An ACE2 decamer viral trap as a durable intervention solution for current and future SARS-CoV (preprint)

The capacity of SARS-CoV-2 to evolve poses challenges to conventional prevention and treatment options such as vaccination and monoclonal antibodies, as they rely on viral receptor binding domain (RBD) sequences from previous strains. Additionally, animal CoVs, especially those of the SARS family, are now appreciated as a constant pandemic threat. We present here a new antiviral approach featuring inhalation delivery of a recombinant viral trap composed of ten copies of angiotensin-converting enzyme 2 (ACE2) fused to the IgM Fc. This ACE2 decamer viral trap is designed to inhibit SARS-CoV-2 entry function, regardless of viral RBD sequence variations as shown by its high neutralization potency against all known SARS-CoV-2 variants, including Omicron BQ.1, BQ.1.1, XBB.1 and XBB.1.5. In addition, it demonstrates potency against SARS-CoV-1, human NL63, as well as bat and pangolin CoVs. The multivalent trap is effective in both prophylactic and therapeutic settings since a single intranasal dosing confers protection in human ACE2 transgenic mice against viral challenges. Lastly, this molecule is stable at ambient temperature for more than twelve weeks and can sustain physical stress from aerosolization. These results demonstrate the potential of a decameric ACE2 viral trap as an inhalation solution for ACE2-dependent coronaviruses of current and future pandemic concerns.

Seasonal Variation and Geographical Distribution of COVID-19 across Nigeria (March 2020–July 2021)

Globally, the novel corona virus infection has continued to witness a growing number of cases since December 2019 when the outbreak was discovered and noted in China. Despite this has not been well studied for the case of COVID-19, human contact, public moveableness and environmental variables could have an impact onairborne'spropagation and virus continuance, such as influenza virus. This study aimed to determine the seasonal variation and geographical distribution of COVID-19 across Nigeria. An internet based archival research design was employed for this study on the seasonal variation and geographical distribution of COVID-19 across Nigeria. This involved the use of goggle mobility data and world map on Corona Virus Infection (COVID-19). The search strategy for getting information for this research was done electronically. The keywords in the case search using the goggle mobility software was "COVID-19 Update”, "COVID-19 Update in Nigeria”, ‘COVID-19 Winter Report', "COVID-19 Case Fatality March 2020–July 2021”, "COVID-19 Case Fatality in Nigeria”. The data gotten from the goggle motor updates were entered into Statistical Package for the Social Sciences (SPSS) which was used in the analysis of the study. Results from the study, reported that official COVID-19 cases number was significantly higher in the Dry season (October 2020–April 2021) with 59.0% (127,213) compared to 41.0% (85,176) in the wet/rainy season (May–September) it revealed that the dry and rainy seasons had a COVID-19 prevalence of 0.063 and 0.041 respectively. Further results from the study showed that the prevalence of COVID-19 was 0.07% in the North-Central, 0.04% in both the North-East and North-West, 0.03% in the South-West, 0.09% in the South-South, and the highest prevalence of 0.16% in the South-East. Considering the case Fatality rate of COVID-19 during the Dry and Wet Seasons. The study revealed that North-Central had a death toll of 196 (10.4%) out of 9457 confirmed COVID-19 cases hence a fatality of 2.07. Fatality rate of 1.49% in South western Nigeria, South-South Nigeria, 1.49%, South-East accounted to a fatality rate of 1.25%. Nigeria based on the finding of this study records increased fatality in Dry season over wet seasons. The study concluded that prevalence of COVID-19 varies in seasons in Nigeria Hence;further Data and Meteorological analysis on weather variations towards the SARS-CoV-2 Virus spread should be evaluated by future researchers. It is imperative to ensure strict and controlled application of social measures, such as social distancing, mandatory wearing of non-medical masks to prevent droplets from entering the respiratory tract, screening of affected patients along with quarantine is essential to defeat and improve infection control.

