In this issue, we cover seasonal vaccines coming due this Fall (Flu, COVID booster and RSV) with some detail on how they are formulated and deemed effective. We borrow heavily from analysis performed by the UK’s Joint Committee on Vaccination and Immunization (or “Immunisation”).
Doses of the 2023/2024 seasonal flu shot are stocked in our office and can be given any time as the best time to receive the vaccine is during the months of September and October.
The rationale for such timing is that annual local epidemics follow a fairly predictable
seasonal pattern with outbreaks in North America occurring between November and March. These begin abruptly, peaking in 3 weeks, and then end about 8 weeks later. Viral spread during winter months is presumed to be favored by improved virus survival in lower temperature environments and, indoor crowding due to cold weather. These annual epidemics can affect 10% to 30% of the world population.
Each year in January, a review of circulating influenza viruses is undertaken by the World Health Organization (WHO) and the most likely epidemic strains from two main categories – Influenza A and Influenza B – are selected. For Influenza A this year’s shot contains the ‘swine flu’ familiar H1N1 as well as H3N2 subtypes (H and N are specific surface proteins termed hemagglutinin and neuraminidase). The Influenza B lineages generally cause less severe disease and are called Yamagata and Victoria. So there are 4 components which is why you will hear the shot referred to as ‘quadrivalent’.
The decision on which strains to include in the vaccine formulation is based on global
surveillance data but, in the end, it is a prediction and not always correct. As such, the
effectiveness of the seasonal flu shot can vary from year to year. Even if the vaccine doesn’t completely prevent the flu, it can still reduce the severity and complications of the illness should you become infected.
Vaccination is associated with a reduced incidence of influenza from 2.3% among adults who were unvaccinated as compared to 0.9% among vaccinated. This effect is even stronger among those 65 years and older, wherein vaccination reduced the incidence from 6% to 2.4%.
Side effects to the flu vaccine are generally mild, most common being local injection site reaction (soreness), headache, muscle aches or low grade fever – all resolving within a day or so. About 15% of flu vaccine recipients experience a side effect.
For the first time ever, our office will be stocking a COVID vaccine, in this case the 2023
booster. We have been able to bypass the LA County Health Department who had been unwilling to supply us with vaccines and instead are receiving them directly frow the manufacturers. Unlike the influenza vaccine which has population-wide applicability, I am favoring a narrow scope of vaccine efforts for COVID-19. Some of this recommendation is based on bivalent booster experience of 2022 wherein only 17% of the total US population ever received a booster dose. That percentage was a bit better for those over the age of 65 years at 43.3%.
Similar to influenza, COVID historically (until 2023 that is) has had a strong Winter surge beginning right after Thanksgiving (not a big surprise why an airborne virus would spike after such). The Fall 2023 COVID booster, which should gained FDA approval this week, targets the XBB.1.5 a coronavirus subvariant that emerged in late 2022. While XBB.1.5 only makes up 3.1% of the currently circulating variants in the US, basic science data has indicated that its offshoots (EG.5, FL.1.5.1, KBB.1.16.1 and KBB.1.16) share a close relationship with KBB.1.5. As such, it is expected that the updated booster will provide protection against these related variants
The UK’s Joint Commission on Vaccination and Immunization (JCVI) has offered some of the most coherent advice on boosters, recommending them for those at high risk of serious disease and therefore most likely to benefit from vaccination. These include:
Similarly, we will advise patients over 65 and those in higher risk groups to strongly consider having the booster by the end of October in time for an expected late November to January surge in cases (this differs from the UK recommendation to have the booster by the end of December). The crux of the JCVI’s advice is based on a coherent analysis of the number needed to vaccinate to prevent a hospitalization or death due to COVID-19. Based on the 2022 booster experience, it would require giving a booster to 240 high risk >90 year olds to prevent one COVID death but over 2 million booster doses to prevent one death amongst healthy 15-19 year olds.
