The use of mechanical ventilation associated with acute hypoxemic respiratory failure, the most common complication in critically ill COVID-19 patients, defines a high risk population that requires specific consideration of outcomes and treatment practices.

Introduction Since the declaration of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in March 2020, Portugal was considered a role model with regards to the first COVID-19 wave. However, a third wave started in 2021 started, turning the country into the worst in the world regarding new infections and death rate per capita in the last weeks of January 2021. No significant data regarding the country's first wave of hospitalized patients have been published. Those data may help understand the differences over time regarding patients and the clinical approach to them. Herein, we present data of COVID-19 patients hospitalized at the main tertiary hospital of the second-most affected county at the time and identify risk factors associated with disease progression and outcomes. Materials and methods We performed a prospective observational study of patients admitted with COVID-19 to a central hospital between March 20 and June 1, 2020. The primary endpoint of this study was 30-day mortality or the need for ventilatory support and the secondary outcomes were both outcomes individually. Results 245 patients were included, with a median age of 79 years, 52% males. Hypertension (n = 172) and dyslipidemia (n = 114) were the most frequent comorbidities. Half of the patients (n = 121) were treated with hydroxychloroquine. The primary outcome occurred in 114 patients; mortality at 30 days was 35%. Age (OR 1.05; 1.02-1.07) and active cancer (OR 3.89; 1.43-10.57) were associated with the primary outcome, with dyslipidemia being protective (OR 0.46; 0.25-0.80). Treatment with hydroxychloroquine or lopinavir/ritonavir was not associated with the main outcome. Patients who had been symptomatic for more than 7 days had lower mortality (OR 0.23; 0.09-0.63). Discussion In the present study, age and cancer were associated with higher mortality, as noted in prior articles. The population had a higher median age than reported in previous studies, which may explain the increased mortality. The protective association of dyslipidemia was not previously described. This association was not related to statin intake. Conclusion The reported high mortality of COVID-19 is rarely seen in other infectious diseases. Our elderly population probably reflects more reliably the incidence of COVID-19 in European countries with constricted age pyramids.

During Switzerland's first wave of COVID-19, clinical pharmacy activities during medical rounds in Geneva University Hospitals were replaced by targeted remote interventions. We describe using the electronic PharmaCheck system to screen high-risk situations of adverse drug events (ADEs), particularly targeting prescriptions of lopinavir/ritonavir (LPVr) and hydroxychloroquine (HCQ) in the presence of contraindications or prescriptions outside institutional guidelines. Of 416 patients receiving LPVr and/or HCQ, 182 alerts were triggered for 164 (39.4%) patients. The main associated risk factors of ADEs were drug-drug interactions, QTc interval prolongation, electrolyte disorder and inadequate LPVr dosage. Therapeutic optimisation recommended by a pharmacist or proposals for additional monitoring were accepted in 80% (n=36) of cases. Combined with pharmacist contextualisation to the clinical context, PharmaCheck made it possible to successfully adapt clinical pharmacist activities by switching from a global to a targeted analysis mode in an emergency context.

Within the COVID-19 pandemic context, the WHO has proposed a list of medicines to treat patients with severe acute respiratory syndrome (SARS-CoV-2). An analysis of their ocular side effects was performed. Only chloroquine and hydroxychloroquine were found to have an ocular impact in the medium and long-term. Detailed search strategies were performed in EMBASE, MEDLINE, SCOPUS and WOS Core Collection. Additionally, the worldwide ongoing clinical trials including chloroquine or hydroxychloroquine were evaluated, and their proposals of drug administration and exclusion criteria analyzed. In general, high maximum cumulative doses of chloroquine or hydroxychloroquine are being used for a short period in 135 currently underway clinical trials (to 21st April 2020). Typically, the doses were 2 to 5 times greater than the AAO recommendation (adjusted to weight) to avoid toxic retinopathy, the most undesirable ocular side effect. Maximum cumulative doses up to 12,000 mg for chloroquine and 18,000 mg for hydroxychloroquine were found. In prophylaxis clinical trials, 72,000 mg and 22,500 mg were the maximum cumulative doses for hydroxychloroquine and chloroquine respectively. Only 48% of the clinical trials considered retinal impairment as an exclusion criterion, and just one referred to an ophthalmic examination previous to study inclusion. How chloroquine and hydroxychloroquine treatment affect patients with a previous retinal condition is still poorly understood. A comprehensive ophthalmological examination 6 months after treatment is recommended in this subgroup. This review provides an overview of this topic and sheds light on the challenges visual caregivers may face regarding these repurposed drugs.

