8: Consider enrollment and objectives carefully
A proportion of people with long COVID will recover in the early months after infection. Ideally, clinical trials will primarily study treatments in patients who have been ill 6 months or longer, as some natural recovery will happen before that can bias studies.
But where resources are abundant, it is ideal for trials to additionally look at whether the treatments can help patients in the early months recover and prevent progression to the later stage.
9: Tracking illness duration is crucial
Research from ME/CFS shows that there may be an immune change in the first few years of the illness, where cytokines decrease without any corresponding change in symptom improvement.
Because of this and the possibility that other markers follow the same pattern, disease duration should be a core feature of all analyses and trial designs. Trial outcomes should be designed to answer the question of whether the medication helps patients at different durations of illness.
10: Prioritize patient populations less likely to recover without intervention
Some long COVID phenotypes seem less likely to recover without intervention. Trials should take care to focus on these patient populations, which include those with neurologic symptoms and those meeting ME/CFS criteria.
11: Account for the relapsing/remitting nature
Outcome measures need to be assessed in a way that can distinguish a temporary remission, which is part of the natural course of the disease, from a permanent cure.
Factors that can contribute to the relapsing/remitting nature include physical and cognitive postexertional malaise, menstrual cycle changes, and seasonal changes.
12: Trial participants should reflect the diversity of the long COVID population
Certain demographics are more likely to be affected by acute and long COVID and need to be appropriately recruited and reflected in research, including in patient engagement.
Trials must include high numbers of Hispanic/Latinx, Black, and indigenous communities, queer and transgender populations, and women. Trial materials and design need to incorporate linguistic diversity in addition to racial/ethnic diversity.
Upward of 75% of long COVID cases happen after mild acute cases; clinical researchers should ensure that nonhospitalized patients make up the bulk of trial participants.
13: Utilize meaningful engagement of patients, especially in treatment selection and study design
Meaningful patient engagement means engaging multiple patients at every step of the trial process, from treatment selection to study design to analysis to communication of the results.
Patient experiences are extremely valuable and contain information that researchers may not be familiar with, including the nature and patterns of the illness, insights into possible treatments, and barriers to documentation and care that may also impact research. Tapping into those patient experiences will make trials stronger.
Overall, the landscape of long COVID clinical trials is ripe for discovery, and researchers choosing to go down this path will be deeply appreciated by the patient community.
Hannah Davis is a long COVID patient-researcher and cofounder of the Patient-Led Research Collaborative, an organization studying the long-term effects of COVID.
A version of this article first appeared on Medscape.com.