Clinical Characteristics of SARS-CoV-2 Omicron Cases in Pune, Maharashtra, India

Background The SARS-CoV-2 Omicron variant, within two months of its detection, replaced the Delta variant to become the dominant circulating variant globally. Therefore, it is essential to understand the characteristics of the disease caused by the variant and its impact on vaccination. Methods A total of 165 confirmed Omicron cases attending a tertiary care hospital in Pune, Maharashtra, between December 2021 to February 2022 were studied. Their demographic, clinical, and immunization history was recorded. Results Among the 165 cases, 7.88% were B.1.1.529 Omicron cases, 25.45% were BA.1 Omicron cases, and 66.67% were BA.2 Omicron cases. Of these 165 patients, 146 (88.48%) were discharged after treatment, 12 (7.27%) died during hospitalization, and seven (4.24%) were brought dead. The presence of one or more comorbid conditions was seen in 15.15%, of which diabetes mellitus and hypertension (28% each) were the most common conditions. Older age (greater than 60 years), an important risk factor for poor outcomes, was present in 9.1% of cases. Among the 165 cases, vaccination with at least one dose of vaccine was found in 80.61% of cases. Out of 165 cases, clinical data was available for 158 cases. Of these 158 cases, 86.71% had symptoms, and 13.29% were asymptomatic. Fever, followed by cough, myalgia, runny nose, and headache, were the most common presenting symptoms. The mean duration of illness was 2.69 days, with 91.14% of cases having the illness for less than five days, and 89.24% of cases had a National Early Warning Score (NEWS) of 1-4, suggesting a good prognosis. In 93.90% of cases, the chest X-ray findings were normal. Of the 158 cases, 92.41% of cases recovered with supportive treatment, and only 7.59% of cases required oxygen therapy. Conclusion The current study shows that the Omicron variant caused mild disease with reduced need for hospital admission and oxygen therapy in India.


Introduction
On 24th November 2021, a novel SARS-CoV-2 variant was first reported from South Africa [1]. The variant was initially identified as Pango lineage B.1.1.529 and was designated as Omicron, a Variant of Concern (VOC) by the World Health Organization on 26th November 2021. This highly mutated SARS-CoV-2 variant had nearly 50 mutations in its genome compared to the original SARS-CoV-2 virus isolated in Wuhan, China. Of these mutations, around 26-30 mutations are of particular interest as they are in the spike protein region, of which 15 were in its receptor-binding domain (RBD) [2]. Since its first identification, the variant has spread rapidly worldwide and accounts for 99% of sequences reported globally [3].
Omicron is a highly transmissible variant with an effective reproduction number 3.19 (95% CI 2.82-3.61) times greater than Delta's. This property accounts for its rapid increase in numbers and higher transmissibility, thus displacing the prevailing Delta variant [4]. Various early studies have shown that extensive immune escape and reduced vaccine effectiveness of the Omicron variant have led to its higher transmission rate. Preliminary studies suggest that the variant causes less severe disease with milder 1 2 2 2 1

Data collection and analysis
Demographic characteristics and the clinical findings of Omicron cases were collected from medical and laboratory records maintained by the medical record section of the hospital. The data were entered in Microsoft Excel, and analysis was done using the JMP statistical software, version 13.0.0 (SAS Institute, Cary, NC). A p-value of less than 0.05 (typically ≤ 0.05) was considered a statistically significant result.

Demographic characteristics of COVID-19 cases infected with the Omicron variant of SARS-CoV-2
The demographic characteristics of 165 confirmed Omicron cases are shown in Table 2. Males (56.97%) were more affected than females (43.03%), with male to female ratio of 1.3: 1. The mean age of the study population was 36.51 (standard deviation = 17.02, 95% CI = 33.89 to 39.13). The age group 21 to 40 years were predominantly affected, followed by 41 to 60 years. Older age (greater than 60 years), an important risk factor for poor outcome, was present in 15/165 (9.1%) of cases. Figure 2 and Table 3 show the relationship between age and disease outcome. The presence of one or more comorbid conditions was seen in 15.15% of cases, diabetes mellitus (28%), hypertension (28%), obesity (16%), and interstitial heart disease (16%) were the most common conditions. Of the 165 cases, 81.82% were vaccinated with at least one dose of the COVID-19 vaccine (92.59% were vaccinated with two doses, and 7.41% were vaccinated with one dose of the vaccine), and 16.36% of the cases were unvaccinated. Figure 3 and Table 4 show the relationship between the vaccination status and the outcome of Omicron-confirmed cases.

Demographic characteristics
The

Clinical profile of COVID-19 cases infected with the Omicron variant of SARS-CoV-2
Out of 165 cases, the clinical characteristics of 158 (95.76%) Omicron cases could be recorded as the remaining seven cases were brought in dead ( Table 5). Of these 158 cases, 86.71% had symptomatic disease, and 13.29% had an asymptomatic infection. Fever (67.72%) was the most common presenting symptom, followed by cough (40.51%), myalgia (35.44%), runny nose (22.78%), and headache (15.82%). The duration of illness was less than five days in 91.14% of cases, and only in 8.86% of cases the illness lasted for more than a week. Figure 4 and Table 6 show the relationship between the duration of illness to Omicron variants. The mean duration of illness on admission was 2.69 days (standard deviation = 2.12, 95% CI = 2.36 to 3.02).    Based on the National Early Warning Score (NEWS), patients were classified as having low scores (NEWS 1-4), medium scores (NEWS of 5-6), and high scores (NEWS > 7). Of the 158 cases, 89.24% had a score of 1-4 (low score), and 8.86% had a score between 5-8. Figure 5 and Table 8    No systemic involvement was seen in 64.56% of the cases, while in 35.44% of cases, one or more organ systems were involved. The gastrointestinal and hepatobiliary system was most commonly affected (55.4%), followed by the cardiac system (50%), central nervous system (10.7%), renal system (8.93%), and hematological system (8.93%). Sepsis was seen in 17.9% of cases. For 82 cases, chest X-ray findings were available, of which 77 (93.90%) cases had normal X-Ray findings, whereas five (6.10%) cases had abnormal findings. Of these five cases, two (40%) had pulmonary infiltrates, and three (60%) had evidence of pulmonary oedema. These abnormal findings were seen in cases that succumbed to the disease.
Out of 158 cases, 146 (92.41%) cases recovered with conservative treatment, and 12 (7.59%) cases required additional oxygen therapy. Among those requiring oxygen therapy, 41.67% of cases required invasive ventilation for six to 12 hours. Of the 82 cases admitted, 48.78% were hospitalized for five to nine days.

