Self-assembly vascularized human cardiac organoids model cardiac diseases in petri dishes and in mice (preprint)

In this study, we generated self-assembly cardiac organoids (COs) from human pluripotent stem cells by dual-phase modulation of Wnt/{beta}-catenin pathway, utilizing CHIR99021 and IWR-1-endo. The resulting COs exhibited a diverse array of cardiac-specific cell lineages, cardiac cavity-like structures and demonstrated the capacity of spontaneous beating and vascularization in vitro. We further employed these complex and functional COs to replicate conditions akin to human myocardial infarction and SARS-CoV-2 induced fibrosis. These models accurately captured the pathological characteristics of these diseases, in both in vitro and in vivo settings. In addition, we transplanted the COs into NOD SCID mice and observed that they survived and exhibited ongoing expansion in vivo. Impressively, over a span of 75-day transplantation, these COs not only established blood vessel-like structures but also integrated with the host mice's vascular system. It is noteworthy that these COs developed to a size of approximately 8 mm in diameter, slightly surpassing the dimensions of the mouse heart. This innovative research highlighted the potential of our COs as a promising avenue for cardiovascular research and therapeutic exploration.

CD4+ T cell senescence is associated with reduced reactogenicity in severe/critical COVID-19 (preprint)

Background: Aging is a critical risk factor for unfavorable clinical outcomes among COVID-19 patients and may affect vaccine efficacy. However, whether the senescence of T cells impact the progression to severe COVID-19 in the elderly individuals remains unclear. Methods: By using flow cytometry, we analyzed the frequency of senescent T cells (Tsens) in the peripheral blood from 100 elderly patients hospitalized for COVID-19 and compared the difference between mild/moderate and severe/critical illness. We also assessed correlations between the percentage of Tsens and the quantity and quality of spike-specific antibodies by ELISA, neutralizing antibody test kit and Elispot assay respectively, cytokine production profile of COVID-19 reactive T cells as well as plasma soluble factors by cytometric bead array (CBA). Results: We found a significant elevated level of CD4+ Tsens in severe/critical disease compared to mild/moderate illness and patients with a higher level of CD4+ Tsens (>19.78%) showed a decreased survival rate as compared to those with a lower level (<19.78%), especially in the breakthrough infection. The percentage of CD4+ Tsens was negatively correlated with spike-specific antibody titers, neutralization ability and COVID-19 reactive IL-2+ CD4+ T cells. Additionally, IL-2 producing T cells and plasma levels of IL-2 were positively correlated with antibody levels. Conclusion: Our data illustrated that the percentage of CD4+ Tsens in the peripheral blood could act as an efficient biomarker for the capacity of spike-specific antibody production and the prognosis of severe COVID-19, especially in the breakthrough infection. Therefore, restoration of the immune response of CD4+ Tsens is one of the key factors to prevent severe illness and improve vaccine efficacy in older adults.

Xuebijing injection inhibited neutrophil extracellular traps to reverse lung injury in sepsis mice via reducing Gasdermin D

The mortality of sepsis and septic shock remains high worldwide. Neutrophil extracellular traps (NETs) release is a major cause of organ failure and mortality in sepsis. Targeting Gasdermin D (GSDMD) can restrain NETs formation, which is promising for sepsis management. However, no medicine is identified without severe safety concerns for this purpose. Xuebijing injection (XBJ) has been demonstrated to alleviate the clinical symptoms of COVID-19 and sepsis patients, but there are not enough animal studies to reveal its mechanisms in depth. Therefore, we wondered whether XBJ relieved pulmonary damage in sepsis by suppressing NETs formation and adopted a clinically relevant polymicrobial infection model to test this hypothesis. Firstly, XBJ effectively reversed lung injury caused by sepsis and restrained neutrophils recruitment to lung by down-regulating proinflammatory chemokines, such as CSF-3, CXCL-2, and CXCR-2. Strikingly, we found that XBJ significantly reduced the expressions of NETs component proteins, including citrullinated histone H3 (CitH3), myeloperoxidase (MPO), and neutrophil elastase (NE). GSDMD contributes to the production of NETs in sepsis. Notably, XBJ exhibited a reduced effect on the expressions of GSDMD and its upstream regulators. Besides, we also revealed that XBJ reversed NETs formation by inhibiting the expressions of GSDMD-related genes. Collectively, we demonstrated XBJ protected against sepsis-induced lung injury by reversing GSDMD-related pathway to inhibit NETs formation. Graphical

