Rare Fundus Lesions in Patients after SARS-Cov-2 Infection: A Multicenter and Multimodal Imaging Study (preprint)

Purpose To define the characteristics of fundus manifestations in patients after SARS-Cov-2 infection with multimodal imaging techniques.Methods This is a retrospective multicenter and multimodal imaging study including 90 patients. All patients with a visual complaint occurring immediately after SARS-Cov-2 infection were referred to six clinics between December 2022 and February 2023. Demographic information and the temporal relationship between SARS-Cov-2 infection and visual symptoms were documented. The characteristics of the fundus lesions were evaluated using multimodal imaging.Results Ninety patients from six hospitals were enrolled in this study, including 24 males (26.67%) and 66 (73.33%) females. Seventy-eight patients (86.66%) (146 eyes) were diagnosed with AMN. The AMN patients were primarily young women (67.95%). Sixty-eight patients (87.18%) had AMN in both eyes. Thirty-eight eyes (24.36%) included Purtscher or Purtscher-like lesions. optical coherence tomography and infrared retinal photographs can show AMN lesions well. Eleven cases were diagnosed with simple Purtscher or Purtscher-like retinopathy (2 cases, 2.22%), VKH or VKH-like uveitis (3 cases, 3.33%), MEWDS (2 cases, 2.22%), and ROCM (5 cases, 5.56%).Conclusions After SARS-Cov-2 infection, diversified fundus lesions were evident in patients with visual complaints. In this report, AMN was the dominant manifestation, followed by Purtscher or Purtscher-like retinopathy, MEWDS, VKH-like uveitis, and ROCM.

De novo generation of antibody CDRH3 with a pre-trained generative large language model (preprint)

Artificial Intelligence (AI) techniques have made great advances in assisting antibody design. However, antibody design still heavily relies on isolating antigen-specific antibodies from serum, which is a resource-intensive and time-consuming process. To address this issue, we propose a Pre-trained Antibody generative large Language Model (PALM) for the de novo generation of artificial antibodies heavy chain complementarity-determining region 3 (CDRH3) with desired antigen-binding specificity, reducing the reliance on natural antibodies. We also build a high-precision model antigen-antibody binder (A2binder) that pairs antigen epitope sequences with antibody sequences to predict binding specificity and affinity. PALM-generated antibodies exhibit binding ability to SARS-CoV-2 antigens, including the emerging XBB variant, as confirmed through in-silico analysis and in-vitro assays. The in-vitro assays validated that PALM-generated antibodies achieve high binding affinity and potent neutralization capability against both wild-type and XBB spike proteins of SARS-CoV-2. Meanwhile, A2binder demonstrated exceptional predictive performance on binding specificity for various epitopes and variants. Furthermore, by incorporating the attention mechanism into the PALM model, we have improved its interpretability, providing crucial insights into the fundamental principles of antibody design.

Changing spatiotemporal patterns for hepatitis of unspecified aetiology in China, 2004-2021: a population-based surveillance study.

Objectives: As global efforts continue toward the target of eliminating viral hepatitis by 2030, the emergence of acute hepatitis of unspecified aetiology (HUA) remains a concern. This study assesses the overall trends and changes in spatiotemporal patterns in HUA in China from 2004 to 2021. Methods: We extracted the incidence and mortality rates of HUA from the Public Health Data Center, the official website of the National Health Commission of the People's Republic of China, and the National Notifiable Infectious Disease Surveillance System from 2004 to 2021. We used R software, ArcGIS, Moran's statistical analysis, and joinpoint regression to examine the spatiotemporal patterns and annual percentage change in incidence and mortality of the HUA across China. Results: From 2004 to 2021, a total of 707,559 cases of HUA have been diagnosed, including 636 deaths. The proportion of HUA in viral hepatitis gradually decreased from 7.55% in 2004 to 0.72% in 2021. The annual incidence of HUA decreased sharply from 6.6957 per 100,000 population in 2004 to 0.6302 per 100,000 population in 2021, with an average annual percentage change (APC) reduction of -13.1% (p < 0.001). The same result was seen in the mortality (APC, -22.14%, from 0.0089/100,000 in 2004 to 0.0002/100,000 in 2021, p < 0.001). All Chinese provinces saw a decline in incidence and mortality. Longitudinal analysis identified the age distribution in the incidence and mortality of HUA did not change and was highest in persons aged 15-59 years, accounting for 70% of all reported cases. During the COVID-19 pandemic, no significant increase was seen in pediatric HUA cases in China. Conclusion: China is experiencing an unprecedented decline in HUA, with the lowest incidence and mortality for 18 years. However, it is still important to sensitively monitor the overall trends of HUA and further improve HUA public health policy and practice in China.

