Host Protective Immunity against Severe Acute Respiratory Coronavirus 2 (SARS-CoV-2) and the COVID-19 Vaccine-Induced Immunity against SARS-CoV-2 and Its Variants.

The world is now apparently at the last/recovery stage of the COVID-19 pandemic, starting from 29 December 2019, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With the progression of time, several mutations have taken place in the original SARS-CoV-2 Wuhan strain, which have generated variants of concern (VOC). Therefore, combatting COVID-19 has required the development of COVID-19 vaccines using several platforms. The immunity induced by those vaccines is vital to study in order to assure total protection against SARS-CoV-2 and its emerging variants. Indeed, understanding and identifying COVID-19 protection mechanisms or the host immune responses are of significance in terms of designing both new and repurposed drugs as well as the development of novel vaccines with few to no side effects. Detecting the immune mechanisms for host protection against SARS-CoV-2 and its variants is crucial for the development of novel COVID-19 vaccines as well as to monitor the effectiveness of the currently used vaccines worldwide. Immune memory in terms of the production of neutralizing antibodies (NAbs) during reinfection is also very crucial to formulate the vaccine administration schedule/vaccine doses. The response of antigen-specific antibodies and NAbs as well as T cell responses, along with the protective cytokine production and the innate immunity generated upon COVID-19 vaccination, are discussed in the current review in comparison to the features of naturally induced protective immunity.

How do the severe acute respiratory coronavirus 2 (SARS-CoV-2) and its variants escape the host protective immunity and mediate pathogenesis?

Background: To protect the global population from the ongoing COVID-19 pandemic caused by the severe acute respiratory ß-coronavirus 2 (SARS-CoV-2), a number of vaccines are currently being used in three dosages (i.e., along with the booster dose) to induce the immunity required to combat the SARS-CoV-2 and its variants. So far, several antivirals and the commercial vaccines have been found to evoke the required humoral and cellular immunity within a huge population around world. However, an important aspect to consider is the avoidance mechanism of the host protective immunity by SARS-CoV-2 variants. Main body of the abstract: Indeed, such an immune escape strategy has been noticed previously in case of SARS-CoV-1 and the Middle East Respiratory Syndrome coronavirus (MERS-CoV). Regarding the SARS-CoV-2 variants, the most important aspect on vaccine development is to determine whether the vaccine is actually capable to elicit the immune response or not, especially the viral spike (S) protein. Short conclusion: Present review thus focused on such elicitation of immunity as well as pondered to the avoidance of host immunity by the SARS-CoV-2 Wuhan strain and its variants.

Overview of dreadful consequences of SARS-CoV-2 invasion in Italy from March 2020 to March 2022.

Background: The unpredicted pandemic disease COVID-19 first flared up adversely in Europe by imparting interminable force of infected and fatality cases to Italy. In late February 2020, the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in northern Italy and swiftly proliferated to the entire country, albeit continuous to date (23 March 2022) with a lesser extent of deadliness. Current review focused on the invasions and the associated consequences by SARS-CoV-2 during the period of March 2020-March 2022. Main body of the abstract: Initially, the lethality and transmissibility of the novel virus made Italy stunned within 1 month, the number of death cases reached 12,428 at the end of March 2020. The Italian Government announced an immediate emergency phase in entire country, educational institutions to local businesses, manufacturing works, cultural activities to elective activities were rescinded and all the hospitals to morgues were swamped, ensuing that fear of epidemic was impended. Besides, the Italian National Health System and Service coordinated massive public health interventions and conferred unprecedented efforts to limit the high mortality rate of the first wave of infection. Amidst 2 years of epidemic (as of 23 March 2022), Italy has documented 14,070,450 (23.74% of the population) confirmed infected cases, 12,685,306 (21.41% of the population) healed cases, 158,254 death cases (0.27% of the population) and ranking 9th worldwide in the number of deaths. Short conclusion: Based on publicly available Italian Ministry of Health COVID-19 data, current review has comprehended region-wise total infected cases, death cases and healed cases for three consecutive years 2020-2022 to foresee different patterns of the regional outbreak and gradual subservience. At a glance, we highlighted the overview of the exhaustion and exertion of COVID-19 crisis throughout the periods in Italy.

