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104 result(s) for "SARS‐CoV‐2 variant"
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Risk of intensive care unit admission and mortality in patients hospitalized due to influenza A or B and SARS‑CoV‑2 variants Omicron or Delta
Background Respiratory viral infections have significant global health impacts. We compared 30‐day intensive care unit (ICU) admission and all‐cause mortality risks in patients with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) Delta and Omicron variants versus influenza A and B (A/B). Methods Data from two retrospective inpatient cohorts in Copenhagen were analyzed. Cohorts included hospitalized influenza A/B patients (2017–2018) and SARS‐CoV‐2 Delta/Omicron patients (2021–2022), aged ≥18 years, admitted within 14 days of a positive real‐time polymerase chain reaction test result. Cumulative ICU admission and mortality rates were estimated using the Aalen–Johansen estimator. Cox regression models calculated hazard ratios (HRs) for ICU admission and mortality. Results The study encompassed 1459 inpatients (Delta: 49%; Omicron: 26%; influenza A: 6.4%; and influenza B: 18%). Cumulative incidence of ICU admission was 11%, 4.0%, 7.5%, and 4.1%, for Delta, Omicron, influenza A, and B, respectively. For ICU admission, adjusted HRs (aHRs) were 3.1 (p < .001) and 1.5 (p = .34) for Delta and Omicron versus influenza B, and 1.5 (p = .36) and 0.71 (p = .48) versus influenza A. For mortality, aHRs were 3.8 (p < .001) and 3.4 (p < .001) for Delta and Omicron versus influenza B, and 2.1 (p = .04) and 1.9 (p = .11) versus influenza A. Conclusion Delta but not Omicron inpatients had an increased risk for ICU admission compared to influenza B; however, both variants were associated with higher risks of mortality than influenza B. Only Delta inpatients had a higher risk of mortality than influenza A inpatients. This study compared the risks of intensive care unit (ICU) admission and mortality among patients with severe acute respiratory syndrome coronavirus 2 Delta and Omicron variants versus those with influenza A and B. It found that patients with the Delta variant had a higher risk of ICU admission and mortality compared to those with influenza B, and a higher mortality risk than those with influenza A. However, while Omicron patients also had a higher mortality risk than influenza B patients, they did not show an increased risk for ICU admission compared to influenza B.
The latest Omicron BA.4 and BA.5 lineages are frowning toward COVID‐19 preventive measures: A threat to global public health
BACKGROUND A cluster of pneumonia cases was reported by the Wuhan Municipal Health Commission, China, Hubei Province, resulting in the identification of a novel coronavirus (SARS-CoV-2). Another vital mutation in BA.4 and BA.5 subvariants is F486V. 10 This mutation occurs in the spike protein region close to the attaching site with the human cell. [...]these new subvariants of Omicron could be more contagious and capable of escaping the human immune system. [...]the hospitalization and death rates associated with BA.4 and BA.5 subvariants are similar to their first Omicron wave. 17 This might be due to the demographic pattern of Portugal, where older people were infected more by BA.4 and BA.5 variants. Epidemiologic studies suggest that consecutive COVID-19 waves are converting to milder. 24 However, viruses do not automatically change to become less lethal. 26–29 Therefore, healthcare authorities across the globe need to be more careful about viral mutations and their impact on human health.
Epidemiological and clinical features of SARS‐CoV‐2 infection in children during the outbreak of Omicron variant in Shanghai, March 7–31, 2022
Objectives This study aimed to understand the epidemiological and clinical characteristics of pediatric SARS‐CoV‐2 infection during the early stage of Omicron variant outbreak in Shanghai. Methods This study included local COVID‐19 cases <18 years in Shanghai referred to the exclusively designated hospital from March 7 to March 31, 2022. Clinical data, epidemiological exposure, and COVID‐19 vaccination status were collected. Relative risks (RRs) were calculated to assess the effect of vaccination on symptomatic infection and febrile disease. Results A total of 376 pediatric cases of COVID‐19 (median age: 6.0 ± 4.2 years) were referred to the designated hospital, including 257 (68.4%) symptomatic cases and 119 (31.6%) asymptomatic cases. Of the 307 (81.6%) children ≥3 years eligible for COVID‐19 vaccination, 110 (35.8%) received two doses of vaccines. The median interval between the completion of two‐dose vaccination and infection was 3.5 (interquartile range [IQR]: 3, 4.5) months. Compared with no vaccination, two‐dose COVID‐19 vaccination reduced the risks of symptomatic infection and febrile disease by 35% (RR 0.65, 95% confidence interval [CI]: 0.53–0.79) and 33% (RR 0.64, 95% CI: 0.51–0.81) among confirmed cases. Eighty‐four percent of symptomatic cases had fever (mean duration: 1.7 ± 1.0.8 days), 40.5% had cough, and 16.4% had transient leukopenia. Three hundred and seven (81.6%) had an epidemiological exposure in household (69.1%), school (21.8%), and residential area (8.8%). Conclusion The surge of pediatric COVID‐19 cases and multiple transmission model reflect wide dissemination of Omicron variant in the community. Asymptomatic infection is common among Omicron‐infected children. COVID‐19 vaccination can offer some protection against symptomatic infection and febrile disease.
