SARS-CoV-2 Delta Variant and Its Effect on Current Prevention and Treatment Strategies

The SARS-CoV-2 Delta variant (B.1.617.2) that first emerged in India is now the most prevalent Variant of Concern (VOC) in the United Kingdom1 and has been detected in almost 10% of all infections in the United States.2 Delta appears to be more transmissible than the Alpha variant (B.1.1.7)1 and carries mutations L452R and K478T in the receptor-binding domain of the spike protein.3 Laboratory studies indicate that monoclonal antibody treatments with Emergency Use Authorization (EUA) may be less effective against variants with these mutations.4,5

Studies of the B.1.427/B1.1.429 variants that were first identified in California and that also carry the L452R mutation show 4.0 to 6.7-fold and 2.0-fold decreases in neutralization titers from convalescent plasma and vaccine recipients, respectively. 6 Extrapolation of these results to the effect of the L452R mutation of the Delta variant indicates a corresponding potential reduction in neutralization.

Recent studies exposing Delta variants to neutralizing antibodies from vaccinated people report a 1.34-fold lower vaccine effectiveness between 4 and 10 weeks after the first dose.7 Fortunately, the Public Health England reports that vaccines are highly effective against this VOC two weeks after the second dose. The Pfizer-BioNTech vaccine and the AstraZeneca vaccine retain 88% and 60% effectiveness compared with 93% and 66% efficacy, respectively, against the alpha (B.1.1.7) variant.8

Vaccine and convalescent sera show 2.7-fold less effectiveness against Delta compared with earlier strains, suggesting that people who were previously infected with other variants may be at risk for reinfection by Delta.7 Neutralization studies of monoclonal antibodies with EUA show potent activity against the Delta variant except for single-agent bamlanivimab, which had no effect and is consistent with observations of single-agent monoclonal antibody therapy against other VOCs.


  1. Allen H, Vusirikala A, Flannagan J, et al. Increased household transmission of COVID-19 cases associated with SARS-CoV-2 Variant of Concern B.2.617.2: a national case-control study. Public Health England. 2021.
  2. Centers for Disease Control (CDC). COVID data tracker ( Accessed 6/21/2021.
  3. CDC. COVID-19 variant classifications ( Accessed 6/21/2021.
  4. Food and Drug Administration (FDA). Fact sheet for health care providers Emergency Use Authorization (EUA) of bamlanivimab and etesevimab. ( Accessed June 21, 2021.
  5. FDA. Fact sheet for health care providers Emergency Use Authorization (EUA) of REGEN-COV (casirivimab and imdevimab). ( Accessed 6/21/2021.
  6. Deng X, Garcia-Knight MA, Khalid MM, et al. Transmission, infectivity, and antibody neutralization of an emerging SARS-CoV-2 variant in California carrying a L452R spike protein mutation. medRxiv. 2021.
  7. Liu C, Ginn HM, Dejnirattisai W, et al. Reduced neutralization of SARS-CoV-2 B.1.617 by vaccine and convalescent serum. Cell. In Press, Journal Pre-proof.
  8. Public Health England (PHE). Vaccines highly effective against B.1.617.2 variant after 2 doses. ( Accessed 6/21/2021.

Updates in the Treatment and Prevention of COVID-19​

Bebtelovimab Is the Only Monoclonal Antibody That Retains Activity Against Omicron Subvariants

The Omicron subvariants BA.2 and BA.2.12.1 now account for 99% of all COVID-19 cases in the United States. Studies assessing the neutralizing activity of monoclonal antibodies for the treatment of COVID-19 have found that only bebtelovimab retains activity against BA.2 and BA.2.12.1. Other monoclonal antibodies, including sotrovimab, bamlanivimab, etesevimab, casirivimab, and imdevimab, are not effective against these new subvariants and are not currently authorized by the US Food and Drug Administration (FDA) to treat COVID-19 due to the high incidence of Omicron BA.2.

Bebtelovimab is authorized for emergency use by the FDA for the treatment of mild-to-moderate COVID-19 in patients 12 years and older weighing at least 40 kg with positive results of direct SARS-CoV-2 viral testing who are at high risk for progression to severe COVID-19, including hospitalization or death. Bebtelovimab should be administered as soon as possible after positive SARS-CoV-2 results and within 7 days of symptom onset.

FDA Approves Baricitinib for Hospitalized COVID-19 Patients

Baricitinib, an oral Janus kinase (JAK) inhibitor, is now FDA-approved for the treatment of COVID-19 in hospitalized adults requiring supplemental oxygen, noninvasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO). It is also authorized for emergency use by the FDA for hospitalized pediatric patients between 2 and 18 years of age who require oxygen support. The approval of baricitinib is based on efficacy and safety data from the ACTT-2 and COV-BARRIER clinical trials. In ACTT-2, baricitinib plus remdesivir was superior to remdesivir alone in reducing recovery time, particularly in patients receiving high-flow oxygen or noninvasive ventilation (10 days vs 18 days; rate ratio for recovery, 1.51; 95% confidence interval (CI), 1.10 to 2.08). The 28-day mortality was 5.1% with baricitinib plus remdesivir and 7.8% with remdesivir alone (hazard ratio [HR] for death, 0.65; 95% CI, 0.39 to 1.09). The COV-BARRIER trial found that baricitinib, in addition to standard of care (SoC), was associated with reduced 28-day mortality in hospitalized adults with COVID-19 compared with SoC alone (8% vs 13%; HR, 0.57; 95% CI, 0.41 to 0.78; P= .0018). The 60-day all-cause mortality was 10% with baricitinib plus SoC versus 15% with SoC (P= .005).

Baricitinib fact sheet for healthcare providers. May 2022. (  Accessed 5.24.2022.

Baricitinib (Olumiant®) PI 2022 ( Accessed 5.24.2022.

Bebtelovimab fact sheet for healthcare providers. May 2022. (  Accessed 5.24.2022.

Centers for Disease Control and Prevention (CDC). COVID data tracker. May 23, 2022. ( Accessed 5.24.2022.

Iketani S, et al. Antibody evasion properties of SARS-CoV-2 Omicron sublineages. Nature. 2022;604:553-556.

Kalil AC, et al. Baricitinib plus remdesivir for hospitalized adults with COVID-19. N Engl J Med. 2021;384:795-807.

Marconi VC, et al. Efficacy and safety of baricitinib for the treatment of hospitalised adults with COVID-19 (COV-BARRIER): a randomised, double-blind, parallel-group, placebo-controlled phase 3 trial. Lancet Resp Med. 2021;9:1407-1418.