An overview of severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2): Pathophysiology, diagnosis, and management tactics

The World Health Organization (WHO) declared an international public health concern on January 30, 2020, in response to the idiopathic Coronavirus disease 2019 (COVID-19) pandemic outbreak. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of the disease being identified as the third human Coronavirus, was discovered in Wuhan, Hubei Province, China. Coronavirus belongs to the Coronaviridae family, Coronavirinae subfamily which according to their genetic structures, are grouped into alphaCoronavirus (aCoV), betaCoronavirus (bCoV), gamma Corona¬virus (yCoV) and deltaCoronavirus (dCoV) of order Nidovirales. Coronaviruses are enveloped, positive-sense, single-stranded RNA viruses invading a wide variety of host species. SARS-CoV-2 belongs to extensively. Angiotensin¬converting enzyme 2 (ACE2) is imperative for Novel SARS-CoV-2 to enter host cells as a substrate receptor. With a high mortality rate in the elderly, immune-compromised, diabetic, and patients with cardiovascular and respiratory diseases, COVID-19 is an extremely contagious disease. Patients who are afflicted experience fever, a nonproductive cough, lethargy, dyspnea, and occasionally diarrhoea as well as radiographic signs of pneumonia. A cytokine storm is a result of the immune system's aggressive response to a virus that has propagated inside the body. Genetic recombination and mutation are the main drivers of the emergence of novel SARS-CoV-2 variants. Variants of concern (VOCs) are used to describe some variants having significant virulence and transmission rates, such as the Omicron variants now. RT-LAMP, RT- qPCR, and High-Resolution Computed Tomography, among other new cutting-edge techniques, are effective at diagnosing SARS-CoV-2 infected patients. Standard treatments involving compounds like Lopinavir/Ritonavir, paxlovid, and molnupiravir have shown to be efficacious to some extent against even the newly emerging strains when it comes to treatment approaches. Additionally, immunization is a crucial strategy for preventing the disease or lessening its impact. Live attenuated vaccines, DNA- and RNA-based vaccines, protein subunit vaccines, and amplifying viral vector vaccines are among the molecular frameworks used in the production of vaccines against SARS-CoV-2. Comirnaty by Pfizer-BioNTech, SpikeVax by Moderna, and Vaxzevria by Oxford- AstraZeneca are three extensively incorporated and validated COVID-19 vaccines. In a similar vein, a variety of vaccinations have been created with varying degrees of potency against VOCs. Nanotechnology and artificial intelligence (AI) advancements may help in the provision of an effective and dependable remedy for the eradication of SARS-CoV-2. Definitive diagnosis, community engagements, and united scientific approaches have effectively addressed public health issues amid the pandemic. Although COVID-19 has presented a significant challenge to the healthcare system, it has also provided a chance for the development of novel and creative roles that could have significant effects on the healthcare system. This pandemic has highlighted the value of prompt diagnosis, the value of universal healthcare as well as the need for cutting-edge methods to contain pandemics around the world. © 2023 Nova Science Publishers, Inc. All rights reserved.

