Given the major impact of underlying heart, lung, and blood diseases and conditions on morbidity and mortality among patients with Coronavirus Disease 2019 (COVID-19), the NHLBI is pursuing a multi-pronged research strategy that leverages NHLBI-supported expertise, research, and infrastructure.

An integral component of the strategy is NHLBI's Collaborating Network of Networks for Evaluating COVID-19 and Therapeutic Strategies (CONNECTS). The goal of this research effort is to build on our existing clinical research networks to better understand the risk of severe illness from COVID-19 and to identify therapies that will slow or halt the disease progression and speed recovery. 

COVID-19 can have severe effects on the heart, lungs, and blood

How COVID-19 affects the heart
Heart inflammation, heart failure, and arrhythmias
How COVID-19 affects the lungs
Acute Respiratory Distress Syndrome (ARDS), Acute Respiratory Failure
How COVID-19 affects the blood
COVID-19 associated coagulopathy (CAC)

Those with underlying health conditions, such as chronic lung disease, cardiovascular disease, diabetes mellitus, and sickle cell disease, appear to be at higher risk for severe COVID-19–associated disease.

Research Strategy Goals

The NHLBI has designed an adaptive, responsive research strategy with short and long-term goals. These goals include:

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Understand pathophysiology and identify potential treatments
Test host-directed interventions and provide evidence base for clinical practice
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Promote blood safety, sero-surveillance, and new blood-derived therapeutics
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Conduct longitudinal/cohort studies to understand natural hx and risk factors
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Test behavioral, social, and community-based interventions
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Provide data and biospecimen resource

NHLBI's Rapid Response

NHLBI’s research response to the COVID-19 crisis has been a rapid, collaborative, and strategic effort.

February 2020
In late February, the trans-NIH and NHLBI COVID-19 response teams were created, soon after the scientific community began to recognize the systemic and multi-organ nature of COVID-19, and after the publication of clinical characteristics of patients from China. This and other data highlighted the extensive involvement of the heart, lung, and blood systems. We immediately began assembling our research strategy.

March 2020

On March 17, we put out our first COVID-19 notice of special interest (NOSI), which called for investigators with active NHLBI grants to propose COVID-related research ranging from preclinical to clinical studies.

To further develop our COVID-19 response, NHLBI staff reached out to thought leaders and experts throughout the research community to determine how to leverage our existing assets, including clinical trial networks and longitudinal cohort studies.

While these discussions were ongoing, Congress passed the Coronavirus Aid, Relief, and Economic Security (CARES) Act, authorizing $103.4 million for the NHLBI to conduct and fund COVID-19 research. In the two-week period that followed, Institute staff created a process to solicit, review, and fund an initial set of clinical trials that spanned the clinical spectrum of disease. On April 9, the first patient was enrolled in an NHLBI-supported clinical trial related to COVID-19, called ORCHID, designed to test the effectiveness of the malaria drug hydroxychloroquine.

During the following weeks, we released two more COVID-19 NOSIs, covering clinical research and observational studies, and collaborated on a third NOSI for behavioral and social dimensions of disease. We also issued a new funding opportunity announcement using our other transaction authority (OTA) to bring together existing clinical trial networks in a more formal "network of networks." The OTA is a special funding mechanism that allows agencies to engage a group of researchers, provides greater speed and more flexibility to perform research, and allows us to redirect efforts as needed. Called the Collaborating Network of Networks for Evaluating COVID-19 and Therapeutic Strategies (CONNECTS), this initiative would officially launch later in the summer, and include a central coordination and organization arm that would help coordinate COVID-19 research studies around the country and the world. 

April 2020

In late April, NIH launched its trans-NIH Accelerating COVID-19 Therapeutics Interventions and Vaccines (ACTIV) initiative, which was created to prioritize the development of new therapeutics and vaccines to address the COVID-19 pandemic. As part of this initiative, the NHLBI issued the Research Opportunity Announcement (ROA), "ACTIV Integration of Host-Targeting Therapies for COVID-19."