Vaccine efficacy of the 2022 booster dropped rapidly from 53% 2-4 weeks after vaccination to 28% at greater than 15 weeks. Protection against hospitalization after an mRNA booster increases in the two weeks after vaccination and then declines towards a stable plateau of around 50-60% by six months.
While you can have both the flu vaccine and COVID booster at the same time, it may be more prudent to separate the two. That way in the case of an unlikely, but possible, vaccine reaction -the cause will be apparent. A recent study from Sheba Medical Center in Israel showed that systemic reactions among those who received a flu+COVID co-administration was 27.6% as compared to 27.4% for COVID only and 12.7% in flu only. However, COVID spike protein antibody levels were 19% higher amongst those who received the COVID booster separately as compared to those who received COVID and flu vaccines together (link:https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2809119
This Fall will be the first time that an RSV (Respiratory Syncytial Virus) vaccine becomes available but is not a vaccine we will stock in the office. It will be available, however, at local pharmacies. Approved in May 2023, two RSV vaccines are available in the prevention of respiratory tract disease – Arevxy (82% effective) and Abrysvo (67% effective)
RSV is a common respiratory illness that infects up to 90% of children in their first two years of life and frequently reinfects both older children and adults. In most cases, RSV infection is mild and may even go unnoticed – with infants under the age of one year and the elderly at greatest risk. For infants, RSV can cause such severe inflammation of the small airways in the lungs that significant breathing difficulties can occur. There is no pharmacotherapy other than supportive care with fluid and respiratory support. RSV is a leading cause of infant mortality globally and, in
some developing countries, is second only to malaria as a cause of death among infants.
The burden of RSV disease in adults is less well understood but undoubtedly
underestimated given that it is most typically (and correctly) associated with respiratory illness in infancy. The same JCVI grappled with a population-wide rollout of RSV vaccine in the UK where the annual number of deaths was estimated to be somewhere between 741 and 6472. The US has about 5 times the population of the UK so that would translate to between 3700 and 32000 deaths here. They also considered the burden of RSV on the health system in general and concluded that a programme for those 75 years and older would be the most ‘efficient’ but one directed at 65 years and older would provide the most benefit. Note: they only considered the Arevxy, noting that these data provided the most ‘comprehensive read out’ and is also more effective. The committee was hopeful that Arevxy would provide multi-year protection, as RSV does not have the same mutation frequency as COVID-19 and influenza. At $336 a dose, one would certainly hope for longer lasting protection.
Side effects seem to be generally mild but common. 34% of recipients reported fatigue, 29% muscle aches and 27% a headache. These typically resolved in 24 to 48 hours.The current RSV vaccine is recommended only as a single dose for individuals 60 years and older in the United States. I would revise that upwards to 65 years of age. Those most likely to benefit would be those with pulmonary disease (such as COPD or asthma), cardiovascular disease, moderate to severe immune compromise, and diabetes. The CDC does not recommend against co-administration with seasonal flu shot or other vaccines although antibody titers for both influenza and RSV were lower when given together. So my recommendation would be to separate RSV vaccination out from other shots by two weeks.
In August, the Los Angeles County Health Department reported a “concerning increase” in reported COVID-19 cases and indeed cases in our clinic showed a notable uptick as compared to much of the Spring of 2023. We had a total of 13 cases, of which 10 were first time infections (Figure 1 below).
Total COVID-19 Cases(Blue) and Repeat Infections (Red) by Month in 2022/2023: Santa Monica Primary Care
Smoothed Daily incident Case Rate (per 100,000 population) of SARS-CoV2: Los Angeles Country, California
While this did represent a significant increase, it is important to contextualize the magnitude of such against the historic low rates of this Spring. Historically, a mid to late summer surge has been seen in every year since the pandemic began, but rates this summer (Green Line in Figure 3 below) were the lowest we have ever seen, including the Summer of 2020 (Blue Line). We were all under shelter-in-place orders during the Summer of 2020 as well.
Smoothed Daily incident Case Rate (per 100,000 population) of SARS-CoV2: Los Angeles Country, California for 2020(Blue), 2021(Red), 2022(Yellow), and 2023 (Green)
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