COVID-19/SARS-CoV-2

Butt, Calfee, Craney, Drelick, Ellman, Ellsworth, Glesby, Gulick, Henry, Johnston, Kodiyanplakkal, Marks, Mazur, Miller, Plate, Satlin, Salvatore, Singh, Small, Soave, Vogler, Walsh, Westblade, Wilkin

The Division of General Internal Medicine created a COVID-19 registry with detailed clinical data suitable for epidemiological investigation. Examples of collaborations using this database include:

• Drs. Gulick and Satlin co-authored one of the first observational studies of the clinical characteristics of COVID-19 in New York City, noted the prominence of gastrointestinal symptoms, and linked obesity to adverse outcomes (published in New England Journal of Medicine).
• ID fellows Drs. Pham and Torres with Drs. Gulick and Satlin examined outcomes in 19 patient with rheumatologic diseases on chronic hydroxychloroquine who developed COVID-19 (manuscript submitted).
• Former ID fellows Drs. Magleby and Trzebucki worked with Drs. Satlin, Simon, and Westblade to discover an important association between admission SARS-CoV-2 viral load level and the risk of intubation and mortality (published in Clinical Infectious Diseases).
• Dr. Satlin collaborated with Dr. Gulick and several ID fellows (Drs. Kondo, Magleby, Maldarelli, and Pham) to describe the safety, tolerability and clinical outcomes of hydroxychloroquine for hospitalized patients with COVID-19 (published in PLoS One).
• Dr Salvatore and Dr Satlin collaborated with colleagues in General Internal Medicine and OB-GYN to describe sex differences in symptoms presentation and outcome (published in Open Forum Infectious Diseases).
• Dr Salvatore collaborated to a paper describing the effects of social and clinical determinants on COVID outcomes (pre-print published).

Drs. Calfee, Singh and Westblade contributed to New York City Department of Health sentinel surveillance efforts for COVID-19 cases and genetic analyses of viral isolates (published in MMWR).

Drs. Ellsworth and Gulick collaborated with the Department of Pathology on an assessment of red blood cell transfusion needs in patients with COVID-19 (manuscript submitted).

Dr. Gulick co-authored a review article on severe COVID-19 with colleagues in the Division of Pulmonary & Critical Care (published in New England Journal of Medicine).

Dr. Miller and Henry described the clinical experience with COVID-19 at the Hospital for Special Surgery, a specialty orthopedic hospital that was converted to a pandemic overflow field hospital (published in HSS J).

Drs. Nixon and Ndhlovu coauthored a letter on vaccine breakthrough Infections with SARS-CoV-2 Variants (published in the New England Journal of Medicine).

Special Populations

• Hepatitis C
• Dr. Butt assessed rates and characteristics of SARS-CoV-2 infection in persons with Hepatitis C Virus infection (manuscript in press at Liver International).
• HIV
• Current ID fellow Dr. Stoeckle and former ID fellow (now faculty member) Dr. Johnston collaborated with Drs. Ellman, Glesby, Gulick, and Vogler on a controlled study evaluating clinical presentations and outcomes of inpatients with COVID-19 and HIV co-infection (published in Open Forum Infectious Diseases).
• Pregnancy
• ID fellow Dr. Maldarelli and Drs. Marks and Salvatore collaborated with colleagues from the Department of Obstetrics and Gynecology to report remdesivir treatment for severe COVID-19 in third-trimester pregnancy (published in Open Forum Infections Diseases).
• Drs. Marks and Mazur contributed to a study of pregnant woman with COVID-19 receiving the investigational antiviral remdesivir on a national compassionate use program (manuscript accepted in Clinical Infectious Diseases).
• Dr. Singh and colleagues from the Department of OB/GYN compared pregnancy outcomes in women with and without COVID-19 (published in BJOG).
• Qatar
• Dr. Butt helped characterize the SARS-CoV-2 outbreak in Qatar (manuscript in press at BMJ Open), the advanced-phase SARS-CoV-2 epidemic in Qatar (pre-print published), hospital admission rates, length of stay and in-hospital mortality for common acute care conditions in the COVID-19 vs. pre-COVID-19 era (in press at Public Health), and COVID-19 infection among healthcare workers in the Qatar national healthcare system (in press at Int J Infect Dis). He also reported on the volume and acuity of emergency department visits before and after COVID-19 (published in The Journal of Emergency Medicine), the impact of COVID-19 upon changes in emergency room visits with chest pain of possible cardiac origin (pre-print published), and how to set up quarantine facilities for pandemics at a national level (manuscript submitted).
• Transplant/Oncology
• Drs. Kodiyanplakkal, Satlin, Small, and Walsh co-authored a report on COVID-19 in solid organ transplant recipients (published in the American Journal of Transplantation).
• Dr. Plate together with Drs. Drelick, Kodiyanplakkal, Satlin, Small, Soave, and Walsh co-authored a study on COVID-19 pneumonia in patients with hematologic malignancies (abstract to be presented at ID Week 2020; manuscript in preparation).
• Dr. Satlin, together with Drs. Plate, Small, Walsh, and Westblade identified that admission SARS-CoV-2 viral load predicts mortality in hospitalized patients with and without cancer and that patients with hematologic malignancies have higher viral loads than patients without cancer (published in Cancer Cell).
• Dr. Small collaborated with colleagues on describing COVID-19 in transplant recipients with HIV under the HOPE Act (manuscript submitted).
• Drs. Small and Satlin collaborated with colleagues in hematology and pathology to characterize serologic responses to mRNA COVID-19 vaccines in patients with lymphoid malignancies (accepted for publication in American Journal of Hematology).

