Very high rates of asymptomatic infection with Omicron compared to prior SARS-CoV-2 variants

The advent of the B.1.1.529 (Omicron) severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) variant, detected initially in Botswana and South Africa and now found in over 135 countries as of January 3, 2022, has sparked fears of a new global wave of infections and hospitalizations. In addition, the significant number of deletions and mutations, some of which are similar to those found in previous Variants of Concern (VoC), are concerning because they could result in enhanced transmissibility, viral binding affinity, and immunologic escape.

These fears have grown as a new generation of COVID-19 cases has emerged in South Africa at a higher rate than any of the preceding three waves, despite continuous mask regulations and high antibody seropositivity due to prior infection or vaccination. The rapid expansion of Omicron in Europe and the United States indicates that a deeper understanding of the transmission dynamics of Omicron, particularly asymptomatic spread among immunocompetent and immunosuppressed populations, is urgently needed.

A preprint version of this study, which is yet to undergo peer review, is available on the medRxiv* server.

Study: High Rate of Asymptomatic Carriage Associated with Variant Strain Omicron. Image Credit: Orpheus FX / Shutterstock.com

Study: High Rate of Asymptomatic Carriage Associated with Variant Strain Omicron. Image Credit: Orpheus FX / Shutterstock.com

The study

On December 2, 2021, A team of researchers from institutions within South Africa and the United States started enrolling people in the Ubuntu multi-center Phase 3 clinical trial in Sub-Saharan Africa to see how effective the COVID-19 mRNA vaccine mRNA-1273 (Moderna) is in people living with HIV (PLWH) and/or with at least one comorbidity known to be associated with severe COVID-19. The experiment also includes a smaller group of HIV-negative people. Patients who have already been immunized are not eligible.

HIV screening, CD4+ T-cell count, HIV viral load (if HIV positive), and a nose swab for reverse-transcriptase polymerase chain reaction (RT-PCR) testing are all part of the baseline testing. The baseline SARS-CoV-2 antibody status was determined using the Assure Ecotest IgG/IgM Rapid Test (Assure Tech). To be vaccinated, study participants must be clinically healthy and have no indications or symptoms of COVID-19.

A total of 330 people had been enrolled throughout seven South African regions as of December 17, 2021. Participants ranged in age from 18 to 76 years old, with 79% having been assigned female sex at birth. For 230/330 registered participants in five provinces, baseline nasal swab data were available. By RT-PCR, 31% (71) of individuals had indications of acute SARS-CoV-2 infection, with Gauteng province having the most significant percentage.

SARS-CoV-2 detection was similar in individuals who were seropositive vs seronegative, and there was no correlation between detection and CD4+ T cell count. The S gene dropout was evaluated in 62 of the detected infections; 56 samples were successfully amplified for the Orf and N genes by TaqPathTM COVID 19 CE IVD RT PCR (ThermoFisher); all showed S gene dropout, indicating Omicron infection.

Several COVID-19 vaccine effectiveness trials have used nasal swab samples at the initial vaccination visit to determine if patients were infected at the time of study entry. Asymptomatic carriage of pre-Omicron variants was found in 1% of individuals in research conducted before Omicron, including a 1,227 PLWH subgroup in the Ensemble 1 research, which was predominantly enrolled during the Beta outbreak in South Africa. In addition to these CoVPN investigations, the Sisonke trial, which was done primarily in South Africa between June and August 2021 during the Delta outbreak, found a 2.4% asymptomatic carriage rate in the subgroup sampled on vaccination day.

To date, 91 of the 577 Sisonke subgroup participants who were resampled from mid-November to December 7, 2021, at the 6-month follow-up visit had SARS-COV-2 found in their nasal swab sample. Between PLWH (27 of 169: 16%) and HIV-negative patients (62 of 405: 153%), the incidence of PCR positivity with Omicron was similar.

Implications

These findings strongly show that Omicron has a significantly greater rate of asymptomatic carriage than other VoC, and that this high rate of asymptomatic infection is likely a major component in the variant's global spread, especially among communities with high past rates of SARS-COV-2 infection. Many of these asymptomatic carriers had high nasal virus titers, implying that subclinical carriage may be a significant component in Omicron's global expansion. Vaccination's impact on the prevalence or titers of asymptomatic infection is unknown.

The Ubuntu research's samples were entirely from unvaccinated people, and the data from the Sisonke trial is only a small portion, making it impossible to compute any estimate of vaccine effectiveness. Nevertheless, it is critical to collect data on asymptomatic carriage and transmissibility among vaccinated people. In high-risk transmission populations like long-term care institutions and hospitals, non-pharmaceutical therapies and quick detection measures for such carriage should be addressed. These findings also lend credence to the continuing endeavor to create second-generation vaccinations that could prevent SARS-CoV-2 infection.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
Colin Lightfoot

Written by

Colin Lightfoot

Colin graduated from the University of Chester with a B.Sc. in Biomedical Science in 2020. Since completing his undergraduate degree, he worked for NHS England as an Associate Practitioner, responsible for testing inpatients for COVID-19 on admission.

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Comments

  1. Paolo Maccallini Paolo Maccallini Italy says:

    The percentage of asymptomatic infections in the second study (Delta variant) on unvaccinated individuals (Sisonke sub-study) is 2.4%, not 24% (see table 1.b).

  2. Paolo Maccallini Paolo Maccallini Italy says:

    I made an attempt at calculating the proportion of asymptomatic Omicron infections in function of the same parameter in the case of Delta infections, among unvaccinated individuals. I used the data presented in the paper mentioned in this article, particularly the data relative to the subjects enrolled in the Ubunto trial (Omicron wave) and those of the population included in the Sisonke sub-study (Delta wave). The result is that, if we assume a proportion of asymptomatic infections of 17% for the Delta variant, then we have that about 60% of all Omicron cases are asymptomatic, in unvaccinated subjects. The details of the calculation I performed can be found here: paolomaccallini.com/2022/01/03/happy-new-variant/

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
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