Omicron SARS-CoV-2 variant: An observational study from a hospital in Southern India

The COVID-19 pandemic has entered its third year of occurrence. COVID-19 was first reported in Wuhan, China in December 2019 and then on has marched relentlessly throughout the globe assuming many forms and names. It has so far affected 332 million people as on 19^th January 2022 and has led to 5.5 million deaths worldwide (1). India has faced two waves of COVID-19 pandemic and witnessed the third wave from the last week of December 2021. In India 38.2 million people were affected due to COVID-19 and 0.49 million have died (2). The B.1.1.529 variant was first reported to World Health Organization (WHO) from South Africa on 24^th November 2021. It was subsequently named as Omicron and was declared as a Variant of Concern (VoC) by WHO (3). This variant has a large number of mutations and the points of concern are increased risk of re-infection as compared to other VoCs, increased risk of transmissibility and a probable immune escape and questionable susceptibility to monoclonal antibody treatment (4).

Omicron has over 50 mutations including 32 on the spike protein. Since its initial detection from a specimen collected on November 8^th 2021, Omicron replaced delta as the dominant variant amounting to 74% of the genome sequenced in South Africa and more than 99% in rest of the world (4). The SARS-CoV-2 Omicron variant harbors 37 Amino acid substitutes in the spike protein, 15 of which are in receptor binding domain. The gold standard for testing is the Reverse Transcription-Polymerase Chain Reaction (RT-PCR) from the nasopharyngeal and oropharyngeal secretions collected with the swab. Ideally COVID-19 is diagnosed if 3 out of 4 genes namely the N gene, E gene, RdRp gene and the S gene are detected. However, the characteristic S Gene Target Failure (SGTF) due to deletion at Spike position 69 – 70 leading to failure of detection of S gene also called the S gene dropout is 98.9% sensitive and 99.9% specific in diagnosis of the Omicron variant and this is being used as a surrogate marker in the diagnosis of Omicron variant infection (5).

The Incidence of Omicron variant cases was confirmed in 149 countries by the WHO as of 6 January 2022. The global weekly incidence of COVID-19 had increased by 71.0% compared with the previous week. The Omicron variant rapidly outpaced Delta with documented community transmission in most countries and had led to an upsurge in cases in most regions. The WHO regions especially the Americas and the South-East Asia Region reported the highest increases of 100% and 78.0%, respectively (4).

India has two major vaccines which are approved and used in the COVID-19 Vaccination program namely the Covishield (ChAdOx1 nCov-19) and Covaxin (BBV152). The Multicentric Case Control study done in India indicated that the overall vaccine effectiveness was 80.0% with two doses of ChAdOx1 nCov-19/Covishield and 69.0% with BBV152/Covaxin against severe COVID-19. The vaccine effectiveness was highest for a 6 to 8 week interval between two doses of the both the vaccines. The study also indicated a substantial reduction in the risk of severe COVID-19, particularly against the Delta strain (6). Similarly, an interim analysis of a multicenter randomized control trial on ChAdOx1 nCoV-19 vaccine in four trials across three continents, showed a significant vaccine efficacy of 70.4% after two doses and protection of 64.1% after at least one standard dose, against symptomatic disease, with no safety concerns (7).

The immune protection offered by vaccines available at present against the Omicron variant is a point of concern. A research study in Denmark done in December 2021 showed majority 76% of the Omicron cases were fully vaccinated while 7.1% had their booster dose. 4.3% of the cases had a previous SARS-CoV-2 infection and almost 76% were symptomatic and community transmission was present (8). The reason for immune evasion, increased transmissibility and escape from neutralizing antibodies of already vaccinated individuals might be due to several mutations, specifically on the S-protein of the Omicron variant. Omicron variant also had a high reinfection capacity and may affect previously infected COVID-19 patients (9).

