Industry Updates Volume 15

28 Days Later: An Omicron ‘Remake’

• The world is now at 285 Million cases, 5.4 Million deaths, 9.1 Billion vaccination doses
• However, since being first detected in South Africa, Omicron has:
  • Been detected in 100+ countries and all U.S. States
  • Contributed to record caseloads, both world-wide, and across 20+ countries in 4 continents, including the U.S., Canada, the UK, France, Italy, Australia, Denmark, Ethiopia, and 7 other countries in Africa
  • Already accounted for 59% of U.S. cases, along with 41% from Delta - acting like a ‘Twindemic’
  • Demonstrated as being 70X more contagious than Delta - contributing to its rapid emergence
  • Been so far seemingly less severe than Delta - but that lag in effect may bias hospitalization and death data, thus not yet revealing the complete story - experts are suggesting this wave needs to mature for a few more weeks into the New Year to get a clearer indication of severity levels
  • Evaded current vaccines - typically requiring Boosters to get to sufficient protection - as well as some of the current therapeutic treatments
  • Caused world-wide disruptions (e.g., Sporting events, concerts, New Years Eve celebrations, and the list goes on), led to thousands of flight cancellations each day, affecting Millions of travelers, and the complete shutdowns of multiple countries
  • Reignited more actions and further debates/protests across multiple countries re: vaccine hesitancy and anti-vax, lockdowns, mandates, business shutdowns, school disruptions, delays on companies bringing employees back to work locations, etc.
  • Pushed many locations to require proof of vaccination
  • Led to a strong demand spike for infection testing, leading to a world-wide shortage of all test types - PCR, antigen/lateral flow, @ home testing, etc. - creating long testing line-ups, delays and frustration in getting results 
  • Demonstrated a general lack in preparation for such a rapidly escalating and contagious Variant of Concern, due to a lack of genetic sequencing, testing, stockpiling of therapeutics and deployment of next generation vaccines, all becoming key issues
  • Elevated the potential of substantial further COVID-19 infections, e.g., modeling in the U.S. suggests that Omicron could infect up to 140 Million Americans from Jan-March 2022, vs 55 Million COVID-19 cases experienced so far in the U.S. - Note: Most of these infections will by asymptomatic, but will still act as carriers/transmitters of the virus

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COVID Continues to Kill - Death Rate in High Income Countries up 6x in 5 Months

• Notwithstanding the fast spread of a supposedly 'milder' version of COVID-19, the death rate has picked up in the High Income Countries.  As shown in Exhibit 1 - This is not being reported generally and is counterintuitive, given that these countries are generally more highly and completely vaccinated
• It is not clear whether the divergence in the death rate in High Income Countries compared to deaths in the Upper/Lower/Low Income countries is due to the different vaccines in use, or some other factor, such as under-reporting in those less-developed countries
• However, with global COVID-19 daily caseloads currently now at all time highs (Exhibit 2), and given that the current number of weekly deaths is more than 50% below its previous peak, the death rate coming from the COVID-19 Pandemic overall has fallen
• Current death rates are driven from the combination of the Delta and Omicron variants being the two dominant current COVID-19 variants
• While Omicron is rapidly becoming the predominant strain, it is not happening as quickly as forecast
  • In the U.S., the CDC revised its U.S. proportions of Omicron down this week vs. last week, but now has Omicron at 59% of all current U.S. cases, so the dominant variant in the U.S. over Delta
• Lower death rates - despite record caseloads - are driven by multiple factors:
  • The still protective effect of vaccines against worst outcomes, despite hundreds of thousands of breakthrough infections
  • Natural immunity from prior COVID-19 infections
  • Different age profiles of the infections - a much higher proportion of Omicron infections have appeared in younger, healthier people
  • Better COVID-19 treatments and therapeutics, even as they show less effectiveness
  • The possibility that Omicron is intrinsically less dangerous than prior variants​​

• From Refana’s 2x2 Scenario Analysis of possible outcomes from the Omicron surge - Figure 1 here - it increasingly appears that we are seeing the lower right quadrant becoming dominant - Combination of higher transmissibility with less severe morbidity
  
  • Driven by some combination of the five reasons outlined above
    

• n​This “Extended Period of COVID-19 Restrictions” Scenario will likely lead to further Booster campaigns around the world, further exacerbating the current vaccine inequity/nationalism issues
• Omicron-driven restrictions have become particularly pronounced with respect to travel.  Examples:
  • Many thousands of flight cancellations or disruptions world-wide
  • Israel and Japan have restricted all foreigners from entering these countries
  • Germany and France have banned the UK
  • UK put the U.S. on its red list 
  • China has locked down 13 million people in a single city, given only 100 infections
• It is questionable how meaningful these international travel restrictions are in reality, given that Omicron has already spread worldwide
  • Indeed, the original travel ban on the Southern African countries has recently been revoked

