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The Yale Paxlovid for Long COVID (PAX LC) Trial

Thank you for being interested in the Yale Paxlovid for Long COVID (PAX LC) Trial!

This research study will test whether 15 days of the study drug Paxlovid, compared with placebo, can improve the health of people living with Long COVID.

One possible cause of Long COVID is persistence of the SARS-CoV-2 virus long after the initial infection. Paxlovid is an anti-viral medication that is authorized by the Food and Drug Administration (FDA) for 5-day treatment of acute COVID infection. This research study will also be collecting blood and saliva samples to understand how our body’s immune system responds to Long COVID.

For this research study, Long Covid is defined as prior infection with SARS-CoV-2, followed by the onset of symptoms within 4 weeks of the initial infection that persist for at least 3 months. The research study uses online study surveys, the Hugo Health digital health platform to engage participants and connect clinical data, and the collection of blood and saliva samples at a convenient place for participants. This type of research study, designed to make participation easy, is called “decentralized”: participants do not need to go to research sites and can be part of the study from home.
The study is co-led by Professors Harlan Krumholz and Akiko Iwasaki. They are committed to working in partnership with the participants and other researchers to generate new knowledge rapidly. People living with Long COVID contributed to the protocol (how the study is conducted). A person living with Long COVID is on the oversight committee for the research study. Everyone who participates in the research study will have opportunities to interact with the investigators and to be among the first to learn of the results.

You May Be Eligible to Participate in This Research Study If You:

  • Have been previously infected by SARS-CoV-2
  • Have symptoms consistent with Long COVID that began within 4 weeks of the infection and continued for more than 12 weeks
  • Were healthy before you developed Long COVID
  • Are not participating in another interventional research study
  • Can access an internet-capable computer or mobile device to access a digital health system
  • Do not have renal or liver dysfunction, HIV, acute SARS-CoV-2, any other medical condition requiring hospitalization and/or surgery within 7 days of study entry
  • Have regular medical care and had a health visit within the last 6 months
  • Are not pregnant or breastfeeding
  • Have connected your health information to Hugo Health and filled out the screening survey
  • Are 18 years of age or older
  • Reside in Alabama, Arizona, California, Colorado, Connecticut, Delaware, District of Columbia, Florida, Georgia, Idaho, Illinois, Indiana, Iowa, Kansas, Kentucky, Louisiana, Maine, Maryland, Massachusetts, Michigan, Minnesota, Mississippi, Missouri, Montana, Nebraska, Nevada, New Hampshire, New Jersey, New York, North Carolina, North Dakota, Ohio, Oklahoma, Oregon, Pennsylvania, Rhode Island, South Carolina, South Dakota, Tennessee, Texas, Utah, Vermont, Virginia, Washington, West Virginia, Wisconsin, and Wyoming.
  • Are willing and able to provide informed consent
  • Are comfortable reading and writing in English

How the Study Works

Eligible participants will be randomized, which means that you will be assigned by chance to either nirmatrelvir/ritonavir or placebo to be taken orally for 15 days. The placebo tablets (pills) contain no nirmatrelvir drug. The placebo includes ritonavir, which does not have an effect on the virus, but will help ensure people don’t know whether they are in the Paxlovid or placebo group. During this time, participants will complete a daily diary and periodical surveys. Participants will also need to provide blood and saliva testing. There will be compensation for people’s time and effort.

How to Join the Study

This research study will recruit from Hugo Health's Kindred, an engagement platform supporting people living with Long COVID to acquire their digital health data and share it. Data only moves with their permission. It is a way to do research that values people’s control over their data and promotes partnership in the studies. This approach is being used to facilitate enrollment and participant partnership – and to make data collection more timely and efficient. Please visit the Hugo Health Kindred Network for more information. The method of recruitment has been approved by the Yale committee that oversees studies and protects the interests of participants.

Additional Details

The Yale Center for Infection and Immunity (CII), the Yale New Haven Hospital Center for Outcomes Research and Evaluation (CORE) and the Yale Center for Clinical Investigation (YCCI) are working together to support this study. Pfizer provided funding for the study and also participated in the design development.

The Yale PAX LC Principal Investigator is Harlan Krumholz, MD, SM. As a disclosure, Dr. Krumholz is a co-founder of Hugo Health. As a developer of the Hugo Health platform, Dr. Krumholz is not receiving financial benefit now but may in the future.

A description of the PAX LC trial can be found at:

If you have further questions, please email us at


If you have any questions regarding the PAXLC Study, please email us at