EFFICACY AND SAFETY OF COVID-19-SPECIFIC TREATMENTS IN SLE: A MULTICENTRE CASE-CONTROL STUDY

BackgroundCOVID-19 is associated with higher morbidity and mortality burdens in immunocompromised individuals, including patients with systemic lupus erythematosus (SLE;1). These patients might benefit from treatment with anti-SARS-CoV-2-specific antiviral agents and monoclonal antibodies, but clinical evidence is to date limited.Objectivesto comparatively assess the course of COVID-19 in patients with SLE treated or untreated with COVID-19-specific agents.MethodsPatients with SLE and COVID-19 treated with antivirals and/or monoclonal antibodies from February 2020 to December 2022 were identified within a three-centre cohort of tertiary referral centres and age-, sex- SLE extension- and SLE duration-matched 1:2 with patients with a history of untreated COVID-19. Data on COVID-19 presentation, course (including time to viral clearance) and sequelae, along with SLE treatment at COVID-19 onset and SLE course after COVID-19 were collected. COVID-19 severity at presentation was quantitated through a 0-4 analogue scale [2]. Data are expressed as median (interquartile range, IQR) unless otherwise specified.ResultsOver three years, 39% of patients with SLE had at least one COVID-19 event. Eighteen subjects (16 women) were treated with antivirals (n=12) or monoclonal antibodies (n=6) and were matched with 36 controls. There was no difference in the frequency of organ involvement between the two groups. Treated patients were receiving significantly higher prednisone daily doses at COVID-19 onset (6.25 (0-10) vs 0 (0-2.5) mg;p=0.005) and had a higher prevalence of previous high-dose steroid treatments (83% vs 47%;p=0.019) compared to controls. SLE disease activity index (3 (0-5) vs 1 (0-4)) and SLE International Collaborating Clinics Damage Index scores (1 (0-3) vs 0 (0-1)) were also numerically higher in treated patients at COVID-19 onset. Patients in the treated group had more severe COVID-19 at presentation but showed no significant differences with control subjects in terms of COVID-19 resolution, prevalence of sequelae and viral clearance (Table 1). There was also no difference in flare occurrence between the two groups (Log-rank=0.02, p=0.889). Two patients reported mild adverse events with monoclonal antibodies (muscle cramps and chest pain, both self-resolving).ConclusionThese data support the safe use of COVID-19 specific treatments in patients with SLE. Patients treated with antivirals and monoclonal antibodies had a favourable COVID-19 course, despite a more severe presentation and a higher risk of deterioration due to SLE and corticosteroid treatment burden, suggesting the potential efficacy of COVID-specific treatments in preventing severe COVID-19 in patients with SLE.References[1]Strangfeld A et al, Ann Rheum Dis, 2021[2]World Health Organization. Clinical management of COVID-19;Interim guidance 27 May 2020.Table 1.COVID-19 presentation and courseTreated (n=18)Untreated (n=36)Number of vaccine doses3 (2-3)3 (2-3)Time from last vaccine administration (days)118 (53-184)134 (30-210)COVID-19 featuresWHO class at presentation1 (1-1)**0 (0-1)Symptoms at presentation: n(%)Dyspnoea3 (17)3 (8)Fever10 (56)22 (61)Upper Respiratory Symptoms16 (89)29 (81)GI symptoms1 (6)2 (6)Pneumonia3 (17)3 (8)COVID-19 courseTime to symptom resolution (days)5 (4-8)7 (3-8)Time to viral clearance (days)10 (7-14)9 (7-14)Any complication: n(%)1 (6)6 (17)Hospitalisations: n(%)1 (6)0 (0)Long COVID: n(%)3 (17)6 (17)Deaths: n(%)0 (0)1 (3)AcknowledgementsWe thank Dr. Giordano Vitali and his staff for assisting and treating patients with SLE and COVID-19 from IRCCS San Raffaele Hospital in the local mild COVID-19 clinic.Disclosure of InterestsGiuseppe Alvise Ramirez Consultant of: Astrazeneca, Maria Gerosa: None declared, Daniel Arroyo-Sánchez: None declared, Chiara Asperti: None declared, Lorenza Maria Argolini: None declared, Gabriele Gallina: None declared, Chiara Bellocchi: None declared, Martina Cornalba: None declared, Isabella Scotti: None declared, Ilaria Suardi: None declared, Lorenzo Beretta: None declared, Luca Moroni Consultant of: strazeneca, Enrica Bozzolo: None declared, Roberto Caporali Speakers bureau: AbbVie, Amgen, BMS, Celltrion, Fresenius, Galapagos, Janssen, Lilly, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Fresenius, Galapagos, Lilly, Novartis, Pfizer, and UCB, Lorenzo Dagna Consultant of: Abbvie, Amgen, Astra-Zeneca, Biogen, Boehringer-Ingelheim, Bristol-Myers Squibb, Celltrion, Eli Lilly and Company, Galapagos, GlaxoSmithKline, Janssen, Kiniksa Pharmaceuticals, Novartis, Pfizer, Roche, Sanofi-Genzyme, Swedish Orphan Biovitrium (SOBI), and Takeda, Grant/research support from: Abbvie, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Kiniksa, Merk Sharp & Dohme, Mundipharma Pharmaceuticals, Novartis, Pfizer, Roche, Sanofi-Genzyme, and SOBI.

