Omicron Variant: Latest Scientific News, Findings, Evidence, and Developments

Highlights

The world community is extremely concerned about the growing threat of the Omicron variant (B.1.1.529) of coronavirus SARS-CoV-2. This is because the new variant is not only spreading rapidly across the planet but is also characterized by an impressive set of mutations. These mutations may well contribute to Omicron becoming more infectious and aggressive, and existing vaccines may not be able to counteract it as effectively, leading to an increase in reinfection.

In the wake of the hype surrounding Omicron, the Internet is overflowing with a slew of disturbing messages. People are worried: “Omicron is more contagious,” “Omicron avoids vaccine-mediated immunity,” “We need new vaccines against Omicron.” Some are more optimistic: “Omicron causes a milder course of the disease,” “Omicron will destroy itself because of the excessive mutations that will eventually render it unable to replicate,” “Omicron is generally harmless.” Others are categorical in their statements: “HIV patients are to blame for the emergence of Omicron.”

Let’s not succumb to panic, but stick to scientific approaches in our assessments.

 

Omicron Variant: Scientific Timeline

January 2022

January 14

Although a number of vaccine manufacturers are preparing vaccine modifications tailored to the mutational specificity of the Omicron variant of SARS-CoV-2 coronavirus, U.S. health officials believe it is not particularly necessary.

On the one hand, the scientific world and the pharmaceutical industry argue that existing vaccines need to be updated for the specifics of Omicron because their effectiveness drops dramatically in its presence. On the other hand, officials at the U.S. Food and Drug Administration (FDA) and the National Institute of Allergy and Infectious Diseases (NIAID) express doubts about such an initiative: first, by the time new vaccines are ready, the Omicron wave may be over, and second, repeated (booster) doses of vaccines will provide quite reliable protection against Omicron.

There is an opinion that it is wise to wait a couple of months or so to see if Omicron becomes the dominant variant in the long term, competing with Delta, or if it quickly recedes like other SARS-CoV-2 variants like Alpha, Beta, and Gamma.

The current uncertainty with the future of Omicron should not negate the fact that premature promotion of new vaccines is risky and costly because manufacturing processes would have to be restructured, and this would disrupt the production of existing vaccines, causing shortages. Again, it is not known whether Omicron vaccines will be as effective against other strains, since the latter may well break out again or evolutionize into other variants. It would be far better to abandon the pursuit of specific variants of coronavirus and devote resources to the development of a universal vaccine that protects against all SARS-CoV-2 mutations in a long-lasting and effective manner.

 

January 13

A third (booster) dose of the viral vector vaccine Vaxzevria/Covishield (AZD1222, ChAdOx1 nCoV-19, ChAdOx1-S) by AstraZeneca enhances antibody response to the Omicron (B.1.1.529) variant of SARS-CoV-2 coronavirus.

Vaxzevria/Covishield booster also enhances the immune response to other coronavirus variants, including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), and Delta (B.1.617.2).

Immunogenicity was evaluated 28 days after the third dose of the vaccine.

This was reported by AstraZeneca, based on preliminary analysis of data collected in the ongoing clinical trial NCT04973449 phase 2/3.

The study is testing the safety and immunogenicity of a booster dose of Vaxzevria/Covishield or AZD2816 experimental vaccine designed to be specific to the Beta variant of coronavirus. Adult volunteers were invited, both unvaccinated and those who had received a full course of two doses of Vaxzevria/Covishield or the mRNA vaccine — Comirnaty (tozinameran; BNT162b2) or Spikevax (elasomeran; mRNA-1273) by Pfizer/BioNTech and Moderna respectively.

 

January 12

Adagio Therapeutics has notified that ADG20 monoclonal antibody it is developing works against the Omicron (B.1.1.529) strain of SARS-CoV-2 coronavirus.

Thus, the half-maximal inhibitory concentration (IC₅₀) of ADG20 is 0.4–1.1 µg/ml, which compares with that of sotrovimab and Evusheld (AZD7442) as a combination of tixagevimab (AZD8895) and cilgavimab (AZD1061) by GlaxoSmithKline/Vir Biotechnology and AstraZeneca, respectively.

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According to the European Medicines Agency (EMA), frequently repeated vaccinations for COVID-19 infection can negatively affect the immune response by overloading and weakening the immune system, ultimately proving impractical.

According to the regulator, repeated booster doses of the vaccine every four months are too frequent an immunization regimen: revaccination should be less frequent, tying it to the beginning of the winter season in each hemisphere, similar to influenza inoculation.

Regarding the need for universal adoption of the fourth dose of vaccines advocated by Israel, the EMA has so far questioned this approach due to a lack of data that would unequivocally support it. Nevertheless, the regulator continues to study Omicron comprehensively in order to propose the best strategy to combat it. But it is already clear that endless boosters do not provide a way out of a pandemic that is highly desirable to bring to a more endemic nature.

When it comes to vaccines specific to the Omicron mutation set, more data needs to be collected on the effect of the new variant on the vaccines available in the armamentarium and a better understanding of the evolution of the current wave. In other words, a strategy that is not just reactive is needed — an approach suitable for preventing future SARS-CoV-2 variants should be developed.

 

January 11

The World Health Organization (WHO) reported a record number of people infected with SARS-CoV-2 coronavirus in the history of the pandemic.

During the first full week of January 2022 (January 3 to 9 inclusive), the number of newly infected people exceeded 15 million. This is a 55% increase over the previous week.

The epidemiological situation is due to the rapid spread of the Omicron variant on the background of reduced circulation of the Delta variant and a very low presence of Alpha, Beta, and Gamma variants.

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There were 1.35 million new cases of SARS-CoV-2 coronavirus in the United States, the highest daily total of any country in the world. The previous anti-record was set on May 3, 2021 — 1.03 million new cases.