​Vaccines, Therapeutics and Vaccination in the West

• At the margin, the existing Wuhan-strain Moderna vaccine shows greater protection than Pfizer, but Moderna’s CEO has still disclosed plans for an Omicron-specific vaccine
• Living with an endemic COVID-19 virus for years-to-come is looking ever more probable, raising the inevitable question of ongoing vaccination strategies, leading to an ongoing need to update vaccines
• Johnson and Johnson looks like it could exit the market, following recent negative comments from the FDA regarding further blood clot risks in younger healthy females
  • However, as with the other vaccines, studies have shown that the J&J shot may still protect ‘enough’
• Notably, AstraZeneca which has similar issues to J&J has still not received U.S. FDA approvals
• A number of newer vaccines are coming forward - most significantly Novavax - which following multiple manufacturing-driven setbacks, has now received emergency approvals from the WHO and the EMA
• The EMA has also placed an order for up to 60 million Valneva doses
  • This is the first large-scale use of a WIV-base vaccine in the West
• The FDA recently issued Emergency Use Authorizations for oral therapeutic drugs from Pfizer and Merck
  • Both are moving to production - they will be expensive, costing $400-$700 per treatment course, vs. $5 - $40 per dose costs for vaccines
  • The U.S. placed a $5.3 Billion order for Pfizers’s Paxlovid drug - 10 Million treatment courses (likely less than expected demand) - some Paxlovid is available now, more to come in next 6 months
  • Paxlovid is claimed to have an almost 90% efficacy in preventing a need for a hospital stay for a COVID-19 infected patient
  • Some emerging issues of side-effects with the Pfizer and Merck therapeutics have been noted, along with Merck’s efficacy dropping from being only at 50% to 30% in more detailed trials
  • Refana was surprised that the FDA approved the Merck therapeutic

Differential Death and Vaccination Rates

• Exhibit 3 shows significant differences in ‘excess death rates’ since last year
• These excess deaths can be due to COVID-19 infections and also additional deaths arising as an indirect effect of COVID-19, such as under-treatment of other ailments
• In most countries, the ratio of reported COVID-19 deaths to the overall excess mortality is consistent
  • Russia is an exception - they may have been only reporting approximately 20% of COVID-19 deaths
• Exhibit 4 shows significant differences in the vaccination/Booster rates world-wide, by country - the U.S. represents approximately a ‘median’ position in terms of vaccinations
  • Countries with equal/lower vaccination rates than the U.S. have higher cumulative death rates
  • However the correlation does not appear to work in the opposite direction, i.e., that as vaccination rates increase above the average in the U.S., this does not correlate proportionally with lower cumulative death rates
  • It appears that as vaccination rates increase above the U.S. threshold, the more significant reduction in the cumulative death rate are driven by the additional public health measures and degree of compliance, as indicated in Japan, Canada, Israel, Germany, Sweden and France
• Exhibit 5 shows that the Upper Middle Income countries have now fully caught up with - even slightly exceeded - the vaccination rates of the High Income countries
  • Lower Middle Income countries are at half this level and should catch up on a two-shot basis (but probably not Boosters) during 2022
  • Lower Income countries however are still only at 12 vaccinations per 100 people, which, on a two-shot vaccine regime, is only a vaccination rate of 6% of the population
• Without a major change in global policies and cooperation, many countries world-wide are unlikely to achieve satisfactory vaccination levels in 2022

Three Key Questions 

• Is Omicron the ‘last’ major Variant of Concern, leading to a final transition from COVID-19 Pandemic to Endemic, and a need for ongoing maintenance (i.e., Boosters) against localized flair-ups of COVID-19?
• Or, will other Variants of Concern continue to emerge from less vaccinated areas of the world, or from emerging ‘reservoirs’ of COVID-19 virus in animals, e.g., white tailed deer, rats, dogs, cats, etc.?
• When will the world begin to collaborate more constructively to solve the COVID-19 Pandemic, getting to more consistent and complete world-wide vaccination rates and the ability to combat local/regional outbreaks of the disease?

Outlook for 2002

• Numerous commentators are predicting a ‘new normal’ in 2022, where we will have to learn to live with an Endemic COVID-19
• The implications are that with the ever greater availability of vaccines from the second half of 2022, an increasing proportion of the entire world's population will be vaccinated
• Ongoing Booster vaccination campaigns are to be expected for the coming years, with the frequency determined by the speed with which vaccines wane and the frequency and severity of highly transmissible or dangerous new variants
• Refana predicts that the recourse to travel bans, lockdowns and long quarantine periods will be abandoned progressively during 2022 as the futility of these actions becomes ever more apparent
• What the world is waiting for is a next generation vaccine that is more effective in: 1) The duration of the protection it provides and 2) Being able to further withstand new Variants of Concern - which is exactly what Refana is working on
  • This appears to be the only ‘Silver Bullet’ on the horizons in Leading Countries​

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​Refana Update

• Refana’s validation of its Delta-specific vaccine is continuing in a pre-clinical trial at the Illinois Institute of Technology Research Institute (IITRI) in Chicago
• The transgenic mice, who have the ACE 2 human gene receptor, received their first vaccine shot three weeks ago, and will receive their second shot next week
• Meanwhile IITRI will commence growing the certified Omicron virus strain they received from the CDC
• Refana’s larger trial will now seek to test a bivalent vaccine - using both the Delta and Omicron variants - on a statistically valid number of animals, and in a comparison with mRNA vaccines

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Follow this link to see the graphs and insight in exhibits 1-5

Exhibits 1-5

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