Discussion
The most recently discovered novel SARS-CoV-2 variant, the Omicron variant, has a much higher effective reproduction number than the Delta variant (3.6 to 4.2 times) and a shorter incubation period. Among all the VOCs detected to date, the Omicron variant possesses the highest number of mutations in its genome, with 32 mutations in its spike protein. Mutations in the spike protein like Q493R, T478K, and N501Y bind to the host cell's angiotensin-converting enzyme 2 (ACE2) receptors with higher affinity than the wild type and other VOCs. Similarly, mutations like H655Y, N679K, and P681H increase cleavage activity by host furin. Such mutations in the spike protein led to increased infectivity and transmissibility [8,4].
The present study suggests that Omicron cases suffered from mild disease with 91.14% of cases having the illness for less than five days. Around 89.24% of cases had a NEWS between 1 to 4 suggesting a good prognosis. More than 90% of cases showed no lung involvement and recovered with conservative treatment. Death due to Omicron infection was seen in 11.5% of cases with most deaths concentrated in the population 60 years and older and those with comorbidities. Our results are consistent with earlier studies in South Africa that suggested a significant reduction in pathogenicity, severity, and mortality rates of the disease during the Omicron wave [9][10][11]. Similar findings have also been reported in countries such as the United States, France, South Korea, Japan [12][13][14][15], and China [8] where both the vaccination coverage and population infection were quite high. However, in the present study, the number of cases was small. As a result, the numbers under different subgroups were even smaller. With increasing numbers of cases presenting with no symptoms or requiring no hospital admission, clinical data in such cases became less available.
Transmembrane serine proteases 2 (TMPRSS2) facilitate viral entry into the host cell. The wild-type variant and other VOCs efficiently utilize this cell surface fusion pathway to enter the host cell. However, in the case of Omicron, the variant is inefficient in using this pathway. Studies indicate that Omicron depends on cathepsins and enters the host cell primarily through the endosomal pathway. The co-expression of ACE2 and cathepsins are abundant in the upper respiratory tract, explaining the increased replication of Omicron in bronchi than in the lungs. Therefore, in Omicron infection, there is reduced lung pathology and diminished pro-inflammatory responses [16]. This property probably explains the reduced disease severity, the reduced need for oxygen and hospital admission, and better survival outcomes in the Omicron cases compared to other VOCs. Our results are consistent with these findings, wherein 93.90% of cases had no lung involvement and 92.41% recovered with conservative treatment without any additional oxygen requirement.
Since the Omicron variant has acquired numerous mutations in its spike protein, particularly in its receptorbinding domain (RBD), this has increased the likelihood of reduced efficacy of the neutralizing antibodies on Omicron. Various studies have shown that Omicron partially or completely escapes neutralization by antibodies present in convalescent sera [17,18] and vaccinated individuals [19][20][21], thus suggesting evasion of natural and vaccine-induced immunity. Also, monoclonal antibodies, either clinically approved or in development for treatment, have completely failed to neutralize Omicron [22,23,18]. Mutations like E484A and K417N dodge the neutralizing antibodies, eventually resulting in an increased ability of immune escape [4]. Therefore, this probably explains the increased frequency of breakthrough infections and reinfection incidents during the Omicron wave. Besides the antibody-mediated immunity, studies have shown that Tcell responses to the Omicron variant are primarily preserved, and T-cell escape is minimal compared to other VOCs. Also, the booster vaccine doses enhance T-cell responses [24]. In the present study, the vaccination rate in the population under investigation was good, and it could have potentially contributed to the reduced severity of the disease. Therefore, good vaccination coverage is desirable for effective protection against severe disease [25].
The present study could not compare the differences in laboratory parameters between the survived and deceased cases due to the unavailability of investigation results for brought-in dead cases and a low number of in-hospital deaths. This fact limited our ability to draw definitive conclusions about the relationship between these laboratory parameters and the survival outcomes.

Conclusions
To conclude, the present study described the baseline characteristics of laboratory-confirmed Omicron variant cases in Pune, Maharashtra. Our analysis indicates Omicron causes a mild disease, with a reduced need for hospital admission, and a lower need for oxygen therapy. The overall lowered disease severity reflects the contribution of attenuated intrinsic virulence of the virus as well as the impact of prior immunity due to natural infection and/or vaccination. Vaccine breakthrough infections were commonly seen. Additional studies will continue to be essential in understanding the evolution of current and future variants in populations with a diverse immunological landscape.

Additional Information Disclosures
Human subjects: Consent was obtained or waived by all participants in this study. Institutional Ethics Committee, B. J. Govt. Medical College & Sassoon General Hospitals, Pune 1 issued approval BJGMC/IEC/Pharmac/ND-Dept 0721233-233, dated 15-09-2021. The Institutional Ethics Committee has unanimously approved your project topic. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.