Making Sense of the COVID-19 Vaccine Recommendations and Guidance

A concise and simplified approach

1. If you decide to get the fall COVID-19 vaccine, what do you ask for?

Answer: Ask for the 2025 – 2026 Updated COVID-19 Vaccine.

1. What vaccine options are there?

Answer: There are four vaccines that will be available in the U.S.:

(Company/Brand name/Vaccine type/Age approval)

1. Pfizer/BioNTech – Comirnaty – mRNA – all adults 65 and older and individuals aged five through 64 years who are at increased risk of severe COVID-19 infection (see list of these risks below).
2. Moderna – Spikevax – mRNA – all adults 65 years of age and older and for those six months through 64 years of age who are at risk for severe disease.
3. Moderna – mNEXSPIKE – mRNA – all adults 65 and above and for ages 12 to 64 years who are at high risk of severe disease and have received the full primary series of COVID-19 vaccine previously.
4. Novavax/Sanofi – Nuvaxovid – protein – all adults 65 years and older and individuals aged 12 through 64 years who have at least one underlying health conditions that increases their risk of developing severe illness from COVID.

1. What is the difference between the two Moderna vaccine options?

Answer:  Spikevax is the same type and dose of vaccine that Moderna has offered throughout the pandemic, though the formulation has been updated over the course of the pandemic to adjust for the evolving virus. Moderna refers to mNEXSPIKE as their next-generation shot, and it just got its approval this past May. The differences between the two formulations are as follows:

1. Spikevax mRNA codes for the entire spike protein (the updated vaccine uses the KP.2 spike variant): mNEXSPIKE mRNA codes for the receptor-binding domain of the spike protein and the N-terminal domain of the JN.1 variant.[1] [2]
2. Spikevax is the only COVID-19 vaccine option available for children ages 6 months to 5years old. Pfizer is an option starting at age 5. mNEXSPIKE and Novavax are only approved for those 12 years old and older.
3. The dose for Spikevax is 50 mcg, whereas the dose for mNEXSPIKE is 10 mcg.[3]
4. In Moderna’s study of the vaccine that was submitted to the FDA for mNEXSPIKE’s approval, mNEXSPIKE showed non-inferiority in reducing COVID-19 infections.[4] [5] The mNEXSPIKE vaccine did demonstrate some superior efficacy in adults over the age of 18.[6]
5. The temperature requirements for the mNEXSPIKE formulation should make its use easier for providers.[7]

1. Which vaccine should I get?

Answer: The simple answer may be whichever one you can find. The production time for the mRNA vaccines (Pfizer or Moderna) is much less than that for the protein-based vaccines (Novavax), so if you go to find a vaccine now (my recommendation is to do it soon), you are likely to find more doctors’ offices, pharmacies or stores offering Pfizer or Moderna than Novavax. Pfizer vaccine began shipping out orders from hospitals, doctors’ offices, pharmacies and stores on 8/28.

If you are concerned about the mRNA vaccines (I don’t think you need to be, but I understand if you are), then go with Novavax – it is a more traditional protein subunit vaccine, not an mRNA vaccine. However, if you have never received a Novavax vaccine in the past, remember to go get your second dose in 2 – 6 months.

If you are leery about mRNA vaccines because you have had strong reactions in the past (I generally feel like I have the flu for less than a day after getting the mRNA vaccines and these kinds of reactions are common), then Novavax could be a good option for you, as reactions to it tend to be much milder, if any at all (I had no reactions to Novavax).

If your child is under the age of 12, your only option is an mRNA vaccine.

• When should I get it?

Answer:  If you are only willing to go to the doctor or pharmacy once for all your seasonal shots, then wait until October (or more precisely when we start seeing influenza activity in your area of the country) in order to time your influenza vaccine most ideally, because it is a bit too early for the flu shot right now. Also, studies thus far show that getting the flu shot together at the same time as your COVID shot may boost the immune response to both.

