The Common Systemic and Local Adverse Effects of the Sinovac COVID-19 Vaccine: An Observational Study From Pakistan.

Background Vaccination acts by boosting the capacity of a person's immune system to identify and effectively resist infection-causing bacteria and viruses, as it stimulates the immune system to respond to the vaccine's antigens. The immunological response may include local and systemic symptoms, including pain at the injection site and fever, respectively. The Sinovac vaccine is an inactivated virus vaccine made in China and is one of the most widely used vaccines in many countries; however, the side effects of the Sinovac vaccine have not been well-studied in our population. Therefore, this study assessed the prevalence of side effects experienced by participants after receiving the Sinovac vaccine. Methodology This multicenter, cross-sectional study was conducted using a non-probability sampling method. The duration of the study was six months from May 1, 2022, to October 31, 2022. A total of 800 participants who were completely vaccinated with the Sinovac vaccine were included in the study. For categorical data, frequencies and percentages were documented, while for continuous data, such as age, height, weight, and the duration of comorbidities, means and standard deviations were evaluated. Results The study findings showed that out of 800 participants, 534 (66.8%) were males and 266 (33.3%) were females, with a mean age of 41.20 ± 13.70 years. Among them, 162 (20.3%) had hypertension, and 104 (13.0%) had diabetes. Following the first dose of the Sinovac vaccine, fever was the most commonly reported side effect in 350 (43.8%) participants. Additionally, pain at the injection site in 238 (29.8%) participants, followed by swelling at the injection site in 228 (28.5%) recipients, were among other common side effects. Following the second dose of the Sinovac vaccine, fever was the most commonly reported side effect in 262 (32.8%) participants. Conclusions This study concluded that fever was the most frequent systemic side effect, whereas pain and swelling at the injection site were the most frequent local side effects following the administration of the first and second doses of the Sinovac vaccine. Both dosages of Sinovac were well-tolerated, and the majority of the adverse effects were minor and self-limiting.

Same day discharge after structural heart disease interventions in the era of the coronavirus-19 pandemic and beyond.

With recent advancements in imaging modalities and techniques and increased recognition of the long-term impact of several structural heart disease interventions, the number of procedures has significantly increased. With the increase in procedures, also comes an increase in cost. In view of this, efficient and cost-effective methods to facilitate and manage structural heart disease interventions are a necessity. Same-day discharge (SDD) after invasive cardiac procedures improves resource utilization and patient satisfaction. SDD in appropriately selected patients has become the standard of care for some invasive cardiac procedures such as percutaneous coronary interventions. This is not the case for the majority of structural heart procedures. With the coronavirus disease 2019 pandemic, safely reducing the duration of time spent within the hospital to prevent unnecessary exposure to pathogens has become a priority. In light of this, it is prudent to assess the feasibility of SDD in several structural heart procedures. In this review we highlight the feasibility of SDD in a carefully selected population, by reviewing and summarizing studies on SDD among patients undergoing left atrial appendage occlusion, patent foramen ovale/atrial septal defect closure, Mitra-clip, and trans-catheter aortic valve replacement procedures.

Comparative mutational analysis of SARS-CoV-2 isolates from Pakistan and structural-functional implications using computational modelling and simulation approaches.

SARS-CoV-2, an RNA virus, has been prone to high mutations since its first emergence in Wuhan, China, and throughout its spread. Its genome has been sequenced continuously by many countries, including Pakistan, but the results vary. Understanding its genomic patterns and connecting them with phenotypic features will help in devising therapeutic strategies. Thus, in this study, we explored the mutation landscape of 250 Pakistani isolates of SARS-CoV-2 genomes to check the genome diversity and examine the impact of these mutations on protein stability and viral pathogenesis in comparison with a reference sequence (Wuhan NC 045512.2). Our results revealed that structural proteins mainly exhibit more mutations than others in the Pakistani isolates; in particular, the nucleocapsid protein is highly mutated. In comparison, the spike protein is the most mutated protein globally. Furthermore, nsp12 was found to be the most mutated NSP in the Pakistani isolates and worldwide. Regarding accessory proteins, ORF3A is the most mutated in the Pakistani isolates, whereas ORF8 is highly mutated in world isolates. These mutations decrease the structural stability of their proteins and alter different biological pathways. Molecular docking, the dissociation constant (KD), and MM/GBSA analysis showed that mutations in the S protein alter its binding with ACE2. The spike protein mutations D614G-S943T-V622F (-75.17 kcal/mol), D614G-Q677H (-75.78 kcal/mol), and N74K-D614G (-73.84 kcal/mol) exhibit stronger binding energy than the wild type (-66.34 kcal/mol), thus increasing infectivity. Furthermore, the simulation results strongly corroborated the predicted protein servers. Our analysis findings also showed that E, M, ORF6, ORF7A, ORF7B, and ORF10 are the most stable coding genes; they may be suitable targets for vaccine and drug development.

Therapeutic and vaccine strategies against SARS-CoV-2: past, present and future

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019. It was first reported in Wuhan, China and has since become a global health concern. Keeping in view, the magnitude of the problem, scientists around the globe are working to develop effective therapeutic strategies. This review focuses on previous findings regarding SARS-CoV, which may prove helpful in future research on SARS-CoV-2. In addition, it also highlights recent developments in medicine and biotechnology toward developing effective drugs and vaccines against SARS-CoV-2. This review will analyze available data on this topic and will help researchers develop new thoughts using information already available as a step toward developing novel therapeutic strategies against SARS-CoV-2.

Structural insights into the mechanism of RNA recognition by the N-terminal RNA-binding domain of the SARS-CoV-2 nucleocapsid phosphoprotein.

The emergence of recent SARS-CoV-2 has become a global health issue. This single-stranded positive-sense RNA virus is continuously spreading with increasing morbidities and mortalities. The proteome of this virus contains four structural and sixteen nonstructural proteins that ensure the replication of the virus in the host cell. However, the role of phosphoprotein (N) in RNA recognition, replicating, transcribing the viral genome, and modulating the host immune response is indispensable. Recently, the NMR structure of the N-terminal domain of the Nucleocapsid Phosphoprotein has been reported, but its precise structural mechanism of how the ssRNA interacts with it is not reported yet. Therefore, here, we have used an integrated computational pipeline to identify the key residues, which play an essential role in RNA recognition. We generated multiple variants by using an alanine scanning strategy and performed an extensive simulation for each system to signify the role of each interfacial residue. Our analyses suggest that residues T57A, H59A, S105A, R107A, F171A, and Y172A significantly affected the dynamics and binding of RNA. Furthermore, per-residue energy decomposition analysis suggests that residues T57, H59, S105 and R107 are the key hotspots for drug discovery. Thus, these residues may be useful as potential pharmacophores in drug designing.