Project description:The outbreak of the SARS-CoV-2 virus responsible for the COVID-19 disease has given rise to a new disease whose boundaries are still to be discovered. While the first data suggested a purely respiratory infection, the most recent publications highlight a large pleomorphism of the disease, responsible for multiple organ damage, of which cardiac injury seems to be the most represented. This cardiac injury can present as acute myocarditis. Our aim was to discuss the pathophysiological rationale underlying the existence of SARS-CoV-2 myocarditis and to analyze the literature data regarding the diagnosis and treatment of this particular entity.
Project description:BackgroundWith limited vaccine supplies, an informed position on the status of SARS-CoV-2 infection in people can assist the prioritization of vaccine deployment.ObjectivesWe performed a systematic review and meta-analysis to estimate the global and regional SARS-CoV-2 seroprevalences around the world.Data sourcesWe systematically searched peer-reviewed databases (PubMed, Embase and Scopus), and preprint servers (medRxiv, bioRxiv and SSRN) for articles published between 1 January 2020 and 30 March 2021.Study eligibility criteriaPopulation-based studies reporting the SARS-CoV-2 seroprevalence in the general population were included.ParticipantsPeople of different age groups, occupations, educational levels, ethnic backgrounds and socio-economic status from the general population.InterventionsThere were no interventions.MethodsWe used the random-effects meta-analyses and empirical Bayesian method to estimate the pooled seroprevalence and conducted subgroup and meta-regression analyses to explore potential sources of heterogeneity as well as the relationship between seroprevalence and socio-demographics.ResultsWe identified 241 eligible studies involving 6.3 million individuals from 60 countries. The global pooled seroprevalence was 9.47% (95% CI 8.99-9.95%), although the heterogeneity among studies was significant (I2 = 99.9%). We estimated that ∼738 million people had been infected with SARS-CoV-2 (as of December 2020). Highest and lowest seroprevalences were recorded in Central and Southern Asia (22.91%, 19.11-26.72%) and Eastern and South-eastern Asia (1.62%, 1.31-1.95%), respectively. Seroprevalence estimates were higher in males, persons aged 20-50 years, in minority ethnic groups living in countries or regions with low income and human development indices.ConclusionsThe present study indicates that the majority of the world's human population was still highly susceptible to SARS-CoV-2 infection in mid-2021, emphasizing the need for vaccine deployment to vulnerable groups of people, particularly in developing countries, and for the implementation of enhanced preventive measures until 'herd immunity' to SARS-CoV-2 has developed.
Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent for the 2019 coronavirus disease (COVID-19) pandemic, has caused a public health emergency. The need for additional research in viral pathogenesis is essential as the number of cases and deaths rise. Understanding the virus and its ability to cause disease has been the main focus of current literature; however, there is much unknown. Studies have revealed new findings related to the full transmission potential of SARS-CoV-2 and its subsequent ability to cause infection by different means. The virus is hypothesized to be of increased virulence compared with previous coronavirus that caused epidemics, in part due to its overall structural integrity and resilience to inactivation. To date, many studies have discussed that the rationale behind its transmission potential is that viral RNA has unexpectedly been detected in multiple bodily fluids, with some samples having remained positive for extended periods of time. Additionally, the receptor by which the virus gains cellular entry, ACE2, has been found to be expressed in different human body systems, thereby potentiating its infection in those locations. In this evidence-based comprehensive review, we discuss various potential routes of transmission of SARS-CoV-2-respiratory/droplet, indirect, fecal-oral, vertical, sexual, and ocular. Understanding these different routes is important as they pertain to clinical practice, especially in taking preventative measures to mitigate the spread of SARS-CoV-2.