Ongoing/Future Work

• Drs. Fitzgerald and Peck were awarded an NIH supplement grant to study COVID-19 in Haiti and Tanzania.
• Dr. Peck was awarded a WCM COVID-19 research grant to study "Chronic Kidney Complications of COVID–19 in a Cohort of HIV-infected on HIV-uninfected African Adults” in Tanzania.
• Dr. Miller was awarded a Hospital of Special Surgery research grant to study surgical outcomes in the COVID-19 pandemic era.
• Drs. Satlin, Small, Singh, Walsh, and Westblade, ICU colleagues, and medical students are studying the patterns of bacterial pneumonia complicating COVID-19.
• Dr. Walsh is Associate Investigator on a CDC-funded observational study of COVID-19 pulmonary aspergillosis.
• Dr. Walsh is Associate Investigator on a collaborative study of “Outcomes of Cancer Patients during the COVID-19 Pandemic: A Prospective Cohort Study” with Dr. Peter Martin from Oncology (Principal Investigator).
• Dr. Walsh is coordinating a multicenter observational study of COVID-19 in patients with hematological malignancies.
• Drs. Johnston, Marks, Ellsworth, and Vogler are working with colleagues in Pediatrics, Pathology, and OB-Gyn to conducts an observational study of SARS-CoV2 vaccination in pregnant women and their neonates.

Brown, Copertino, Corley, Craney, de Mulder Rougvie, Duarte, Ellsworth, Gulick, Iñiguez, Jones, Kapadia, Marin-Hernandez, Morales, Ndhlovu, Nixon, Petraitis, Powell, Saito, Salvatore, Satlin, Singh, Soave, Vorkas, Westblade, Walsh, Wilkin

Drs. Corley and Ndhlovu collaborated with colleagues from OHSU describe virological and immunological consequences of disruption of the CCR5 pathway in critical COVID-19 (published in International Journal of Infectious Diseases).

Drs. Corley, Evering and Ndhlovu, report on the role of caspases, pyroptosis, the inflammasome and the therapeutic potential of caspase inhibitors in SARS CoV2 infection and long COVID. (published in Allergy).

Mr. Copertino and Drs. de Mulder Rougvie, Duarte, Gulick, Nixon and Wilkin reported on antiretroviral drug activity and potential for pre-exposure prophylaxis against COVID-19 and HIV infection (pre-print published).

Drs. Craney, Salvatore, ad Westblade collaborated with colleagues from the Department of Physiology on the characterization of COVID-19 isolates in NYC and the development of a novel diagnostic method (published in Cell).

Drs. Craney, Satlin, and Westblade in collaboration with additional colleagues from the Department of Pathology compared two high-throughput reverse transcription-PCR systems for SARS-CoV-2 (published in the Journal of Clinical Microbiology).

Drs. Duarte, Iñiguez, Nixon, and Powell, Mr. Copertino and WCM medical student Jez Marston reported a data-driven approach to repurposing FDA-approved drugs for COVID-19 (pre-print published).

