The FDA granted an emergency use authorization (EUA) for the combination of nirmatrelvir and ritonavir (Paxlovid, Pfizer), on 12/22/21, for the treatment of mild-to-moderate COVID-19 in patients 12 years of age and older weighing at least 88 pounds who are at high risk for progression to severe COVID-19. The treatment is dosed as two tablets of nirmatrelvir and one tablet of ritonavir taken together orally twice daily for five days. Please see the Fact Sheet for Healthcare Providers and Fact Sheet for Patients and Caregivers for additional information. Pfizer will begin shipping nirmatrelvir and ritonavir to the U.S. government immediately and expects to complete delivery of 10 million courses of treatment in 2022.
The FDA granted an emergency use authorization (EUA) for molnupiravir (Lagevrio, Merck), on 12/23/21, for the treatment of mild-to-moderate COVID-19 in patients 18 years of age and older who are at high risk for progression to severe COVID-19 and alternative COVID-19 treatment options authorized by the FDA are not accessible or clinically appropriate. The treatment is dosed as four tablets twice daily for five days. Molnupiravir is not recommended for use during pregnancy. Please see the Fact Sheet for Healthcare Providers and Fact Sheet for Patients and Caregivers for additional information. Merck will begin shipping 3.1 million doses of molnupiravir to the U.S. government as soon as a final label is approved by the FDA.
In the 29-day, 1,443 patient, Phase II/III, MOVe-OUT trial (NCT04575597), 6.8% of patients treated with a five-day course of molnupiravir were hospitalized or died compared to 9.7% with placebo in unvaccinated outpatients with mild-to-moderate COVID-19 with at least one risk factor to progress to severe disease. An interim analysis from 775 patients had suggested that 7.3% of patients treated with molnupiravir were hospitalized or died compared to 14.1% with placebo.
In the 28-day, 562 patient, Phase III, PINETREE trial (NCT04501952), 0.7% of patients treated with a 3-day course of remdesivir were hospitalized or died compared to 5.3% with placebo in nonhospitalized patients with at least one risk factor to progress to severe disease.
The CDC’s ACIP recommended that COVID-19 vaccines from Pfizer and Moderna should be preferred over the J&J vaccine due to the risk for a rare but potentially fatal thrombosis with thrombocytopenia syndrome with the J&J vaccine.
Moderna announced that preliminary lab results found that antibody levels after a booster (third) dose of their COVID-19 vaccine increased antibody levels that are thought to be high enough to neutralize the Omicron variant. A pre-print draft described how antibody levels were not high enough after two doses of the vaccine to neutralize the Omicron variant.
In a review of 4, 155, 361 patients that received an mRNA vaccine the rate of myocarditis was estimated to be 1.4 per 100 ,000 patients with the Pfizer-BioNTech COVDI-19 vaccine and 4.2 per 100 ,000 patients with the Moderna vaccine.
Sanofi and GSK announced that in a 521 patient, Phase I/II trial (NCT04537208), using their COVID-19 vaccine as a booster dose for vaccines from Pfizer/BioNTech, Moderna, Johnson & Johnson, and AstraZeneca resulted in an increase in neutralizing antibodies of 9- to 43-fold.
In the 29,582 patient, Phase III, PREVENT-19 trial (NCT04611802), two immunizations of NVX-CoV2373 (Novavax)ngiven 21-days apart resulted in 90.4% efficacy for developing a COVID-19 infection and 100% efficacy in preventing severe COVID-19.
Pfizer and BioNTech announced that in 4,500 patient, Phase I/II/III trial (NCT04816643), two 3 mcg doses of their COVID-19 vaccine given to patients 6 to 24 months old demonstrated immunogenicity similar to that seen with the adult dose in patients 16 to 25 years old. An inadequate response was elicited in patients 2 to under 5 years old with the 3 mcg dose, so a third dose will be evaluated in patients 6 months to under 5 years.
In a pre-print draft of 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.
Pfizer announced that in the 28-day, 2,246 patient, Phase II/III, EPIC-HR trial (NCT04960202), where 0.7% of patients treated with the combination of nirmatrelvir and ritonavir were hospitalized with no deaths compared to 6.5% who were hospitalized or died with placebo in unvaccinated patients with mild-to-moderate COVID-19 at risk to progress to severe illness. After an interim analysis found an 89% reduction in COVID-19 related hospitalization or death, the FDA agreed with the Data Monitoring Committee, that the trial could be stopped in November 2021.
Pfizer and BioNTech announced that preliminary lab results found that antibody levels after a booster (third) dose of their COVID-19 vaccine neutralized the Omicron variant. There was a 25-fold reduction in neutralization in patients that received just two vaccine doses. This may not be enough to prevent infection but may protect against severe disease. South African scientists tested antibody neutralization with serum from 12 patient that had received the Pfizer-BioNTech COVID-19 vaccine. Half of the patients had recovered from COVID-19. There was a 41-fold decrease in neutralization, but previously infected patients have high neutralization. Therefore, patients that have received a booster (third) dose may maintain neutralization against Omicron.
