An anti-infodemic virtual center for the Americas.

The Pan American Health Organization/World Health Organization (PAHO/WHO) Anti-Infodemic Virtual Center for the Americas (AIVCA) is a project led by the Department of Evidence and Intelligence for Action in Health, PAHO and the Center for Health Informatics, PAHO/WHO Collaborating Center on Information Systems for Health, at the University of Illinois, with the participation of PAHO staff and consultants across the region. Its goal is to develop a set of tools-pairing AI with human judgment-to help ministries of health and related health institutions respond to infodemics. Public health officials will learn about emerging threats detected by the center and get recommendations on how to respond. The virtual center is structured with three parallel teams: detection, evidence, and response. The detection team will employ a mixture of advanced search queries, machine learning, and other AI techniques to sift through more than 800 million new public social media posts per day to identify emerging infodemic threats in both English and Spanish. The evidence team will use the EasySearch federated search engine backed by AI, PAHO's knowledge management team, and the Librarian Reserve Corps to identify the most relevant authoritative sources. The response team will use a design approach to communicate recommended response strategies based on behavioural science, storytelling, and information design approaches.

El centro virtual contra la infodemia para la Región de las Américas de la Organización Panamericana de la Salud/Organización Mundial de la Salud (OPS/OMS) es un proyecto liderado por el Departamento de Evidencia e Inteligencia para la Acción en la Salud de la OPS y el Center for Health Informatics de la Universidad de Illinois, centro colaborador de la OPS/OMS en sistemas de información para la salud, con la participación de personal y consultores de la OPS en toda la Región. Su objetivo es crear un conjunto de herramientas que combinen inteligencia artificial (IA) y los criterios humanos para apoyar a los ministerios de salud y las instituciones relacionadas con la salud en la respuesta a la infodemia. Los funcionarios de salud pública recibirán formación sobre las amenazas emergentes detectadas por el centro y recomendaciones sobre cómo abordarlas. El centro virtual está estructurado en tres equipos paralelos: detección, evidencia y respuesta. El equipo de detección empleará una combinación de consultas mediante búsqueda avanzada, aprendizaje automático y otras técnicas de IA para evaluar más de 800 millones de publicaciones nuevas en las redes sociales al día con el fin de detectar amenazas emergentes en el ámbito de la infodemia tanto en inglés como en español. El equipo de evidencia hará uso del motor de búsqueda federado EasySearch y, con el apoyo de la IA, el equipo de gestión del conocimiento de la OPS y la red Librarian Reserve Corps, determinará cuáles son las fuentes autorizadas más pertinentes. El equipo de respuesta utilizará un enfoque vinculado al diseño para difundir las estrategias recomendadas sobre la base de las ciencias del comportamiento, la narración de historias y el diseño de la información.

O Centro Virtual Anti-Infodemia para as Américas (AIVCA, na sigla em inglês) da Organização Pan-Americana da Saúde/Organização Mundial da Saúde (OPAS/OMS) é um projeto liderado pelo Departamento de Evidência e Inteligência para a Ação em Saúde da OPAS e pelo Centro de Informática em Saúde da Universidade de Illinois, EUA (Centro Colaborador da OPAS/OMS para Sistemas de Informação para a Saúde), com a participação de funcionários e consultores da OPAS de toda a região. Seu objetivo é desenvolver um conjunto de ferramentas ­ combinando a inteligência artificial (IA) com o discernimento humano ­ para ajudar os ministérios e instituições de saúde a responder às infodemias. As autoridades de saúde pública aprenderão sobre as ameaças emergentes detectadas pelo centro e obterão recomendações sobre como responder. O centro virtual está estruturado com três equipes paralelas: detecção, evidência e resposta. A equipe de detecção utilizará consultas de pesquisa avançada, machine learning (aprendizagem de máquina) e outras técnicas de IA para filtrar mais de 800 milhões de novas postagens públicas nas redes sociais por dia, a fim de identificar ameaças infodêmicas emergentes em inglês e espanhol. A equipe de evidência usará o mecanismo de busca federada EasySearch, com apoio de IA, da equipe de gestão de conhecimento da OPAS e do Librarian Reserve Corps (LRC), para identificar as fontes abalizadas mais relevantes. A equipe de resposta usará uma abordagem de design para comunicar estratégias de resposta recomendadas com base em abordagens de ciência comportamental, narração de histórias e design da informação.

