Antivirals for COVID-19: A critical review.

No specific drugs have been approved for coronavirus disease 2019 (COVID-19) to date as the development of antivirals usually requires time. Therefore, assessment and use of currently available antiviral drugs is critical for a timely response to the current pandemic. Here, we have reviewed anti-SARS-CoV-2 potencies of available antiviral drug groups such as fusion inhibitors, protease inhibitors, neuraminidase inhibitors, and M2 ion-channel protein blockers. Although clinical trials to assess the efficacy of these antivirals are ongoing, this review highlights important information including docking and modeling analyses, in vitro studies, as well as results from clinical uses of these antivirals against COVID-19 pandemic.

Safety & effectiveness of COVID-19 vaccines: A narrative review.

There are currently eight vaccines against SARS-CoV-2 that have received Emergency Use Authorization by the WHO that can offer some protection to the world's population during the COVID-19 pandemic. Though research is being published all over the world, public health officials, policymakers and governments are collecting evidence-based information to establish the public health policies. Unfortunately, continued international travel, violations of lockdowns and social distancing, the lack of mask use, the emergence of mutant strains of the virus and lower adherence by a sector of the global population that remains sceptical of the protection offered by vaccines, or about any risks associated with vaccines, hamper these efforts. Here we examine the literature on the efficacy, effectiveness and safety of COVID-19 vaccines, with an emphasis on select categories of individuals and against new SARS-CoV-2 strains. The literature shows that these eight vaccines are highly effective in protecting the population from severe disease and death, but there are some issues concerning safety and adverse effects. Further, booster shots and variant-specific vaccines would also be required.

Willingness to Pay (WTP) for COVID-19 Vaccine Booster Dose and Its Determinants in Indonesia.

Willingness to pay (WTP) for booster doses of coronavirus disease 2019 (COVID-19) vaccines is an under studied research topic. Therefore, the current study aimed to investigate the WTP for the booster doses of COVID-19 vaccines and its predictors in Indonesia using an online survey distributed all over the provinces of this low-middle-income country. The WTP was evaluated using a basic dichotomous contingent valuation approach, and its associated determinants were evaluated using a linear regression model. Out of 2935 responders, 66.2% (1942/2935) were willing to pay for a booster dose of the COVID-19 vaccine. The majority of respondents (63.5%) were willing to pay within a price range of 100,000-500,000 Indonesian rupiah (IDR), i.e., USD 6.71-33.57. Being older than 40 years, having a higher educational level, having a higher income, knowing and understanding that booster doses were important, and having a vaccine status that is certified halal (permissible in Islamic law), were all associated with a higher WTP for the booster dose of COVID-19 vaccines. The study findings imply that the WTP for a booster dose of COVID-19 vaccination in Indonesia is lower compared to acceptance of vaccines provided free of charge. This WTP data can be utilized to develop a pricing scheme for the booster doses of COVID-19 vaccination in the country with potential benefits in other low-income countries. The government may be required to provide subsidies for the herd immunity vaccination process to proceed as anticipated. Furthermore, the public community must be educated on the importance of vaccination as well as the fact that the COVID-19 epidemic is far from being over.

Antioxidant effects of seaweeds and their active compounds on animal health and production - a review.

Natural antioxidants applied as feed additives can improve not only animals' health and overall performance but also increase their resistance to environmental stress such as heat stress, bad housing conditions, diseases, etc. Marine organisms, for example seaweeds - red, brown, and green macroalgae contain a plethora of biologically active substances, including phenolic compounds, polysaccharides, pigments, vitamins, micro- and macroelements, and proteins known for their antioxidant activity, which can help in the maintenance of appropriate redox status in animals and show pleiotropic effects for enhancing good health, and productivity. The dysregulated production of free radicals is a marked characteristic of several clinical conditions, and antioxidant machinery plays a pivotal role in scavenging the excessive free radicals, thereby preventing and treating infections in animals. Supplementation of seaweeds to animal diet can boost antioxidant activity, immunity, and the gut environment. Dietary supplementation of seaweeds can also enhance meat quality due to the deposition of marine-derived antioxidant components in muscles. The use of natural antioxidants in the meat industry is a practical approach to minimize or prevent lipid oxidation. However, overconsumption of seaweeds, especially brown macroalgae, should be avoided because of their high iodine content. An important point to consider when including seaweeds in animal feed is their variable composition which depends on the species, habitat, location, harvest time, growing conditions such as nutrient concentration in water, light intensity, temperature, etc. This review highlights the beneficial applications of seaweeds and their extracted compounds, which have antioxidant properties as feed additives and impact animal health and production.

