Targeted next-generation sequencing of pathogens reveals the profile of secondary infections in COVID-19 patients (preprint)

PURPOSE: To use targeted next-generation sequencing (tNGS) of pathogens for analysing the etiological distribution of secondary infections in patients with severe and critical novel coronavirus pneumonia (COVID-19), to obtain microbial epidemiological data on secondary infections in patients with COVID-19, and to provide a reference for early empirical antibiotic treatment of such patients. METHODS: Patients with infections secondary to severe and critical COVID-19 and hospitalised at the First Affiliated Hospital of Shandong First Medical University between 1 December 2022 and 30 June 2023 were included in the study. The characteristics and etiological distribution of secondary infections in these patients were analysed using tNGS. RESULTS: A total of 95 patients with COVID-19 secondary infections were included in the study, of whom 87.37% had one or more underlying diseases. Forty-eight pathogens were detected, the most common being HSV-4, Candida albicans, Klebsiella pneumoniae, Enterococcus faecium, HSV-1, Staphylococcus aureus, Aspergillus fumigatus, Acinetobacter baumannii, HSV-5, and Stenotrophomonas maltophilia, with Pneumocystis jirovecii being detected in 14.29% of cases. The majority (76.84%) of COVID-19 secondary infections were mixed infections, with mixed viral-bacterial-fungal infections being the most common (28.42%). CONCLUSION: Most secondary infections in severe and critical COVID-19 patients are mixed, with high rates of viral and fungal infections. In clinical settings, monitoring for reactivation or secondary infections by Herpesviridae viruses is crucial; additionally, these patients have a significantly higher rate of P. jirovecii infection. tNGS testing on bronchoalveolar lavage fluid can help determine the aetiology of secondary infections early in COVID-19 patients and assist in choosing appropriate antibiotics.

A field epidemiological investigation and emergency response of a confirmed COVID-19 case of a foreign airline cargo service personnel in Shanghai's international airport

Objective: To conduct on-site epidemiological investigation, emergency response, tracing of infection source and analysis of a confirmed COVID-19 case of a foreign airline cargo service staff member in Shanghai's international airport, aiming to provide reference for prevention of imported COVID-19 cases under regular prevention and control of COVID-19.

Cardiac Arrhythmia after COVID-19 Vaccination versus Non-COVID-19 Vaccination: A Systematic Review and Meta-Analysis (preprint)

Aims: Cardiac arrhythmia is a rare complication after vaccination. Recently, reports of arrhythmia after COVID-19 vaccination have increased. Whether the risk for cardiac arrhythmia is higher with COVID-19 vaccines than with non-COVID-19 vaccines remains controversial. This meta-analysis explored the incidence of arrhythmia after COVID-19 vaccination and compared it with the incidence of arrhythmia after non-COVID-19 vaccination. Methods: We searched the MEDLINE, Scopus, Cochrane Library, and Embase databases for English-language studies reporting the incidence of arrhythmia (the primary endpoint) after vaccination from January 1, 1947 to October 28, 2022. Secondary endpoints included incidence of tachyarrhythmia and all-cause mortality. Subgroup analyses were conducted to evaluate the incidence of arrhythmia by age (children [<18 years] versus adults [[≥]18 years]), vaccine type (mRNA COVID-19 vaccine versus non-mRNA COVID-19 vaccine; individual non-COVID-19 vaccines versus COVID-19 vaccine), and COVID-19 vaccine dose (first versus second versus third). Random-effects meta-analyses were performed, and the intrastudy risk for bias and the certainty of evidence were evaluated. This study was registered with PROSPERO (CRD42022365912). Results: The overall incidence of arrhythmia from 36 studies (1,528,459,662 vaccine doses) was 291.8 (95% CI 111.6-762.7) cases per million doses. The incidence of arrhythmia was significantly higher after COVID-19 vaccination (2263.4 [875.4-5839.2] cases per million doses; 830,585,553 doses, 23 studies) than after non-COVID-19 vaccination (9.9 [1.3-75.5] cases per million doses; 697,874,109 doses, 14 studies; P<0.01). Compared with COVID-19 vaccines, the influenza, pertussis, human papillomavirus, and acellular pertussis vaccines were associated with a significantly lower incidence of arrhythmia. The incidence of tachyarrhythmia was significantly higher after COVID-19 vaccination (4367.5 [1535.2-12,360.8] cases per million doses; 1,208,656 doses, 15 studies) than after non-COVID-19 vaccination (25.8 [4.5-149.4] cases per million doses; 179,822,553 doses, 11 studies; P<0.01). Arrhythmia was also more frequent after the third dose of COVID-19 vaccine (19,064.3 [5775.5-61,051.2] cases per million doses; 7968 doses, 3 studies) than after the first dose (3450.9 [988.2-11,977.6] cases per million doses; 41,714,762 doses, 12 studies; P=0.05) or second dose (2262.5 [2205.9-2320.7] cases per million doses; 34,540,749 doses, 10 studies; P<0.01). All-cause mortality was comparable between the COVID-19 and non-COVID-19 vaccination groups. Conclusions: The overall risk for arrhythmia after COVID-19 vaccination was relatively low, although it was higher in COVID-19 vaccine recipients than in non-COVID-19 vaccine recipients. This increased risk should be evaluated along with other important factors, such as the incidence of local outbreaks and the risk for arrhythmia due to COVID infection itself, when weighing the safety and efficacy of COVID-19 vaccines.