Evolution of SARS-CoV-2 Variants: Implications on Immune Escape, Vaccination, Therapeutic and Diagnostic Strategies.

The COVID-19 pandemic caused by SARS-CoV-2 is associated with a lower fatality rate than its SARS and MERS counterparts. However, the rapid evolution of SARS-CoV-2 has given rise to multiple variants with varying pathogenicity and transmissibility, such as the Delta and Omicron variants. Individuals with advanced age or underlying comorbidities, including hypertension, diabetes and cardiovascular diseases, are at a higher risk of increased disease severity. Hence, this has resulted in an urgent need for the development of better therapeutic and preventive approaches. This review describes the origin and evolution of human coronaviruses, particularly SARS-CoV-2 and its variants as well as sub-variants. Risk factors that contribute to disease severity and the implications of co-infections are also considered. In addition, various antiviral strategies against COVID-19, including novel and repurposed antiviral drugs targeting viral and host proteins, as well as immunotherapeutic strategies, are discussed. We critically evaluate strategies of current and emerging vaccines against SARS-CoV-2 and their efficacy, including immune evasion by new variants and sub-variants. The impact of SARS-CoV-2 evolution on COVID-19 diagnostic testing is also examined. Collectively, global research and public health authorities, along with all sectors of society, need to better prepare against upcoming variants and future coronavirus outbreaks.

Nasal swab is a good alternative sample for detecting SARS-CoV-2 with rapid antigen test: A meta-analysis.

BACKGROUND: We aim to determine if nasal samples have equivalent detection sensitivity to nasopharyngeal swabs for RAT and evaluate the diagnostic accuracy of nasal swabs with RAT. METHODS: PubMed and Web of Science were searched for eligible studies published before August 23, 2022. A bivariate random effects model was used to perform the quantitative synthesis. RESULTS: The pooled sensitivity, pooled specificity, positive likelihood ratio, negative likelihood ratio, and summary AUC on nasal swabs with RAT were 0.81 (95% CI, 0.77-0.85), 1.00 (95% CI: 0.99-1.00), 0.97 (95% CI, 0.95-0.98), 298.91 (95% CI, 144.71-617.42) and 0.19 (95% CI, 0.15-0.23), respectively. WHO required RAT kits to perform with a sensitivity of 0.80 and a specificity of 0.97, nasal swabs (0.81) achieved the required sensitivity while nasopharyngeal swabs (0.75) did not. The symptomatic population yielded higher pooled sensitivity than the asymptomatic population (0.86 versus 0.71), with a pooled sensitivity of 0.90 for five days of symptom onset. CONCLUSION: Nasal sampling had a great performance and yielded a high sensitivity in detecting SARS-CoV-2 using RAT, we believe that RAT performed with nasal swabs is a good alternative for detecting SARS-CoV-2, especially early in the onset of symptoms.

Evaluating the Value of Anti-SARS-CoV-2 Antibody-Based Tests for COVID-19 Diagnosis.

BACKGROUND: The early detection of COVID-19 patients is fundamental for containing the pandemic. A reverse-transcriptase quantitative polymerase chain reaction (RT-PCR), which detects SARS-CoV-2 RNA, is the gold standard diagnostic test, although it can contribute to false-negative results. Consequently, supplementary diagnostic tests are urgently needed. METHODS: To assess the value of anti-SARS-CoV-2 antibody-based tests for confirming COVID-19, a retrospective study was conducted on 3120 inbound overseas travelers who underwent a 14-day government quarantine in Xiamen from August 2020 to October 2020. The diagnostic accuracy of the total antibody that detected the anti-SARS-CoV-2 antibody and the RT-PCR that detected SARS-CoV-2 RNA was determined in comparison to the clinical diagnosis. RESULTS: The COVID-19 positive rate was 3.14% (98/3120). The sensitivity and specificity of the RT-PCR test on the first day of quarantine were 14.29% and 100%, respectively, and the sensitivity and specificity of the total antibody were 93.88% and 99.40%, respectively. The kappa value between an RT-PCR on the first day of quarantine and a clinical diagnosis was 0.24 (95% CI, 0.14-0.35), indicating poor consistency. The kappa value between total antibodies and a clinical diagnosis was 0.88 (95% CI, 0.83-0.93), indicating perfect consistency. There were no differences in the positive rates of an RT-PCR in symptomatic COVID-19 (7.41% (2/27)) and asymptomatic COVID-19 (16.90 (12/71) (p = 0.338). Similarly, the positive rate of the total antibody tests showed no difference in symptomatic COVID-19 (96.30% (26/27)) and asymptomatic COVID-19 (92.96% (66/71)) (p = 0.676). CONCLUSION: SARS-CoV-2 antibodies are developed by the body in response to an infection or after vaccination; this can easily lead to a missed diagnosis. In the context of low sensitivity for an RT-PCR, SARS-CoV-2 antibody detection is an effective adjunct to RT-PCR detection, which can improve the diagnostic accuracy of COVID-19 and provide an effective complement to the false-negative results of an RT-PCR.