Bovine-derived antibodies and camelid-derived nanobodies as biotherapeutic weapons against SARS-CoV-2 and its variants: A review article.

The Coronavirus Disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected 305 million individuals worldwide and killed about 5.5 million people as of January 10, 2022. SARS-CoV-2 is the third major outbreak caused by a new coronavirus in the previous two decades, following SARS-CoV and MERS-CoV. Even though vaccination against SARS-CoV-2 is considered a critical strategy for preventing virus spread in the population and limiting COVID-19 clinical manifestations, new therapeutic drugs, and management strategies are urgently needed, particularly in light of the growing number of SARS-CoV-2 variants (such as Delta and Omicron variants). However, the use of conventional antibodies has faced many challenges, such as viral escape mutants, increased instability, weak binding, large sizes, the need for large amounts of plasma, and high-cost manufacturing. Furthermore, the emergence of new SARS-CoV-2 variants in the human population and recurrent coronavirus spillovers highlight the need for broadly neutralizing antibodies that are not affected by an antigenic drift that could limit future zoonotic infection. Bovine-derived antibodies and camelid-derived nanobodies are more potent and protective than conventional human antibodies, thanks to their inbuilt characteristics, and can be produced in large quantities. In addition, it was reported that these biotherapeutics are effective against a broad spectrum of epitopes, reducing the opportunity of viral pathogens to develop mutational escape. In this review, we focus on the potential benefits behind our rationale for using bovine-derived antibodies and camelid-derived nanobodies in countering SARS-CoV-2 and its emerging variants and mutants.

Vaccine hesitancy among communities in ten countries in Asia, Africa, and South America during the COVID-19 pandemic.

Vaccine hesitancy is considered one of the greatest threats to the ongoing coronavirus disease 2019 (COVID-19) vaccination programs. Lack of trust in vaccine benefits, along with concerns about side effects of the newly developed COVID-19 vaccine, might significantly contribute to COVID-19 vaccine hesitancy. The objective of this study was to determine the level of vaccine hesitancy among communities in particular their belief in vaccination benefits and perceived risks of new vaccines. An online cross-sectional study was conducted in 10 countries in Asia, Africa, and South America from February to May 2021. Seven items from the WHO SAGE Vaccine Hesitancy Scale were used to measure a construct of belief in vaccination benefit, and one item measured perceived riskiness of new vaccines. A logistic regression was used to determine which sociodemographic factors were associated with both vaccine hesitancy constructs. A total of 1,832 respondents were included in the final analysis of which 36.2% (range 5.6-52.2%) and 77.6% (range 38.3-91.2%) of them were classified as vaccine hesitant in terms of beliefs in vaccination benefits and concerns about new vaccines, respectively. Respondents from Pakistan had the highest vaccine hesitancy while those from Chile had the lowest. Being females, Muslim, having a non-healthcare-related job and not receiving a flu vaccination during the past 12 months were associated with poor beliefs of vaccination benefits. Those who were living in rural areas, Muslim, and those who did not received a flu vaccination during the past 12 months had relatively higher beliefs that new vaccines are riskier. High prevalence of vaccine hesitancy in some countries during the COVID-19 pandemic might hamper COVID-19 vaccination programs worldwide. Programs should be developed to promote vaccination in those sociodemographic groups with relatively high vaccine hesitancy.

SARS-CoV-2 vaccine for domestic and captive animals: An effort to counter COVID-19 pandemic at the human-animal interface.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has already affected millions worldwide. The emergence of multiple SARS-CoV-2 variants may pose a significant threat to our efforts in controlling the pandemic. The impact of SARS-CoV-2 variants on the efficacy of available vaccines, therapeutics, and diagnostics is currently being investigated. SARS-CoV-2 has been implicated to be originated from animals due to cross-species jumping and raises zoonotic concerns due to the potential for reintroduction into the human populations via interspecies transmission between humans and animals. Natural SARS-CoV-2 infections have been reported in domestic animals (dog, cat, and ferret), captive animals (tiger, lion, snow leopard, puma, otter, and gorilla), and wild and farmed minks. Vaccination of domestic animals can prevent the possible introduction of SARS-CoV-2 into the feral population and subsequent transmission to wildlife. Although the need to vaccinate susceptible animal species, such as cats, minks, and great apes, might seem irrational from a public health standpoint, the successful elimination of SARS-CoV-2 will only be possible by controlling the transmission in all susceptible animal species. This is necessary to prevent the re-emergence of SARS-CoV-2 in the future.

