ABSTRACT
BACKGROUND: Although COVID-19 booster vaccination is widely recommended, there is limited long-term, population-level, real-world evidence on the magnitude of improved protection against severe COVID-19 conferred by boosting with monovalent COVID-19 vaccines developed against ancestral SARS-CoV-2, especially in low- or middle-income countries. We present interim results from the first large-scale assessment of the relative vaccine effectiveness (rVE) of first and second booster doses against severe COVID-19 in a low-/middle-income country. METHODS: REFORCO-Brazil is an ongoing, test-negative case-control study (NCT05697705) utilizing Brazil national severe acute respiratory syndrome (SARS) surveillance and vaccination data. In SARS hospitalizations from August 1, 2021 to July 31, 2022, we matched test-positive (via SARS-CoV-2 antigen/reverse transcription polymerase chain reaction [RT-PCR]) cases and test-negative case-controls (via RT-PCR) based on admission date, preceding vaccinations, and age. We evaluated the rVEs of four monovalent COVID-19 vaccines (AZD1222, Ad26.COV2.S, CoronaVac, and BNT162b2) as second boosters compared with any first boosters received ≥4 months previously, and as first boosters compared with primary-series vaccinations completed ≥4 months previously. RESULTS: The overall rVE of second boosters, from 5668 (2238 test-positive) evaluated hospitalizations, was 24.7 % (95 % confidence interval [CI]: 12.6-35.1); the overall rVE of first boosters, from 30,272 (12,063 test-positive) hospitalizations, was 46.8 % (95 % CI: 43.3-50.0). The rVEs of AZD1222 and BNT162b2 were similar: 29.4 % (95 % CI: 8.6-45.5) and 25.5 % (95 % CI: 4.2-42.2), respectively, for second boosters; and 42.5 % (95 % CI: 28.0-54.0) and 50.8 % (95 % CI: 47.5-54.0), respectively, for first boosters. In general, rVEs were higher in elderly (≥80 years) and immunocompromised/high-risk individuals. CONCLUSIONS: Our results support the use of AZD1222 and other adenoviral/mRNA vaccine boosters to maintain protection against COVID-19 hospitalization from Omicron subvariants, including in elderly and immunocompromised individuals at increased risk of accelerated waning or severe outcomes.
Subject(s)
COVID-19 Vaccines/adverse effects , Databases, Factual , Global Health , Thrombocytopenia/epidemiology , Thrombosis/epidemiology , Aged , Aged, 80 and over , ChAdOx1 nCoV-19 , European Union , Female , Humans , Male , Middle Aged , Thrombocytopenia/etiology , Thrombosis/etiology , United Kingdom/epidemiologyABSTRACT
The authors studied the effect of raltegravir on the pharmacokinetics of the antiepileptic agent lamotrigine. Twelve healthy volunteers (group A) received 400 mg raltegravir twice daily from days 1 to 5. On day 4, a single dose of 100 mg lamotrigine was administered. After a washout period, participants received a second single dose of 100 mg of lamotrigine but now without raltegravir (day 32). In group B, 12 participants received the same treatment as in group A but in reverse order. On days 4 and 32, 48-hour pharmacokinetic curves were drawn. Geometric mean ratios (+90% confidence intervals [CIs]) of lamotrigine area under the plasma concentration-time curve (AUC(0-->48)) and peak plasma concentration (C(max)) for raltegravir + lamotrigine versus lamotrigine alone were 0.99 (0.96-1.01) and 0.94 (0.89-0.99), respectively. The mean ratio of the AUC(0-->48) of lamotrigine-2N-glucuronide to lamotrigine was similar when lamotrigine was taken alone (0.35) or when taken with raltegravir (0.36). Raltegravir does not influence the glucuronidation of lamotrigine.
