Due to continuous technical developments and new insights into the high complexity of infectious diseases such as COVID-19, there is an increasing need for multiplex biomarkers to aid clinical management and support the development of new drugs and vaccines. COVID-19 disease requires rapid diagnosis and stratification to enable the most appropriate treatment course for the best possible outcomes for patients. In addition, these tests should be rapid, specific, and sensitive. They should rule out other potential causes of illness with simultaneous testing for other diseases. Elevated levels of specific biomarkers can be used to establish severity risks of chronic diseases so that patients can be provided the proper medication at the right time. This review describes the state-of-the-art technologies in proteomics, transcriptomics, and metabolomics, for multiplex biomarker approaches in COVID-19 research.