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Covid-19 vaccine booster

Indications: - immunocompromised individuals - immunocompromised children ages 5-11 at least 28 days after their two-dose primary series [40] - adults, adolescents 12 & up (5 months after 2nd dose) (Pfizer or Moderna) [40] - mix & match equally safe & effective [46] - during Omicron predominance, COVID-19 hospitalization rates in Los Angeles County among unvaccinated persons were 23.0 times those of fully vaccinated persons with a booster, & 5.3 times those among fully vaccinated persons without a booster [45] - previously unvaccinated individuals will be eligible for a single dose of bivalent Moderna or Pfizer Covid-19 vaccine [82] - they will then be considered fully vaccinated (after 2 weeks) & not eligible for a Covid-19 vaccine booster [82] Adverse effects: - see Covid-19 vaccine - swollen lymph nodes most common (5%) [19] - urticaria 12 days after Covid-19 mRNA vaccine booster [50] - monovalent Moderna COVID-19 booster vaccine may be associated with an increased risk for new-onset chronic spontaneous urticaria lasting > 6 weeks [77] - stroke risk within 21 days detected by CDC's Vaccine Safety Datalink in adults >= 65 years who received Pfizer-BioNTech's bivalent COVID-19 vaccine booster [74] - Vaccine Adverse Event Reporting System, the Centers for Medicare & Medicaid Services database, & a preliminary study of the Veterans Affairs database found no evidence for an increased risk with either Pfizer or Moderna's bivalent vaccines [74] - no increase in risk of stroke after bivalent Covid-19 vaccine booster except if administered with or separately from high-dose influenza vaccine [87] - no evidence for increased risk of cardiovascular events after Pfizer-BioNTech's bivalent COVID-19 vaccine booster [80] - ipsilateral axillary lymphadenopathy after COVID-19 vaccine booster is common & can persist for months [84] Notes: === WHO did not support booster vaccinations early in the pandemic === - richer countries should focus on ramping up vaccine supply to billions who are still waiting for their first dose [4,5] - solely for the purpose of managing a pandemic (independent of alleviating death & suffering in low & lower-middle income countries where < 15% of people are vaccinated), preventing the emergence of variants is far better managed by vaccinating the underserved unvaccinated than to vaccinate the vaccinated [4,22] - Covid-19 is likely here to stay as SARS-CoV2 continues to mutate in unvaccinated countries across the world & previous hopes of eradicating it diminish (WHO) [16] - WHO says wealthy nations are prolonging pandemic by hoarding Covid treatments & vaccines offering boosters to the vaccinated while leaving the unvaccinated underserved populations of the world to serve as incubation reservoirs for mutations of SARS-CoV2 & emergence of treatment & vaccine-resistant variants [18] * see pandemic management === 2 dose mRNA vaccines produce strong protection === - multiple studies show that 2 dose mRNA vaccines provide strong protection against severe disease (95% against hospitalization) [5] - data from the Israeli Ministry of Health suggests protection against severe disease is nearly 92% for people < 50 years & 85% for those > 50 years (without booster) - overall effectiveness of Pfizer vaccine decreases from 96% to 84% after 6 months [9] - antibody titer decline faster in cipients of the Pfzer vaccine than in COVID-19 survivors [11] - antibody titers decline by up to 40% per month in vaccinated persons, vs < 5% per month in Covid-19 convalescents - at 6 months, ~84% of vaccine recipients still have detectable antibody titers, whereas ~90% of Covid-19 convalescents still have detectable antibodies titers after 9 months [11] - a 3rd dose of Pfizer vaccine increases immune response 11 times higher than after the 2nd dose in older patients 65-85 years of age [9] (12 people studied) - a 3rd dose of Pfizer vaccine increases protection against Covid-19 infection 4-fold after 10 days in adults > 60 years according to Israeli Health Ministry [10] - early supporting evidence for booster largely from Israel for Pfizer vaccine - 4th Pfizer vaccine of marginal benefit to Israeli healthcare workers [47] - vaccine effectiveness generally decreases over time against SARS-CoV-2 infections, hospitalizations, & mortality [79] === breakthrough infections likely due to Delta variant, not waning immunity === - vaccine efficacy