Evaluation of the cycle threshold values of RT-PCR for SARS-CoV-2 in COVID-19 patients in predicting epidemic dynamics and monitoring surface contamination.

To evaluate the application of cycle threshold (Ct) values of coronavirus disease 2019 (COVID-19) patients in predicting epidemic dynamics and monitoring surface contamination. The Ct value of reverse transcriptase-polymerase chain reaction for SARS­CoV-2 from COVID-19 patients inbound overseas in Xiamen, China was collected from October 2020 to December 2021, and the correlation of patients' Ct values with epidemic dynamics and surface contamination was evaluated. The results showed that there was an extreme inverse correlation of positivity rate in the current calendar month (ORF1ab, r = -0.692, P = 0.004; N,r = -0.629, P = 0.012) and the following calendar month (ORF1ab,r = -0.801, P = 0.001; N,r = -0.620, P = 0.018) with the median Ct values. Ct value showed better performance for monitoring surface contamination, with the area under the curve value 0.808(95 %CI: 0.748-0.869) for ORF1ab and 0.807(95 %CI:0.746-0.868) for the N gene. The patients' ORF1ab Ct value< 29.09 or N Ct value< 28.03 were 11.25 times and 10.48 times more likely to result in surface contamination than those with ORF1ab Ct value ≥ 29.09 or N Ct value≥ 28.03 (OR:11.25,95 % CI: 5.52-22.35; OR:10.48,95 % CI:5.29-20.70). Ct values were associated with the positivity rate in the current or following calendar month and predicted the epidemic dynamics. The Ct values can be used as a predictor for monitoring surface contamination to develop public health responses to COVID-19.

SARS-CoV-2 Non-Structural Proteins and Their Roles in Host Immune Evasion.

Coronavirus disease 2019 (COVID-19) has caused an unprecedented global crisis and continues to threaten public health. The etiological agent of this devastating pandemic outbreak is the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). COVID-19 is characterized by delayed immune responses, followed by exaggerated inflammatory responses. It is well-established that the interferon (IFN) and JAK/STAT signaling pathways constitute the first line of defense against viral and bacterial infections. To achieve viral replication, numerous viruses are able to antagonize or hijack these signaling pathways to attain productive infection, including SARS-CoV-2. Multiple studies document the roles of several non-structural proteins (NSPs) of SARS-CoV-2 that facilitate the establishment of viral replication in host cells via immune escape. In this review, we summarize and highlight the functions and characteristics of SARS-CoV-2 NSPs that confer host immune evasion. The molecular mechanisms mediating immune evasion and the related potential therapeutic strategies for controlling the COVID-19 pandemic are also discussed.

Diagnostic accuracy of rapid antigen test for SARS-CoV-2: A systematic review and meta-analysis of 166,943 suspected COVID-19 patients.

