Under the Microscope with David Weber: Update on the COVID-19 Variant, Omicron

Author: David Weber, MD, MPH, FSHEA, FIDSA, FMSM (London)

January 11, 2022

As of 10 January 2022, the United States has had 60,090,637 cases of COVID-19 leading to 837,664 deaths. COVID-19 cases in the United States are now exceeding greater than 500,000 cases per day; the current level of cases has exceeded those seen during the Delta-peak in August-September 2021. Although according to the New York Times, as of January 9th, 2022, the 14 day change is as follows: COVID-19 cases have increased by 215%, hospitalizations have increased 82% and deaths have increased by 16%. The Centers for Disease Control and Prevention now reports that constitutes ~95% of all cases of SARS-CoV-2 in the United States.

The dramatic increase in COVID-19 cases worldwide and in the United States is being driven by the immergence of the Omicron variant of SARS-CoV-2.  SARS-CoV-2 is an enveloped RNA virus.  All viruses, but especially RNA viruses, change over time due to mutations (see Table 1 for definitions).  The U.S. Centers for Disease Control and Prevention (CDC)1 and the World Health Organization2 classify and track SARS-CoV-2 variants.  Variants are categorized as variants of concern (VOC), variants of interest (VOI), or variants of high consequence (VOOHC) (see Table 2).  The Omicron variant was first reported from South Africa in November 2021.  This variant is now the predominant variant both worldwide and in the United States.

On November 30, 2021, Omicron was designated by the U.S. Government as a variant of concern based on the following:

  • Detection of cases attributed to Omicron in multiple countries, including among those without travel history;
  • Transmission and replacement of the Delta variant in South Africa.;
  • A large number of mutations;
  • Likely reduction of effectiveness of certain monoclonal antibody therapy;
  • Likely reduced effectiveness of vaccines; and
  • 6) Likely reduced effectiveness of natural immunity (i.e., people who had previously been infected with an earlier variant such as Beta or Delta).

Omicron has replaced Delta as the dominant variant worldwide and in the U.S. for the following reason:

  • More infectious
  • Reduced protection from immunity produced by prior COVID-19 infection
  • Reduced protection from immunity produced by COVID-19 vaccines, including in those “fully” vaccinated (i.e., a couple of series of Pfizer or Moderna vaccines).

Due to these characteristics, the doubling time of Omicron is ~1.5 to 2.0 days.3  Prior infection with COVID-19 (Delta or a non-Omicron variant) provides limited protection against acquiring Omicron with a risk of reinfection 5.41-fold higher than with Delta.3  There is a significantly higher risk with Omicron than with Delta in persons fully vaccinated (i.e., 2 weeks after completing a complete two-dose series of Pfizer or Moderna) of 2.68-fold.3  However, persons who have had a primary vaccine series plus a booster dose have substantially better protection, 55 to 80% against acquiring Omicron.3

Another study reported that 15 weeks after a two-dose series of Pfizer vaccines, vaccine effectiveness was ~34 to 37% but rose to ~75.% after a booster dose.4  Discovery Health reported that 2 doses of Pfizer vaccine provided 33% protection against infection with Omicron but 70% protection against severe disease.5  Omicron has been associated with a lower rate of hospitalization than Delta.3  One study reported that the overall risk of hospitalization with Omicron was 1.2% compared with 1.5% with Delta.6  A more recent study reported persons with Omicron compared to previous variants had a lower frequency of requiring oxygen therapy, mechanical ventilation, and admission to an intensive care unit.7 They also had a shorter length of stay and a lower frequency of death.7 An explanation for the greater infectiousness of Omicron and reduced severity is explained by a study that demonstrated that Omicron multiples 70 times faster in the upper airways (hence, increased infectiousness) but much slower in the lung (hence, reduced virulence).8

Based on in vitro tests, Omicron also is not treatable by most currently available monoclonal antibody therapies.  However, Sotrovimab is still effective but likely to be in short supply.  Other effective therapies include the new oral drugs Molunpiravir and Paxlovid which are~30% and ~90% effective against serious diseases such as hospitalizations, respectively.7  Remdesivir, an FDA-approved drug, can also be used off-label for therapy of persons with mild to moderate infection who are at high risk for progression to serious disease.7  Evusheld (tixagevimab co-packaged with cilgavimab), a monoclonal antibody combination is FDA authorized for pre-exposure therapy of highly immunocompromised persons; the drug provides protection for 6 months, at which time it can be redosed.7

Omicron is now the dominant variant worldwide and in the United States.  Preventive measures include the following:

  • All eligible persons should be fully vaccinated (i.e., persons 5 years or older).
  • All eligible persons who are fully vaccinated should receive a booster vaccine dose (i.e., persons 16 years and older).
  • Masking remains effective in preventing Omicron. Therefore, all persons but especially those who are a high risk for serious infection (i.e., older, underlying medical conditions, unvaccinated) should wear a mask whenever indoors outside their home.
  • Avoid unmasked community gatherings.
  • If ill, contact your primary care providers and DO NOT GO TO WORK.


