Emerging treatments for COVID-19 should lessen the impact of Omicron

Public health officials have raised alarms over a new surge in COVID-19 cases, fueled by the Omicron variant. The reaction has spurred school closures and the reintroduction of mask mandates before the Christmas holiday.

Where the numbers go over the next two weeks will tell us a lot about whether Omicron is a true threat. In particular, updated hospitalization and death counts after the Christmas holiday will indicate whether this winter will be as bad—or worse—than last winter.

The CDC has determined that Omicron is now the dominant variant in the U.S. as of Dec. 25, accounting for nearly 59% of cases sequenced. Just 3 weeks prior, Omicron represented 0.6% of sequenced cases. It is particularly dominant in the mid-Atlantic states of New York and New Jersey (88.4% of sequenced cases), the Southeast (78.3%), Texas and surrounding states (86.7%), and the Pacific Northwest (74.8%).

Cases across the U.S. are increasing rapidly and have surpassed the peak level of cases during the Delta wave. Hospitalizations have increased as well, and the fall in deaths experienced as the Delta wave waned has ceased.

But these statistics need context. In particular, we should look at the gap between hospitalizations and deaths when getting a sense of a variant's severity.

Last winter's Alpha wave was particularly tragic because, in the absence of widespread vaccine availability, a high proportion of hospitalizations ended in death. While the Delta wave was also severe, hospitalizations were less frequent, and a smaller proportion of the hospitalized succumbed to the virus – in no small part due to COVID vaccines. As vaccination rates continued to increase, boosters were made available, and more people obtained immunity through natural infection, the Omicron wave is taking this pattern further; while hospitalizations have increased again since mid-November, deaths have not increased at a commensurate rate, remaining essentially flat. This could change since death reports lag by a couple weeks, but at this point, each wave appears less severe as the one before it.

The following chart illustrates this phenomenon.

The gap between hospitalizations and deaths has widened during each successive wave since last winter. This trend suggests that the percentage of hospitalized patients dying from the virus has declined. A number of factors could be responsible, including increased population immunity through vaccinations and natural infection, improved treatment protocols, winter weather, and natural evolution of the virus. While it is too early to make definitive conclusions, the data suggests the Omicron wave results in milder infection, resulting in higher survival rates among the hospitalized.

The trajectory of Omicron has sparked a debate about whether the variant represents an evolutionary change of SARS-CoV-2 into a more transmissible but less virulent (deadly) form. Early observational results are promising from South Africa -- where Omicron was first discovered -- suggesting both the chances of hospitalization as well as the severity of a hospitalization stay is lower than the Delta variant.

Despite these results, no one knows yet whether the virus is naturally evolving to become less severe. A recent study suggests that Omicron infects the upper airways at a much greater rate, but largely spares deeper lung tissue that is often implicated in severe disease. However, it should be noted that COVID's severity is also dependent on how the immune system responds to infection (i.e., cytokine storm), which was not considered in the study. And while it is suspected that a few of today's circulating coronaviruses that cause the common cold were once deadlier versions of themselves hundreds of years ago, other viruses such as ebola and measles are no less deadly or debilitating to unvaccinated and untreated individuals than they were in the past. Society therefore cannot rely on the virus evolving into a less dangerous form.

Instead, the events of the last 21 months have taught us that society can rely on advancements in science and technology to tame the virus. The vaccines have had a major effect at decreasing severe outcomes from the disease, and the mRNA platform used by the Pfizer/BioNTech and Moderna vaccines can be tailored for future variants.

Up to this point, therapeutics have been overlooked as well. This week, the FDA granted emergency use authorization to Pfizer's Paxlovid and Merck's molnupiravir to treat COVID-19 in individuals who have tested positive and are at high risk for severe disease. Paxlovid is approved for those age 12 and older while molnupiravir is approved for those 18 and older.

Of the two drugs, Paxlovid appears to be safer and more effective. Paxlovid reduced the risk of COVID-19 hospitalization or death by 89% in clinical trials, a figure that remained consistent with preliminary results released in November. In contrast, Merck's initial report of nearly 50% relative risk reduction in hospitalization or death was revised to just 30% when additional data was released. In addition, molnupiravir's mechanism of action has some scientists concerned that Merck's treatment will have unintended mutagenic effects, including the development of cancer and birth defects.

As the first official FDA-approved COVID treatment in pill form, Paxlovid will spare hospital resources and staff by allowing people to take the treatment course at home. Importantly, the drug is likely to remain effective because it targets protease enzymes for destruction, which are essential for the virus' replication and remains highly conserved (unchanged) from one variant to the next.

Preliminary evidence leans toward a less deadly variant in Omicron. Regardless, it is pharmaceutical advancement that will allow the human race to truly reduce COVID-19's severity. Policymakers should focus their energy on reducing regulatory and supply barriers to get the most promising treatments to market as quickly as possible.