|Year : 2021 | Volume
| Issue : 4 | Page : 608-610
With the emergence of Omicron, SARS-CoV-2 is getting weaker and human species is getting stronger due to our inherent cellular intelligence
Pankaj Chaturvedi, Rajendra A Badwe
Department of Surgical Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India
|Date of Submission||05-Dec-2021|
|Date of Decision||07-Dec-2021|
|Date of Acceptance||08-Dec-2021|
|Date of Web Publication||29-Dec-2021|
Tata Memorial Center, Homi Bhabha National Institute, Mumbai, Maharashtra
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Chaturvedi P, Badwe RA. With the emergence of Omicron, SARS-CoV-2 is getting weaker and human species is getting stronger due to our inherent cellular intelligence. Cancer Res Stat Treat 2021;4:608-10
|How to cite this URL:|
Chaturvedi P, Badwe RA. With the emergence of Omicron, SARS-CoV-2 is getting weaker and human species is getting stronger due to our inherent cellular intelligence. Cancer Res Stat Treat [serial online] 2021 [cited 2022 Aug 11];4:608-10. Available from: https://www.crstonline.com/text.asp?2021/4/4/608/334235
With 270 million infections and 5 million deaths across the globe as of December 07, 2021, SARS-CoV-2 has become a household name. It is indeed the worst calamity that the modern world has ever faced and exposes the fragility of an “evolved” human race when faced with a non-living entity that cannot even multiply outside a cell. While the world was recovering from the spell of the Delta variant, the emergence of the Omicron variant has revived the fear of a looming crisis. However, we have tried to explain that Omicron is a boon in disguise that will contribute to the end of the COVID era. Mother nature, through Omicron and future variants, will continue to immunize human beings and save humankind from this misery.
A lot is being discussed about the mutations (such as Delta or Omicron variants) and their potential to evade immune response leading to higher infectivity and fatality. Mutation denotes alteration of the genetic structure of the genes or chromosomes that may be transmitted to the next generations. We all know that virus mutates faster than human cells do. Based on the intra-cellular environment, the virus undergoes random mutations that can either give it a survival advantage or the failure to thrive. While the virus would struggle for advantageous mutations, cells would aim to tame it or eliminate it. Having said that, these smart invaders cannot defy the intelligence of our cells that have mastered the art of survival through the process of evolution over millions of years. We have tried to analyze whether the SARS-CoV-2 is getting stronger or weaker by way of its mutations. The popular perception in society is that the Delta variant-led second wave in 2021 was deadlier than the first wave in 2020. It is feared that the third wave led by the Omicron variant might be even worse.
First of all, let us talk about the mutations in viruses and their consequences. In the absence of an in-built proof-reading mechanism, RNA viruses such as coronavirus, influenza, and HIV are unstable molecules, unlike DNA viruses. The higher vulnerability of RNA viruses is due to their mechanism of genome replication. In the case of influenza virus, as mutations accumulate, the outer surface of the newer strains is significantly different from the ancestor strain leading to “antigenic drift” that evades the host's immune system or susceptibility to the vaccine. It is also known that two or more different variants of influenza A combine to form a variant that is totally different from the parent strains and is not recognizable to the immune system. This is why new influenza vaccines are often created for each season. The HIV reproduces very fast, producing billions of copies of itself every day. This is the reason why none of the candidate HIV vaccines have performed well in clinical trials necessary for approval. In summary, mutations are routine happenings in the life cycle of a virus, and COVID-19 virus is no different. However, majority of the mutated variants are weaker and lose the ability of infection and transmission. These weaker viruses result in less symptomatic infections that contribute to herd immunity, similar to what vaccination achieves. This herd immunity can be achieved much faster if the mutations increase the transmissibility but reduce the severity. Therefore, it is likely that the mutants of COVID-19 are beneficial in bringing an end to the pandemic or at least reducing its severity. Fortunately, as per the current trends, the Omicron variant is highly transmissible but significantly less fatal. While the developed world has failed to provide vaccine to the less developed world, Omicron will immunize the deprived strata that may be more effective than vaccines.
