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Messenger RNA Vaccines Against COVID-19 and its Variants

The novel messenger RNA (mRNA) vaccines developed by Pfizer-BioNTech (BNT162b2) and Moderna (mRNA-1273) carry the genetic code the host cell needs to make the surface spike protein antigen to closely mimic a natural infection.1

To study the effectiveness of these vaccines, the US Centers for Disease Control and Prevention (CDC) conducted a longitudinal real-world study evaluating BNT162b2 and mRNA-1273 in nearly 4,000 healthcare professionals and first responders. Interim results show reduced risk of infection by 80% after partial vaccination, which fell to 90% after the second dose.2 These findings are similar to later stage trials showing that two-dose regimens of BNT162b2 and mRNA-1273 provide approximately 95% protection against COVID-19.3,4

Trials of mRNA vaccines were mainly conducted in the United States before variants of concern had been detected. Variants of concern are strains of SARS-CoV-2 that show evidence of increased transmissibility and/or disease severity and reduced effectiveness against therapies developed for prevention and treatment.5 These include the emergence of variants first identified in the United Kingdom (B.1.1.7, B.1.1.7+E48K), South Africa (B.1.351), Brazil (P.1), and California (B.1.427, B.1.429).
Much of the data of mRNA vaccine efficacy against new strains of the virus comes from laboratory models of SARS-CoV-2 variants. Serum samples from people immunized with BNT162b2 were exposed to genetically engineered versions of variants: B.1.1.7-spike, P.1-spike, and B.1.351-spike.6,7 This study showed approximately equivalent neutralizing antibodies of B.1.1.7-spike and P.1-spike, and robust but lower levels of neutralizing antibodies against B.1.351-spike.7

Serum samples of people who received mRNA-1273 were assayed against a recombinant vesicular stomatitis virus (rVSV)-based SARS-CoV-2 model of pseudoviruses carrying the strains B.1.1.7, B.1.351, P.1, B.1.427, B.1.429, B.1.1.7+E484K, and other variants.8 The study showed no significant effect on neutralization of B.1.1.7, but a decrease in titers of neutralizing antibodies against P.1, B.1.427, B.1.429, B.1.1.7+E484K, and B.1.351 variants.8

References
 

  1. Abbasi J. COVID-19 and mRNA vaccines—first large test for a new approach. JAMA. 2020;324(12):1125-1127.
  2. Thompson MG, Burgess JL, Naleway AL, et al. Interim estimates of vaccine effectiveness of BNT162b2 and mRNA-1273 COVID-19 vaccines in preventing SARS-CoV-2 infection among health care personnel, first responders, and other essential and frontline workers — Eight U.S. Locations, December 2020-March 2021. MMWR Morb Mortal Wkly Rep. ePub: 29 March 2021.
  3. Polack FP, Thomas SJ, Kitchin N, et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med. 2020;383:2603-2615.
  4. Baden LR, El Sahly HM, Essink B, et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med. 2021;384:403-416. 5. CDC. SARS-CoV-2 Variant Classifications and Definitions. Available at https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/variant-surveillance/variant-info.html. Accessed March 31, 2021.
  5. Rubin R. COVID-19 vaccines vs variants—determining how much immunity is enough. JAMA. Published online March 17, 2021. Accessed March 30, 2021.
  6. Liu Y, Liu J, Xia H, et al. Neutralizing activity of BNT162b2-elicited serum. N Engl J Med. March 8, 2021. DOI: 10.1056/NEJMc2102017

This activity is co-provided by Ultimate Medical Academy/Complete Conference Management (CCM).
This activity is supported by educational grants from AbbVie, Astellas, Genentech, Lilly, Merck & Co., Inc., Pfizer and Regeneron Pharmaceuticals, Inc.

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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).

References:
Baricitinib fact sheet for healthcare providers. May 2022. (https://www.fda.gov/media/143823/download).  Accessed 5.24.2022.

Baricitinib (Olumiant®) PI 2022 (https://pi.lilly.com/us/olumiant-uspi.pdf). Accessed 5.24.2022.

Bebtelovimab fact sheet for healthcare providers. May 2022. (https://www.fda.gov/media/156152/download).  Accessed 5.24.2022.

Centers for Disease Control and Prevention (CDC). COVID data tracker. May 23, 2022. (https://covid.cdc.gov/covid-data-tracker/#variant-proportions). 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.