The spike in incidence is due to the continued spread of the Omicron (B.1.1.529) variant of coronavirus.

Although Omicron causes perhaps a less severe course of COVID-19 infection than other variants, the huge flood of patients is putting tremendous pressure on hospital systems.

 

January 10

An experimental ensovibep, developed by Molecular Partners and Novartis and suitable for fighting the Omicron variant of SARS-CoV-2 coronavirus, provided an 87% reduction in risk of hospitalization and/or death relative to placebo among outpatients with mild-to-moderate COVID-19 infection.

 

December 2021

December 29

The Delta (B.1.617.2) and Omicron (B.1.1.529) variants of the SARS-CoV-2 coronavirus now circulating are twin threats that are causing huge numbers of hospitalizations and deaths. Total vaccination of the world’s population can help control the problem. However, fewer than half of the World Health Organization’s (WHO) member states have met the plan to immunize 40% of their people.

According to Tedros Adhanom Ghebreyesus, WHO’s director-general, as the COVID-19 pandemic drags on, new variants of the coronavirus could become completely resistant to existing vaccines, requiring them to adapt accordingly. And any renewal of vaccines potentially means another shortage in supply. Therefore, vaccine production must be ramped up locally. But this is not possible without the consolidation of vaccine technologies when all patents and intellectual property rights become the public domain. This has not happened so far: every pharmaceutical company is busy making crazy profits.

The moment has come when the leaders of the countries must put aside the politics of populism and self-interest.

 

December 24

Within the next two to three months, 3 billion or more people on the planet will be infected with the Omicron (B.1.1.529) variant of the SARS-CoV-2 coronavirus. This is equivalent to nearly 40% of the world’s population.

According to the predictive model of the Institute for Health Metrics and Evaluation (IHME) at the University of Washington School of Medicine, the accelerated transmissibility (contagiousness) of Omicron will result in multiple increases in reported COVID-19 infections and a global spike in hospitalizations. However, the number of fatalities will not rise significantly.

• COVID-19 results briefing. IHME, December 22, 2021. [PDF]

 

December 23

Researchers at Oxford University who tested the neutralizing activity of antibodies against the Omicron (B.1.1.529) variant of the SARS-CoV-2 coronavirus made the following conclusions:

• A third (booster) dose of the viral vector vaccine Vaxzevria/Covishield (AZD1222, ChAdOx1 nCoV-19, ChAdOx1-S) promoted by AstraZeneca could potentially protect against Omicron, although the degree of protection would be relatively weak.

• A third dose of the mRNA vaccine Comirnaty (tozinameran; BNT162b2) by Pfizer/BioNTech is quite capable of putting up a strong shield against Omicron.

• The protective immunity developed in unvaccinated individuals after naturally exposed to non-Omicron COVID-19 variants is comparable to that after two doses of AstraZeneca or Pfizer/BioNTech vaccine, which means it will not save them from Omicron — well, except to avoid the development of severe COVID-19 that requires hospitalization.

Thus, 28 days after the third dose of Vaxzevria/Covishield, the titer of Omicron neutralizing antibodies in the sera of the vaccinated increased 2.7-fold compared to their level after 28 days after the second dose. However, the titer after the booster was still 3.6 and 12.7 times lower compared with the booster titer of neutralizing antibodies against the Delta variant and the original non-mutant SARS-CoV-2.

After the Comirnaty booster, the titer of Omicron neutralizing antibodies in the sera of vaccinated subjects increased 34.2-fold compared with their levels after the second dose. At the same time, it was 3.6 and 14.2 times lower relative to the booster titer against Delta and non-mutant coronavirus. It would seem that this reduction is comparable to that for the AstraZeneca’s vaccine, but in absolute terms the level of neutralizing antibodies against Omicron after the third dose of Comirnaty was 11.4 times higher compared to the level after the third dose of Vaxzevria/Covishield.

Looking at titers of Omicron neutralizing antibodies in the sera of unvaccinated and COVID-19 survivors, they, compared with titers against the original coronavirus, dropped significantly — by 16.9, 33.8, 11.8, 3.1, and 1.7 times for COVID-19 caused by non-mutant SARS-CoV-2, its Alpha (B.1 .1.7), Beta (B.1.351), Gamma (P.1), and Delta (B.1.617.2) variants, respectively. At the same time, their levels in absolute values were comparable to that after the second dose of AstraZeneca or Pfizer/BioNTech vaccine, i.e., decisively insufficient to counteract omicron.

• Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses. bioRxiv, December, 22, 2021. [PDF]

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Russia has approved MIR 19, a new drug for the treatment of COVID-19 infection caused by the SARS-CoV-2 coronavirus.

MIR 19, which inhibits coronavirus replication and prevents the development of severe COVID-19, including acute respiratory distress syndrome (ARDS), is based on RNA interference (RNAi) technology. Because of its specific mechanism of action, MIR 19 retains antiviral activity regardless of the variant of coronavirus, whether it is Omicron or Delta.

MIR 19, indicated for the treatment of COVID-19 in the non-serious form, is administered by inhalation for 14 days.

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Merck & Co. has offered oral molnupiravir, a new drug indicated to treat mild-to-moderate COVID-19 infection in adult patients who are at high risk for progression to severe disease that requires hospitalization or may end in death.

According to a clinical trial of the antiviral, molnupiravir reduced the risk of hospitalization or death by 30%.

According to Merck & Co., molnupiravir maintains its antiviral efficacy against the Omicron variant.

 

December 22

Pfizer has released oral Paxlovid (nirmatrelvir + ritonavir), a new drug indicated to treat mild-to-moderate COVID-19 infection in adults and children who are at high risk for progression to severe disease that requires hospitalization or may end in death.

