Heterologous third and fourth dose vaccine to reduce severity and mortality in COVID-19 patients during delta and omicron predominance: A cohort study in Chiang Mai, Thailand

Abstract

Background The Coronavirus disease 2019 (COVID-19) pandemic has evolved quickly, with numerous waves of different variants of concern resulting in the need for countries to offer continued protection through booster vaccinations. To ensure adequate coverage, Thailand has proactively adopted heterologous vaccination schedules. While studies have assessed homologous schedules in detail, the effectiveness of heterologous booster vaccine schedules against severity and mortality of COVID-19 patients, particularly with newer variants, remains to be explored fully. Methods Utilising an active Hospital Information System for COVID-19 established in Chiang Mai, Thailand, we conducted a cohort study by linking patient-level data on laboratory-confirmed COVID-19 cases to the national immunization records, during delta-predominant (1st October – 31st December 2021) and omicron predominant (1st February – 30th April 2022) periods. Demographic and baseline clinical characteristics associated with severe COVID-19 outcomes and mortality were examined for each period. Results COVID-19 cases during delta predominance were ten times more likely to have severe outcomes and in-hospital deaths as compared to omicron predominance. During omicron predominance, a third vaccine dose was associated with 89% reduced risk of both severe COVID-19 and deaths, as compared to the unvaccinated group. Those who received the third dose 14–90 days prior to the date of positive SARS-CoV-2 test had the highest protection against severe COVID-19 outcomes (93%) followed by a drop to 87% among those who received their last dose > 90 days prior. Severe outcomes were not observed among third dose recipients during delta predominance and fourth dose recipients during omicron predominance. All the vaccine types used for boosting in Thailand offered similar protection against severe COVID-19. Conclusions The risk of severe outcomes were significantly lower for COVID-19 patients with omicron as compared to delta. Booster doses provided very high level of protection against severe COVID-19 outcomes and deaths. Ongoing booster campaigns should focus on improving coverage utilising all available vaccines to ensure optimal protection.

Comparative effectiveness of the bivalent BA.4-5 and BA.1 mRNA-booster vaccines in the Nordic countries

“…Covid-19 vaccination policies recommending the bivalent mRNA-booster vaccines as a fourth dose are mainly supported by studies on immunogenicity where some have shown higher induction of antibody levels against omicron subvariants including BA.4-5 compared with monovalent boosters. [4][5][6][7][8] Previous observational effectiveness studies of fourth dose monovalent vaccination, primarily on data from before BA.4-5 subvariant predominance, [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] also lend some indirect support to these recommendations.…”

“…[9][10][11][12] Previous observational studies of fourth doses are primarily limited to the monovalent mRNA Covid-19 vaccines and mainly during periods prior to the emergence of the current predominating omicron subvariants BA.4 and BA.5. [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] As such, data on the effectiveness of the bivalent mRNA-vaccines are needed to guide Covid-19 vaccination policy and to evaluate the benefit of developing variant-adapted Covid-19 vaccines.…”