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COVID-19 Research

The Department of Pathology has a long and rich history of fighting pandemics. In fact, the first Director of Pathology, William Henry Welch, helped lead America's effort to fight the great influenza pandemic of 1918. Today, the Department of Pathology's efforts to help manage the COVID-19 crisis, extends from front line clinical diagnostics to the development of novel therapeutic approaches.

Mostafa Carroll Coronavirus Testing
Karen Carroll, M.D. & Heba Mostafa, M.B.B.Ch., Ph.D.

COVID-19 Testing

The clinical molecular virology lab in Pathology, led by Karen Carroll, M.D. and Heba Mostafa, M.B.B.Ch., Ph.D., was one of the first to implement a high throughput, in-house coronavirus screening test in the United States, soon to allow the health system to test as many as 1,000 people per day. The lab used the test, which analyzes a nasal or oral swab, for the first time on March 11, 2020. Over 1,000 patients have been tested using this protocol. Soon we will be testing over 1,000 patients a day.

Ongoing Research

Efforts continue to improve diagnostic testing and to develop new treatments, so that the Department of Pathology can provide cutting-edge patient care for COVID-19. From developing a new serology test to determine who has recovered from the infection to coming up with new approaches to treat infected patients using plasma antibodies from recovered patients to working to develop a novel vaccine, our researchers are learning about various aspects of this virus.

Read more about individual COVID-19 research projects in our department below.

Daniela Cihakova, M.D., Ph.D.
Daniela Čiháková, M.D., Ph.D.

Myocarditis in COVID-19

Myocarditis has been identified as a serious complication of SARS-CoV-2 infection. We will employ three approaches to understand how the SARS-CoV-2 is attacking the heart. First, we will use mouse models to identify COVID-19 receptors, such as ACE2 and DS-SIGN expression by cardiomyocytes, cardiac fibroblasts, endothelial cells, and other cardiac stroma cells. Second, in collaboration with Nisha Gilotra (Department of Cardiology, JHU), we will compare the immune profile of patients with COVID-19 myocarditis and those without the heart involvement. Third, we will examine antibodies against cardiac tissue to explore a hypothesis that there is an autoimmune component in the COVID-19 associated myocarditis.

Visit Dr. Daniela Čiháková's Research Lab

Mary Kathryn Grabowski, Ph.D., Sc.M.
Kate Grabowski, Ph.D., Sc.M.

Novel Coronavirus Research Compendium

As the pandemic unfolds, we face a rapid proliferation of literature on SARS-CoV-2. Reliable and rapidly curated literature is needed to inform the public, programs, policy, and research during this ongoing pandemic. The 2019 Novel Coronavirus Research Compendium (NCRC) is a group of informationists, faculty, and students from the Johns Hopkins Bloomberg School of Public Health, Johns Hopkins School of Medicine, and the Welch Library. The NCRC was established to develop and maintain a centralized compendium of emerging scientific articles on SARS-CoV-2. As part of its efforts, the NCRC conducts reviews of manuscripts appearing in PubMed, BioXriv, and MedXriv on a weekly basis in eight topic areas deemed to be of relevance to global public health audiences. NCRC expert reviews include a brief summary of results, strengths, limitations and value added of the research. Topic areas covered by the compendium include: ecology and spillover, vaccines, epidemiology, mathematical modeling, non-pharmeutical interventions, pharmeutical interventions, clinical presentation and prognostic risk factors, and diagnostics. The NCRC will be a publicly available resource for audiences with a semi-technical background in the public health sciences, including researchers, practitioners, policy makers, and STEM journalists.

Visit the Novel Coronavirus Research Compendium (NCRC) website

Jody E. Hooper, M.D.
Jody Hooper, M.D.

Autopsy for Elucidation of Disease Process and Collection of Tissue for Researchers

Clinicians consenting family members for autopsies on deceased COVID positive patients should call the Legacy Gift Rapid Autopsy Program number at 1-800-886-6696 at any time 24/7 so that consenting for research on specimens can also be completed.

The effect of the COVID-19 virus on organs besides the lungs has only begun to be investigated. The Johns Hopkins Autopsy Service is prepared to perform focused autopsies on patients testing positive for COVID-19. Histologic and electron microscopy evaluation will be completed on multiple organs and frozen and other tissue as well as blood or fluid samples can be collected for laboratories which are prepared to receive samples. Please contact Dr. Jody Hooper and Dr. Tamara Lotan to be added to the collection protocol.

