Covid-19 – A High Rate of Asymptomatic Carriage Associated with Variant Strain Omicron

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The early widespread dissemination of Omicron indicates the urgent need to better understand the transmission dynamics of this variant, including asymptomatic spread among immunocompetent and immunosuppressed populations.

In early December 2021, the Ubuntu clinical trial, designed to evaluate efficacy of the mRNA-1273 vaccine (Moderna) among persons living with HIV (PLWH), began enrolling participants. Nasal swabs are routinely obtained at the initial vaccination visit, which requires participants to be clinically well to receive their initial jab.

Of the initial 230 participants enrolled between December 2 and December 17, 2021, 71 (31%) were PCR positive for SARS-CoV-2: all of whom were subsequently confirmed by S gene dropout to be Omicron; 48% of the tested samples had cycle threshold (CT) values <25 and 18% less than 20, indicative of high titers of asymptomatic shedding. Asymptomatic carriage rates were similar in SARS-CoV-2 seropositive and seronegative persons (27% respectively).

These data are in stark contrast to COVID-19 vaccine studies conducted pre-Omicron, where the SARS-CoV-2 PCR positivity rate at the first vaccination visit ranged from <1%-2.4%, including a cohort of over 1,200 PLWH largely enrolled in South Africa during the Beta outbreak.

We also evaluated asymptomatic carriage in a sub study of the Sisonke vaccine trial conducted in South African health care workers, which indicated 2.6% asymptomatic carriage during the Beta and Delta outbreaks and subsequently rose to 16% in both PLWH and PHLWH during the Omicron period.

These findings strongly suggest that Omicron has a much higher rate of asymptomatic carriage than other VOC and this high prevalence of asymptomatic infection is likely a major factor in the widespread, rapid dissemination of the variant globally, even among populations with high prior rates of SARS-COV-2 infection.

reference link : DOI: 10.1101/2021.12.20.21268130


This study is among the first from India to provide the evidence of community transmission of Omicron with significantly increased breakthrough infections, decreased hospitalization rates, and lower rate of symptomatic infections among individuals with high seropositivity against SARS-CoV-2 infections.

Findings: Out of the 264 cases included during study period, 68.9% (n=182)were identified as Delta and its sub-lineages while 31.06% (n=82) were Omicron with BA.1 as the predominant sub-lineage (73.1%). Most of the Omicron cases were asymptomatic (n=50,61%) and not requiring any hospitalizations. A total of 72 (87.8%) cases were fully vaccinated. 39.1% (n=32) had a history of travel and/or contacts while 60.9 (n=50) showed a community transmission. A steep increase in the daily progression of Omicron cases with its preponderance in the community was observed from 1.8% to 54%.

The median age of Omicron infected cases was 35 years (IQR 24-53) with male (57.3%, n=47) predominance. Demographic description of all 82 Omicron cases is depicted in Table

2. Majority of the cases (n=50, 61%) were asymptomatic. Hospitalization was recorded in only 3.6% (n=3) cases with diabetes mellitus and hypertension as an underlying comorbidity. None of the admitted cases required intensive care throughout their hospital stay. Time since RT-PCR negativity was 10±3days. Looking at the vaccination status, total of 87.8% (n=72) cases were fully vaccinated and an additional 01 (1.2%) had received heterologous vaccination (2 doses of mRNA-1273 [Moderna] and 1 dose of BBV152 Covaxin vaccine).

Epidemiological description of Omicron cases

In the present study, the first two cases of Omicron were detected during the first week of December with travelling history from South Africa. Afterwards we observed a steep increase in the daily progression of Omicron cases with its preponderance in the community from 1.8% to 54% (Figure 4).

History of international travel was documented among 19 cases [South Africa (n=6),UK (n=5), UAE (n=4), USA(n=3) and Canada(n=1)] while thirteen cases were the contacts of such travellers. On comparing cases with history of recent international travel and/or their contacts (n=32) with no travel history (n=50), no statistically significant difference could be ascertained (Table 3). However, the proportion of asymptomatic cases (n=23, 71.8%) was higher among travellers/ and or contacts in comparison to the community (n=27, 54%), suggesting acquisition of new variant by some cases from abroad with local importation.

Among total of 82 Omicron cases, 87.8% (n=72) were fully vaccinated. ChAdOx1 nCoV-19 (Covishield) was the most common administered vaccine in around 56% of cases. The other vaccines included BBV152 Covaxin (12%), BNT162b2 [Pfizer] (11%), mRNA-1273 (Moderna) (4%), Sputnik V vaccine (Gam-COVID-Vac) (4%) and Ad26.COV2.S vaccine (Johnson & Johnson–Janssen) (1%).

Discussion

Since the first confirmed Omicron reported from Delhi, a steep increase in the number of cases has been observed (Figure 7). To the best of our knowledge this is the first study from India to provide the evidence of community transmission of Omicron with significantly increased breakthrough infections, decreased hospitalization rates, and lower rates of symptomatic infections.

