A sick caucasian Man wearing face mask feeling sick headache and cough because of Coronavirus Covid-19 on the sofa in quarantine
Director's Messages

Tackling the Mysteries of the Long-term Effects of SARS-CoV-2 Infection


As we enter our second year of the devastating COVID-19 pandemic, we have learned much about the SARS-CoV-2 virus and how it can acutely affect multiple organs and systems, especially the heart, lungs, and blood vessels. Now, with the rollout of vaccines and new insights into treatments, we can begin to feel optimistic about beating back the worst of the pandemic.

But coupled with this good news is a worrisome trend. As National Institutes of Health (NIH) Director Dr. Francis Collins recently described, recovery from SARS-CoV-2 infection can vary. Some patients seem to recover quickly and completely, while others report symptoms that persist weeks to months after the acute phase of illness has passed (often referred to as “Long COVID”).  These symptoms range from mild to incapacitating, may involve multiple organs and systems, and can adversely affect overall quality of life. In other cases, new symptoms and findings are reported that appear linked to the timing of acute infection, but they only emerge afterwards and evolve over time.  The public health impact of these post-acute sequelae of SARS-CoV-2 infection is currently unknown, but it is potentially large given the numbers of individuals in all age groups who have been or will be infected with SARS-CoV-2.  

In recognition of this emerging public health challenge, Congress recently appropriated $1.15B in NIH funding over four years to support research into the long-term health consequences of SARS-CoV-2 infection. With this support, the agency has taken swift action to develop a trans-NIH, multi-disciplinary research agenda and is announcing the Post-acute Sequelae of SARS-CoV-2 infection (PASC) Initiative. PASC is an umbrella term intended to encompass the full clinical spectrum of post-acute SARS-CoV-2 infection, including but not limited to multisystem inflammatory syndrome in children and adults (MIS-C and MIS-A), and potentially other disorders. MIS-C and MIS-A are rare but severe immune responses to SARS-CoV-2 that can entail cardiovascular complications.

In light of the prevalence of impaired heart, lung, blood, and sleep health associated with acute and post-acute SARS-CoV-2 infection, the NHLBI is taking a lead role in the PASC Initiative. It is noteworthy that a significant proportion of hospitalized COVID-19 patients exhibit evidence of cardiac injury as reflected by EKG changes and elevations in troponin levels. Yet, the long-term implications of this acute cardiac injury are not understood. A recent study in Germany found that a significant proportion of adult patients with a history of SARS-CoV-2 infection exhibit ongoing cardiac inflammation, the presence of which can increase the risk of arrhythmia, cardiomyopathy, or heart attack down the line. [i] Still others, especially those who had severe illness, are left with lingering pulmonary abnormalities. In one study, about half of patients who needed ventilation for acute COVID-19 had lower blood oxygenation capacity six months later.[ii]  Surprisingly, even some who were asymptomatic in the acute phase of SARS-CoV-2 infection ended up with symptoms in the post-acute phase.

The PASC Initiative will direct efforts into creating a multidisciplinary consortium of investigators, patients, and resources to begin to unlock the mysteries of the long-term effects of SARS-CoV-2 infection. A key feature will be the establishment of a SARS-CoV-2 Recovery Meta-Cohort that includes diverse populations of adults and children, inclusive of MIS-C. This Meta-Cohort will engage new cohorts as well as leverage ongoing NIH-supported COVID-19 studies, networks, and longitudinal cohort studies previously established by NHLBI and multiple other NIH Institutes.

The Initiative also aims to coordinate large data studies informed by electronic health records and health systems, and to provide emerging analytics tools to the broader research community by  extending NIH-funded communal data resources and platforms such as NHLBI’s BioData Catalyst. The Initiative will establish a biobank of  biospecimens and tissue samples that can be used to analyze the breadth of tissue and organ injury caused by SARS-CoV-2 infection and PASC. With these coordinated cohorts and datasets, we will better understand the adult and pediatric population burden of PASC, as well as its biological bases and clinical spectrum; identify ways to improve recovery after SARS-CoV-2 infection; and potentially test interventions to prevent long-term disability from SARS-CoV-2 infection.

Throughout this pandemic, I have been heartened by the resilience and resolve of our scientific community to come together and engage fully in our evolving fight against SARS-CoV-2. I am inspired by the clinicians on the front lines of the pandemic, and grateful for the patients and families who have shared with us how COVID-19 has impacted their lives. To ensure our research efforts are informed by the patient experience, the PASC Initiative will engage patient voices through multiple phases. I look forward to working with investigators, patients, and our circle of partners to fully understand and conquer the long-term effects of this virus.


[i] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7385689/

[ii] https://pubmed.ncbi.nlm.nih.gov/33428867/