To assess the diagnostic accuracy of the rapid antigen test (RAT) compared with RT-PCR (reference standard) for SARS-CoV-2, we searched MEDLINE/PubMed and Web of Science for relevant records. The QUADAS-2 tool was used to assess study quality, and quantitative synthesis was conducted using a bivariate random-effects model. The meta-analysis included 135 studies (166,943 samples). The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 0.76 (95%CI: 0.73-0.79), 1.00 (95%CI: 1.00-1.00), 276.1 (95% CI, 184.1-414.1), 0.24 (95% CI, 0.21-0.27), and 1171 (95% CI, 782-1755), respectively. Compared to other sample types, nasal samples had the best RAT sensitivity [0.79 (95%CI: 0.71-0.85)]. The sensitivities of the different RAT kits ranged from 0.41 (95%CI: 0.23-0.61) to 0.90 (95%CI: 0.70-0.97). Sensitivity was markedly better in samples with lower Ct, and RAT achieved excellent pooled sensitivity at 1.00 (95%CI: 0.70-1.00) among samples with Ct < 20. Testing within 10 days of symptom onset resulted in a high sensitivity. For ≤ 3, ≤ 7, and ≤ 10 days, the sensitivities were 0.91 (95%CI: 0.83-0.96), 0.89 (95%CI: 0.84-0.93), and 0.88 (95%CI: 0.83-0.92), respectively. RAT kits show high sensitivity and specificity in early infection, especially when the viral load is high. Moreover, using nasal samples for antigen testing, which are moderately sensitive and patient-friendly, is a reliable alternative to nasopharyngeal sampling. RAT might be effective for fighting the COVID-19 pandemic; however, it must be complemented by the careful handling of negative test results.

A 14+7 day quarantine period and a dual nucleic acid testing reagent strategy detect potentially indiscoverable Coronavirus disease 2019 infections in Xiamen, China.

BACKGROUND: Determining what quarantine period and detection strategy are more effective and sustainable remains a challenge for further prevention and social stability. METHODS: From October 2020 to December 2021, 290,547 inbound overseas travelers were subject to government quarantine in Xiamen, China. The detection rate of COVID-19 during different quarantine periods using dual or single nucleic acid testing reagents. RESULTS: The COVID-19 positive rate was 1.79% (519/290,547). The detection rates during the 7-day, 14-day and 14+7-day quarantine periods using the dual reagents were 78.4%, 91.7%, and 100%, respectively. The detection rate of the 7-day, 14-day and 14+7-day quarantine periods were 73.99%, 86.51%, and 94.22%, respectively, using the Liferiver reagent and 72.25%, 84.59%, and 91.91%, respectively, using the Daan reagent. Based on the 14+7 day strategy, dual nucleic acid testing reagent strategy detected all imported cases, but 30 cases (5.78%) were not detected via Liferiver reagent and 42 (8.09%) cases not detected via Daan reagent. CONCLUSION: A 14+7-day quarantine period and dual nucleic acid testing reagent strategy are effective screening methods for COVID-19 among inbound overseas travelers. The superior detection rate of these strategies reduce the risk of secondary transmission of the SARS-CoV-2 virus.

Repurposing Molnupiravir for COVID-19: The Mechanisms of Antiviral Activity.

Molnupiravir is a ß-d-N4-hydroxycytidine-5'-isopropyl ester (NHC) compound that exerts antiviral activity against various RNA viruses such as influenza, SARS, and Ebola viruses. Thus, the repurposing of Molnupiravir has gained significant attention for combatting infection with SARS-CoV-2, the etiological agent of COVID-19. Recently, Molnupiravir was granted authorization for the treatment of mild-to-moderate COVID-19 in adults. Findings from in vitro experiments, in vivo studies and clinical trials reveal that Molnupiravir is effective against SARS-CoV-2 by inducing viral RNA mutagenesis, thereby giving rise to mutated complementary RNA strands that generate non-functional viruses. To date, the data collectively suggest that Molnupiravir possesses promising antiviral activity as well as favorable prophylactic efficacy, attributed to its effective mutagenic property of disrupting viral replication. This review discusses the mechanisms of action of Molnupiravir and highlights its clinical utility by disabling SARS-CoV-2 replication, thereby ameliorating COVID-19 severity. Despite relatively few short-term adverse effects thus far, further detailed clinical studies and long-term pharmacovigilance are needed in view of its mutagenic effects.

