What a Doctor Is Seeing In COVID-19 Today

Hospitalizations for COVID-19 have been on the rise since the beginning of July. Then came the identification of the heavily mutated and possibly highly-transmissible BA.2.86 variant by the global surveillance network. Such a variant has the potential to evade our vaccine- and infection-induced antibodies and cause a surge of seasonal hospitalizations. The recommendation by the FDA’s VRBPAC in June that the Fall updated vaccine be composed of an XBB-lineage of the Omicron variant appeared to be at risk. There was mounting concern we be faced with a similar situation from last year where the virus had already mutated well beyond the BA.4/5-bivalent vaccines by the time they were rolled out.

But the landscape of the pandemic—especially the clinical disease caused by SARS-CoV-2—has significantly changed. On the front lines of the emergency department (ED), we are seeing a different virus. This is likely a combination of both high levels of population hybrid immunity and evolution of the virus itself to favor infection of the upper airway and cause less severe disease.

The CDC’s recent decision to universally recommend vaccines for everyone, while falling short of a much-needed targeted recommendation for high-risk groups, paves the way for equity of access and insurance coverage for Americans needing to top up their protection against infection. And recent preliminary studies from multiple labs on BA.2.86 has actually been reassuring.

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New hospital admissions had increased nationally by 9% in the first week of September and have been on an upward trajectory since the beginning of July driven by EG.5, FL.1.5.1, and the XBB subvariants. At 16,000 current hospitalizations, this is still far below the Omicron peak of 145,000 hospitalizations that overwhelmed our health care system in January 2022.

Hospitalizations are highest in those patients 70 and older. Compared to earlier in the pandemic when our ED and hospitals were overrun with patients suffering from hypoxia and viral pneumonia requiring various oxygen modalities, proning techniques, and ventilators—elderly patients are lately presenting to my ED with weakness, fatigue, dehydration, and electrolyte abnormalities. Even though these symptoms are caused by covid infection, they are less staff- and resource-intensive compared to years past. Management of such illness is less challenging, and patients are discharged home after a few days.

Immunologically, this is not surprising that older Americans are becoming sick with COVID as head into the fall. It’s been a year or more since many of them last had a COVID-19 infection or a vaccine dose. In fact, only 46.5% of those 75 and older ever received the most recent bivalent booster.

Even though protection against severe disease remains robust, protection against any infection has most certainly waned. For healthy individuals under 65 years, current variants are expressing a predilection for the upper respiratory tract and follow a particular pattern. Symptoms typically start with a sore throat, and progress to headache, rhinorrhea, and nasal congestion.

This tracks with what we observed from Omicron in multiple lab studies since early 2022. Omicron family variants are approximately 10-times less efficient than the Delta variants at replicating in lung tissue and mutations favor preference for upper airway tissue.

A UNIVERSAL RECOMMENDATION

Recently the CDC’s Advisory Committee on Immunizations Practice (ACIP) voted to approve the updated XBB.1.5 monovalent vaccine for everyone 6 months and older. ACIP members were likely convinced mostly by data that a universal recommendation will prevent 400,000 hospitalizations and 40,000 deaths due to COVID-19 infection.

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As this is the first vaccine rollout since the end of the pandemic emergency that is not financed by the federal government, a universal recommendation also paves the way for insurance coverage. For those without insurance, the CDC announced its Bridge Access Program for the 25-30 million Americans without insurance.

Some ACIP members and other front-line physicians like myself would still like to see the CDC more strongly advocate for vaccination in high-risk groups who stand to benefit the most from updated protection. The Joint Committee on Vaccination and Immunisation—the United Kingdom’s version of our ACIP—outlined such a targeted, evidence-based strategy focused on adults 65 and older and those in care homes, frontline health care staff, and those 6 months–64 years with underlying medical problems, such as chronic kidney and lung disease, and those who are immune-compromised, from chemotherapy treatment, for example. The Infectious Diseases Society of America echoed this support for a targeted strategy in its own response to the CDC decision—that certain high-risk groups are at increased risk of severe disease and should be prioritized for vaccination this fall.

Even for healthy individuals under 65, the XBB.1.5 monovalent updated vaccine is a good match for currently circulating variants and enables a top up of protection against any infection. While on the decline, the XBB family subvariants still comprises a large percentage of new infections. In addition, the widespread EG.5 variant is different from XBB.1.5 by just two new mutations, at F456L and Q52H; suggesting the updated vaccine will work well against it. And a switch back to a monovalent formulation ensures that those vaccinated receive a full undiluted dose against the most prevalent variants.

ACIP members were also likely reassured by recent preliminary pseudovirus and sera neutralization studies from four laboratories—two in the U.S. and in Sweden and China—demonstrating that BA.2.86 is likely 1) not more immune evasive than previous variants and 2) not very efficient at infecting our cells.

Most importantly, the sera of those previously infected with XBB was able to generate a significant response against BA.2.86 portending that the updated XBB-targeted vaccine will maintain its protection if BA.2.86 takes hold as the fall and winter unfolds. In the only human clinical trials to date, Moderna announced its XBB.1.5 vaccine generated an 8.7-11-fold increase in neutralizing antibodies against BA.2.86, EG.5 and FL.1.5.1 variants.