Paxlovid is the first oral antiviral drug for home use with reliably proven therapeutic efficacy.

In a clinical trial of the antiviral, Paxlovid reduced the risk of hospitalization or death by 89% and 88% when administered within 3 and 5 days of onset of COVID-19 symptoms, respectively. Among older patients, the risk reduction was even better, at 94%.

According to Pfizer, Paxlovid maintains its highest antiviral efficacy against the Omicron variant.

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Israel became the first country in the world to launch a mass immunization campaign with a fourth dose. The initiative responds to scientific evidence showing that even three doses of vaccines are insufficient to provide reliable protection against the Omicron variant of SARS-CoV-2 coronavirus.

The fourth dose of Pfizer/BioNTech’s mRNA vaccine Comirnaty (tozinameran; BNT162b2) will initially be given to the elderly (60 years and older), those with compromised immune systems, and healthcare workers. To receive it, at least four months must pass after the third dose of inoculation.

In addition, the period between the second and third doses was reduced from five to three months.

Earlier, Israel became the first country in the world to start immunizing its population with the third (booster) dose of the vaccine.

Of Israel’s 9.3 million population, nearly 70% were inoculated with two doses, while 45% received three doses.

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The Danish Staten Serum Institut (SSI) evaluated the protective efficacy of vaccines against the Omicron (B.1.1.529) variant of SASR-CoV-2 coronavirus. mRNA vaccines Comirnaty (tozinameran; BNT162b2) and Spikevax (elasomeran; mRNA-1273) by Pfizer/BioNTech and Moderna were tested.

The effectiveness of mRNA vaccines against Omicron was found to be catastrophically reduced, both disproportionately inferior to protection against the Delta strain (B.1.617.2) and weakening very rapidly over time. And even the third (booster) dose protects against Omicron significantly worse than against Delta.

Thus, immunization with two doses of Comirnaty provided 87%, 81%, 73%, and 54% protection against Delta for up to one month after inoculation, one to two months, two to three months, and three to five months, respectively. In the case of Omicron, vaccine effectiveness was 55%, 16%, 9%, and −77%.

Vaccination with two doses of Spikevax protected against Delta at 88%, 82%, 72%, and 65% in the above periods. The Omicron variant reduced its effectiveness to 37%, 30%, 4%, and −39%.

A third (booster) dose of Comirnaty brought the level of protection against Delta and Omicron to the corresponding 81% and 55% for periods up to one month after its administration.

• Vaccine effectiveness against SARS-CoV-2 infection with the Omicron or Delta variants following a two-dose or booster BNT162b2 or mRNA-1273 vaccination series: A Danish cohort study. medRxiv, December 21, 2021. [PDF]

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December 21

According to a study by the Icahn School of Medicine at Mount Sinai (ISMMS), the neutralizing antibody activity of those who recovered from a COVID-19 infection or who received two doses of mRNA vaccines — Comirnaty (tozinameran; BNT162b2) or Spikevax (elasomeran; mRNA-1273) by Pfizer/BioNTech and Moderna — is decidedly insufficient to successfully protect against the Omicron (B.1.1.529) variant of SASR-CoV-2 coronavirus.

However, protection against Omicron will remain (albeit at a decently weakened level) in those who have previously been exposed to coronavirus three or four times: either they were vaccinated with three doses, or they were infected and then vaccinated with two doses, or they were infected and vaccinated with three doses.

The reduction in neutralizing activity of serum antibodies against Omicron was as follows when compared with activity against the original non-mutant SARS-CoV-2 as measured by the 50% inhibitory dose (ID₅₀; the antibody titer required to suppress replication of 50% of the viral culture):

• COVID-19: 11.1-fold reduction — in most cases (73%) the neutralizing activity against omicron was below the limit of detection (LOD)
• two doses of Comirnaty: 23.3-fold (p=0.0043) — 30% LOD
• two doses of Spikevax: 42.6-fold (p=0.0005)
• three doses of Comirnaty: 7.5-fold (p=0.0007)
• three doses of Spikevax: 16.7-fold (p=0.0437)
• COVID-19 and two doses of Comirnaty: 13.7-fold (p=0.0165)
• COVID-19 and two doses of Spikevax: 10.6-fold (p=0.0075)
• COVID-19 and three doses of Comirnaty: 13.1-fold (p=0.0462).

The researchers also examined the binding activity of serum antibodies, one of the correlates of protection against SARS-CoV-2, which provides it through Fc-mediated effector functions. If binding activity to the receptor-binding domain (RBD) of the coronavirus is maintained (even with a significant decrease in antibody titer), it indicates the presence of cognate B cells. The latter can be rapidly activated during infection with a variant of coronavirus or a vaccine specific to it, inducing a strong plasmoblast response that provides control over the spread of the virus. In addition, B cells, characterized by low-affinity binding to proteins of the variant with the antigenic drift, enter the lymph nodes and participate in germinal center reactions leading to the formation of antibodies capable of restoring neutralizing activity due to affinity maturation.

In general, the binding activity of antibodies against Omicron decreased significantly less than the neutralizing activity. It decreased most dramatically (7.5-fold reduction) in previously exposed to COVID-19 but not vaccinated, and in two-thirds to an undetectable threshold. In all other groups, binding was relatively stable, and its reduction ranged from 2.9-fold for two doses of Spikevax to 1.5-fold for three doses of Comirnaty.

Finally, the experts checked serum antibody binding activity to the N-terminal domain (NTD) of the coronavirus, which, in addition to RBD, is the main target of B cells after inoculation with mRNA vaccines. The NTD at Omicron carries a large number of amino acid substitutions, three deletions, and one insertion of three amino acids in length, all of which significantly modify the immunodominant “supersite” binding as well as the neutralizing epitopes beyond it.