On December 5th 2021, the national capital New Delhi identified the state’s first and country’s fifth case of Omicron from a traveller returning from Tanzania4. Since then the cases are increasing with a doubling growth rate of 3-4 days, and replacing Delta as the dominant VoC in the time span of less than a month. Our study is based on epidemiological, clinical and genome sequence analysis of 264 cases since the day Omicron was designated as VoC by WHO.

We observed a definite shift from Delta predominance7 to Omicron along with its community spread. Similar findings were observed from various part of the world including South Africa and Denmark where the new variant simultaneously emerged at the end of November 2021 and rapidly became the predominant strain8,9. Interestingly in our study, the initial few cases were of BA.1 (73.1%) while 26.8% were of BA.2 sub-lineage.

This shift of sub-lineage in Omicron was also documented from Australia among 300 cases with travel history to South Africa10. The matter of concern is BA.2 sub-lineage, which has 303 additional unique mutations in comparison to BA.1. Of this mutational difference the most highlighting is the lack of spike protein deletion at amino acid 69/70 in BA.2, hence could not be detected by the SGTF(S-gene target failure) assay10.

We observed young adults and males were infected more in comparison to children and elderly population which could be because of more socialising habits and close connections than other mentioned groups. Our results suggest a large reduction in protection against COVID-19 infection with the Omicron variant as 87.8% population got reinfected after full primary vaccination thus implying increased breakthrough infections. This is in concordance with in- vitro studies that showed a significant reduction in neutralisation of the Omicron variant with convalescent sera or sera of fully vaccinated individual11.

The data is too immature to analyse these breakthrough infections based on the type of the vaccine. However, it is worth mentioning that a population of 148.33 lakhs in Delhi had already completed its first dose of vaccination by December 24th 2021 and two-third of them had been fully vaccinated with double doses12. Also the latest sero-survey study among Delhi population showed 89.5% seropositivity in the month of September-October 20216 .Amid increasing COVID-19 cases in the country, the Government on December 25th had announced vaccination for the 15-18 year age group from January 3rd 2022 and booster doses for healthcare and frontline workers from January 10th 2022 13.

Despite small numbers, we showed that individuals with a previous infection also had a clear increased risk of infection with Omicron compared with naïve individuals, suggesting that previous infection with another SARS-CoV-2 variant provides low levels of protection against Omicron infection. Our finding of reduced protection against reinfection with Omicron is in line with surveillance data from South Africa, showing increased risk of reinfections with the Omicron variant14.

Our findings strongly suggest that Omicron has a much higher rate of asymptomatic carriage resulting in high prevalence of asymptomatic infection, a likely major factor in the rapid dissemination of the variant locally and globally. Our results suggest a large decrease in protection from vaccine or natural immunity against COVID-19 infections caused by the Omicron variant.

This emphasizes the urgent need for booster vaccination and will warrant implementing non-pharmaceutical interventions along with the installation of rapid detection strategies for asymptomatic carriage in high-risk transmission populations especially with those having comorbidities.
The majority of Omicron patients (60.9%) had no documented international travel history or contact hence undoubtedly acquired the infection locally, thus signifying the community spread and imposing further challenges in epidemic control. The study emphasized how the formation of local clusters from imported cases eventually led to community transmission. Now, we are on a war-footing to deal with the upcoming outbreak of the third wave of Covid-19

Parts of the world are approaching a transition or a new phase of the COVID-19 pandemic.
It is too soon to know the exact extent to which vaccination or previous infection will provide protection against reinfection with Omicron. The present study highlight several reasons for concern: (i) the rapid community transmission shortly after introduction of the first case in the National Capital with higher seropositivity rates (ii) High proportion of fully vaccinated individuals.

In our study we are able to document the initial few cases of an unusual rapid community spread by the Omicron variant in Delhi State. In addition our study provides an insight about clinical course in a population with high vaccination coverage and seropositivity against COVID-19 infection. Also, our data emphasized the role of near-real time genomic surveillance in the low-middle income countries as the Omicron community transmission surge continues, the virus evolves, and new variants with potentially altered fitness and bio medically relevant phenotypes might generate in near future.

The present data did not give a true magnitude of community transmission in Delhi State as positive cases from five districts had been studied. Therefore further studies incorporating wider population of national capital are warranted for better understanding the clinical course and epidemiology of this emerged variant in the community.

Conclusion: To the best of our knowledge, this is the first study in which the early-stage representative data of local and community level transmission of infection from Delhi is investigated. Omicron infection was found to be associated with significantly increased breakthrough infections, decreased hospitalization rates, and less of symptomatic disease among individuals with high seropositivity against SARS CoV-2 infections. We observed a definite shift from Delta predominance to Omicron along with its community spread

reference link : https://doi.org/10.1101/2022.01.10.22269041

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