Comparison of the Clinico-Demographic and Molecular Profile of SARS-CoV-2 Omicron Variants BA.1 and BA.2 from North-East India

Neelanjana Sarmah¹, Nargis K Bali², Biswajyoti Borkakoty³*, Aktarul Islam Siddique⁴, Rahul Hazarika⁵, Parismita Borah⁵, Chandra Kanta Bhattacharjee^6
1Scientist C, Regional Viral Research and Diagnostic Laboratory (Regional VRDL), Indian Council of Medical Research-Regional Medical Research Centre for NE region, Bokel, Dibrugarh-786010, Assam, India
²Associate Professor, Department of Clinical Microbiology, Sher-i-Kashmir Institute of Medical Sciences, Soura, Srinagar-190011, India
³Scientist F, Regional Viral Research and Diagnostic Laboratory (Regional VRDL), Indian Council of Medical Research-Regional Medical Research Centre for NE region, Bokel, Dibrugarh-786010, Assam, India
⁴Research Scientist, Regional Viral Research and Diagnostic Laboratory Regional Viral Research and Diagnostic Laboratory (Regional VRDL), Indian Council of Medical Research-Regional Medical Research Centre for NE region, Bokel, Dibrugarh-786010, Assam, India
⁵Research Assistant, Regional Viral Research and Diagnostic Laboratory (Regional VRDL), Indian Council of Medical Research-Regional Medical Research Centre for NE region, Bokel, Dibrugarh-786010, Assam, India
⁶Research Scientist, Regional Viral Research and Diagnostic Laboratory (Regional VRDL), Indian Council of Medical Research-Regional Medical Research Centre for NE region, Bokel, Dibrugarh-786010, Assam, India
*Correspondence author: Biswajyoti Borkakoty, Scientist F and Nodal Officer, Regional VRDL, ICMR-Regional Medical Research Centre (ICMR-RMRC), North East Region, Dibrugarh-786010, Assam, India; Email: [email protected]

Citation: Sarmah N, et al. Comparison of the Clinico-Demographic and Molecular Profile of SARS-CoV-2 Omicron Variants BA.1 and BA.2 from North-East India. J Clin Immunol Microbiol. 2025;6(2):1-12.

Copyright^© 2025 by Sarmah N, et al. All rights reserved. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Table 1: Demographic and clinical profile of the SARS-CoV-2 Omicron positive cases based on telephonic interview.

Table 2: Demographic and clinical profile of the patients with respect to SARS-CoV-2Omicron sub-lineages.

Table 3: Comparison of the symptomatic and asymptomatic group of individuals infected with SARS-CoV-2 Omicron variant.

Figure 1: Percentage (%) of the symptomatic and asymptomatic SARS-CoV-2 Omicron positive cases with age.

Figure 2: Evolutionary analysis of the SARS-CoV-2 Omicron variants by Maximum Likelihood method. The evolutionary history of 36 whole genome sequence (~29.9kb) of SARS-COV-2 was inferred by using the Maximum Likelihood method and General Time Reversible model. A discrete Gamma distribution was used to model evolutionary rate differences among sites. The rate variation model allowed for some sites to be evolutionarily invariable. The tree is drawn to scale, with branch lengths measured in the number of substitutions per site. Evolutionary analyses were conducted in MEGA X. The tree is rooted to the reference strain NC 045512.2 of Dec 2019. Representative WGS of SARS-CoV-2 strains from Dibrugarh, Assam are tagged in light blue dot, while Omicron variant BA.1 sub-lineage are coloured in blue while BA.2 strains are coloured in green.

Discussion

The current study aimed to compare the demographic and clinical characteristics of patients infected with SARS-CoV-2 Omicron BA.1 and BA.2 sub-lineages during December 2021 to January 2022. To the best of our knowledge, this is the first report to provide a clinical and demographic comparison of Omicron-positive patients from North-East India. Among the participants randomly selected for this study, a higher number of cases were infected with the BA.2 variant compared to BA.1, confirming BA.2 as the predominant circulating strain during the study period. The uneven distribution of cases between BA.1 and BA.2 is reasonable, considering the higher global prevalence of BA.2 compared to BA.1 [8]. Therefore, our data on the higher incidence of BA.2-associated SARS-CoV-2 infections is not surprising and is supported by previous studies reporting increased BA.2 cases in various regions [9-11]. NGS based validation of the samples showed mutations in the different positions which were either commonly or distinctly related with BA.1 and BA.2. Our findings were concomitant with the earlier studies where authors too reported about specific mutations associated with different SARS-CoV-2 variants [12-13]. Mutational analysis data further confirmed that mutations G446S and G496S are associated with only BA.1 variant and not with BA.2 as reported by a previously published study [14].