The impact of COVID-19 lockdown on maternal and neonatal outcomes of uninfected woman in late pregnancy: A multicenter study in China (preprint)

Background COVID-19 pandemic has had direct and indirect impacts on health-care system and maternal and neonatal health, but no multicenter evidence from China of this effects has been undertaken. The purpose of this study was to investigate the impacts of COVID-19 lockdown on maternal and fetal outcomes in China.Methods This retrospective cohort study included 3540 women in their late pregnancy without COVID-19 who received perinatal healthcare in three hospitals in Wuhan, Shanghai and Haikou during COVID-19 lockdown period in 2020 or the non-lockdown period in 2019. Propensity-score matching was used to compare preterm birth (< 37 weeks) and its classification, very preterm birth (< 34 weeks), caesarean section and its indications, the length of hospital stay, birth weight and other pregnancy outcomes between two groups.Results Preterm births before 37 weeks’ gestation (5.4% vs. 5.3%, P = 0.83) and very preterm birth (0.7% vs. 0.8%, P = 0.58) were not significantly changed overall. But medical-induced preterm birth before 37 weeks’ gestation in Wuhan was decreased (0.8% vs. 1.7%, P = 0.04). The cesarean section for maternal factors was decreased (21.4% vs. 24.3%, P = 0.003). The length of maternal (4.2d vs 4.5d, P < 0.001) and neonatal (3.4d vs 3.7d, P < 0.001) hospital stay was shortened. No overall significant effects were identified for other outcomes included in the quantitative analysis: maternal gestational diabetes; pregnancy-induced hypertension; preterm birth with premature rupture of membranes; low birthweight (< 2500 g); neonatal intensive care unit admission; or abnormal Apgar score.Conclusions This study demonstrated that there was protective impact of the COVID-19 lockdown on maternal and neonatal outcomes among women in their late pregnancy in China.

Uncontrolled Disposal of Used Masks Resulting in Release of Microplastics and Co-Pollutants into Environment

The global panic caused by COVID-19 has continued to increase people's demand for masks. However, due to inadequate management and disposal practice, these masks have, unfortunately, entered the environment and release a large amount of microplastics (MPs), posing a serious threat to the environment and human health. Understanding the occurrence of mask waste in various environments, release of mask-origin MPs, and related environmental risk is essential to mask-waste management in current and future epidemic prevention and control. This paper focuses on the global distribution of mask waste, the potential release of waste-origin MPs, and the impact on the environment. Specifically, the physical and chemical properties of polypropylene (the most common plastic material in a mask), which show a high adsorption capacity for heavy metals and organic pollutants and play a role as a support for microbial growth, were extensively reported. In addition, several important issues that need to be resolved are raised, which offers a direction for future research. This review focuses on the essentiality of handling masks to avoid potential environmental issues.

A pH-dependent switch mediates conformational masking of SARS-CoV-2 spike

SARS-CoV-2 has emerged as a global pathogen, sparking urgent vaccine development efforts with the trimeric spike. However, the inability of antibodies like CR3022, which binds a cryptic spike epitope with nanomolar affinity, to neutralize virus, suggests a spike-based means of neutralization escape. Here, we show the SARS-CoV-2 spike to have 10% the unfolding enthalpy of a globular protein at physiological pH, where it is recognized by antibodies like CR3022, and up to 10-times more unfolding enthalpy at endosomal pH, where it sheds such antibodies, suggesting that the spike evades potentially neutralizing antibody through a pH-dependent mechanism of conformational masking. To understand the compatibility of this mechanism with ACE2-receptor interactions, we carried out binding measurements and determined cryo-EM structures of the spike recognizing up to three ACE2 molecules at both physiological and endosomal pH. In the absence of ACE2, cryo-EM analyses indicated lower pH to reduce conformational heterogeneity. Single-receptor binding domain (RBD)-up conformations dominated at pH 5.5, resolving into a locked all-down conformation at lower pH through lowering of RBD and refolding of a pH-dependent switch. Notably, the emerging Asp614Gly strain partially destabilizes the switch that locks RBD down, thereby enhancing functional interactions with ACE2 while reducing evasion by conformational masking.