Seasonal Variation and Geographical Distribution of COVID-19 across Nigeria (March 2020-July 2021).

Globally, the novel corona virus infection has continued to witness a growing number of cases since December 2019 when the outbreak was discovered and noted in China. Despite this has not been well studied for the case of COVID-19, human contact, public moveableness and environmental variables could have an impact onairborne'spropagation and virus continuance, such as influenza virus. This study aimed to determine the seasonal variation and geographical distribution of COVID-19 across Nigeria. An internet based archival research design was employed for this study on the seasonal variation and geographical distribution of COVID-19 across Nigeria. This involved the use of goggle mobility data and world map on Corona Virus Infection (COVID-19). The search strategy for getting information for this research was done electronically. The keywords in the case search using the goggle mobility software was "COVID-19 Update", "COVID-19 Update in Nigeria", 'COVID-19 Winter Report', "COVID-19 Case Fatality March 2020-July 2021", "COVID-19 Case Fatality in Nigeria". The data gotten from the goggle motor updates were entered into Statistical Package for the Social Sciences (SPSS) which was used in the analysis of the study. Results from the study, reported that official COVID-19 cases number was significantly higher in the Dry season (October 2020-April 2021) with 59.0% (127,213) compared to 41.0% (85,176) in the wet/rainy season (May-September) it revealed that the dry and rainy seasons had a COVID-19 prevalence of 0.063 and 0.041 respectively. Further results from the study showed that the prevalence of COVID-19 was 0.07% in the North-Central, 0.04% in both the North-East and North-West, 0.03% in the South-West, 0.09% in the South-South, and the highest prevalence of 0.16% in the South-East. Considering the case Fatality rate of COVID-19 during the Dry and Wet Seasons. The study revealed that North-Central had a death toll of 196 (10.4%) out of 9457 confirmed COVID-19 cases hence a fatality of 2.07. Fatality rate of 1.49% in South western Nigeria, South-South Nigeria, 1.49%, South-East accounted to a fatality rate of 1.25%. Nigeria based on the finding of this study records increased fatality in Dry season over wet seasons. The study concluded that prevalence of COVID-19 varies in seasons in Nigeria Hence; further Data and Meteorological analysis on weather variations towards the SARS-CoV-2 Virus spread should be evaluated by future researchers. It is imperative to ensure strict and controlled application of social measures, such as social distancing, mandatory wearing of non-medical masks to prevent droplets from entering the respiratory tract, screening of affected patients along with quarantine is essential to defeat and improve infection control.

Efficacy of intravenous vitamin C in management of moderate and severe COVID-19: A double blind randomized placebo controlled trial.

