Variants of SARS-CoV-2: Influences on the Vaccines' Effectiveness and Possible Strategies to Overcome Their Consequences.

The immune response elicited by the current COVID-19 vaccinations declines with time, especially among the immunocompromised population. Furthermore, the emergence of novel SARS-CoV-2 variants, particularly the Omicron variant, has raised serious concerns about the efficacy of currently available vaccines in protecting the most vulnerable people. Several studies have reported that vaccinated people get breakthrough infections amid COVID-19 cases. So far, five variants of concern (VOCs) have been reported, resulting in successive waves of infection. These variants have shown a variable amount of resistance towards the neutralising antibodies (nAbs) elicited either through natural infection or the vaccination. The spike (S) protein, membrane (M) protein, and envelope (E) protein on the viral surface envelope and the N-nucleocapsid protein in the core of the ribonucleoprotein are the major structural vaccine target proteins against COVID-19. Among these targets, S Protein has been extensively exploited to generate effective vaccines against COVID-19. Hence, amid the emergence of novel variants of SARS-CoV-2, we have discussed their impact on currently available vaccines. We have also discussed the potential roles of S Protein in the development of novel vaccination approaches to contain the negative consequences of the variants' emergence and acquisition of mutations in the S Protein of SARS-CoV-2. Moreover, the implications of SARS-CoV-2's structural proteins were also discussed in terms of their variable potential to elicit an effective amount of immune response.

Regulatory T Cells (Tregs) and COVID-19: Unveiling the Mechanisms, and Therapeutic Potentialities with a Special Focus on Long COVID.

The COVID-19 pandemic has caused havoc all around the world. The causative agent of COVID-19 is the novel form of the coronavirus (CoV) named SARS-CoV-2, which results in immune system disruption, increased inflammation, and acute respiratory distress syndrome (ARDS). T cells have been important components of the immune system, which decide the fate of the COVID-19 disease. Recent studies have reported an important subset of T cells known as regulatory T cells (Tregs), which possess immunosuppressive and immunoregulatory properties and play a crucial role in the prognosis of COVID-19 disease. Recent studies have shown that COVID-19 patients have considerably fewer Tregs than the general population. Such a decrement may have an impact on COVID-19 patients in a number of ways, including diminishing the effect of inflammatory inhibition, creating an inequality in the Treg/Th17 percentage, and raising the chance of respiratory failure. Having fewer Tregs may enhance the likelihood of long COVID development in addition to contributing to the disease's poor prognosis. Additionally, tissue-resident Tregs provide tissue repair in addition to immunosuppressive and immunoregulatory activities, which may aid in the recovery of COVID-19 patients. The severity of the illness is also linked to abnormalities in the Tregs' phenotype, such as reduced expression of FoxP3 and other immunosuppressive cytokines, including IL-10 and TGF-beta. Hence, in this review, we summarize the immunosuppressive mechanisms and their possible roles in the prognosis of COVID-19 disease. Furthermore, the perturbations in Tregs have been associated with disease severity. The roles of Tregs are also explained in the long COVID. This review also discusses the potential therapeutic roles of Tregs in the management of patients with COVID-19.

Spectrum, Outcomes, and Mortality Predictors of Acute Kidney Injury among Non-COVID-19 Patients during COVID-19 Pandemic: Data from Four Intensive Care Units.