As of 23 January 2022, a total of 9.62 billion vaccine doses were administered worldwide with 52.5% of global population being completely vaccinated as per WHO (10). As on 25^th January 2022, India’s Cumulative COVID-19 Vaccination Coverage exceeded 1.63 billion doses with 67.4% of population being vaccinated with at least one dose of vaccine and 49.6% being completely vaccinated and 0.6% has received its precautionary dose (11). In spite of a robust COVID-19 vaccination programme being carried out in India since January 2021, Omicron cases surged in early part of January 2022. Not many studies have been carried out in this part of southern India related to clinic-epidemiological profile of omicron variant and also related to the vaccination status of such omicron cases. Hence the present study was conducted with the following objectives:

1. To describe the socio-demographic and clinical profile of Omicron (SGTF) cases treated at our tertiary care institution.

2. To assess the factors associated with the vaccination status of such Omicron (SGTF) cases.

This prospective observational study was conducted in the southern region of India at a hospital in Chennai city which is a 500 bedded public health facility which mainly caters to the healthcare needs of people around the city as well as to the people within the state of Tamil Nadu. This study was conducted for a period of two months from 15^th of December 2021 to 5^th of February 2022. All the omicron suspect cases with SGTF registered at the COVID-19 clinic of the Hospital who consented were included as the study subjects. Patients with hearing, speech and metal impairment and those outpatients on home isolation who could not be contacted through telephone were excluded. There were 333 patients who were registered at the outpatient COVID-19 clinic of the hospital who were tested positive for COVID-19 by RT-PCR along with SGTF (using TaqPath™ COVID-19 RT-PCR Kit (Thermo Fisher Scientific, California, USA)) were considered as omicron suspect cases.

Response rate of the study participants was 60.96%. Of the 333 patients who were registered, 203 patients who consented for the study were included as per the inclusion criteria and were telephonically interviewed. For patients under supplemental oxygen support, socio-demographic details were collected from their family members and clinical data from their medical records respectively. Inclusion criteria was based on the Clinical and laboratorial parameters of COVID-19 as per the Indian Council for Medical Research (ICMR) guidelines. Patients were categorized into mild, moderate and severe cases accordingly. Mild cases were those COVID-19 cases who presented with upper respiratory tract symptoms and or fever without hypoxia while moderate cases defined as those COVID-19 cases with breathlessness i.e, a respiratory rate of ≥ 24/ minute and/or SpO2 of 90% to ≤ 93% on room air and severe cases were defined as those COVID-19 cases with breathlessness i.e, a respiratory rate of > 30/ minute and/or SpO2 of < 90% on room air. Accordingly, mild cases were sent for home isolation or those eligible were advised observation at a COVID-19 care center. Moderate and severe cases of COVID-19 were hospitalized and managed as per established protocols of the hospital in inpatient ward and intensive care unit respectively (12). Data was collected in a pre-designed semi-structured questionnaire and entered through google forms and recorded in google spreadsheet. Data on socio-demographic details, symptoms, vaccination status, travel history, past history of COVID-19 infection, co-morbidities, treatment details, duration of hospital stay and prognosis were collected by interview method as well from scrutiny of their medical records. Vital parameters including pulse rate, respiratory rate, blood pressure, temperature and oxygen saturation (SpO2) in blood and a baseline complete blood count were recorded. Data was collected after obtaining the informed consent and on prior approval from the Institutional Ethics Committee (IEC). Data was entered in google spreadsheet was statistically analyzed with descriptive statistics like mean, median, standard deviation, range, inter-quartile range and inferential statistics like Mann Whitney U test, Chi-square test using SPSS software trial version 28.0 and OpenEpi software. At 95% confidence level, a P value of ≤ 0.05 was considered as statistically significant.

Age of the 203 study subjects ranged between 7 and 86 years with a mean age (95% CI) of 42 years (40, 45 years). Table 1 shows majority 79 (38.9%) and 78 (38.4%) of them were in the age group of 21 to 40 years and 41 to 60 years. Of the total 203 subjects with RT-PCR positivity with SGTF studied, 129 (63.5%) were males and 74 (36.5%) were females. 39 (19.2%) patients had comorbidities like Type II Diabetes Mellitus, Hypertension etc. 29 (14.3%) subjects had travelled to various national and international regions 14 days prior to their diagnosis of COVID-19 infection. Among the study subjects, 16 (7.9%) patients had past history of COVID-19 infection while 14 (6.9%) of them were not sure about it. The duration of past COVID-19 infection and the present infection ranged between 1 month to 18 months with a mean duration (95% CI) of 8 months (6, 10 months).