As it turned out, antibody binding to NTD was preserved with a relatively small decrease (1.9-fold at most), indicating either the maintenance of binding (e.g., with lower affinity) to the “supersite,” or the presence of a large number of unchanged epitopes in this domain.

• Activity of convalescent and vaccine serum against a B.1.1.529 variant SARS-CoV-2 isolate. medRxiv, December 21, 2021. [PDF]

 

December 20

Moderna has disclosed preliminary data regarding the efficacy of a third (booster) dose of the mRNA vaccine Spikevax (elasomeran; mRNA-1273) in the task of counteracting the Omicron (B.1.1.529) variant of SARS-CoV-2 coronavirus.

Administration of the booster at a dose of 50 mcg (this dose is officially approved by regulators) resulted (after 29 days) in a 37-fold increase in neutralizing antibody levels against Omicron compared to levels before its administration. A booster at a dose of 100 μg (the doubled dose is experimental) resulted in an 83-fold increase.

Nevertheless, even after the boosters, the level of neutralizing antibodies against Omicron was 2.9 and 3.0 times lower when compared with that after the boosters surrounded by the original coronavirus with the D614G mutation.

• The D614G mutation was previously one of the most common mutations in the world: as of mid-2020 (during the first wave of COVID-19), it was the dominant mutation in the coronavirus pandemic. One of the clinical features of D614G is loss of smell.

A doubled third dose of Spikevax was characterized by acceptable tolerability, although adverse reactions were more frequent than with the standard 50-μg dose.

Moderna is about to complete a clinical trial of the 100-μg booster and then send the collected data to regulators.

In parallel, Moderna is developing mRNA-1273.529, a variant of Spikevax, that takes into account Omicron mutation specificity; appropriate clinical trials will be launched in early 2022.

At the same time, Moderna is studying the possibility of incorporating Omicron mutations into an experimental program of multivalent boosters that take into account the mutational specificities of several coronavirus strains at once, including Delta (B.1.617.2) and Beta (B.1.351).

• Omicron booster strategy update. Moderna, December 20, 2021. [PDF]

 

December 19

Switzerland-based Molecular Partners reported that an experimental ensovibep (MP0420) being developed with Novartis for the treatment and prevention of COVID-19 infection remains fully functional in the presence of the Omicron (B.1.1.529) variant of SARS-CoV-2 coronavirus.

According to in vitro studies in a pseudoviral system mimicking the Omicron variant, ensovibep retained high neutralizing activity comparable to that against the original non-mutant SARS-CoV-2. Thus, while the half-maximal inhibitory concentration (IC₅₀) of ensovibep against the latter is 1.6 ng/ml, in the case of Omicron it only increases by a factor of 1.3–1.4 to 2.1–2.2 ng/ml.

The neutralizing activity of ensovibep against all other strains of coronavirus, including the variants of concern such as Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), and Delta (B.1.617.2), is very high: IC₅₀ falls within a narrow range of 1–8 ng/ml.

• Ensovibep, a novel trispecific DARPin candidate that protects against SARS-CoV-2 variants. bioRxiv, December 17, 2021. [PDF]

 

December 18

Sputnik V, virus vector vaccine for COVID-19, also known as Gam-COVID-Vac, induces a sustained neutralizing antibody response against the Omicron variant (B.1.1.529) of SARS-CoV-2 coronavirus.

It was announced by Russia’s Gamaleya Research Institute of Epidemiology and Microbiology whose specialists performed a preliminary analysis of the neutralizing activity of Sputnik V and found that it decreases by 11.8 times in the presence of Omicron.

The indicated reduction in the activity of Sputnik V is said to be substantially less than that demonstrated in the case of Comirnaty (tozinameran; BNT162b2) and Spikevax (elasomeran; mRNA-1273), mRNA vaccines for COVID-19 by Pfizer/BioNTech and Moderna, which showed 41- and 49–84-fold reductions, respectively.

• However, revised results for Comirnaty revealed a 21-fold decrease in neutralizing activity.

Moreover, the neutralizing activity of Sputnik V was tested on sera taken more than 6 months after vaccination, while the activity of Comirnaty and Spikevax was tested on sera taken a short period after vaccination, 12–27 and 28 days respectively.

In other words, it is claimed that Sputnik V provides long-term and reliable protection against Omicron.

Finally, the administration of a third (booster) dose of the vaccine, Sputnik Light, is expected to bring protection against Omicron to more than 80%. It is reported that after 2–3 months of administration of Sputnik Light, 100% of those vaccinated had antibodies against Omicron, while the third dose of Comirnaty provided antibodies only in 25% at 3 months after vaccination.

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December 17

A study conducted by Imperial College London has come to a conclusion that differs dramatically from the universally replicated one. The course of COVID-19 infection caused by the Omicron variant (B.1.1.529) of SARS-CoV-2 is said to be as severe as that of the Delta variant (B.1.617.2).

It is stated that no evidence has been found that COVID-19 due to Omicron is milder, as judged by the proportion of symptomatic patients and the proportion who sought hospitalization. Despite the still limited data set, the severity of COVID-19 in Omicron is only marginally different from Delta.

• Meanwhile, media outlets around the world have been circulating the idea that Omicron does not pose any threat: they say Omicron is easy and people recover very quickly.

The British experts’ statement may well be correct because even those vaccinated and previously infected with COVID-19 are known to be infected with Omicron much more frequently than during outbreaks caused by other variants of the coronavirus. If the degree of protective immunity against severe COVID-19 still remains at a high level in such patients, the pattern would be that infection with Omicron leads to a milder course of the disease. Conversely, in the case of the unvaccinated and those who have not yet had COVID-19, infection with Omicron may well be as dangerous as other variants of coronavirus.