against all SARS-CoV2 infections in New York dropped from 92% to 80% between May & July 2021, as the Delta variant took over in the region [6] === in immunocompromised patients === - response to primary vaccination series of Pfizer vaccine predicts response to booster - patient with primary solid tumor including those undergoing active chemotherapy have adequate response to Pfizer Covid-19 vaccine booster [36] - 4th dose of Covid-19 vaccine (Pfizer or Moderna) available to immunocompromised Jan 2022 [42] - in the pre-Omicron era, nursing home residents receiving ancestral Covid-19 vaccine booster were less likely to be hospitalized or to die than unboosted residents [73] === Covid-19 vaccine booster marketing === - Pfizer vaccine booster does substantially increase serum anti-spike protein antibody levels [35] - Moderna seeks FDA-approval for Covid-19 vaccine booster September 2021 [14] - Moderna's Covid-19 vaccine booster will be 1/2 the dose of its original vaccine [17] - a Pfizer BNT162b2 vaccine booster among fully vaccinated Israeli citizens >= 60 years at least 5 months after 2nd dose had 11 fold decrease in risk of confirmed Covid-19 infection & > 19-fold decrease in risk of severe disease [15] - methods include 1,144,690 individuals >= 60 years followed between July 30 & August 22, 2021 & adjusting for possible confounding factors - reported follow-up period for that trial only went to 25 days post vaccination [15] - a 2nd dose of J&J Ad26.COV2.S vaccine induces high antibody levels [2] - Covid-19 vaccine makers plan for annual boosters [37] - Omicron variant could make it more likely that people will need a 4th Covid-19 vaccine earlier than expected [39] === boosters & Omicron === - a 3rd dose of Pfizer or Moderna mRNA vaccine increases cross-reactive antibody responses sufficient to neutralize Omicron [41] - a 3rd dose of Pfizer or Sinovac Covid-19 vaccine reduced Covid-19 related mortality compared with only 2 doses by 90% [78] - 4th Pfizer dose with limited defense against Omicron variant [44] - at 4 weeks after 4th dose of Pfizer vaccine,risk of Covid-19 infection lower than after 3 doses (RR-0.38), but protection waned with time [49] - protection against severe disease did not wane within 6 weeks after 4th dose [49] - protection against Covid-19 related hospitalization or death in 30 day period after 4th vaccination [52] - 3 doses of mRNA COVID-19 vaccine, vs none or 2 doses associated with protection against both the Omicron & Delta variants, although less protection for Omicron than for Delta [43] - vaccinated persons better protected against Omicron variants after a breakthrough case of Omicron than after an additional booster shot [54] - 44% of hospitalizations among adults during the Omicron dominance period were vaccinated & double boosted [62] - Moderna & Bancel have announced bivalent mRNA vaccine boosters that provide superior protection against Omicron [51] - contains the original mRNA-1273 (Spikevax) vaccine & mRNA specifically designed to target Omicron BA.4 & BA.5 Omicron subvariants - Moderna mRNA-1273.214 50 ug dose - Moderna says it will have large amounts of an Omicron-specific booster available by late summer/fall 2022 [51,53,55] - Moderna says its mRNA-1273.214 vaccine has neutralizing antibody response against Omicron & a potent response against subvariants BA.4 & BA.5 - Moderna is also developing a bivalent booster vaccine candidate that specifically targets Omicron subvariants BA.4 & BA.5 [57] - Moderna's vaccine contains 25 ug of its original vaccine + 25 ug of an Omicron subvariant [58] - Moderna's vaccine increases neutralizing antibody titers 6.3-fold against Omicron subvariants BA.4 & BA.5 vs the 3.5-fold increase with its original vaccine [58] - Pfizer vaccine targets spike protein of omicron BA.1 variant [61] - Pfizer bivalent vaccine increases protective antibodies against the Omicron BA.5 subvariant in adults after 1 week [66] - Pfizer bivalent vaccine provides protection against omicron BQ.1 & BQ.1.1 [69] - bivalent vaccines protective against Omicron Subvariant BA.2.75 [70] - FDA approves bivalent ancestral + Omicron-specific COVID-19 vaccines from Pfizer & Moderna [63] - Moderna's bivalent omicron-containing vaccine mRNA-1273.214 elicits neutralizing antibody responses against omicron superior to mRNA-1273, without evident safety concerns [64] - Omicron BQ & XBB subvariants may be resistant to Pfizer & Moderna bivalent vaccines [71] - Moderna's mRNA-1273 