Long COVID: The latest manifestations, mechanisms, and potential therapeutic interventions
COVID‐19 caused by SARS‐CoV‐2 infection affects humans not only during the acute phase of the infection, but also several weeks to 2 years after the recovery. SARS‐CoV‐2 infects a variety of cells in the human body, including lung cells, intestinal cells, vascular endothelial cells, olfactory epithelial cells, etc. The damages caused by the infections of these cells and enduring immune response are the basis of long COVID. Notably, the changes in gene expression caused by viral infection can also indirectly contribute to long COVID. We summarized the occurrences of both common and uncommon long COVID, including damages to lung and respiratory system, olfactory and taste deficiency, damages to myocardial, renal, muscle, and enduring inflammation. Moreover, we provided potential treatments for long COVID symptoms manifested in different organs and systems, which were based on the pathogenesis and the associations between symptoms in different organs. Importantly, we compared the differences in symptoms and frequency of long COVID caused by breakthrough infection after vaccination and infection with different variants of concern, in order to provide a comprehensive understanding of the characteristics of long COVID and propose improvement for tackling COVID‐19. Long COVID manifests in different organs of different patients. In this manuscript, symptoms, mechanism, and potential interventions of long COVID in different organs were discussed as follows: pulmonary and respiratory involvement, neurological involvement, smell and taste dysfunction, vascular involvement, muscular involvement, cardiac involvement, intestinal involvement, immunological dysfunction, kidney involvement, biochemical abnormalities of liver, ocular involvement, and sexual dysfunction. In addition, the differences in symptoms and frequency of long COVID caused by breakthrough infection after vaccination and infection with different variants of concern are discussed in the manuscript.
Understanding the Driving Forces That Trigger Mutations in SARS-CoV-2: Mutational Energetics and the Role of Arginine Blockers in COVID-19 Therapy
SARS-CoV-2 is a global challenge due to its ability to mutate into variants that spread more rapidly than the wild-type virus. Because the molecular biology of this virus has been studied in such great detail, it represents an archetypal paradigm for research into new antiviral drug therapies. The rapid evolution of SARS-CoV-2 in the human population is driven, in part, by mutations in the receptor-binding domain (RBD) of the spike (S-) protein, some of which enable tighter binding to angiotensin-converting enzyme (ACE2). More stable RBD-ACE2 association is coupled with accelerated hydrolysis of furin and 3CLpro cleavage sites that augment infection. Non-RBD and non-interfacial mutations assist the S-protein in adopting thermodynamically favorable conformations for stronger binding. The driving forces of key mutations for Alpha, Beta, Gamma, Delta, Kappa, Lambda and Omicron variants, which stabilize the RBD-ACE2 complex, are investigated by free-energy computational approaches, as well as equilibrium and steered molecular dynamic simulations. Considered also are the structural hydropathy traits of the residues in the interface between SARS-CoV-2 RBD and ACE2 protein. Salt bridges and π-π interactions are critical forces that create stronger complexes between the RBD and ACE2. The trend of mutations is the replacement of non-polar hydrophobic interactions with polar hydrophilic interactions, which enhance binding of RBD with ACE2. However, this is not always the case, as conformational landscapes also contribute to a stronger binding. Arginine, the most polar and hydrophilic among the natural amino acids, is the most aggressive mutant amino acid for stronger binding. Arginine blockers, such as traditional sartans that bear anionic tetrazoles and carboxylates, may be ideal candidate drugs for retarding viral infection by weakening S-protein RBD binding to ACE2 and discouraging hydrolysis of cleavage sites. Based on our computational results it is suggested that a new generation of “supersartans”, called “bisartans”, bearing two anionic biphenyl-tetrazole pharmacophores, are superior to carboxylates in terms of their interactions with viral targets, suggesting their potential as drugs in the treatment of COVID-19. In Brief: This in silico study reviews our understanding of molecular driving forces that trigger mutations in the SARS-CoV-2 virus. It also reports further studies on a new class of “supersartans” referred to herein as “bisartans”, bearing two anionic biphenyltetrazole moieties that show potential in models for blocking critical amino acids of mutants, such as arginine, in the Delta variant. Bisartans may also act at other targets essential for viral infection and replication (i.e., ACE2, furin cleavage site and 3CLpro), rendering them potential new drugs for additional experimentation and translation to human clinical trials.
