COVID Update - August 1st, 2022 Episode

Updated: Oct 17




https://www.science.org/doi/10.1126/science.abq0203

Here we report that the BA.1, BA.2, BA.2.12.1, and BA.4/5 Omicron sublineages, which account for over 99% of all infections worldwide over the first half of 2022, have increased ACE2 binding affinity, decreased fusogenicity and markedly evade neutralizing antibody responses relative to the Wuhan-Hu-1 and Delta strains (3). Collectively, these data suggest that enhanced receptor engagement and immune evasion are key changes that may have promoted the rapid spread of these Omicron sublineages and could contribute to the current rise in prevalence of BA.4 and BA.5.

Vaccine efficacy:

NSW report https://www.health.nsw.gov.au/Infectious/covid-19/Pages/weekly-reports.aspx

146 COVID-19 deaths were reported this week, a 3% increase from 142 reported last week. All 146 deaths were eligible for a third dose of COVID-19 vaccine and 100 (68%) had received a third dose. Five deaths were in people aged under 65 years.

https://www.science.org/doi/10.1126/science.abq0203

Overall, these data underscore the magnitude of evasion of polyclonal plasma neutralizing antibody responses for Omicron sublineages in humans after primary vaccine series or infection (resulting from the accumulation of S mutations (12)), with a subtle but consistently more marked effect for BA.1 and even more so for BA.4/5 compared to BA.2 and BA.2.12.1.

Natural immunity

https://www.nature.com/articles/d41586-022-01950-2?utm_source=Nature+Briefing&utm_campaign=d266f4379d-briefing-dy-20220722&utm_medium=email&utm_term=0_c9dfd39373-d266f4379d-46499490

Protection against severe reinfection remains very strong, with no evidence for waning, irrespective of variant, for over 14 months after primary infection.

https://www.medrxiv.org/content/10.1101/2022.07.06.22277306v1

Effectiveness of a previous pre-Omicron infection against symptomatic BA.4/BA.5 reinfection was 15.1% (95% CI: -47.1-50.9%), and against any BA.4/BA.5 reinfection irrespective of symptoms was 28.3% (95% CI: 11.4-41.9%)

Effectiveness of a previous Omicron infection against symptomatic BA.4/BA.5 reinfection was 76.1% (95% CI: 54.9-87.3%), and against any BA.4/BA.5 reinfection was 79.7% (95% CI: 74.3-83.9%).

Novavax

Novavax's product is a protein subunit vaccine that contains the SARS-CoV-2 spike protein plus an adjuvant to enhance the recipient's immune response.

Approved EUA as a primary vaccine not booster

https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-emergency-use-novavax-covid-19-vaccine-adjuvanted

Good evidence for boosting antibody production with less Transient Systemic Reactogenicity

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02718-5/fulltext

https://www.science.org/doi/10.1126/science.abq0203

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02717-3/fulltext

Not approved because efficacy trial for boosting still ongoing and changes made to manufacturing process

https://www.cnbc.com/2022/06/09/fda-decision-on-novavaxs-covid-shots-could-be-delayed-.html

https://ir.novavax.com/2022-03-25-Novavax-Announces-Participation-in-Two-Booster-Studies-Using-its-COVID-19-Vaccine

FDA Approved therapies

Remdesivir (Veklury) - HIV anti-retroviral

https://www.veklury.com/about-veklury/

People who take it in one study had a 50% better chance of recovery at 15 days and may recover 5 days sooner

Baricitinib (Olumiant) -

https://www.olumiant.com/rheumatoid-arthritis/what-is-olumiant?utm_id=go_cmp-15584346143_adg-137950164664_ad-569916896303_kwd-343657218204_dev-c_ext-_prd-_mca-_sig-Cj0KCQjw852XBhC6ARIsAJsFPN3q6ZkS7Tus5rQphjegjC0Q741pTPSy38M0xSwF26l58yhar3jBXhkaAhTJEALw_wcB&utm_source=google&gclid=Cj0KCQjw852XBhC6ARIsAJsFPN3q6ZkS7Tus5rQphjegjC0Q741pTPSy38M0xSwF26l58yhar3jBXhkaAhTJEALw_wcB

Serious infections, cancer, major cardiac events, blood clots, allergy, stomach or intestinal tears

Emergency use auth:

Paxlovid

Wow. Just wow…

https://www.fda.gov/media/155050/download

 History of clinically significant hypersensitivity reactions to the active ingredients (nirmatrelvir or ritonavir) or any other components. (4)

 Co-administration with drugs highly dependent on CYP3A for clearance and for which elevated concentrations are associated with serious and/or life-threatening reactions. (4, 7.3)

 Co-administration with potent CYP3A inducers where significantly reduced nirmatrelvir or ritonavir plasma concentrations may be associated with the potential for loss of virologic response and possible resistance. (4)

https://www.med.umich.edu/asp/pdf/outpatient_guidelines/Paxlovid-DDI.pdf?utm_source=substack&utm_medium=email

Paxlovid, a drug with 120 important drug interactions across 25 different classes of very commonly prescribed medications. It cannot be given concurrently with 75 of them and you have to adjust doses with an additional 29. Even Biden had to be taken off of two of his medications to be treated with it.

Other therapies

Fluvoxamine:

Treatment with fluvoxamine (100 mg twice daily for 10 days) among high-risk outpatients with early diagnosed COVID-19 reduced the need for hospitalisation defined as retention in a COVID-19 emergency setting or transfer to a tertiary hospital.

https://www.thelancet.com/journals/langlo/article/PIIS2214-109X(21)00448-4/fulltext

These findings suggest that fluvoxamine, a widely available and inexpensive treatment for outpatients with COVID-19, was associated with a reduction in hospitalizations.

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2790742

https://jamanetwork.com/journals/jama/fullarticle/2773108