Emergence of novel coronavirus-2019 has become an international health concern. The objective of this review is to focus on 2019-nCoV emergence, prophylaxis and to predict the treatment approaches. The first case of 2019-nCoV was noted in Wuhan, China. The WHO has announced this epidemic as pandemic. The 2019-nCoV has +ve ssRNA (29903bp), lipid-bilayer envelope spiked with glycoprotein and bears genome sequences similar to bat coronavirus RaTG13. Antiviral agents like Interferon, Darunavir, Ribavirin, Lopinavir, Remdesivir, Chloroquine and Camostat mesylate may be considered for clinical trials. Chinese herbals may be effective against 2019-nCoV. These include Saikosaponins (triterpene glycosides), Amentoflavone, Scutellarein, Myricetin, extracts of Isatis indigotica, and Houttuynia cordata. Another treatment approach is to administer plasma from COVID-19 recovered patients. RNA vaccines, recombinant vector based vaccine and ACE-2 receptor like molecules may be employed for immunization against COVID-19. Moreover, immunity can be boosted against 2019-nCoV by regular exercise. We have checked Thymoquinone as ligand for various targets of 2019-nCoV (receptor binding domain of spike, RNA polymerase, protease, Nsp9 RNA binding protein, nucleocapsid phosphoprotein, endoribonuclease) by protein-ligand docking server SwissDoc. Thymoquinone can bind effectively to the targets of 2019-nCoV. Hence, it may be an effective candidate for the treatment of COVID-19.

With the emergence of COVID-19 (Corona virus Disease 19), the workers tried to search the drug/s for its management. Chloroquine, hydroxychloroquine and protease inhibitors including Ritonavir have been tested. But the safety and efficacy of these drugs for the treatment of COVID-19 were not very strong. Fusion inhibitors may be used for the management or prophylaxis of viral diseases. Objective of the present study was to design a fusion inhibitor for specific management of COVID-19. A series of BLAST was performed to get an optimized and conservative region of the spike protein of the virus which is used in fusion process. Based on the recent data available, residue 1160-1189 of spike protein of Novel coronavirus-2019 (2019-nCoV) was found highly conserved region with 100% similarity, with maximum score of 99.5 and with an E-value of 5e-24. Thus, this sequence was selected as a drug. This drug is a synthetic peptide composed of 30 amino acids of Heptad Repeat 2 (HR2) region of spike protein of 2019-nCoV and was named as QadirVID-19 (Qadir, name of the scientist who developed it and VID-19 from COVID-19).

Novel coronavirus disease (COVID-19) has become a pandemic threat to public health. Vaccines and targeted therapeutics to prevent infections and stop virus proliferation are currently lacking. Endoribonuclease Nsp15 plays a vital role in the life cycle, including replication and transcription as well as virulence of the virus. Here, we investigated Vitamin D for its in silico potential inhibition of the binding sites of SARS-CoV-2 endoribonuclease Nsp15. In this study, we selected Remdesivir, Chloroquine, Hydroxychloroquine and Vitamin D to study the potential binding affinity with the putative binding sites of endoribonuclease Nsp15 of COVID-19. The docking study was applied to rationalize the possible interactions of the target compounds with the active site of endoribonuclease Nsp 15. Among the results, Vitamin D was found to have the highest potency with strongest interaction in terms of LBE, lowest RMSD, and lowest inhibition intensity Ki than the other standard compounds. The investigation results of endoribonuclease Nsp15 on the PrankWeb server showed that there are three prospective binding sites with the ligands. The singularity of Vitamin D interaction with the three pockets, particularly in the second pocket, may write down Vitamin D as a potential inhibitor of COVID-19 Nsp15 endoribonuclease binding sites and favour addition of Vitamin D in the treatment plan for COVID-19 alone or in combination with the other used drugs in this purpose, which deserves exploration in further in vitro and in vivo studies.

