Mpox impact on different organ systems: Complications, mechanisms, and management.

Mpox (previously known as monkeypox) continues to raise concerns since many cases are still being recorded globally. Various reports have shown changing epidemiology of the disease, together with different atypical clinical characteristics of affected patients. The condition has reportedly been self-limited since most patients do not usually require hospitalisation. However, recent reports showed that some patients might suffer from related complications and require hospitalisation. Different systems were reportedly affected, including cardiac, neurological, respiratory, and renal events. In the present literature review, we aim to review these complications, discuss their potential mechanisms, and provide insight into the currently recommended diagnostic and management practices.

Antibody evasion associated with the RBD significant mutations in several emerging SARS-CoV-2 variants and its subvariants.

Since the origin of the wild strain of SARS-CoV-2, several variants have emerged, which were designated as VOC, VOI, and VUM from time to time. The Omicron variant is noted as the recent VOC. After the origin of the Omicron variant on November 2021, several subvariants of Omicron have originated subsequently, like BA.1/2, BA.2.75/2.75.2, BA.4/5, BF.7, BQ.1/1.1, XBB.1/1.5, etc. which are circulated throughout the globe. Scientists reported that antibody escape is a common phenomenon observed in all the previous VOCs, VOIs, including Omicron and its subvariants. The mutations in the NTD (N-terminal domain) and RBD (Receptor-binding domain) of the spike of these variants and subvariants are responsible for antibody escape. At the same time, it has been noted that spike RBD mutations have been increasing in the last few months. This review illustrates significant RBD mutations namely R346T, K417N/T, L452R, N460K E484A/K/Q, and N501Y found in the previous emerging SARS-CoV-2 variants, including Omicron and its subvariants in high frequency and their role in antibody evasion and immune evasion. The review also describes the different classes of nAb responsible for antibody escape in SARS-CoV-2 variants and the molecular perspective of the mutation in nAb escape. It will help the future researchers to develop efficient vaccines which can finally prevent the pandemic.

Intriguing insight into unanswered questions about Mpox: exploring health policy implications and considerations.

The 2022 multi-country Monkeypox (Mpox) outbreak has added concerns to scientific research. However, unanswered questions about the disease remain. These unanswered questions lie in different aspects, such as transmission, the affected community, clinical presentations, infection and prevention control and treatment and vaccination. It is imperative to address these issues to stop the spread and transmission of disease. We documented unanswered questions with Mpox and offered suggestions that could help put health policy into practice. One of those questions is why gay, bisexual or other men who have sex with men (gbMSM) are the most affected community, underscoring the importance of prioritizing this community regarding treatment, vaccination and post-exposure prophylaxis. In addition, destigmatizing gbMSM and implementing community-based gbMSM consultation and action alongside ethical surveillance can facilitate other preventive measures such as ring vaccination to curb disease transmission and track vaccine efficacy. Relevant to that, vaccine and drug side effects have implied the questionability of their use and stimulated the importance of health policy development regarding expanded access and off-label use, expressing the need for safe drug and vaccine development manufacturing. The possibility of reverse zoonotic has also been raised, thus indicating the requirement to screen not only humans, but also their related animals to understand the real magnitude of reverse zoonosis and its potential risks. Implementing infection prevention and control measures to stop the virus circulation at the human-animal interface that includes One Health approach is essential.

Sensitivity to Vaccines, Therapeutic Antibodies, and Viral Entry Inhibitors and Advances To Counter the SARS-CoV-2 Omicron Variant.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) keeps evolving and mutating into newer variants over time, which gain higher transmissibility, disease severity, and spread in communities at a faster rate, resulting in multiple waves of surge in Coronavirus Disease 2019 (COVID-19) cases. A highly mutated and transmissible SARS-CoV-2 Omicron variant has recently emerged, driving the extremely high peak of infections in almost all continents at an unprecedented speed and scale. The Omicron variant evades the protection rendered by vaccine-induced antibodies and natural infection, as well as overpowers the antibody-based immunotherapies, raising the concerns of current effectiveness of available vaccines and monoclonal antibody-based therapies. This review outlines the most recent advancements in studying the virology and biology of the Omicron variant, highlighting its increased resistance to current antibody-based therapeutics and its immune escape against vaccines. However, the Omicron variant is highly sensitive to viral fusion inhibitors targeting the HR1 motif in the spike protein, enzyme inhibitors, involving the endosomal fusion pathway, and ACE2-based entry inhibitors. Omicron variant-associated infectivity and entry mechanisms of Omicron variant are essentially distinct from previous characterized variants. Innate sensing and immune evasion of SARS-CoV-2 and T cell immunity to the virus provide new perspectives of vaccine and drug development. These findings are important for understanding SARS-CoV-2 viral biology and advances in developing vaccines, antibody-based therapies, and more effective strategies to mitigate the transmission of the Omicron variant or the next SARS-CoV-2 variant of concern.