  1. Centers for Disease Prevention and Control. SARS-CoV-2 Variant Classifications and Definitions.  Available at: https://www.cdc.gov/coronavirus/2019-ncov/variants/variant-classifications.html?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fcoronavirus%2F2019-ncov%2Fvariants%2Fvariant-info.html.
  2. World Health Organization. Tracking SARS-CoV-2 Variants.  Available at: https://www.who.int/en/activities/tracking-SARS-CoV-2-variants/.
  3. Ferguson N, Ghani A, Cori A, Hogan A, Hinsley W, Volz E. Report 49: Growth, population distribution and immune escape of Omicron in England.  Available at:  https://spiral.imperial.ac.uk/handle/10044/1/93038.  Accessed 1 January 2021.
  4. Andrews N, Stowe J, Kirsebom F, et al. Effectiveness of COVID-19 vaccines against the Omicron (B.1.1.529) variant of concern.  Available at:  https://www.medrxiv.org/content/10.1101/2021.12.14.21267615v1.  Accessed 1 January 2021.
  5. Discovery Health. Discovery Health, South Africa’s largest private health insurance administrator, releases at-scale, real-world analysis of Omicron outbreak based on 211 000 COVID-19 test results in South Africa, including collaboration with the South Africa.  Available at: https://www.discovery.co.za/corporate/news-room.  Accessed 1 January 2021.
  6. Espenhain L, Funk T, Overvad M, et al. Epidemiological characterisation of the first 785 SARS-CoV-2 Omicron variant cases in Denmark, December 2021.  Available at:  https://www.eurosurveillance.org/docserver/fulltext/eurosurveillance/26/50/eurosurv-26-50-3.pdf?expires=1639934672&id=id&accname=guest&checksum=8B1B0A274F85DEC7EF02293BB7DFE5B3.  Accessed 1 January 2021.
  7. Maslo C, Friedland R, Toubkin M, Laubscher A, Akaloo T, Kama B. Characteristics and Outcomes of Hospitalized Patients in South Africa During the COVID-19 Omicron Wave Compared With Previous Waves. JAMA. 2021 Dec 30.
  8. HKU Med.  HKUMed finds Omicron SARS-CoV-2 can infect faster and better than Delta in human bronchus but with less severe infection in lung.  Available at:  https://www.med.hku.hk/en/news/press/20211215-omicron-sars-cov-2-infection?utm_medium=social&utm_source=twitter&utm_campaign=press_release.  Accessed 10 January 2022.
  9. Infectious Disease Society of America. IDSA Guidelines on the Treatment and Management of Patients with COVID-19.  Available at:  https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/.  Accessed 1 January 2021.
  10. National Institutes of Health. COVID-19 treatment guidelines.  Available at:  https://www.covid19treatmentguidelines.nih.gov/about-the-guidelines/whats-new/.  Access 1 January 2021.
  11. Johns Hopkins University & Medicine. Coronavirus map. Available at: https://coronavirus.jhu.edu/map.html Access 1 January 2021.
  12. Centers for Disease Prevention and Control. Coronavirus data tracker. Available at:  https://covid.cdc.gov/covid-data-tracker/#trends_dailycases Access 1 January 2021


David Weber MD, MPH
Dr. David Weber, Associate Chief Medical Officer for UNC Medical Center Associate Chief Medical Officer for UNC Medical Center


Dr. David Jay Weber received his Bachelors of Arts (B.A.) degree from Wesleyan University in 1973, his Medical Degree (M.D.) from the University of California, San Diego in 1977, a Master’s in Public Health (M.P.H.) from Harvard University in 1985, and completed his medicine residency and infectious disease fellowship at the Massachusetts General Hospital in 1985.

He is Board Certified in Internal Medicine, Infectious Disease, Critical Care Medicine, and Preventive Medicine.  Dr. Weber has been on the faculty of the University of North Carolina at Chapel Hill since 1985 where he is currently the Charles Addison and Elizabeth Ann Sanders Distinguished Professor of Medicine, Pediatrics and Epidemiology in the UNC School of Medicine, and UNC Gillings School of Global Public Health.

He serves as an Associate Chief Medical Officer for UNC Medical Center. He also serves as Medical Director of the Department of Infection Prevention UNC Medical Center. He is the Medical Director of the North Carolina Statewide Infection Control Program (SPICE), a Chair of UNC Biomedical IRB, and serves as the UNC Principle Investigator on the CDC sponsored Duke-UNC Epicenter. Dr. Weber is an Associate Editor of Infection Control Hospital Epidemiology and the Secretary of the SHEA Board. He is the Chair of the NC Health Department’s Tuberculosis Advisory Committee.

Dr. Weber has published more than 470 scientific papers in the peer-reviewed literature and more than 650 total papers and chapters. He is the Senior Editor of Mayhall’s “Hospital Epidemiology and Infection Prevention, 2020”. His research interests include the epidemiology of healthcare-associated infections, disinfection and sterilization, new and emerging infectious diseases (novel influenza, SARS-coV-2, MERS-coV, Ebola, Candida auris), response to biothreats, nontuberculous mycobacteria, control of drug resistant pathogens, immunization practices (especially of healthcare personnel), zoonotic diseases, and epidemiology of tuberculosis.

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