Novel Coronavirus disease 2019 (COVID-19) has spread rapidly around the world. Individuals with immune dysregulation and/or on immunosuppressive therapy, such as rheumatic patients, are considered at greater risk for infections. However, the risks of patients with each subcategory of rheumatic diseases have not been reported. Here, we identified 100 rheumatic patients from 18,786 COVID-19 patients hospitalized in 23 centers affiliated to Hubei COVID-19 Rheumatology Alliance between January 1 and April 1, 2020. Demographic information, medical history, length of hospital stay, classification of disease severity, symptoms and signs, laboratory tests, disease outcome, computed tomography, and treatments information were collected. Compared to gout and ankylosing spondylitis (AS) patients, patients with connective tissue disease (CTD) tend to be more severe after COVID-19 infection (p = 0.081). CTD patients also had lower lymphocyte counts, hemoglobin, and platelet counts (p values were 0.033, < 0.001, and 0.071, respectively). Hydroxychloroquine therapy and low- to medium-dose glucocorticoids before COVID-19 diagnosis reduced the progression of COVID-19 to severe/critical conditions (p = 0.001 for hydroxychloroquine; p = 0.006 for glucocorticoids). Our data suggests that COVID-19 in CTD patients may be more severe compared to patients with AS or gout.

Across three studies, we investigated who expresses concern for COVID-19, or coronavirus, and engages in behaviors that are consistent with slowing the spread of COVID-19. In Studies 1 and 2 (n = 415, n = 199), those with warmer feelings toward scientists were more concerned and engaged in greater COVID-preventative behaviors, regardless of partisanship. That is, an anti-scientists bias was related to lessened concern and toward less preventive behaviors. Furthermore, those who were the most optimistic about hydroxychloroquine, a purported but unproven treatment against the virus, were less likely to engage in behaviors designed to decrease the spread of COVID-19. In Study 3 (n = 259), asking participants to watch a scientist discuss hydroxychloroquine on Fox News led people to greater endorsement of COVID behaviors. In short, positive feelings toward scientists, rather than political attitudes or knowledge, related to who was concerned and those willing to engage in pandemic reducing behaviors. These behaviors were not immutable and can be changed by scientific out-reach.

By 9 February 2021, the Coronavirus has killed 2,336,650 people worldwide and it has been predicted that this number continues to increase in year 2021. The study aimed to identify therapeutic approaches and drugs that can potentially be used as interventions in Coronavirus 2019 (COVID-19) management. A systematic scoping review was conducted. Articles reporting clinical evidence of therapeutic management of COVID-19 were selected from three different research databases (Google Scholar, PubMed, and Science Direct). From the database search, 31 articles were selected based on the study inclusion and exclusion criteria. This review paper showed that remdesivir and ivermectin significantly reduced viral ribonucleic acid (RNA) activity. On the other hand, convalescent plasma (CP) significantly improved COVID-19 clinical symptoms. Additionally, the use of corticosteroid increased survival rates in COVID-19 patients with acute respiratory distress syndrome (ARDS). Findings also indicated that both hydroxychloroquine and favipiravir were effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, lopinavir-ritonavir combination was not effective against COVID-19. Finally, ribavirin, galidesivir, and sofosbuvir showed potential therapeutic benefit in treating COVID-19, but there is a lack of clinical evidence on their effectiveness against SARS-CoV-2. Remdesivir, ivermectin, favipiravir, hydroxychloroquine, dexamethasone, methylprednisolone, and CP are the therapeutic agents that can potentially be used in COVID-19 management.

The COVID-19 disease caused by the SARS-CoV-2 virus is a health crisis worldwide. While developing novel drugs and vaccines is long, repurposing existing drugs against COVID-19 can yield treatments with known preclinical, pharmacokinetic, pharmacodynamic, and toxicity profiles, which can rapidly enter clinical trials. In this study, we present a novel network-based drug repurposing platform to identify candidates for the treatment of COVID-19. At the time of the initial outbreak, knowledge about SARS-CoV-2 was lacking, but based on its similarity with other viruses, we sought to identify repurposing candidates to be tested rapidly at the clinical or preclinical levels. We first analyzed the genome sequence of SARS-CoV-2 and confirmed SARS as the closest virus by genome similarity, followed by MERS and other human coronaviruses. Using text mining and database searches, we obtained 34 COVID-19-related genes to seed the construction of a molecular network where our module detection and drug prioritization algorithms identified 24 disease-related human pathways, five modules, and 78 drugs to repurpose. Based on clinical knowledge, we re-prioritized 30 potentially repurposable drugs against COVID-19 (including pseudoephedrine, andrographolide, chloroquine, abacavir, and thalidomide). Our work shows how in silico repurposing analyses can yield testable candidates to accelerate the response to novel disease outbreaks.