Aim: To study the efficacy of intravenous vitamin C in management of moderate and severe COVID-19. Objective: To determine the efficacy of intravenous vitamin C in reducing in-hospital mortality in moderate and severe cases of COVID-19. Design: Parallel, double-blinded randomized controlled trial with placebo. Ethical clearance was obtained from the institutional ethics committee, AIIMS Patna. The trial was registered with the Clinical Trials Registry - India (registration number- CTRI/2020/11/029230.). Setting: A tertiary care centre in Bihar, India. Participants: All patients above the age of 18 years both males and females, admitted in ICU with a diagnosis of moderate and severe COVID-19 (on the basis of a positive reverse transcriptase polymerase chain reaction (RT-PCR) report) at our facility during the study period (01/10/2020-31/12/2020) not having any of the exclusion criteria. Intervention: The patients in the intervention arm were given 1 gram (2 ampoules of 2 ml each containing 500 mg of vitamin C mixed in 100 ml normal saline) intravenous vitamin C 8 hourly for four days. The patients in the placebo arm received similar looking ampoules (2 ampoules of 2 ml sterile water for injection mixed in 100 ml normal saline) intravenously 8 hourly for four days. The rest of the treatment was given as per the standard operating procedure (SOP) of the institute with adjustments as per treating team's judgement. Outcome Measures: Primary outcome was reduction in in-hospital mortality. Secondary outcomes were improvement in qSOFA score, pO2/fiO2 ratio, fall in inflammatory markers, need for mechanical ventilation and vasopressors. Results: Regarding primary outcome, 10 (33.3%) patients died in intervention group compared to 13 (43.3%) in placebo. Worth noting from baseline characteristics is that 86.7% in intervention arm were of severe category compared to 66.7% severe category patients in placebo group. Though number of severe cases were more in intervention arm there has been comparatively less mortality in this group. Regarding secondary outcomes, amongst 30 patients in vitamin C group, 11 (36.7%) required invasive mechanical ventilation compared to 14 (46.7%) out of 30 in placebo group but the difference was not statistically significant. Although there were a greater number of moderate cases in placebo group, invasive ventilation requirement (and NIV requirement) was more in this group, thus it could be considered that vitamin C might have a role in reducing the severity of disease. The need for vasopressor therapy was higher in intervention arm 33.3% compared to 26.7% in placebo but not significant statistically. The secondary outcomes of the study such as improvement in organ failure score (qSOFA Score), fall in level of inflammatory markers, improvement in respiratory index (pO2/fiO2 ratio), need for mechanical ventilation and need for vasopressors also shown encouraging results but not up to the statistically significant level due to moderate dosage of the drug and small sample size. Conclusion: In the current study, by the observations and results of the double-blind placebo controlled randomised trial, we concluded that as the primary outcome of the study, there was reduction in In-hospital mortality and need for mechanical ventilation in the vitamin C intervention group compared to placebo, although these results did not reach statistical significance due to small sample size and use of moderate dose of IV vitamin C. The secondary outcomes of the study such as improvement in organ failure score (qSOFA Score), fall in level of inflammatory markers, improvement in respiratory index (pO2/fiO2 ratio), need for mechanical ventilation and need for vasopressors also shown encouraging results but not up to the statistically significant level due to moderate dosage of the drug and small sample size. In summary, high dose of intravenous vitamin C may reduce inflammatory reaction, improve oxygen support status, and reduce mortality in COVID-19 patients, without adverse events. High dose intravenous vitamin C may be a promising therapy for patients of moderate to severe COVID-19.

Association of COVID-19 with hepatic metabolic dysfunction.

The coronavirus disease 2019 (COVID-19) pandemic continues to be a global problem with over 438 million cases reported so far. Although it mostly affects the respiratory system, the involvement of extrapulmonary organs, including the liver, is not uncommon. Since the beginning of the pandemic, metabolic com-orbidities, such as obesity, diabetes, hypertension, and dyslipidemia, have been identified as poor prognostic indicators. Subsequent metabolic and lipidomic studies have identified several metabolic dysfunctions in patients with COVID-19. The metabolic alterations appear to be linked to the course of the disease and inflammatory reaction in the body. The liver is an important organ with high metabolic activity, and a significant proportion of COVID-19 patients have metabolic comorbidities; thus, this factor could play a key role in orchestrating systemic metabolic changes during infection. Evidence suggests that metabolic dysregulation in COVID-19 has both short- and long-term metabolic implications. Furthermore, COVID-19 has adverse associations with metabolic-associated fatty liver disease. Due to the ensuing effects on the renin-angiotensin-aldosterone system and ammonia metabolism, COVID-19 can have significant implications in patients with advanced chronic liver disease. A thorough understanding of COVID-19-associated metabolic dysfunction could lead to the identification of important plasma biomarkers and novel treatment targets. In this review, we discuss the current understanding of metabolic dysfunction in COVID-19, focusing on the liver and exploring the underlying mechanistic pathogenesis and clinical implications.

Protecting health care workers from COVID-19: implementing a training programme on personal protective equipment in Pakistan.