Immunological aspects and gender bias during respiratory viral infections including novel Coronavirus disease-19 (COVID-19): A scoping review.

The human immune system is not adequately equipped to eliminate new microbes and could result in serious damage on first exposure. This is primarily attributed to the exaggerated immune response (inflammatory disease), which may prove detrimental to the host, as evidenced by SARS-CoV-2 infection. From the experiences of Novel Coronavirus Disease-19 to date, male patients are likely to suffer from high-intensity inflammation and disease severity than the female population. Hormones are considered the significant pillars of sex differences responsible for the discrepancy in immune response exhibited by males and females. Females appear to be better equipped to counter invading respiratory viral pathogens, including the novel SARS-CoV-2, than males. It can be hypothesized that females are more shielded from disease severity, probably owing to the diverse action/influence of estrogen and other sex hormones on both cellular (thymus-derived T lymphocytes) and humoral immunity (antibodies).

SARS-CoV-2 infection in domestic and feral cats: current evidence and implications.

Current evidence indicates that cats play a limited role in COVID-19 epidemiology, and pets are probably dead-end hosts of SARS-CoV-2 and pose negligible risks of transmission to humans. Still, one health concept is to be adopted widely as a component of mitigation strategies to tackle the ongoing pandemic. Therefore, in terms of the magnitude of infection and potential to transmit SARS-CoV-2 to humans, our surveillance efforts should mainly focus on mustelids (especially minks, ferrets, and others) for early detection and control of infection. This will ensure that SARS-CoV-2 will not get established in the wild animal population of these susceptible species. We agree with Dr. Passarella Teixeira on the possibility of domestic and feral cats acting as an urban reservoir, subsequently transmitting the virus to human beings. However, it is less likely that such a phenomenon will be reported even if it has occurred due to the efficient and extensive human-to-human transmission of SARS-CoV-2.

COVID-19 vaccination passport: prospects, scientific feasibility, and ethical concerns.

A vaccination passport (also known as "vaccination certificate," "immunization passport," or "digital health pass") is a document that provides proof of vaccination and certifies that the holder is protected from illness. It is a more reliable and practical substitute for immunity passports since COVID-19 vaccination is considered a better correlate of protection. Vaccination passport can be considered as a tool offering the holder the privilege of traveling freely within countries without any restrictions. The majority of the countries that are dependent on travel and tourism have exhibited a positive inclination toward implementing COVID-19 vaccination passports, while others have a mixed opinion. The successful implementation of vaccination passports will be a complex task for the policymakers as it requires addressing several ethical, legal, and data security concerns outlined in this article. However, vaccination passports can offer economic and health benefits that will allow the gradual recovery of the economy.

COVID-19 vaccine hesitancy - reasons and solutions to achieve a successful global vaccination campaign to tackle the ongoing pandemic.

The ongoing coronavirus disease (COVID-19) vaccination drive aims to achieve global vaccination coverage that will help to control the pandemic. Therefore, the individuals who are reluctant to be vaccinated or forego COVID-19 vaccination can delay the progress of overall vaccination coverage, leading to slower vaccination rates and may create obstacles in global efforts to control the circulation of SARS-CoV-2 as unvaccinated individuals can act as reservoirs of SARS-CoV-2 and could drive further outbreaks. Vaccine hesitancy is one of the major threats that directly impact global health as it challenges our ability to eradicate infectious diseases and achieve significant herd immunity through vaccination. One of the strategies to counter vaccine hesitancy is to follow a multisectoral approach that involves the collaboration between various stakeholders, such as government, private companies, religious groups, and other agencies, to leverage the knowledge, expertise, and resources, thereby enabling the creation of longstanding public trust of vaccines.

Emerging SARS-CoV-2 variants: impact on vaccine efficacy and neutralizing antibodies.

The genetic variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been emerging and circulating in different parts of the world from the beginning of the coronavirus disease (COVID-19) pandemic. Variants are divided into three classes: variant of interest, variant of concern, and variant of high consequence depending on its impact on the transmission, disease severity, diagnostics, vaccines, and therapeutics. The variants of concern include the United Kingdom variant (B.1.1.7), South Africa variant (B.1.351), two related California variants (B.1.427 and B.1.429), and Brazil variant (P.1). These SARS-CoV-2 variants have a direct impact on the available COVID-19 vaccines and immunotherapeutics as they can alter the neutralizing activity of vaccine-elicited antibodies and monoclonal antibodies resulting in mild-to-substantial loss of efficacy. There is a need to establish surveillance systems that can monitor the emergence of novel SARS-CoV-2 variants worldwide.