Influenza’s plummeting and future dynamics: the roles of mask wearing, mobility change and SARS-CoV-2 interference (preprint)

Untangling lessons from the influenza’s plummeting during the COVID-19 pandemic is critical for mitigating seasonal and pandemic influenza. Here we explored a country-specific inference model to estimate the effects of mask-wearing, mobility changes (international and domestic) and SARS-CoV-2 interference in China, England and the United States. We found that mask wearing had a larger reduction than mobility changes in all the regions. Only in 2019-2020, SARS-CoV-2 interference had an observable effect, with values varying at the timing of the influenza season and the speed of SARS-CoV-2 community transmission. Compared to the epidemics in 2017–2019, longer and blunter rebounds could occur in the incoming 2021–2022 season, but the rebound would be smaller if less stringent mask mandates continued or the international mobility stayed low. Our results bear implications for understanding how influenza evolves under non-pharmaceutical interventions and other respiratory diseases, and will inform designing of tailored public health measures.

Risk Factors of SARS-CoV-2 and Follow-up in Patients with Common Underlying Diseases on the Dynamic Changes of Antibodies: A Cross-sectional Study (preprint)

Background: Assessing the humoral immunity of patients with underlying diseases after being infected with SARS-CoV-2 is essential for determining effective prevention and control strategies. The purpose of this study is to investigate whether underlying disease is a risk factor for SARS-CoV-2 infection, reveal the seroprevalence of people with underlying disease and the characteristics of dynamic changes in anti-SARS-CoV-2 antibodies, and provide evidence for the scientific formulation of COVID-19 vaccination strategies. Methods: : The probability ratio sampling method was adopted to systematically select 100 communities from 13 districts in Wuhan, China, followed by a random selection of households from 100 communities according to a list provided by the local government. Individuals who have lived in Wuhan for at least 14 days since December 2019 and were ≥40 years old were included. Individuals with other serious diseases besides COVID-19, from whom a sample could not be obtained or refused to participate, were excluded. All eligible subjects signed a written informed consent form and completed a standardized electronic questionnaire before being enrolled in the group. From April 9–13, 2020, venous blood samples were collected from all individuals; from June 11–13, 2020, and from October 9–December 5, 2020, all positive and matched negative families were followed up. Results: : The seroprevalence of SARS-CoV-2 in people with underlying diseases was 6.30% (95% CI [5.09-7.52]), and that of people without underlying diseases was 6.12% (95% CI [5.33-6.91]). Among people with underlying diseases, retirees, health workers, and people who have been exposed to fever or respiratory symptoms since December 2019 were more likely to be infected with SARS-CoV-2. The IgG titer of people with underlying disease decreased significantly over time (P <0.05), but the neutralizing antibody titer remained relatively stable throughout the follow-up period. There was no significant difference between the IgG titer decline rate of people with underlying disease and those without. The IgG titer of people with underlying disease and asymptomatic infection was lower than that in symptomatic infection. Conclusion: These findings imply that vaccination strategies for people with and without underlying diseases may not require special adjustments.

The Effects of Mask Wearing, Mobility Change and SARS-CoV-2 Interference on Seasonal Influenza in Northern China, Southern China, England, and the United States (preprint)