Coronavirus (COVID-19), an enveloped RNA virus, primarily affects human beings. It has been deemed by the World Health Organization (WHO) as a pandemic. For this reason, COVID-19 has become one of the most lethal viruses which the modern world has ever witnessed although some established pharmaceutical companies allege that they have come up with a remedy for COVID-19. To that end, a set of carboxamides sulfonamide derivatives has been under study using 3D-QSAR approach. CoMFA and CoMSIA are one of the most cardinal techniques used in molecular modeling to mold a worthwhile 3D-QSAR model. The expected predictability has been achieved using the CoMFA model (Q2 = 0.579; R2 = 0.989; R2test = 0.791) and the CoMSIA model (Q2 = 0.542; R2 = 0.975; R2test = 0.964). In a similar vein, the contour maps extracted from both CoMFA and CoMSIA models provide much useful information to determine the structural requirements impacting the activity; subsequently, these contour maps pave the way for proposing 8 compounds with important predicted activities. The molecular surflex-docking simulation has been adopted to scrutinize the interactions existing between potentially and used antimalarial molecule on a large scale, called Chloroquine (CQ) and the proposed carboxamides sulfonamide analogs with COVID-19 main protease (PDB: 6LU7). The outcomes of the molecular docking point out that the new molecule P1 has high stability in the active site of COVID-19 and an efficient binding affinity (total scoring) in relation with the Chloroquine. Last of all, the newly designed carboxamides sulfonamide molecules have been evaluated for their oral bioavailability and toxicity, the results point out that these scaffolds have cardinal ADMET properties and can be granted as reliable inhibitors against COVID-19.

Coronavirus disease (COVID-19) pandemic is instigated by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As of March 13, 2021, more than 118.9 million cases were infected with COVID-19 worldwide. SARS-CoV-2 is a positive-sense single-stranded RNA beta-CoV. Most COVID-19 infected individuals recover within 1-3 weeks. Nevertheless, approximately 5% of patients develop acute respiratory distress syndrome and other systemic complications, leading to death. Structural genetic analyses of SARS-CoV-2 have shown genomic resemblances but a low evolutionary correlation to SARS-CoV-1 responsible for the 2002-2004 outbreak. The S glycoprotein is critical for cell adhesion and the entrance of the virus into the host. The process of cell entry uses the cellular receptor named angiotensin-converting enzyme 2. Recent evidence proposed that the CD147 as a SARS-CoV-2's potential receptor. The viral genome is mainly held by two non-structural proteins (NSPs), ORF1a and ORF1ab, along with structural proteins. Although NSPs are conserved among the βCoVs, mutations in NSP2 and NSP3 may play critical roles in transmitting the virus and cell tropism. To date, no specific/targeted anti-viral treatments exist. Notably, more than 50 COVID-19 candidate vaccines in clinical trials, and a few being administered. Preventive precautions are the primary strategy to limit the viral load transmission and spread, emphasizing the urgent need for developing significant drug targets and vaccines against COVID-19. This review provides a cumulative overview of the genomic structure, transmission, phylogeny of SARS-CoV-2 from Indian clusters, treatment options, updated discoveries, and future standpoints for COVID-19.

Current pandemic of COVID-19 caused by SARS-CoV-2 has raised global health concerns. RNA dependent RNA polymerase (RdRp) is the prime component of viral replication/proliferation machinery and is considered to be a potential drug target against SARS-CoV-2. Present study investigated the anti-RdRp activity of phytochemicals against SARS-CoV-2 infection. Virtual ligand screening was carried out to determine the potent compounds against RdRp. Molecular docking and MD Simulation study was employed to evaluate the spatial affinity of selected phytochemicals for the active sites of RdRp. Structural stability of target compounds was determined using RMSD computational analysis and drug like abilities were investigated using ADMET. Bond distance between ligand and receptor were marked to predict the strength of interaction. Aloe, azadirachtin, columbin, cirsilineol, nimbiol, nimbocinol and sage exhibited highest binding affinity and interacted with active sites of RdRp surpassing the ability of chloroquine, lamivudine, favipiravir and remdesivir to target the same. All the natural metabolites exhibited stable conformation during MD Simulation of 101ns at 310K. Kinetic, potential and electrostatic energy were observed to be least in case of natural metabolites in comparison to synthetic analogs. Deviation and fluctuations were observed to be structurally least in target phytochemicals. Physiochemical and biological properties of these compounds further validated their drug like properties. Non-bonded distance was found to be short enough to form hydrogen bonding or hydrophobic interactions which revealed that these target compounds can strongly bind with RdRp. The study brings forth the potential phytochemicals to disrupt the replication domain of SARS-CoV-2 by hindering RdRp. We therefore anticipate that the current findings could be considered as valuable for development of an efficient preventive/therapeutic expedient against COVID-19.