Background: Pakistan's Ministry of National Health Services, Regulations and Coordination, with support from the World Health Organization, developed and implemented the "We Care" programme to protect frontline health care workers engaged in the coronavirus disease 2019 (COVID-19) response. Aims: This paper reports on the training part of the programme, which aimed to train 100 000 frontline health care workers on the proper use of personal protective equipment (PPE) and on the lessons learnt from implementation of the training. Methods: A team of experts developed the curriculum and its accompanying material. Initial training was given to deans of all participating institutions and to master trainers from each university. Staff of all public and private hospitals enrolled in the training and other frontline health care workers were invited to register individually. Four types of educational material were produced and used a guidance booklet, a training video, a set of PowerPoint presentations to explain the PPE and their use, and a poster. Results: A total of 2000 training sessions were conducted across the country from May to December 2020 and 100 000 frontline health care workers were trained on the use of PPE. Of those trained, 25% were doctors, 35% were nurses and paramedics, and 40% were allied health staff, with an almost equal gender distribution. Conclusions: With limited resources and over a short period, the We Care programme trained a large number of frontline health care workers, which enhanced their safety and reduced the irrational use of PPE.

Psychological impact of COVID-19 and lock down measures: An online cross-sectional multicounty study on Asian university students.

The COVID-19 pandemic and the lockdown measures have taken a toll on every level of the society, worldwide. This study examines their psychological impact on university students in Asia. A cross-sectional online survey was conducted between April and May 2020 in Malaysia, Saudi Arabia, Pakistan, Bangladesh, China, India and Indonesia. The Zung's self-rating anxiety scale (SAS) and questions on adaptive and maladaptive coping strategies were used in this study. A total of 3,679 students from the seven countries participated in this study. Overall, 21.9% and 13.7% of the students in this study experienced mild to moderate and severe to extreme levels of anxiety. More than 20% of the students from China and Bangladesh reported severe to extreme level of anxiety compared to below 10% of the students from Indonesia, Malaysia and India. Among the female students, 15.9% experienced severe to extreme level of anxiety compared to 10.6% among the males. Females from Bangladesh, China, Malaysia, Pakistan and Saudi Arabia experienced significantly higher levels of anxiety compared to their male counterparts. Acceptance was the most used and Seeking Social Support was the least used coping strategies among the students. There were significant differences in the usage of the four strategies by countries. Stressors are predominantly financial constraints, remote online learning, and uncertainty related to their academic performance, and future career prospects.

Forecasting daily new infections, deaths and recovery cases due to COVID-19 in Pakistan by using Bayesian Dynamic Linear Models.

The COVID-19 has caused the deadliest pandemic around the globe, emerged from the city of Wuhan, China by the end of 2019 and affected all continents of the world, with severe health implications and as well as financial-damage. Pakistan is also amongst the top badly effected countries in terms of casualties and financial loss due to COVID-19. By 20th March, 2021, Pakistan reported 623,135 total confirmed cases and 13,799 deaths. A state space model called 'Bayesian Dynamic Linear Model' (BDLM) was used for the forecast of daily new infections, deaths and recover cases regarding COVID-19. For the estimation of states of the models and forecasting new observations, the recursive Kalman filter was used. Twenty days ahead forecast show that the maximum number of new infections are 4,031 per day with 95% prediction interval (3,319-4,743). Death forecast shows that the maximum number of the deaths with 95% prediction interval are 81 and (67-93), respectively. Maximum daily recoveries are 3,464 with 95% prediction interval (2,887-5,423) in the next 20 days. The average number of new infections, deaths and recover cases are 3,282, 52 and 1,840, respectively, in the upcoming 20 days. As the data generation processes based on the latest data has been identified, therefore it can be updated with the availability of new data to provide latest forecast.

Role of Host-Mediated Post-Translational Modifications (PTMs) in RNA Virus Pathogenesis.