Of the other findings of the London experts the following:

• the number of Omicron infections doubles every 2.5 days
• the risk of reinfection with Omicron versus Delta is increased by a factor of 5.41 (95% CI: 4.87–6.00), indicating a relatively low level of immunity remaining after earlier COVID-19
• the immunity developed in COVID-19 disease survivors protects by 19% against reinfection under Omicron conditions within 6 months, whereas prior to Omicron, post-COVID-19 immunity protected by 85%
• the Omicron reinfection rates are highest among 18- to 29-year-olds
• the efficacy of vaccines against Omicron was drastically reduced: protective efficacy after two doses of vaccines was 0%–20%, after three doses it was 55%–80%.

• Report 49: Growth, population distribution and immune escape of Omicron in England. Imperial College London, December 16, 2021. [PDF]
• Report 48: The value of vaccine booster doses to mitigate the global impact of the Omicron SARS-CoV-2 variant. Imperial College London, December 16, 2021. [PDF]

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According to a study by American and Hong Kong scientists, the Omicron variant (B.1.1.529) of SARS-CoV-2 coronavirus seriously suppresses the activity of neutralizing antibodies that are either produced by the body in response to vaccination, are ingested when monoclonal antibody therapeutic or preventative drugs are given, or are produced independently after having had COVID-19 disease. Omicron is a serious threat, raising the question of developing new vaccines and drugs that can deal with it.

First, the neutralizing activity of sera taken from unvaccinated and COVID-19 sufferers, tested in a pseudoviral system, was found to be 32 times reduced in the presence of the Omicron variant when compared to the antibody titer for the original non-mutant SARS-CoV-2 strain. At the same time, only 2 of its 10 samples had an antibody titer that exceeded the detection limit.

Second, the neutralizing activity of the vaccines fell sharply in the presence of Omicron, even if the serum samples were obtained from simultaneously vaccinated and transfected individuals. An additional (booster) dose of vaccine determined a rise in titers, but they were still decently low.

• The vaccines in question are the mRNA vaccines Comirnaty (tozinameran; BNT162b2) and Spikevax (elasomeran; mRNA-1273) by Pfizer/BioNTech and Moderna and the viral vector vaccines Vaxzevria/Covishield (AZD1222, ChAdOx1 nCoV-19, ChAdOx1-S) and Ad26. COV2.S by AstraZeneca and Janssen/Johnson & Johnson.

Third, monoclonal antibodies have shown, similar to vaccines, a decided lack of neutralizing activity against Omicron. And only a few have confirmed their ability to fight Omicron — at least their activity has not decreased so much as to speak boldly about the disappearance of efficacy. By the way, the researchers cite data on the change in neutralizing activity according to the presence of each of the three dozen mutations in the Omicron’s S protein.

• Among the monoclonal antibodies working against Omicron are Xevudy (sotrovimab, VIR-7831, GSK4182136), romlusevimab (BRII-198) and Evusheld (AZD7442) as a combination of tixagevimab (AZD8895) and cilgavimab (AZD1061) developed by GlaxoSmithKline/Vir Biotechnology, China’s Brii Biosciences, and AstraZeneca, respectively.

• Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2. bioRxiv, December 15, 2021. [PDF]

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December 16

New coronaviruses will continue to infect bats and other animal reservoirs and potentially represent a pandemic threat to humanity. To counter future outbreaks of coronavirus infections, the global scientific and medical research community must focus its efforts on three goals. First, to characterize the range of genetic diversity of coronaviruses in different animal species. Second, to understand the pathogenesis of coronavirus infections. Third, to apply the accumulated knowledge to develop universal coronavirus vaccines.

Universal vaccines that work against all coronaviruses should be ideal.

Leading experts from the National Institute of Allergy and Infectious Diseases (NIAID), part of the U.S. National Institutes of Health (NIH), David Morens, Jeffery Taubenberger, and Anthony Fauci, have urged the global biotechnology industry to develop universal coronavirus vaccines.

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Evusheld (AZD7442), an AstraZeneca drug that is a combination of tixagevimab (AZD8895) and cilgavimab (AZD1061) monoclonal antibodies, retains neutralizing activity against the Omicron variant (B.1.1.529) of SARS-CoV-2 coronavirus, according to an FDA study.

The half-maximal inhibitory concentration (IC₅₀), as an indicator of the neutralizing ability of the antibody, for Evusheld under the Omicron conditions decreased dramatically but still fell within the range of 171–277 μg/mL, which is in between neutralizing titers in people previously infected with the coronavirus. By comparison, the IC₅₀ of Evusheld in the original non-mutant SARS-CoV-2 is 1.3–1.5 μg/mL.

Evusheld is approved by FDA for use in pre-exposure COVID-19 prophylaxis in individuals who, for health reasons or immune status, cannot mount an adequate immune response after vaccination against SARS-CoV-2. Evusheld protects against the development of COVID-19 for six months or longer.

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Regeneron Pharmaceuticals reported that its REGEN-COV/Ronapreve (casirivimab + imdevimab) is active against all known SARS-CoV-2 variants of concern, including Omicron (B.1.1.529) and Delta (B.1.617.2). However, casirivimab and imdevimab are less active against Omicron than Delta.

Regeneron is said to have several experimental monoclonal antibodies against SARS-CoV-2 in its hands that neutralize Omicron and Delta. Their clinical trials are scheduled for 2022.

The REGEN-COV/Ronapreve monoclonal cocktail is now being used to treat mild-to-moderate COVID-19 in high-risk patients at danger of hospitalization or death, as well as for post-exposure prophylaxis of COVID-19 in individuals at risk for severe disease.

