| Summary: | Due to the widespread Omicron variant of SARS-CoV-2 in Thailand, the effectiveness of COVID-19 vaccines has become a major issue. The primary objective of this study is to examine the real-world effectiveness of COVID-19 vaccines based on secondary data acquired under normal circumstances in a real-world setting, to protect against treatment with invasive ventilation of pneumonia during January to April 2022, a period when Omicron was predominant. We conducted a nationwide test-negative case–control study. The case and control were matched with a ratio of 1:4 in terms of age, date of specimen collection, and hospital collection specimen and the odds ratio was calculated using conditional logistic regression. Overall, there was neither a distinction between mix-and-match regimens and homologous mRNA regimens against severe symptoms, nor was there a decline of the protective effect over the study period. The third and fourth dose boosters with ChAdOx1 nCoV-19 or mRNA vaccines provided high levels of protection against severe outcomes, approximately 87% to 100%, whereas two doses provided a moderate degree (70%). Thus, this study concludes that current national vaccine strategies provide favourable protective benefits against the Omicron variant. All Thais should receive at least two doses, while high-risk or vulnerable groups should be administered at least three doses.
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