COVID-19 and sunlight: Impact on SARS-CoV-2 transmissibility, morbidity, and mortality.

Coronavirus disease 2019 (COVID-19) has already affected millions of people worldwide. There are reports of SARS-CoV-2 transmission as a consequence of environmental contamination. The SARS-CoV-2 laden infective droplets can actively persist on the surface of different materials for several hours to days. Sunlight can affect the stability of SARS-CoV-2 in these aerosols and thereby have an impact on the decay rate of the virus. Solar radiation might play an important role in inactivating SARS-CoV-2 that persists in different surfaces and the environment. Among the different climatological factors, ultraviolet radiation was found to have an important role in determining the spread of SARS-CoV-2. Although ultraviolet radiation C (UVC), UVB, UVA, visible light, and infrared radiation possess germicidal properties, human CoVs including the recently emerged SARS-CoV-2 are inherently sensitive to UVC. However, the successful decontamination using other wavebands requires higher dosages and longer administration times. Furthermore, studies have also identified association between COVID-19 fatalities and the latitude. The intensity of sunlight is highest near the equator, and therefore populations in these regions with more regular exposure to sunlight are less susceptible to vitamin D deficiency. This article has analyzed the potential impact of sunlight in reducing SARS-CoV-2 transmissibility, morbidity, and mortality. It is evident that there exists an interesting link between sunlight exposure, latitude, and vitamin D status with COVID-19 incidence, fatality and recovery rates that requires further investigation.

The role of disinfectants and sanitizers during COVID-19 pandemic: advantages and deleterious effects on humans and the environment.

Disinfectants and sanitizers are essential preventive agents against the coronavirus disease 2019 (COVID-19) pandemic; however, the pandemic crisis was marred by undue hype, which led to the indiscriminate use of disinfectants and sanitizers. Despite demonstrating a beneficial role in the control and prevention of COVID-19, there are crucial concerns regarding the large-scale use of disinfectants and sanitizers, including the side effects on human and animal health along with harmful impacts exerted on the environment and ecological balance. This article discusses the roles of disinfectants and sanitizers in the control and prevention of the current pandemic and highlights updated disinfection techniques against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This article provides evidence of the deleterious effects of disinfectants and sanitizers exerted on humans, animals, and the environment as well as suggests mitigation strategies to reduce these effects. Additionally, potential technologies and approaches for the reduction of these effects and the development of safe, affordable, and effective disinfectants are discussed, particularly, eco-friendly technologies using nanotechnology and nanomedicine.

Diverse Immunological Factors Influencing Pathogenesis in Patients with COVID-19: A Review on Viral Dissemination, Immunotherapeutic Options to Counter Cytokine Storm and Inflammatory Responses.

The pathogenesis of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still not fully unraveled. Though preventive vaccines and treatment methods are out on the market, a specific cure for the disease has not been discovered. Recent investigations and research studies primarily focus on the immunopathology of the disease. A healthy immune system responds immediately after viral entry, causing immediate viral annihilation and recovery. However, an impaired immune system causes extensive systemic damage due to an unregulated immune response characterized by the hypersecretion of chemokines and cytokines. The elevated levels of cytokine or hypercytokinemia leads to acute respiratory distress syndrome (ARDS) along with multiple organ damage. Moreover, the immune response against SARS-CoV-2 has been linked with race, gender, and age; hence, this viral infection's outcome differs among the patients. Many therapeutic strategies focusing on immunomodulation have been tested out to assuage the cytokine storm in patients with severe COVID-19. A thorough understanding of the diverse signaling pathways triggered by the SARS-CoV-2 virus is essential before contemplating relief measures. This present review explains the interrelationships of hyperinflammatory response or cytokine storm with organ damage and the disease severity. Furthermore, we have thrown light on the diverse mechanisms and risk factors that influence pathogenesis and the molecular pathways that lead to severe SARS-CoV-2 infection and multiple organ damage. Recognition of altered pathways of a dysregulated immune system can be a loophole to identify potential target markers. Identifying biomarkers in the dysregulated pathway can aid in better clinical management for patients with severe COVID-19 disease. A special focus has also been given to potent inhibitors of proinflammatory cytokines, immunomodulatory and immunotherapeutic options to ameliorate cytokine storm and inflammatory responses in patients affected with COVID-19.