Global dynamics of a diffusive SIR epidemic model with saturated incidence rate and discontinuous treatments

In this paper, we study a diffusive SIR epidemic model with saturated incidence rate and discontinuous treatments under Neumann boundary conditions. Firstly, the existence and boundedness of the solution of the system are addressed. Then, on the basis of the differential inclusions theory, we analysis the existence of endemic equilibrium. Furthermore, by constructing different appropriate Lyapunov functions, we investigate the global asymptotic stability of the disease free equilibrium(DFE) and the endemic equilibrium(EE), respectively. Additionally, numerical simulations are given to confirm the correctness of theorem. Finally, we give a brief conclusion and discussion in the end of the paper.

The regulation of ISG20 expression on SARS-CoV-2 infection in cancer patients and healthy individuals

ISG20 inhibits viruses such as SARS-CoV-2 invasion;however, details of its expression and regulation with viral susceptibility remain to be elucidated. The present study analyzed ISG20 expression, isoform information, survival rate, methylation patterns, immune cell infiltration, and COVID-19 outcomes in healthy and cancerous individuals. Cordycepin (CD) and N6, N6-dimethyladenosine (m62A) were used to treat cancer cells for ISG20 expression. We revealed that ISG20 mRNA expression was primarily located in the bone marrow and lymphoid tissues. Interestingly, its expression was significantly increased in 11 different types of cancer, indicating that cancer patients may be less vulnerable to SARS-CoV-2 infection. Among them, higher expression of ISG20 was associated with a long OS in CESC and SKCM, suggesting that ISG20 may be a good marker for both viral prevention and cancer progress. ISG20 promoter methylation was significantly lower in BLCA, READ, and THCA tumor tissues than in the matched normal tissues, while higher in BRCA, LUSC, KIRC, and PAAD. Hypermethylation of ISG20 in KIRC and PAAD tumor tissues was correlated with higher expression of ISG20, suggesting that methylation of ISG20 may not underlie its overexpression. Furthermore, ISG20 expression was significantly correlated with immune infiltration levels, including immune lymphocytes, chemokine, receptors, immunoinhibitors, immunostimulators, and MHC molecules in pan-cancer. STAD exhibited the highest degree of ISG20 mutations;the median progression-free survival time in months for the unaltered group was 61.84, while it was 81.01 in the mutant group. Isoforms ISG20-001 and ISG20−009 showed the same RNase_T domain structure, demonstrating the functional roles in tumorigenesis and SARS-CoV-2 invasion inhibition in cancer patients. Moreover, CD and m62A increase ISG20 expression in various cancer cell lines, implying the antiviral/anti-SARS-CoV-2 therapeutic potential. Altogether, this study highlighted the value of combating cancer by targeting ISG20 during the COVID-19 pandemic, and small molecules extracted from traditional Chinese medicines, such as CD, may have potential as anti-SARS-CoV-2 and anticancer agents by promoting ISG20 expression.

