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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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COVID

Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| COVID 19<br>Patients requiring ICU treatment due to severe COVID 19 interstitial pneumonia or otherwise COVID-19 related disease | |

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MAS, HLH, COVID