How do we prove the beneficial role of these mutations for society? The second wave was largely driven by the mutant strains. Let us look at the behavior of these two different strains by comparing the infectivity and mortality in the first and second waves. Infection-fatality rate (IFR) and case-fatality rate (CFR) are two parameters of the severity of viral infections. IFR is the number of COVID deaths divided by the number of people carrying the SARS-CoV-2 antibody. There are only two ways to acquire antibodies to SARS-CoV-2, firstly through infection (symptomatic or asymptomatic) and secondly after vaccination. This can be estimated in a population by the various seroprevalence studies undertaken at different timepoints of the pandemic. CFR is the number of COVID deaths divided by the number of people detected positive on COVID testing. IFR is likely to be more robust considering the underperformance of COVID tests at the community level. The difference between the IFR and CFR offers an estimate of the underreporting factor.
In May 2021, Purkayastha et al. published a paper utilizing the seroprevalence data to estimate the IFR in India. Considering the extremely low level of fully vaccinated population in India till the end of May 2021, most of the antibodies in seroprevalence studies were due to the viral infection. Therefore, results of seroprevalence studies are the most reliable estimates of viral infection in the population rather than the viral test results. The study considered the first wave as April 01, 2020–January 31, 2021, and the second wave as February 01, 2021–May 15, 2021. Based on the deaths reported by the government, the IFR estimate is 0.13% for wave 1 and 0.03% for part of wave 2. If we take into account the underreporting of deaths, the IFR estimate is 0.46% for wave 1 and 0.18% for wave 2. When the mortality rates in waves 1 and 2 are combined, India reported (as of May 2021) a total of 270 thousand deaths among nearly 25 million cases. Taking into account the underreporting, an estimated 1.21 million deaths may have occurred among 491 million Indians (36% of the population as per the seroprevalence study), infected Indians, yielding an estimated 0.25% IFR. The latest seroprevalence study released on July 20, 2021, revealed that nearly 68% of the population has antibodies mainly because of the infection. This will decrease the IFR due to the second wave in India to a much lower level.
Just like India, most European nations also witnessed a two-wave pattern in the 2020 pandemic, with the first wave during the spring followed by the second wave during late summer or autumn triggered by a new variant. A study among hospitalized patients in Spain compared the patterns between the first wave (March 15, 2020 to June 30, 2020) and the second wave (July 1, 2020 to October 15, 2020). The study reported that the patients in the second wave were younger with a shorter duration of hospitalization and lower CFR compared to the first wave. Based on the French hospital data, a study reported that the number of deaths among hospitalized patients since mid-June 2020 was lower than that of the March–April 2020 mortality. A Canadian study also reported that the CFR decreased significantly in Ontario during the second wave, with July 31, 2020, as the division between the first and second waves. The authors concluded that COVID-19 testing was not a driving factor for this decrease in CFR.
Another study compared the raw CFR between waves 1 and 2 in the 53 countries where the mortality rate was reported to be the highest. CFR is defined as the number of deaths divided by the total number of test-positive cases. It is an established tool to report the severity of infection and efficacy of management. Interestingly, 43 countries had lower CFR estimates in the second wave compared to the first wave.
How do we explain this significant reduction in IFR and CFR? The reductions in mortality in the two time periods in the above studies cannot be entirely attributed to better treatment. Many of the drugs that were used during those times, such as hydroxychloroquine, azithromycin, ritonavir, lopinavir, and tocilizumab, were found to be ineffective in well-conducted studies. One plausible explanation regarding the reduced mortality lies in the attenuation of the virus due to mutations or cross-reactivity that is well studied in the influenza virus. It is possible that today's common cold coronaviruses commenced their evolution with a SARS-CoV-2-like pandemic and were finally tamed into benign variants.
Some of the recent variants, such as Delta or Omicron, with mutations in spike proteins first detected in India, Brazil, and South Africa may have increased transmissibility, but no proportionate increase in the severity or fatality has been reported till date. The higher transmissibility and lower fatality are likely to be beneficial in achieving faster herd immunity and the end of the pandemic. Needless to say, it may be premature to make such a conclusion given that many of the mutations could be responsible for an immune escape and its consequences.
