Clinical Characteristics and Clusters Analysis of 1009 COVID-19 Patients in Taiwan: A Registry Study (preprint)

Rationale, aims and objectives: The purpose of this study is to describe the symptoms and clusters characteristics of COVID-19 patients in Taiwan. Method: The Central Epidemic Command Center (CECC) from Taiwan CDC daily press release publications were extracted for patient demographic information (age, gender, case type and cluster) and the symptoms exhibited by the patients before diagnosis were collected. Results: A total of 1030 COVID-19 cases were reported in Taiwan up until the end of March 2021, of which 1009 patients had symptoms available. Of available patient data, 633 patients (62.74%) were symptomatic and 376 patients (37.26%) were asymptomatic, as classified in our study based on the published list of potential symptoms of COVID-19 by WHO. The most prevalent symptoms of our patients were coughing (29.33%), fever (26.56%) and nasal symptoms (20.22%). Our regression analysis found when the first detected patient of the cluster had a subjective sensation of feeling feverish, the number of infected cases in the cluster increased by 4.59 cases. Similarly, patients who experienced a slightly elevated body temperature or fever were associated with an increase of 2.37 and 0.35 cases in each cluster, respectively. Furthermore, increasing one new COVID-19 test per thousand population reduces 7.22 cases per cluster. Conclusions: The majority of reported cases in Taiwan were symptomatic. Symptoms which had the greatest number of patients overall were cough, fever, and nasal symptoms. It is our hope to help physicians to better diagnose current Taiwan COVID-19 patients, while aiding the government in stopping the spread of new cases.

Efficacy of the oral nucleoside prodrug GS-5245 (Obeldesivir) against SARS-CoV-2 and coronaviruses with pandemic potential (preprint)

Despite the wide availability of several safe and effective vaccines that can prevent severe COVID-19 disease, the emergence of SARS-CoV-2 variants of concern (VOC) that can partially evade vaccine immunity remains a global health concern. In addition, the emergence of highly mutated and neutralization-resistant SARS-CoV-2 VOCs such as BA.1 and BA.5 that can partially or fully evade (1) many therapeutic monoclonal antibodies in clinical use underlines the need for additional effective treatment strategies. Here, we characterize the antiviral activity of GS-5245, Obeldesivir (ODV), an oral prodrug of the parent nucleoside GS-441524, which targets the highly conserved RNA-dependent viral RNA polymerase (RdRp). Importantly, we show that GS-5245 is broadly potent in vitro against alphacoronavirus HCoV-NL63, severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV-related Bat-CoV RsSHC014, Middle East Respiratory Syndrome coronavirus (MERS-CoV), SARS-CoV-2 WA/1, and the highly transmissible SARS-CoV-2 BA.1 Omicron variant in vitro and highly effective as antiviral therapy in mouse models of SARS-CoV, SARS-CoV-2 (WA/1), MERS-CoV and Bat-CoV RsSHC014 pathogenesis. In all these models of divergent coronaviruses, we observed protection and/or significant reduction of disease metrics such as weight loss, lung viral replication, acute lung injury, and degradation in pulmonary function in GS-5245-treated mice compared to vehicle controls. Finally, we demonstrate that GS-5245 in combination with the main protease (Mpro) inhibitor nirmatrelvir had increased efficacy in vivo against SARS-CoV-2 compared to each single agent. Altogether, our data supports the continuing clinical evaluation of GS-5245 in humans infected with COVID-19, including as part of a combination antiviral therapy, especially in populations with the most urgent need for more efficacious and durable interventions.

The global COVID-19 vaccine surplus: tackling expiring stockpiles.

