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 the Known…

• Global impacts to date: 260+ Million confirmed cases, 5.2+ Million confirmed deaths
• Delta variant-driven caseloads increasing again world-wide - some locations back to previous highs
  • This has led to lockdowns and/or severe restrictions in Europe (e.g., Austria, Germany), tightening in the UK, and significant caseload increases and selected restrictions in the U.S. and Canada
  • Three European countries experienced riots over the past two weeks - protestors reacted to the increasing social restrictions and the threat of compulsory vaccine mandates to combat Delta surge
  • U.S. caseload range.: Florida (best) at ~30 cases/100K, Michigan (worst) at ~390 cases/100K (7 day rolling average) - a 13X difference
  • Multiple court challenges ongoing against U.S. vaccine mandates
  • Dr. Scott Gottlieb, former FDA Commissioner, hypothesizes that with waning vaccine immunity levels, the number of “breakthrough’ infections is much larger than what is being reported
• ~8 Billion vaccine shots administered globally; however, 70% of these in 10 countries; 30% in China
  • According to the WHO, for every 100 people in high-income countries, 133 doses of COVD-19 vaccine have been administered, while in low-income countries, 4 doses per 100 people have been administered → Clear indication of ‘Vaccine Nationalism’ at play
• In the U.S., recent CDC analysis suggests that if someone is not vaccinated, they are:
  • 5-6X more likely to get infected with COVID-19, even if previously recently infected 
  • 10X more likely to end up in hospital if infected
  • 11X more likely to die from COVID-19

• Fully-vaccinated people make up less than 1% of COVID-19 deaths in the U.S.

...to the Highly Unknown - Omicron Variant (Breaking News - Refana is Monitoring Carefully)

• We have entered a frequently predicted - and almost inevitable - situation, where a major new, highly differentiated, variant has emerged from countries with much lower vaccination rates → Omicron
• World Health Organization and others have been warning for months that Vaccine Nationalism and hoarding of supplies by the richest nations would ultimately prove counterproductive
• Many large populations, for example in Africa, are still almost completely unvaccinated, and thus remain strong breeding grounds for new strains of COVID-19
• Despite all these prior warnings, Omicron’s emergence seems to have caught the world unprepared
• So far, small numbers of Omicron cases have been detected in multiple countries - including Australia, Belgium, Botswana, Canada, Denmark, Germany, Hong Kong, Israel, Netherlands, UK, and South Africa - suggesting that the variant is already spreading (Note: Current data is quite limited)
• Many countries - including the U.S. - have already banned flights from 8 countries in Southern Africa
  • This may prove futile if Omicron didn't originate there, or has already escaped in sufficient volumes over the past 2-4 weeks before the initial sequencing in South Africa identified this new variant
• Israel and Japan have banned all travel with incoming foreigners
  • Fully-vaccinated returning Israelis - even w/negative PCR tests - will need mandatory quarantining
  • These measures were introduced for two weeks, to give time to assess a more complete risk profile
• The severity of Omicron infection, and its ability to overcome vaccinations, is unknown at this point

• Currently the world is lacking key information about this new variant - other than the highly concerning point that Omicron has 50 mutations, of which 32 are on the Spike Protein
  • This suggest that the Spike Protein-based vaccines’ ability to protect may be further weakened 
  • Both mRNA manufacturer CEOs have publicly reiterated this point this over the past few days, building on Pfizer CEO Alber Bourla’s similar comments from six months ago
  • However, Refana has previously observed that 'WIV-centric’ countries have suffered much less severe Delta surges than 'mRNA-centric’ countries
• Regeneron and Eli Lilly have already reported their COVID-19 therapeutic solutions are less effective vs. the Omicron variant; no updates yet re Omricon’s impact on the Pfizer/Merck/AstraZeneca solutions
  • Meanwhile, Merck’s efficacy levels have been lowered from 50% to 30%, given further testing
• South Africa has protested that it is being unfairly punished for ‘discovering’ this variant
  • For both the Alpha strain, discovered in Britain, and the Gamma strain, discovered in South Africa, there was no evidence that those variants had actually emerged in those countries
  • Rather, they have much better testing and sequencing infrastructures than their neighbors
• The timing of Omricon’s arrival is unhelpful:
  • The recent world-wide unrest and protests to the restrictions, mandates and lockdowns could further amplify if these measures need to be strengthened
• Dr. Scott Gottlieb, former FDA Commissioner, summarized the current Omicron situation well over the past weekend (28 November 2021): https://www.cbsnews.com/news/transcript-dr-scott-gottlieb-on-face-the-nation-november-28-2021​