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Specialists at the Li Ka Shing Faculty of Medicine of the University of Hong Kong (HKUMed) have figured out the specifics of how the Omicron variant (B.1.1.529) of SARS-CoV-2 coronavirus infects human respiratory tracts.

Thus, Omicron infects the bronchi and replicates in them 70 times faster than the Delta variant (B.1.617.2) and the original non-mutant coronavirus do. This fact likely explains why Omicron is transmitted faster from the infected to the healthy.

Omicron replicates 10-fold slower in the lungs compared to the original SASR-CoV-2, and therefore COVID-19 disease is probably milder.

It should be understood, however, that Omicron, while highly contagious, infects many more people and therefore statistically can cause more severe illness and death, even if it is less pathogenic. Given that Omicron, which has an abundance of mutations, is able to evade vaccines and the immunity acquired after suffering COVID-19, the degree to which Omicron threatens humanity is quite significant.

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According to the U.S. study, Moderna’s Spikevax (elasomeran; mRNA-1273) mRNA vaccine showed a 49–84-fold decrease in neutralizing activity against the Omicron variant (B.1.1.529) of SARS-CoV-2 coronavirus based on serum samples taken 4 weeks after receiving it in two doses.

The addition of a third (booster) dose of Spikevax increased neutralizing antibody titers, thereby reducing the risk of symptomatic breakthrough COVID-19 infection. However, vaccine activity was still reduced 4.2–6.5-fold.

• Booster of mRNA-1273 vaccine reduces SARS-CoV-2 omicron escape from neutralizing antibodies. medRxiv, December 15, 2021. [PDF]

 

December 15

Experts from Humabs BioMed, a Swiss company owned by Vir Biotechnology, analyzed many vaccines and monoclonal antibodies approved by regulators in terms of their ability to fight the Omicron variant (B.1.1.529) of SARS-CoV-2 coronavirus. The efficacy of the vaccines and monoclonal antibodies has been found to drop dramatically in the presence of Omicron. Experts recommend a third (booster) dose of vaccine as a matter of urgency to do something about the situation.

The neutralizing anti-Omicron activity of the following vaccines and monoclonal antibodies was analyzed:

• mRNA vaccine Spikevax (elasomeran; mRNA-1273) by Moderna
• mRNA vaccine Comirnaty (tozinameran; BNT162b2) by Pfizer and BioNTech
• viral vector vaccine Vaxzevria/Covishield (AZD1222, ChAdOx1 nCoV-19, ChAdOx1-S) by AstraZeneca
• viral vector vaccine Ad26.COV2.S by Janssen, part of Johnson & Johnson
• viral vector vaccine Sputnik V (Gam-COVID-Vac) by Russia’s Gamaleya Research Institute of Epidemiology and Microbiology
• inactivated whole-virion vaccine BBIBP-CorV [SARS-CoV-2 Vaccine (Vero Cell), Hayat-Vax] by China’s Sinopharm, also known as the China National Pharmaceutical Group
• monoclonal antibodies bamlanivimab (LY-CoV555) and etesevimab (LY-CoV016) by Eli Lilly, Canada’s AbCellera Biologics, and China’s Shanghai Junshi Biosciences
• monoclonal antibodies casirivimab (REGN-10933) and imdevimab (REGN-10987) — REGEN-COV/Ronapreve by Regeneron Pharmaceuticals
• monoclonal antibodies tixagevimab (AZD8895) and cilgavimab (AZD1061) — Evusheld (AZD7442) by AstraZeneca
• monoclonal antibody regdanvimab — Regkirona by Korea’s Celltrion
• monoclonal antibody sotrovimab (VIR-7831, GSK4182136) — Xevudy by GlaxoSmithKline and Vir Biotechnology.

An in vitro test in a pseudovirus system revealed that a full course of vaccination (two doses each; in the case of Ad26.COV2.S one dose) with Ad26.COV2.S, Sputnik V, or BBIBP-CorV would not protect against the Omicron infection. The titer of neutralizing antibodies produced by the body in response to administration of these vaccines was too low compared to the original non-mutant SARS-CoV-2 to reliably control Omicron. In other words, Ad26.COV2.S, Sputnik V, and BBIBP-CorV vaccines are ineffective against Omicron — in any case without a booster dose.

The Gamaleya Research Institute of Epidemiology and Microbiology in response to the results stated the following:

A recently published small study addresses Sputnik vaccine’s efficacy against Omicron variant deliberately using serum samples that are not representative. For example, this study used Sputnik samples with a lower virus neutralization ability against SARS-COV-2 than AstraZeneca’s vaccine while a much larger study in Argentina based on representative serum samples demonstrated 1.8 times higher virus neutralizing titers against SARS-COV-2 for Sputnik, which is explained by its heterologous boosting advantage. Therefore, conclusions about Sputnik efficacy against Omicron based on wrong serum samples, cannot be made. Within the next 7 days the Gamaleya Center will publish its own positive data based on representative serum samples on Omicron neutralization ability for both Sputnik V vaccine and one-shot Sputnik Light as a booster.

Vaccination with two doses of Spikevax, Comirnaty, or Vaxzevria/Covishield provided antibody activity against Omicron, although the neutralizing antibody titer decreased by a factor of 33, 44, and 36, respectively. Remarkably, the decrease was less pronounced (5-fold) in Comirnaty vaccinated individuals who had been previously infected, indicating an extended antigenic response due to maturation of affinity due to multiple antigenic stimulations.

The neutralizing activity of most monoclonal antibodies proved insufficient to counteract Omicron. Simply put, they are useless against Omicron. Only sotrovimab, Evusheld (tixagevimab + cilgavimab), and the experimental VIR-7832 (GSK4182137) by Vir worked against Omicron.