Effectiveness of ivermectin and atazanavir on time to resolution from COVID-19 symptoms: a prospective cohort

Objective: to evaluate the effectiveness of Ivermectin and Atazanavir compared to placebo in the time to resolution of symptoms and duration of illness due to COVID-19. Method: observational, prospective, longitudinal, descriptive and analytical cohort study with symptomatic outpatients, followed for 06 months in two Basic Health Units for COVID-19 care in Teresina-Piaui, Brazil, from November to April 2021 identified by 1:1:1 random sampling. Reverse transcription polymerase chain reaction (RT-PCR) tests were performed for laboratory confirmation of suspected infection with the new coronavirus and sociodemographic and clinical evaluation. Results: of the 87 randomized patients, 62.1% (n=54) were male, with a mean age of 35.1 years, had a partner (53.9%), low income (50.6%), eutrophic (40.7%) and without health comorbidities (78.2%). There was no difference between the median time to resolution of symptoms, which was 21 days (IQR, 8-30) in the atazanavir group, 30 days (IQR, 5-90) in the ivermectin group compared with 14 days (IQR, 9-21) in the control group. At day 180, there was resolution of symptoms in 100% in the placebo group, 93.9% in the atazanavir group, and 95% in the ivermectin group. The median duration of illness was 8 days in all study arms. Conclusion: Treatment with atazanavir (6 days) and ivermectin (3 days) did not reduce the time to symptom resolution or the duration of illness among outpatients with mild COVID-19 compared to the placebo group. The results do not support the use of ivermectin and atazanavir for the treatment of mild to moderate COVID-19.

Assessing the clinical manifestations, laboratory and radiological findings of hospitalization of pediatrics patients with COVID-19 in pediatric hospital of Amirkola, Babol

Variant Omicron was discovered as a newest severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The first emergence of the omicron variant was detected in November 2021. In this study, we investigated the clinical manifestation, laboratory and radiological findings and responding to treatment of 70 pediatric patients with positive RT- PCR COVID-19 in Omicron peak. We described 20 criteria associated with efficacy, such as demographic data, clinical manifestation, laboratory and radiological findings. All of the patients received Remdesivir that 5.7% of patients responded to the treatment. No patients were given Intravenous Immunoglobulin (IVIG). This is the first study aimed at assessing symptoms clinical manifestation among hospitalization pediatrics patients in pediatric Hospital of Amir kola, Babol. The findings of this study can be effective in preventing and controlling disease transmission among children.

Postnatal SARSCOV2 Infection in Neonates, Characteristics and Outcomes: An Observational Study

Background: Many aspects of the severe acute respiratory syndrome coronavirus 2 (SARSCoV2) pandemic in 2019 have been unclear, especially in newborns, and reports of neonatal diseases are usually associated with perinatal infection. Objective(s): The purpose of this study was to evaluate clinical and para-clinical manifestations in newborns that contracted the infection after birth. Method(s): This observational research was conducted from October 2020 to March 2022 to examine postnatal SARSCoV2 infection in infants admitted to the NICU or neonatal ward at the Children's Medical Center in Tehran, Iran. Inclusion in the study was open to neonates who had positive RT-PCR results postnatally. Result(s): In total, 55 newborns were confirmed to have postnatal SARSCOV2. Fever was the most frequently observed symptom, with 35 (61%). Necrotizing enterocolitis was seen in 18% of neonates, and 30% of them were preterm. Neutropenia was seen in 34% of cases, with five cases having severe neutropenia. All neonates had a normal platelet count. Twenty percent of patients showed C-reactive protein higher than 6 mg/L. Two newborns had co-existing bacterial urinary tract infections. Our neonates didn't require antiviral, anticoagulant, or corticosteroid medications, and they recovered while receiving only supportive care. Everyone in the group of newborns was discharged without complications, and there were no deaths. Conclusion(s): The high rate of fever, high C-reactive protein, and neutropenia in SARSCoV2 neonates suggests that more observational research is needed to compare these symptoms to bacterial sepsis to avoid the overuse of antibiotics in these patients.Copyright © 2023, Author(s).

