NHLBI's COVID-19 Guidance for Practicing Clinicians

Healthcare providers, patients, and policy experts seeking information about appropriate COVID-19 treatment may consult treatment guidelines developed by a panel of U.S. physicians, statisticians, and other experts. These guidelines are based on published and preliminary data and the clinical expertise of the panelists, many of whom are frontline clinicians caring for COVID-19 patients. The guidelines are updated as new data are published in peer-reviewed scientific literature and as other authoritative information emerges.

The CDC has also published updated infection control guidelines for patients infected with COVID-19. This guidance covers clinical presentation, vaccination, testing, diagnosis, and clinical management and treatment, among other topics. These guidelines were last updated in May 2023 to reflect vaccine-and-infection based immunity and available treatments and prevention tools.

NHLBI COVID-19 research and clinical trials

Several COVID-19 research initiatives leverage NHLBI-supported clinical trial networks and research study cohorts that existed before the COVID-19 pandemic started.

The Collaborating Network of Networks for Evaluating COVID-19 and Therapeutic Strategies (CONNECTS) builds 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. 

As a result of these efforts, a number of clinical trials and observational studies are underway, or have been completed, including:

COVID-19 clinical trials

• The NIH Researching COVID to Enhance Recovery (RECOVER) Studies aim to learn how to better prevent and treat Long COVID in the future. 
• The Colchicine Coronavirus SARS-CoV-2 (COLCORONA) trial evaluated the gout drug colchicine to see whether it limits inflammation in the heart and lungs in patients with COVID-19. Findings showed that colchicine might reduce the risk of death or hospitalization compared to patients given a placebo.
• The Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) is evaluating complications of SARS-CoV-2 infection among people with HIV and whether statins can help.
• The Accelerating COVID-19 Therapeutic Interventions and Vaccines 3 (ACTIV-3) studies evaluated whether monoclonal antibodies and other immune-modulating therapies can improve recovery in hospitalized patients. As of March 2021, two of the studies closed enrollment due to no evidence of benefit. There were no safety concerns or indication of harm.
• ACTIV-4 includes three trials that evaluated whether anticoagulants or antiplatelet drugs reduced life-threatening blood clots in patients with various stages of COVID-19. The study found that full-dose blood thinners reduced the need for organ support in patients who had mild to moderate COVID-19 but not for those who were critically ill. Read more about the ACTIV-4 studies and their findings in our Q&A with W. Keith Hoots, M.D., former director of the NHLBI Division of Blood Diseases and Resources.
• The Clinical Trial of COVID-19 Convalescent Plasma of Outpatients (C3PO) evaluated the use of convalescent plasma to treat non-hospitalized patients with mild COVID-19. The trial ended in February 2021 after an independent data and safety monitoring board determined that convalescent plasma use caused no harm but was unlikely to benefit patients with mild to moderate COVID-19 symptoms. Read more about the trial results.
• The Outcomes Related to COVID-19 treated with hydroxychloroquine among In-patients with symptomatic Disease (ORCHID) Study evaluated an anti-malaria drug in hospitalized COVID-19 patients. It found no evidence of benefit.

COVID-19 observational studies

• The COVID-19 Observational Study (PETAL-RED CORAL) is examining the pathobiology and outcomes among more than 3,000 adults hospitalized with COVID-19 for up to 6 months after discharge.
• The Collaborative Cohort of Cohorts for COVID-19 Research (C4R) is combining existing diverse population studies to look at long-term COVID-19-related outcomes and factors that affect risk and resilience.
• The Recipient Epidemiology and Donor Evaluation Study (REDS), an NHLBI program that monitors threats to the U.S. blood supply, is analyzing the prevalence of SARS-CoV-2 antibodies (seroprevalence) among blood donors in six cities with high COVID-19 rates, setting up a framework for a nationwide seroprevalence survey. REDS researchers found that U.S. blood donations are safe under current COVID-19 screening guidelines.