Learning Complex Technology Online: Effect of Challenge and Hindrance Techno-stressors on Student Satisfaction and Retention

Despite increasing attention to online learning worldwide, learning complex technologies online has always been challenging and even hindersome to students, who are subjected to elevated levels of technostress. In contrast to most previous studies that focused on the negative side of technostress, this study investigated both the negative and positive sides of technostress. Based on the challenge hindrance framework (CHF), the holistic stress model (HSM), and the person-environment fit (P-E Fit) model, we examined how challenge and hindrance techno-stressors caused distress and eustress in online students and lead to associated outcomes. We empirically validated the research model by analyzing survey data collected from 565 online graduate business students enrolled at a university in the United States. The results revealed that some hindrance and challenge techno-stressors were associated with techno-distress and techno-eustress, which further impacted student satisfaction and student retention. We discussed the contributions and implications and provided future research directions.

The clinical and virological features of two children's coinfections with human adenovirus type 7 and human coronavirus-229E virus.

Objective: Human adenovirus (HAdV) coinfection with other respiratory viruses is common, but adenovirus infection combined with human coronavirus-229E (HCoV-229E) is very rare. Study design and setting: Clinical manifestations, laboratory examinations, and disease severity were compared between three groups: one coinfected with HAdV-Ad7 and HCoV-229E, one infected only with adenovirus (mono-adenovirus), and one infected only with HCoV-229E (mono-HCoV-229E). Results: From July to August 2019, there were 24 hospitalized children: two were coinfected with HAdV-Ad7 and HCoV-229E, and 21 were infected with a single adenovirus infection. Finally, one 14-year-old boy presented with a high fever, but tested negative for HAdV-Ad7 and HCoV-229E. Additionally, three adult asymptotic cases with HCoV-229E were screened. No significant difference in age was found in the coinfection and mono-adenovirus groups (11 vs. 8 years, p = 0.332). Both groups had the same incubation period (2.5 vs. 3 days, p = 0.8302), fever duration (2.5 vs. 2.9 days, p = 0.5062), and length of hospital stay (7 vs. 6.76 days, p = 0.640). No obvious differences were found in viral loads between the coinfection and mono-adenovirus groups (25.4 vs. 23.7, p = 0.570), or in the coinfection and mono-HCoV-229E groups (32.9 vs. 30.06, p = 0.067). All cases recovered and were discharged from the hospital. Conclusion: HAdV-Ad7 and HCoV-229E coinfection in healthy children may not increase the clinical severity or prolong the clinical course. The specific interaction mechanism between the viruses requires further study.

A vaccine based on the yeast-expressed receptor-binding domain (RBD) elicits broad immune responses against SARS-CoV-2 variants