Operator impact assessment on qualitative and quantitative parameters of canine platelet-rich plasma.

Platelet-rich plasma (PRP) has emerged as a cornerstone in veterinary regenerative medicine. The present study evaluated the impact of the operator on the qualitative and quantitative features of non-activated PRP derived from canine whole blood. Blood was collected in anticoagulant acid citrate dextrose from twelve healthy adult dogs and PRP was prepared according to the double-spin method. Both operators followed an identical protocol and utilized the same equipment for PRP preparation from the pooled blood samples. The resulting PRP underwent characterization, classification and coding based on minimum reporting standards. The consistency and internal reliability of different parameters were also assessed using the intraclass correlation coefficient and Cronbach's alpha values. Variables such as white blood cell (WBC) concentration, relative WBC composition and mean platelet volume (MPV) showed poor reliability, and WBC concentration and MPV also had unacceptable internal consistency. Significant differences were observed in several qualitative and quantitative parameters of the prepared PRP, highlighting the influence of the operator even when the same protocol and equipment were used. Our study has direct implications to regenerative medicine, reinforcing the urgency to set minimum requirements for reporting PRP in research studies.

Evolutionary and codon usage preference insights into spike glycoprotein of SARS-CoV-2.

Interaction of SARS-CoV-2 spike glycoprotein with the ACE2 cell receptor is very crucial for virus attachment to human cells. Selected mutations in SARS-CoV-2 S-protein are reported to strengthen its binding affinity to mammalian ACE2. The N501T mutation in SARS-CoV-2-CTD furnishes better support to hotspot 353 in comparison with SARS-CoV and shows higher affinity for receptor binding. Recombination analysis exhibited higher recombination events in SARS-CoV-2 strains, irrespective of their geographical origin or hosts. Investigation further supports a common origin among SARS-CoV-2 and its predecessors, SARS-CoV and bat-SARS-like-CoV. The recombination events suggest a constant exchange of genetic material among the co-infecting viruses in possible reservoirs and human hosts before SARS-CoV-2 emerged. Furthermore, a comprehensive analysis of codon usage bias (CUB) in SARS-CoV-2 revealed significant CUB among the S-genes of different beta-coronaviruses governed majorly by natural selection and mutation pressure. Various indices of codon usage of S-genes helped in quantifying its adaptability in other animal hosts. These findings might help in identifying potential experimental animal models for investigating pathogenicity for drugs and vaccine development experiments.

Immunotherapeutics in lung cancers: from mechanistic insight to clinical implications and synergistic perspectives.

BACKGROUND: Lung cancer is one of the highly lethal forms of cancer whose incidence has worldwide rapidly increased over the past few decades. About 80-85% of all lung cancer cases constitute non-small cell lung cancer (NSCLC), with adenocarcinoma, squamous cell carcinoma and large cell carcinoma as the main subtypes. Immune checkpoint inhibitors have led to significant advances in the treatment of a variety of solid tumors, significantly improving cancer patient survival rates. METHODS AND RESULTS: The cytotoxic drugs in combination with anti-PD-(L)1 antibodies is a new method that aims to reduce the activation of immunosuppressive and cancer cell prosurvival responses while also improving direct cancer cell death. The most commonly utilized immune checkpoint inhibitors for patients with non-small cell lung cancer are monoclonal antibodies (Atezolizumab, Cemiplimab, Ipilimumab, Pembrolizumab etc.) against PD-1, PD-L1, and CTLA-4. Among them, Atezolizumab (TECENTRIQ) and Cemiplimab (Libtayo) are engineered monoclonal anti programmed death ligand 1 (PD-L1) antibodies that inhibit binding of PD-L1 to PD-1 and B7.1. As a result, T-cell proliferation and cytokine synthesis are inhibited leading to restoring the immune homeostasis to fight cancer cells. CONCLUSIONS: In this review article, the path leading to the introduction of immunotherapeutic options in lung cancer treatment is described, with analyzing the benefits and shortages of the current immunotherapeutic drugs. In addition, possibilities to co-administer immunotherapeutic agents with standard cancer treatment modalities are also considered.