However, if you are willing to get your COVID shot now and wait for your flu shot until it is better timed to flu activity, then start looking for the COVID vaccine now and today is a fine time to get your dose (though it may still be a week or two before the vaccines have made it to your doctors’ office or pharmacy). We are experiencing a new rise in COVID-19 activity in the U.S., so that makes now a good time for the updated vaccine, but we are also anticipating that the FDA and CDC will take more steps to cut back access to these vaccines in the near future, so I am not sure how much longer you will even be able to get or afford these vaccines.

• What underlying conditions will qualify me for the vaccine if I am under the age of 65[8]?[9]

Answer:

1. Residents of long-term care facilities are at increased risk, making up less than 1% of the U.S. population but accounting for more than 35% of all COVID-19 deaths.
2. Asthma
3. Cancer, especially hematologic malignancies (e.g., leukemia)
4. Cerebrovascular disease (e.g., strokes)
5. Chronic kidney disease, especially those undergoing dialysis
6. Bronchiectasis
7. Chronic obstructive pulmonary disease (COPD – emphysema and chronic bronchitis)
8. Interstitial lung disease
9. Pulmonary embolism (blood clots to the lungs)
10. Cystic fibrosis
11. Pulmonary hypertension
12. Cirrhosis
13. Alcoholic liver disease
14. Non-alcoholic fatty liver disease
15. Autoimmune hepatitis
16. Diabetes mellitus – types 1 and 2
17. Disabilities
    1. Attention-deficit/hyperactivity disorder (ADHD)
    1. Autism
18. 1. Cerebral palsy
19. 1. Charcot foot
20. 1. Chromosomal disorders
21. 1. Chromosome 17 and 19 deletion
22. 1. Chromosome 18q deletion
23. 1. Cognitive impairment
24. 1. Congenital hydrocephalus
25. 1. Congenital malformations
26. 1. Deafness/hearing loss
27. 1. Disability indicated by Barthel Index
28. 1. Down syndrome
29. 1. Fahr’s syndrome
30. 1. Fragile X syndrome
31. 1. Gaucher disease
32. 1. Hand and foot disorders
33. 1. Learning disabilities
34. 1. Leber’s hereditary optic neuropathy (LHON) or Autosomal dominant optic atrophy (ADOA)
35. 1. Leigh syndrome
36. 1. Limitations with self-care or activities of daily living
37. 1. Maternal inherited diabetes and deafness (MIDD)
38. 1. Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) and risk markers
39. 1. Mobility disability
40. 1. Movement disorders
41. 1. Multiple disability (referred to in research papers as “bedridden disability”)
42. 1. Multisystem disease
43. 1. Myoclonic epilepsy with ragged red fibers (MERRF)
44. 1. Myotonic dystrophy
45. 1. Neurodevelopmental disorders
46. 1. Neuromuscular disorders
47. 1. Neuromyelitis optica spectrum disorder (NMOSD)
48. 1. Neuropathy, ataxia, and retinitis pigmentosa (NARP)
49. 1. Perinatal spastic hemiparesis
50. 1. Primary mitochondrial myopathy (PMM)
51. 1. Progressive supranuclear palsy
52. 1. Senior-Loken syndrome
53. 1. Severe and complex disability (referred to in research papers as “polyhandicap disability”)
54. 1. Spina bifida and other nervous system anomalies
55. 1. Spinal cord injury
56. 1. Tourette syndrome
57. 1. Traumatic brain injury
58. 1. Visual impairment/blindness
59. Heart disease, including coronary artery disease, congestive heart failure and cardiomyopathies
60. HIV infection
61. Mood disorders including depression
62. Schizophrenia spectrum disorders
63. Dementia
64. Parkinson’s disease
65. Obesity (BMI >30 kg/m² or >95^th percentile in children)
66. Physical inactivity
67. Pregnancy and recent pregnancy
68. Primary immunodeficiencies
69. Current or former smoker
70. Solid organ or blood stem cell transplantation
71. Tuberculosis
72. Use of corticosteroids or other immunosuppressive therapies
73. Epilepsy
74. Hemophilia
75. Overweight (BMI >25 kg/m² but <30 kg/m²)
76. Sickle cell anemia
77. Thalassemia
78. Substance abuse disorder

• How can I find a place to get vaccinated?