Introduction: The data of acute kidney injury (AKI), that is, community-acquired AKI (CA-AKI) and hospital-acquired AKI (HA-AKI) among non-COVID patients from intensive care units (ICU) during the coronavirus disease-2019 (COVID-19) pandemic are scarce. We planned to study the change in the profile of such patients compared to the pre-pandemic era. Materials and methods: This prospective observational study was conducted at four ICUs dealing with non-COVID patients at a government hospital in North India, and was aimed at assessing outcomes, and mortality predictors of AKI among non-COVID patients during the COVID-19 pandemic. Renal and patient survival at ICU transfer-out and hospital discharge, ICU and hospital stay duration, mortality predictors, and dialysis requirement at discharge were evaluated. The current or previous COVID-19 infection, previous AKI or chronic kidney disease (CKD), organ donors, and organ transplant patients were excluded. Results: Among the 200 non-COVID-19 AKI patients, diabetes mellitus (DM), primary hypertension, and cardiovascular diseases were the predominant comorbidities in descending order. The commonest cause of AKI was severe sepsis, followed by systemic infections and post-surgery patients. Dialysis requirements at ICU admission during ICU stay and above 30 days were seen in 20.5, 47.5, and 6.5% of patients, respectively. Incidence of CA-AKI and HA-AKI was 1.24:1, whereas dialysis requirement above 30 days was 0.85:1, respectively. The 30-day mortality was 42%. Hepatic dysfunction [hazard ratio (HR): 3.471], septicemia (HR: 3.342), age above 60 years (HR: 4.000), higher sequential organ failure assessment (SOFA) score (HR: 1.107; p = 0.001), anemia (p = 0.003), and low serum iron (p = 0.001) were important mortality predictors in AKI. Conclusion: Compared to the pre-COVID era, CA-AKI was more common than HA-AKI due to restricted elective surgeries during the COVID-19 pandemic. Acute kidney injury with multiorgan involvement and hepatic dysfunction, elderly age with higher SOFA score and sepsis were predictors of adverse renal and patient outcomes. How to cite this article: Singh B, Dogra PM, Sood V, Singh V, Katyal A, Dhawan M, et al. Spectrum, Outcomes, and Mortality Predictors of Acute Kidney Injury among Non-COVID-19 Patients during COVID-19 Pandemic: Data from Four Intensive Care Units. Indian J Crit Care Med 2023;27(2):119-126.

Updated Insights into the T Cell-Mediated Immune Response against SARS-CoV-2: A Step towards Efficient and Reliable Vaccines.

The emergence of novel variants of SARS-CoV-2 and their abilities to evade the immune response elicited through presently available vaccination makes it essential to recognize the mechanisms through which SARS-CoV-2 interacts with the human immune response. It is essential not only to comprehend the infection mechanism of SARS-CoV-2 but also for the generation of effective and reliable vaccines against COVID-19. The effectiveness of the vaccine is supported by the adaptive immune response, which mainly consists of B and T cells, which play a critical role in deciding the prognosis of the COVID-19 disease. T cells are essential for reducing the viral load and containing the infection. A plethora of viral proteins can be recognized by T cells and provide a broad range of protection, especially amid the emergence of novel variants of SARS-CoV-2. However, the hyperactivation of the effector T cells and reduced number of lymphocytes have been found to be the key characteristics of the severe disease. Notably, excessive T cell activation may cause acute respiratory distress syndrome (ARDS) by producing unwarranted and excessive amounts of cytokines and chemokines. Nevertheless, it is still unknown how T-cell-mediated immune responses function in determining the prognosis of SARS-CoV-2 infection. Additionally, it is unknown how the functional perturbations in the T cells lead to the severe form of the disease and to reduced protection not only against SARS-CoV-2 but many other viral infections. Hence, an updated review has been developed to understand the involvement of T cells in the infection mechanism, which in turn determines the prognosis of the disease. Importantly, we have also focused on the T cells' exhaustion under certain conditions and how these functional perturbations can be modulated for an effective immune response against SARS-CoV-2. Additionally, a range of therapeutic strategies has been discussed that can elevate the T cell-mediated immune response either directly or indirectly.

Omicron variant (B.1.1.529) and its sublineages: What do we know so far amid the emergence of recombinant variants of SARS-CoV-2?