• Broadly neutralizing antibodies overcome SARS-CoV-2 Omicron antigenic shift. bioRxiv, December 14, 2021. [PDF]

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German scientists analyzed the neutralizing activity of a number of monoclonal antibodies, both commercially available and still experimental, assessing their ability to cope with the Omicron variant (B.1.1.529) of SARS-CoV-2 coronavirus.

The monoclonal antibodies in question are the following:

• bamlanivimab (LY-CoV555) and etesevimab (LY-CoV016) by Eli Lilly, Canada’s AbCellera Biologics, and China’s Shanghai Junshi Biosciences
• casirivimab (REGN-10933) and imdevimab (REGN-10987) — REGEN-COV/Ronapreve by Regeneron Pharmaceuticals
• sotrovimab (VIR-7831, GSK4182136) — Xevudy by GlaxoSmithKline and Vir Biotechnology
• P2B-2F6, Fab2-36, and C102 are being studied in academia [1] [2] [3] [4]
• BI 767551 (DZIF-10c) by Boehringer Ingelheim (development stopped in summer 2021 due to strong market competition).

A study of the Omicron variant in pseudovirus neutralization assays found that in vitro the monoclonal antibodies indicated were very poor at suppressing it. Thus, starting from a half-maximal inhibitory concentration (IC₅₀) exceeding 10 µg/ml, we can safely declare a failure against Omicron. Here too, only sotrovimab and BI 767551 emerged victorious, convincingly defeating Omicron as well as Alpha (B.1.1.7), Beta (B.1.351), and Delta (B.1.617.2) variants.

As shown, bamlanivimab, etesevimab, casirivimab, and imdevimab, actively promoted for the treatment of mild-to-moderate COVID-19 among high-risk patients, could not deal with Omicron.

• mRNA booster immunization elicits potent neutralizing serum activity against the SARS-CoV-2 Omicron variant. medRxiv, December 14, 2021. [PDF]

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Adagio Therapeutics reported that experimental monoclonal antibody ADG20 did not work against the Omicron variant. When this drug candidate was tested in vitro on the coronavirus itself and in a pseudovirus system, ADG20’s neutralizing activity against Omicron dropped by more than 300 times. Adagio believes the failure is due to an abundance of mutations in the Omicron’s S protein, a combination of which helps the variant evade ADG20. ADG10, another experimental monoclonal antibody, also failed at suppressing Omicron. The disappointing news collapsed Adagio’s stock price by 75%.

ADG20 was considered a very promising drug for therapy and prophylaxis of any variant of coronavirus, current and upcoming, because, unlike other monoclonal antibodies against SARS-CoV-2, it targets an epitope of the virus that is highly conserved, immunoreactive, and not an easy target for the endogenous neutralizing antibody response.

 

December 14

Discovery Health, the largest private health insurance provider in the Republic of South Africa (RSA), has shared the results of a large-scale analysis of the outbreak of the Omicron variant (B.1.1.529) of SARS-CoV-2 coronavirus based on data from over 211 000 tests. The conclusions, based on real data rather than theoretical or laboratory ones, are as follows.

Omicron is now the dominant variant in South Africa, accounting for 90% of new coronavirus cases, with an exponential increase in infections.

The Omicron outbreak is characterized by a higher number of reinfections and breakthrough infections than other coronavirus variants, including among vaccinated individuals.

Clinical features of Omicron in adults include a shortened incubation period of up to three to four days; a generally mild course of illness with recovery within three days; scratchy and/or sore throat is the most common early symptom (as with other SARS-CoV-2 variants, however); and nasal congestion, dry cough, and myalgia (especially low back pain) among others symptoms of Omicron.

In adults hospitalized with Omicron, there is a reduced incidence of acute respiratory distress syndrome (ARDS); a reduced rate of ICU admission; and a reduced proportion of patients requiring oxygen support, which, if needed, is provided in most cases to the unvaccinated.

Clinical features of Omicron in children and adolescents, which, incidentally, is diagnosed more frequently than in coronavirus waves of other variants, include mostly mild course of illness with recovery within three days; symptoms of Omicron include sore throat, nasal congestion, headache, and fever for two to three days.

Children and adolescents are hospitalized with Omicron complications such as bronchiolitis and pneumonia; diarrhea, vomiting, and dehydration are common.

Two doses of mRNA vaccine Comirnaty (tozinameran; BNT162b2) by Pfizer and BioNTech provided 70% protection (compared with unvaccinated individuals) against development of Omicron-induced COVID-19 infection that was severe or critical and required hospitalization, and 33% against development of symptomatic COVID-19.

• Against the Delta variant (B.1.617.2), Comirnaty protected better: at 93% and 80%, respectively.

There was a correlation between age and the level of vaccine protection of Comirnaty against Omicron, infection with which led to hospitalization. Thus, the effectiveness of Comirnaty generally fell as a function of age: 82% for ages 40–49 years, 74% for ages 50–59 years, 67% for ages 60–69 years, and 59% for ages 70–79 years.

In the presence of comorbidities contributing to an increased risk of hospitalization due to COVID-19, Comirnaty in the Omicron setting provided the following level of protection: 68% for diabetes mellitus, 69% for hypertension, 63% for hypercholesterolemia, and 64% for coronary heart disease.

For people who have already been infected with COVID-19, the risk of reinfection with Omicron is significantly higher when compared to other variants of the coronavirus. Thus, among those previously infected with the Delta variant, the risk of reinfection with Omicron increased by 40%, with the Beta variant (B.1.351) by 60%, and with the original coronavirus with the D614G mutation by 73%.

• The D614G mutation was previously one of the most common mutations in the world: as of mid-2020 (during the first COVID-19 wave), it was the dominant mutation in the coronavirus pandemic. One of the clinical features of D614G is loss of smell.