Our finding on a greater number of symptomatic caseswith SARS-CoV-2 Omicron infections is consistent with a previously published study from England conducted in 1,542,510 adults [15]. The severity in terms of hospital admissions during the Omicron wave was lower based on the data from our study and these findings align with a previous study by Webster, et al., which also reported a relatively lower or comparable risk of severe outcomes in BA.2 lineage infections compared to BA.1 [16]. Additionally, a study from Denmark demonstrated a lower risk of hospitalization for the Omicron variant compared to the Delta variant [17].

It is important to note that multiple waves of the pandemic have already passed, contributing to the development of protective immunity among regions exposed to SARS-CoV-2 globally. Therefore, the lower severity of the Omicron BA.2 variant may be attributed to the already acquired herd immunity from previous waves of SARS-CoV-2. However, the scenario could be different for populations with no prior exposure, where the Omicron wave may lead to more severe outcomes, as previously reported in China [18]. Furthermore, the absence of ICU requirements and only one hospitalization among the re-infected cases (37 out of 349) further indicates that previous infection with pre-Omicron waves provided some level of protection to individuals and reduced the risk of severe disease outcomes during re-infection, as discussed in a recently published review article [19]. This further supports the notion that hybrid immunity derived from past infection and vaccine administration may play a crucial role in reducing the severity of re-infection cases compared to previous infection.

Despite the development and widespread administration of effective vaccines against COVID-19 globally, various variants of SARS-CoV-2 with distinct structural changes have emerged, raising concerns about the effectiveness of these vaccines in eliciting sufficient protective immune responses. In light of this, the present study aimed to speculate on the SARS-CoV-2 Omicron variant’s positivity rate in relation to the vaccination status of the study participants. The findings of the present study align with earlier reports indicating the limited effectiveness of vaccines against SARS-CoV-2 infection [20-22]. It is worth noting that most currently used vaccines were developed based on the original wild-type strain of SARS-CoV-2, while the virus has undergone rapid structural changes, giving rise to the circulation of multiple variants. Therefore, there is a pressing need for comprehensive investigations to understand the efficacy of administered vaccines in protecting against the currently circulating SARS-CoV-2 strains and the development of suitable vaccines targeting specific variants. One possible explanation for the higher proportion of symptomatic cases among the vaccinated individuals could be increased viral replication in these cases due to Antibody-Dependent Enhancement (ADE). This phenomenon involves elevated activation of immune cells, leading to severe inflammation or increased viral replication mediated by poorly neutralizing antibodies [23].

In the present study, the patients infected with the BA.2 sub-lineage exhibited a higher frequency of symptoms (79.87%, 258/323). This finding aligns with earlier research where the BA.2 sub-lineage was associated with a higher prevalence of symptomatic cases [15]. However, previous reports have indicated comparable severity between BA.1 and BA.2-induced SARS-CoV-2 positive cases [24-25]. Importantly, all 37 cases of SARS-CoV-2 reinfection reported in this study were positive for the BA.2 variant. A recently published study documented that protection obtained from previous infection with pre-Omicron variants against Omicron sub-lineages, including BA.2, was comparatively lower than protection obtained from past infection with the Omicron variant [26]. Thus, our finding further suggests that the BA.2 variant can bypass the herd immunity generated by previous SARS-CoV-2 infections.

The present study had certain limitations. The study group had only 25 unvaccinated individuals. Additionally, a higher number of BA.2 sub-lineage infections were detected compared to Omicron BA.1 sub-lineage infections, leading to an uneven distribution of cases between the two groups. Furthermore, the present study did not perform a comparative analysis of the clinical and demographic profiles of SARS-CoV-2 positive patients across different waves of the pandemic.

The present study had certain limitations. The study group had only 25 unvaccinated individuals. Additionally, a higher number of BA.2 sub-lineage infections were detected compared to Omicron BA.1 sub-lineage infections, leading to an uneven distribution of cases between the two groups. Furthermore, the present study did not perform a comparative analysis of the clinical and demographic profiles of SARS-CoV-2 positive patients across different waves of the pandemic.