BACKGROUND: A global surplus of coronavirus disease 2019 (COVID-19) vaccines exists as a result of difficulties in aligning the demand and supply for vaccine manufacturing and delivery. World leaders have accelerated vaccine development, approval, production and distribution as a pragmatic approach to addressing the immediate public health challenges of the first two and a half years of the pandemic. MAIN BODY: The currently predominant, highly transmissible Omicron variant of severe acute respiratory syndrome coronavirus 2 has brought us closer to the threshold required to achieve herd immunity by greatly increasing rates of natural infection. Paradoxically, in parallel with rising vaccination levels in industrialized nations, this indirectly reduces the need for mass vaccine campaigns. Principal concerns that contribute to low vaccination rates which persist in several other countries, particularly of the Global South, are vaccine hesitancy and unequal access to vaccination. Social uncertainty fueled by fake news, misinformation, unfounded lay opinions and conspiracy theories has inevitably led to an erosion of public trust in vaccination. CONCLUSION: To address the current mismatch between supply and demand of COVID-19 vaccines, there should be a focus on three principles: decelerating vaccine production, increasing distribution across communities, and optimizing cost-effectiveness of distribution logistics. Slowing down and switching from large-scale production to effectively 'made to order' is a feasible option, which should be commensurate with management capacity. Transparent and evidence-based data should be widely and freely disseminated to the public through multimedia channels to mitigate miscommunication and conspiracy theories. Use of soon-to-expire stockpiles should be prioritized not only to enhance booster dose rollouts in adults but to expand immunization campaigns to children (especially those aged 5-11 years), subject to national approval. Future research should ideally aim to develop vaccines that only require basic, affordable storage and maintenance procedures as opposed to sophisticated and expensive protocols.

Telepharmacy: A Systematic Review of Field Application, Benefits, Limitations, and Applicability During the COVID-19 Pandemic.

Introduction: Telepharmacy is widely known as the delivery of pharmacy care offered by registered pharmacists and pharmacies using telecommunication technologies to patients at a distance. We conducted a systematic review of the reported usages, benefits, and limitations of telepharmacy models worldwide to further clarify the pros and cons of a telepharmacy model. Methods: A total of 39 relevant articles was included after searching for articles with a fixed term on four databases, including PubMed, Virtual Health Library (VHL), Global Health Library (GHL), and Google Scholar, as of April 2021. Results: Our review suggested that telepharmacy has played an essential role in addressing pharmacist shortages and helping patients both safely and effectively administer medications in underserved areas. During the COVID-19 pandemic, remote dispensing and counseling are effective measures to avoid infection. Conclusion: Telepharmacy could potentially replace or complement pharmaceutical-related activities, facilitating future innovation in the health care industry.

A robust Platform for Integrative Spatial Multi-omics Analysis to Map Immune Responses to SARS-CoV-2 infection in Lung Tissues (preprint)

The SARS-CoV-2 (COVID-19) virus has caused a devastating global pandemic of respiratory illness. To understand viral pathogenesis, methods are available for studying dissociated cells in blood, nasal samples, bronchoalveolar lavage fluid, and similar, but a robust platform for deep tissue characterisation of molecular and cellular responses to virus infection in the lungs is still lacking. We developed an innovative spatial multi-omics platform to investigate COVID-19-infected lung tissues. Five tissue-profiling technologies were combined by a novel computational mapping methodology to comprehensively characterise and compare the transcriptome and targeted proteome of virus infected and uninfected tissues. By integrating spatial transcriptomics data (Visium, GeoMx and RNAScope) and proteomics data (CODEX and PhenoImager HT) at different cellular resolutions across lung tissues, we found strong evidence for macrophage infiltration and defined the broader microenvironment surrounding these cells. By comparing infected and uninfected samples, we found an increase in cytokine signalling and interferon responses at different sites in the lung and showed spatial heterogeneity in the expression level of these pathways. These data demonstrate that integrative spatial multi-omics platforms can be broadly applied to gain a deeper understanding of viral effects on cellular environments at the site of infection and to increase our understanding of the impact of SARS-CoV-2 on the lungs.

Guillain-Barré syndrome after COVID-19 vaccination: report of two cases from Vietnam.

Coronavirus disease 2019 (COVID-19) was declared a pandemic by the World Health Organization in March 2020 and since then it has spread to almost every country around the world. Vaccines against COVID-19 are considered an essential measure to curb this pandemic. However, side effects, including local and systemic reactions, after administering the COVID-19 vaccine have been defined, and some side effects have been reported. We present two cases of Guillain-Barré Syndrome (GBS) after receiving the ChAdOx1 nCoV-19 vaccine (Oxford- AstraZeneca). Both cases were admitted to the 108 Military Central Hospital, Vietnam, and received plasmapheresis therapy with satisfactory recovery after treatment.