Development of safe and efficient vaccines is still necessary to deal with the COVID-19 pandemic. Herein, we reported that yeast-expressed recombinant RBD proteins either from wild-type or Delta SARS-CoV-2 were able to elicit immune responses against SARS-CoV-2 and its variants. The wild-type RBD (wtRBD) protein was overexpressed in Pichia pastoris, and the purified protein was used as the antigen to immunize mice after formulating an aluminium hydroxide (Alum) adjuvant. Three immunization programs with different intervals were compared. It was found that the immunization with an interval of 28 days exhibited the strongest immune response to SARS-CoV-2 than the one with an interval of 14 or 42 days based on binding antibody and the neutralizing antibody (NAb) analyses. The antisera from the mice immunized with wtRBD were able to neutralize the Beta variant with a similar efficiency but the Delta variant with 2~2.5-fold decreased efficiency. However, more NAbs to the Delta variant were produced when the Delta RBD protein was used to immunize mice. Interestingly, the NAbs may cross react with the Omicron variant. To increase the production of NAbs, the adjuvant combination of Alum and CpG oligonucleotides was used. Compared with the Alum adjuvant alone, the NAbs elicited by the combined adjuvants exhibited an approximate 10-fold increase for the Delta and a more than 53-fold increase for the Omicron variant. This study suggested that yeast-derived Delta RBD is a scalable and an effective vaccine candidate for SARS-CoV-2 and its variants.

The clinical and virological features of two children's coinfections with human adenovirus type 7 and human coronavirus-229E virus

Objective Human adenovirus (HAdV) coinfection with other respiratory viruses is common, but adenovirus infection combined with human coronavirus-229E (HCoV-229E) is very rare. Study design and setting Clinical manifestations, laboratory examinations, and disease severity were compared between three groups: one coinfected with HAdV-Ad7 and HCoV-229E, one infected only with adenovirus (mono-adenovirus), and one infected only with HCoV-229E (mono-HCoV-229E). Results From July to August 2019, there were 24 hospitalized children: two were coinfected with HAdV-Ad7 and HCoV-229E, and 21 were infected with a single adenovirus infection. Finally, one 14-year-old boy presented with a high fever, but tested negative for HAdV-Ad7 and HCoV-229E. Additionally, three adult asymptotic cases with HCoV-229E were screened. No significant difference in age was found in the coinfection and mono-adenovirus groups (11 vs. 8 years, p = 0.332). Both groups had the same incubation period (2.5 vs. 3 days, p = 0.8302), fever duration (2.5 vs. 2.9 days, p = 0.5062), and length of hospital stay (7 vs. 6.76 days, p = 0.640). No obvious differences were found in viral loads between the coinfection and mono-adenovirus groups (25.4 vs. 23.7, p = 0.570), or in the coinfection and mono-HCoV-229E groups (32.9 vs. 30.06, p = 0.067). All cases recovered and were discharged from the hospital. Conclusion HAdV-Ad7 and HCoV-229E coinfection in healthy children may not increase the clinical severity or prolong the clinical course. The specific interaction mechanism between the viruses requires further study.

Interpretation of Guidelines for medical observation management of close contacts with COVID-19 cases Part 3: home-based medical observation

Effectively blocking the transmission route of coronavirus and protecting the susceptible population play significant roles in the control of COVID-19 pandemic.Strengthening home-based medical observation is one of the key points in preventing the spread of SARS-CoV-2 virus in families and communities.Therefore, in order to meet the needs for COVID-19 prevention and control in Beijing, a group of experts organized by Beijing Association of Preventive Medicine developed the Guidelines for medical observation management of close contacts with COVID-19 cases Part 3: home-based medical observation（T/BPMA007.3-2020）, which offers the specific provisions for close contacts of COVID-19 cases who need home-based medical observation as well as home environmental condition, prevention and control requirements, waste disposal, disinfection, community prevention and control work requirements, basic requirements for training and education and management guidelines.It provides standard support for home-based medical observation of close contacts with COVID-19 cases.