Role of Inflammatory Cytokines in COVID-19 Patients: A Review on Molecular Mechanisms, Immune Functions, Immunopathology and Immunomodulatory Drugs to Counter Cytokine Storm.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a severe pandemic of the current century. The vicious tentacles of the disease have been disseminated worldwide with unknown complications and repercussions. Advanced COVID-19 syndrome is characterized by the uncontrolled and elevated release of pro-inflammatory cytokines and suppressed immunity, leading to the cytokine storm. The uncontrolled and dysregulated secretion of inflammatory and pro-inflammatory cytokines is positively associated with the severity of the viral infection and mortality rate. The secretion of various pro-inflammatory cytokines such as TNF-α, IL-1, and IL-6 leads to a hyperinflammatory response by recruiting macrophages, T and B cells in the lung alveolar cells. Moreover, it has been hypothesized that immune cells such as macrophages recruit inflammatory monocytes in the alveolar cells and allow the production of large amounts of cytokines in the alveoli, leading to a hyperinflammatory response in severely ill patients with COVID-19. This cascade of events may lead to multiple organ failure, acute respiratory distress, or pneumonia. Although the disease has a higher survival rate than other chronic diseases, the incidence of complications in the geriatric population are considerably high, with more systemic complications. This review sheds light on the pivotal roles played by various inflammatory markers in COVID-19-related complications. Different molecular pathways, such as the activation of JAK and JAK/STAT signaling are crucial in the progression of cytokine storm; hence, various mechanisms, immunological pathways, and functions of cytokines and other inflammatory markers have been discussed. A thorough understanding of cytokines' molecular pathways and their activation procedures will add more insight into understanding immunopathology and designing appropriate drugs, therapies, and control measures to counter COVID-19. Recently, anti-inflammatory drugs and several antiviral drugs have been reported as effective therapeutic drug candidates to control hypercytokinemia or cytokine storm. Hence, the present review also discussed prospective anti-inflammatory and relevant immunomodulatory drugs currently in various trial phases and their possible implications.

COVID-19 Vaccine Diplomacy and Equitable Access to Vaccines Amid Ongoing Pandemic.

The wealthy countries have already secured 60% of the total coronavirus disease (COVID-19) vaccine supplies for their citizens. Some of these countries have pre-ordered vaccine doses sufficient enough to vaccinate their population multiple times. India has recently initiated a diplomatic mission named "Vaccine Maitri" to provide COVID-19 vaccine doses to needy low-income countries. The ability of the country to manufacture cost-effective vaccines along with the ability to export large vaccine consignments worldwide will help to meet the global COVID-19 vaccine requirements. Furthermore, global vaccination coverage can only be achieved by ensuring equitable access to COVID-19 vaccines.

SARS-CoV-2 in animals: potential for unknown reservoir hosts and public health implications.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, previously 2019-nCoV) is suspected of having originated in 2019 in China from a coronavirus infected bat of the genus Rhinolophus. Following the initial emergence, possibly facilitated by a mammalian bridge host, SARS-CoV-2 is currently transmitted across the globe via efficient human-to-human transmission. Results obtained from experimental studies indicate that animal species such as cats, ferrets, raccoon dogs, cynomolgus macaques, rhesus macaques, white-tailed deer, rabbits, Egyptian fruit bats, and Syrian hamsters are susceptible to SARS-CoV-2 infection, and that cat-to-cat and ferret-to-ferret transmission can take place via contact and air. However, natural infections of SARS-CoV-2 have been reported only in pet dogs and cats, tigers, lions, snow leopards, pumas, and gorillas at zoos, and farmed mink and ferrets. Even though human-to-animal spillover has been reported at several instances, SARS-CoV-2 transmission from animals-to-humans has only been reported from mink-to-humans in mink farms. Following the rapid transmission of SARS-CoV-2 within the mink population, a new mink-associated SARS-CoV-2 variant emerged that was identified in both humans and mink. The increasing reports of SARS-CoV-2 in carnivores indicate the higher susceptibility of animal species belonging to this order. The sporadic reports of SARS-CoV-2 infection in domestic and wild animal species require further investigation to determine if SARS-CoV-2 or related Betacoronaviruses can get established in kept, feral or wild animal populations, which may eventually act as viral reservoirs. This review analyzes the current evidence of SARS-CoV-2 natural infection in domestic and wild animal species and their possible implications on public health.