Prevalence of Sarcopenia in Patients With COVID-19: A Systematic Review and Meta-Analysis

Background It has been speculated that patients with sarcopenia are aggravated by the current novel coronavirus disease 2019 (COVID-19) epidemic. However, there is substantial uncertainty regarding the prevalence of sarcopenia in patients with COVID-19. Objectives The purpose of the study was to systematically evaluate the prevalence of sarcopenia in patients with COVID-19, including stratification by gender, study location, study population, study design, and diagnostic criteria. Design This is the systematic literature review and meta-analysis. Methods An electronic search was performed in MEDLINE/PubMed, Embase, Cochrane Library, and Web of Science and Scopus to identify observational studies reporting a prevalence estimate for sarcopenia in patients with COVID-19. Studies were reviewed in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines and a meta-analysis was performed. Risk of bias (RoB) was assessed using the Newcastle–Ottawa Scale (NOS) for cohort studies and Joanna Briggs Institute (JBI) manual for cross-sectional studies, and Stata 14.0 was used to perform meta-analyses. Results A total of 4,639 studies were initially identified. After removing the duplicates and applying the selection criteria, we reviewed 151 full-text studies. A total of 21 studies, including 5,407 patients, were eligible for inclusion in this review finally. The prevalence of sarcopenia in patients with COVID-19 in individual studies varied from 0.8 to 90.2%. The pooled prevalence of sarcopenia in COVID-19 was 48.0% (95% confidence interval, CI: 30.8 to 65.1%, I2 = 99.68%, p = 0.000). We did not find any significant differences in the prevalence estimates between gender specificity (OR = 1.34;95% CI = 0.80–2.26;p = 0.001). By sex, the prevalence was 42.5% (95% CI: 31.7 to 53.4%) in men and 35.7% (95% CI: 24.2 to 47.2%) in women. The prevalence estimates significantly varied based on population settings and different diagnostic criteria of sarcopenia. ICU patients (69.7, 95% CI: 51.7 to 85.2%) were more likely to suffer from sarcopenia compared to other population settings. Conclusion To our knowledge, this is the first meta-analysis reporting on the prevalence of sarcopenia in patients with COVID-19. Sarcopenia is frequently observed in patients with COVID-19, with varying prevalence across population settings. This study would be useful for clinicians to prompt the increasing awareness of identifying sarcopenia and developing interventions at patients with COVID-19 with high risk of sarcopenia. Further prospective longitudinal studies to define the association of sarcopenia and its prognostic outcomes in COVID-19 survivors are urgently needed to propose the most appropriate treatment strategies during their admission and discharge. Systematic Review Registration [www.crd.york.ac.uk/prospero/], identifier [CRD42022300431].

Repurposing Molnupiravir for COVID-19: The Mechanisms of Antiviral Activity

Molnupiravir is a β-d-N4-hydroxycytidine-5′-isopropyl ester (NHC) compound that exerts antiviral activity against various RNA viruses such as influenza, SARS, and Ebola viruses. Thus, the repurposing of Molnupiravir has gained significant attention for combatting infection with SARS-CoV-2, the etiological agent of COVID-19. Recently, Molnupiravir was granted authorization for the treatment of mild-to-moderate COVID-19 in adults. Findings from in vitro experiments, in vivo studies and clinical trials reveal that Molnupiravir is effective against SARS-CoV-2 by inducing viral RNA mutagenesis, thereby giving rise to mutated complementary RNA strands that generate non-functional viruses. To date, the data collectively suggest that Molnupiravir possesses promising antiviral activity as well as favorable prophylactic efficacy, attributed to its effective mutagenic property of disrupting viral replication. This review discusses the mechanisms of action of Molnupiravir and highlights its clinical utility by disabling SARS-CoV-2 replication, thereby ameliorating COVID-19 severity. Despite relatively few short-term adverse effects thus far, further detailed clinical studies and long-term pharmacovigilance are needed in view of its mutagenic effects.

Repositioning Ivermectin for Covid-19 treatment: Molecular mechanisms of action against SARS-CoV-2 replication.