Since the start of the COVID-19 pandemic, numerous variants of SARS-CoV-2 have been reported worldwide. The advent of variants of concern (VOCs) raises severe concerns amid the serious containment efforts against COVID-19 that include physical measures, pharmacological repurposing, immunization, and genomic/community surveillance. Omicron variant (B.1.1.529) has been identified as a highly modified, contagious, and crucial variant among the five VOCs of SARS-CoV-2. The increased affinity of the spike protein (S-protein), and host receptor, angiotensin converting enzyme-2 (ACE-2), due to a higher number of mutations in the receptor-binding domain (RBD) of the S-protein has been proposed as the primary reason for the decreased efficacy of majorly available vaccines against the Omicron variant and the increased transmissible nature of the Omicron variant. Because of its significant competitive advantage, the Omicron variant and its sublineages swiftly surpassed other variants to become the dominant circulating lineages in a number of nations. The Omicron variant has been identified as a prevalent strain in the United Kingdom and South Africa. Furthermore, the emergence of recombinant variants through the conjunction of the Omicron variant with other variants or by the mixing of the Omicron variant's sublineages/subvariants poses a major threat to humanity. This raises various issues and hazards regarding the Omicron variant and its sublineages, such as an Omicron variant breakout in susceptible populations among fully vaccinated persons. As a result, understanding the features and genetic implications of this variant is crucial. Hence, we explained in depth the evolution and features of the Omicron variant and analyzed the repercussions of spike mutations on infectiousness, dissemination ability, viral entry mechanism, and immune evasion. We also presented a viewpoint on feasible strategies for precluding and counteracting any future catastrophic emergence and spread of the omicron variant and its sublineages that could result in a detrimental wave of COVID-19 cases.

Modern drug discovery applications for the identification of novel candidates for COVID-19 infections.

In early December 2019, a large pneumonia epidemic occurred in Wuhan, China. The World Health Organization is concerned about the outbreak of another coronavirus with the powerful, rapid, and contagious transmission. Anyone with minor symptoms like fever and cough or travel history to contaminated places might be suspected of having COVID-19. COVID-19 therapy focuses on treating the disease's symptoms. So far, no such therapeutic molecule has been shown effective in treating this condition. So the treatment is mostly supportive and plasma. Globally, numerous studies and researchers have recently started fighting this virus. Vaccines and chemical compounds are also being investigated against infection. COVID-19 was successfully diagnosed using RNA detection and very sensitive RT-PCR (reverse transcription-polymerase chain reaction). The evolution of particular vaccinations is required to reduce illness severity and spread. Numerous computational analyses and molecular docking have predicted various target compounds that might stop this condition. This paper examines the main characteristics of coronavirus and the computational analyses necessary to avoid infection.

Role of natural products towards the SARS-CoV-2: A critical review.

Despite the fact that various therapeutic compounds are being investigated, there is still a scarcity of effective and reliable therapeutic regimens to treat COVID-19. Ever since the COVID-19 pandemic, a diversity of traditional herbal treatments has been investigated to cure infected people, either alone or in conjunction with mainstream pharmaceuticals, with encouraging outcomes. In this article, we look at the latest research on the usage of natural products to alleviate the severity of COVID-19. To determine the activity of the natural products, act against SARS-CoV-2 to various targets like Mpro, ACE-II, papain-like, chymotrypsin-like proteases, and some antiviral targets. The processes underlying this preventative or therapeutic action are also examined. We used PubMed, Scopus, Google Scholar, and the WHO site to perform our review. The anti-SARS-CoV-2 impacts of various herbal extracts and purified compounds may be mediated via direct prevention of viral replication or entrance. Interestingly, certain items might avert SARS-CoV-2 from infecting human cells by blocking the ACE-2 protein or the serine protease TMPRRS2. Natural products have also been stated to suppress proteins intricate in the virus life cycle, like papain-like and chymotrypsin-like proteases. To conclude, natural products can be used alone or in combination as remedies or treatments for COVID-19. In addition, their compositions may provide insight into the development of effective and reliable antiviral drugs.

Strengthening vaccines and medicines manufacturing capabilities in Africa: challenges and perspectives.