Scientific evidence on the origin of SARS-CoV-2.

Even reaching the end of the year 2022, there is still a controversy on the origin of the SARS-CoV-2 virus. This Virtual Special Issue (VSI), focused on the "Scientific evidence on the origin of SARS-CoV-2", was launched some months ago with the aim of stimulating the submission of new high quality scientific research papers on the matter, to shed light on it. As indicated in the call for papers, the Editors involved in the VSI were aware of the difficulties of presenting concluding facts on that issue, however, bearing in mind that some teams of researchers had started investigations regarding this subject, a VSI like this (searching for stimulating the scientific controversy while requiring scientific evidence), could help to elucidate complicated aspects, going a step ahead in this way. The Editors made a call encouraging interested teams of researchers having solid results to submit high quality manuscripts dealing with this crucial theme. We thought -and we still think-that it is of maximum interest for the scientific community, as well as for the whole society, now and probably for the future. The VSI have received 50 submissions, which could be considered a limited number highlighting the difficulties of elaborating new high-quality manuscripts providing solid evidence on the matter. After a careful peer-review, those manuscripts considered to reach the highest scientific value were accepted for publication. The Editors think that the set of papers included in this VSI constitute interesting and high-quality contributions, providing further scientific knowledge on this issue. In this editorial piece, the Editors make some comments on the papers published, including some additional reflections.

Layered double hydroxides and their tailored hybrids/composites: Progressive trends for delivery of natural/synthetic-drug/cosmetic biomolecules.

Layered double hydroxides (LDHs) are well-known and important class of hydrotalcite-type anionic clays (HTs) materials that are cost-effective with additional advantages of facile synthesis, composition, tenability, and reusability. These convincing characteristics are liable for their applications in various fields related to energy, environment, catalysis, biomedical, and biotechnology. HTs/LDHs are generally synthesized from low cost abundantly available chemical precursors through the aqueous synthetic pathways under mild reaction conditions. These materials can be termed green materials based on their non-toxic nature, availability of precursors, facile and low-cost production using aqueous medium conditions with less hazardous effluents. Diverse and fascinating characteristics have been attributed to HTs/LDHs like anion exchange ability, surface basicity, biocompatibility, controlled release of the anion specific area, porosity, easy surface modification, and pH dependent biodegradability. Hence, HTs/LDHs and their modified and/or functionalized nanohybrids/nanocomposites are reported as the potential drug delivery carriers with a capability to stabilize the susceptible bioactive molecules, may enhance the solubility of poorly soluble drugs along with controlled drug/bioactive molecule release and delivery. These clay and bioactive hybrid materials have good biocompatibility, less cytotoxicity, and better site-targeting with improved cellular uptake than that of free parent biomolecules. These lamellar solids of micro/nanostructure are compatible, host-guest materials and able to fabricate with drugs/cosmeceutical/bio- or synthetic polymers without any change in their molecular structure and reactivity along with improvement in their stabilities. Other important features are facile synthesis, basicity, high stability with easy storage, and efficient administration with low bio-toxicity. This study enlightens the applications of HTs/LDHs along with their hybrids/composites in the field of drug/cosmeceutical/gene delivery systems of natural/synthetic biomolecules.

Approaches for in vitro propagation and production of plumbagin in Plumbago spp.

