What is the goal of CONNECTS?

The NHLBI’s Collaborating Network of Networks for Evaluating COVID-19 and Therapeutic Strategies (CONNECTS) is an important and innovative research effort. 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.  

Why is CONNECTS important?

Coordinating and streamlining efforts under one organizational umbrella enables us to respond quickly and efficiently by promoting standardization, collaboration, and sharing of resources and data. As part of this coordination, studies conducted under CONNECTS will use an adaptive design that will allow research to be quickly started, stopped, and adjusted as data emerges. In addition, we will leverage existing programs to expand community-based research and address the needs of at-risk populations at the community level.

Clinical trials usually test one intervention at a time within a single network of clinical trial sites. CONNECTS provides the opportunity to conduct adaptive trials across multiple networks. Researchers across these sites can test a variety of interventions simultaneously, sharing data and identifying the most—or least—promising treatments more quickly.  

The CONNECTS studies will also enroll participants with health conditions, such as heart disease, high blood pressure, and chronic lung disease, that are known to increase their risk for severe complications from COVID-19.

How will CONNECTS contribute to COVID-19 scientific advances?

The CONNECTS initiative provides the infrastructure to implement the NHLBI’s COVID-19 research strategy. Through the initiative, the NHLBI is building a network of networks to quickly and efficiently investigate risk factors and potential therapies for COVID-19, and to rapidly share their results to help improve patient outcomes.

The interventions tested in CONNECTS trials will focus on:

  1. Targeting the virus itself. Interventions such as monoclonal antibodies directly attack the virus to prevent it from infecting or multiplying. Another example of virus-targeted treatments uses plasma from people who have recovered from COVID-19 to try and build “passive” immunity in others who are at risk of a serious infection.
  2. Targeting the body. Called “host-targeted” treatments, these seek to  limit damage to the body from the viral infection. Examples of these are anticoagulants, which help break apart and prevent blood clots from forming in blood vessels, and immune modulators, which activate or suppress the immune system’s response to the virus.
The Approaches to Prevent and Treat COVID-19 table features two rows and three columns including the type of treatment approach, how it works in the body, and examples of each. The virus-targeted approach targets the virus itself to prevent it from infecting or multiplying. Examples include monoclonal antibodies and hyperimmune globulin. Monoclonal antibodies target cells in the heart, lungs, blood, or blood vessels to reduce the impact of the virus on the body. Hyperimmune globulin uses plasma from people who have recovered from COVID-19 to try and build “passive” immunity in others who are at risk of a serious infection. Host-targeted approaches seek to limit damage to the body from the viral infection. Examples include anticoagulation therapies and immunomodulation. Anticoagulation therapies involve using medicines to break apart and prevent blood clots in veins and arteries. Immunomodulation involves using medicines to activate or suppress the immune system’s response to the virus.


The CONNECTS initiative will also leverage process, data, and biospecimens from existing observational cohort studies. This will help establish a cohort of cohorts that will study the characteristics of people who do and do not develop SARS-CoV-2, the virus that causes COVID-19. This can help us identify risk factors, inform strategies for prevention, and suggest biomarkers of infection to improve patient outcomes.

How does CONNECTS align with other COVID-19 programs?

The NHLBI will provide strategic direction, oversight, and key partnerships, in collaboration with the Department of Health and Human Service’s Biomedical Advanced Research and Development Authority (BARDA) and the federal partnership Operation Warp Speed; and other NIH Institutes and Centers, such as the National Institute of Allergy and Infectious Diseases (NIAID).

The CONNECTS initiative aims to:

  • Integrate major NHLBI trial networks and observational cohort studies under one organizational umbrella. This will help create a standard and efficient process for collaboration and sharing of data and resources.  
  • Adopt a nimble and adaptive strategy for shifting studies as needed, based on new knowledge and changing pandemic clinical landscape.
  • Align clinical trials with other trans-NIH efforts. These include innovative, community-based interventions to work with vulnerable populations, data coordination, and collaboration with industry. NIH-led efforts include Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) initiative, which was created to prioritize and speed development of the most promising COVID-19 treatments and vaccines. The clinical research that fall under the NHLBI-CONNECTS umbrella are among the first projects of this public-private partnership.  

A Steering Committee was established to provide oversight of the large group of networks and studies including:

  • Compliance with Program policies and procedures
  • Design, implementation, and analysis of CONNECTS study protocols
  • Interpretation and presentation of results in publications, press releases and scientific meetings
  • Use of common data elements and data standards across CONNECTS study protocols
  • Sharing of data, biospecimens, images, and other research products developed by CONNECTS

A Data and Safety Monitoring Board (DSMB) monitors the safety of all CONNECTS ongoing trials.

What clinical trial networks are part of CONNECTS?

NHLBI-CONNECTS leverages existing clinical research networks across the nation and around the world, which allows us to test treatments with a wide variety of patient populations.

Some of the networks already involved and supporting studies include Prevention and Early Treatment of Acute Lung Injury (PETAL), Recipient Epidemiology and Donor Evaluation Study (REDS), and Strategies to Innovate Emergency Care (SIREN).