Riding the Waves of the COVID-19 Pandemic

“Waves are now so frequent that they’re colliding and uplifting like tectonic plates, the valleys between them filling with virological rubble.”

- Katherine J. Wu, staff writer for The Atlantic

“There are more copies of the virus because BA.5 has far better ability to get into cells . . . which may help explain why this version of the virus has caused a lot of trouble, more than other Omicron subvariants.”

- Eric Topel, M.D., American scientist, founder and director, Scripps Translational Research Institute

As we are all aware, the SARS-Co-V-2 virus that causes COVID-19 continues to mutate. There are now thousands of mutations of this virus. This is not a surprise. From the onset of the pandemic in December 2019, scientists anticipated that these mutations would occur and that we would need to modify our strategies to fight the virus in light of the mutations.

A large majority of these SARS-CoV-2 mutants aren’t any more problematic than the original “wildtype” or “ancestral” virus that triggered the COVID-19 pandemic. Variants of Concern and their subvariants, however, do cause big problems. Such variants have popped up at a dizzying pace causing new waves of the pandemic and, in turn, requiring that we modify our approach to battling this virus. In this Germ Gems post, I provide an update on the latest versions of SARS-CoV-2 virus and discuss the impact of these viral mutants on recommendations regarding vaccines and treatment for COVID-19.

What SARS-CoV-2 mutants are of most concern? The World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) adopted a classification system of SARS-CoV-2 genetic mutants called “variants” that convey three levels of associated risk: “variant of interest” (VOI), “variant of concern” (VOC), and “variant of high consequence” (VHC). (Fortunately, no VHC has yet debuted.) The WHO and the CDC along with many other research institutions closely track certain VOIs and VOCs because these mutations are more contagious, more virulent (make people sicker), or have the ability to evade immunity conferred by vaccines.

We are all now familiar with the fact that the SARS-CoV-2 classification system is based on letters of the Greek alphabet. Since the system was implemented, the world has witnessed multiple “waves” or “surges” of COVID-19 cases caused by VOCs labeled “Alpha,” “Beta,” “Gamma,” “Delta,” and beginning in late 2021, “Omicron.” At this time, the WHO is only tracking one VOC (Omicron) and its subvariants, also referred to as lineages: B.1.1.529, BA.1, BA.1.1, BA.2, BA.3, BA.4, BA.5, and BA.2.75 that recently emerged in India. The WHO has downgraded all other VOCs, from Alpha up to Omicron (the 14th letter in the Greek alphabet) to the status of “variants being monitored” (VBM). (For a more detailed accounting of the genetics and evolution of SARS-CoV-2 variants and subvariants [lineages], see the April 26, 2022 CDC website article, “SARS-CoV-2 Variant Classifications and Definitions.”)

What’s the big deal about Omicron BA.4 and BA.5? The Omicron subvariants BA.4 and BA.5 are especially contagious. You may recall that last summer we were battling the “Delta wave.” Well, this summer we’re riding the “Omicron wave,” led by the subvariants BA.4 and BA.5. According to the CDC, as of the end of this June, BA.4 and BA.5 became the dominant SARS-CoV-2 strains in the U.S.

Articles in the New York Times on July 7, “What the BA.5 Subvariant Could Mean for the United States,” and in The Atlantic on July 11, “Is BA.5 the Reinfection Wave?,” underscore the ability of this subvariant to cause reinfection in those naturally infected by other viral strains or in people who have been vaccinated. Evidence is mounting that these subvariants are not only more contagious but possibly more virulent (numbers of hospitalizations and deaths are trending up in some areas experiencing a COVID-19 surge).

On July 12, the WHO also sounded the alarm regarding BA.4 and BA.5 declaring that Europe is at the center of a new wave of cases driven by people attending large gatherings and resuming travel after two years of staying close to home.