The genus Plumbago (family Plumbaginaceae), commonly known as leadwort, is a sub-tropical shrub that produces secondary metabolite plumbagin, which is employed by pharmaceutical companies and in clinical research. Plumbagin is a potent pharmaceutical because of its anti-microbial, anti-malarial, antifungal, anti-inflammatory, anti-carcinogenic, anti-fertility, anti-plasmodium, antioxidant, anti-diabetic, and other effects. This review documents the biotechnological innovations used to produce plumbagin. The use of modern biotechnological techniques can lead to a variety of benefits, including better yield, increased extraction efficiency, mass production of plantlets, genetic stability, increased biomass, and more. Large-scale in vitro propagation is necessary to minimize over-exploitation of the natural population and allow the use of various biotechnological techniques to improve the plant species and secondary metabolite production. During in vitro culture, optimum conditions are requisites for explant inoculation and plant regeneration. In this review, we provide information on various aspects of plumbagin, depicting its structure, biosynthesis, and biotechnological aspects (both conventional and advanced) along with the future prospects. KEY POINTS: • Critical assessment on in vitro biotechnology in Plumbago species • In vitro propagation of Plumbago and elicitation of plumbagin • Biosynthesis and sustainable production of plumbagin.

Biotechnology of Passiflora edulis: role of Agrobacterium and endophytic microbes.

Two forms of the genus Passiflora, belonging to the Passifloraceae family, are commonly called yellow and purple passion. These perennial woody climbers are found in the cooler regions at higher altitudes and in lowlands of tropical areas. The presence of alkaloids, terpenes, stilbenes, flavonoids, glycosides, carotenoids, etc. in different parts of the plant provides several pharmacological properties. Because of the various uses in foods and pharmaceuticals, in vitro propagation of this genus has been performed hugely and is of great interest to researchers. From different explants via direct organogenesis under controlled aseptic conditions, callus, root, shoot, and somatic embryos are induced successfully. Different PGRs are augmented in the media for the rapid multiplication or organogenesis, especially, the high ratio of cytokinin and auxin in the basal media efficiently regenerates the shoot and root respectively. The in vitro regenerated plantlets are then acclimatized and hardened properly before transferring to the field conditions. Thus, the present first of its kind review on P. edulis exclusively encompasses the wide applications of biotechnology for this species alongside its organogenesis, embryogenesis, cytology, and endophytic microbes with special emphasis on the role of genetic transformation studies mediated by Agrobacterium sp. KEY POINTS: • Critical assessment on in vitro biotechnology in P. edulis. • Agrobacterium-mediated transformation in P. edulis. • Role of endophytic microbes in P. edulis.

Mung bean as a potent emerging functional food having anticancer therapeutic potential: Mechanistic insight and recent updates.

Cancer is still a major challenge for humans. In recent years, researchers have focused on plant-based metabolites as a safe, efficient, alternative or combinatorial, as well as cost-effective preventive strategy against carcinogenesis. Mung bean is an important nutritious legume, and known for providing various health benefits due to various bioactive phytochemicals and easily digestible proteins. Regular intake of mung bean helps to regulate metabolism by affecting the growth and survival of good microbes in the host gut. Mung bean has also been reported to have anti-inflammatory, antioxidant, antiproliferative, and immunomodulatory properties. These properties may possess the preventive potential of mung bean against carcinogenesis. Bibliographic databases for peer-reviewed research literature were searched through a structured conceptual approach using focused review questions on mung beans, anticancer, therapeutics, and functional foods along with inclusion/exclusion criteria. For the appraisal of the quality of retrieved articles, standard tools were employed. A deductive qualitative content analysis methodology further led us to analyze outcomes of the research and review articles. The present review provides recent updates on the anticancer potential of mung bean and the possible mechanism of action thereof to prevent carcinogenesis and metastasis. Extensive research on the active metabolites and mechanisms of action is required to establish the anticancer potential of mung bean. Keeping the above facts in view, mung bean should be investigated for its bioactive compounds, to be considered as functional food of the future.

Molecular mechanisms behind ROS regulation in cancer: A balancing act between augmented tumorigenesis and cell apoptosis.

ROS include hydroxyl radicals (HO.), superoxide (O2..), and hydrogen peroxide (H2O2). ROS are typically produced under physiological conditions and play crucial roles in living organisms. It is known that ROS, which are created spontaneously by cells through aerobic metabolism in mitochondria, can have either a beneficial or detrimental influence on biological systems. Moderate levels of ROS can cause oxidative damage to proteins, DNA and lipids, which can aid in the pathogenesis of many disorders, including cancer. However, excessive concentrations of ROS can initiate programmed cell death in cancer. Presently, a variety of chemotherapeutic drugs and herbal agents are being investigated to induce ROS-mediated cell death in cancer. Therefore, preserving ROS homeostasis is essential for ensuring normal cell development and survival. On account of a significant association of ROS levels at various concentrations with carcinogenesis in a number of malignancies, further studies are needed to determine the underlying molecular mechanisms and develop the possibilities for intervening in these processes.

