Omicron variant: Act fast. Sequence everything. Vaccinate the world.

Time will tell whether the B.1.1.529 COVID-19 variant of concern (AKA: Omicron variant) is a more severe, highly transmissible, breakthrough-infection-causing version of COVID-19. For now, South African scientists, clinicians, and the worldwide research community have given us a gift: the ability to be proactive in how we manage the spread of this variant and learn from it.

We learned a lot from the Delta variant, but unfortunately so, at the expense of significant worldwide morbidity and mortality. This time we have the opportunity to do things differently. We can: act fast, sequence everything, and vaccinate the world. In doing so, we will hopefully curtail the Omicron threat, and potentially limit the development of other viral variants.

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1. Act fast. There are three main sets of questions (Exhibit 1) that need to be answered on Omicron (and any other upcoming variant). Until those questions are answered in population-wide studies, it’s prudent to already assume that this variant is dangerous. If we’re right, then we’ve used the lead time we have to prevent disaster. If we’re wrong and the variant is mild or easily contained through vaccination, then acting fast will have helped us learn quickly and ease any restrictions accordingly. (The sociologist Zeynep Tufekci covers this well in her Sunday NYT Op-ed).

Exhibit 1: Key questions on the new Omicron variant.

What does “acting fast” entail? Pursuing all the best practices we should have pursued since the beginning of the pandemic:

• Flatten the curve by following WHO/CDC best practices around hygiene, mask utilization, social distancing, better ventilation, and by vaccinating. This is something we can all act upon in our homes and our communities. We can be stewards of our health and others’. (I’m skeptical of the travel restrictions imposed on certain countries, as those restrictions are being implemented unevenly, and potentially in a discriminatory way).
• Collect (and connect!) data early and often. This includes sequencing data (more on that below), but also clinical outcome cases to determine disease severity, population data to determine transmissibility, and linkage to prior vaccination data to determine breakthrough infection potential. As my colleagues and others have discussed before, this is not an easy task. Fragmentation issues in how data are collected today will continue to be a challenge as we attempt to learn about the biology and clinical outcome of disease in as near-real-time as possible. The benefits of expanded COVID-19 surveillance in the US are nicely covered here.
• Share data and insights ASAP. While we should pay close attention to data quality and very strictly evaluate the insights we get from data, time is still our best weapon. Data should be shared with the world as soon as we have reliable insights. Data sharing and visibility impacts population health responses, but also world economics. The WHO recommends data is shared through the WHO global clinical platform for COVID-19 and generally, it’s been encouraging to see scientists collaborate across the world on the biology and epidemiology of this new variant. The researchers who first shared sequence data on this variant gave us the gift of time, because they collected and shared those data in record time.

2. Sequence everything. We must not squander that gift of time. I was struck by this tweet by Dr. Ingrid Katz at Harvard. “We know what we know BECAUSE South Africa invested in genetic sequencing. We owe them a debt of gratitude — not punishment.” Because of those COVID-19 genomic sequences, we now know that this variant has 50+ mutations, many of which affect the COVID-19 Spike protein, the target of most vaccines available today (Exhibit 2). We are starting to get early answers on whether the immune response generated upon vaccination with our currently authorized vaccines is sufficient to detect this transformed version of the virus. For more information, this Nature article covers the sequencing timeline, from the first identified case in Botswana to the increased incidence of infection back in South Africa, where most infections to date of this publication have been sequenced.

We should commend and encourage sequencing and tracking of these variants, and do it more consistently. The United States has been notoriously behind on sequencing implementation, and this was a significant problem during the Delta wave. To answer the question on how transmissible the Omicron variant is, we need to sequence, not guess. If our sequencing efforts in the US are at the level of Delta earlier this year, we will have huge gaps in our understanding of variant spread and vaccine efficacy against the new variant. Sequencing as a default also helps us catch the next mutated version (and helps all vaccine manufacturers do early tests for vaccine efficacy against new variants).