Peptide Nucleic Acid Clamp‐Assisted Photothermal Multiplexed Digital PCR for Identifying SARS‐CoV‐2 Variants of Concern
The unprecedented demand for variants diagnosis in response to the COVID‐19 epidemic has brought the spotlight onto rapid and accurate detection assays for single nucleotide polymorphisms (SNPs) at multiple locations. However, it is still challenging to ensure simplicity, affordability, and compatibility with multiplexing. Here, a novel technique is presented that combines peptide nucleic acid (PNA) clamps and near‐infrared (NIR)‐driven digital polymerase chain reaction (dPCR) to identify the Omicron and Delta variants. This is achieved by simultaneously identifying highly conserved mutated signatures at codons 19, 614, and 655 of the spike protein gene. By microfluidically introducing graphene‐oxide‐nanocomposite into the assembled gelatin microcarriers, they achieved a rapid temperature ramping‐up rate and switchable gel‐to‐sol phase transformation synchronized with PCR activation under NIR irradiation. Two sets of duplex PCR reactions, each classifying respective PNA probes, are emulsified in parallel and illuminated together using a homemade vacuum‐based droplet generation device and a programmable NIR control module. This allowed for selective amplification of mutant sequences due to single‐base‐pair mismatch with PNA blockers. Sequence‐recognized bioreactions and fluorescent‐color scoring enabled quick identification of variants. This technique achieved a detection limit of 5,100 copies and a 5‐fold quantitative resolution, which is promising to unfold minor differences and dynamic changes. PNA‐assisted NIR photothermal multiplexed dPCR technique recognizes SNPs at codons T19R, O614G, and H655Y of the spike protein gene, thereby discriminating Omicron and Delta variants from the wild‐type of SARS‐CoV‐2. Gelatin microcarriers loaded with GO nanocomposite assist PCR thermocycling under NIR irradiation, where three PNA probes target against SNPs to selectively amplify mutated templates via replication with multi‐color labeling.
Analyzing the emerging patterns of SARS‐CoV‐2 Omicron subvariants for the development of next‐gen vaccine: An observational study
Background and Aim Understanding the prevalence and impact of SARS‐CoV‐2 variants has assumed paramount importance. This study statistically analyzed to effectively track the emergence and spread of the variants and highlights the importance of such investigations in developing potential next‐gen vaccine to combat the continuously emerging Omicron subvariants. Methods Transmission fitness advantage and effective reproductive number (Re) of epidemiologically relevant SARS‐CoV‐2 sublineages through time during the study period based on the GISAID data were estimated. Results The analyses covered the period from January to June 2023 around an array of sequenced samples. The dominance of the XBB variant strain, accounting for approximately 57.63% of the cases, was identified during the timeframe. XBB.1.5 exhibited 37.95% prevalence rate from March to June 2023. Multiple variants showed considerable global influence throughout the study, as sporadically documented. Notably, the XBB variant demonstrated an estimated relative 28% weekly growth advantage compared with others. Numerous variants were resistant to the over‐the‐counter vaccines and breakthrough infections were reported. Similarly, the efficacy of mAB‐based therapy appeared limited. However, it's important to underscore the perceived benefits of these preventive and therapeutic measures were restricted to specific variants. Conclusion Given the observed trends, a comprehensive next‐gen vaccine coupled with an advanced vaccination strategy could be a potential panacea in the fight against the pandemic. The findings suggest that targeted vaccine development could be an effective strategy to prevent infections. The study also highlights the need of global collaborations to rapidly develop and distribute the vaccines to ensure global human health.
A Smart Single‐Loop‐Mediated Isothermal Amplification Facilitates Flexible SNP Probe Design for On‐Site Rapid Differentiation of SARS‐CoV‐2 Omicron Variants
Rapid on‐site typing methods for SARS‐CoV‐2 variants of concern are crucial for its effective surveillance and control. Herein, a smart single‐loop‐mediated isothermal amplification (ssLAMP) method with the absence of an inner primer but the addition of a swarm primer for differentiation of SARS‐CoV‐2 Omicron variants is developed. This unique primer design strategy offers greater flexibility in introducing single nucleotide polymorphism (SNP) identification probes and enables multiple detection assays for SARS‐CoV‐2 Omicron variants including BA.1, BA.2, BA.3, BA.4, and BA.5. A 3D‐printed portable dual fluorescence visualization device and smartphone app are developed to enable point‐of‐care testing. This assay is rapid (within 90 min), highly sensitive (100 copies/reaction), and specific (identification of SNP) for SARA‐CoV‐2 Omicron variants. The ssLAMP method identifies five BA.5‐positive samples among 97 nasopharyngeal swab samples from the clinic, with a 100% concordance rate with Sanger sequencing. The ssLAMP assay system is expected to be utilized for on‐site, highly specific, and rapid visualization detection of SARS‐CoV‐2 and its variants, with great application potential in pathogen genotyping, early cancer screening, and other areas of SNP mutation detection. The ssLAMP method amplifies the nucleic acid of pathogen and identifies SNP mutations. By combining the portable detection device with smartphone‐based analysis software, enables rapid, on‐site SNP detection and genotyping of SARS‐Cov‐2 Omicron variants, providing a cost‐effective and field‐deployable solution for precise pathogen identification in clinical and resource‐limited settings.