Pathology, virulence-associated gene profiling, antimicrobial susceptibility, and pathogenicity of untypeable capsular serotypes of Pasteurella multocida isolated from slaughtered pigs of India.

Pasteurella multocida is widely distributed in all pig-rearing countries, affecting the economic viability and profitability of pig production. The present research highlights the molecular characterization and pathology of untypeable capsular serotypes of P. multocida in slaughtered pigs from prominent pig-rearing states of India. The prevalence of Pasteurellosis was 27.17% by Pasteurella multocida specific Pasteurella multocida specific PCR (PM-PCR). assay, while isolation rate was 7.62%. The microscopic lesions of bronchopneumonia, tonsillitis, and the presence of bacterial antigens in immunohistochemistry confirmed P. multocida with pathologies. In capsular typing, the majority of the isolates were untypeable with prevalence of 52.15% and 43.58% in molecular and microbiological methods, respectively. All the isolates showed the uniform distribution of virulence genes such as exbB, nanB, sodC, plpB, and oma87 (100%), while the variations were observed in ptfA, hasR, ptfA, pfhA, hsf-1, and plpE genes. The untypeable isolates showed higher prevalence of hsf-1 gene as compared to others. The untypeable serotypes showed a higher degree of resistance to ampicillin, amoxicillin, and penicillin antibiotics. The mouse pathogenicity testing of untypeable capsular isolates confirmed its pathogenic potential. The higher frequency of pathogenic untypeable isolates with antibiotic resistance profile might pose a serious threat to the pigs, and therefore, preventive measures should be adopted for effective control.

Phytosterol: nutritional significance, health benefits, and its uses in poultry and livestock nutrition.

Medicinal plants with active ingredients have shown great potential as natural and sustainable additives in livestock and poultry diets as growth promoters, performance, feed conversion ratio, digestibility of nutrient enhancers, and antioxidants and immune system modulators. Among active ingredients, phytosterols, which are plant-based bio-factors that may be found in seeds, fruits, grains, vegetables and legumes, are thought to be involved in the aforementioned activities but are also widely known in human medicine due to their efficacy in treating diabetes, coronary heart disease, and tumors. Nevertheless, phytosterols can also promote carcinogens production, angiogenesis inhibition, metastasis, infiltration, and cancer cells proliferation. This review focuses on the deepening of the biological role and health benefits of phytosterols and their new potential application in poultry and livestock nutrition.

Challenges of the Omicron (B.1.1.529) Variant and Its Lineages: A Global Perspective.

The SARS-CoV-2 virus has shown increased ability to mutate over the past two years, especially in the regions of the spike protein and receptor binding sites. Omicron (B.1.1.529) is the fifth variant of concern (VOC) after the emergence of the Alpha, Beta, Gamma, and Delta VOCs of SARS-CoV-2. This new variant has now circulated in 128 countries and according to the Global Initiative on Sharing All Influenza Data (GISAID), these 128 countries have shared 650,657 Omicron genome sequences as of 26 January, 2022. In this article, we highlight the real challenges of Omicron and its different lineages.

Twin combination of Omicron and Delta variants triggering a tsunami wave of ever high surges in COVID-19 cases: A challenging global threat with a special focus on the Indian subcontinent.

The emergence of Omicron (B.1.1.529) variant of SARS-CoV-2 has resulted into a very massive surge in COVID-19 cases worldwide. Due to continuous emergence of multiple variants of SARS-CoV-2, the ongoing pandemic has caused severe morbidity and mortality in last two years. The rate of infectivity of Omicron variant is much higher than Delta variant and in a very quick time Omicron has displaced the Delta variant and now become a dominant variant across the globe. The twin combination of Omicron and Delta variant is triggering a Tsunami wave of ever high surges in COVID-19 cases worldwide. This article highlights the global threats and challenges posed by Omicron, and strategies to counter it with a particular focus on Indian sub-continent.