Oridonin Inhibits SARS‐CoV‐2 by Targeting Its 3C‐Like Protease

Oridonin Inhibits SARS‐CoV‐2 Oridonin, a natural product extracted from Rabdosia rubescens, possesses a wide range of pharmacological properties, including anti‐inflammatory, anti‐cancer, anti‐microbial, neuroprotection, immunoregulation, etc. In article number 2100124, Baisen Zhong, Litao Sun, and co‐workers demonstrate that Oridonin targets the SARS‐CoV‐2 3CL protease by covalently binding to cysteine145 in its active pocket to exert an anti‐SARS‐CoV‐2 effect, which provides a novel candidate for the treatment of COVID‐19. © 2022 WILEY‐VCH GmbH

Constructing Multiple-Objective Portfolio Selection for Green Innovation and Dominating Green Innovation Indexes

Green innovation investments have rapidly grown since 2000. Green innovation indexes play important roles and are typically constructed by screening and indexing. However, Nobel Laureate Markowitz emphasizes portfolio selection instead of security selection and accentuates that “A good portfolio is more than a long list of good stocks.” Moreover, the screening-indexing strategies ignore that investors can take green innovation as an additional objective and thus gain additional utility. We consequently construct 3-objective portfolio selection for green innovation in addition to variance and expected return. An efficient frontier of portfolio selection then extends to an efficient surface which is a panorama of the optimal variance, expected return, and expected green innovation. Investors thus fully envisage the trade-offs and enjoy the freedom of choosing preferred portfolios on the surface. In contrast, the screening-indexing strategies inflexibly leave investors with only one point (i.e., the green innovation index). As the originality, we prove in a theorem that there typically exists a curve on the efficient surface so all portfolios on the curve dominate the green innovation index. We test the dominance by component stocks of China Securities Index 300 and obtain affirmative results out of sample. The results still hold in robustness tests. At last, we classify green innovation into categories, further model the categories by general k-objective portfolio selection, and still illustrate the dominance. Consequently, investors can consider and control each category.

Beneficial Effects of 1500 MHz Microwave on Old 5×FAD Mice (preprint)

Background: Treatment of Alzheimer’s disease is still a medical challenge now. Some researchers have tried to use electromagnetic therapy to treat Alzheimer’s disease, but there are no clear conclusions. 1500 MHz microwave was used to expose young and old 5×FAD mice here to explore the beneficial effect of microwave on Alzheimer’s disease.Methods: Young and old 5×FAD mice were exposed to 1500 MHz microwave at SARs of 2 or 4 W/kg for 5-months (2 h/day, 5 days/week). The cognitive function and emotional behavior were detected by Morris Water Maze, Y-Maze, Open Field Test and Elevated Plus Maze respectively. Amyloid β peptides, BACE1 expression, and inflammatory cytokines interleukin were detected by ELISA and qPCR. Amyloid β peptides and Iba1 in hippocampus of old FAD mice were further detected with immunohistochemistry.Results: Microwave treatment obviously improved the learning and memory in old AD mice after 5 months of exposure, which was confirmed by the significant decreased Aβ42 peptides and downregulated BACE1 expression in hippocampus. 1500 MHz microwave exposure caused anxiety-like behavior in young and old AD mice at a SAR of 2 W/kg and 4 W/kg respectively. IL-6 mRNA levels were significantly decreased while IL-4 and IL-10 were significantly increased in old AD mice after exposure at a SAR of 2 W/kg. At the same time, the amount of microglia along with Aβ deposition were significantly decreased in hippocampus. The weight loss of aged AD mice slowed down and no obvious increase of anal temperature was found during exposure.Conclusions: 1500 MHz microwave exposure can significantly improve the symptoms of AD in aged mice at a SAR of 2 W/kg with the regulations of inflammatory reaction in hippocampus, which may provide an effective clinical choice for treatment of elderly patients with AD.