Association of Gut Microbiota with Inflammatory Bowel Disease and COVID-19 Severity: A Possible Outcome of the Altered Immune Response.

Inflammatory bowel disease could be induced by SARS-CoV-2, involved in alteration of gut microbiota during the respiratory viral infection. Presence of viral RNA in fecal samples for longer period, even after the clearance of the virus from respiratory tract, is suggestive of dysbiosis leading to the poor prognosis of COVID-19 in hospitalized patients. Gut microbiome (GM) plays a significant role to stimulate the modulated antiviral immune response against invading pathogens regulating the physiological homeostasis. GM profile of COVID-19 patients has revealed the drastic depletion of dominant families of commensals in the gut such as, Bacteroidaceae, Lachnospiraceae and Ruminococcaceae to be replaced with Enterococcus, Staphylococcus, Streptococcus, Serratia etc. Immune dysfunction of Th1-Th17 cells along gut-lung axis impairs the mucosal lining translocating the microorganisms including commensals and metabolites to other body organs like lungs, brain, kidney through circulation. These events may cause hyper inflammations associated with excessive secretion of cytokines and chemokines to form the cytokine storm causing ARDS. Gut virome could interact with microbiome and immune cells, help establishing the antiviral immune signaling, important for health maintenance/ or in disease progression. Essentially, these immunological strategies are needed to use in future prospective therapeutics to control the severity events.

COVID-19 vaccines: their effectiveness against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its emerging variants.

Background: The world has been suffering from the COVID-19 pandemic (officially declared by WHO in March 2020), caused by the severe acute respiratory ß-coronavirus 2 (SARS-CoV-2) since the last week of December 2019. The disease was initially designated as a Public Health Emergency of International Concern on January 30, 2020. In order to protect the health of mass public, an array of research on drugs and vaccines against SARS-CoV-2 has been conducted globally. However, the emerging variants of SARS-CoV-2, i.e., Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), and Delta (B.1.617.2) variants which evolved in late 2020 and the Omicron variant (B.1.1.529) which emerged in November 2021 along with its subvariant BA.2 which was first identified in India and South Africa in late December 2021, have raised the doubt about the efficiency of the currently used vaccines especially in terms of the consistent potential to produce neutralizing antibodies targeting the viral spike (S) protein. Main body of the abstract: The present review discussed the functional details of major vaccines regarding their efficiency against such variants during the pandemic. Overall, the mRNA vaccines have shown around 94% effectiveness; the adenovector vaccine showed approximately 70% efficacy, whereas Sputnik V vaccines showed around 92% effectiveness; the inactivated whole-virus vaccine CoronaVac/PiCoVacc and BBIBP-CorV showed a varying effectiveness of 65-86% according to the geographic locations; the subunit vaccine NVX-CoV2373 has shown 60-89% effectiveness along with the global regions against the wild-type SARS-CoV-2 strain. However, reduced effectiveness of these vaccines against the SARS-CoV-2 variants was noticed which is suggestive for the further administration of booster dose. Short conclusion: Maximum variants of SARS-CoV-2 emerged during the second wave of COVID-19; and extensive studies on the viral genomic sequences from all geographical locations around the world have been conducted by an array of groups to assess the possible occurrence of mutations(s) specially within the receptor binding domain of the viral spike (S) protein. Mutational similarities and the new or critical mutations within all variants have been clearly identified so far. The study of effectiveness of the currently used vaccines is also ongoing. The persistence of memory B cell action and the other immune components as well as the administration of booster dose is expected to mitigate the disease.

mRNA Vaccines as an Efficient Approach for the Rapid and Robust Induction of Host Immunity Against SARS-CoV-2.