Molnupiravir: A lethal mutagenic drug against rapidly mutating severe acute respiratory syndrome coronavirus 2-A narrative review.

Broad-spectrum antiviral agents targeting viral RNA-dependent RNA polymerase (RdRp) are expected to be a key therapeutic strategy in the ongoing coronavirus disease 2019 (COVID-19) pandemic and its future variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19. Molnupiravir is a nucleoside analog that in vivo experiments have been reported to inhibit the replication of SARS-CoV-2, the virus that causes COVID-19. Clinical trials of molnupiravir as a therapy for patients with mild-to-moderate COVID-19 also suggest its significant therapeutic efficacy in comparison to placebo. Molnupiravir is lethally mutagenic against viral RNA, but its effect on host cell DNA is being questioned. Herein, the safety concerns of molnupiravir are discussed with recent findings from published reports and clinical trials. The unchanged efficacy of molnupiravir against mutated SARS-CoV-2 variants is also highlighted. With its administration via the oral route, molnupiravir is expected to turn the tide of the COVID-19 pandemic.

Transchromosomic bovines-derived broadly neutralizing antibodies as potent biotherapeutics to counter important emerging viral pathogens with a special focus on SARS-CoV-2, MERS-CoV, Ebola, Zika, HIV-1, and influenza A virus.

Historically, passive immunotherapy is an approved approach for protecting and treating humans against various diseases when other alternative therapeutic options are unavailable. Human polyclonal antibodies (hpAbs) can be made from convalescent human donor serum, although it is considered limited due to pandemics and the urgent requirement. Additionally, polyclonal antibodies (pAbs) could be generated from animals, but they may cause severe immunoreactivity and, once "humanized," may have lower neutralization efficiency. Transchromosomic bovines (TcBs) have been developed to address these concerns by creating robust neutralizing hpAbs, which are useful in preventing and/or curing human infections in response to hyperimmunization with vaccines holding adjuvants and/or immune stimulators over an extensive period. Unlike other animal-derived pAbs, potent hpAbs could be promptly produced from TcB in large amounts to assist against an outbreak scenario. Some of these highly efficacious TcB-derived antibodies have already neutralized and blocked diseases in clinical studies. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has numerous variants classified into variants of concern (VOCs), variants of interest (VOIs), and variants under monitoring. Although these variants possess different mutations, such as N501Y, E484K, K417N, K417T, L452R, T478K, and P681R, SAB-185 has shown broad neutralizing activity against VOCs, such as Alpha, Beta, Gamma, Delta, and Omicron variants, and VOIs, such as Epsilon, Iota, Kappa, and Lambda variants. This article highlights recent developments in the field of bovine-derived biotherapeutics, which are seen as a practical platform for developing safe and effective antivirals with broad activity, particularly considering emerging viral infections such as SARS-CoV-2, Ebola, Middle East respiratory syndrome coronavirus, Zika, human immunodeficiency virus type 1, and influenza A virus. Antibodies in the bovine serum or colostrum, which have been proved to be more protective than their human counterparts, are also reviewed.

Tracing the origin of Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2): A systematic review and narrative synthesis.

The aim of the study was to trace and understand the origin of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through various available literatures and accessible databases. Although the world enters the third year of the coronavirus disease 2019 pandemic, health and socioeconomic impacts continue to mount, the origin and mechanisms of spill-over of the SARS-CoV-2 into humans remain elusive. Therefore, a systematic review of the literature was performed that showcased the integrated information obtained through manual searches, digital databases (PubMed, CINAHL, and MEDLINE) searches, and searches from legitimate publications (1966-2022), followed by meta-analysis. Our systematic analysis data proposed three postulated hypotheses concerning the origin of the SARS-CoV-2, which include zoonotic origin (Z), laboratory origin (L), and obscure origin (O). Despite the fact that the zoonotic origin for SARS-CoV-2 has not been conclusively identified to date, our data suggest a zoonotic origin, in contrast to some alternative concepts, including the probability of a laboratory incident or leak. Our data exhibit that zoonotic origin (Z) has higher evidence-based support as compared to laboratory origin (L). Importantly, based on all the studies included, we generated the forest plot with 95% confidence intervals (CIs) of the risk ratio estimates. Our meta-analysis further supports the zoonotic origin of SARS/SARS-CoV-2 in the included studies.