Project description:Coronaviruses (CoVs) are a group of RNA viruses that are associated with different diseases in animals, birds, and humans. Human CoVs (HCoVs) have long been known to be the causative agents of mild respiratory illnesses. However, two HCoVs associated with severe respiratory diseases are Severe Acute Respiratory Syndrome-CoV (SARS-CoV) and Middle East Respiratory Syndrome-CoV (MERS-CoV). Both viruses resulted in hundreds of deaths after spreading to several countries. Most recently, SARS-CoV-2 has emerged as the third HCoV causing severe respiratory distress syndrome and viral pneumonia (known as COVID-19) in patients from Wuhan, China, in December 2019. Soon after its discovery, SARS-CoV-2 spread to all countries, resulting in millions of cases and thousands of deaths. Since the emergence of SARS-CoV, many research groups have dedicated their resources to discovering effective antivirals that can treat such life-threatening infections. The rapid spread and high fatality rate of SARS-CoV-2 necessitate the quick discovery of effective antivirals to control this outbreak. Since SARS-CoV-2 shares 79% sequence identity with SARS-CoV, several anti-SARS-CoV drugs have shown promise in limiting SARS-CoV-2 replication in vitro and in vivo. In this review, we discuss antivirals described for SARS-CoV and provide an update on therapeutic strategies and antivirals against SARS-CoV-2. The control of the current outbreak will strongly depend on the discovery of effective and safe anti-SARS-CoV-2 drugs.
Project description:Since the outbreak of the novel coronavirus disease 2019 (COVID-19) in Wuhan, China, many health care systems have been heavily engaged in treating and preventing the disease, and the year 2020 may be called as "historic COVID-19 vaccine breakthrough". Due to the COVID-19 pandemic, many companies have initiated investigations on developing an efficient and safe vaccine against the virus. From Moderna and Pfizer in the United States to PastocoVac in Pasteur Institute of Iran and the University of Oxford in the United Kingdom, different candidates have been introduced to the market. COVID-19 vaccine research has been facilitated based on genome and structural information, bioinformatics predictions, epitope mapping, and data obtained from the previous developments of severe acute respiratory syndrome coronavirus (SARS-CoV or SARS-CoV-1) and middle east respiratory syndrome coronavirus (MERS-CoV) vaccine candidates. SARS-CoV genome sequence is highly homologous to the one in COVID-19 and both viruses use the same receptor, angiotensin-converting enzyme 2 (ACE2). Moreover, the immune system responds to these viruses, partially in the same way. Considering the on-going COVID-19 pandemic and previous attempts to manufacture SARS-CoV vaccines, this paper is going to discuss clinical cases as well as vaccine challenges, including those related to infrastructures, transportation, possible adverse reactions, utilized delivery systems (e.g., nanotechnology and electroporation) and probable vaccine-induced mutations.
Project description:Knowledge of structural details is very much essential from the drug-design perspective. In the systematic review, we systematically reviewed the structural basis of different target proteins of SARS-corona virus (CoV2) from a viral life cycle and from drug design perspective. We searched four literature (PubMed, EMBASE, NATURE, and Willey online library) databases and one structural database (RCSB.org) with appropriate keywords till April 18, and finally, 26 articles were included in the systematic review. The published literature mainly centered upon the structural details of "spike protein," "main protease/M Pro/3CL pro," "RNA-dependent RNA polymerase," and "nonstructural protein 15 Endoribonuclease" of SARS-CoV-2. However, inhibitor bound structures were very less. We need better structures elucidating the interactions between different targets and their inhibitors which will help us in understanding the atomic level importance of different amino acid residues in the functionality of the target structures. To summarize, we need structures with fine resolution, co-crystallized structures with biologically validated inhibitors, and functional characterization of different target proteins. Some other routes of entry of SARS-CoV-2 are also mentioned (e.g., CD147); however, these findings are not structurally validated. This review may pave way for better understanding of SARS-CoV-2 life cycle from structural biology perspective.