H. Benjamin Larman, Ph.D.
Ben Larman, Ph.D.

Immune response biomarkers for COVID-19 patient stratification

The Larman Laboratory develops and deploys cutting edge molecular assays to characterize human immune responses. Three technologies are being employed to identify biomarkers for COVID-19 patient stratification. First, we are measuring host immune response genes directly from nasal swabs. Second, we are profiling serum anti-viral antibody responses using a comprehensive binding assay. Third, adaptive immune receptor repertoires will be sequenced from peripheral blood mononuclear cells. Each approach provides a unique opportunity to identify immune response signatures with prognostic utility.

Visit Dr. Ben Larman's Research Lab

Mark Marzinke, Ph.D.
Mark Marzinke, Ph.D.

Development of Analytical Pharmacology Assays to Evaluate COVID-19 Therapies

As the pandemic continues to unfold, clinicians and researchers are working to identify strategies to mitigate COVID-19 symptoms. Several prophylactic agents, including anti-malarial agents, antibiotics, and antivirals are currently under investigation for disease treatment. The nucleotide analog remdesivir is an antiviral compound currently being evaluated in a number of clinical trials as a therapy for patients with moderate to severe COVID-19 symptoms. Bioanalytical assays to evaluate the pharmacology of this experimental agent can provide additional insight regarding the drug’s pharmacokinetics in these patients and correlate with therapeutic outcomes. The Marzinke Lab-Clinical Pharmacology Analytical Laboratory (CPAL) has experience in the development, validation, and implementation of liquid chromatographic-mass spectrometric (LC-MS) assays. We are currently developing a bioanalytical assay for remdesivir quantitation in plasma, and are building additional infrastructure for measuring other investigational agents. More information on Dr. Marzinke's Laboratory may be found at the following website:

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Heba Mostafa, M.B.B.Ch., Ph.D.
Heba Mostafa, M.B.B.Ch., Ph.D.

Elucidating the genetics of SARS-CoV-2 and the association with disease progression

Our research interest is in viral genomics, and the correlation of viral polymorphisms with disease severity.

Whole genome sequencing of SARS-CoV-2 isolated strains will be performed with a focus on phylogenetics and genetic epidemiology of transmission. The project will dissect the genetic diversity of the virus in Baltimore/DC and the differences between the viral genomes in the beginning of the outbreak versus later with a study of the genomic change overtime. The study will also examine the correlation between certain polymorphic events and the disease state. This project will be in collaboration with Peter Thielen and Thomas Mehoke (Applied Physics Laboratory).

Metagenomics and whole genome sequencing of SARS-CoV-2 positive specimens for correlating changes in microbiome with viral loads and the disease progression and severity. This project will be in collaboration with Trish Simner (Department of Pathology).

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Maxim Rosario, D.Phil., M.B. B.CH. B.A.O., M.Sc., Ph.D.
Maxim Rosario, D.Phil., M.B. B.CH. B.A.O., M.Sc., Ph.D.

Developing a T-cell Vaccine for Covid-19

Over time infectious agents such as SARS-CoV-2 accrue mutations. These mutations can make the virus more pathogenic by helping it evade the immune system. However, the virus faces a fitness cost in making these changes. When comparing various SARS isolates both over time and from different animal species, there are parts of the virus that are strictly conserved. We believe that these conserved regions are the most vulnerable proteins within the virus and are the focus of our vaccine strategy.

Vaccine development has traditionally relied on the generation of antibodies to neutralize infectious virus. Although successful in dealing with many pathogens, this strategy commonly neglects vulnerable parts of a virus. T-cells represent another avenue of attack. T-cells can recognize infected host cells and kill them by direct cell-to-cell contact. If properly induced, T-cells can target parts of a virus not open to antibody attack.

Our vaccine links highly conserved and functionally important segments of SARS-CoV-2 that can be targeted by T-cells into one immunogen. We are now designing and testing “vehicles” in which to deliver the immunogen.

Scheherazade Sadegh-Nasseri, Ph.D. & Nilabh Shastri, M.Sc., Ph.D.
Scheherazade Sadegh-Nasseri, Ph.D. & Nilabh Shastri, M.Sc., Ph.D.

COVID-19 Vaccine

Effective vaccines require knowledge of unique elements (e.g. proteins, peptides etc.) of pathogens that the immune system can recognize and "memorize" for future encounters. This memory response provides long term protection against the pathogen. For example, the small pox, measles and polio vaccines that have saved millions of lives are all based on this principle. Our immediate goal is therefore to identify these unique pathogen elements - ideally in humans - so we can proceed to package these elements into an effective vaccine. The combined expertise of our laboratories and the available Johns Hopkins' resources from Covid-19 patients are uniquely suited for this enterprise.