Omicron-infected adult patients have a 29% lower risk of hospitalization when compared to infection with the original coronavirus with the D614G mutation.

Despite the very low absolute incidence of COVID-19 disease in children and adolescents, preliminary data suggest that those under 18 years of age infected with Omicron have a 20% higher risk of hospitalization when compared with infection with the D614G mutant original coronavirus. At the same time, the maximum risk of hospitalization due to Omicron was recorded for children under 5 years of age.

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It should be understood that the conclusions are based on data from the first three weeks of the Omicron outbreak, and therefore are preliminary and may change in the future. The conclusions may have been affected by biases associated with the high prevalence of antibodies against SARS-CoV-2 in the general South African population.

A study conducted by experts at the Li Ka Shing Faculty of Medicine of the University of Hong Kong (HKUMed) found that the Omicron variant (B.1.1.529) of SARS-CoV-2 coronavirus escapes the neutralizing antibodies produced by the organism after vaccination, and therefore the effectiveness of existing vaccines drops dramatically.

Geometric mean titer (GMT) of neutralizing antibodies in serum samples taken from those vaccinated with two doses of mRNA vaccine Comirnaty (tozinameran; BNT162b2) by Pfizer and BioNTech, was 39.9 and 35.7 times lower in Vero E6 cell culture of Omicron isolates HKU691 and HKU344-R346K when compared with titers in the culture of the original non-mutant coronavirus. At the same time, the seropositive rate (the frequency with which antibodies occur) against these Omicron isolates was only 20% and 24%. The GMT against Beta (B.1.351) and Delta (B.1.617.2) variants decreased 8.9- and 1.8-fold, but the seropositive rate remained 100%.

• Omicron isolates HKU691 and HKU344-R346K differ in two nucleotides: HKU344-R346K contains the nonsynonymous G22599A mutation leading to the R346K mutation in S protein; it was found in 8.5% of sequenced Omicron genomes in the GISAID database as of December 10, 2021. The R346K mutation is of particular concern because it affects receptor-binding domain (RBD), which was once reflected in reduced vaccine efficacy against the Mu variant, which also carries this mutation.

The GMT of neutralizing antibodies in serum samples taken from two doses of inactivated whole-virion vaccine CoronaVac developed by China’s Sinovac Biotech, which is considered to be the most popular in the world, was 4.3 times lower in Vero E6 cell culture of HKU691 and 157 HKU344-R346K Omicron isolates and 4.4 and 2.1 times lower in the culture of Beta and Delta variants when compared with the titer in the culture of the original non-mutant coronavirus. The seropositive rate was zero for Omicron and Beta variants and 68% for Delta variant.

To summarize, the efficacy of Comirnaty vaccine against Omicron decreased dramatically, but was maintained against Delta and Beta. The CoronaVac vaccine against Omicron and Beta did not work at all and was characterized by reduced efficacy against Delta.

• Neutralization of SARS-CoV-2 Omicron variant by sera from BNT162b2 or Coronavac vaccine recipients. medRxiv, December 14, 2021. [PDF]

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The National Health Security Agency (HSA) of the United Kingdom has conducted a more thorough analysis of vaccines for COVID-19 in terms of their protective effectiveness against the development of symptomatic COVID-19 infection caused by the Omicron (B.1.1.529) and Delta (B.1.617.2) variants strains of SARS-CoV-2 coronavirus.

Two vaccine products were studied: the mRNA vaccine Comirnaty (tozinameran; BNT162b2) by Pfizer and BioNTech and the viral vector vaccine Vaxzevria/Covishield (AZD1222, ChAdOx1 nCoV-19, ChAdOx1-S) by AstraZeneca. One group of people received the full course of two doses of Comirnaty, the second group received two doses of Vaxzevria/Covishield. Everyone then received a third (booster) dose of Comirnaty.

Two doses of Comirnaty were found to be significantly more effective in protecting against Omicron and Delta when compared to the two doses of Vaxzevria/Covishield. However, this is still not enough — the level of protection decreases seriously over time. The third dose of Comirnaty raises the level of protection dramatically. However, we don’t know yet how long it will last.

Thus, 25 weeks or more after receiving two doses of Comirnaty, the level of vaccine protection against Omicron was 34.2% (95% CI: −5.0 to 58.7), and against Delta was 63.5% (95% CI: 61.4 to 65.5). After two doses of Vaxzevria/Covishield, 5.9% (95% CI: −29.7 to 31.7) and 41.8% (95% CI: 39.4 to 44.1), respectively.

After receiving a booster dose of Comirnaty, effectiveness against Omicron and Delta after 2 weeks or more in the group initially vaccinated with Comirnaty increased to 75.5% (95% CI: 56.1 to 86.3) and 92.6% (95% CI: 92.0 to 93.1), respectively, whereas it increased to 71.4% (95% CI: 41.8-86.0) and 93.8% (95% CI: 93.2-94.3) in the group initially vaccinated with Vaxzevria/Covishield.

As we can see, even a third dose of the vaccine does not protect against Omicron at the same level as Delta. At any rate, this is true for protection against mild-to-moderate COVID-19 infection that does not require hospitalization. When it comes to protection against severe or critical COVID-19 leading to hospitalization or death, we would expect the third dose to raise its level even higher. This follows from the observations noted with previous variants of coronavirus. [1] [2]

• Effectiveness of COVID-19 vaccines against the Omicron (B.1.1.529) variant of concern. Preprint. [PDF]

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December 13

Boris Johnson, the Prime Minister of Great Britain, has reported the death of a patient from the Omicron variant (B.1.1.529) of SARS-CoV-2 coronavirus. This is the first officially reported death worldwide due to Omicron.

Omicron is so transmissible that the number of cases of this variant doubles every two to three days.