Future trends in coaching: Results from a global coach survey, 2021

This paper presents the results from a global survey of 1200 coaches undertaken in Summer 2021, as the world emerged from global locksdowns and the 18 months of the Covid-19 pandemic. The survey gathered data on the make-up of the global coach community, including biographical data on national residence, gender, race, ethnicity, sexual orientation and disability. Secondly the research explored attitudes towards future trends. The findings indicate that, while the coaching industry is over-represented by female coaches when compared to the global population, it is broadly representative in terms of sexual orientation, while BIPOC coaches are under-represented. Further, the research confirmed that during 2020 coaches shifted their practices online, that most coaches see benefits for themselves and their clients and are likely to continue with online coaching. At the same time coaches are skeptical about the role of AI in coaching, while there are national differences about the importance of supervision as a reflective tool. [ FROM AUTHOR] Copyright of Coaching Psychologist is the property of British Psychological Society and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Would you enjoy virtual travel? The characteristics and causes of virtual tourists’ sentiment under the influence of the COVID-19 pandemic

There are numerous arguments regarding the attitudes of different tourists and scenic destination managers regarding virtual tourism. However, it remains difficult to understand the public's attitude towards virtual tourism in a crisis situation. In this way, under the influence of COVID-19, this study explores the public sentiment and drivers of virtual tourism using Python and the grounded theory method. The results reveal that tourists' positive sentiment in virtual tourism dominates, with few tourists showing negative or neutral sentiment polarity. Furthermore, there is an obvious law of time decay in the intensity of public sentiment. Especially as the crisis fades, the supplementary effect of virtual tourism on on-site tourism weakens. Moreover, project design, experience quality, travel convenience, travel cost, travel motivation and destination attractiveness are the critical factors affecting tourist sentiment. The findings provide implications for the sustainable development of both destination and virtual tourism in a new world order post-COVID-19.

Integrated Analysis of microRNAs and Metabolomics in Rat’s Serum Reveals Multi-action Modes of Qingfei Paidu Decoction for COVID-19 Treatment (preprint)

Background: During the fight against coronavirus disease 2019 (COVID-19) in China, Qingfei Paidu decoction (QFPDD) has been widely applied to treat COVID-19 patients. Retrospective studies showed that QFPDD could improve clinical outcomes of COVID-19. Thus, it is necessary and interesting to explore the action mode of QFPDD for further application and development. Methods: Sprague-Dawley (SD) rats were randomly divided into two groups, QFPDD (n=9) and control (n=10) groups. They were parallelly treated for 12 days with QFPDD and warm distilled water, respectively. At the endpoint, the microRNA (miRNA or miR) profiles in serum were detected to identify differently expressed miRNAs (DEMs). Then, the action mode of QFPDD were explored via review of potential roles of DEMs and functional enrichment analysis of their targets (e.g., GO enrichment and KEGG pathway analysis), especially focusing on the aspects of immunity, inflammation, virus infection and pulmonary fibrosis. Core genes were identified based on KEGG pathway analysis. Metabolomics were detected in serum and significantly changed metabolites (SCMs), especially the metabolic substrates and products of enzyme of core gene were identified as biomarkers to validate the regulation of DEMs to enzyme activity of core gene through metabolomic analysis and linear correlation analysis between SCMs and DEMs. Results: 23 DEMs were identified in the serum between QFPDD and control groups, with 1636 predicted genes. Reported evidence has showed that both the DEMs and their target genes involve regulation of immunity, inflammation, virus infection and pulmonary fibrosis. Phospholipase C, gamma 1 (Plcg1) was identified as a core gene and predicted to be upregulated attributed to downregulation of novel-89-mature. The levels of three SCMs, PC(P-18:1(11Z)/22:5(4Z,7Z,10Z,13Z,16Z)), PC(22:5(4Z,7Z,10Z,13Z,16Z)/P-18:0) and PC(16:1(9Z)/16:1(9Z)), which were the metabolic substrates of phospholipase C, were significantly reduced in QFPDD group, in addition, PC(P-18:1(11Z)/22:5(4Z,7Z,10Z,13Z,16Z)) and PC(22:5(4Z,7Z,10Z,13Z,16Z)/P-18:0) presented positively linear correlation with the expression level of novel-89-mature. The level of phosphorylcholine, a product of PCs metabolized by phospholipase C, was significantly elevated in QFPDD group. Conclusion: QFPDD can induce modification of miRNAs profile, and subsequently multi-regulate the immunity, inflammation, virus infection and pulmonary fibrosis in vivo, playing an important role for the positive outcomes of COVID-19 patients treated by QFPDD in China.