Tiredness, depression, and sleep disorders in frontline healthcare workers during COVID-19 pandemic in Vietnam: A field hospital study

Background The COVID-19 outbreak witnessed in the autumn of 2021 led to unprecedented changes in healthcare systems in some emerging countries. Many field-hospitals, temporary sites of care for COVID-19 patients, were built around the country and followed by the healthcare workers who were mobilized. This study aimed to measure sleep disorders, depression, and fatigue in volunteers working at field hospitals during the COVID-19 outbreak. Methods This was a cross-sectional study. The self-report questionnaire was used for each study subject. Sleep characters, including STOP's elements were questioned. Healthcare workers' burnout was detected by using Pichot's questionnaire. Results One hundred front-line healthcare workers (FHWs), predominantly last year and graduated medical students, were included in the study (86% female subjects). The mean sleep-time of FHWs before, while working, and during the isolation period after working at COVID-19 field hospitals were: 7.78 ± 1.48, 5.71 ± 1.40, and 8.78 ± 2.31 h per day, respectively. Burnout was not a crucial issue for these volunteer subjects. The mean scores of Pichot's Fatigue Scale and Pichot's Depression Scale, measured after 4 weeks working at field hospitals, were 4.18 ± 5.42 and 2.54 ± 3.36, respectively. Thirteen participants were suspected of depression. The fatigue scores decreased significantly in the group who claimed short sleep latency. The factor that increased the depression score was “anxious feeling” (p = 0.001). Other significant factors were “short sleep latency,” “observed sleep apnea,” “tiredness, daily sleepiness” and “snoring.” Conclusion Appropriate work schedule, better sleep conditions, and mental health support could be helpful for FHWs. The mandatory 2 weeks of isolation after working in field hospitals provided opportunity for FHWs' recovery.

Baseline Marine Litter Surveys along Vietnam Coasts Using Citizen Science Approach

Marine litter is a significant threat to the marine environment, human health, and the economy. In this study, beach litter surveys along Vietnamese coasts were conducted in a local context to quantify and characterize marine litter using the modified GESAMP marine litter monitoring guideline. A total of 21,754 items weighing 136,820.2 g was recorded across 14 surveys from September 2020 to January 2021. Plastic was the most abundant type of litter by both quantity (20,744 items) and weight (100,371.2 g). Fishing gear 1 (fishing plastic rope, net pieces, fishing lures and lines, hard plastic floats) and soft plastic fragments were the most frequently observed items (17.65% and 17.24%, respectively). This study not only demonstrates the abundance and composition of marine litter in Vietnam, it also provides valuable information for the implementation of appropriate preventive measures, such as the redesign of collection, reuse, and recycling programs, and informs policy and priorities, with a focus on action and investment in Vietnam. Moreover, insights from this study indicate that citizen science is a useful approach for collecting data on marine litter in Vietnam.

Potential inhibitors for SARS-CoV-2 Mpro from marine compounds† † Electronic supplementary information (ESI) available: Marine compounds and docking energy to SARS-CoV-2 Mpro, docked and MD-refined structures of SARS-CoV-2 Mpro + top-lead ligands, pulling force in displacement dependence over FPL simulations, the computational values using FPL simulations of available inhibitors, and ADME profile of potential compounds. See DOI: 10.1039/d1ra03852d

