Get to know the Research we Fund

Long Covid (PASC) Study

Background Information:

Acute SARS-CoV-2 infection (COVID-19) is associated with both high cardiovascular morbidity and mortality. After an acute infection, some patients fail to fully recover and suffer for an extended period of time. Commonly referred to as “Long Covid,” this phenomenon is technically called Post-Acute Sequelae of SARS-CoV-2 (PASC). PASC is characterized by a high prevalence of persistent cardiac symptoms (such as chest pain, shortness of breath, arrhythmias, and decreased cardiac function). Remarkably, more than 25% of patients hospitalized with COVID-19 are found to have myocardial injury. However, the extent to which immune responses—such as myeloid cells, lymphocytes, and cytokines—may contribute to cardiovascular involvement in acute COVID-19 and in PASC is unknown. The duration of cardiovascular morbidity in PASC patients is also unknown.

The immune profile of patients with cardiovascular PASC is understudied. To date, there have been no long-term studies investigating systemic markers in patients with PASC. Consequently, there is a need to understand the determinants of cardiovascular sequelae along the acute COVID-19 to PASC disease spectrum with attention to the immune profile.

Research Aims:

Daniela Čiháková, M.D., Ph.D., has assembled a team of cardiologists, virologists, and experts in animal modeling at Johns Hopkins to collaborate with her on this project. The team will examine sera and immune cells from the blood of patients that were seen at the Johns Hopkins’ Long Covid clinic. These samples will be compared to healthy controls and samples from patients who tested positive for Covid in the past but completely recovered. The samples will undergo immunological, clinical, and imaging assessments.

Cancer Therapy Induced Autoimmune Myocarditis Study

Background Information:

Myocarditis is an inflammatory disease of the heart muscle cells, and myocarditis is most often caused by a viral infection. Giant cell myocarditis and eosinophilic myocarditis are rare but particularly severe types of myocarditis. About 30% of myocarditis survivors develop dilated cardiomyopathy (an enlargement and weakening of the heart muscle), one of the most common reasons for heart transplantation in all ages.

Immune checkpoint inhibitors (ICI) have transformed the treatment of a wide spectrum of cancers. These therapies target molecules called “programmed cell death protein 1” (PD-1) and its ligand (PD-L1) (anti-PD-1/PD-L1 therapy). However, this new cancer therapy can lead to immune-related adverse events when autoimmune inflammation affects various organs. Immune-related adverse events are typically not life-threatening and manageable. However, autoimmune myocarditis has emerged as a rare but fatal complication of ICI therapies. Mortality for this ICI-associated myocarditis is high—50% of affected patients died.

Research Aims:

Dr. Čiháková’s team will investigate the protective mechanism of the PD-1/PD-L1 interaction in the myocardium (the cardiac source of PD-L1 that protects the heart from myocarditis), the ability of the PD-1/PD-L1 pathway to prevent myocarditis progression to dilated cardiomyopathy, and the therapeutic potential of forced PD-L1 overexpression in myocarditis/dilated cardiomyopathy treatment.

GAI-Funded Publications

• Daoud, A., Kalinoski, H., Talor, M. V., Welsh, R. A., Jo, W., Jaime, C. M., Kolim, B., Mahto, N., Kveton, M., Weislová, I., Melenovský, V., Fabián, O., Kiemen, A. L., & Čiháková, D. (2025). Whole-heart 3D reconstruction of mouse CVB3 myocarditis reveals spatial and transcriptomic heterogeneity of immune foci. Cardiovascular research, 121(17), 2777–2790. https://doi.org/10.1093/cvr/cvaf209
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• Campos Ramos, Gustavo, Daniela Čiháková, Christoph Maack, and Sumanth D. Prabhu. “Interface Between Cardioimmunology, Myocardial Health, and Disease: A Compendium.” Circulation Research 134, no. 12 (2024): 1661-1662.
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• Čiháková, Daniela. “T Cells and Macrophages Drive Pathogenesis of Immune Checkpoint Inhibitor Myocarditis.” Circulation 149.1 (2024): 67-69.
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• Jo, Wonyoung, Taejoon Won, Abdel Daoud, and Daniela Čiháková. “Immune checkpoint inhibitors associated cardiovascular immune-related adverse events.” Frontiers in immunology 15 (2024): 1340373.
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• Kalinoski, et al;“Injury-induced myosin-specific tissue-resident memory T cells drive immune checkpoint inhibitor myocarditis.” PNAS (2024)
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• Won, Taejoon, Evelyn J. Song, Hannah M. Kalinoski, Javid J. Moslehi, and Daniela Čiháková. “Autoimmune myocarditis, old dogs and new tricks.” Circulation Research 134, no. 12 (2024): 1767-1790.
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• Won, Taejoon, Hannah M. Kalinoski, Megan K. Wood, David M. Hughes, Camille M. Jaime, Paul Delgado, Monica V. Talor, Ninaad Lasrado, Jay Reddy, and Daniela Čiháková. “Cardiac myosin-specific autoimmune T cells contribute to immune-checkpoint-inhibitor-associated myocarditis.” Cell reports 41, no. 6 (2022). https://doi.org/10.1016/j.celrep.2022.111611
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• Daoud, Abdel, Diego A. Lema, Taejoon Won, and Daniela Čiháková. “Integrative single-cell analysis of cardiac and pulmonary sarcoidosis using publicly available cardiac and bronchoalveolar lavage fluid sequencing datasets.” Frontiers in Cardiovascular Medicine 10 (2023): 1227818.
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     This GAI-LJI collaboration seeks to leverage LJI’s expertise in immunology through the Center for Autoimmunity and Inflammation to unravel the mysteries of autoimmune disease and develop novel treatments.

     In 2024, GAI launched a new research partnership with LJI, including the creation of the Global Autoimmune Institute Assistant Professorship. Seminars such as Life Without Disease and Live from the Lab, a short film, a digital resource guide, and Immune Matters magazine features were also supported through this collaboration.

     In 2025, this support expanded to a five-year, $1 million commitment, deepening our investment in long-term autoimmune research.

Learn more about our strategic partnership with LJI here.

Background:

The research team at Boston Children’s Hospital will use blood samples to simultaneously test for multiple autoantibodies associated with many different autoimmune conditions using autoantigen microarray panels. Utilizing this technology, the team will investigate whether there are identifiable autoantibody signatures that can distinguish individuals who have only one autoimmune condition from those who have multiple.