Characterizing cellular and molecular variabilities of peripheral immune cells in healthy inactivated SARS-CoV-2 vaccine recipients by single-cell RNA sequencing (preprint)

We systematically investigated the transcriptomes of the peripheral immune cells from 6 inactivated vaccine, BBIBP-CorV recipients at 4 pivotal time points using single-cell RNA-seq technique. First, the significant variation of the canonical immune-responsive signals of both humoral and cellular immunity, as well as other possible symptom-driver signals were evaluated in the specific cell types. Second, we described and compared the common and distinct variation trends across COVID-19 vaccination, disease progression, and flu vaccination to achieve in-depth understandings of the manifestation of immune response in peripheral blood under different stimuli. Third, the expanded T cell and B cell clones were correlated to the specific phenotypes which allowed us to characterize the antigen-specific ones much easier in the future. At last, other than the coagulopathy, the immunogenicity of megakaryocytes in vaccination were highlighted in this study. In brief, our study provided a rich data resource and the related methodology to explore the details of the classical immunity scenarios.

A Survey of Knowledge Tracing (preprint)

High-quality education is one of the keys to achieving a more sustainable world. The recent COVID-19 epidemic has triggered the outbreak of online education, which has enabled both students and teachers to learn and teach at home. Meanwhile, it is now possible to record and research a large amount of learning data using online learning platforms in order to offer better intelligent educational services. Knowledge Tracing (KT), which aims to monitor students' evolving knowledge state, is a fundamental and crucial task to support these intelligent services. Therefore, an increasing amount of research attention has been paid to this emerging area and considerable progress has been made. In this survey, we propose a new taxonomy of existing basic KT models from a technical perspective and provide a comprehensive overview of these models in a systematic manner. In addition, many variants of KT models have been proposed to capture more complete learning process. We then review these variants involved in three phases of the learning process: before, during, and after the student learning, respectively. Moreover, we present several typical applications of KT in different educational scenarios. Finally, we provide some potential directions for future research in this fast-growing field.

DNA damage contributes to age-associated differences in SARS-CoV-2 infection (preprint)

Coronavirus disease 2019 (COVID-19), caused by coronavirus SARS-CoV-2, is known to disproportionately affect older individuals1,2. How aging processes affect the disease progression remains largely unknown. Here we found that DNA damage, one of the major causes of aging3, promoted susceptibility to SARS-CoV-2 infection in cells and intestinal organoids. SARS-CoV-2 entry was facilitated by DNA damage caused by telomere attrition or extrinsic genotoxic stress and hampered by inhibition of DNA damage response (DDR). Mechanistic analysis revealed that DDR increased expression of ACE2, the receptor of SARS-CoV-2, by activation of transcription factor c-Jun in vitro and in vivo. Expression of ACE2 was elevated in the older tissues and positively correlated with γH2Ax and phosphorylated c-Jun (p-c-Jun). Finally, targeting DNA damage by increasing the DNA repair capacity, alleviated cell susceptibility to SARS-CoV-2. Our data provide insights into the age-associated differences in SARS-CoV-2 infection and a novel target for anti-viral intervention.