Recent advances on CRISPR/Cas system-enabled portable detection devices for on-site agri-food safety assay

Background Agri-food safety has been considered as one of the most important public concerns worldwide. From farm to table, food crops and foods are extremely vulnerable to the contamination by a variety of pollutants from their growth and processing. Moreover, the SARS-CoV-2 detected in the food supply chain during COVID-19 pandemic has posed a greater challenge for rapid and on-site detection of agri-food contaminants in complex and volatile environments. Therefore, the development of rapid, accurate, and on-site detection technologies and portable detection devices is of great importance to ensure the agri-food security. Scope and approach This review comprehensively summarized the recent advances on the construction of CRISPR/Cas systems-based biosensing technologies and their portable detection devices, as well as their promising applications in the field of agri-food safety. First of all, the classification and working principles of CRISPR/Cas systems were introduced. Then, the latest advances on the CRISPR/Cas system-based on-site detection technologies and portable detection devices were also systematically summarized. Most importantly, the state-of-the-art applications of CRISPR/Cas systems-based on-site detection technologies and portable detection devices in the fields of agri-food safety were comprehensively summarized. Impressively, the future opportunities and challenges in this emerging and promising field were proposed. Key findings and conclusions Emerging CRISPR/Cas system-based on-site detection technologies have showed a great potential in the detection of agri-food safety. Impressively, the integration of CRISPR/Cas systems-based biosensing technologies with portable detection devices (e.g., nanopore-based detection devices, lateral flow assay, smartphone-based detection devices, and microfluidic devices) is very promising for the on-site detection of agri-food contaminants. Additionally, CRISPR/Cas system-based biosensing technologies can be further integrated with much more innovative technologies for the development of novel detection platforms to realize the more reliable on-site detection of agri-food safety.

Strategies for screening, occupational prevention, and management of COVID-19 in outpatient clinics in Shandong

Objective We hope to analyze the information of outpatients in a tertiary care hospital during the epidemic of COVID-19, so as to formulate effective regulations for the prevention and control of COVID-19. Methods We collected information from outpatients from January 28, 2020 to March 2, 2020 and performed the statistical analysis. Results During the study period, there were more than 60,000 outpatients. Among them, 404 patients with a body temperature above 37.3°C who had not been to Wuhan and had no contact with people from Wuhan. There were 8 people who had contact with people from Wuhan, such as 4 people with fever, 3 people with normal body temperature but cough symptoms, and 1 person with normal body temperature and no other discomfort. There were 2 patients with high body temperature from the epidemic area in Wuhan, and one novel Coronavirus patient was confirmed as the final result. Conclusion During the COVID-19 pandemic, outpatient medical staff should enhance their awareness of protection, hospitals should standardize the outpatient COVID-19 prevention and control system, improve the prevention and emergency system, and reduce occupational exposure hazards and the occurrence of post-exposure infections.

Therapeutic prospects of ceRNAs in COVID-19

Since the end of 2019, COVID-19 caused by SARS-CoV-2 has spread worldwide, and the understanding of the new coronavirus is in a preliminary stage. Currently, immunotherapy, cell therapy, antiviral therapy, and Chinese herbal medicine have been applied in the clinical treatment of the new coronavirus;however, more efficient and safe drugs to control the progress of the new coronavirus are needed. Long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs) may provide new therapeutic targets for novel coronavirus treatments. The first aim of this paper is to review research progress on COVID-19 in the respiratory, immune, digestive, circulatory, urinary, reproductive, and nervous systems. The second aim is to review the body systems and potential therapeutic targets of lncRNAs, miRNAs, and circRNAs in patients with COVID-19. The current research on competing endogenous RNA (ceRNA) (lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA) in SARS-CoV-2 is summarized. Finally, we predict the possible therapeutic targets of four lncRNAs, MALAT1, NEAT1, TUG1, and GAS5, in COVID-19. Importantly, the role of PTEN gene in the ceRNA network predicted by lncRNA MALAT1 and lncRNA TUG1 may help in the discovery and clinical treatment of effective drugs for COVID-19.