Among the currently used COVID-19 vaccines, the mRNA-based vaccines drew the interest of the scientists because of its potent and versatile nature in mitigating the disease efficiently through increased translation as well as the robust modulation of the innate and adaptive immune responses within the host. The naked or lipid encapsulated mRNAs are usually optimized in order to formulate the vaccine. One of the interesting advantage of using mRNA vaccines is that such platform can even be used to mitigate other infectious diseases like influenza, zika, and rabies. However, the leading COVID-19 mRNA vaccines, i.e., mRNA-1273 and BNT162b2, have already been noticed to possess around 95% efficacy in provoking both the humoral and cell mediated immunity against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, causing the ongoing COVID-19 pandemic.

A review on the induction of host immunity by the current COVID-19 vaccines and a brief non-pharmaceutical intervention to mitigate the pandemic.

BACKGROUND: To mitigate the current COVID-19 pandemic by the severe acute respiratory coronavirus 2 (SARS-CoV-2), designing of repurposed antiviral drugs and the development of vaccines using different platforms have been the most significant work by the scientists around the world since the beginning of 2020. MAIN BODY OF THE ABSTRACT: While positive results are being noticed with the currently used vaccines, the emerging variants of SARS-CoV-2 as well as the second wave of COVID-19 pandemic put the global public health in the deadliest health issue. Present review attempted to focus on the development of the current COVID-19 situation in the light of knowledge gathered from the recently published literature. An important facet regarding the COVID-19 severity is the avoidance of host immunity by the SARS-CoV-2 and its variants. Indeed, the genetic similarities between SARS-CoV-2, SARS-CoV-1 and the Middle East respiratory syndrome coronavirus (MERS-CoV) showed the viral escape strategies of the protective host immunity which appeared as the major problem for the effective vaccine development. SHORT CONCLUSION: Present review discussed the prescribed platforms of vaccine development and pondered on the cellular and humoral immune responses by vaccines; and apart from vaccination approaches, non-pharmaceutical intervention approaches have also been pondered based on modeling rules.

COVID-19 Pandemic and the Convalescent Plasma Therapy: Possible Benefits and Risks.

PURPOSE OF REVIEW: COVID-19 pandemic has been the major threat to the global public health for a year (last of 2019-till date); and unfortunately, there is still as no specific antiviral agent which can be effectively used against this disease curation. Present review focused on the application of the convalescent plasma (CP) therapy as a quick remediation of the disease severity. RECENT FINDINGS: While several drugs have been repurposed based on a number of completed clinical trials together with a huge ongoing effort to develop appropriate vaccine against the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the therapeutic approach of the CP therapy appears to be one of the effective methods to rescue the severely affected COVID-19 patients. Such a therapy based on passive immunity evolved from the SARS-CoV-2-infected patients who have fully recovered from COVID-19; and hence these individuals are quite likely to possess high titers of the SARS-CoV-2-neutralizing immunoglobulins (antibodies). However, there are some risks such therapy, and its effectivity also appeared doubtful in some cases. Thus, the current review discussed the issues raised by the administration of such plasma into the SARS-CoV-2-infected individuals. SUMMARY: Application of CP therapy has been conducted since long time; and for the mitigation of COVID-19 severity, such pharmaceutical strategy is also being employed in spite of several risks which actually can be monitored as well as optimized in order to combat the SARS-CoV-2 infection.

A Review on the Effectivity of the Current COVID-19 Drugs and Vaccines: Are They Really Working Against the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variants?

PURPOSE OF REVIEW: In order to eradicate the COVID-19 pandemic, scientists around the world have been working very hard for a year or more with the motto of designing effective drugs and vaccines against the severe acute respiratory coronavirus 2 (SARS-CoV-2). Along with the positive results with the antiviral drugs and a few commercialized vaccines, the unresponsiveness as well as some side effects of such therapies have also been noticed, possibly due to the emergence of the SARS-CoV-2 variants. Therefore, current review summarized the actual effectiveness of the antivirals and vaccines which are in current use for the treatment of the COVID-19 patients. RECENT FINDINGS: So far, some drugs have been found with hopeful results among which remdesivir and arbidol are with momentous clinical progress. Besides drug designing, vaccine development has been a major effort whereby the mRNA-1273 (Moderna) and BNT162b2 (Pfizer-BioNTech) vaccines showed the required efficacy and have been approved by the US Food and Drug Administration (USFDA). SUMMARY: While a number of existing/repurposed/repositioned or new drugs and the currently used commercial vaccines against SARS-CoV-2 apparently seem to be effective against COVID-19 mitigation, the new variants of the virus as well as the recently increased cases raised the doubt about the usefulness of these agents. Current review figured out the efficacy of different drugs and vaccines in terms of their action potential against SARS-CoV-2 and further recommended some useful measures which may be useful for future remedies.