Sequencing information is at the top of the funnel of data needed to answer the questions on Exhibit 1 around transmissibility, severity, and immune resistance. Once we have that information, we can then connect that data to other healthcare information about the patients infected, both retrospectively and prospectively. Retrospectively, it would be insightful to know whether patients were vaccinated, whether they received a booster, what pre-existing medical conditions those patients have, etc. Prospectively, determining disease severity (e.g., hospitalization needs) and segmenting by mutation status will help us better understand whether the Omicron variant is more or less dangerous.

The good news: Given what we know about the Omicron mutations, we could probably do sequencing a lot more efficiently at scale. To quote the Nature article summarizing a statement by Dr. Richard Lessells, an Infectious Diseases Specialist at the University of KwaZulu-Natal in Durban, South Africa: “The variant harbours a spike mutation that allows it to be detected by genotyping tests that deliver results much more rapidly than genome sequencing does”. Genotyping tests (in this case, sequencing for a unique single mutation in Omicron, with well-defined primers) are much faster and easier to perform than whole-genome sequencing, which can be expensive and cumbersome, even for an organism as small as COVID-19. In fact, most researchers around the world who work with animal models perform genotyping experiments daily! That said, the operational intricacies of generating genomic data at scale, even when looking at a single mutation, are not negligible. In the US, funding and coordination roadblocks have been well-covered, including here and here.

But this is doable. So, let’s do it.

Exhibit 2: Omicron mutational burden. Source: Coronavirus antiviral and resistance database, Stanford University.

3. Vaccinate the world. How did we get a variant with so many mutations? One hypothesis (yet to be validated at scale, or for Omicron) is that prolonged replication in immunocompromised patients could lead to increased mutational burden to attempt immune escape (see an article from earlier this year researching this). The more we let the virus spread among hosts, the more likely it will be for prolonged replication to happen. Thus, one of the solutions to our current problem is, and will continue to be, vaccinations.

It is a privilege to be eligible for my vaccine booster dose this week (and if you’re in the US and eligible, I hope you’re getting your vaccination courses ASAP!) However, I keep thinking about the map of vaccinations across the world. The global vaccination rate (and in particular, in the continent of Africa) is still dismally low. The more a virus has a chance to spread, the more it has a chance to mutate and create immune-escape variants. In the NYT opinion article mentioned earlier, Dr. Tufekci theorizes that “It’s possible Omicron developed through a persistent infection in an immunocompromised patient, such as someone who may not have been treated properly to control an H.I.V. infection” to call for holistic financial support for countries like South Africa. If that hypothesis is scientifically validated (but even if it’s not the case) increased vaccination rates will only help protect us all, and especially the most vulnerable patient populations. While I’m glad I’m getting my booster shot, I wish we had a better answer on global health priorities around vaccine equity. This Science editorial makes a compelling and passionate plea to “vax the world” and is a highly recommended read.

Hopefully, we are fortunate and current vaccines produce sufficient protection around the Omicron variant. The faster we vaccinate the world, the more manageable any escape variants will be. Conversely, the more we allow for humanity to be an experimental petri dish for COVID-19 evolution, the more overwhelmed our scientific and clinical colleagues will be. Vaccinating the world is, and will continue to be, one of the best levers we can pull in support of global public health. In a few years, when we (hopefully) write the global retrospective on the pandemic, I wish we can say we made the right scientific, supply chain, financial, and policy decisions to help vaccinate the world as soon as possible.

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I am a huge believer in learning from real-world data. I hope this time around data gets generated, shared, and analyzed in a responsible way, in as near-real time as possible. If we act fast, this article could become irrelevant in 1–2 months because the Omicron variant fizzled out, and nothing would make me happier.

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Note 1: I am employed by Datavant, however thoughts here are my own and do not necessarily represent the views of my employer.

Note 2: If you’re excited about contributing to scientific and health economics research based on connected health data, please consider checking out the COVID-19 Research Database and submitting a research proposal: https://covid19researchdatabase.org/

Thanks to Elenee Argentinis, Claire Cravero, and Devin Gilliam for feedback on this article.