Answer:

1. Check with your doctors’ office and your child’s pediatrician or family medicine office to see if they have or are expecting to have vaccine.

2. Check with your friends and social network if they have already located a pharmacy or store with the vaccine you are interested in.

3. Check your preferred pharmacy’s website as you can often see the options available and schedule your immunization at the same time.

4. You can use a vaccine finder:

              a. Novavax https://bechoosy.dev.novavaxcovidvaccine.com/vaccine-finder. You can view a list of pharmacies that have ordered Novavax or enter your information and search for sites near where you live.

              b. Moderna https://products.modernatx.com/finder.

              c. Pfizer https://www.comirnaty.com/.

VIII. If I am healthy, but pregnant, should I still get a COVID-19 vaccine?[10]

Answer: YES! Pregnancy itself significantly increases your risk for severe disease. Plus, by getting vaccinated during your pregnancy, you will pass on antibodies to your baby that will help protect them for the first six months of life until they are able to receive the vaccine directly. Children under the age of six months have the second highest rate of developing severe disease and requiring hospitalization (only second to adults > 75 years of age).

1. What about children age 4 and younger?

Answer: Please read my prior blog post to see the special concerns for children with COVID-19. Because the American Academy of Pediatrics has been concerned about vaccine mis/disinformation relating to children, they issued their own recommendations relating to COVID-19 vaccines in infants, children and adolescents.[11] In their guidance, they point out that “Infants and children 6 through 23 months of age are at high risk for severe COVID-19. The AAP recommends that all infants and children in this age group who do not have contraindications receive 2025-2026 COVID-19 vaccine.” While you likely will find it difficult to find a pharmacy that will vaccinate your child, your pediatrician’s office should be able to arrange for the vaccine and for coverage of the cost of the vaccine by designating your child to be at high risk as indicated by the AAP.

The AAP goes on to recommend a single dose of age-appropriate 2025-2026 COVID-19 vaccine for all children and adolescents ages 2 – 18 years of age if they are at high risk of severe COVID-19, if they have never been vaccinated against COVID-19[12], and for those who have household contacts who are at high risk for severe COVID-19.

• Are there other reasons to get the 2025 – 2026 updated COVID-19 vaccine other than concerns about severe illness, hospitalization and death?

Answer:  Yes. COVID-19 vaccination reduces the risks of developing Long COVID, though certainly the greatest impact was earlier in the pandemic. Second, any reduction in the risk of infection is helpful because we have very strong evidence that the risk for cardiovascular complications following COVID-19 is increased at least for one year. Third, there are many signals (not proof) that SARS-CoV-2 can increase the risk for many other possible disorders later in life. This is consistent with our expanding knowledge of the role some viruses can play in developing medical conditions decades after infection (e.g., Epstein Barr Virus (EBV)’s role in the development of multiple sclerosis (MS); Human Papilloma Virus (HPV) in the development of cervical cancer; Hepatitis B and C viruses’ role in the development of chronic liver disease and liver cancer).

I hope that I have anticipated most of your questions, but if you have others, submit a comment and I will answer the question if I know, otherwise I will research it for you.

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[1] There are two camps of thought with respect to whether to use KP.2 spike or JN.1 spike for this year’s updated vaccine. I previously wrote in detail about the ideas that support each approach. I personally fall into the JN.1 camp for reasons I explained in that prior blog post, but no one knows, and frankly, pretty much everyone that I know that has advocated for one over the other, including me, isn’t sure that in the end, it will really make that much of a difference. (Pfizer’s vaccine is based on the LP.8.1 spike protein, which is an even more recent circulating variant, however, all of these variants are closely enough related that each is expected to provide roughly the same degree of protection.