Developmental Status of the Potential Vaccines for the Mitigation of the COVID-19 Pandemic and a Focus on the Effectiveness of the Pfizer-BioNTech and Moderna mRNA Vaccines.

PURPOSE OF REVIEW: Along with the continued in silico-based studies for drug designing and repurposing followed by the corresponding cell culture studies, the ongoing clinical trials with some completed regarding finding the drug efficacy and the vaccine development against the severe acute respiratory coronavirus 2 (SARS-CoV-2) have been the most functional and indispensable issue during the current COVID-19 pandemic within 2020 and onward. The present review attempted to figure out the update on this effective vaccine and discussed the other promising vaccines. RECENT FINDINGS: A range of investigations on the SARS-CoV-2 genomics, on its similarities with SARS-CoV-1, and with the Middle East respiratory syndrome coronavirus (MERS-CoV) have been accomplished and the host immune dodging mechanisms by the SARS-CoV-2 have been unraveled which in turn led the scientists around the world to work rigorously on the vaccine development. Working with various vaccine platforms so far revealed the efficacy of the mRNA-1273 vaccine as the most effective one as resulted through the clinical trials which resulted in 95% positive output. SUMMARY: Although currently commercialized mRNA-1273 vaccine appears to be effective, still several points are to be pondered regarding the sustainability of vaccine efficacy against the rising variants of SARS-CoV-2.

A comparative review of pathogenesis and host innate immunity evasion strategies among the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV).

COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has put the global public health at its highest threat around the world. Previous epidemic caused by the acute respiratory syndrome coronavirus (SARS-CoV) in 2002 is also considered since both the coronaviruses resulted in the similar clinical complications. The outbreak caused by the Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 had a low rate of disease transmission and death cases. Modes of entry by MERS and SARS coronaviruses are similar to that of SARS-CoV-2, except MERS-CoV utilize different receptor. They all belong to the lineage C of ß-coronavirus. Based on the information from the previous reports, the present review is mainly focused on the mechanisms of disease progression by each of these viruses in association to their strategies to escape the host immunity. The viral entry is the first step of pathogenesis associated with attachment of viral spike protein with host receptor help releasing the viral RNA into the host cell. Models of molecular pathogenesis are outlined with virus strategies escaping the host immunity along with the role of various inflammatory cytokines and chemokines in the process. The molecular aspects of pathogenesis have also been discussed.

Antiviral drugs against severe acute respiratory syndrome coronavirus 2 infection triggering the coronavirus disease-19 pandemic.

So far, lots of analyses have been conducted to invent the appropriate therapeutic targets for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The category and the strategies for treating the virus are described in this review together with mentioning some specific drugs. Of them, saikosaponin possesses affinity of the drug toward nonstructural protein 15 and the spike glycoprotein of the SARS-CoV-2. The nucleotide inhibitors such as sofosbuvir, ribavirin, galidesivir, remdesivir, favipiravir, cefuroxime, tenofovir, and hydroxychloroquine (HCHL), setrobuvir, YAK, and IDX-184 were found to be effective in binding to SARS-CoV-2 RNA-dependent RNA polymerase. From the antimalarial and anti-inflammatory category, chloroquine and its derivative HCHL have already been approved by the U.S. Food and Drug Administration for emergency treatment of SARS-CoV-2 infection. The other drugs such as favipiravir and lopinavir/ritonavir under the antiviral category, the angiotensin-converting enzyme 2 (the renin-angiotensin system inhibitors), remdesivir (RNA polymerase inhibitor) from antiviral category, cepharanthine from anti-inflammatory category, etc., have been pointed based on the previous literature published. Besides, the assessment of the drug repositioning candidates with the related targets is also significant for the viral mitigation.