CLINICAL COURSE IN COVID 19 DISEASE IN IMMUNOSUPRESSED PATIENTS DIAGNOSED WITH RHEUMATIC DISEASES

BackgroundPatients with pre-existing rheumatic diseases may be exacerbated during SARS-CoV-2 infection, or may develop new autoimmune features. Furthermore, immunosuppressive agents used to treat autoimmunity-inflammation as well as comorbidities can also affect the disease outcome.ObjectivesTo evaluate the outcome of rheumatic diseases after Covid 19 infection in patients diagnosed with rheumatic diseases, under various immunosuppressive treatment, as well as the effects of vaccines against Covid or antiviral treatment in this sensitive population group.MethodsDuring the pandemic, 1493 patients with autoimmune or autoinflammatory disease who were continuously followed up in two tertiaries hospitals in northern and northwestern Greece were included in the current study. The patients were compared with 769 controls after adjustment for age, sex, weight, vaccination status and comorbidities. Of the 1493 patients, 648 had rheumatoid arthritis, 282 psoriatic arthritis, 173 ankylosing spondylitis, 122 systemic lupus erythematosus, 98 Sjogren's syndrome, 43 polymyalgia rheumatica, 34 mixed connective tissue disease or overlapping syndromes, 31 vasculitis, 27 systemic sclerosis, 18 myositis, 10 Behcet syndrome, 5 primary antiphospholipid syndrome and 2 had Familial Mediterranean Fever. The vast majority of patients and controls were fully vaccinated (82%) and 397 patients received antiviral treatment, 94% of them were fully vaccinated.ResultsCovid 19 disease in vaccinated patients with rheumatic diseases was shown to perform the same or about the same as those in the control group after adjustment for risk factors for severe disease. 19 of our patients required admission in the intensive care unit (62% full vaccinated) while a total of 12 died (66% non vaccinated). Major risk factors for severe disease were previous respiratory failure, chronic renal impairment, obesity, and failure to receive antiviral therapy. It was also shown that infection with Covid led to an exacerbation or induction of autoimmune disorders in 25 of the participants.ConclusionIn this large cohort, Covid 19 disease was shown to affect patients with autoimmune rheumatic diseases the same or approximately the same way as the general population if they are fully vaccinated and if they start timely antiviral treatment where indicated. Further research and monitoring of the results after the multiple mutations of the virus is advisable.ReferencesNone.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Individual intensive nursing care plan for pseudomembranous colitis due to antibiotic treatment of COVID-19

In recent years, a number of complications have been observed as a result of uncontrolled antibiotic treatment. One of them is gastrointestinal dysbiosis. Not infrequently it is the cause of pseudomembranous colitis, a disease with a remarkably high associated mortality. It can be severe and requires serious medical care. This report presents a clinical case of a patient who developed the disease pseudomembranous colitis after antibiotic treatment for a Covid infection. The aim of the report is to define and present in a systematized manner the nursing care provided in the specific case. The daily analysis of the patient's condition allows to offer complex, adequate and individual nursing care, which, in addition to meeting her needs, also aims to alleviate her condition.

Preparing for the next viral threat with broad-spectrum antivirals

There is a large global unmet need for the development of countermeasures to combat hundreds of viruses known to cause human disease and for the establishment of a therapeutic portfolio for future pandemic preparedness. Most approved antiviral therapeutics target proteins encoded by a single virus, providing a narrow spectrum of coverage. This, combined with the slow pace and high cost of drug development, limits the scalability of this direct-acting antiviral (DAA) approach. Here, we summarize progress and challenges in the development of broad-spectrum antivirals that target either viral elements (proteins, genome structures, and lipid envelopes) or cellular proviral factors co-opted by multiple viruses via newly discovered compounds or repurposing of approved drugs. These strategies offer new means for developing therapeutics against both existing and emerging viral threats that complement DAAs.

The effects of COVID-19 on the water sector

The COVID-19 pandemic affected public health, economy, social life, and the environment. It infected and killed millions of people around the world. Most of the recent literature has focused on the medications to combat this virus, including antivirals and vaccines, but studies about its effect on the environment are still rare, particularly on the water sector. Most of the studies concentrate on the effect of water availability on COVID-19, the effect of the used medications on the water, and the probability of transmission of SARS-CoV-2 through water. Herein, we have summarized the effects of COVID-19 on the water sector from many perspectives. We show different methods to detect the effect of the pandemic on water and also methods to investigate the presence of the virus or its RNA in the water. We also show the different effects of its presence in the wastewater, the probability of transmission, the detection of different variants, and the prediction of new waves. We also show the disadvantages and advantages of the pandemic in the water sector. We finally suggest some recommendations to face this pandemic and the future pandemics for the governments and water policymakers, water treatment plants, general population, and researchers. The aim of this review is to show the different aspects of the pandemic in order to give a general idea about what must be done in order to minimize its effect and any probable pandemic in the future.