Of the 203 cases studied, majority 149 (73.4%) were symptomatic. As shown in table 2, among the 149 symptomatic cases, almost 114 (76.5%) had fever, 72 (48.3%) had cough and 29 (19.5%) had myalgia. Among the 203 subjects studied, 193 (95.1%) cases were categorized as mild, 8 (3.9%) as moderate and 2 (1.0%) as severe cases of COVID-19 with SGTF. Majority 114 (56.1%) were initiated treatment at the outpatient clinic and were monitored under home isolation through teleconsultation services while 89 (43.8%) cases were admitted in In-patient ward and treated. Most of the patients were independent of supplementary oxygen support, while only 10 (4.9%) patients received supplementary oxygen support of which 8 (80%) received the support through simple face mask and 2 (20.0%) received through Continuous Positive Airway Pressure (CPAP). Of the 203 study subjects, majority 134 (66.0%) were monitored under home isolation following their treatment at outpatient clinic or in-patient ward, 60 (29.6%) were discharged following their treatment completion at in-patient ward, 7(3.4%) were referred to higher centers for further management and 2 (1.0%) had died.

Table 3 shows that almost 158 patients (77.8%) were vaccinated against COVID-19. Among the 158 subjects who were vaccinated majority 106 (67.0%) were vaccinated with Covishield vaccine followed by 50 (31.7%) of them with Covaxin. Of the 158 vaccinated subjects, 126 (79.7%) patients were completely vaccinated with 2 doses of any COVID-19 vaccine and 32 (20.3%) were partially vaccinated with a single dose of any COVID-19 vaccine. Among the 32 partially vaccinated subjects 6 (18.8%) had taken Covaxin, 25 (78.1%) had taken Covishield and 1(3.1%) had taken Pfizer vaccine. Among the 126 completely vaccinated subjects 44 (34.9%) had taken Covaxin, 81(64.3%) had taken Covishield and 1(0.8%) had taken Sputnik vaccine.

As shown in table 4, there was no statistically significant association between the vaccination status and symptomatic status of the study subjects (P = 1.004). The proportion of patients who received in-patient course of treatment was higher among the unvaccinated compared to the vaccinated. This association between the vaccination status and course of treatment was statistically significant (P < 0.001, OR = 3.356, 95% CI of OR = 1.669, 6.748). Among those study subjects who required supplemental oxygen (n = 10), the proportion of those vaccinated was lower compared to those who were unvaccinated. This association between supplemental oxygen requirement and vaccination status was statistically significant (P = 0.003, OR = 0.169, 95% CI of OR = 0.045, 0.628).

In India since Covaxin and Covishield vaccines are the two major vaccines under usage. Among the 158 vaccinated subjects, only 2 were vaccinated with other vaccines like Pfizer and Sputnik vaccines. Hence the 2 subjects were omitted in further analysis of data and results would limit to those 156 subjects who were vaccinated with either Covishield or Covaxin only. Therefore 125 completely vaccinated subjects and 31 partially vaccinated subjects would be considered for comparison between completely and partially vaccinated subjects.

Table 5 shows that among the 125 completely vaccinated subjects, the mean interval between two doses of Covaxin vaccine taken was 48 (95% CI = 40, 55) days [SD = 25; median (IQR) = 33 (30 - 60 days)] and mean interval between two doses of Covishield vaccine taken was 85 (95% CI = 76, 94) days [SD = 39; median (IQR) = 89 (51 – 97 days)]. This mean differen ce (95% CI) of 37 (24, 50) days between Covishield and Covaxin vaccine among the completely vaccinated subjects was statistically significant (P < 0.001).

