February 15, 2024

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RSV

Early Estimates of Nirsevimab Immunoprophylaxis Effectiveness against Hospital Admission for Respiratory Syncytial Virus Lower Respiratory Tract Infections In infants, Spain, October 2023 to January 2024
In late September 2023, Spain introduced universal RSV prophylaxis into its national immunization program for all infants born after 1 April 2023. Here, we see the early estimates of the effectiveness of nirsevimab against hospital admission for RSV-LRTI in infants (< 9 months old) in three autonomous regions of Spain. These results are from multicenter hospital-based active surveillance in nine hospitals located in three autonomous regions (five hospitals in Valencia, three in Murcia and one in Valladolid, a province of Castilla y León) in Spain. The population during the data collection period consisted of all infants eligible for immunization with nirsevimab during their first RSV season (born from 1 April 2023, n = 15,676 infants, representing 6.4% of the entire Spanish infant population eligible for immunization). The surveillance period lasted from 1 October 2023 to between 31 December 2023 and 10 January 2024, depending on the hospital. All infants admitted with LRTI were included. Effectiveness of nirsevimab immunoprophylaxis by region was assessed by the screening method, in which the proportion of infants immunized with nirsevimab among RSV-LRTI hospitalized cases was compared to the proportion of immunized infants in the corresponding region/hospital catchment area. They calculated that Nirsevimab effectiveness against hospital admission with RSV-LRTI admission was 69.3% in Valencia, 86.9% in Murcia, and 97.0% in Valladolid.

FLU

Redirecting Antibody Responses from Egg-adapted Epitopes Following Repeat Vaccination with Recombinant or Cell Culture-based versus Egg-based Influenza Vaccines
There is a concern that repeat vaccination with egg-based influenza vaccines could preferentially boost antibodies targeting the egg-adapted epitopes and reduce immunogenicity to circulating viruses. In this randomized trial (Clinicaltrials.gov: NCT03722589), sera pre- and post-vaccination with quadrivalent inactivated egg-based (IIV4), cell culture-based (ccIIV4), and recombinant (RIV4) influenza vaccines were collected from healthcare personnel (18-64 years) in 2018−19 (N = 723) and 2019−20 (N = 684) influenza seasons. They report that vaccine egg-adapted changes had the most impact on A(H3N2) immunogenicity. In year 1, RIV4 induced higher neutralizing and total HA head binding antibodies to cell- A(H3N2) virus than ccIIV4 and IIV4. In year 2, among the seven repeat vaccination arms (IIV4-IIV4, IIV4-ccIIV4, IIV4-RIV4, RIV4-ccIIV4, RIV4-RIV4, ccIIV4-ccIIV4 and ccIIV4-RIV4), repeat vaccination with either RIV4 or ccIIV4 further improved antibody responses to circulating viruses with decreased neutralizing antibody egg/cell ratio. RIV4 also had higher post-vaccination A(H1N1)pdm09 and A(H3N2) HA stalk antibodies in year 1, but there was no significant difference in HA stalk antibody fold rise among vaccine groups in either year 1 or year 2. They suggested that multiple seasons of non-egg-based vaccination may be needed to redirect antibody responses from immune memory to egg-adapted epitopes and re-focus the immune responses towards epitopes on the circulating viruses to improve vaccine effectiveness.
Risk of Cardiovascular Events after Influenza: A Population-based Self-controlled Case Series Study, Spain, 2011-2018
A population-based self-controlled case series design was used with individual-level data from electronic registries (n = 2,230,015). The risk of atherothrombotic events in subjects ≥50 years old increased more than two-fold during the 14 days after the mildest influenza cases in patients with fewer risk factors and more than four-fold after severe cases in the most vulnerable patients, remaining in them more than two-fold for two months.
Risk of Death Following Chikungunya Virus Disease in the 100 Million Brazilian Cohort, 2015–18: A Matched Cohort Study and Self-controlled Case Series
Investigators looked at 143,787 individuals that had CHIK compared to matched controls and looked at all-cause natural mortality up to 728 days after onset of chikungunya virus disease symptoms, and secondary outcomes were cause-specific deaths, including ischemic heart diseases, diabetes, and cerebrovascular diseases. They reported that the incidence rate ratio (IRR) of death within seven days of chikungunya symptom onset was 8·40 (95% CI 4·83–20·09) as compared with the unexposed group and decreased to 2·26 (1·50–3·77) at 57–84 days. For the secondary outcomes, the IRR of deaths within 28 days after disease onset were: 1·80 (0·58–7·00) for cerebrovascular diseases, 3·75 (1·33–17·00) for diabetes, and 3·67 (1·25–14·00) for ischemic heart disease.

COVID: Active Vaccination/Immunity

Comparative Effectiveness of Alternative Intervals Between First and Second Doses of the mRNA COVID-19 Vaccines
Here the investigators use a target trial emulation approach. This is a way of looking at observational data that adjusts things to try to avoid many of the biases such as immortal time bias and other confounders but this is still observational data, with inherent limitations. The investigators used this study design to compare the effectiveness of different interdose intervals among >6 million mRNA vaccine recipients in Georgia, USA, from December 2020 to March 2022. The compared three different vaccine schedules: recommended by the Food and Drug Administration (FDA) (17-25 days for Pfizer-BioNTech; 24-32 days for Moderna), the late-but-allowable (26-42 days for Pfizer-BioNTech; 33-49 days for Moderna) late ( ≥ 43 days for Pfizer-BioNTech; ≥50 days for Moderna). The effectiveness endpoint here is SARS-CoV-2 infection. They report that in the short-term, the risk of SARS-CoV-2 infection was lowest under the FDA-recommended protocol. Longer-term, the late-but-allowable protocol resulted in the lowest risk (risk ratio on Day 120 after the first dose administration compared to the FDA-recommended protocol: 0.83 [95% confidence interval: 0.82-0.84]).
Early Mortality After the First Dose of Coronavirus Disease 2019 Vaccination: A Target Trial Emulation
A problem that we encountered with COVID vaccinations was a hesitancy surrounding safety concerns. We still hear lots of anecdotes about how high-risk elderly patients would die in the two months after getting a COVID vaccine. Is this because elderly people with lots of medical problems have an increased risk of death from an adverse vaccine side effect, or is this a group with a high incidence of mortality to begin with? Here these investigators conducted a target trial emulation to estimate and compare risk of death up to 60 days under two COVID-19 vaccination strategies: vaccination within seven days of enrollment versus no vaccination through follow-up. The study cohort included individuals aged ≥18 years enrolled in the Veterans Health Administration system and eligible to receive a COVID-19 vaccination according to guideline recommendations from 1 March 2021 through 1 July 2021. The outcomes of interest included deaths from any cause and excluding a COVID-19 diagnosis. (This is an important distinction because you do not get credit for saving people from COVID, you just risk getting penalized if there is a safety issue with the vaccine.) They included 3,158,507 veterans. 364 993 received the vaccine within seven days. At 60 days, there were 156 deaths per 100,000 veterans among those that were vaccinated versus 185 deaths in the group that did not get vaccinated, corresponding to an absolute risk difference of −25.9 (95% confidence limit [CL], −59.5 to 2.7) and relative risk of 0.86 (95% CL, .7 to 1.0). When we exclude those with a COVID-19 infection in the first 60 days, the absolute risk difference was −20.6 (95% CL, −53.4 to 16.0) with a relative risk of 0.88, so a 12% reduction from all causes excluding COVID-19.