The effect of hydroxychloroquine in COVID-19 patients who did not receive corticosteroids

Background and Objective: At the beginning of the pandemic, Hydroxychloroquine (HCQ) was one of the most widely used drugs prescribed to patients admitted to hospitals with coronavirus disease 2019 (COVID-19). We try to find the effect of HCQ on the severity and mortality of patients who did not receive corticosteroids. Methods: In this retrospective study, patients with COVID-19 disease were collected from February 20, 2020, to July 21, 2020, at Rouhani Hospital in Babol. Patients were followed up until December 6, 2021. In this study, 170 patients in case and control groups were studied. We used logistic and COX regression models to explore the effects of drugs. Data were analyzed by SPSS version 22. Findings: The use of HCQ did not affect mortality (p=0.46, 95%CI= 0.63 to 2.71, OR= 1.31) and final severity (p= 0.75, 95%CI= 0.59 to 2.06, OR= 1.10) at admission time. However, azithromycin remained in the final model but did not have a significant effect (P= 0.08, HR= 0.28, 95%CI= 0.06 to 0.18). Heparin use was not associated with severity improvement (p= 0.06, 95%CI= 0.97 to 2.81, HR= 1.65), while ceftriaxone remained a factor affecting severity in the model (p = 0.03, 95% CI= 0.29 to 0.95, HR = 0.52). Conclusion: In this study, HCQ harmed mortality admission time and was ineffective in the long term. The use of ceftriaxone compared to other drugs showed protective effects against the mortality hospitalization time. Heparin is not recommended without considering the risk of bleeding in COVID-19 patients.

Retrospective nested study of demographic characteristics, lethality and discharge rate of COVID-19 inpatients in central south of Bulgaria

Introduction: SARS-CoV-2 infection has affected more than 683 million people worldwide with 6.8 million deaths. Unfortunately, Bulgaria is one of the most severely affected European Union (EU) member-states with one of the highest mortality rates. Aim: The study aims to provide a description of the demographic characteristics, discharge rate, and fatality rate of COVID-19-diagnosed patients in one region of Central South Bulgaria in 2021. Materials and methods: A retrospective nested case series study was conducted among patients hospitalized with a confirmed diagnosis of SARS-CoV-2 infection between January 1st and December 31st, 2021. Anonymized patient data on age, sex, admission and discharge dates, treatment, and the outcome was collected from hospital electronic patient records and analyzed using descriptive statistics. Results: Data from 1630 (51% male) patients were identified. The mean age was 63.64 years (+or-15.23). 1342 (82%) of the patients were discharged. The mean age of the diseased was 70.88 years (+or-10.05). 1455 (89%) patients received only symptomatic therapy, 155 (10%) patients were treated with remdesivir (VekluryR), 11 (1%) patients were treated with casirivimab/imdevimab (RonapreveR) and 9 (1%) patients were administered regdanvimab (RegkironaR). Conclusions: The study results demonstrate that Bulgarian patients with COVID-19 were treated according to the best global and national evidencebased guidelines. Lethality and discharge rates are in concordance with global trends and outcomes.

