Health disparities are an immense challenge to American society. Clinical and Translational Science Awards (CTSAs) housed within the National Center for Advancing Translational Science (NCATS) are designed to accelerate the translation of experimental findings into clinically meaningful practices and bring new therapies to the doorsteps of all patients. Research Centers at Minority Institutions (RCMI) program at the National Institute on Minority Health and Health Disparities (NIMHD) are designed to build capacity for biomedical research and training at minority serving institutions. The CTSA created a mechanism fostering formal collaborations between research intensive universities and minority serving institutions (MSI) supported by the RCMI program. These consortium-level collaborations activate unique translational research approaches to reduce health disparities with credence to each academic institutions history and unique characteristics. Five formal partnerships between research intensive universities and MSI have formed as a result of the CTSA and RCMI programs. These partnerships present a multifocal approach; shifting cultural change and consciousness toward addressing health disparities, and training the next generation of minority scientists. This collaborative model is based on the respective strengths and contributions of the partnering institutions, allowing bidirectional interchange and leveraging NIH and institutional investments providing measurable benchmarks toward the elimination of health disparities.

Background

While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection.

Methods

In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7-15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures.

Findings

Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05-0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01-0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease.

Interpretation

Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection.

Funding

National Institutes of Health.