Ivermectin (IVM) is an FDA approved macrocyclic lactone compound traditionally used to treat parasitic infestations and has shown to have antiviral potential from previous in-vitro studies. Currently, IVM is commercially available as a veterinary drug but have also been applied in humans to treat onchocerciasis (river blindness - a parasitic worm infection) and strongyloidiasis (a roundworm/nematode infection). In light of the recent pandemic, the repurposing of IVM to combat SARS-CoV-2 has acquired significant attention. Recently, IVM has been proven effective in numerous in-silico and molecular biology experiments against the infection in mammalian cells and human cohort studies. One promising study had reported a marked reduction of 93% of released virion and 99.98% unreleased virion levels upon administration of IVM to Vero-hSLAM cells. IVM's mode of action centres around the inhibition of the cytoplasmic-nuclear shuttling of viral proteins by disrupting the Importin heterodimer complex (IMPα/ß1) and downregulating STAT3, thereby effectively reducing the cytokine storm. Furthermore, the ability of IVM to block the active sites of viral 3CLpro and S protein, disrupts important machinery such as viral replication and attachment. This review compiles all the molecular evidence to date, in review of the antiviral characteristics exhibited by IVM. Thereafter, we discuss IVM's mechanism and highlight the clinical advantages that could potentially contribute towards disabling the viral replication of SARS-CoV-2. In summary, the collective review of recent efforts suggests that IVM has a prophylactic effect and would be a strong candidate for clinical trials to treat SARS-CoV-2.

Recombinant angiopoietin-like protein 4 attenuates intestinal barrier structure and function injury after ischemia/reperfusion.

BACKGROUND: Intestinal barrier breakdown, a frequent complication of intestinal ischemia-reperfusion (I/R) including dysfunction and the structure changes of the intestine, is characterized by a loss of tight junction and enhanced permeability of the intestinal barrier and increased mortality. To develop effective and novel therapeutics is important for the improvement of outcome of patients with intestinal barrier deterioration. Recombinant human angiopoietin-like protein 4 (rhANGPTL4) is reported to protect the blood-brain barrier when administered exogenously, and endogenous ANGPTL4 deficiency deteriorates radiation-induced intestinal injury. AIM: To identify whether rhANGPTL4 may protect intestinal barrier breakdown induced by I/R. METHODS: Intestinal I/R injury was elicited through clamping the superior mesenteric artery for 60 min followed by 240 min reperfusion. Intestinal epithelial (Caco-2) cells and human umbilical vein endothelial cells were challenged by hypoxia/ reoxygenation to mimic I/R in vitro. RESULTS: Indicators including fluorescein isothiocyanate-conjugated dextran (4 kilodaltons; FD-4) clearance, ratio of phosphorylated myosin light chain/total myosin light chain, myosin light chain kinase and loss of zonula occludens-1, claudin-2 and VE-cadherin were significantly increased after intestinal I/R or cell hypoxia/reoxygenation. rhANGPTL4 treatment significantly reversed these indicators, which were associated with inhibiting the inflammatory and oxidative cascade, excessive activation of cellular autophagy and apoptosis and improvement of survival rate. Similar results were observed in vitro when cells were challenged by hypoxia/reoxygenation, whereas rhANGPTL4 reversed the indicators close to normal level in Caco-2 cells and human umbilical vein endothelial cells significantly. CONCLUSION: rhANGPTL4 can function as a protective agent against intestinal injury induced by intestinal I/R and improve survival via maintenance of intestinal barrier structure and functions.

Exploring experiences of COVID-19-positive individuals from social media posts.

AIMS: This study aimed to explore the experience of individuals who claimed to be COVID-19 positive via their Twitter feeds. BACKGROUND: Public social media data are valuable to understanding people's experiences of public health phenomena. To improve care to those with COVID-19, this study explored themes from Twitter feeds, generated by individuals who self-identified as COVID-19 positive. DESIGN: This study utilized a descriptive design for text analysis for social media data. METHODS: This study analysed social media text retrieved by tweets of individuals in the United States who self-reported being COVID-19 positive and posted on Twitter in English between April 2, 2020, and April 24, 2020. In extracting embedded topics from tweets, we applied topic modelling approach based on latent Dirichlet allocation and visualized the results via LDAvis, a related web-based interactive visualization tool. RESULTS: Three themes were mined from 721 eligible tweets: (i) recognizing the seriousness of the condition in COVID-19 pandemic; (ii) having symptoms of being COVID-19 positive; and (iii) sharing the journey of being COVID-19 positive. CONCLUSION: Leveraging the knowledge and context of study themes, we present experiences that may better reflect patient needs while experiencing COVID-19. The findings offer more descriptive support for public health nursing and other translational public health efforts during a global pandemic.