Visit Dr. Sadegh-Nasseri's Research Lab

Visit Dr. Nilabh Shastri's Research Lab

Jonathan Schneck, M.D., Ph.D.
Jonathan Schneck, M.D., Ph.D.

Understanding the Role of Immune Cells in COVID-19

T cells are critical players in infectious disease, autoimmunity, wound healing, and cancer. Yet, even for virus-specific T cell responses, it has been difficult to identify and study them. Current approaches are limited in terms of sensitivity, throughput, and/or ease of use. We address these challenges by engineered magnetic nanoparticle tools called artificial antigen presenting cells (aAPCs) for isolating and expanding human virus-specific T cells with great specificity and to large numbers. Our approach has increased throughput and translatability by streamlining processes for T cell culture and enrichment, as well as particle and detection reagent production. These innovations dramatically increase the multiplexing ability and decrease the barrier of entry for other researchers/clinicians and commercial labs to adopt this technology and investigate virus-specific T cells. The ability to expand T cells to large numbers enables unique downstream analyses, lead to better understanding of disease and the generation of novel therapies. We are now using our core aAPC technology to address the urgent need for analysis of immune responses to the COVID-19 pandemic. Our ability to quantitate and expand COVID-19-specific T cells will help us understand our body's ability to fight the virus, develop new diagnostics, and novel anti-COVID-19 therapies.

Visit Dr. Jonathan Schneck's Research Lab

Visit The Johns Hopkins Translational ImmunoEngineering Center

Aaron Tobian, M.D., Ph.D. & Evan Martin Bloch, M.B.Ch.B., M.S.

Harnessing the Power of Convalescent Plasma for Treatment of COVID-19

Our laboratory research is focused on using blood plasma from recovered coronavirus patients to treat those who were exposed to the virus or those who have COVID-19. This work will harness the power of antibodies developed by recovered patients to treat current patients.

  • Human Anti- SARS-CoV-2 plasma as post-exposure prophylaxis: a randomized, blinded Phase 2 trial will compare the efficacy and safety of Human Anti-SARS-CoV-2 plasma vs. control (SARS-CoV-2 non-immune plasma) among adults (age ≥ 18yrs) who have been exposed to COVID-19 but have not manifested symptoms. Subjects will be stratified by risk (i.e. healthy adults, vs those of advanced age [≥65yrs] and/ or comorbid medical risk factors for severe disease e.g. immunocompromise).
  • Human Anti- SARS-CoV-2 plasma to treat "Green Zone" patients: a randomized, blinded Phase 2 trial will compare efficacy and safety of Human Anti-SARS-CoV-2 plasma vs. control (SARS-CoV-2 non-immune plasma) in hospitalized patients with COVID-19 who manifest symptoms but are not of sufficient acuity to warrant ICU admission
  • Human Anti-SARS-CoV-2 plasma treatment as terminal intervention: a randomized, blinded Phase 2 trial will compare efficacy and safety of Human Anti-SARS-CoV-2 plasma vs. control (SARS-CoV-2 non-immune plasma) in patients who are admitted to ICU with severe COVID-19.

Tzyy-Choou Wu, M.D., M.P.H., Ph.D. & Chien-Fu Hung, Ph.D.
T.C. Wu & Chien-Fu Hung

Vaccine Experts Work on the Development of COVID-19 Vaccine

When Dr. T.C. Wu and Dr. Chien-Fu Hung heard earlier this year about a new coronavirus that was spreading in China, their pathology labs immediately started developing a vaccine. This vaccine development is reminiscent of nearly 20 years ago when Wu and Hung worked on a vaccine for another coronavirus that originated in China - SARS. So far Wu and Hung have observed that COVID-19 is "smarter" and "sneakier" than SARS, and they are concerned it will not go away like SARS did. Wu's and Hung's lab administered their naked DNA vaccines to mice, and preliminary results seem encouraging. Wu oversees the Cervical Cancer Research Lab at Johns Hopkins and is a professor of pathology, oncology, and obstetrics and gynecology at the Johns Hopkins University School of Medicine. He holds a joint appointment in the Bloomberg School of Public Health Department of Molecular Microbiology and Immunology. Dr. Hung is an Associate Professor in the Department of Pathology at the Johns Hopkins University. For further information, please see the following link: https://www.hopkinsmedicine.org/coronavirus/vaccine-development.html