Africa carries a high burden of infectious diseases. Every year, millions of Africans contract tuberculosis, malaria, and many other diseases. Malaria kills hundreds of thousands of children under the age of five years annually. More than 11,000 people died during the 2014-2016 Ebola outbreak in West Africa; still, occasional cases of Ebola, as well as monkeypox, periodically appear in the Democratic Republic of Congo. Since most of the African countries gained their independence during the 1960s, the continent has relied heavily on the outside world for diagnostics, medicines, vaccines, personal protective equipment, and other medical supplies. Africa consumes nearly 25% of the globally produced vaccines but imports 99% and 95% of its vaccines and medicines, respectively. The 55 African countries were not able to ensure the health of 1.3 billion Africans during the COVID-19 pandemic but had to rely on other global initiatives and other countries for help and support. However, the pandemic and the shortage of vaccines may have been the much-needed trigger for this situation to change. "When misfortunes increase, they erase each other." Naguib Mahfouz (1911-2006).

MicroRNAs in the development of potential therapeutic targets against COVID-19: A narrative review.

BACKGROUND: As the therapeutic regimens against the COVID-19 remain scarce, the microRNAs (miRNAs) can be exploited to generate efficient therapeutic targets. The miRNAs have been found to play pivotal roles in the several regulatory functions influencing the prognosis of viral infection. The miRNAs have a prospective role in the up and down regulation of the ACE2 receptors. This review examines the clinical applications, as well as the possible threats associated with the use of miRNAs to combat the deleterious consequences of SARS-CoV-2 infection. METHODOLOGY: This article was compiled to evaluate how the miRNAs are involved in the SARS-CoV-2 pathogenesis and infection, and their potential functions which could help in the development of therapeutic targets against the COVID-19. The sources of the collected information include the several journals, databases and scientific search engines such as the Google scholar, Pubmed, Science direct, official website of WHO, among the other sites. The investigations on the online platform were conducted using the keywords miRNA biogenesis, miRNA and ACE2 interaction, therapeutic role of miRNAs against SARS-CoV-2 and miRNA therapy side effects. RESULTS: This review has highlighted that the miRNAs can be exploited to generate potential therapeutic targets against the COVID-19. Changes in the miRNA levels following viral replication are an essential component of the host response to infection. The collection and modification of miRNA modulates may help to minimize the deleterious consequences of SARS-CoV-2 infection, such as by controlling or inhibiting the generation of cytokines and chemokines. The degradation of viral RNA by the cellular miRNAs, along with the reduced expression of ACE2 receptors, can substantially reduce the viral load. Specific miRNAs have been found to have an antiviral influence, allowing the immune system to combat the infection or forcing the virus into a latency stage. CONCLUSION: This review summarizes several studies revealing the involvement of miRNAs in diverse and complex processes during the infection process of SARS-CoV-2. The miRNAs can substantially reduce the viral load by degradation of viral RNA and reduced expression of ACE2 receptors, besides mitigating the deleterious consequences of the exaggerated secretion of cytokines. Extensive investigations need to be done by the scientific community to utilize the miRNA based strategies for the development of effective therapeutic targets against the COVID-19.

Comparative overview of emerging RNA viruses: Epidemiology, pathogenesis, diagnosis and current treatment.