Evaluation of indoor environmental quality, personal cumulative exposure dose, and aerosol transmission risk levels inside urban buses in Dalian, China (preprint)

The transmission of pollutants in buses has an important impact on personal exposure to airborne particles and spread of the COVID-19 epidemic in enclosed spaces. We conducted the following real-time field measurements inside buses: CO2, airborne particle concentration, temperature, and relative humidity data during peak and off-peak hours in spring and autumn. Correlation analysis was adopted to evaluate the dominant factors influencing CO2and particle mass concentrations in the vehicle. The cumulative personal exposure dose to particulate matter and reproduction number were calculated for passengers on a one-way trip. The results showed the in-cabin CO2concentrations, with 22.11% and 21.27% of the total time exceeding 1,000 ppm in spring and autumn respectively. In-cabin PM2.5 mass concentration exceeded 35 μm/m3 by 57.35% and 86.42% in spring and autumn, respectively. CO2 concentration and the cumulative number of passengers were approximately linearly correlated in both seasons, with R value up to 0.896. The cumulative number of passengers had the most impact on PM2.5 mass concentration among tested parameters. The cumulative personal exposure dose to PM2.5 during a one-way trip in autumn was up to 43.13 μg. The average reproductive number throughout the one-way trip was 0.26; it was 0.57 under the assumed extreme environment. The results of this study provide an important basic theoretical guidance for the optimization of ventilation system design and operation strategies aimed at reducing multi-pollutant integrated health exposure and airborne particle infection (such as SARS-CoV-2) risks.

Distinct gut microbiota and health outcomes in asymptomatic infection, viral nucleic acid test re-positive, and convalescent COVID-19 cases

Gut microbiota composition is suggested to associate with coronavirus disease 2019 (COVID-19) severity, but the impact of gut microbiota on health outcomes is largely unclear. We recruited 81 individuals from Wuhan, China, including 13 asymptomatic infection cases (Group A), 24 COVID-19 convalescents with adverse outcomes (Group C), 31 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) re-positive cases (Group D), and 13 non-COVID-19 healthy controls (Group H). The microbial features of Groups A and D were similar and exhibited higher gut microbial diversity and more abundant short-chain fatty acid (SCFA)-producing species than Group C. Group C was enriched with opportunistic pathogens and virulence factors related to adhesion and toxin production. The abundance of SCFA-producing species was negatively correlated, while Escherichia coli was positively correlated with adverse outcomes. All three groups (A, C, and D) were enriched with the mucus-degrading species Akkermansia muciniphila, but decreased with Bacteroides-encoded carbohydrate-active enzymes. The pathways of vitamin B6 metabolic and folate biosynthesis were decreased, while selenocompound metabolism was increased in the three groups. Specifically, the secondary bile acid (BA) metabolic pathway was enriched in Group A. Antibiotic resistance genes were common among the three groups. Conclusively, the gut microbiota was related to the health outcomes of COVID-19. Dietary supplementations (SCFAs, BA, selenium, folate, vitamin B6) may be beneficial to COVID-19 patients.

A single-cell atlas reveals shared and distinct immune responses and metabolism during SARS-CoV-2 and HIV-1 infections (preprint)

SARS-CoV-2 and HIV-1 are RNA viruses that have killed millions of people worldwide. Understanding the similarities and differences between these two infections is critical for understanding disease progression and for developing effective vaccines and therapies, particularly for 38 million HIV-1+ individuals who are vulnerable to SARS-CoV-2 co-infection. Here, we utilized single-cell transcriptomics to perform a systematic comparison of 94,442 PBMCs from 7 COVID-19 and 9 HIV-1+ patients in an integrated immune atlas, in which 27 different cell types were identified using an accurate consensus single-cell annotation method. While immune cells in both cohorts show shared inflammation and disrupted mitochondrial function, COVID-19 patients exhibit stronger humoral immunity, broader IFN-I signaling, elevated Rho GTPase and mTOR pathway activities, and downregulated mitophagy. Our results elucidate transcriptional signatures associated with COVID-19 and HIV-1 that may reveal insights into fundamental disease biology and potential therapeutic targets to treat these viral infections.