Background: Seasonal influenza activity typically peaks in winter months but plummets globally during the COVID-19 pandemic. Untangling lessons from the influenza’s unprecedented low profile is critical for informing preparedness for incoming influenza seasons.Methods: We collect data from public sources in Northern China, Southern China, England and the United States. We estimate the individual effects of mask-wearing, mobility change (international and domestic) and SARS-CoV-2 interference, and forecast the influenza activity in the incoming 2021–2022 influenza season, using a country-specific inference model.Findings: The one-week increase of the mask-wearing intervention has a percent reduction of 11·3% to 35·2% on influenza activity in the four regions. The one-week mobility mitigation has smaller effects, 1·7% to 6·5% for the international and 1·6% to 2·8% for the domestic. In 2020–2021, the mask-wearing intervention alone could decline 13·3 to 19·8 percent positivity. The mobility change alone could reduce 5·2 to 14·0 percent positivity, of which 79·8% to 98·2% are attributed to the deflected international travel. Only in 2019–2020, SARS-CoV-2 interference has statical significant effects, and in Northern China and England only, reducing 7·6 (2·4 to 14·4) and 10·2 (7·2 to 13·6) percent positivity respectively. Compared to the epidemics in 2017–2019, longer and blunter rebounds could occur in the incoming 2021–2022 season should the mask-wearing be lifted, but the rebound would be smaller if the international mobility stayed low.Interpretation: Mask-wearing is more effective than mobility mitigation in all the four regions, although the relative advantage depends on the timing and duration of the interventions. Effects of SARS-CoV-2 interference vary at the timing of the influenza season and the speed of SARS-CoV-2 community transmission. The results improve our understandings of nonpharmaceutical interventions and other respiratory disease on influenza, and will inform the tailored public health measures for mitigating seasonal influenza and future pandemics.Funding: National Natural Science Foundation, Chinese Academy of Medical Sciences & Peking Union Medical College, and the Bill & Melinda Gates FoundationDeclaration of Interest: The authors declare no competing interests.

Stringent Government Policies Are Associated With a Lower COVID-19 Spread Rate (preprint)

The outbreak of COVID-19 has prompted a wide range of policy responses from governments around the world. In this study, we investigate the effect of governmental policies on the spread of the COVID-19 in a cross-country setting using the Oxford COVID-19 Government Response Stringency Index. We find that stringent government policies overall, and the following policies in particular, are associated with a lower spread rate of COVID-19 cases: workplace closing, restrictions on gatherings, close of public transport, stay-at-home order, restrictions on internal movement, and international travel controls; while school closing and public events cancellation are not associated with a lower COVID-19 spread. After including all policies into one single regression and examining their associations simultaneously with the virus spread, we find that the two policies stand out and remain to have a negative association with the COVID-19 spread: close of public transport and restrictions on international travel. Finally, we show that when countries are more oriented toward a tight culture, their governmental strict policies effect on the spread of COVID-19 becomes 1.5 – 3 times stronger than countries more toward a loose culture. Our findings suggest that the governments need to carefully implement policies to cope with the COVID-19 spread in their own social and cultural context.  

Online Proctoring Discount: The Role of Measured Stressors (preprint)

We examine the exam score effect of online proctoring with a comprehensive split sample of proctored and unproctored students in an upper-level economics class. Ours is the first study to measure the online proctoring effect, to our knowledge, that combines student in-class performance metrics, measured student perceptions and stress, and administrative data. We first document a proctoring discount (i.e., the tendency for lower scores on proctored exams versus on unproctored exams). We also find a relationship between students’ perceptions of the online proctoring environment and their performance on online exams. Our analysis highlights the importance of student perceptions and beliefs in determining performance and suggests that educators need to address student perceptions in order to accurately assess student mastery of course materials.Using ordinary least squares regressions and multilevel mixed-effects models, our findings show that students’ perceptions and characteristics can affect online exam performance and, potentially, contribute to the observed proctoring discount. Assuming that the proctoring discount is caused, at least in part, by undesirable phenomena (i.e., academic dishonesty and/or student discomfort with online proctoring), we suggest policy implications that the elimination of this proctoring discount is a worthwhile goal of the educational community in an environment where online teaching and learning is prevalent and growing due to the COVID-19 pandemic.

Deconvoluting the T cell response to SARS-CoV-2: specificity versus chance- and cognate cross-reactivity (preprint)

