For those of you who are not physicians, you may be unaware of where doctors go for information. We have many options, medical journals and continuing education conferences among them. One source of medical information stands out above all others - UPTODATE. It is THE online clinical decision support tool used at nearly every major academic medical center and teaching hospital in the world. What makes UPTODATE so good? They continuously scour the medical literature using critical appraisal processes and criteria to identify quality research and weed out poor quality studies. UPTODATE maintains topic summaries on over 7000 medical disorders which are updated in real time as new information comes in, literally by the day. With this tool doctors know exactly where the medical literature stands on most any clinical issue. It is bulletproof. It is the standard of care. Most doctors use UPTODATE in their practices. If they don’t, they are not up to date. What does UPTODATE have to say about the COVID vaccines? Sit down. You may be shocked. This is the truth. This is current best evidence as of today. Anyone suggesting anything other than this is misinformed.
“Indications and vaccine selection — We recommend COVID-19 vaccination for all individuals aged six months and older.
For individuals who are eligible for any COVID-19 vaccine, we suggest an mRNA vaccine (BNT162b2 [Pfizer COVID-19 vaccine] or mRNA-1273 [Moderna COVID-19 vaccine]) or NVX-CoV2373 (Novavax COVID-19 vaccine) rather than Ad26.COV2.S (Janssen/Johnson & Johnson COVID-19 vaccine). Extensive data supporting the use of mRNA vaccines have accumulated since their availability. Less data on safety and efficacy of NVX-CoV2373 are available, but it is also highly effective and may be an attractive option for individuals with concerns about the novelty of the mRNA vaccine platform (table 1). We reserve Ad26.COV2.S for individuals who have contraindications or no access to other COVID-19 vaccines, in agreement with the Centers for Disease Control and Prevention (CDC) and the terms of the EUA for Ad26.COV2.S (see 'Contraindications and precautions (including allergies)' below). Nevertheless, if other vaccines are not options, we recommend vaccination with Ad26.COV2.S rather than forgoing COVID-19 vaccination.
●Rationale for vaccine recommendations – Vaccines available in the United States are highly effective, substantially reduce the risk of COVID-19, especially severe/critical disease, and have been associated with substantial reductions in COVID-19-associated hospitalizations and deaths [16-23], even in the context of variants that partially evade vaccine-induced immune responses. Hospitalization and mortality rates for COVID-19 have been consistently higher among unvaccinated compared with vaccinated individuals, with or without booster doses [24]. In addition to direct reductions in COVID-19-associated morbidity and mortality, vaccination has been associated with lower non-COVID-19 mortality rates, supporting evidence that COVID-19 vaccination does not increase the risk of death [25]. Details on the efficacy and safety of the individual vaccines are discussed elsewhere. (See 'Immunogenicity, efficacy, and safety of select vaccines' below and 'Waning effectiveness over time and with variants of concern' below.)
The preference for mRNA vaccines over Ad26.COV2.S is based on a more favorable risk-benefit profile with the mRNA vaccines. Ad26.COV2.S has been associated with thrombosis with thrombocytopenia and possibly Guillain-Barre syndrome, and the mRNA vaccines have been associated with myocarditis. The risks of these events are extremely small, and the benefits of all the vaccines outweigh them. However, cases of vaccine-associated thrombosis with thrombocytopenia and Guillain-Barre syndrome have been more severe with greater morbidity compared with cases of vaccine-associated myocarditis. Potential recipients of any vaccine should be aware of the specific risks, which are discussed in detail elsewhere. (See 'Specific safety concerns' below.)
Additionally, although precise comparative efficacy is uncertain because the different vaccines have not been compared directly in trials, limited evidence suggests that mRNA vaccines may be more effective than Ad26.COV2.S, including against severe infection, and mRNA-1273 may be slightly more effective than BNT162b2 [26-31].
•In several observational studies, vaccine effectiveness associated with two doses of the mRNA vaccines is higher than that with one dose of Ad26.COV2.S [16,26,32-34]. As an example, in a case control study of 3689 immunocompetent adults hospitalized for COVID-19, estimated effectiveness against COVID-19-related hospitalization was 93 and 88 percent for mRNA-1273 and BNT162b2, respectively, compared with 71 percent for Ad26.COV2.S. Although the analysis adjusted for age, sex, admission date, geographic region, and race, the contribution of these and other unmeasured confounders, such as variable exposure risk, to the apparent differences in effectiveness is uncertain.
•Several observational studies also suggest that mRNA-1273 vaccine effectiveness is slightly higher than that of BNT162b2, although it is unclear whether there is a clinically significant difference [26-31,35]. In a study from the United States that compared over 400,000 veterans who received either mRNA-1273 or BNT162b2, mRNA-1273 was associated with lower rates of documented infection, symptomatic COVID-19, and associated hospitalization over 24 weeks, but the absolute differences were low (differences of 1.23, 0.44, and 0.55 cases per 1000 people, respectively) [28]. Safety of the mRNA vaccines in the same cohort was largely comparable, with only small differences in serious adverse events of uncertain clinical significance [36].
Because it has not been available for as long as the other vaccines, data on NVX-CoV2373 are more limited, although large randomized trials support its efficacy; there may be a risk for myocarditis with this vaccine as well.” (See 'NVX-CoV2373 (Novavax COVID-19 vaccine)'