New York, NY—Years into the COVID-19 pandemic, understanding is increasing about what clinical and demographic factors are associated with rates of COVID-19, severe COVID-19, and SARS-CoV-2 infection.

A secondary analysis of 57,692 participants randomized to the placebo groups of four COVID-19 vaccine phase III efficacy trials found that exposure risks, demographics (age and race), and evidence of previous infection had the strongest associations with study outcomes. The results were published in the Journal of the American Medical Association Network Open.

The Columbia University Irving Medical Center–led authors pointed out that current data identifying COVID-19 risk factors lack standardized outcomes and insufficient controls for confounders. The study team sought to remedy that by conducting a secondary cross-protocol analysis of four multicenter, international, randomized, blinded, placebo-controlled, COVID-19 vaccine efficacy trials with harmonized protocols established by the COVID-19 Prevention Network.

To do that, the researchers combined and analyzed individual-level data from participants randomized to receive a placebo within each trial. Enrollment began July 2020, and the last data cutoff was in July 2021. Participants included adults in stable health, at risk for SARS-CoV-2, and assigned to the placebo group within each vaccine trial. Data were analyzed from April 2022 to February 2023.

The coprimary outcomes were defined as COVID-19 and severe COVID-19. Secondary outcomes included severe COVID-19 among people with COVID-19, subclinical SARS-CoV-2 infection, and SARS-CoV-2 infection.

The 57,692 participants had a median age of 51 years, with 20.3% aged 65 years and older. The analysis population was 70.6% white, with 5.7% American Indian or Alaska Native participants, 13.9% black participants, and 30.6% Hispanic participants. The study noted that annualized incidence was 13.9% (95% CI, 13.3%-14.4%) for COVID-19 and 2.0% (95% CI, 1.8%-2.2%) for severe COVID-19.

The results indicated that factors associated with increased rates of COVID-19 included workplace exposure (high vs. low: adjusted hazard ratio [aHR], 1.35 [95% CI, 1.16-1.58]; medium vs. low: aHR, 1.41 [95% CI, 1.21-1.65]; P <.001) and living condition risk (very high vs. low risk: aHR, 1.41 [95% CI, 1.21-1.66]; medium vs. low risk: aHR, 1.19 [95% CI, 1.08-1.32]; P <.001).

In contrast, factors associated with decreased rates of COVID-19 included previous SARS-CoV-2 infection (aHR, 0.13 [95% CI, 0.09-0.19]; P <.001); aged 65 years or older (aHR vs. aged younger that 65 years, 0.57 [95% CI, 0.50-0.64]; P <.001); and black or African American race (aHR vs. white race, 0.78 [95% CI, 0.67-0.91]; P = .002).

In analyses restricted to participants who contracted COVID-19, increased severe COVID-19 rates were associated with:

• Age 65 years or older (aHR vs. <65 years, 1.75 [95% CI, 1.32-2.31]; P <.001)
• Race (American Indian or Alaska Native vs. white: aHR, 1.98 [95% CI, 1.38-2.83]; black or African American vs. white: aHR, 1.49 [95% CI, 1.03-2.14]; and multiracial: aHR, 1.81 [95% CI, 1.21-2.69]; overall P = .001)
• BMI (aHR per 1-unit increase, 1.03 [95% CI, 1.01-1.04]; P = .001)
• Diabetes (aHR, 1.85 [95% CI, 1.37-2.49]; P <.001).

Previous SARS-CoV-2 infection was associated with decreased severe COVID-19 rates (aHR, 0.04 [95% CI, 0.01-0.14]; P <.001).

“In this secondary cross-protocol analysis of 4 randomized clinical trials, exposure and demographic factors had the strongest associations with outcomes; results could inform mitigation strategies for SARS-CoV-2 and viruses with comparable epidemiological characteristics,” the authors wrote.

Noting that ARS-CoV-2 infection and COVID-19 remain a significant global health challenge,” the researchers pointed out that “despite the development of safe and effective vaccines, globally, billions of people remain unvaccinated. Greater understanding of risk factors for infection and severe disease can guide future vaccine uptake prioritization strategies and therapeutic allocation policies.”

The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.

 « Click here to return to Weekly News.