PRE-EXPOSURE PROPHYLAXIS WITH TIXAGEVIMAB/CILGAVIMAB: SINGLE CENTRE EXPERIENCE IN A COHORT OF RHEUMATIC PATIENTS

BackgroundVaccination against SARS-CoV2 had a critical role in the fight against COVID19 pandemic.A weaker humoral response to COVID19 vaccine has been found in rheumatic patients treated with Rituximab (RTX) or Mycophenolate Mofetil (MMF)[1]. Despite the evidence that anti-SARS-CoV-2 mRNA vaccines can elicit a T-cell response [2], some data show that even the cellular immunity could be impaired in rheumatic patients [3] but COVID19 serology is the only parameter that is feasible to measure in daily practice.Tixagevimab+cilgavimab are two human-derived monoclonal antibodies administered parenterally and authorized by regulatory agencies in February 2022 for pre-exposure prophylaxis (PrEP) against COVID19 from different virus variants in fragile patients.ObjectivesTo demonstrate safety and effectiveness of tixagevimab+cilgavimab.MethodsPatients with autoimmune rheumatic diseases undergoing immunosuppressive treatment with RTX or MMF during the vaccination campaign were enrolled between April and June 2022. All patients must have anti-spike antibody levels below the protective threshold (defined by anti-spike IgG titre <250 BAU/ml) after receiving at least 2 vaccine doses.Patients were monitored with a questionnaire every month about COVID19 symptoms (including respiratory and gastrointestinal symptoms, anosmia and ageusia, skin rash and potential contact with COVID19+ subjects) and were checked for anti-spike and anti-nucleocapside antibodies titres every 2 months for a total of a 6 month follow-up. MMF dose was reduced at 1 g/die at the time of vaccine administration.ResultsFifteen patients were enrolled: 9 participants had a connective tissue disease (CTD;1 dermatomyositis, 3 anti-syntethase syndrome, 4 systemic sclerosis, 1 systemic lupus erythematosus) and 6 had vasculitis (all granulomatosis with polyangiitis). 12 of them received RTX in the preceding 12 months and 3 were taking MMF.About safety, the therapy was very well tolerated and only 4 patients (26%) reported a non-severe adverse event in the 2 weeks following drug administration (2 myalgia, 1 headache, 1 fatigue), none of them requiring hospitalization nor pharmacologic treatment.Regarding effectiveness, 3/15 patients contracted SARS-Cov2 infection (20%) with mild symptoms and no need for hospitalization nor oxygen therapy. Only 1 of them received an antiviral drug (nirmatrelvir+ritonavir). All infected patients had a CTD diagnosis. No significant correlation was observed between the type of rheumatic disease and the risk of infection or response to tixagevimab+cilgavimab.ConclusionNone of our patients developed severe adverse events after tixagevimab+cilgavimab administration and, among the 3 SARS-CoV2 infected patients, none required hospitalization nor oxygen therapy.We conclude that in our experience tixagevimab+cilgavimab is a safe and useful complementary immunization strategy to vaccination for COVID19 prophylaxis.These data will be implemented in a larger study, comprehending various immunocompromised patients from several departments.References[1] Furer et al., Ann Rheum Dis, 2021[2] Mangalakumari et al., Nat Rev Immunol, 2020[3] Picchianti-Diamanti et al., Front Immunol, 2021Charateristic of the cohortIdentificativeAgeDiagnosisRTX/MMFSARS-CoV2 InfectionHospitalizationAntiviral drugs180SScMMF-//270ASSDRTX+nono370ASSDRTX+noyes452GPARTX-//551GPARTX-//649SSc+SSjRTX-//768SScMMF-//847LESRTX-//964ASSDRTX-//1068GPARTX-//1123GPARTX-//1258DMRTX+nono1361SScMMF-//1475GPARTX-//1569GPARTX-//Figure 1.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Drug utilization study in patients affected with COVID-19 in a dedicated COVID hospital

Background: There exists a treatment dilemma regarding the optimal and effective use of therapeutic drugs (hydroxychloroquine/chloroquine/azithromycin) for COVID-19. Furthermore, with changing guidelines, the data on drug utilization patterns across India are limited. Hence, this study was conducted to assess the prescription pattern and drug utilization trends in COVID-19 patients with the aim to study the drug utilization pattern in patients affected with COVID-19 in a dedicated COVID-19 hospital. Aims and Objectives: The objectives of the study are as follows: (1) To study drug utilization patterns according to the severity of the disease. (2) To study the prevalence of adverse drug reactions (ADRs). Materials and Methods: Data were collected retrospectively from 100 medical records of patients 18 years irrespective of sex admitted in the COVID ward and ICU of a dedicated COVID hospital from May to August 2020. Pregnant and lactating women were excluded from the study. ADRs reported were also analyzed. Results: About 71% were mild in this study, 18% were moderate, and 11% were severe COVID-19 patients. Overall, the most common drugs prescribed were multivitamins, followed by pantoprazole, paracetamol, and azithromycin. Hydroxychloroquine was prescribed in 22%, favipiravir in 7%, and remdesivir in 3% of cases. The majority of moderate COVID patients received injectables piperacillin-tazobactam, methylprednisolone, and enoxaparin. The mean number of medications, duration of admission, and number of days on oxygen were higher and significant in moderate compared to mild and severe COVID patients. Overall, ADRs were encountered in 9% of cases. Conclusion: The prescribed pattern of drugs was by the national standard guidelines. Multivitamins, followed by pantoprazole, paracetamol, and azithromycin dominated the prescription pattern. Polypharmacy was encountered, which needs to be addressed for the rational use of drugs.