SARS-CoV-2 infection takes a mild or clinically inapparent course in the majority of humans who contract this virus. After such individuals have cleared the virus, only the detection of SARS-CoV-2-specific immunological memory can reveal the exposure, and hopefully the establishment of immune protection. With most viral infections, the presence of specific serum antibodies has provided a reliable biomarker for the exposure to the virus of interest. SARS-CoV-2 infection, however, does not reliably induce a durable antibody response, especially in sub-clinically infected individuals. Consequently, it is plausible for a recently infected individual to yield a false negative result within only a few months after exposure. Immunodiagnostic attention has therefore shifted to studies of specific T cell memory to SARS-CoV-2. Most reports published so far agree that a T cell response is engaged during SARS-CoV-2 infection, but they also state that in 20-81% of non-SARS-CoV-2-exposed individuals, T cells respond to SARS-CoV-2 antigens (mega peptide pools), allegedly due to T cell cross-reactivity with coronaviruses causing Common Cold (CCC), or other antigens. Here we show that by introducing irrelevant mega peptide pools as negative controls to account for chance cross-reactivity, and by establishing the antigen dose-response characteristic of the T cells, one can clearly discern between cognate T cell memory induced by SARS-CoV-2 infection vs. cross-reactive T cell responses in individuals who had not been infected with SARS-CoV-2.

A Remote Management System for Control and Surveillance of Echinococcosis: Design and Implementation Based on Internet of Things (preprint)

Background: As a neglected cross-species parasitic disease transmitted between canines and livestock, echinococcosis remains a global public health concern with a heavy disease burden. In China, especially in the epidemic pastoral communities on the Qinghai-Tibet Plateau, the harsh climate, low socio-economic status, poor overall hygiene, and remote and insufficient access to all owned dogs exacerbate the difficulty in implementing the ambitious control programme for echinococcosis. New methods and tools are urgently needed to increase the deworming coverage and frequency, promote real-time scientific surveillance, and prevent transmission of echinococcosis. Methods: We propose the remote management system (RMS) based on IoT as a novel tool to control smart deworming devices to deliver efficient PZQ baits to dogs regularly and automatically and also as a smart digital management platform to monitor, analyse, and display the epidemic trends of echinococcosis dynamically, in real time. The RMS is an excellent alternative to existing manual deworming methods and management for surveillance of echinococcosis.Results: The smart collars are fully capable of anti-collision, waterproof, and cold-proof performance, and the battery’s energy is sufficient. The RMS can accurately analyse the monitoring data and parameters including positive rates of canine faeces, and the prevalence of echinococcosis in the general population livestock, and children. The data of dogs deworming and surveillance for echinococcosis is able to be controlled using RMS and has expanded gradually in townships to the whole Hezuo region. A total of 48 administrators (3, 3, 8, 11, 23 at the provincial, municipal, county, township, village levels, respectively) participated in the questionnaire survey, with 93.8% of its overall satisfaction rate.Conclusion: The existing difficulties and challenges in the way of prevention and control for echinococcosis can partially be resolved using the innovative, IoT-based technologies and tools. The proposed RMS to advance the upgrade of existing manual prevention and control models for echinococcosis, especially in the current ongoing COVID-19 pandemic, as social distance and community blockade continue.

Vulnerability of Young Children with COVID-19: Impacts of ACE2 Expression Patterns and Lung Progenitor Cells on Infants (preprint)

Background: An increasing number of children with severe coronavirus disease 2019 (COVID-19) is being reported, yet the spectrum of disease severity and expression patterns of angiotensin- converting enzyme 2 (ACE2) in children at different developmental stages are largely unknow. Methods: We analysed clinical features in a cohort of 173 children with COVID-19 (0-15 yrs.-old) between January 22, 2020 and March 25, 2020. We systematically examined the expression and distribution of ACE2 in different developmental stages of children by using a combination of children’s lung biopsies, pluripotent stem cell-derived lung cells, RNA-sequencing profiles, and ex vivo SARS-CoV-2 pseudoviral infections. Findings: It revealed that infants (<1yrs.-old), with a weaker potency of immune response, are more vulnerable to develop pneumonia whereas older children (>1 yrs.-old) are more resistant to lung injury. The expression levels of ACE2 however do not vary by age in children’s lung. ACE2 is notably expressed not only in Alveolar Type II (AT II) cells, but also in SOX9 positive lung progenitor cells detected in both pluripotent stem cell derivatives and infants’ lungs. The ACE2+ SOX9+ cells are readily infected by SARS-CoV-2 pseudovirus and the numbers of the double positive cells are significantly decreased in older children. Interpretation: Infants (<1 yrs.-old) with COVID-19 infection are more vulnerable to lung injuries. ACE2 expression in multiple types of lung cells including SOX9 positive progenitor cells, in cooperation with an unestablished immune system, could be risk factors contributing to vulnerability of infants with COVID-19. There is a need to continue monitoring lung development in young children who have recovered from COVID-19 infection. Funding: National Natural Science Grant of China (No 31571407; 31970910); Hong Kong Health and Medical Research Fund (HMRF) (No:06172956), and Stem Cell and Regenerative Medicine Fund (Guangzhou Women and Children's Medical Centre, Grant No:5001-4001010)Declaration of Interests: The authors declare no competing interest.Ethics Approval Statement: This study was approved by the respective Institutional Review Board. Written informed consent was obtained from patients and/or guardians before data collected.