The data are mixed on whether BA.4 and BA.5 can evade monoclonal antibodies. It appears, however, that the long-acting antibody combination, Evusheld, retains its neutralizing capacity. While some studies suggest that BA.4 and BA.5 are more evasive of antibodies, there’s also evidence that cellular immunity against these strains is holding up. This is probably due to the fact that T-cell immunity from the vaccines protects across variants from Alpha to Omicron. Cellular immunity in the U.S. is growing and results from both vaccination (78% of the total American population have received at least one dose of a COVID-19 vaccine) and natural infection.

In the face of new waves of SARS-CoV-2 infections, what should everyone do? On July 12, 2022, the New York Timesreported that despite the accelerating number of SARS-CoV-2 cases sparked by the BA.4 or BA.5 subvariants, most New York city residents were ignoring the surge or, at most, paying it little attention. New Yorkers, like the rest of us, are sick and tired of hearing about this infection; we have “COVID-19 fatigue.” But we cannot relax or let our guard down. We must prepare ourselves for the possibility that the Omicron subvariant BA.2.75 that emerged in India in early June will take off in the U.S. (Two cases due to this subvariant, dubbed “Centaurus,” were identified in the U.S. in early July). So, what can one do?

If you live in a state or area that is seeing a surge of COVID-19 cases, it is a good time to revisit the practices of social distancing when in group settings as well as wearing a properly fitted face mask when indoors. (More than 1 in 2 Americans live in an area where the CDC now recommends indoor masking to curb COVID-19 surges.)

But of utmost importance, review your vaccination status to ensure that you are properly immunized. The CDC urges all adults 50 and older to get a second booster shot. Recently, the White House also promoted boosters to protect against the BA.5 subvariant.

Part of the the failure of many Americans to get themselves and their children properly immunized against SARS-CoV-2 is that the decision is complicated (considerations that need to be factored in are age, immunodeficiency, and vaccine efficacy and safety). For help with these considerations, I highly recommend you turn to your healthcare provider. I also suggest that you visit the CDC’s on-line article, “Interim Clinical Considerations for Use of COVID-19 Vaccines Currently Approved or Authorized in the United States.” Even though we are not certain if these recommended regimens are protective against Omicron BA.4 and BA.5, the evidence continues to favor vaccination, especially to prevent severe outcomes.

Finally, you should be aware that another kind of genetic change of SARS-CoV-2 is being closely monitored, that is, emergence of resistance to antiviral drugs. At this time, Paxlovid is the drug of choice for early treatment of COVID-19. According to a July 8, 2022 article in Science, “Bad news for Paxlovid? Resistance may be coming,” a bevy of lab studies show that SARS-CoV-2 can mutate in ways that make it less susceptible to the drug, and researchers have found some of those mutations in variants circulating in infected people. Currently, this is a small problem. But, the challenges of drug resistance of another RNA virus, namely, HIV, are still vivid in the memories of doctors who were treating HIV/AIDS patients in the late 1980s. Fortunately, the pharmaceutical industry rallied and developed many antiviral drugs that target different components of HIV and prevent emergence of drug resistance.

What’s next? Both Pfizer-BioN-Tech and Moderna debated the value of adding components of BA.4 and BA.5 to their current COVID-19 vaccines. Nonetheless, both companies have promised a “bivalent vaccine” with BA.4 and BA.5 that should be available this fall. (Recommendations from the CDC regarding their use is pending results of clinical trials).

On the longer-term horizon, it is encouraging to know that there are public-private partnerships that haven’t taken their eyes off the emerging pandemic ball. Some that I’ve mentioned before are working on universal vaccines that protect against a large number of coronaviruses or influenza viruses. In the case of COVID-19, everyone recognizes the extraordinary achievement of developing and delivering COVID-19 vaccines in less than a year’s time. But according to a July 14, 2022 article in the New England Journal of Medicine, “Delivering Pandemic Vaccines in 100 Days,” the Coalition for Epidemic Preparedness Innovations (CEPI) believes there’s room for improvement. Because mutations of SARS-CoV-2 and new pandemics caused by other pathogens are emerging at breakneck speed, I wish the CEPI godspeed!