Molnupiravir and combination of nirmatrelvir and ritonavir (PaxlovidTM) - oral anti-viral drugs in COVID-19: a systematic review

The COVID-19 pandemic situation demands the discovery of newer drugs and/ or repurposing of the existing drugs. The anti-viral drugs approved for COVID-19 are remdesivir and favipiravir. Two more directly acting oral anti-viral drugs have been granted Emergency Use Authorization by US-FDA, molnupiravir on December 23, 2021, and nirmatrelvir and ritonavir (PaxlovidTM) on December 22, 2021. Molnupiravir, an RNA-dependent RNA polymerase (RdRp) inhibitor, has also been approved in the UK and is under review with other regulatory agencies. PaxlovidTM (a combination of the new anti-viral drugs nirmatrelvir and ritonavir) has been developed and approved by US-FDA and CDSCO, India. Nirmatrelvir acts by inhibiting 3CL (chymotrypsin-like) protease enzyme and it is combined with ritonavir to slow down its breakdown by cytochrome P450 enzymes and to increase the bioavailability. Both molnupiravir and PaxlovidTM have been approved for mild and moderate COVID-19 and in patients who have a higher risk of disease progression to severe disease including hospitalisation and death. This article systematically reviews the clinical trials of molnupiravir and PaxlovidTM that evaluated their efficacy and safety against COVID-19 in both published and unpublished literature.

Special Issue: Honor of Dr. Mike Bray on his retirement as the editor-in-chief of antiviral research. (Special Issue: Honor of Dr. Mike Bray on his retirement as the editor-in-chief of antiviral research.)

This special issue contains 23 articles that discuss various aspects of antiviral research, focusing on the contributions and legacy of Dr. Mike Bray, the retiring Editor-in-Chief of Antiviral Research. The articles cover a range of topics, including the underappreciated mouse model for Ebola virus disease, the history and impact of the mouse-adapted Ebola virus model, and the characterisation of CD-1 mice infected with different strains of Ebola virus. Other articles delve into transplacental vertical transmission of flaviviruses, the development of reverse genetic systems for SARS-CoV-2, and the mechanisms of action and drug resistance of nucleotide analogues against the virus. The special issue also explores therapeutics for flaviviral infections, alternative splicing in RNA virus infections, and targeted protein degradation as an antiviral approach.

19th Seminar on Tropical Pathology and Public Health 12th Biotechnology Week 1st Physical Therapy Week, Virtual, 23-25 November 2022

These proceedings comprise 85 articles spanning diverse fields such as bacteriology, molecular biology, biotechnology, dermatology, infectious and parasitic diseases, epidemiology, physiotherapy, immunology, mycology, parasitology, pathology, collective health, and virology. The articles delve into a wide range of research topics, from repurposing drugs for Mycobacterium abscessus complex infections to utilising artificial intelligence for SARS-CoV-2 diagnosis. In bacteriology, investigations explore the correlation between smoking and Helicobacter pylori infection in gastric adenocarcinoma patients, as well as the resistance profiles of Staphylococcus aureus and Pseudomonas aeruginosa in tracheostomised children. Molecular biology studies focus on gene polymorphisms related to diseases like paracoccidioidomycosis. Biotechnology research emphasises bioactive molecules in species like Croton urucurana and the development of computational models for cytotoxicity prediction. Dermatology articles address stability characterisation in vegetable oil-based nanoemulsions. The section on infectious and parasitic diseases encompasses studies on COVID-19 vaccine response in pregnant women and the impact of infection prevention measures in rehabilitation hospitals. Epidemiology investigations analyse trends in premature mortality, tuberculosis in diabetic patients, and public adherence to non-pharmacological COVID-19 measures. Physiotherapy research covers topics such as telerehabilitation through a developed game and the prevalence of congenital anomalies. Immunology studies explore immune responses in HIV and Leishmaniasis, whilst mycology investigates the biotechnological potential of fungi from the cerrado biome. Parasitology research evaluates treatment efficacy against vectors parasites such as Aedes aegypti and Toxoplasma gondii. Pathology articles discuss intentional intoxication in cattle and the influence of curcumin on acute kidney injury therapy. Collective health studies focus on intervention plan development in healthcare settings and pesticide use in horticulture. Lastly, virology research investigates parvovirus occurrence in hospitalised children during the COVID-19 pandemic, hidden hepatitis B virus infection in inmates, and the prevalence of HPV and HTLV-1/2 infections in specific populations.