The Application of Tissue Glue in Eyelid Laceration Repair in Children During the Coronavirus Disease 2019 Pandemic Lockdown in Wuhan.

OBJECTIVE: To discuss a rapid and effective treatment used for children with eyelid lacerations during the COVID-19 lockdown in Wuhan to limit the risk of cross-infection. METHODS: A comparative study was conducted of forty-five patients with eyelid lacerations who attended the Ophthalmology Department of Wuhan Children's Hospital between January 23, 2020 and March 6, 2020. The tissue glue Histoacryl was used to bond the wounds in 24 cases, while the traditional suture method was used for 21 cases. The wound healing time, complications, treatment satisfaction, and number of visits of the two groups were compared. RESULTS: The two groups had similar baseline characteristics. The wound healing time (from wound disinfection to wound dressing) was shorter in the tissue glue group (4.35 ± 0.47min versus 11.71 ± 1.85 min, P< 0.01). There was 1 case of wound dehiscence in the tissue glue group. Twenty-two cases in the tissue glue group were satisfied, 2 cases were basically satisfied, and 0 were dissatisfied. Eleven cases in the traditional suture group were satisfied, 9 cases were basically satisfied, and 1 case was dissatisfied. The difference was statistically significant (P < 0.05). In terms of the number of visits, the tissue glue group visited (1.54 ± 0.88) times, while the traditional suture group visited (2.38 ± 0.59) times. The difference between the two groups was statistically significant (P < 0.01). The real-time reverse transcriptase polymerase chain tests for severe acute respiratory syndrome coronavirus 2 of all medical staff in the ophthalmology emergency room were negative. CONCLUSION: Compared with the traditional suture method, tissue glue used in eyelid laceration in children has the advantages of painlessness, shorter operation duration, higher safety and satisfaction, greater ease of care, and fewer hospital visits. Tissue glue can be widely used to reduce the risk of cross-infection.

Shrinkage in serial intervals across cluster transmission generations of COVID-19 (preprint)

The COVID-19 pandemic poses a serious threat to global health, and one of the key epidemiological factors that shape the transmission of COVID-19 is its serial interval (SI). Although SI is commonly considered following a probability distribution at a population scale, slight discrepancies in SI across different transmission generations are observed from the aggregated statistics in recent studies. To explore the change in SI across transmission generations, we develop a likelihood-based statistical inference framework to examine and quantify the change in SI. The COVID-19 contact tracing surveillance data in Hong Kong are used for exemplification. We find that the individual SI of COVID-19 is likely to shrink with a rate of 0.72 per generation and 95%CI: (0.54, 0.96) as the transmission generation increases. We speculate that the shrinkage in SI is an outcome of competition among multiple candidate infectors within a cluster of cases. The shrinkage in SI may speed up the transmission process, and thus the nonpharmaceutical interventive strategies are crucially important to mitigate the COVID-19 epidemic.

Environmental monitoring shows SARS-CoV-2 contamination of surfaces in food plants (preprint)

The SARS-CoV-2 pandemic has presented new challenges to food manufacturers. In addition to preventing the spread of microbial contamination of food, with SARS-CoV-2, there is an additional focus on preventing SARS-CoV-2 infections in food plant personnel. During the early phase of the pandemic, several large outbreaks of Covid-19 occurred in food manufacturing plants resulting in deaths and economic loss. In March of 2020, we assisted in implementation of environmental monitoring programs for SARS-CoV-2 in 116 food production facilities. All participating facilities had already implemented measures to prevent symptomatic personnel from coming to work. During the study period, from March 17, 2020 to September 3, 2020, 1.23% of the 22,643 environmental samples tested positive for SARS-CoV-2, suggesting that infected individuals are actively shedding virus. Virus contamination was commonly found on frequently touched surfaces. Most plants managed to control their environmental contamination when they became aware of the positive findings. Comparisons of the personnel test results to environmental contamination in one plant showed a good correlation between the two. Our work illustrates that environmental monitoring for SARS-CoV-2 can be used as a surrogate for identifying the presence of asymptomatic and pre-symptomatic personnel in workplaces and may aid in controlling infection spread. HighlightsO_LIEnvironmental contamination by SARS-CoV-2 virus was detected in food plants C_LIO_LIOut of 22,643 environmental swabs, 278 (1.23%) were positive for SARS-CoV-2 C_LIO_LIFrequently touched surfaces had the most contamination C_LIO_LISurface testing for SARS-CoV-2 may indicate presence of asymptomatic carriers C_LI