Evaluation of SARS‐CoV‐2 Variants After the Declaration of End of COVID‐19 Pandemic: BA.2.86 (Pirola) and EG.5 (Eris) Variants as Global Public Health Concerns
Background and Aims Coronavirus disease 2019 (COVID‐19) caused by SARS‐CoV‐2 was first reported to the World Health Organization (WHO) on December 31, 2019. The WHO declared the COVID‐19 pandemic on March 11, 2020, after considering its impact on global public health. Therefore, we aim to assess the existing SARS‐CoV‐2 variants to understand their pathogenicity and threat after the pandemic phase of COVID‐19 so that the healthcare authorities can take prompt preventive measures. Methods We conducted a comprehensive literature search to gather information from publicly available sources. We extracted the relevant data from Google Scholar, PubMed, and Scopus. Results The virus infected over 770 million people and caused more than 6.9 million deaths worldwide. Since the inception of COVID‐19, the world has developed several therapeutic drugs and vaccines. Healthcare authorities worldwide have administered more than 13 billion vaccine doses. On May 5, 2023, the WHO declared the end of the COVID‐19 pandemic based on its global threat and impacts on human health. However, SARS‐CoV‐2 continues to mutate to create new variants that can threaten global public health anytime. We observed that BA.2.86 (Pirola) and EG.5 (Eris) variants as global public health concerns. Conclusion Genomic evolution of SARS‐CoV‐2 variants is a global public health concern for immune escape, vaccination effectiveness, therapeutic and diagnostic strategies. Therefore, we recommend close surveillance of these variants to determine their potential to cause severe disease and countermeasures.
Potent Anti‐SARS‐CoV‐2 Efficacy of COVID‐19 Hyperimmune Globulin from Vaccine‐Immunized Plasma
Coronavirus disease 2019 (COVID‐19) remains a global public health threat. Hence, more effective and specific antivirals are urgently needed. Here, COVID‐19 hyperimmune globulin (COVID‐HIG), a passive immunotherapy, is prepared from the plasma of healthy donors vaccinated with BBIBP‐CorV (Sinopharm COVID‐19 vaccine). COVID‐HIG shows high‐affinity binding to severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) spike (S) protein, the receptor‐binding domain (RBD), the N‐terminal domain of the S protein, and the nucleocapsid protein; and blocks RBD binding to human angiotensin‐converting enzyme 2 (hACE2). Pseudotyped and authentic virus‐based assays show that COVID‐HIG displays broad‐spectrum neutralization effects on a wide variety of SARS‐CoV‐2 variants, including D614G, Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Kappa (B.1.617.1), Delta (B.1.617.2), and Omicron (B.1.1.529) in vitro. However, a significant reduction in the neutralization titer is detected against Beta, Delta, and Omicron variants. Additionally, assessments of the prophylactic and treatment efficacy of COVID‐HIG in an Adv5‐hACE2‐transduced IFNAR−/− mouse model of SARS‐CoV‐2 infection show significantly reduced weight loss, lung viral loads, and lung pathological injury. Moreover, COVID‐HIG exhibits neutralization potency similar to that of anti‐SARS‐CoV‐2 hyperimmune globulin from pooled convalescent plasma. Overall, the results demonstrate the potential of COVID‐HIG against SARS‐CoV‐2 infection and provide reference for subsequent clinical trials. Coronavirus disease 2019 (COVID‐19) hyperimmune globulin (COVID‐HIG) prepared from the plasma of healthy donors vaccinated with BBIBP‐CorV (Sinopharm COVID‐19 vaccine) exhibits broad‐spectrum neutralization effects against multiple severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) variants of concern in vitro and shows protective effect against SARS‐CoV‐2 infection in vivo. It is currently under clinical evaluation for the treatment of COVID‐19 (NCT05173441).