Being opportunistic intracellular pathogens, viruses are dependent on the host for their replication. They hijack host cellular machinery for their replication and survival by targeting crucial cellular physiological pathways, including transcription, translation, immune pathways, and apoptosis. Immediately after translation, the host and viral proteins undergo a process called post-translational modification (PTM). PTMs of proteins involves the attachment of small proteins, carbohydrates/lipids, or chemical groups to the proteins and are crucial for the proteins' functioning. During viral infection, host proteins utilize PTMs to control the virus replication, using strategies like activating immune response pathways, inhibiting viral protein synthesis, and ultimately eliminating the virus from the host. PTM of viral proteins increases solubility, enhances antigenicity and virulence properties. However, RNA viruses are devoid of enzymes capable of introducing PTMs to their proteins. Hence, they utilize the host PTM machinery to promote their survival. Proteins from viruses belonging to the family: Togaviridae, Flaviviridae, Retroviridae, and Coronaviridae such as chikungunya, dengue, zika, HIV, and coronavirus are a few that are well-known to be modified. This review discusses various host and virus-mediated PTMs that play a role in the outcome during the infection.

The Indian perspective of COVID-19 outbreak.

The emerging infection of COVID-19 was initiated from Wuhan, China, have been spread to more than 210 countries around the globe including India. The clinical symptoms of COVID-19 are very similar to other respiratory viruses. The number of laboratory-confirmed cases and associated deaths are increasing regularly in various parts of the World. Seven coronaviruses (229E, NL63, OC43, HKU1, SARS, MERS and, COVID-19) can naturally infect human beings. Out of these four (229E-CoV, NL63-CoV, OC43-CoV, HKU1-CoV) are responsible for mild upper respiratory infections, while SARS-CoV, MERS-CoV, and COVID-19 are well known for their high mortality. Few mild strains of coronaviruses are circulating in India but there is no evidence of SARS and MERS outbreaks. The COVID-19 is an emerging viral infection responsible for pandemics. Fortunately, the mortality of COVID-19 is low as compared with SARS and MERS, the majority of its cases are recovered. The death toll of COVID-19 is high even after its low mortality because COVID-19 causes a pandemic while SARS-CoV and MERS-CoV cause epidemics only. COVID-19 influenced the large segments of the world population, which led to a public health emergency of international concern, putting all health organizations on high alert. COVID-19 is the first coronavirus after Spanish Flu 1918-1919, who has extremely influenced the health system, economy, and psychology of India. The present study review is on the general continent, virology, pathogenesis, global epidemiology, clinical presentation, diagnosis, treatment and control of COVID-19 with the reference to India.

Outcome of Conservative Therapy in Coronavirus disease-2019 Patients Presenting With Gastrointestinal Bleeding.

BACKGROUND/OBJECTIVE: There is a paucity of data on the management of gastrointestinal (GI) bleeding in patients with Coronavirus disease -2019 (COVID-19) amid concerns about the risk of transmission during endoscopic procedures. We aimed to study the outcomes of conservative treatment for GI bleeding in patients with COVID-19. METHODS: In this retrospective analysis, 24 of 1342 (1.8%) patients with COVID-19, presenting with GI bleeding from 22nd April to 22nd July 2020, were included. RESULTS: The mean age of patients was 45.8 ± 12.7 years; 17 (70.8%) were males; upper GI (UGI) bleeding: lower GI (LGI) 23:1. Twenty-two (91.6%) patients had evidence of cirrhosis- 21 presented with UGI bleeding while one had bleeding from hemorrhoids. Two patients without cirrhosis were presumed to have non-variceal bleeding. The medical therapy for UGI bleeding included vasoconstrictors-somatostatin in 17 (73.9%) and terlipressin in 4 (17.4%) patients. All patients with UGI bleeding received proton pump inhibitors and antibiotics. Packed red blood cells (PRBCs), fresh frozen plasma (FFPs) and platelets were transfused in 14 (60.9%), 3 (13.0%) and 3 (13.0%), respectively. The median PRBCs transfused was 1 (0-3) unit(s). The initial control of UGI bleeding was achieved in all 23 patients and none required an emergency endoscopy. At 5-day follow-up, none rebled or died. Two patients later rebled, one had intermittent bleed due to gastric antral vascular ectasia, while another had rebleed 19 days after discharge. Three (12.5%) cirrhosis patients succumbed to acute hypoxemic respiratory failure during hospital stay. CONCLUSION: Conservative management strategies including pharmacotherapy, restrictive transfusion strategy, and close hemodynamic monitoring can successfully manage GI bleeding in COVID-19 patients and reduce need for urgent endoscopy. The decision for proceeding with endoscopy should be taken by a multidisciplinary team after consideration of the patient's condition, response to treatment, resources and the risks involved, on a case to case basis.