Working from Home: Small Business Performance and the COVID-19 Pandemic (preprint)

During the COVID-19 pandemic many firms began operating in a working-from-home environment (WFH). This study focuses on the relationship between WFH and small business performance during the pandemic. We built a theoretical framework based on firm profit maximization, compiled an up-to-date (March through November) real-time daily and weekly multifaceted data set, and empirically estimated fixed-effect panel data, fractional logit, and multilevel mixed effects models to test our hypotheses. We find that in states with higher WFH rates, small businesses performed better overall with industry variations, controlling for the local pandemic, economic, demographic and policy factors. We also find that WFH rates increased even after stay-at-home orders (SHOs) were rescinded. With the ready technology and practice of WFH in the pandemic, our robust empirics confirm our theory and hypotheses and demonstrate WFH as a potential force that may expedite “creative destruction” instance and permanently impact industrial structure and peoples’ work lives.

Small Business and the COVID-19 Pandemic: The Role of Work from Home (preprint)

While work from home (WFH) becomes the new norm in the COVID-19 pandemic and while small businesses could be more vulnerable in crisis, whether the WFH norm will fade after the stay-at-home mandate ended and whether WFH could be a Schumpeterian “creative” force that helps small businesses do well in the pandemic is unknown. The study first builds a theoretical framework based on marginal revenue product cost utility theory subject to a “contagion” agglomeration parameter and argues that WFH is a rational choice for businesses. Then, we compiled from multiple data sources an up-to-date real-time daily and weekly multifaceted data set tracking WFH propensity from March 20 through July 28.  Our empirical analysis estimated a variety of fixed-effects panel data models, population-averaged generalized linear panel-data models with the generalized estimating equation (GEE) approach, and two-level mixed-effects panel-data models. After controlling for the local pandemic, economic, and demographic factors, we find (1) after the stay-at-home order ended, WFH rate got higher; (2) small businesses in states with higher WFH rate are more likely to have higher increases in operating revenue, better cash flow and lower chances of temporary closure.  Our robust empirics confirm our theories and hypotheses and demonstrate WFH as a potential force that expedited the “creative destruction” into a new efficient work paradigm. 

Single-cell analysis reveals the function of lung progenitor cells in COVID-19 patients (preprint)

The high mortality of severe 2019 novel coronavirus disease (COVID-19) cases is mainly caused by acute respiratory distress syndrome (ARDS), which is characterized by increased permeability of the alveolar epithelial barriers, pulmonary edema and consequently inflammatory tissue damage. Some but not all patients showed full functional recovery after the devastating lung damage, and so far there is little knowledge about the lung repair process1. Here by analyzing the bronchoalveolar lavage fluid (BALF) of COVID-19 patients through single cell RNA-sequencing (scRNA-Seq), we found that in severe (or critical) cases, there is remarkable expansion of TM4SF1+ and KRT5+ lung progenitor cells. The two distinct populations of progenitor cells could play crucial roles in alveolar cell regeneration and epithelial barrier re-establishment, respectively. In order to understand the function of KRT5+ progenitors in vivo, we transplanted a single KRT5+ cell-derived cell population into damaged mouse lung. Time-course single-cell transcriptomic analysis showed that the transplanted KRT5+ progenitors could long-term engrafted into host lung and differentiate into HOPX+ OCLN+ alveolar barrier cell which restored the epithelial barrier and efficiently prevented inflammatory cell infiltration. Similar barrier cells were also identified in some COVID-19 patients with massive leukocyte infiltration. Altogether this work uncovered the mechanism that how various lung progenitor cells work in concert to prevent and replenish alveoli loss post severe SARS-CoV-2 infection.