Broad-Spectrum Antivirals Derived from Natural Products.

Scientific advances have led to the development and production of numerous vaccines and antiviral drugs, but viruses, including re-emerging and emerging viruses, such as SARS-CoV-2, remain a major threat to human health. Many antiviral agents are rarely used in clinical treatment, however, because of their inefficacy and resistance. The toxicity of natural products may be lower, and some natural products have multiple targets, which means less resistance. Therefore, natural products may be an effective means to solve virus infection in the future. New techniques and ideas are currently being developed for the design and screening of antiviral drugs thanks to recent revelations about virus replication mechanisms and the advancement of molecular docking technology. This review will summarize recently discovered antiviral drugs, mechanisms of action, and screening and design strategies for novel antiviral agents.

Targeting CMV Reactivation to Optimize Care for Critically Ill COVID-19 Patients: A Review on the Therapeutic Potential of Antiviral Treatment.

Cytomegalovirus (CMV) reactivation has been linked to adverse clinical outcomes in critically ill patients, with emerging evidence suggesting a potential connection with severe COVID-19. Mechanisms driving this association may include primary lung injury, amplification of systemic inflammation, and secondary immunosuppression. Diagnostic challenges in detecting and assessing CMV reactivation necessitate a comprehensive approach to improve accuracy and inform treatment decisions. Currently, there is limited evidence on the efficacy and safety of CMV pharmacotherapy in critically ill COVID-19 patients. Although insights from non-COVID-19 critical illness studies suggest a potential role for antiviral treatment or prophylaxis, the risks and benefits must be carefully balanced in this vulnerable patient population. Understanding the pathophysiological role of CMV in the context of COVID-19 and exploring the advantages of antiviral treatment are crucial for optimizing care in critically ill patients. This review provides a comprehensive synthesis of available evidence, emphasizing the need for additional investigation to establish the role of CMV treatment or prophylaxis in the management of severe COVID-19 and to develop a framework for future research on this topic.

Statins in hospitalized COVID-19 patients: A systematic review and meta-analysis of randomized controlled trials.

This systematic review and meta-analysis aimed to determine the efficacy of statins in hospitalized patients with coronavirus disease-2019 (COVID-19). A systematic search was made of PubMed, Embase, Cochrane Library, and clinicaltrials.gov, without language restrictions. Randomized controlled trials (RCTs) on treatment of COVID-19 with statins, compared with placebo or standard of care, were reviewed. Seven RCTs (enrolling 1830 participants) met the inclusion criteria. There was no statistically significant difference in all-cause mortality (risk ratio [RR]: 0.92, 95% confidence interval [CI]: 0.75-1.13), length of hospital stay (weighted mean difference: -0.21 days, 95% CI: -1.01 to 0.59 days), intensive care unit (ICU) admission (RR: 1.84, 95% CI: 0.45-7.55), and mechanical ventilation (RR: 1.09, 95% CI: 0.70-1.70) between the two groups. Statins failed to reduce mortality, ICU admission, mechanical ventilation, and length of stay in hospitalized patients with COVID-19. Statins probably should not be used routinely in COVID-19 patients.

A mathematical model of SARS-CoV-2 immunity predicts paxlovid rebound.

Nirmatrelvir/ritonavir (Paxlovid), an oral antiviral medication targeting SARS-CoV-2, remains an important treatment for COVID-19. Initial studies of nirmatrelvir/ritonavir were performed in SARS-CoV-2 unvaccinated patients without prior confirmed SARS-CoV-2 infection; however, most individuals have now either been vaccinated and/or have experienced SARS-CoV-2 infection. After nirmatrelvir/ritonavir became widely available, reports surfaced of "Paxlovid rebound," a phenomenon in which symptoms (and SARS-CoV-2 test positivity) would initially resolve, but after finishing treatment, symptoms and test positivity would return. We used a previously described parsimonious mathematical model of immunity to SARS-CoV-2 infection to model the effect of nirmatrelvir/ritonavir treatment in unvaccinated and vaccinated patients. Model simulations show that viral rebound after treatment occurs only in vaccinated patients, while unvaccinated (SARS-COV-2 naïve) patients treated with nirmatrelvir/ritonavir do not experience any rebound in viral load. This work suggests that an approach combining parsimonious models of the immune system could be used to gain important insights in the context of emerging pathogens.