Omicron and Caseloads: A Numbers Game

Omicron and Caseloads - A Numbers Game

• One estimate is that the Omicron variant is twice as infectious as Delta, leading  to an exponential growth of cases.
  • Theoretically, over a month with 6 replication cycles, we possibly could have 2⁶ (64) times the number of cases of the prior month.
  • This is an estimate and does not take into account the current level of protection is out there with both vaccinations and prior infection.
  • Even if Omicron was only half as deadly as Delta, increases in severity of illness are linear, whereas increases in transmissibility result in the geometric (exponential) growth. In other words, a huge increase in cases will overwhelm the system and cause an increase in mortality, even if the risk of severe illness is less in any one individual person.

• Preliminary data from the U.K. Health Security Agency indicates protection from symptomatic infection with omicron may be close to zero for those vaccinated with double AstraZeneca, and less than 40 per cent for those with two shots of Pfizer (for any infection, not for severe disease protection).
• The same report indicated that booster doses could increase protection to around 75 per cent. This is bolstered by other research that has shown third shots increase antibodies about 40 times
• Report also suggests Omicron is 2-3 times more infectious than Delta variant

• In the US on Dec 11th, 12% of new cases were caused by the Omicron variant. By December 18th, 75% of new cases were Omicron.

PERSPECTIVES

• Protection against severe disease is what really matters and it is still unclear what the effect of this new variant will be on this metric.

Antibody Therapy Evasion:

• Early data suggest that most of the major antibody therapies will be ineffective or much less effective with Omicron and will need to be reformulated to regain effectiveness.

mRNA Doses

• Early data suggest that 2 doses of mRNA vaccine are significantly less effective than 3 doses for prevention of any infection.
• It is less clear how effective the 3 dose regimen will be against severe disease. 

Azithromycin:

• A meta-analysis of 16 studies (5 RCT’s, 11 observational studies) including 22,984 patients receiving azithromycin was recently published in the Journal of Antimicrobial Therapy.
• No difference was found in mortality or admission rate.

High Flow Oxygen:

• A recent open label study in JAMA enrolled 220 adult patients with respiratory distress (median age 60).
• Patients were randomized to high flow vs. standard nasal O2.
• 34.3% high flow group and 51% nasal cannula group were intubated (primary outcome) with a  shorter time to recovery in the high flow group.

Anticoagulation:

• In August 2021, NEJM published a randomized trial comparing therapeutic dose anticoagulation vs. prophylactic dose anticoagulation in non-critically ill patients with COVID-19.
• 2219 patients were enrolled. The trial was stopped early.
• The number need to treat (NNT) to prevent “organ support therapies” was 20
• Major bleeding occurred in 1.9% vs 0.9% of patients (number need to harm of 100 for therapeutic dosing)
• They concluded that therapeutic-dose anticoagulation with heparin “increased the probability of survival to hospital discharge with reduced use of cardiovascular or respiratory organ support as compared with usual-care thromboprophylaxis.”
• However, similar benefit has not been found in critically ill patients.
  • Results of HEP-COVID (JAMA Int Med 2021) also showed benefit in non-critically ill patients but no benefit in the critically ill.

• The MICHELLE study(Lancet Dec 2021) showed apparent benefit to  outpatient treatment after hospitalization.
  • COVID survivors may benefit from short term anticoagulation upon hospital discharge.

Children and Vaccination

• Pfizer recently released information regarding its study of children 6 months to 5 year of age. The study is ongoing.
  • Children received a 3 microgram dose x 2 (lower dose but same as adult regimen)
    • Note: the adult dose is 30 micrograms and for children ages 5-12 it is 10 micrograms
  • Children in the 6 month to 2 years had adequate response.
  • Children in the 2-5 age group had an inadequate response. A third dose of vaccine is now being studied for this age group.
  • No safety concerns were reported.

Remdesivir:

• The WHO study as well as DISCOVERY tells us that remdesivir likely has no effect on COVID outcomes.

Fluvoxamine:

• Promising (and cheap) but we need more data to justify use.

Other things that work:

• Tocilizumab (IL-6 inhibitor) + steroids show benefit in the critically ill.
• Baricitinib (JAK inhibitor) demonstrated a signal of mortality benefit in the COV-BARRIER study but the study was inadequately powered. We need more data.
• High-dose steroidsin critically ill patients
  • A recent JAMA study suggests incremental benefit with the higher dose dexamethasone (12mg) vs. 6mg.
  • Outcomes (including mortality, a secondary outcome) did not reach statistical significance but the trend to benefit with the higher dose was strong.
  • It is unclear if you should pair the higher dose with tocilizumab.

References:

Monoclonal evasion: https://www.biorxiv.org/content/10.1101/2021.12.07.470392v1.full.pdf

UK health department report Dec 10 2021: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1042367/technical_briefing-31-10-december-2021.pdf

mRNA Booster and Omicron: https://www.medrxiv.org/content/10.1101/2021.12.14.21267769v1?rss=1%22

Azithromycin: https://academic.oup.com/jac/advance-article/doi/10.1093/jac/dkab404/6430403

High Flow Nasal O2:https://jamanetwork.com/journals/jama/article-abstract/2786830

Anticoagulation: https://pubmed.ncbi.nlm.nih.gov/34351721/

Vaccines 2-5 Years: https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-provide-update-ongoing-studies-covid-19

Remdesivir: https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(21)00485-0/fulltext

This Week in Virology has exceptional updates weekly 

12mg Dexamethasone vs. 6 mg:

https://jamanetwork.com/journals/jama/fullarticle/2785529#:~:text=Findings%20In%20this%20randomized%20trial,difference%20was%20not%20statistically%20significant.

 

Combination therapy of Tocilizumab and steroid for management of COVID-19 associated cytokine release syndrome:

https://journals.lww.com/md-journal/Fulltext/2021/07230/Combination_therapy_of_Tocilizumab_and_steroid_for.46.aspx

 

Baricitinib (JAK inhibitor): https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(21)00331-3/fulltext

 

HEP-COVID: https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2785004

 

MICHELLE study: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02392-8/fulltext