The Impact of COVID-19 Pandemic on Colorectal Cancer Patients: A Single-Center Retrospective Study (preprint)

Background: Since December 2019, China has experienced the public health emergency of coronavirus disease, which has expanded globally and is impacting the care of cancer patients. This study evaluated the impact of the pandemic on colorectal cancer (CRC) patients at our center and aimed to share lessons learned with clinics currently experiencing this impact. Methods: We retrospectively collected data on CRC patients admitted between January 1, 2020 and May 3, 2020; the control group comprised patients admitted between January 1, 2019 and May 3, 2019. Results: During the pandemic, outpatient volumes decreased significantly, especially among nonlocal and elderly patients, whereas the number of patients who received chemotherapy and surgery were maintained. During the pandemic, 710 CRC patients underwent curative enterectomy. The proportion of laparoscopic surgery was 49.4%, which was significantly higher than the 39.5% patients who received a laparoscopic surgery during the same period in 2019. The proportion of major complication during the pandemic was not significantly different from that of the control group. The mean hospital stay was significantly longer than that of the control group. Conclusions: CRC patients who are confirmed to be infection-free can receive routine treatment. Using online medical counseling and appropriate identification, treatment and follow-up was effectively maintained. Adjuvant and palliative chemotherapy should not be discontinued. Endoscopic polypectomy, elective, palliative, and multidisciplinary surgeries can be postponed, whereas curative surgery should be performed. For elderly CRC patients, endoscopic surgery and neoadjuvant radiotherapy are recommended.Trial registration: retrospectively registered

The impact of COVID-19 pandemic on colorectal cancer patients: A single-center retrospective study (preprint)

Background: Since December 2019, China has experienced the public health emergency of coronavirus disease, which has expanded globally and is impacting the care of cancer patients. This study evaluated the impact of the pandemic on colorectal cancer (CRC) patients at our center and aimed to share lessons learned with clinics currently experiencing this impact. Methods: We retrospectively collected data on CRC patients admitted between January 1, 2020 and May 3, 2020; the control group comprised patients admitted between January 1, 2019 and May 3, 2019. Results: During the pandemic, outpatient volumes decreased significantly, especially among nonlocal and elderly patients, whereas the number of patients who received chemotherapy and surgery were maintained. During the pandemic, 710 CRC patients underwent curative enterectomy. The proportion of laparoscopic surgery was 49.4%, which was significantly higher than the 39.5% patients who received a laparoscopic surgery during the same period in 2019. The proportion of major complication during the pandemic was not significantly different from that of the control group. The mean hospital stay was significantly longer than that of the control group. Conclusions: CRC patients who are confirmed to be infection-free can receive routine treatment. Using online medical counseling and appropriate identification, treatment and follow-up was effectively maintained. Adjuvant and palliative chemotherapy should not be discontinued. Endoscopic polypectomy, elective, palliative, and multidisciplinary surgeries can be postponed, whereas curative surgery should be performed. For elderly CRC patients, endoscopic surgery and neoadjuvant radiotherapy are recommended.

Clinical efficacy of corticosteroids in the early stage of worsening of COVID-19 pneumonia (preprint)

Background: The World Health Organization (WHO) recommends using corticosteroids in patients with severe coronavirus disease 2019 (COVID-19) and acute respiratory distress syndrome (ARDS), and a large randomized controlled clinical trial in the UK found that dexamethasone was effective in reducing the number of deaths in patients with severe COVID-19.Case presentation: Herein, we described a case of COVID-19 with the clinical characteristics of the mild-symptomatic stage deteriorating to a critically ill state, who showed dramatic improvement with corticosteroids in the early stage of worsening of COVID-19 pneumonia.Discussion: This article further discusses the most suitable timing and dosage of corticosteroid to maximize its effect during the worsening of COVID-19 pneumonia.Learning points:• One of the main pathophysiological hypotheses for severe COVID-19 pneumonia is related to cytokine storm and viral load.• The clinical factors should be considered as the initial sign of a cytokine storm, and corticosteroid therapy may be useful in these patients. 

