October 19, 2022

As of Oct 16, 2022, the CDC is reporting almost 97M COVID cases and over 1M COVID deaths in total for the United States. Daily COVID cases (35.7K) and daily death (313) rates have decreased to the lowest levels seen this year in April/May. The low COVID activity during April/May 2002 is explained by the cooling-off period between the end of the Delta surge and the rise of Omicron.  
 
As we approach the cold and flu season it is important that we prepare for any new variants and the potential surge in COVID and influenza cases. Our prevention measures are still the same: (1) Be up to date on your COVID and Influenza vaccinations (2) Know your personal risk and those around you – use mitigation strategies whenever possible. Consider following these tips for being COVID prepared so you can keep yourself and others protected this holiday season.
 
It remains Ventegra's deep commitment to our clients to provide the most updated and relevant one-stop-shop resource on COVID-19.
Key Highlights for This Update
  • COVID-19 variants

  • COVID-19 Risk Continuum by the CDC and IDSA 

  • New Bivalent COVID-19 vaccines

  • COVID-19 therapeutics update

  • Long COVID-19 
COVID-19 Variants
The BA.5 sublineage remains the dominant strain in the U.S., accounting for 67.9% of sequenced specimens; however, its estimated prevalence has decreased for eight consecutive weeks. The BA.4.6 had been rising but has leveled off (12.3% to 12.2%) the last 2 weeks. Several other Omicron sublineages continue to exhibit increasing trends. Notably BQ.1.1 and BQ.1 have made their way up to 5.7% each. BF.7 is up to 5.3% to round out the top 5. The increasing trends suggest that these subvariants may have some growth advantage over BA.5. 

In part of Europe (Germany, France and Italy), there has been an uptick in cases being driven by less prevalent Omicron sublineages in the U.S. How the early trends in Europe translate to the U.S. remains to be seen.  
 
COVID-19 Risk Continuum by the CDC and IDSA 
The Centers for Disease Control and the Infectious Diseases Society of America created the graphic below summarizing an individual’s risk for COVID-19.
New Bivalent COVID-19 Vaccines
The FDA issued EUA’s for two mRNA Bivalent COVID-19 booster vaccines manufactured by Moderna and Pfizer-BioNTech. The bivalent formulation contains a component of the original monovalent formulation with the addition of the Omicron strain, BA.4/BA.5. Most recently, the age group eligible for the bivalent booster was lowered to 6 years for Moderna and 5 years for the Pfizer-BioNTech vaccine. 
 
Both vaccines are indicated AFTER any COVID-19 vaccine primary series formulation (JnJ/Janssen, Moderna, Novavax, Pfizer-BioNTech). If an individual has received their primary series and has been boosted with a monovalent COVID-19 vaccine, they can be given ANY age-appropriate bivalent vaccine if > 2 months from their last COVID vaccination. All recommended booster doses should receive the age-appropriate bivalent formulation in the future. 
 
The CDC advises that if you have had COVID, you can still be vaccinated, but you may consider delaying your next vaccine dose by 3 months. It is also safe to receive the COVID and Flu vaccines at the same visit.

Click here for a complete COVID-19 Immunization schedule.
COVID-19 Therapeutics Update
Paxlovid (nirmatrelvir and ritonavir)
The American College of Cardiology (ACC) recently published a review outlining several specific cardiovascular (CV) drug interactions with Paxlovid. ACC highlights coadministration with Paxlovid with commonly prescribed CV drugs can lead to clinically significant drug interactions. Dosage adjustment or temporary discontinuation of certain CV drugs may be required during the Paxlovid treatment period and the 3 – 5 days after completion the treatment course. If discontinuation of CV drug is not feasible or not advised, Paxlovid treatment should be avoided and other treatments considered (e.g., remdesivir, molnupiravir, monoclonal antibodies).
 
Rebound COVID-19 infection is a known potential side effect of Paxlovid therapy documented by researchers and the CDC. Currently the frequency and clinical significance is unknown. The NEJM presented data on the occurrence of viral load rebound from the EPIC-HR trial indicating the incidence of viral load rebound was similar in the Paxlovid group and placebo group and the occurrence of rebound was not retrospectively associated with low Paxlovid exposure, recurrence of moderate-to-severe symptoms, or development of resistance to Paxlovid. One study sponsored by the NIH and published this week in Clinical Infectious Diseases concluded that Paxlovid does not stymie adaptive immune responses to SARS-CoV-2 and the clinical rebound corresponds to the development of a robust antibody and T-cell immune response.
 
Evusheld (tixagevimab copackaged with cilgavimab)
The FDA recently updated the emergency use authorization fact sheet for Evusheld warning certain SARS-CoV-2 variants may not be neutralized. The FDA continues to recommend the use of Evusheld but warns the increased risk of contracting COVID due to variants not neutralized by Evusheld, e.g. the Omicron variant BA.4.6. 
 
Long COVID-19
Post-COVID-19 conditions, commonly known as long COVID, can include a wide collection of new, on-going, or returning symptoms that individuals experience for greater than 4 weeks after getting COVID. Commonly reported symptoms include fatigue, worsening symptoms post physical or mental effort, fever, or respiratory symptoms (difficult breathing, shortness of breath, cough). 
 
Growing evidence indicates a significant number of those infected with SARS-CoV-2 do not fully recover months after an acute infection. A recent on-line modeling study published in JAMA evaluating a database of more than 1.2 million COVID-19 patients in 22 countries estimates 6.2% of people had long COVID symptoms 3 months after symptomatic infection. Reported proportion estimates of those with at least 1 of 3 self-reported long COVID symptom sequelae included persistent fatigue with bodily pain or mood swings (3.2%), ongoing respiratory problems (3.7%), or cognitive problems (2.2%) after adjusting for health status before COVID. Hospitalized COVID-19 patients had a longer estimated symptom duration of 9 months compared to non-hospitalized of 4 months. Fifteen percent of people continued to experience symptoms after 1 year. 

A large pair matched study conducted in Scotland and recently published in Nature Communications evaluated long-COVID outcomes in a large cohort of 33,000 people with laboratory confirmed SARS-CoV-2 infection and 63,000 not infected at several time points including at 6, 12, and 18 months. Of those with symptomatic infection, 6% reported no recovery and 42% reported partial recovery. Factors associated with these outcomes included severe (hospitalized) infection, older age, female sex, deprivation, white ethnicity, and pre-existing health conditions. There was no association between asymptomatic infection and adverse outcomes, and pre-infection vaccination was associated with a reduction in certain persistent symptoms (change in smell, taste, and hearing).
 
Medium COVID, referring to a middle phase of COVID-19 infection recovery spanning approximately 12 weeks post infection, is gaining some attention. A few studies indicate that the most severe post-COVID complications may occur during this window. In a self-controlled case series and matched cohort study from Sweden, incidence rates were significantly higher for deep vein thrombosis (70 days), pulmonary embolism (110 days) and bleeding (110 days) post COVID infection. Rate ratios were highest in those with critical COVID infection and during the first COVID wave vs. subsequent second and third waves in Sweden. These findings are supported by a similar U.K. study published earlier this year.
We will continue to update the Ventegra COVID-19 Resource Center as new information becomes available and encourage you to check back frequently.
For questions, please contact:
Mark Shinmoto, Pharm.D., V.P. Chief Pharmacy Officer
Ventegra, Inc.