The fall and winter are commonly accompanied by an increase in respiratory viruses. Covid, influenza, and respiratory syncytial virus (RSV) may conspire to increase hospitalizations, especially in people 65 and above. To combat these viruses, health officials will roll out new vaccines for RSV and updated Covid boosters.
NEW COVID BOOSTER: The new Covid booster will likely be available in early October. The new booster will target the XBB lineage of the omicron variant. The most common Omicron variant circulating in the US is the EG.5 subvariant. The EG.5 subvariant has similarities to XBB and should be effective against it.
Recommendations: The vaccine is most beneficial for higher-risk individuals: adults 65 and above, adults with heart or lung disease, and those who are immunocompromised, including cancer patients receiving chemotherapy and patients with autoimmune disease receiving immunosuppressive medications. This high-risk group can also be segmented with the oldest patients (80 and above) and the patients with the largest number of high-risk medical conditions, deriving the greatest benefit.
For people in high-risk groups, it is reasonable to get the new booster if you have not received a Covid vaccine or been infected with Covid in the preceding six months. For younger and healthier people, it is reasonable to wait for data demonstrating clinical efficacy.
Vaccine Efficacy: The new booster may provide partial protection against infection for weeks to months and likely protection against hospitalization. The true benefit is difficult to calculate. As explained below, it is unclear which Covid variants will dominate in subsequent months. Also, many people have received multiple previous vaccinations and have some degree of native immunity from Covid exposure. Of note, a recent study that has not been peer-reviewed showed no increase in peak antibody titers following a 2nd bivalent booster.
SARS-CoV-2 Neutralizing Antibodies Following a Second BA.5 Bivalent Booster
A DEEPER DIVE INTO NEW VARIANTS AND THEIR POTENTIAL IMPACT ON VACCINE EFFICACY
EG.5 VARIANT: The EG.5 variant is the fastest-growing variant in several areas of the world. In the US, EG.5 and its sublineages overtook the previously dominant XBB variants in early August to become the most common variant as per projections from the Centers for Disease Control and Prevention (CDC). EG.5 has a higher effective reproduction number, the number of additional infections caused by an initial infection at a specific point in time. This may be driven in part by EG.5’s antibody escape properties. It has a spike protein mutation that may make it less sensitive to neutralizing antibodies from past infections or vaccines.
In the US, COVID test positivity, wastewater levels, emergency department visits, hospitalizations, and deaths are all increasing based on CDC data through late August. This could reflect the transmissibility of the EG.5 variant, changes in health behaviors, and waning immunity from past vaccines.
EG.5 is an offshoot of XBB variants, the basis for the new Covid vaccines. While the spike protein mutation in EG.5 may make it less sensitive to the vaccine-induced antibodies, the expectation is that the newest vaccine will offer some increased protection.
What to Know About EG.5, the Latest SARS-CoV-2 “Variant of Interest”
BA.2.86 VARIANT: BA.2.86 is another variant commanding attention because it has 34 mutations on the spike protein targeted by the vaccines. Most other variants have 1-2 mutations on the spike protein. This high number of spike protein mutations might render the upcoming vaccine less effective.
Wastewater surveillance has identified BA.2.86 in 6 countries including the US. BA.2.86 comprises less than 1% of the circulating SARS-CoV-2 over the past two weeks in the US preceding 8.30.23. It is too soon to evaluate the transmissibility of this variant. Only if BA.2.86 is capable of outcompeting EG.5, will this pose a challenge for the upcoming vaccine. Of note, there is no early indication that BA 2.86 causes more severe illness but additional monitoring of hospitalization and mortality will clarify this.
Update on SARS CoV-2 Variant BA.2.86
COMPARING COVID RELATED HOSPITALIZATIONS and MORTALITY OVER THE LAST YEAR
While Covid case numbers are at a high level, hospitalizations and deaths are dramatically lower than a year ago. Additionally, hospitalization and death are very unlikely in patients who are fully boosted.
According to the World Health Organization, in July there were 5400 COVID-related hospitalizations in the US and in August this increased to 9400. This increase is significant but far below the 36000 COVID-related hospitalizations in July of 2022.
The daily death rate due Covid is about 70 deaths per day as per the National Center For Health Statistics (these numbers may be as low as 30 deaths per day according to other sources) with about 88% of the deaths in patients 65 and above. Also of note, unvaccinated patients are about 4x as likely to die from Covid as unvaccinated patients. Patients who received the initial vaccine series followed by the Bivalent vaccine compared to patients only receiving the initial vaccine are 25% less likely to die from Covid.
REPEATED VACCINES IN THE SAME ARM ENHANCE THE IMMUNE RESPONSE
A recent German study looked at the immune response in 300 patients receiving a series of 2 Pfizer mRNA vaccines in the same arm versus contralateral vaccination (the first vaccine in one arm and the subsequent vaccine in the other arm).
The study showed increased neutralizing activity of antibodies and an increased number of protective killer T Cells in participants who received both shots in the same arm. Repeated vaccinations in the same arm may be more effective because the cells driving our immune response are in local lymph nodes. A greater immunological response may be triggered by restimulating the immune cells in lymph nodes in the same location.
Differences in SARS-CoV-2 specific humoral and cellular immune responses after contralateral and ipsilateral COVID-19 vaccination
RSV VACCINE: The new RSV (Respiratory Syncytial Virus) vaccine is available for adults over 60. RSV causes a viral upper respiratory infection. It is also a cause of hospitalizations in young children, especially infants, and can be complicated by pneumonia in older adults. Each year RSV leads to about 100,000 hospitalizations in adults over 65 and about 8,000 deaths.
RSV Surveillance and Research (CDC)
Studies of the RSV vaccine have demonstrated a moderate ability to prevent mild to moderate upper respiratory infections due to RSV. On the other hand, there is no significant data on the prevention of hospitalization or death. Also, the RSV vaccines are understudied in people 75 and above, the population that would potentially benefit the most. These key issues should be clarified in subsequent studies.
Recommendation: The RSV is recommended and likely most beneficial for people 75 and above, especially if they have heart or lung disease or conditions that weaken their immune system. In younger and healthier patients this is a gray area that each patient may consider in the context of their willingness to receive an extra vaccine in exchange for a decreased risk of a cold-like illness. Future data on important outcomes such as hospitalization and potential adverse effects (there are rare reports of a neurologic syndrome called Guillane Barre) will make it easier to balance the benefits and risks.
Vaccines like every other story change in appearance depending on the vantage point used to view the evidence.
Brad Rabin MD is a concierge medicine doctor caring for patients in the San Francisco Bay Area including Palo Alto, Menlo Park, Los Altos, Portola Valley, and Woodside.
BRIEF RECOMMENDATIONS ON VACCINES:
Covid Vaccine: recommended for patients 65 and above. Timing: when available in early October and should be 6 months from your last Covid vaccine or Covid infection.
RSV Vaccine: recommended for patients 75 and above. recommended for patients 65 and above with health conditions that place them at higher risk (see above). Timing: available now
FLU Vaccine: recommended for patients 65 and above. Timing: October or early November