COVID-19 in the Fall of 2023—Forgotten but Not Gone | Infectious Diseases | JAMA

Since the end of the US Public Health Emergency on May 11, 2023, there has been a desire from elected officials and the public to put COVID-19 in the rearview mirror. However, the emergence of new variants and a summer wave of infections remind us that SARS-CoV-2 is here for the foreseeable future. This Viewpoint addresses the current state of COVID-19 in the US and summarizes key clinical information for health care professionals and patients.

With the end of the Public Health Emergency, COVID-19 surveillance in the US is no longer performed using case counts. Instead, wastewater surveillance and tracking of hospitalizations and deaths are the major indicators being used to understand trends. Since late June 2023, there has been a steady increase in the detection of SARS-CoV-2 in wastewater, a change that correlates with a bump in reported hospitalizations and deaths.

However, these increases are small compared with those seen early in the pandemic when most of the population lacked any protective immunity to the virus and infection not uncommonly led to severe illness and even death for a substantial proportion of those infected. As a result of vaccination and infection, population immunity has increased. By the end of 2022, an estimated 97% of people aged 16 years or older had infection or vaccination-induced antibodies,1 and the estimated age-adjusted COVID-19–associated death rate decreased 47%, from 115.6 per 100 000 persons in 2021 to 61.3 per 100 000 persons in 2022.²

Hybrid immunity (vaccination plus infection) provides the most robust protection against severe disease, hospitalization, and death.1 However, the prevalence of hybrid immunity appears to be lowest among those aged 65 years and older, and immunity from vaccines wanes over time and that decrease is faster among older adults. This is why the US Centers for Disease Control and Prevention (CDC) has recommended that those 65 years and older receive an additional booster.³

Since the initial emergence of the Omicron variant in November 2021, the virus has continued to rapidly evolve, acquiring mutations that provide it with increasing immune escape. The XBB.1.5 variant was first detected in the US in October 2022 and by January 2023 it had become the dominant variant observed. This prompted the US Food and Drug Administration (FDA) to recommend that the fall 2023 COVID-19 vaccine be a monovalent preparation targeting XBB.1.5. However, since then, 3 additional variants have emerged, EG.5, FL.1.5.1, and now BA.2.86. XBB.1.5 shares a nearly identical spike amino acid profile with EG.5 and FL.1.5.1, so there is confidence that the new monovalent vaccine will be protective. However, the large number of mutations in the spike protein of BA.2.86 raises concerns for greater immune escape from existing immunity from vaccines and prior infection and the possibility of a massive wave of cases as occurred with Omicron.4 It is currently unknown if the BA.2.86 variant is highly transmissible or if the monovalent XBB.1.5 vaccine will provide protection. However, there is also no evidence that infection with BA.2.86 is more severe or that the mutations present in this variant will affect the utility of diagnostic tests or antivirals.

The need for nonpharmacologic interventions (NPIs) was greatest early in the pandemic when the population was immunologically naive. As population immunity increased through vaccination, infection, or both, the relative importance of NPIs decreased, but their value may differ depending on the medical vulnerability of individual patients (eg, someone who is highly immunocompromised) and populations (eg, older adults living in a nursing home). Face coverings (masks) have become politicized and their role poorly understood. Not all face masks are the same, and mask quality and proper use are both essential to overall effectiveness. In general, older adults and those who are immunocompromised should strongly consider masking during influenza, respiratory syncytial virus (RSV), and COVID-19 surges while in crowded indoor public spaces. For everyone else, the decision to use a mask depends on their risk tolerance. In health care settings, masking remains a highly effective intervention during periods of peak respiratory virus transmission.5 Ventilation is also an important measure to reduce risk of transmission not only of SARS-CoV-2 but other respiratory viruses and bacteria.⁶

COVID-19 vaccination is recommended for everyone 6 months and older in the US. Vaccination is safe and effective and protects against the most serious effects of SARS-CoV-2 infection, specifically hospitalization and death. However, protection against symptomatic infection is limited, and waning of immunity is a reality with the currently available vaccines. Among adults who are otherwise healthy (“immunocompetent”), recent estimates of vaccine effectiveness of a bivalent vaccine against hospitalization for COVID-19 were 62% compared with no vaccination in the 2 months after the bivalent dose but decreasing to 24% 4 to 6 months after the bivalent dose.7 The CDC considers an individual who has completed a primary series and received a single booster as “up to date” in their COVID-19 vaccination. If they have completed a primary series and are not yet eligible for a booster, they are also up to date. However, an individual who has completed a primary series and is eligible for a booster but has not received a booster is not up to date.³ For people aged 65 years and older, there is the option to receive 1 additional bivalent mRNA vaccine dose if it has been at least 4 months since their first bivalent vaccine dose.

Pfizer/BioNTech and Moderna have filed applications with the FDA for their XBB.1.5 monovalent COVID-19 vaccine for individuals 6 months of age and older. The CDC is expected to issue recommendations on who should receive this updated vaccine by mid-September. Given that there is unlikely to be much protection against symptomatic infection, it may be that the CDC recommendations will focus on providing additional protection to more vulnerable populations (older adults and individuals who are immunocompromised), but it is likely that the recommendation will be for everyone 6 months and older to be up to date in their immunizations and thus receive this vaccine.

Diagnostic testing and antiviral medications are additional tools to manage COVID-19. Antigen tests (“home tests”) are less likely to detect the virus than polymerase chain reaction (PCR) assays, but antigen tests are readily available and thus used most frequently. All currently approved tests can detect circulating variants. When a person is symptomatic, a single negative antigen test result cannot rule out infection and another test should be done 48 hours later.

Nirmatrelvir-ritonavir (Paxlovid), which received full FDA approval in May 2023, is the preferred outpatient antiviral medication and the drug prescribed most frequently. This medication reduces the risk of severe illness, including hospitalization and death, by about half in those at high risk (older persons, those who are immunocompromised, and patients with underlying neurological and cardiovascular disease) regardless of vaccination status.8 However, despite its effectiveness, many who are at increased risk of severe illness are not being prescribed this medication. Several reasons are thought to be causing this underutilization of nirmatrelvir-ritonavir, but drug-drug interactions and the fear of a rebound are commonly cited. Improving education among the public as well as among prescribing clinicians about the benefits of antivirals is essential to limit severe outcomes among the most medically vulnerable.

COVID-19 may be forgotten but it is not gone. As the US continues to emerge from the pandemic it is essential that clinicians and patients keep SARS-CoV-2 on the list of viral pathogens that cause major respiratory illness. Protecting the most vulnerable populations should be a priority. This includes making vaccinations, high-quality masks, testing, and antivirals easily available. Finally, perhaps the most important way to limit transmission is self-isolation of those who are infected. Regardless of test results, any person with symptoms of a respiratory infection should remain home and avoid going to school or work. While COVID-19 is no longer a public health threat, waves of infection will occur for the foreseeable future. How disruptive these are will depend on the behavior of the virus but also, more importantly, on the behavior of humans.

Corresponding Author: Carlos del Rio, MD, Emory University School of Medicine, 100 Woodruff Circle, James B. Williams Medical Education Building, Room 423, Atlanta, GA 30322 (cdelrio@emory.edu).

Published Online: September 12, 2023. doi:10.1001/jama.2023.19049

Conflict of Interest Disclosures: Dr del Rio reported receiving grants from NIH/NIAID via the Emory Vaccine and Treatment Evaluation Unit during the conduct of this work. No other disclosures were reported.