HETEROLOGOUS THIRD AND FOURTH DOSE VACCINE TO REDUCE SEVERITY AND MORTALITY IN COVID-19 PATIENTS DURING DELTA AND OMICRON PREDOMINANT IN THAILAND

INTRO: To ensure adequate coverage against numerous waves of different variants of concern, Thailand has proactively adopted heterologous primary and booster 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 (CMC-19 HIS) network established in Chiang Mai, Thailand, we conducted a cohort study by linking patient-level data on laboratory-confirmed hospitalised 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, mortality were examined for each period. FINDINGS: Patients hospitalised during delta predominance were ten times more likely to have severe COVID-19 outcomes, in-hospital deaths, and a longer median hospital stay 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. CONCLUSION: The risk of severe outcomes were significantly lower for COVID-19 patients hospitalised 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.