Establishing a COVID-19 Prospective Cohort for Identification of Secondary HLH (COVIDHLH)

Establishing a Covid-19 Prospective Cohort to Document Cases of Secondary Hemophagocytic Lymphohistiocytosis (sHLH, Synonoums to Macrophage Activation Syndrome)

SARS-CoV2 has become a pandemic disease putting an enormous burden on health care systems around the world. A considerable amount of patients require intensive care treatment for Covid-19 associated pneumonia. At this point there is no specific treatment, apart from supportive intensive care treatment protocols for severe COVID-19 disease.The latest reports describe massive hyperinflammation in some of the severe COVID-19 patients, which is not a typical finding in virus associated pneumonia. The H-score and the modified HLH 2004 score offer diagnostic tools, that help establishing the diagnosis of HLH. Even more important is the expert clinical judgment to establish the diagnosis of sHLH.

Study Overview

• Status: Unknown
• Conditions: COVID

Detailed Description

SARS-CoV2 has become a pandemic disease putting an enormous burden on health care systems around the world. The course of disease is relatively mild in most of the patients, but there is a considerable amount of patients that require intensive care treatment for Covid-19 associated pneumonia. At this point there is no specific treatment, apart from supportive intensive care treatment protocols for severe COVID-19 disease.The latest reports describe massive hyperinflammation in some of the severe COVID-19 patients. The H-score and the modified HLH 2004 score offer diagnostic tools, that helps establishing the diagnosis of HLH. Moreover expert clinical judgment is key to establish a diagnosis of sHLH. Still, so far no systematic analysis has been carried out answering the question as to whether or not these patients suffer from secondary HLH and could potentially benefit from immunomodulatory drugs.

• Study Type: Observational
• Enrollment (Anticipated): 20

Contacts and Locations

• Study Contact: Name: Christoph Schmaderer, M.D.; Phone Number: 5231 0049-89-4140; Email: christoph.schmaderer@mri.tum.de
• Study Contact Backup: Name: Philipp Moog, M.D.; Phone Number: 5231 0049-89-4140; Email: philipp.moog@mri.tum.de

Study Locations

• Germany
  • Bavaria
    • München, Bavaria, Germany, 81675
      • Recruiting
      • Department of nephrology, Klinikum rechts der Isar
      • Contact: Christoph Schmaderer, M.D.; Phone Number: 5231 0049-89-4140; Email: christoph.schmaderer@mri.tum.de
      • Contact: Georg Lorenz, M.D.; Phone Number: 5231 0049-89-4140; Email: georg.lorenz@mri.tum.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

We will recruit patients with COVID 19 interstital pneumonia with need of ICU treatment at the Klinikum rechts der Isar.

Description

Inclusion Criteria:

• Age > 17a
• diagnosis of SARS CoV 2 by PCR testing
• Hospitalized due to clinical severity of the disease
• written and informed consent or consent of the family
• GFR<30 is not an exclusion criterion

Exclusion Criteria:

• not fulfilling the inclusion criteria
• missing written and informed consent

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
COVID 19; Patients requiring ICU treatment due to severe COVID 19 interstitial pneumonia or otherwise COVID-19 related disease

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Presence of sHLH as determined by expert chart review by two independent reviewers	blinded chart review by a hematooncologist and a rheumatologist having expert experience in HLH diagnosis and treatment	in the first week after admission to the ICU
Determine the incidence of patients fulfilling HLH criteria in Covid 19 viral infection	Calculate HScore in all recruited patients	in the first week after admission to the ICU
Determine the incidence of patients fulfilling modified 2004 HLH diagnostic criteria (Ferritin > 10000 μg/L) in Covid 19 viral infection	Calculate modified 2004 HLH diagnostic criteria in all study participants	in the week after admission to the ICU
Characterization and incidence of the hyper-inflammatory state in COVID-19	characterized by sIL-2, Ferritin, Il-6, CRP, PCT and aberrant cellular activation (differential blood count and immunophenotypic analysis)	assessed within 15 days post ICU-admission

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
all cause mortality assesed on day 15	vital status of patients will be assesed by clinical records or phone calls to patient or relatives or other hospitals involved in the care of the patient	assesed on study day 15
all cause mortality assesed on day 29	vital status of patients will be assesed by clinical records or phone calls to patients or relatives or other hospitals involved in the care of the patient	assesed on study day 29
immunophenotpye	characterize immune cell populations	in the first days after admission to the ICU

Collaborators and Investigators

• Sponsor: Technical University of Munich
• Investigators: Principal Investigator: Christoph Schmaderer, M.D., Department of Nephrology, TUM Medical School, Klinikum rechts der Isar

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 27, 2020
• Primary Completion (ANTICIPATED): July 1, 2020
• Study Completion (ANTICIPATED): August 31, 2020

Study Registration Dates

• First Submitted: April 8, 2020
• First Submitted That Met QC Criteria: April 11, 2020
• First Posted (ACTUAL): April 15, 2020

Study Record Updates

• Last Update Posted (ACTUAL): April 15, 2020
• Last Update Submitted That Met QC Criteria: April 11, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: COVID; MAS; HLH
• Other Study ID Numbers: 161/20 S

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No