COVID-19 Update #127 4/8/2022

COVID-19 Vaccines
 
The FDA's Vaccines and Related Biological Products Advisory Committee (VRBPAC) did not develop a plan for COVID-19 vaccine booster composition or timing of additional boosters. In addition to attempting to predict which variant will be dominant, half of the U.S. population has not received a booster dose, so how to optimize protection for everyone will be more of a challenge. VRBPAC members agreed the goal for booster doses should be prevention of hospitalization and death in at least 80% of patients. Peter Marks, the director of the FDA’s Center for Biologics Evaluation and Research, said the fourth dose vaccine dose was a reasonable approval until a new booster, that would preferably have longer-lasting protection, was available. He felt frequent use of boosters was not a strategy that should be continued. VRBPAC will meet again to discuss more specific details of a booster program for COVID-19.
 
The CDC endorsed the FDA’s approval of a second booster vaccination and recommended certain immunocompromised individuals and people over the age of 50 who received an initial booster dose at least 4 months be eligible for a second booster (fourth dose) or an mRNA COVID-19 vaccine. 
 
A CDC analysis of COVID-19 vaccine effectiveness (VE) from 12/16/2021 to 3/7/2022 found that for preventing emergency department/urgent care visits VE was 24% for one J&J vaccination, 54% after two J&J doses, 79% after one J&J vaccination followed by one mRNA dose, and 83% after three mRNA doses. VE for the same vaccine regimens to prevent COVID-19 associated hospitalizations was 31%, 67%, 78%, and 90% respectively.
 
In a 2,812 patient, case–control, test-negative trial, vaccine effectiveness (VE), of the Pfizer-BioNTech COVID-19 vaccine, for the Omicron variant was 20% for non-critical COVID-19, 40% to prevent COVID-19 hospitalizations and 79% for critical COVID-19 in adolescents 12 to 18 years of age with a median interval since vaccination of 162 days. VE was 68% to prevent COVID-19 hospitalizations in children 5 to 11 years of age, with a median interval since vaccination of 34 days.
 
A CDC analysis of EHR data from 40 health systems found the risk for myocarditis, pericarditis, or multisystem inflammatory syndrome to be 2 to 6 times higher in 12 to 17 year old boys who experienced a COVID-19 infection compared to receiving an mRNA COVID-19 vaccine. In young men 18 to 29 years, the risk is 7 to 8 times higher with infection over vaccination.
 
An analysis of EHR data from 1,252,331 Israeli patients, who were 60 and older, found that a fourth vaccination with an mRNA COVID-19 vaccine lowers the risk by half for a confirmed infection. But the protection wanes and only lasts about eight weeks. Protection against severe cases of COVID-19 were three times lower and did not appear to decrease over time. The study was too short to estimate the duration of protection against severe disease. 
 
NIH Outpatient Treatment Update
 
NIH recommend that nonhospitalized patients with mild to moderate COVID-19 who are at high risk of disease progression, be treated with (in order of preference):
 

1. Nirmatrelvir 300 mg with ritonavir 100 mg orally twice daily for 5 days and initiated within 5 days of symptom onset in patients at least 12 years old, who weigh at least 40 Kg. The patient’s current drugs should be reviewed for drug interactions using data provided from NIH.
2. Remdesivir 200 mg IV on Day 1, followed by remdesivir 100 mg IV daily on Days 2 and 3, initiated within seven days of symptom onset in in patients at least 12 years old, who weigh at least 40 Kg.

 
Alternative Therapies if nirmatrelvir boosted with ritonavir or remdesivir are not available or an inappropriate choice for the patient, then one of the following therapies can be used.
 

• Bebtelovimab 175 mg as a single IV infusion, administered as soon as possible and within 7 days of symptom onset in those aged ≥12 years and weighing ≥40 
• Molnupiravir 800 mg orally twice daily for 5 days, initiated within 5 days of symptom onset in patients at least 18 years and only when none of the above options can be used. Molnupiravir is not recommended in pregnant patients due to concerns for fetal toxicity, but the drug can be considered if none of the other recommended treatments are available. Molnupiravir has not been tested in vaccinated patients.​

Additional Considerations
 

• Neither remdesivir, dexamethasone, or baricitinib should be continued after hospital discharge.
• Dexamethasone 6 mg PO once daily for the duration of supplemental oxygen (dexamethasone use should not exceed 10 days) with careful monitoring for adverse effect.
• Remdesivir can be considered for up to five days in outpatients requiring supplemental oxygen.

 
COVID-19 Antibodies
 
The FDA no longer authorizes sotrovimab to treat COVID-19 in the U.S. due to the Omicron BA.2 sub-variant becoming the dominant variant. The CDC reports that BA.2 now accounts for 72.2% of all COVID-19 cases with BA.1.1 accounting for most of the remaining cases.
 
In a 28-day, 1,181 patient, Phase II trial (NCT04373460), 2.9% of patients treated with high titer convalescent plasma were hospitalized for COVID-19 compared to 6.3% with placebo in outpatients with recent onset of COVID-19.
 
COVID-19 Antivirals
 
In the 28-day, 3,515 patient, Phase III, TOGETHER trial (NCT04727424), treatment with ivermectin did not reduce COVID-19 hospitalizations or urgent-care visits compared to placebo in high-risk Brazilian outpatients with COVID-19.​
 
The FDA placed a partial hold on leronlimab HIV trials and a full hold on leronlimab COVID-19 trials in the United States. At the same time, CytoDyn decided to place a hold on its leronlimab COVID-19 Brazilian trial pending review of two cardiac events by the data safety monitoring board.