We’re Not Out of the Pandemic Woods YetJune 14, 2022
The emergency phase of the pandemic may be fading per the World Health Organization, the European CDC, and U.S. public health officials. But the pandemic is not over. We have the tools at our disposal to continue to save lives and keep the burden on our hospitals low. This is what we need to do next.
Better Hospitalization Tracking Metrics
We need better tracking of COVID-19 in hospitals. We previously proposed delineating hospitalizations by “for COVID” rather than “with COVID,” but disease progression is dynamic during a hospital admission. A better metric, as is being looked at in Massachusetts, is to track use of the steroid dexamethasone as a surrogate for hospitalized patients with severe COVID-19 illness. Another possibility is to directly track which patients require oxygen.
In the emergency department (ED), the presence of hypoxia is the primary determinant of whether a COVID-19 patient needs hospitalization. These patients are treated with dexamethasone and require a higher level of care, including pulmonary, infectious disease, and respiratory therapist consultations. Delineating hospitalizations for COVID-19 by use of dexamethasone or supplemental oxygen would give us a more accurate, bird’s-eye view of hospital resource use and help public health officials understand when hospitals are being overwhelmed with severely ill patients.
Link Home Rapid Tests With Reporting Mechanism and Expand Wastewater Sites
The U.S. government recently provided a third round of free at-home rapid tests through its centralized covid.gov hub. This has been a great resource for Americans to safely test at home and quickly begin isolating if COVID-positive.
However, home testing has led to significant underreporting of COVID-19 cases. We need greater effort from government and testing companies to encourage and incentivize people to report the results of their home tests, as is being done in the U.K. through the National Health Service. Many kits already include a way to report results through their mobile apps, and the government should launch public awareness campaigns to facilitate this reporting. Testing companies must then share results with local county health departments.
Expansion of COVID-19 wastewater surveillance sites is also critical. Increased incidence of COVID-19 here can precede officially recorded cases by a matter of weeks, allowing time for health systems to prepare for a possible surge in patients and for public officials to consider re-implementing stricter public health measures.
Continue the Push for Vaccines
Vaccines targeting the wild type spike have continued to hold up well in preventing severe disease and hospitalization by the more immune-evasive Omicron and its subvariants. The reason: T cells and memory B cells continue to work against variants, even Omicron.
However, some groups remain vulnerable: we must double down on boosters for the elderly. A large Veterans Affairs study of patients with a median age of 71 during the Omicron surge showed those with three doses had a lower rate of hospitalization and need for ICU level of care than those with only two doses. Despite the apparent less intrinsically severe nature of Omicron, almost as many Americans over 65 died during the winter surge as died from last year’s Delta variant surge. A second booster is now available for those over 50 in the U.S., although most other countries have decided on an older age cut-off for this dose. This second booster unfortunately wanes faster than the first booster in terms of antibodies, but each booster (or exposure) diversifies and broadens T-cell responses to the virus and expands the potency of B cells. Therefore, boosters are important for those at high risk for severe COVID-19.
The next step for the FDA is to expand our vaccine arsenal.
Most urgent is the need to authorize vaccines (from both Moderna and Pfizer) for kids under 5. Once authorized, we need additional research to determine the most effective dosing schedule. For older age groups, an extended 8-week or longer interval schedule has been shown to maximize immunogenicity and effectiveness. We’ll need to determine the best approach for young kids under 5 too, and investigate how previous COVID infection factors into this.
Considering alternative vaccine technologies is also a priority. The Novavax vaccine, which involves the spike protein combined with an adjuvant, was recommended by an FDA advisory committee earlier this month and now awaits FDA authorization, pending a manufacturing review. Perhaps a more familiar vaccine technology will sway some who remain hesitant about mRNA vaccines. FDA should also consider nasal vaccines an important next step in our armamentarium. These vaccines induce faster mobilization of antibodies to our throats and nasal passages, which, beyond just preventing severe COVID-19, may better protect people from getting infected in the first place.
Finally, the FDA needs to determine the makeup for the next generation of vaccines due this fall. There are several contenders: the Omicron bivalent vaccine booster by Moderna increases neutralizing antibodies more than a booster directed against the old strain, although studies in primates previously performed by the NIH did not demonstrate superior protection against disease by the Omicron-specific vaccine. The Covaxin vaccine is an inactivated whole virus vaccine that is effective against all of the emerging variants, with a recent study showing strong cellular immune responses against Omicron. FDA will need to thoroughly assess which options offer the most safety and efficacy.
Ensure Access to Therapeutics
With a non-eradicable virus like SARS-CoV-2, therapeutics are essential to keeping our rates of severe disease low among older and high-risk patients.
Real-world data show a clear benefit of nirmatrelvir-ritonavir (Paxlovid) in those high-risk for severe COVID-19, whether vaccinated or not (the original clinical trial studied the drug only among unvaccinated individuals). Even against the more immune-evasive Omicron variant, in those age 65 and above there was an 81% reduction in death and 67% reduction in hospitalization. There was no benefit for nirmatrelvir-ritonavir in those 40 to 64 years for protecting against severe disease. Unlike nirmatrelvir-ritonavir, oral antiviral molnupiravir has no known drug-drug interactions, since it does not require a ritonavir booster. In a recent subset analysis from the MOVe-OUT study, molnupiravir demonstrated an 89% reduction in hospitalization or death among immune-compromised participants.
These therapeutics are in robust supply. At the end of May, only around 30% of nirmatrelvir-ritonavir doses ordered by the government had been used. After a White House initiative to transform testing sites into federally funded “test to treat” locations, more than 182,000 prescriptions for oral antivirals were filled during the last week of May, and 40,000 pharmacies and other locations now have antiviral pills in stock. We need to ensure continued — and equal — access among all high-risk Americans.
Monoclonal antibodies also remain in our treatment and prevention arsenal. Bebtelovimab remains a powerful option to prevent severe disease and hospitalization in high-risk patients, with persistent activity against BA.2.12.1. As EDs across the country return to peak pre-pandemic patient volume for other medical conditions, bebtelovimab is a great one-and-done option since it’s given as an intravenous dose pushed over 30 seconds. For certain immunocompromised patients who are unable to mount a significant protective response from vaccines, a long-acting dual-monoclonal antibody can help. Tixagevimab co-packaged with cilgavimab (Evusheld) given as preexposure prophylaxis demonstrated an impressive 82.8% relative risk reduction for all COVID-19 symptoms at 6 months, with retained activity against subvariants BA.4 and BA.5.
What about treatment for long COVID? While an exact etiology remains elusive, one of its proposed mechanisms is a high viral load. Vaccination is highly protective against long COVID. For those with residual symptoms, some case studies have offered evidence that oral antivirals could reduce symptoms, so this must be studied further.
On to the Next Phase
We are certainly in a much stronger position against SARS-COV-2 than we have ever been. Vaccines continue to provide robust protection against severe illness and death. Therapeutics can keep high-risk patients out of the hospital. The emergency phase of the pandemic may be fading. We now need to avoid backsliding and instead look toward better future COVID management.
The next phase will require increasing trust in our public health system, updating vaccines for all, continued ease-of-access of therapeutics, new whole virus vaccines in the future, novel therapeutics currently in development, and nasal vaccines. Let’s remain vigilant and continue to move ahead.
Monica Gandhi, MD, MPH, is a professor of medicine in the school of medicine at University of California San Francisco. Michael Daignault, MD, is an emergency physician at Providence Saint Joseph Medical Center in Burbank, California.