Also in April, NIH launched the Rapid Acceleration of Diagnostics (RADx) initiative, through which NHLBI supports four funding opportunities to improve COVID-19 testing in underserved and vulnerable populations (RADx Underserved Populations, RADx-UP). 

June 2020

In June, the NHLBI halted the ORCHID clinical trialThe trial found that while the drug did not cause harm, it was not beneficial to hospitalized patients with COVID-19.

NHLBI also launched the CONNECTS initiative. The goal of CONNECTS is to build on NHLBI’s existing clinical research networks across the nation and around the world to better understand the risk of severe illness from COVID-19 and to identify therapies that will slow or halt the disease progression and speed recovery.

As part of CONNECTS, the NHLBI launched ACTIV-4 Antithrombotics, a series of adaptive clinical trials evaluating the safety and effectiveness of varying doses of blood thinners to treat adults diagnosed with COVID-19. The trials involve several categories of patients—those who do not need hospitalization, those currently hospitalized, and those discharged after hospitalization for moderate to severe disease.

September 2020

In September, the NIH announced a $12 million award for outreach and engagement efforts in ethnically and racially diverse communities disproportionately affected by the COVID-19 pandemic. The award to RTI International, a non-profit research institution, supports research teams in 11 states established as part of the NIH Community Engagement Alliance (CEAL) Against COVID-19 Disparities. The NHLBI co-leads CEAL with the National Institute of Minority Health and Health Disparities (NIMHD).

October 2020

The NHLBI announced the Collaborative Cohort of Cohorts (C4R) observational study, which will collect participant data and samples to better understand COVID-19 and the associated symptoms and side effects. 

March  2021

The NHLBI, as part of a trans-NIH effort, announced a research initiative to understand how SARS-CoV-2 affects children, called Collaboration to Assess Risk and Identify Long-term Outcomes for Children with  COVID (CARING for Children with COVID). The research program is funding studies to find out why some children are at greater risk for infection than others, why symptoms vary among children who are infected, why some children have more severe illness than others (like Multisystem Inflammatory Syndrome in Children, or MIS-C), and what the long-term outcomes are for children who have become infected with SARS-COV-2. A primary component of this work is an NHLBI study called Long-TerM OUtcomes After the Multisystem Inflammatory Syndrome in Children (MUSIC). First launched in October 2020, MUSIC is conducted in partnership with the Pediatric Heart Network and is focusing on cardiovascular complications of MIS-C. The NHLBI is also supporting research around the trans-NIH initiative to study Post-Acute Sequelae of SARS-CoV-2 Infection (PASC). The PASC Initiative, which includes the study of “Long COVID,” aims to understand why some patients continue to experience symptoms, or even develop new symptoms, long after SARS-CoV-2 infection seems to have ended, as well as to identify potential treatments.

Read more about our research response strategy and COVID-19 research efforts.

What’s Next

We continue to develop new initiatives and funding opportunities as part of our ongoing research response strategy.

A Collaborative Effort

A visual demonstrating the collaborative efforts of the COVID-19 research response, including HHS collaborations and trans-NIH efforts.

NHLBI COVID-19 Research Response

Teams helping to design and implement the COVID response span subject areas such as preclinical studies, clinical trials, longitudinal cohort studies, community-based interventions, data mining and resources, and communications.

  • Pre-clinical Studies 
  • Clinical Trials 
  • Longitudinal/Cohort Studies 
  • Data Mining and Resources 
  • Communication 
  • Community-based Interventions 
  • Community-engaged Research 

The NHLBI is working with NIH and HHS in collaboration to end the pandemic. 

    Trans-NIH Efforts

    Much of NHLBI staff are part of trans-NIH efforts that include community-based interventions to work with vulnerable populations, data coordination, and collaboration with industry. 

    HHS Collaborations

    At an HHS level, the NHLBI works closely with our government partners, including the FDA and CDC, and participates in working groups, such as the medical countermeasures and clinical working group. We engage in an exchange of information with patient groups to learn about their needs. The information they share helps us set our research agenda. 

    • HHS Clinical Working Group 
    • HHS MCM Working Group