Poor outcomes in patients with cirrhosis and Corona Virus Disease-19.

BACKGROUND AND AIM: There is a paucity of data on the clinical presentations and outcomes of Corona Virus Disease-19 (COVID-19) in patients with underlying liver disease. We aimed to summarize the presentations and outcomes of COVID-19-positive patients and compare with historical controls. METHODS: Patients with known chronic liver disease who presented with superimposed COVID-19 (n = 28) between 22 April 2020 and 22 June 2020 were studied. Seventy-eight cirrhotic patients without COVID-19 were included as historical controls for comparison. RESULTS: A total of 28 COVID-19 patients (two without cirrhosis, one with compensated cirrhosis, sixteen with acute decompensation [AD], and nine with acute-on-chronic liver failure [ACLF]) were included. The etiology of cirrhosis was alcohol (n = 9), non-alcoholic fatty liver disease (n = 2), viral (n = 5), autoimmune hepatitis (n = 4), and cryptogenic cirrhosis (n = 6). The clinical presentations included complications of cirrhosis in 12 (46.2%), respiratory symptoms in 3 (11.5%), and combined complications of cirrhosis and respiratory symptoms in 11 (42.3%) patients. The median hospital stay was 8 (7-12) days. The mortality rate in COVID-19 patients was 42.3% (11/26), as compared with 23.1% (18/78) in the historical controls (p = 0.077). All COVID-19 patients with ACLF (9/9) died compared with 53.3% (16/30) in ACLF of historical controls (p = 0.015). Mortality rate was higher in COVID-19 patients with compensated cirrhosis and AD as compared with historical controls 2/17 (11.8%) vs. 2/48 (4.2%), though not statistically significant (p = 0.278). Requirement of mechanical ventilation independently predicted mortality (hazard ratio 13.68). Both non-cirrhotic patients presented with respiratory symptoms and recovered uneventfully. CONCLUSION: COVID-19 is associated with poor outcomes in patients with cirrhosis, with worst survival rates in ACLF. Mechanical ventilation is associated with a poor outcome.

COVID-19 diagnostic approaches: different roads to the same destination.

"SARS-CoV2", a previously unknown strain of coronaviruses caused a severe respiratory disease called Coronavirus disease (COVID-19) which emerged from Wuhan city of China on 30 December 2019, and declared as Global health problem by World Health Organisation within a month. In less than two and half months (11 March, 2020) it was declared as a pandemic disease due to its rapid spreading ability, it covered more than 211 countries infecting around 1.7 million persons and claiming around 1.1 lakhs lives within merely 100 days of its emergence. Containment of the infection of this virus is the only available measure to control the disease as no vaccine or specific antiviral treatment is available. Confirmed detection of the virus followed by isolation of the infected person at the earliest possible is the only measure to prevent this disease. Although there are number of methods available for detection of virus and to combat this disease in the present pandemic situation, but these available diagnostic methods have their own limitations. The speedy and exponential global spread of this disease strongly urges the fast and economic diagnostics tools. Additional to the available diagnostic methods, there is a sudden surge for development of various of methods and platforms to diagnose the COVID-19. The review summarized the advantage and disadvantage of various diagnostic approaches being used presently for COVID-19, newer detection methods in developmental stage and the feasibility of advanced platforms like newer nano-sensor based on-the-spot detection technologies.