Lundquist Institute investigator Eric S. Daar, MD, is among the authors of a new ACTIV-2/ACTG A5401 (Advancing Clinical Therapeutics Globally) analysis examining how sex-related differences in viral shedding and symptom burden may vary by timing since symptom onset during acute COVID-19.

About the Study

The study analyzed data from 668 placebo recipients enrolled in ACTIV-2/ACTG A5401 between August 2020 and August 2021 across six countries. A primary analysis included 469 participants with quantifiable baseline viral loads. Participants self-collected anterior nasal swabs for SARS-CoV-2 RNA testing and completed daily symptom diaries tracking 13 targeted symptoms over 29 days

Key Findings

• Male and female participants had comparable nasal SARS-CoV-2 RNA levels at study entry and throughout follow-up when analyzed by study day.
• When results were evaluated by days since symptom onset, female participants had higher nasal SARS-CoV-2 RNA levels than male participants during the earliest symptomatic phase—the first three days after symptoms began.
• Later in infection, viral RNA levels were generally similar or lower among female participants compared with male participants.
• Female participants tended to report higher symptom scores across days since symptom onset.
• The study found no significant correlation between nasal SARS-CoV-2 RNA levels and symptom score, regardless of sex.

Why It Matters

The analysis points to a practical consideration for clinical research: study day alone may not capture where a participant is in the course of infection. For acute respiratory illnesses such as COVID-19, influenza, RSV, and other viral respiratory infections, accounting for days since symptom onset may improve how investigators evaluate viral load, symptom trends, and potential antiviral treatment effects. This is especially important because a participant’s stage of illness may affect how trial results are interpreted, even when viral RNA levels and symptom scores are not directly correlated.

HIV Medicine Leadership

Eric S. Daar, MD, is an Investigator in HIV Medicine and Executive Medical Officer at The Lundquist Institute, Professor of Medicine at the David Geffen School of Medicine at UCLA, and Chief of the Division of HIV Medicine at Harbor-UCLA Medical Center. An infectious diseases-trained clinician-investigator, Dr. Daar has more than 30 years of experience in HIV care and clinical and translational research. His work has focused on HIV pathogenesis, HIV prevention, optimal HIV management, SARS-CoV-2 pathogenesis, and COVID-19 treatment and prevention trials.

 For more information on Dr. Daars research or about the Division of HIV Medicine at The Lundquist Institute, please visit : Lundquist.org/eric-s-daar-MD.