated, as booster doses of BBIBP-CorV are recommended and are being used.

Ligand/Receptor-mediated Cell Communication Alteration Causes the Lung Inflammation Microenvironment and the Redistribution of Inter-tissue Immune Cells in COVID-19 Patients (preprint)

How SARS-CoV-2 causes disturbances of the lung microenvironment and systemic immune response remains a mystery. Here, we first analyze detailedly paired single-cell transcriptome data of the lungs, blood and bone marrow of two patients who died of COVID-19. Second, our results demonstrate that SARS-CoV-2 infection significantly increases the cellular communication frequency between AT1/AT2 cells and highly inflammatory myeloid cells, and induces the pulmonary inflammation microenvironment, and drives the disorder of fibroblasts, club and ciliated cells, thereby causing the increase of pulmonary fibrosis and mucus accumulation. Third, our works reveal that the increase of the lung T cell infiltration is mainly recruited by myeloid cells through certain ligands/receptors (ANXA1/FPR1, C5AR1/RPS19 and CCL5/CCR1), rather than AT1/AT2. Fourth, we find that some ligands and receptors such as ANXA1/FPR1, CD74/COPA, CXCLs/CXCRs, ALOX5/ALOX5AP, CCL5/CCR1, are significantly activated and shared among patients’ lungs, blood and bone marrow, implying that dysregulated ligands and receptors may cause the migration, redistribution and the inflammatory storm of immune cells in different tissues. Overall, our study reveals a latent mechanism by which the disorders of ligands and receptors caused by SARS-CoV-2 infection drive cell communication alteration, the pulmonary inflammatory microenvironment and systemic immune responses across tissues in COVID-19 patients.

The trustworthiness and impact of trial preprints for COVID-19 decision-making: A methodological study (preprint)

Purpose: To assess the trustworthiness and impact of preprint trial reports during the COVID-19 pandemic. Data sources: WHO COVID-19 database and the L-OVE COVID-19 platform by the Epistemonikos Foundation (up to August 3rd, 2021) Design: We compare the characteristics of COVID-19 trials with and without preprints, estimate time to publication of COVID-19 preprint reports, describe discrepancies in key methods and results between preprint and published trial reports, report the number of retracted preprints and publications, and assess whether including versus excluding preprint reports affects meta-analytic estimates and the certainty of evidence. For the effects of eight therapies on mortality and mechanical ventilation, we performed meta-analyses including preprints and excluding preprints at 1 month, 3 months, and 6 months after the first trial addressing the therapy became available either as a preprint or publication (120 meta-analyses in total). Results: We included 356 trials, 101 of which are only available as preprints, 181 as journal publications, and 74 as preprints first and subsequently published in journals. Half of all preprints remain unpublished at six months and a third at one year. There were few important differences in key methods and results between trial preprints and their subsequent published reports. We identified four retracted trials, three of which were published in peer-reviewed journals. With two exceptions (2/60; 3.3%), point estimates were consistent between meta-analyses including versus excluding preprints as to whether they indicated benefit, no appreciable effect, or harm. There were nine comparisons (9/60; 15%) for which the rating of the certainty of evidence differed when preprints were included versus excluded, for four of these comparisons the certainty of evidence including preprints was higher and for five of these comparisons the certainty of evidence including preprints was lower. Limitations: The generalizability of our results is limited to COVID-19. Preprints that are subsequently published in journals may be the most rigorous and may not represent all trial preprints. Conclusion: We found no compelling evidence that preprints provide less trustworthy results than published papers. We show that preprints remain the only source of findings of many trials for several months, for a length of time that is unacceptable in a health emergency. We show that including preprints may affect the results of meta-analyses and the certainty of evidence. We encourage evidence users to consider data from preprints in contexts in which decisions are being made rapidly and evidence is being produced faster than can be peer-reviewed.