From many decades, emerging infections have threatened humanity. The pandemics caused by different CoVs have already claimed and will continue to claim millions of lives. The SARS, Ebola, MERS epidemics and the most recent emergence of COVID-19 pandemic have threatened populations across borders. Since a highly pathogenic CoV has been evolved into the human population in the twenty-first century known as SARS, scientific advancements and innovative methods to tackle these viruses have increased in order to improve response preparedness towards the unpredictable threat posed by these rapidly emerging pathogens. Recently published review articles on SARS-CoV-2 have mainly focused on its pathogenesis, epidemiology and available treatments. However, in this review, we have done a systematic comparison of all three CoVs i.e., SARS, MERS and SARS-CoV-2 along with Ebola and Zika in terms of their epidemiology, virology, clinical features and current treatment strategies. This review focuses on important emerging RNA viruses starting from Zika, Ebola and the CoVs which include SARS, MERS and SARS-CoV-2. Each of these viruses has been elaborated on the basis of their epidemiology, virulence, transmission and treatment. However, special attention has been given to SARS-CoV-2 and the disease caused by it i.e., COVID-19 due to current havoc caused worldwide. At the end, insights into the current understanding of the lessons learned from previous epidemics to combat emerging CoVs have been described. The travel-related viral spread, the unprecedented nosocomial outbreaks and the high case-fatality rates associated with these highly transmissible and pathogenic viruses highlight the need for new prophylactic and therapeutic actions which include but are not limited to clinical indicators, contact tracing, and laboratory investigations as important factors that need to be taken into account in order to arrive at the final conclusion.

Swine coronaviruses (SCoVs) and their emerging threats to swine population, inter-species transmission, exploring the susceptibility of pigs for SARS-CoV-2 and zoonotic concerns.

Swine coronaviruses (SCoVs) are one of the most devastating pathogens affecting the livelihoods of farmers and swine industry across the world. These include transmissible gastroenteritis virus (TGEV), porcine epidemic diarrhea virus (PEDV), porcine respiratory coronavirus (PRCV), porcine hemagglutinating encephalomyelitis virus (PHEV), swine acute diarrhea syndrome coronavirus (SADS-CoV), and porcine delta coronavirus (PDCoV). Coronaviruses infect a wide variety of animal species and humans because these are having single stranded-RNA that accounts for high mutation rates and thus could break the species barrier. The gastrointestinal, cardiovascular, and nervous systems are the primary organ systems affected by SCoVs. Infection is very common in piglets compared to adult swine causing high mortality in the former. Bat is implicated to be the origin of all CoVs affecting animals and humans. Since pig is the only domestic animal in which CoVs cause a wide range of diseases; new coronaviruses with high zoonotic potential could likely emerge in the future as observed in the past. The recently emerged severe acute respiratory syndrome coronavirus virus-2 (SARS-CoV-2), causing COVID-19 pandemic in humans, has been implicated to have animal origin, also reported from few animal species, though its zoonotic concerns are still under investigation. This review discusses SCoVs and their epidemiology, virology, evolution, pathology, wildlife reservoirs, interspecies transmission, spill-over events and highlighting their emerging threats to swine population. The role of pigs amid ongoing SARS-CoV-2 pandemic will also be discussed. A thorough investigation should be conducted to rule out zoonotic potential of SCoVs and to design appropriate strategies for their prevention and control.

Understanding the omicron variant (B.1.1.529) of SARS-CoV-2: Mutational impacts, concerns, and the possible solutions.

Despite many nations' best efforts to contain the so-called COVID-19 pandemic, the emergence of the SARS-CoV-2 Omicron strain (B.1.1.529) has been identified as a serious concern. After more than two years of COVID-19 pandemic and more than a year of worldwide vaccination efforts, the globe will not be free of COVID-19 variants such as Delta and Omicron variants. According to current statistics, the Omicron variant has more than 30 mutations when contrasted to other VOCs such as Alpha (B.1.1.7), Beta (B.1.351), and Delta (B.1.617.2). High numbers of changes, particularly in the spike protein (S-Protein), raise worries about the virus's capacity to resist pre-existing immunity acquired by vaccination or spontaneous infection and antibody-based therapy. The Omicron variant raised international concerns, resuming travel bans and coming up with many questions about its severity, transmissibility, testing, detection, and vaccines efficiency against it. Additionally, inadequate health care infrastructures and many immunocompromised individuals increase the infection susceptibility. The current status of low vaccination rates will play a significant role in omicron spreading and create a fertile ground for producing new variants. As a result, this article emphasizes the mutational changes and their consequences. In addition, the potential preventing measures have been examined in detail.