Preventing the biological activity of SARS-CoV-2 main protease using natural compounds is of great interest. In this context, using a combination of AutoDock Vina and fast pulling of ligand simulations, eleven marine fungi compounds were identified that probably play as highly potent inhibitors for preventing viral replication. In particular, four compounds including M15 (3-O-(6-O-α-l-arabinopyranosyl)-β-d-glucopyranosyl-1,4-dimethoxyxanthone), M8 (wailupemycins H), M11 (cottoquinazolines B), and M9 (wailupemycins I) adopted the predicted ligand-binding free energy of −9.87, −9.82, −9.62, and −9.35 kcal mol−1, respectively, whereas the other adopted predicted ligand-binding free energies in the range from −8.54 to −8.94 kcal mol−1. The results were obtained using a combination of Vina and FPL simulations. Notably, although, AutoDock4 adopted higher accurate results in comparison with Vina, Vina is proven to be a more suitable technique for rapidly screening ligand-binding affinity with a large database of compounds since it requires much smaller computing resources. Furthermore, FPL is better than Vina to classify inhibitors upon ROC-AUC analysis. Preventing the biological activity of SARS-CoV-2 main protease using natural compounds is of great interest.

IFI27 transcription is an early predictor for COVID-19 outcomes; a multi-cohort observational study (preprint)

Background. Robust biomarkers that predict disease outcomes amongst COVID19 patients are necessary for both patient triage and resource prioritisation. Numerous candidate biomarkers have been proposed for COVID19. However, at present, there is no consensus on the best diagnostic approach to predict outcomes in infected patients. Moreover, it is not clear whether such tools would apply to other potentially pandemic pathogens and therefore of use as stockpile for future pandemic preparedness. Methods. We conducted a multi cohort observational study to investigate the biology and the prognostic role of interferon alpha inducible protein 27 (IFI27) in COVID19 patients. Findings. We show that IFI27 is expressed in the respiratory tract of COVID19 patients and elevated IFI27 expression is associated with the presence of a high viral load. We further demonstrate that systemic host response, as measured by blood IFI27 expression, is associated with COVID19 severity. For clinical outcome prediction (e.g. respiratory failure), IFI27 expression displays a high positive (0.83) and negative (0.95) predictive value, outperforming all other known predictors of COVID19 severity. Furthermore, IFI27 is upregulated in the blood of infected patients in response to other respiratory viruses. For example, in the pandemic H1N1/09 swine influenza virus infection, IFI27 like genes were highly upregulated in the blood samples of severely infected patients. Interpretation. These data suggest that prognostic biomarkers targeting the family of IFI27 genes could potentially supplement conventional diagnostic tools in future virus pandemics, independent of whether such pandemics are caused by a coronavirus, an influenza virus or another as yet to be discovered respiratory virus.

A multi centre randomized open label trial of chloroquine for the treatment of adults with SARS-CoV-2 infection in Vietnam.

Background: COVID-19 is a respiratory disease caused by a novel coronavirus (SARS-CoV-2) and causes substantial morbidity and mortality. There is currently no vaccine to prevent COVID-19 or therapeutic agent to treat COVID-19. This clinical trial is designed to evaluate chloroquine as a potential therapeutic for the treatment of hospitalised people with COVID-19. We hypothesise that chloroquine slows viral replication in patients with COVID-19, attenuating the infection, and resulting in more rapid decline of viral load in throat/nose swabs. This viral attenuation should be associated with improved patient outcomes. Method: The study will start with a 10-patient prospective observational pilot study following the same entry and exclusion criteria as for the randomized trial and undergoing the same procedures. The main study is an open label, randomised, controlled trial with two parallel arms of standard of care (control arm) versus standard of care with 10 days of chloroquine (intervention arm) with a loading dose over the first 24 hours, followed by 300mg base orally once daily for nine days. The study will recruit patients in three sites in Ho Chi Minh City, Vietnam: the Hospital for Tropical Diseases, the Cu Chi Field Hospital, and the Can Gio COVID hospital. The primary endpoint is the time to viral clearance from throat/nose swab, defined as the time following randomization until the midpoint between the last positive and the first of the negative throat/nose swabs. Viral presence will be determined using RT-PCR to detect SARS-CoV-2 RNA. Discussion: The results of the study will add to the evidence-based guidelines for management of COVID-19. Given the enormous experience of its use in malaria chemoprophylaxis, excellent safety and tolerability profile, and its very low cost, if proved effective then chloroquine would be a readily deployable and affordable treatment for patients with COVID-19. Trial registration: Clinicaltrials.gov NCT04328493 31/03/2020.