Drs. Ellsworth and Wilkin worked with colleagues in Department of Pathology and the blood bank to determine clinical factors in COVID-19 that were predictive of serologic responses in a convalescent plasma donor screening program (manuscript in preparation).

Dr. Jones co-authored a study that reported suboptimal biological sampling as a probable cause of false-negative COVID-19 diagnostic test results (published in the Journal of Infectious Diseases).

Dr. Jones co-authored a study that reported SARS-CoV-2-specific T-cells can be rapidly expanded for therapeutic use and target conserved regions of the membrane protein, (manuscript under revision in Blood).

Dr. Jones made his BSL-2+ space available as the primary site of processing of blood samples from SARS-CoV2-infected donors, for the WCMC Biobank effort (with Dr. Ross). He also supplied protocols to several other laboratories to establish their BSL-2+ procedures.

Drs. Marín-Hernández and Nixon and colleagues from the Division of Gastroenterology published epidemiological evidence for an association between higher influenza vaccine uptake in the elderly and lower COVID-19 deaths in Italy (published in the Journal of Medical Virology).

Dr. Ndhlovu collaborated with colleagues from the Division of Cardiology on the additive prognostic utility of adverse right ventricular remodeling in relation to conventional risk stratification among patients with COVID-19 (published in Journal of the American College of Cardiology).

Drs. Ndhlovu and Corley worked with colleagues from Mount Sinai and report on the overlap of intestinal inflammation and the pathogenesis of COVID-19 related disease on the SAR-CoV-2 receptors (published in Gastroenterology).

Dr. Nixon with medical students Jez Marston and Robert Wozniak reported on involvement of cisgender and transgender individuals in studies on the impact of hormonal therapy on COVID-19 (published in AIDS Patient Care and STDs).

Drs. Petraitis and Walsh used focal multivector ultraviolet technology (FMUV) for environmental control of SARS CoV-2 (technical report published).

Dr. Salvatore with colleagues Drs. Brown, Ellsworth, Kapadia, Morales, Saito, Singh, Soave, and Vorkas, working with a broad multi-disciplinary group recruited subjects to develop a biobank of specimens from hospitalized patients with acute COVID-19 as well as from outpatients who recovered (convalescent) to determine virologic and immunologic determinants of disease recovery or progression (published in Life Science Alliance).

Drs. Satlin and Westblade collaborated on a retrospective cohort study of blood culture utilization in COVID-19 and found bacteremia was very rare (published in the Journal of Clinical Microbiology).

Dr. Westblade has also collaborated on a number of SARS-CoV-2 diagnostic related studies (published in the Journal of Clinical Microbiology, Biosensors and Bioelectronics, and Clinica Chimica Acta).

Dr. Walsh in collaboration with Dr. Matt McCarthy received a grant from the Henry Schueler Foundation for translational research for new therapeutics with binary antiviral and anti-inflammatory properties in treatment of COVID-19.

Ongoing/Future Work

• Dr. Ellsworth is working with colleagues in the Department of Pathology and Laboratory Medicine to define the specificity of SARS-CoV-2 serology by examining the test those that have recovered from other common coronavirus infections.
• Dr. Evering is the site principal investigator for an NIH ACTG study to investigate SARS-CoV-2 immune responses after COVID-19 therapy and subsequent vaccine.
• Dr. Jones was awarded an internal WCM grant as co-I (PI – Julie Blander from Gastroenterology) which aims to study antigen presentation mechanisms of SARS-CoV2.
• Dr. Jones generated a panel of SARS-CoV2-specific CD4+ T-cell clones from a convalescent donor, and has made these available to WCMC investigators, including collaborations with Drs. Robert Schwartz and Melody Zheng.
• Dr. Jones is serving as section editor for a special issue of Current Opinion in HIV & AIDS on intersections between the responses to HIV and COVID.
• Dr. Jones is serving as section editor for an issue of Frontiers in Microbiology on Immune Evasion Mechanisms by RNA Viruses, which will also emphasize intersections between HIV and COVID.
• Dr. Lee with Drs. Gramatica, Jones, and Wilkin are pursuing a Merck COVID-19 research grant, entitled “The LOVE Study: hyperacute and longitudinal dynamics of SARS-CoV-2 viral load and host immune responses in high-risk health care workers.”
• Dr. Salvatore is the site principal investigator of the Predictors of Severe Covid-19 Outcome (PRESCO) Study, a longitudinal multi-center, prospective, observational study collecting diverse biological measurements and clinical and epidemiological data to identify early signatures that predict progression to ARDS, mortality, and/or other comorbid conditions.
• Dr. Salvatore and others are conducing additional immune and biomarker development studies.
• Dr. Walsh and colleagues are submitting a grant proposal through the National Institute for Allergy and Infectious Diseases for the study of bacteriophages in treatment of bacterial pneumonia complicating experimental COVID-19.