Multi-Level Attention Graph Neural Network for Clinically Interpretable Pathway-Level Biomarkers Discovery (preprint)

Precision medicine, regarded as the future of healthcare, is gaining increasing attention these years. As an essential part of precision medicine, clinical omics have been successfully applied in disease diagnosis and prognosis using machine learning techniques. However, existing methods mainly make predictions based on gene-level individual features or their random combinations, none of the previous work has considered the activation of signaling pathways. Therefore, the model interpretability and accuracy are limited, and reasonable signaling pathways are yet to be discovered. In this paper, we propose a novel multi-level attention graph neural network (MLA-GNN), which applies weighted correlation network analysis (WGCNA) to format the omic data of each patient into graph-structured data, and then constructs multi-level graph features, and fuses them through a well-designed multi-level graph feature fully fusion (MGFFF) module to conduct multi-task prediction. Moreover, a novel full-gradient graph saliency mechanism is developed to make the MLA-GNN interpretable. MLA-GNN achieves state-of-the-art performance on transcriptomic data from TCGA-LGG/TCGA-GBM and proteomic data from COVID-19/non-COVID-19 patient sera. More importantly, the proposed model's decision can be interpreted in the signaling pathway level and is consistent with the clinical understanding.

Could the Ambient Higher Temperature Decrease the Transmissibility of COVID-19 in China? (preprint)

Background: Existing literatures demonstrated that meteorological factors could be of importance in affecting the spread patterns of the respiratory infectious diseases. However, how ambient temperature may influence the transmissibility of COVID-19 remains unclear. Objectives: We explore the association between ambient temperature and transmissibility of COVID-19 in different regions across China. Methods: : The surveillance data on COVID-19 and meteorological factors were collected from 28 provincial level regions in China, and estimated the instantaneous reproductive number ( R t ). The generalized additive model was used to assess the relationship between mean temperature and R t . Results: : There were 12745 COVID-19 cases collected in the study areas. We report the effect of temperature on R t is not of statistical significance, which holds for most of included regions except for those in North China. Conclusions: We found little statistical evidence for that the higher temperature may reduce the transmissibility of COVID-19.

Acute Demyelinating Encephalomyelitis (ADEM) in COVID-19 infection: A Case Series. (preprint)

Objective: To report three patients infected with COVID-19 with severe respiratory syndrome requiring intubation, who developed acute demyelinating encephalomyelitis (ADEM). Method: Patient data were obtained from medical records from the North Memorial Health Hospital, Robbinsdale, MN, USA Results: Three patients (two men and one woman, aged 38 - 63) presented with fatigue, cough and fever leading to development of acute respiratory distress syndrome secondary to COVID-19 infection requiring intubation and ventilatory support. Two patients were unresponsive, one with strong eye deviation to the left and the third patient had severe diffuse weakness. MRI in all patients showed findings consistent with ADEM. CSF showed elevated protein in all patients with normal cell count and no evidence of infection, including negative COVID-19 PCR. All three of the patients received Convalescent plasma therapy for COVID-19. All patients were treated with intravenous corticosteroids and improved, although two responded minimally. Two patients treated with IVIG showed no further improvement. Conclusion: Neurological complications from COVID-19 are being rapidly recognized. Our three cases highlight the occurrence of ADEM as a postinfectious/immune mediated complication of COVID-19 infection, which may be responsive to corticosteroid treatment. Early recognition of this complication and treatment is important to avoid long term complications.