Project description:Non-structural protein 3 (nsp3) from all coronaviruses (CoVs) contains a conserved macrodomain, known as Mac1, that has been proposed as a potential therapeutic target for CoVs due to its critical role in viral pathogenesis. Mac1 is an ADP-ribose binding protein and ADP-ribosylhydrolase that promotes replication and blocks IFN responses, though the precise mechanisms it uses to carry out these functions remain unknown. Over the past 3 years following the onset of COVID-19, several groups have used high-throughput screening with multiple assays and chemical modifications to create unique chemical inhibitors of the SARS-CoV-2 Mac1 protein. Here, we summarize the current efforts to identify selective and potent inhibitors of SARS-CoV-2 Mac1.
Project description:Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic caused by it, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been undergoing a genetic diversification leading to the emergence of new variants. Nevertheless, a clear definition of the genetic signatures underlying the circulating variants is still missing. Here, we provide a comprehensive insight into mutational profiles characterizing each SARS-CoV-2 variant, focusing on spike mutations known to modulate viral infectivity and/or antigenicity. We focused on variants and on specific relevant mutations reported by GISAID, Nextstrain, Outbreak.info, Pango, and Stanford database websites that were associated with any clinical/diagnostic impact, according to published manuscripts. Furthermore, 1,223,338 full-length high-quality SARS-CoV-2 genome sequences were retrieved from GISAID and used to accurately define the specific mutational patterns in each variant. Finally, mutations were mapped on the three-dimensional structure of the SARS-CoV-2 spike protein to assess their localization in the different spike domains. Overall, this review sheds light and assists in defining the genetic signatures characterizing the currently circulating variants and their clinical relevance. IMPORTANCE Since the emergence of SARS-CoV-2, several recurrent mutations, particularly in the spike protein, arose during human-to-human transmission or spillover events between humans and animals, generating distinct worrisome variants of concern (VOCs) or of interest (VOIs), designated as such due to their clinical and diagnostic impacts. Characterizing these variants and their related mutations is important in tracking SAR-CoV-2 evolution and understanding the efficacy of vaccines and therapeutics based on monoclonal antibodies, convalescent-phase sera, and direct antivirals. Our study provides a comprehensive survey of the mutational profiles characterizing the important SARS-CoV-2 variants, focusing on spike mutations and highlighting other protein mutations.
Project description:BackgroundThe durability of the antibody response after SARS-CoV-2 infection and the role of antibodies in protection against reinfection are unclear.PurposeTo synthesize evidence on the SARS-CoV-2 antibody response and reinfection risk with a focus on gaps identified in our prior reports.Data sourcesMEDLINE (Ovid), EMBASE, CINAHL, World Health Organization Research Database, and reference lists from 16 December 2021 through 8 July 2022, with surveillance through 22 August 2022.Study selectionEnglish-language, cohort studies evaluating IgG antibody duration at least 12 months after SARS-CoV-2 infection, the antibody response among immunocompromised adults, predictors of nonseroconversion, and reinfection risk.Data extractionTwo investigators sequentially extracted study data and rated quality.Data synthesisMost adults had IgG antibodies after SARS-CoV-2 infection at time points greater than 12 months (low strength of evidence [SoE]). Although most immunocompromised adults develop antibodies, the overall proportion with antibodies is lower compared with immunocompetent adults (moderate SoE for organ transplant patients and low SoE for patients with cancer or HIV). Prior infection provided substantial, sustained protection against symptomatic reinfection with the Delta variant (high SoE) and reduced the risk for severe disease due to Omicron variants (moderate SoE). Prior infection was less protective against reinfection with Omicron overall (moderate SoE), but protection from earlier variants waned rapidly (low SoE).LimitationSingle review for abstract screening and sequential review for study selection, data abstraction, and quality assessment.ConclusionEvidence for a sustained antibody response to SARS-CoV-2 infection is considerable for both Delta and Omicron variants. Prior infection protected against reinfection with both variants, but, for Omicron, protection was weaker and waned rapidly. This information may have limited clinical applicability as new variants emerge.Primary funding sourceAgency for Healthcare Research and Quality. (PROSPERO: CRD42020207098).