Attitudes towards COVID-19 precautionary measures and willingness to work during an outbreak among medical students in Singapore: a mixed-methods study.

BACKGROUND: The COVID-19 pandemic has revealed challenges that medical students face when healthcare systems are under intense pressure. There is a need to assess medical students' education needs in pandemic preparedness. The objective of this mixed-methods study was threefold: (1) to assess COVID-19 perceived efficacy, susceptibility, and anxiety in relation to health literacy; (2) to describe attitudes towards a policy of precautionary measures against COVID-19 and willingness to work during an outbreak; and (3) to examine multilevel factors associated with willingness to work. METHODS: An online survey was conducted among 263 medical students in Singapore during the lockdown period in July 2020. Participants were surveyed on COVID-19 related literacy, perceptions, anxiety, attitudes towards a policy of precautionary measures, and willingness to work during an outbreak. Bivariate and multivariate analyses were used to determine the factors associated with the key outcome variable of willingness to work. In addition, open-ended questions were used to assess medical education needs, which were reported using thematic analysis. RESULTS: Perceived adequacy of COVID-19 information was associated with higher perceived efficacy, lower perceived susceptibility, and lower anxiety levels among the students. Medical students were mostly supportive of COVID-19 precautionary measures except for relatively intrusive measures like in-home surveillance. The degree of willingness to work during an outbreak varied based on certain conditions, in particular family's health and safety, and was associated with self-efficacy, perceived susceptibility, and hospital capacity of outbreak management. CONCLUSIONS: Medical students' attitudes towards a policy of precautionary measures varied depending on legality, financial and psychological support, and privacy concerns. Health literacy played an important role in increasing the efficacy of protection against COVID-19 and reducing pandemic-related anxiety among medical students. Their willingness to work during an outbreak was increased by an effective policy of precautionary measures, hospital capacity to manage a pandemic, and assurance of family safety. Medical education should include pandemic preparedness to better prepare students to aid in pandemics, with emphasis on public health policy and ethics coupled with clinical training targeted to managing outbreaks.

SARS coronavirus outbreaks past and present-a comparative analysis of SARS-CoV-2 and its predecessors.

The Coronavirus Disease 2019 (COVID-19), a pneumonic disease caused by the SARS Coronavirus 2 (SARS-CoV-2), is the 7th Coronavirus to have successfully infected and caused an outbreak in humans. Genome comparisons have shown that previous isolates, the SARS-related coronavirus (SARSr-CoV), including the SARS-CoV are closely related, yet different in disease manifestation. Several explanations were suggested for the undetermined origin of SARS-CoV-2, in particular, bats, avian and Malayan pangolins as reservoir hosts, owing to the high genetic similarity. The general morphology and structure of all these viral isolates overlap with analogous disease symptoms such as fever, dry cough, fatigue, dyspnoea and headache, very similar to the current SARS-CoV-2. Chest CT scans for SARS-CoV-2, SARS-CoV and MERS-CoV reveal pulmonary lesions, bilateral ground-glass opacities, and segmental consolidation in the lungs, a common pathological trait. With greatly overlapping similarities among the previous coronavirus, the SARS-CoV, it becomes interesting to observe marked differences in disease severity of the SARS-CoV-2 thereby imparting it the ability to rapidly transmit, exhibit greater stability, bypass innate host defences, and increasingly adapt to their new host thereby resulting in the current pandemic. The most recent B.1.1.7, B.1.351 and P.1 variants of SARS-CoV-2, highlight the fact that changes in amino acids in the Spike protein can contribute to enhanced infection and transmission efficiency. This review covers a comparative analysis of previous coronavirus outbreaks and highlights the differences and similarities among different coronaviruses, including the most recent isolates that have evolved to become easily transmissible with higher replication efficiency in humans.

Single-Cell RNA-seq Reveals Angiotensin-Converting Enzyme 2 and Transmembrane Serine Protease 2 Expression in TROP2+ Liver Progenitor Cells: Implications in Coronavirus Disease 2019-Associated Liver Dysfunction.

