key: cord-0734728-q59iwhbv authors: Choudhary, Om Prakash; Priyanka; Ali, Rezhna Kheder; Maulud, Sazan Qadir; Dhawan, Manish; Mohammed, Teroj A. title: Will the next spillover pandemic be deadlier than the COVID-19?: A wake-up call date: 2022-01-04 journal: Int J Surg DOI: 10.1016/j.ijsu.2021.106208 sha: dd0423ef503f99c7a4763f25b8e077f7e99f3f5c doc_id: 734728 cord_uid: q59iwhbv nan spillover event and emergence process of SARS-CoV-2 is still unclear, and more information from the earliest stage of the epidemic is essential to understand how SARS-CoV-2 came into contact with people [4] . (Fig. 1) . The evolution of SARS-CoV-2 via the accumulation of mutations is slower than that of certain other RNA viruses such as influenza. Nonetheless, the emergence of novel variants of SARS-CoV-2 possess a serious threat against the antiviral therapeutic regimens, and some of these strains are thought to be more infectious than the wild type of virus [5] . RNA viruses have been commonly identified as the most common class of pathogens responsible for new human illnesses, with a rate of 2-3 new viruses unearthed each year. They have a higher probability of infecting new host species due to their incredibly short generation periods and rapid evolutionary levels. They are distinguished by an extraordinary ability to adapt to new habitats, initial selection pressures, and various hosts when the chance arises [6] . Coronaviruses (CoVs) are more stable and have fewer alterations than other RNA viruses because they encode an enzyme that rectifies some of the replication faults [7] . For the prediction of the epidemic trend and infection control, it is crucial to understand if natural selection is effectively influencing the adaptive evolution of SARS-CoV-2 transmissibility and severity during the pandemic. When it is under selection, more investigation is necessary to discover the functional mutations that are related to the developing epidemiological and pathogenic traits [8] . According to recent computational model research, SARS-CoV-2 may further evolve in its human host by a combination of missense, deletion, insertion, and other mutations. For example, various alterations in the Spike (S) protein, which interacts with the ACE2 receptors on human cells to enable viral entry, have resulted in the dramatic variations and strengthening of the existing spike-ACE2 binding affinity [9] . Almost every country on the planet has been affected by cases and mortality caused by the COVID-19, breaking the backbone of the global healthcare system. The emergence of several variants of concern (VOC), including Alpha (B. resurgence of the consequent waves of the pandemic [10] . Aside from the control approaches that rely on the use of face masks, social distancing, hand washing, and environmental sterilization [11] , the worldwide vaccination effort is in full gear, with the overall aim of mitigating the succeeding waves of COVID-19. However, this is not the end, as we must be prepared for the next plausible pandemic, which would be as unexpected as the previous COVID-19. The evolution of various SARS-CoV-2 variants have also put the vaccine's effectiveness into contention. The major issue remains whether we are prepared for what comes next? Vaccine enhancers have already been deployed for the COVID-19 to restrict the several variants of SARS-CoV-2 [12] . Since we all know, the Delta variant was extremely dangerous and was also responsible for a significant fatality rate in different countries, and now a novel SARS-CoV-2 VOC named Omicron (previously named B.1.1.529), that has been stipulated to be more transmissible than the Delta variant, has been appearing in many regions within the South Africa, especially Gauteng. The fast spread, particularly in the younger age group, in Gauteng, South Africa, has drawn the attention of the World Health Organization (WHO) and worldwide health care systems. The major concerns regarding the omicron variant are whether it is highly infectious or virulent as compared to the other variants and whether it may evade the protection accorded by the COVID-19 vaccines. Whereas the immunological and clinical findings are insufficient to give conclusive proof yet, we may generalize according to what we understand about the Omicron mutations to offer early evidence of disease transmission, lethality, as well as immunological evasion. Omicron has multiple deletions and over 30 mutations in the spike protein, including some (for example, 69-70del, T95I, G142D/ 143-145del, K417 N, T478K, N501Y, N655Y, N679K, and P681H) that coincide with those in the alpha, beta, gamma, or delta versions. Such deletions and alterations have been associated with enhanced disease transmission, stronger binding ability of virus, and escape from the antibodies. Other mutations in the Omicron variant with documented effects include those that improve the transmissibility and change the binding affinity [13] . Also, several changes in the receptor-binding domain (RBD) and N-terminal domain (NTD) are also of concern since they have been linked to the resistance to neutralizing antibodies and enhanced transmissibility. As a result, various mitigation methods, including wearing a mask, adequate sanitization, and maintaining social distance, have already been adopted to mitigate the upcoming waves of the COVID-19. The purpose of this letter article is to emphasize the severity and mortality of the next probable pandemic following the Spanish flu, SARS, MERS and the most recent COVID-19. In conclusion, the COVID-19 pandemic has not been over yet, and there is an urgent need to ramp up the vaccination in humans as well as animals, as these are also susceptible in a considerable proportion. Besides investing in the global efforts aimed at mitigation, we must gain a valuable lesson from the continuing COVID-19 pandemic and prepare for any future occurrence of novel pandemic. This article does not require any human/animal subjects to acquire such approval. This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Name of the registry: Not applicable. Unique Identifying number or registration ID: Not applicable. Hyperlink to your specific registration (must be publicly accessible and will be checked): Not applicable. Om Prakash Choudhary, Assistant Professor, Department of Veterinary Anatomy and Histology, College of Veterinary Sciences and Animal Husbandry, Central Agricultural University (I), Selesih, Aizawl-796015, Mizoram, India. Tel: +91-9928099090; Email: dr.om.choudhary@ gmail.com. Not commissioned, internally peer-reviewed. All authors report no conflicts of interest relevant to this article. The proximal origin of SARS-CoV-2 The origins of SARS-CoV-2: a critical review Receptor binding, immune escape, and protein stability direct the natural selection of SARS-CoV-2 variants The emergence, genomic diversity and global spread of SARS-CoV-2 COVID-19 and future pandemics: a global systems approach and relevance to SDGs RNA viruses-evolution in action Genetic variants of SARS-CoV-2-what do they mean On the origin and evolution of SARS-CoV-2 On the evolutionary epidemiology of SARS-CoV-2 Omicron variant (B.1.1.529) of SARS-CoV-2: threat assessment and plan of action Aerosol transmission of SARS-CoV-2: the unresolved paradox Intranasal COVID-19 vaccines: is it a boon or bane? Omicron SARS-CoV-2 variant: a new chapter in the COVID-19 pandemic All the authors acknowledge and thank their respective Universities and Institutes. The figure has been created with BioRender (htt ps://biorender.com/). Supplementary data to this article can be found online at https://doi. org/10.1016/j.ijsu.2021.106208.