vaccine effectiveness against Omicron may disappear after 90 days [65] - booster (3rd dose) appears to provide some protection against Omicron [68] - bivalent boosters > 80% in keeping older adults (> 65 years) out of the hospital (Dec 2022) [72] - bivalent booster of limited efficacy - imprinting results in immune system primed to respond to antigens of first vaccine received [75] - relative risk reduction in preventing hospitalization or death due to COVID-19 is 67% at 2 weeks after vaccination, declining to 38% at > 20 weeks [83] - bivalent COVID-19 boosters provide similar protection against symptomatic illness from XBB/XBB.1.5 Omicron subvariants as from BA.5-related subvariants (CDC) [76] - a single dose of mRNA bivalent COVID-19 booster after August 16, 2022 is considered fully vaccinated [82] (see Indications: above) - unsatisfactory antibody response to Omicron variant of Covid-19 after bivalent Covid-19 vaccine booster in ~25% of patients with NSCLC [83] - Sanofi, GSK adjuvanted bivalent D614 & Beta (B.1.351) vaccine candidate - Novavax: Omicron BA.4/5 - adults can receive Novavax booster 6 months after primary series - Novavax booster for adults unable to get Pfizer of Moderna bivalent Covid-19 vaccine booster or who otherwise would not receive a COVID-19 vaccine booster shot at all [67] - Moderna, Pfizer & Novavax offer Covid-19 vaccine boosters that target Omicron XBB.1.5 in fall of 2023 (no coverage of ancestral strain) [85] - Covid-19 monovalent XBB.1.5 vaccine 54% effective in preventing symptomatic Covid-19 infection, January 2024 [86] - Covid-19 revised for 2024-2025 to target the KP.2 variant of SARS-CoV2 [88] === Federal Agencies on Covid-19 vaccine booster === - FDA & CDC joint statements: (historical) - Covid-19 vaccine booster not needed (July 8, 2021) [8] - Covid-19 vaccine booster would be offered Sept 20, 2021 (August 18, 2021) [8] - 2 high-level officials in the FDA's Office of Vaccines Research & Review resigned reportedly because they were angry that the Biden administration was making decisions that should be left up to that agency [13] - FDA advisory panel voted unanimously on Sept 17, 2021 to recommend a 3rd dose of Pfizer's mRNA COVID-19 vaccine for elderly >=65 & those at high risk for severe outcomes [19,26] - the FDA advisory panel voted 16-2 against a 3rd dose of Pfizer vaccine for Americans >= 16 years [26] - CDC confirms recommendation of a 3rd dose of Pfizer's mRNA COVID-19 vaccine for elderly >=65 & those at high risk for severe outcomes, but not for healthcare or other frontline workers [28] - FDA advisory panel VRBPAC [31] & CDC [34] recommends approval of Moderna booster - dose 50 ug - adults ages >= 65 years - younger adults with high-risk medical conditions - high risk of occupational or institutional exposure - FDA advisory panel VRBPAC recommends a booster dose of Johnson & Johnson's COVID-19 vaccine for all individuals who received the single-dose vaccine [32] - FDA approves Johnson & Johnson's vaccine booster [34] - to be given >= 2 months after the initial dose - safe for people who got the Johnson & Johnson vaccine follow up with a dose of an mRNA vaccine from Pfizer or Moderna [33] - FDA approves 2nd booster dose of Pfizer or Moderna's mRNA COVID-19 vaccine for adults ages >= 50 years, & immunocompromised persons [48]* - FDA approves 2nd booster dose of Pfizer or Moderna's mRNA COVID-19 vaccine for adults >= 65 years or immunocompromised persons [81] - large study supports the recommendation for a second Pfizer booster in long-term care residents June 2022 [59] - senior author with signficant financial ties to Pfizer - study in Isreal among healthcare workers Jan 2-Jan 31, 2022 reports 4th dose of Pfizer vaccine (given on Jan 2) reduced infection from 19.8% to 6.9% [60] * immunocompromised people will receive 5 doses of Covid-19 mRNA vaccine in total: a 3-dose primary series, & 2 boosters [48] === Pfizer Covid-19 vaccine booster in Israel === - Pfizer Covid-19 vaccine booster decreased risk of severe disease by a factor of 18 in persons > 60 years and 22 in younger persons - risk of death was reduced by a factor of 15 [38] - a 4th dose of Pfizer BNT162b2 vaccine effectiveness against infection peaked at 65% during week 3 after vaccination but declined to 22% by week 10 - 72% effective in preventing severe disease for >= 10 weeks [56]

General

COVID-19 vaccine; SARS CoV-2 vaccine

References

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