As it is presented in table 6, it is inferred that among the partially vaccinated subjects (n = 31), the mean (95% CI) interval between the last dose of vaccine taken and date of RT-PCR positivity with SGTF was 115 (39, 191) days for Covaxin vaccine and was 126 (98, 154) days for Covishield vaccine. Among the partially vaccinated individuals, there was no statistically significant difference in mean interval between the last dose of vaccine taken and date of RT-PCR positivity with SGTF between Covaxin and Covishield vaccinated subjects (P = 0.960). It is also inferred that among the completely vaccinated subjects (n = 125), the mean (95% CI) interval between the last dose of vaccine taken and date of RT-PCR positivity with SGTF was 186 (162, 210) days for Covaxin vaccine and was 131 (114, 148) days for Covishield vaccine. Among the completely vaccinated individuals, there was a statistically significant difference in mean interval between the last dose of vaccine taken and date of RT-PCR positivity with SGTF between Covaxin and Covishield vaccinated subjects (P < 0.001).

According to the Directorate of Public Health of Tamil Nadu in India, the third wave of COVID-19 was predominantly due to Omicron variant which surged since 12_th of December 2021 and lasted till the first week of February 2022. The transmission rate was higher but the disease was less severe leading decreased hospitalization, reduced supplemental oxygen utilization and deaths. The third wave predominantly due to Omicron variant took three weeks to attain its peak from onset compared to the second wave which was predominantly due to delta variant which took nine weeks to attain its peak (13). The mean age of study subjects was 42 years (range: 7 – 86 years) in our study. Similarly, Kim MK et al study had reported that the median age of omicron cases was 39.5 years [range: 2 – 69 years] (14).

The Kumar RM et al study showed that 19.9% had comorbidity which was in similar to our study where 19.2% of the patients had comorbidities (15). International travel of people during a Pandemic result in importing of cases while travelling within the country leads to spread of the disease across the states. In our study 14.3% subjects had travelled to various national and international regions 14 days prior to their diagnosis of COVID-19 infection. In contrast Kim MK et al reported 45% of subjects had travel history prior to their infection (14).

As per Meo SA et al study, infection due to Omicron variant mostly resulted in mild symptoms like mild cough, fever, generalized myalgia, malaise, a scratchy but not sore throat, headache, body ache, and moderate to severe fatigue (16). Kumar RM et al study done in Chennai reported that 64.5% had symptoms of which 43.2% had fever, 23.4% had body pain, 22.2% had running nose and 21.2% had cough as their predominant symptoms (15). Similarly in our study we found that majority 73.4% were symptomatic of which 76.5% had fever, 48.3% has cough and 19.5% had myalgia as their predominant symptoms. Several data sources on the Omicron variant suggest that the risk of hospitalization and the requirement for mechanical ventilation are lower than for the Delta variant. Research from, south Africa suggests that people infected with Omicron have 80% less likely to be admitted in the hospital than when they contract other strains (17). In similar to the study done by Sharma RP et al in Rajasthan (northern India) where almost 99.7% recovered, 33.0% had mild disease, 9.2% had moderate disease and 0.7% had severe disease requiring hospitalization, in our study we observed that majority 95.1% cases were categorized as mild, 3.9% as moderate and 1.0% as severe cases of COVID-19 with SGTF (18). This decrease in severity of Omicron variant of COVID-19 and reduction in hospitalization could be due to the repeated mutations of the virus strain resulting in its reduced pathogenicity. Also, this could be attributed to increase in herd immunity of the population due to COVID-19 immunization campaign and natural immunity gained from COVID-19 infection due to the previous variants.

Vaccination against COVID-19 and public health measures like social distancing, compliance to face mask and handwashing practices have played a major role in control of the COVID-19 pandemic. Vaccination has been proven to be the most effective means for COVID-19 prevention and control (19). WHO has indicated that a COVID-19 Vaccine with a minimum efficacy of 50% would be approved for emergency use in its target product profile (20). A study done by Bartsch SM et al found that a vaccine with efficacy of 60 – 80% could allow reduction in physical distancing measures, but this would still require high coverage (21).