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• Given the high rate of breakthrough infections from Delta, the potential community protection of 'herd immunity' is elusive.
• See attached figure showing vaccination rates of the ‘best’ countries in the world - even they are not good enough.
• McKinsey estimates vaccination rates needed by countries to achieve herd immunity. Ranges from ~100% vaccination in isolated countries like Australia - which have had little natural infection - to < 50% in countries like Brazil.
• A key change in the McKinsey model - they assume that "Natural infection is ~100% effective,  lasts long enough to reach herd immunity".
• In the U.S., sharp differences have emerged between the White House, the FDA and the CDC re: policies for further booster shots of existing vaccines, leading to the resignation of two senior FDA vaccine officials.
• Data is not clear whether boosters provide much additional protection to healthy younger adults, but have been recommended for the 65 plus by the FDA, and approved for a wider audience to include younger people with weakened immune systems by the CDC. 
• The absence of a vaccine which could directly protect against the Delta variant has become evident in this debate - most officials believe that the pandemic will become endemic, with further new variants arising.
• Albert Bourla, the CEO of Pfizer, has said that he expects that current vaccines may not be protective against new variants which may arise after Delta.
• It is not clear whether issues facing countries which have relied primarily on mRNA vaccines from Pfizer and Moderna (e.g. U.S., UK, Israel) will also apply to countries which have relied primarily on other vaccines, and particularly Whole Inactivated Viral (WIV) vaccines.
• If natural infection with the whole virus has been shown to be 13 times more protective than Pfizer after 6 months, then a vaccine which most closely replicates natural infection (a WIV vaccine) should also provide wider, longer term protection.
• Four important charts showing infections and death rates included below.​​

Graphs courtesy of Our World In Data

Appendix 

Calculation of the comparable protection against breakthrough Delta Infection: Two shots of Pfizer Covid Vaccine vs Recovery from prior natural infection with Covid.

Number of Double Vaccinated people in Israel:  5.4 million
Number of Recovered people in Israel from Natural Covid Infection:  900,000
Ratio of Double Vaccinated to Recovered:  6:1 (This is the scaling factor of 6)

​Given the broad and extensive coverage by the media and the scientific literature on how the Pharma/Biotech world is doing in the development and deployment of COVID-19 Vaccines in 2020-2021, Refana decided to take an objective, systematic look at the 'current state' of the approved COVID-19 vaccine world, to assess how these vaccines were doing in the fight against the COVID-19 Pandemic.  As a result, this 'White Paper' addresses six key questions:
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1. How are the currently approved COVID-19 vaccines doing overall in the fight against the Pandemic?
2. How are they doing against the emerging 'Variants of Concern' (Alpha - UK, Beta - South Africa, Gamma - Brazil and Delta - India) vs. the original Wuhan virus?
3. What are the key side-effects of each approved COVID-19 vaccine
4. How well are the approved COVID-19 vaccines doing as far as levels and lengths of immunity and the need for further Booster shots?
5. How have these vaccine manufacturers' done as they transitioned from development to production of their vaccines?
6. How have other factors - Government-driven vaccine diplomacy, vaccine hoarding/equity issues, and vaccine hesitancy - impacted the roll-out of these approved Vaccines?

Refana summarized its findings in a short-form outline style to make these insights more accessible.  Refana have also provided detailed Appendices with more specific info to support the summary outline, plus a detailed listing of all source links to the original articles and research papers that drove the assessment.

This material is not meant to be a detailed scientific review of the approved vaccines, but more of a summary of the ongoing findings related to the approved vaccines with respect to these six key questions, based on the substantial amount of reporting that has been published world-wide during the COVID-19 Pandemic.  As such - and as an objective assessment of where things stand - Refana believes this material represents a good consolidated reference document on the current 'State of the Art' for the approved COVID-19 vaccines.    

Since this is a highly dynamic situation, Refana is referring to this White Paper as the June 2021 Release V1.0. Refana intends to regularly update this material with the latest info on all approved COVID-19 vaccines on a periodic basis.