The emergence of highly virulent CoVs (SARS-CoV-2), the etiologic agent of novel ongoing "COVID-19" pandemics has been marked as an alarming case of pneumonia posing a large global healthcare crisis of unprecedented magnitude. Currently, the COVID-19 outbreak has fueled an international demand in the biomedical field for the mitigation of the fast-spreading illness, all through the urgent deployment of safe, effective, and rational therapeutic strategies along with epidemiological control. Confronted with such contagious respiratory distress, the global population has taken significant steps towards a more robust strategy of containment and quarantine to halt the total number of positive cases but such a strategy can only delay the spread. A substantial number of potential vaccine candidates are undergoing multiple clinical trials to combat COVID-19 disease, includes live-attenuated, inactivated, viral-vectored based, sub-unit vaccines, DNA, mRNA, peptide, adjuvant, plant, and nanoparticle-based vaccines. However, there are no licensed anti-COVID-19 drugs/therapies or vaccines that have proven to work as more effective therapeutic candidates in open-label clinical trial studies. To counteract the infection (SARS-CoV-2), many people are under prolonged treatment of many chemical drugs that inhibit the PLpro activity (Ribavirin), viral proteases (Lopinavir/Ritonavir), RdRp activity (Favipiravir, Remdesivir), viral membrane fusion (Umifenovir, Chloroquine phosphate (CQ), Hydroxychloroquine phosphate (HCQ), IL-6 overexpression (Tocilizumab, Siltuximab, Sarilumab). Mesenchymal Stem Cell therapy and Convalescent Plasma Therapy have emerged as a promising therapeutic strategy against SARS-CoV-2 virion. On the other hand, repurposing previously designed antiviral agents with tolerable safety profile and efficacy could be the only promising approach and fast response to the novel virion. In addition, research institutions and corporations have commenced the redesign of the available therapeutic strategy to manage the global crisis. Herein, we present succinct information on selected anti-COVID-19 therapeutic medications repurposed to combat SARS-CoV-2 infection. Finally, this review will provide exhaustive detail on recent prophylactic strategies and ongoing clinical trials to curb this deadly pandemic, outlining the major therapeutic areas for researchers to step in.

Coronaviruses are a large family of zoonotic RNA viruses, whose infection can lead to mild or lethal respiratory tract disease. Severe Acute Respiratory Syndrome-Coronavirus-1 (SARS-CoV-1) first emerged in Guangdong, China in 2002 and spread to 29 countries, infecting 8089 individuals and causing 774 deaths. In 2012, Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) emerged in Saudi Arabia and has spread to 27 countries, with a mortality rate of ~34%. In 2019, SARS-CoV-2 emerged and has spread to 220 countries, infecting over 100,000,000 people and causing more than 2,000,000 deaths to date. These three human coronaviruses cause diseases of varying severity. Most people develop mild, common cold-like symptoms, while some develop acute respiratory distress syndrome (ARDS). The success of all viruses, including coronaviruses, relies on their evolved abilities to evade and modulate the host anti-viral and pro-inflammatory immune responses. However, we still do not fully understand the transmission, phylogeny, epidemiology, and pathogenesis of MERS-CoV and SARS-CoV-1 and -2. Despite the rapid application of a range of therapies for SARS-CoV-2, such as convalescent plasma, remdesivir, hydroxychloroquine and type I interferon, no fully effective treatment has been determined. Remarkably, COVID-19 vaccine research and development have produced several offerings that are now been administered worldwide. Here, we summarise an up-to-date understanding of epidemiology, immunomodulation and ongoing anti-viral and immunosuppressive treatment strategies. Indeed, understanding the interplay between coronaviruses and the anti-viral immune response is crucial to identifying novel targets for therapeutic intervention, which may even prove invaluable for the control of future emerging coronavirus.