The FDA and CDC authorized a booster dose given six-months after their second dose of the Pfizer-BioNTech COVID-19 vaccine for 16 and 17 year-olds, on 12/9/2021.
The FDA approved an Emergency Use Authorization (EUA) for the combination of tixagevimab and cilgavimab (Evusheld, AstraZeneca) on 12/8/2021, for pre-exposure prophylaxis (prevention) of COVID-19 in patients 12 and older and weighting at least 40 kg with moderate to severe immune compromise due to a medical condition or immunosuppressive medications and who may not mount an adequate immune response to COVID-19 vaccination, currently have COVID-19 or if COVID-19 vaccination is not recommended. Tixagevimab and cilgavimab are administered as a one-time intramuscular dose. The FDA advised against using the drug in hospitalized patients, because a benefit has not been demonstrated. Healthcare providers should review the Fact Sheet for information on the authorized use of casirivimab and imdevimab and mandatory requirements of the EUA. Please see the FDA Letter of Authorization, Fact Sheet for Healthcare Providers, and Fact Sheet for Patients, Parents, and Caregivers. The U.S. government has purchased 700,000 doses that will be distributed at no charge.
In a 14-day, 941 patient, Phase III, CONTAIN COVID-19 trial (NCT04364737), treatment with convalescent plasma did not increase the number of patients that achieved clinical improvement compared to placebo in hospitalized COVID-19 patients.
ISMP issued a warning regarding use of an incorrect dose of the Pfizer-BioNTech COVID-19 vaccine. The pediatric vaccine (10 mcg/0.2 ml) has been used in patients 12 and older and the adult dosage (30 mcg/0.3 ml) has been used in patients under 12. ISMP further warns against diluting the adult vaccine to make a pediatric vaccine. Due to the vaccine being a suspension and the small volume, it would not be possible to create an accurate dose. To avoid errors, ISMP recommends
Medicago and GSK announced that in a 24,000 patient, Phase II/III trial (NCT04636697), where use of their COVID-19 vaccine had an overall vaccine efficacy 71% and 75.3% against the Delta variant.
A retrospective study of patients 21 years or younger who experienced myocarditis within 30 days of COVID-19 vaccination found most cases had a mild clinical course with rapid resolution of symptoms.
The 2,878 patient, Phase II, British COV-BOOST trial found that any COVID-19 vaccine can be used as a booster, regardless of the initial vaccine given. Patients received the Pfizer-BioNTech or AstraZeneca COVID-19 vaccines. After the Pfizer-BioNTech vaccine a good immunity boost was achieved with vaccines from Pfizer-BioNTech, Moderna, Johnson & Johnson, Novavax, AstraZeneca and CureVac. There was also a good boost in immunity after the AstraZeneca vaccine with the same set of vaccines, plus an investigational vaccine from Valneva
In the 1,072 patient, Phase III, Com-COV2 trial, patients received their first COVID-19 immunization with either the AstraZeneca or Pfizer-BioNTech vaccines. The second dose was given with the same vaccine, a vaccine from Moderna or Novovax. Both the Moderna and Novovax vaccines elicited higher antibody titers following the AZ vaccine than AZ’s own vaccine. Compared to a second dose of the Pfizer-BioNTech vaccine, Moderna elicited higher antibody titers, but Novovax did not.
In the 28-day, 479 patient, Phase III, LIVE-AIR trial (NCT04351152), 84% of patients treated with lenzilumab were alive and did not require invasive mechanical ventilation compared to 78% with placebo in hospitalized patients with COVID-19, not requiring ventilation. 94% of patients received a corticosteroid, 72% received remdesivir and 69% received both.
A new variant of concern, designated Omicron, has been identified. The variant has several mutations that have been associated with increased transmissibility and higher immune evasion in other variants. Omicron also has new mutations in the spike protein that vaccine antibodies target. Right now, the threat is theoretical. But the vaccine manufacturers are already working on a vaccine to combat omicron, if tests show that current vaccine antibodies do not provide protection.
A review of French National Health Data from 3.9 million patients 75 years or older who had received at least 1 dose of Pfizer-BioNTech COVID-19 vaccine and 3.2 million who had received 2 doses found no increase in the incidence of acute myocardial infarction, stroke, or pulmonary embolism within 14 days of vaccine administration.
Merck announced that in the 29-day, 1,443 patient, Phase II/III, MOVe-OUT trial (NCT04575597), 6.8% of patients treated with a five-day course of molnupiravir were hospitalized or died compared to 9.7% with placebo in outpatients with mild-to-moderate COVID-19 with at least one risk factor to progress to severe disease. An interim analysis from 775 patients had suggested that 7.3% of patients treated with molnupiravir were hospitalized or died compared to 14.1% with placebo. The FDA’s Antimicrobial Drugs Advisory Committee voted 13 to 10 to recommend an emergency use authorization for molnupiravir.
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