Butt, Drelick, Ellsworth, Glesby, Gulick, Horowitz, Kapadia, Marks, Singh, Small, Walsh, Wilkin

Antivirals

Drs. Horowitz, Kapadia, Marks, Miller and Singh conducted the expanded access/compassionate use study of remdesivir.

Dr. Marks conducted a Phase 3 randomized study of remdesivir in severe COVID-19 (published in the New England Journal of Medicine).

Dr. Marks also conducted a phase 3 randomized study to evaluate safety and antiviral activity of remdesivir in moderate COVID-19 (published in JAMA).

Drs. Small and Walsh co-led a phase 2 study of selinexor for severe COVID-19 (manuscript in preparation):

• Abstract accepted for Late Breaker session in the International Society for Influenza and Respiratory Virus Diseases (ISIRV). Oct 6-8th, 2020.
• Abstract submitted to IDWeek Late Breaker Session. Oct 22-25th 2020.

Immunomodulators

Dr. Glesby conducted an adaptive Phase 2/3 study of the safety and efficacy of sarilumab, an IL6 antagonist, for severe COVID-19 (manuscript in preparation).

Ongoing/Future Work

• Antivirals
• Drs. Small and Walsh, in collaboration with colleagues from the Division of Hematology/Oncology are preparing a manuscript on the mechanisms, in vitro, and in vivo properties of selinexor against SARS CoV-2 and experimental COVID-19.
• Dr. Walsh and his Laboratory will study the cytokine, chemokines, and proteomic profiles of patients in the Phase 2 randomized study to evaluate the activity and safety of selinexor for severe COVID-19.
• Dr. Wilkin conducted a study of hydroxychloroquine for the prevention of COVID-19 in healthcare workers.
• Cellular Therapies
• Dr. Walsh is serving as Associate Investigator on a protocol for cellular therapy using iNKT cells in patients with severe COVID-19 led by oncology colleague, von Biesen.
• Environmental Control
• Drs. Petraitis and Walsh in collaboration with colleagues at Hackensack Meridian Health, University Medical Center, Center for Discovery and Innovation and Purple Sun are conducting a study of focal multivector ultraviolet (FMUV) technology against COVID-19 coronavirus in vitro in the hospital environment.
• Monoclonal Antibodies and other Therapies
  
• Dr. Evering is the site principal investigator for an NIH sponsored Phase II/III adaptive platform trial of interventions for outpatients with COVID-19 is investigating several putative therapies for COVID-19, including monoclonal antibodies, a polyclonal antibody, and oral agent, and an inhaled agent.
• Passive Antibodies
• Drs. Glesby and Singh are enrolling a phase 3 Canadian-sponsored randomized study of convalescent plasma for hospitalized patients with COVID-19.
• Vaccine
• Dr. Marks is the site principal investigator enrolling the NIH sponsored phase 3 randomized controlled trial of mRNA-1273 SARS-CoV-2 vaccine.

Dr. Butt is a member of the Scientific Review and Reference Team and the Policy, Planning and Performance Team of the Ministry of Public Health in Qatar. He is also a member of the Hamad Medical Center, Qatar Ad Hoc COVID-19 Research Prioritization Committee.

Dr. Gulick co-chairs the U.S. NIH COVID-19 Treatment Guidelines Panel.

Dr. Kodiyanplakkal is a member of the American Society of Transplantation’s COVID-19 Taskforce.

Dr. Pape coordinated COVID-19 efforts in Haiti.

Dr. Westblade is a member of a steering committee for the American Association for Cancer Research for the AACR Report on the Impact of the COVID-19 Pandemic on Cancer Science and Medicine.

Weill Cornell COVID-19 Clinical Research Task Force: Dr. Gulick, chair; Drs. Glesby, Marks, Walsh, members.