Surface texture limits transfer of S. aureus, T4 Bacteriophage, Influenza B virus and Human coronavirus (preprint)

Spread of pathogens on contaminated surfaces plays a key role in disease transmission. Surface technologies that control pathogen transfer can help control fomite transmission and are of great interest to public health. Here, we report a novel bead transfer method for evaluating fomite transmission in common laboratory settings. We show that this method meets several important criteria for quantitative test methods, including reasonableness, relevancy, resemblance, responsiveness, and repeatability, and therefore may be adaptable for standardization. In addition, this method can be applied to a wide variety of pathogens including bacteria, phage, and human viruses. Using the bead transfer method, we demonstrate that an engineered micropattern limits transfer of Staphylococcus aureus by 97.8% and T4 bacteriophage by 93.0% on silicone surfaces. Furthermore, the micropattern significantly reduces transfer of influenza B virus and human coronavirus on silicone and polypropylene surfaces. Our results highlight the potential of using surface texture as a valuable new strategy in combating infectious diseases. Importance Disease transmission often occurs through contact with contaminated surfaces, called fomites. Efforts to reduce this method of fomite transmission include surface cleaning, personal hygiene, alteration of habits, and novel technologies to reduce pathogen spread. This manuscript presents a novel method for the consistent contamination of surfaces to mimic the transmission of pathogens via fomites. Using this method, we present a surface texture modeled on shark skin that significantly reduces the transfer of a variety of pathogens, including Staphylococcus aureus , influenza B virus, and human coronavirus 229E. Utilization of novel technologies to limit pathogen spread can enhance existing methods of disease mitigation.

Clinical course and management of 73 hospitalized moderate patients with COVID-19 outside Wuhan (preprint)

Background: Moderate cases account for the majority in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and can also progress to severe/critical condition. Here, we investigated the clinical course and management of hospitalized moderate SARS-CoV-2 patients.Methods: The medical records and follow-up data were analyzed from the SARS-CoV-2 patients outside Wuhan.Results: A total of 73 moderate patients (38 men, 35 women) were included, with median age of 47.0 (38.5-57.5) years. Among them, only one patient (1.4%) died using active treatment to improve symptoms. The median duration of the four main symptoms cough, fever, chest tightness, and fatigue were about 1-2 weeks; the median duration of the positive nucleic acid test (NAT) results for SARS-CoV-2 was slightly more than 2 weeks; the median hospitalization time was almost four weeks in 72 moderate survivors. The duration of cough and fever was positively correlated with the duration of the positive NAT results. On admission, 50% had lymphopenia; less than 30% had abnormal blood biochemistry findings involving hyperglycemia, liver function and myocardial enzymes. At discharge, the laboratory indexes were substantially improved. Two weeks after discharge, 5.6% survivors experienced a recurrence of the positive NAT results. Conclusions: Moderate SARS-CoV-2 patients have a good prognosis by the active treatment. After discharge, it is necessary that moderate survivors undergo at least a 2-week collective medical observation in quarantine places, which can identify and treat a proportion of patients with re-positive NAT results and to prevent the spread of the potential sources of infection.

Ongoing natural selection drives the evolution of SARS-CoV-2 genomes (preprint)

SARS-CoV-2 is a new RNA virus affecting humans and spreads extensively through world populations since its first outbreak in late December, 2019. Whether the transmissibility and pathogenicity of SARS-CoV-2 is actively evolving, and driven by adaptation to the new host and environments is still unknown. Understanding the evolutionary mechanism underlying epidemiological and pathological characteristics of COVID-19 is essential for predicting the epidemic trend, and providing guidance for disease control and treatments. Interrogating 22,078 SARS-CoV-2 genome sequences of 84 countries, we demonstrate with convincing evidence that (i) SARS-CoV-2 genomes are overall conserved under purifying selection. (ii) Ongoing positive selection is actively driving the evolution of specific genes. Notably, genes related to coronavirus infection and host immune system defense are under adaptive evolution while genes related to viral RNA replication, transcription and translation are under purifying selection. A spatial and temporal landscape of 54 critical mutants is constructed based on their divergence among viral haplotype clusters, of which multiple mutants potentially conferring viral transmissibility, infectivity and virulence of SARS-CoV-2 are highlighted.