Afebrile patients with severe acute respiratory syndrome coronavirus 2 infection have a longer viral positivity duration: a retrospective analysis of 143 patients (preprint)

Background A pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is on-going. Clinical characters of afebrile cases infected with SARS-CoV-2 remain poorly understood and informations are limited on the duration of SARS-CoV-2 viral positivity.Methods We performed a single-center retrospective study of 143 patients with SARS-CoV-2 infection in Beijing Ditan Hospital, Capital Medical University from January 26 to April 15, 2020. Differences were compared among patients with/without fever. Risk factors for the duration of SARS-CoV-2 viral positivity were evaluated.Results A total of 143 patients with positive SARS-CoV-2 test were enrolled, including 38 afebrile patients and 105 febrile patients. On admission, a total of 40 (28%) patients had leukopenia, 44 (30.8%) had lymphopenia and 8 (5.6%) had thrombocytopenia. 78 patients (54.5%) had decreased T lymphocytes and 105 patients (73.4%) had decreased CD4+T lymphocytes. Compared with febrile cases, afebrile patients had a significantly higher white blood cell count (P = 0.02), total lymphocytes (P < 0.01), platelet count (P < 0.01), T lymphocytes (P < 0.01) and CD8+ T lymphocytes (P = 0.02). The median SARS-CoV-2 viral positivity duration of these 143 patients was 14 days (IQR, 10-30 days) and for febrile and afebrile group were 13 days (IQR, 10-29 days) and 20 days (IQR, 11-31 days) respectively. Multivariate Cox regression results showed that the fever [hazard ratio (HR) = 0.49, P < 0.01]and higher count of platelet (HR = 5.47, P = 0.02) were the predominant risk factor for the SARS-CoV-2 viral positivity duration.Conclusion The SARS-CoV-2 virial positivity duration of the afebrile group was significantly longer than that in the febrile group. Fever and a higher count of platelet were the independent protective factors for a shorter SARS-CoV-2 RNA positivity duration.

Significance of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio for predicting clinical outcomes in COVID-19 (preprint)

Background The epidemic of 2019 novel coronavirus (COVID-19) struck China in late December,2019, resulting in about 200000 deaths all over the world. Numerous observational studies have suggested that the neutrophil-to-lymphocyte ratio (NLR) and lymphocyte proportion and the platelet-to-lymphocyte ratio (PLR) are inflammatory markers. Our study aimed to detect the role of NLR, PLR in predicting the prognosis of COVID-19.Results Four hundred and fifteen consecutive patients were enrolled in Shanghai Public Health Clinical Center affiliated to Fudan University, between 20 January and 11 April 2020 with confirmed COVID-19,among which 386 (93%) patients were not severe, and 27 (7%) were severe. The proportion of males in severe cases is higher than in non-severe cases (75.86% vs. 50.52%, P = 0.008). The age between the two groups is different (p = 0.022). Compared with non-severe patients, severe patients exhibited more comorbidities, including hypertension (48.28% vs. 19.43%, p < 0.001), diabetes (20.69% vs. 6.99%, p = 0.009), chronic obstructive pulmonary disease (51.72% vs. 6.22%, p < 0.001), and fatty liver (37.93% vs. 15.8%, p = 0.002), respectively. NLR and PLR showed significant difference (p < 0.001). Diabetes (OR 0.28; 95% CI 15.824-187.186), fatty liver (OR 21.469; 95% CI 2.306-199.872), coronary heart disease (OR 18.157; 95% CI 2.085-158.083), NLR (OR 1.729; 95% CI 1.050–2.847) were significantly associated with severe cases with COVID-19. The NLR of patients in severe group had a 1.729-fold higher than that of no-severe group (OR 1.729; 95% CI 1.050–2.847, P = 0.031).Conclusions NLR is an independent risk factor of severe COVID-19 patients. PLR, NLR were significantly different between severe and non-severe patients, so assessment of NLR, PLR may help identify high risk cases with COVID-19.