WHO has defined breakthrough infection post vaccination as detection of SARS-CoV-2 RNA or antigen in a respiratory specimen collected from a person with or without COVID-19 like symptoms ≥ 14 days after completion of all recommended doses of the vaccine series (22). In our study we found that among the completely vaccinated subjects (n = 125), the mean (95% CI) interval between the last dose of Covaxin vaccine taken and date of RT-PCR positivity with SGTF was 186 (162, 210) days and for Covishield vaccine taken was 131 (114, 148) days. This suggests that booster doses to the vaccinated individuals could increase the duration of protection offered by these vaccines. Dejnirattisai W et al study reported that neutralization titers of Omicron by sera from vaccinees and convalescent subjects infected with early pandemic as well as Alpha, Beta, Gamma, Delta were substantially reduced or failed to neutralize. Although breakthrough infections could occur, vaccines would still offer protection from severe disease perhaps by T cells and complete failure of vaccines is unlikely. It was likely that the vaccine induced T cell response to SARS-CoV-2 would be less affected than the antibody response. Titers against Omicron were significantly boosted by third doses of vaccine and were high in cases both vaccinated and infected by Delta and hence booster vaccine campaign would add considerable protection against Omicron infection (23).

In our study we found that almost 77.8% were vaccinated against COVID-19 of which 67% were vaccinated with Covishield vaccine followed by 31.7% of them with Covaxin. Of the vaccinated subjects, 79.7% patients were completely vaccinated with two doses of any COVID-19 vaccine and 20.3% were partially vaccinated with a single dose of any COVID-19 vaccine. Similarly, Kumar RM et al study showed that 14.2% and 67.4% suspected omicron cases had received one and two doses of COVID-19 vaccines (15). In our study the proportion of patients who received in-patient course of treatment was higher among the unvaccinated compared to the vaccinated. This association was statistically significant (P < 0.001, OR = 3.356, 95% CI of OR = 1.669, 6.748). Also, we found that among those study subjects who required supplemental oxygen, the proportion of those vaccinated was lower compared to those who were unvaccinated. This association between supplemental oxygen requirement and vaccination status was statistically significant (P = 0.003, OR = 0.169, 95% CI of OR = 0.045, 0.628).

Similarly, Menni C et al study found that those who had received two or three vaccine doses had a lower risk of hospitalization during omicron prevalence which was statistically significant (OR = 0.75, 95% CI = 0.57 - 0.98; P = 0.03). Of the vaccinated individuals only 1.9% of them were hospitalized due to omicron and only 2.6% due to delta variant (24). Also, Karim SSA et al observed that vaccinated individuals were likely to have a much lower risk of severe disease from omicron infection. A combination of preventive measure such as vaccination and public health measures is expected to remain an effective strategy in control of the surge in cases due to Omicron variant (25).

Omicron (SGTF) cases manifests mostly as mild cases with symptoms like fever, cough, myalgia and majority were independent of oxygen supplementation and had good prognosis. Since majority of the Omicron cases were treated under home isolation, policies to strengthen the surveillance of home isolation cases and remote monitoring of cases through teleconsultation is necessary to prevent widespread transmission. Omicron infection has been delayed over six months among completely vaccinated subjects especially those who were vaccinated with Covaxin. Though the immune protection offered by the currently available vaccines against omicron variant remains to be a point of concern, vaccination would still play a major role in delaying the occurrence of a new episode as well as in minimizing the severity of illness. Improving the vaccination coverage and adherence to preventive public health measures like usage of face mask, hand hygiene and physical distancing would remain as the major strategy in control of COVID-19 pandemic amidst its periodic fluctuations due to variants of concern. Above all community participation is the keystone in successful implementation of public health measures for prevention and control of diseases, especially during a pandemic.

The study was conducted among only 203 study subjects, a larger sample size could have given more information on the objectives of the study. Both univariate and bivariate analysis were used for statistical analysis. Multivariate analysis could have addressed the potential confounders in the study. Being a hospital based cross sectional study rather than a community-based field study, only vaccination status of patients who sought medical care from the hospital were studied.