[2] Moderna selected the receptor-binding domain (RBD) as opposed to the entire spike protein (the RBD is located on the spike protein) because it appears to be the part of the spike protein that generates the strongest neutralizing antibodies (neutralizing antibodies are the kinds of antibodies that tend to most strongly impede binding of the virus to the receptor on the cell, which is the step required for the virus to enter cells and cause infection and to make more copies of the virus to infect more cells). The selection of the N-terminal domain is not based upon neutralizing antibody response, but rather that significant mutations occur far more often in the spike protein than in the nucleocapsid protein, which is where the N-terminal domain is located. Thus, the hope would be that by including the N-terminal domain of the nucleocapsid protein, the effectiveness of the vaccine may be better maintained against the virus’ constantly evolving immune escape properties.

[3] Theoretically, that should mean lower reactogenicity (immediate reactions – arm swelling, redness, muscle pain, etc.), but in looking at the comparison groups in Moderna’s study, I didn’t see much of a difference.

[4] When approving a new formulation of a vaccine, it is standard to compare the new formulation to the already approved version to ensure it is non-inferior (which simply means that it works at least as well as the already approved version), and in this case, it did, and in fact, it seemed a bit better.

[5] Notice that this study was looking at the rate of infections, not severe disease, hospitalizations or death. While vaccine misinformation tends to promote the idea that the COVID-19 vaccines do not prevent transmission or infections, that is not a true statement. We have strong evidence for a decrease (decrease, not complete protection) in transmission and infections in vaccinated individuals for the first couple of years of the vaccine’s availability, though it was never perfect, it has significantly declined, but the main benefit has always been the protection against severe disease, hospitalization, and death.

[6] During a median follow-up of 8 months, the incidence of COVID-19 occurring > 2 weeks after immunizations was 9.9% with mNEXSPIKE and 10.8% with Spikevax. The seroresponse rates and geometric mean neutralizing antibody titers were higher among those who received the mNEXSPIKE formulation, especially those over the age of 18. The mNEXSPIKE vaccine elicited a stronger immune response against both the Omicron BA.4/BA.5 variants and the original strain of SARS-CoV-2. However, it is noteworthy that the participants under the age of 18 were only required to have received the primary series of mRNA vaccine, whereas those over 18 were also required to have received at least one booster.

[7] Both formulations should be stored in a freezer, however, while Spikevax can be refrigerated for up to 60 days or kept at room temperature for up to 12 hours, mNEXSPIKE can be refrigerated for up to 90 days or at room temperature for up to 24 hours.

[8] Age remains the strongest risk factor for severe COVID-19 outcomes, with risk of severe outcomes increasing markedly with increasing age. Compared with ages 18–29 years, the risk of death is 25 times higher in those ages 50–64 years, 60 times higher in those ages 65–74 years, 140 times higher in those ages 75–84 years, and 340 times higher in those ages 85+ years. https://www.cdc.gov/covid/hcp/clinical-care/underlying-conditions.html.

[9] https://www.cdc.gov/covid/risk-factors/index.html.

[10] The American College of Obstetrics and Gynecology just updated their guidance on August 22. See here for more complete recommendations: https://www.acog.org/news/news-releases/2025/08/acog-releases-updated-maternal-immunization-guidance-covid-influenza-rsv.

[11] http://publications.aap.org/pediatrics/article-pdf/doi/10.1542/peds.2025-073924/1843884/peds_2025073924.pdf.

[12] This is good advice because half of children who end up with severe disease and hospitalized for COVID-19 have no identifiable risk factors. Further, two advantages of vaccination in children prior to their first infection are the head start in preparing the immune system to fight the virus as described in my prior blog post, but also the taming effect that vaccination has to avoid an over-reactive immune response to the first time it sees this new virus, which itself can cause severe harm (immunopathology).