Conclusion

In conclusion, this study revealed that BA.2 was the predominant variant in the region during the study period and was associated with a higher frequency of symptomatic cases compared to the BA.1 variant. The lower number of hospitalizations and ICU admissions indicated a milder severity of the BA.2 variant, potentially attributable to the protective immunity developed during the pre-Omicron waves of the SARS-CoV-2 pandemic. Moreover, the occurrence of re-infection cases with the BA.2 variant suggests that BA.2 can evade and circumvent the herd immunity established through prior infections. However, the hybrid immunity resulting from a combination of past infection and vaccine administration may play a crucial role in reducing the severity of re-infection cases compared to primary infections.

Conflict of Interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential source of conflict of interest.

Source of Funding

The financial support for conducting the laboratory investigations is obtained under the scheme Regional VRDL, Dibrugarh which is funded by the Department of Health Research (DHR), Government of India.

Ethical Statement

The study was conducted under the Regional Viral Research and Diagnostic Laboratory (Regional VRDL), Dibrugarh which is approved by the institutional ethics committee of the Regional Medical Research Centre, N.E. Region (ICMR), Dibrugarh (letter No.RMRC/Dib/IEC (Human)/2019-20/135 date:12/08/2020). All the procedures in the study were in accordance with the ethical standards of the Committee.

Acknowledgement

The authors sincerely acknowledge the Regional Viral Research Diagnostic Laboratory (Regional VRDL), Dibrugarh funded by the Department of Health Research (DHR), Govt. of India for providing the facility to carry out the present work. In addition, authors would also like to acknowledge the German Epidemic Preparedness Team (SEEG), Germany for providing the Illumina MiSeq NGS system and the required comsumables to carry out the whole genome sequencing of the SARS-CoV-2 Omicron variant.

Author Contribution

BB performed the conceptualization, study design, data analysis, manuscript drafting, editing and critical review. NS performed thestudy design, telephonic interview, laboratory tests, data analysis, manuscript drafting and editing. NKB performed data analysis, manuscript editing and critical review.AIS and CKBperformed laboratory tests, telephonic interview, data analysis. RH performed laboratory tests, telephonic interview. PB and NK performed the telephonic interview.