The recent coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2. COVID-19 was first reported in China (December 2019) and is now prevalent across the globe. Entry of severe acute respiratory syndrome coronavirus 2 into mammalian cells requires the binding of viral Spike (S) proteins to the angiotensin-converting enzyme 2 receptor. Once entered, the S protein is primed by a specialized serine protease, transmembrane serine protease 2 in the host cell. Importantly, besides the respiratory symptoms that are consistent with other common respiratory virus infections when patients become viremic, a significant number of COVID-19 patients also develop liver comorbidities. We explored whether a specific target cell-type in the mammalian liver could be implicated in disease pathophysiology other than the general deleterious response to cytokine storms. Here, we used single-cell RNA-seq to survey the human liver and identified potentially implicated liver cell-type for viral ingress. We analyzed ~300,000 single cells across five different (i.e., human fetal, healthy, cirrhotic, tumor, and adjacent normal) liver tissue types. This study reports on the co-expression of angiotensin-converting enzyme 2 and transmembrane serine protease 2 in a TROP2+ liver progenitor population. Importantly, we detected enrichment of this cell population in the cirrhotic liver when compared with tumor tissue. These results indicated that in COVID-19-associated liver dysfunction and cell death, a viral infection of TROP2+ progenitors in the liver might significantly impair liver regeneration in patients with liver cirrhosis.

Discharge may not be the end of treatment: Pay attention to pulmonary fibrosis caused by severe COVID-19.

Since December 2019, coronavirus disease (COVID-19) has rapidly swept the world. So far, more than 30 million people have been infected and nearly one million have died. Although the world is still in the stage of COVID-19 pandemic, the treatment of new cases and critically ill patients is the focus of the current work. However, COVID-19 patients lead to pulmonary fibrosis, such a serious threat to the prognosis of complications were also worthy of our attention. First of all, we proposed the possible mechanism of pulmonary fibrosis caused by SARS-CoV-2, based on the published data of COVID-19 ((i) Direct evidence: pulmonary fibrosis was found in autopsy and pulmonary puncture pathology. (ii) Indirect evidence: increased levels of fibrosis-related cytokines[transforming growth factor [TGF]- ß, tumor necrosis factor [TNF]- α, interleukin [IL]-6, etc] in peripheral blood of severe patients.) What is more, we summarized the role of three fibrosis-related signaling pathways (TGF- ß signal pathway, WNT signal pathway and YAP/TAZ signal pathway) in pulmonary fibrosis. Finally, we suggested the therapeutic value of two drugs (pirfenidone and nintedanib) for idiopathic pulmonary fibrosis in COVID-19-induced pulmonary fibrosis.

The relationship between SARS-COV-2 RNA positive duration and the risk of recurrent positive.

BACKGROUND: The management of discharge COVID-19 patients with recurrent positive SARS-CoV-2 RNA is challenging. However, there are fewer scientific dissertations about the risk of recurrent positive. The aim of this study was to explore the relationship between SARS-COV-2 RNA positive duration (SPD) and the risk of recurrent positive. METHODS: This case-control multi-center study enrolled participants from 8 Chinese hospital including 411 participants (recurrent positive 241). Using unadjusted and multivariate-adjusted logistic regression analyses, generalized additive model with a smooth curve fitting, we evaluated the associations between SPD and risk of recurrent positive. Besides, subgroup analyses were performed to explore the potential interactions. RESULTS: Among recurrent positive patients, there were 121 females (50.2%), median age was 50 years old [interquartile range (IQR): 38-63]. In non-adjusted model and adjusted model, SPD was associated with an increased risk of recurrent positive (fully-adjusted model: OR = 1.05, 95% CI: 1.02-1.08, P = 0.001); the curve fitting was not significant (P = 0.286). Comparing with SPD < 14 days, the risk of recurrent positive in SPD > 28 days was risen substantially (OR = 3.09, 95% CI: 1.44-6.63, P = 0.004). Interaction and stratified analyses showed greater effect estimates of SPD and risk of recurrent positive in the hypertension, low monocyte count and percentage patients (P for interaction = 0.008, 0.002, 0.036, respectively). CONCLUSION: SPD was associated with a higher risk of recurrent positive and especially SPD > 28 day had a two-fold increase in the relative risk of re-positive as compared with SPD < 14 day. What's more, the risk may be higher among those with hypertension and lower monocyte count or percentage.