Mid-2022 is an opportune moment to review the COVID-19 timeline and reflect on where we are in the pandemic, including advancements made, what is going well, and to plan and be prepared. As a country, we have more than 220 million Americans fully vaccinated, with over 105 million having received their first booster. 

Despite the greater degree of immunity in the U.S. population, 7-day average infection rates are over 120,000 reported daily cases and greater than 300 daily deaths. The rapidly evolving Omicron subvariants are driving COVID-19 infections, raising concerns of greater transmissibility and immunity evasion but fortunately without a proportional increase in serious illness.

In recent months, multiple lineages of the Omicron variant have emerged with higher transmissibility rates and increased neutralization escape. The subvariant BA.5 has overtaken BA.12.2.1 as the dominant strain, accounting for more than 65% of cases in the U.S and threatens a fresh wave of COVID-19 infections.

Data show neutralizing antibody titers against the BA.4 and BA.5 and (to a lesser extent) against the BA.2.12.1 subvariant were lower than titers against BA.1 and BA.2, which suggests the BA.4 and BA.5 Omicron subvariants are the most capable yet at evading immunity from vaccination or previous infection. It is too early to fully forecast what BA.4 and BA.5 may bring to the United States. The CDC says there is no evidence that BA.4 or BA.5 is inherently more lethal than other Omicron subvariants, but as the number of infections increases, so will the number of hospitalizations and death. As scientists work to learn more about these Omicron subvariants or possibly new variants, we must remain steadfast in preparing and protecting ourselves.

With infections on the rise in the U.S. and the strong possibility of another surge this Fall or coming winter, the Biden Administration outlined a plan for managing BA.5. There are also things we can do individually to ensure we are prepared. 

Recently the FDA authorized, and the CDC endorsed, both the Moderna and Pfizer-BioNTech COVID-19 vaccines for children 6 months of age and older. For Moderna, the FDA Emergency Use Authorization (EUA) had been authorized for 18 years and older and amended the EUA to include those 6 months through 17 years. For Pfizer-BioNTech, the FDA EUA had been authorized for those 5 years and older and amended it to include those 6 months to 5 years. The CDC Interim COVID-19 Immunization Schedule for 6 Months and older is now available.

The FDA has granted expanded approval of the Pfizer-BioNTech COVID-19 vaccine (Comirnaty^®) to include primary series vaccination in those 12 – 15 years of age.

The FDA issued a EUA for the Novavax COVID-19 Vaccine, Adjuvanted (Novavax) for the prevention of COVID-19 in 18 yrs.+ as a primary series of 2 doses, 3 weeks apart. On July 19^th, 2022, ACIP reviewed the Novavax COVID-19 Vaccine, Adjuvanted, and voted 12 to 0 recommending its use in adults, 18 yrs +.  CDC Director Rochelle Walensky, MD, M.P.H., endorsed the ACIP recommendations later that day.

Novavax is the first protein-based COVID vaccine and uses older vaccine development technology (HPV and hepatitis B are protein-based vaccines). Unlike other COVID vaccines, which use host cells to create the spike protein fragments, Novavax contains harmless protein fragments that elicit an immune response and antibody production once in the host. It also contains an adjuvant (an immune response booster) used in many other vaccines. A COVID-19 vaccine with a mechanism of action that uses older technology provides another option for patients and may alleviate concerns with the newer technology COVID-19 vaccines. Novavax does not require the special cold storage requirement associated with the mRNA vaccines and only needs to be refrigerated between 36 – 46°F which may lessen the burden of vaccine distribution and storage.

The CDC is hosting a Clinical Outreach and Communication Activity (COCA) Call on July 28, 2022 regarding the Recommendations for the Novavax COVID-19 Primary Series in Adults.

The FDA recommends the inclusion of an Omicron BA.4/5 component for COVID-19 vaccine booster doses. Manufacturers seeking to update their COVID-19 vaccines are advised to develop modified vaccines that include an Omicron BA.4/5 spike protein component to their current vaccine to create a bivalent booster for use potentially starting early to mid-fall 2022. Both Moderna and Pfizer have reported positive data on their Omicron-adapted COVID-19 boosters targeting the BA.1 subvariant, and Moderna recently released positive data on their Omicron-containing bivalent booster candidate M-1273.214. The FDA has advised the companies to submit these data for evaluation before any potential authorization of an Omicron BA.4/5 modified vaccine.

The FDA recently revised the EUA for Paxlovid, authorizing state-licensed pharmacists to prescribe Paxlovid to eligible patients. The FDA believes the terms and conditions of an EUA issued under section 564 preempt any state or local regulations. Patients with a positive COVID-19 test are encouraged to seek care from their regular healthcare provider or locate a Test-to-Treat site. Certain limitations are outlined in the EUA to ensure appropriate patient assessment and prescribing, and state-licensed pharmacist should refer patients for clinical evaluation with a physician, advanced practice nurse, or physician assistant licensed or authorized under state law to prescribe when any of the following apply:

Rebound COVID-19 infection is a known potential side effect of Paxlovid therapy. Additional analysis of Paxlovid clinical trial data indicated that 1 – 2% of those taking Paxlovid experienced rebound. The CDC Health Advisory emphasizes that Paxlovid continues to be recommended for early stage treatment of mild to moderate COVID-19 among people at risk for progression to severe disease and that a brief return of symptoms may be part of the natural history of a SARS-CoV-2 infection in some people, independent of Paxlovid treatment and regardless of vaccination status. 

Limited case study information suggests that those experiencing COVID-19 after Paxlovid therapy have mild illness. A recent MMR report of real-world evidence shows hospital admissions and emergency department (ED) visits 5-15 days after Paxlovid therapy occurred infrequently (<1%) during the study period. Currently there is no evidence that additional Paxlovid treatment is needed where COVID-19 rebound is suspected.  People with COVID rebound are advised to follow CDC’s isolation guidance and take precautions to prevent transmission. Healthcare providers are encouraged to report cases of COVID-19 rebound.

The FDA conducts ongoing evaluation of Evusheld’s efficacy against COVID-19 variants and subvariants. Based on recent data, Evusheld may be less active against certain Omicron subvariants leading the FDA to update the Evusheld EUA recommending repeat dosing every six months with tixagevimab 300 mg and cilgavimab 300 mg in those patients requiring on-going protection. Previous guidance did not provide a dosing interval recommendation.

The CDC Data Tracker includes a new Post COVID Conditions tab. The new page highlights data from the Innovate Support for Patients with SARS-CoV-2 infection (INSPIRE) study. The INSPIRE study is funded by the CDC with the purpose of learning more about the long-term health effects of COVID-19. Researchers are seeking participants for the study.

A non-peer reviewed pre-print of a large national database study (VA system) shows that compared to people with first infection, people with reinfection exhibited increased risks of all-cause mortality, hospitalization, and several pre-specified outcomes. The risk of adverse health outcomes increased as the number of infections increased. The findings highlight the potential impact of reinfection and emphasize the importance of preventing reinfection. 

We will continue to update the Ventegra COVID-19 Resource Center as new information becomes available and encourage you to check back frequently.

Mark Shinmoto, Pharm.D., V.P. Chief Pharmacy Officer