References

1. He X, Hong W, Pan X, Lu G, Wei X. SARS‐CoV‐2 omicron variant: Characteristics and prevention. Med. 2021;2(4):838-45.
2. Fantini J, Yahi N, Colson P, Chahinian H, La Scola B, Raoult D. The puzzling mutational landscape of the SARS‐2‐variant Omicron. J Med Virol. 2022;94(5):2019-25.
3. Genomic epidemiology of novel coronavirus. 2022. [Last accessed on: July 7, 2025] https://nextstrain.org/ncov/gisaid/global
4. Gu H, Ng DYM, Liu GYZ, Cheng SSM, Krishnan P, Chang LDJ, et al. Recombinant BA.1/BA.2 SARS-CoV-2 virus in arriving travelers, Hong Kong, February 2022. Emerg Infect Dis. 2022;28(6):1276-8.
5. Guo Y, Han J, Zhang Y, He J, Yu W, Zhang X, et al. SARS-CoV-2 omicron variant: Epidemiological features, biological characteristics and clinical significance. Front Immunol. 2022;13:877101.
6. Chowdhury S, Bappy MH, Chowdhury S, Chowdhury MS, Chowdhury NS. Omicron variant (B.1.1.529) of SARS-CoV-2, a worldwide public health emergency! Eur J Clin Med. 2022;3(1):5-9.
7. Majumdar S, Sarkar R. Mutational and phylogenetic analyses of the two lineages of the Omicron variant. J Med Virol. 2022;94(5):1777-9.
8. Callaway E. Why does the Omicron sub-variant spread faster than the original? Nature. 2022;602(7898):556-7.
9. Rahimi F, Bezmin Abadi AT. The Omicron subvariant BA.2: Birth of a new challenge during the COVID-19 pandemic. Int J Surg. 2022;99:106261.
10. Fonager J, Bennedbæk M, Bager P, Wohlfahrt J, Ellegaard KM, Ingham AC, et al. Molecular epidemiology of the SARS-CoV-2 variant Omicron BA.2 sub-lineage in Denmark, 29 November 2021 to 2 January 2022. Euro Surveill. 2022;27(10):2200181.
11. Karyakarte RP, Das R, Taji N, Yanamandra S, Shende S, Joshi S, et al. An early and preliminary assessment of the clinical severity of the emerging SARS-CoV-2 omicron variants in Maharashtra, India. Cureus. 2022;14(11):e31352.
12. Fan Y, Li X, Zhang L, Wan S, Zhang L, Zhou F. SARS-CoV-2 Omicron variant: Recent progress and future perspectives. Signal Transduct Target Ther. 2022;7(1):141.
13. Ou J, Lan W, Wu X, Zhao T, Duan B, Yang P, et al. Tracking SARS-CoV-2 Omicron diverse spike gene mutations identifies multiple inter-variant recombination events. Signal Transduct Target Ther. 2022;7(1):138.
14. Chatterjee S, Bhattacharya M, Nag S, Dhama K, Chakraborty C. A detailed overview of SARS-CoV-2 omicron: Its sub-variants, mutations and pathophysiology, clinical characteristics, immunological landscape, immune escape and therapies. Viruses. 2023;15(1):167.
15. Whitaker M, Elliott J, Bodinier B, Barclay W, Ward H, Cooke G, et al. Variant-specific symptoms of COVID-19 in a study of 1,542,510 adults in England. Nat Commun. 2022;13(1):6856.
16. Webster HH, Nyberg T, Sinnathamby MA, Aziz NA, Ferguson N, Seghezzo G, et al. Hospitalisation and mortality risk of SARS-CoV-2 variant omicron sub-lineage BA.2 compared to BA.1 in England. Nat Commun. 2022;13(1):6053.
17. Bager P, Wohlfahrt J, Bhatt S, Stegger M, Legarth R, Møller CH, et al. Risk of hospitalisation associated with infection with SARS-CoV-2 omicron variant versus delta variant in Denmark: An observational cohort study. Lancet Infect Dis. 2022;22(7):967-76.
18. Chen Z, Deng X, Fang L, Sun K, Wu Y, Che T, et al. Epidemiological characteristics and transmission dynamics of the outbreak caused by the SARS-CoV-2 Omicron variant in Shanghai, China: A descriptive study. Lancet Reg Health West Pac. 2022;29:100592.
19. Deng J, Ma Y, Liu Q, Du M, Liu M, Liu J. Severity and outcomes of SARS-CoV-2 reinfection compared with primary infection: A systematic review and meta-analysis. Int J Environ Res Public Health. 2023;20(4):3335.
20. Kislaya I, Casaca P, Borges V, Sousa C, Ferreira BI, Fonte A, et al. Comparative effectiveness of COVID-19 vaccines in preventing infections and disease progression from SARS-CoV-2 omicron BA.5 and BA.2, Portugal. Emerg Infect Dis. 2023;29(3):569-75.
21. Zhou Z, Zhu Y, Chu M. Role of COVID-19 vaccines in SARS-CoV-2 variants. Front Immunol. 2022;13:898192.
22. Eythorsson E, Runolfsdottir HL, Ingvarsson RF, Sigurdsson MI, Palsson R. Rate of SARS-CoV-2 reinfection during an Omicron wave in Iceland. JAMA Netw Open. 2022;5(8):e2225320.
23. Lee WS, Wheatley AK, Kent SJ, DeKosky BJ. Antibody-dependent enhancement and SARS-CoV-2 vaccines and therapies. Nat Microbiol. 2020;5(10):1185-91.
24. Butt AA, Dargham SR, Coyle P, Yassine HM, Al-Khal A, Abou-Samra AB, et al. COVID-19 disease severity in persons infected with omicron BA.1 and BA.2 sublineages and association with vaccination status. JAMA Intern Med. 2022;182(10):1097-9.
25. Kung YA, Chuang CH, Chen YC, Yang HP, Li HC, Chen CL, et al. Worldwide SARS-CoV-2 Omicron variant infection: Emerging sub-variants and future vaccination perspectives. J Formos Med Assoc. 2024.
26. COVID-19 Forecasting Team. Past SARS-CoV-2 infection protection against re-infection: A systematic review and meta-analysis. Lancet. 2023;401(10379):833-42.

Supplementary Figures

Supplementary Fig. 1: Study design and screening of the participants for the comparative analysis.

Supplementary Fig. 2: Representative spike protein mutations of BA.1 SARS-CoV-2 Omicron variant.

Supplementary Fig. 3: Representative spike protein mutations of BA.2 SARS-CoV-2 Omicron variant.