Whenever pandemics and epidemics occur, the pathogen and the populations must either adapt or risk the possibility of becoming extinct. Most of the viruses with high fatality rates such as Marburg virus, Ebola virus, hantavirus, and Lassa virus threaten their own survival death as they kill their host, whereas the viruses that are less fatal peacefully coexist with living beings ensuring their own existence through favorable adaptive mutations. Over millions of years, these viruses have contributed to shaping the evolution of Homo sapiens and their genome. In 2016, scientists discovered an endogenous retrovirus integrated in the human genome that is postulated to have come from our ancestors, who may have been infected nearly 45 to 60 million years ago. There are many such examples of a virus that may have shaped our genome and human evolution. Are the viruses friends or enemies of human beings? Evolution biologists would call them “frenemies” because in terms of the immediate impact, they are undoubtedly our enemies. However, looking at human evolution over thousands of years, they contribute to the betterment of our genome and creation of superior species.
To conclude, as the pandemic continues to ravage the populations across the world despite medical advances, we can trust our inherent cellular intelligence to help the human species conquer the pandemic and come out stronger.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Dong E, Du H, Gardner L. An interactive web-based dashboard to track COVID-19 in real time. Lancet Infect Dis 2020;20:533-4.
Long SW, Olsen RJ, Christensen PA, Bernard DW, Davis JJ, Shukla M, et al.
Molecular architecture of early dissemination and massive second wave of the SARS-CoV-2 virus in a major metropolitan area. mBio 2020;11:e02707-20.
Murhekar MV, Bhatnagar T, Selvaraju S, Saravanakumar V, Thangaraj JW, Shah N, et al.
SARS-CoV-2 antibody seroprevalence in India, August-September, 2020: Findings from the second nationwide household serosurvey. Lancet Glob Health 2021;9:e257-66.
Purkayastha S, Kundu R, Bhaduri R, Barker D, Kleinsasser M, Ray D, et al.
Estimating the wave 1 and wave 2 infection fatality rates from SARS-CoV-2 in India. BMC Res Notes 2021;14:262.
Soriano V, Ganado-Pinilla P, Sanchez-Santos M, Gómez-Gallego F, Barreiro P, de Mendoza C, et al.
Main differences between the first and second waves of COVID-19 in Madrid, Spain. Int J Infect Dis 2021;105:374-6.
Iftimie S, López-Azcona AF, Vallverdú I, Hernández-Flix S, de Febrer G, Parra S, et al.
First and second waves of coronavirus disease-19: A comparative study in hospitalized patients in Reus, Spain. PLoS One 2021;16:e0248029.
Banoun H. Evolution of SARS-CoV-2: Review of mutations, role of the host immune system. Nephron 2021;145:392-403.
Hsu SH, Chang SH, Gross CP, Wang SY. Relative risks of COVID-19 fatality between the first and second waves of the pandemic in Ontario, Canada. Int J Infect Dis 2021;109:189-91.
Fan G, Yang Z, Lin Q, Zhao S, Yang L, He D. Decreased case fatality rate of COVID-19 in the second wave: A study in 53 countries or regions. Transbound Emerg Dis 2021;68:213-5.
Katsura Y, Asai S. Evolutionary medicine of retroviruses in the human genome. Am J Med Sci 2019;358:384-8.
|This article has been cited by|
||Omicron variant infection and the associated immunological scenario
| ||Anirban Goutam Mukherjee, Uddesh Ramesh Wanjari, Reshma Murali, Uma Chaudhary, Kaviyarasi Renu, Harishkumar Madhyastha, Mahalaxmi Iyer, Balachandar Vellingiri, Abilash Valsala Gopalakrishnan |
| ||Immunobiology. 2022; : 152222 |
|[Pubmed] | [DOI]|
||Back to basics: Updating the differential diagnosis with COVID-19
| ||ClariceK Y. Su, SunnyChi Lik Au |
| ||Cancer Research, Statistics, and Treatment. 2022; 5(2): 302 |
|[Pubmed] | [DOI]|
||COVID-19 in patients with cancer: Lessons learnt and future directions
| ||MonicaM Irukulla, Deepthi Valiyaveettil |
| ||Cancer Research, Statistics, and Treatment. 2022; 5(2): 360 |
|[Pubmed] | [DOI]|