Study of Lymphopenia as a Specific Biomarker or Prognostic Risk Factor for Disease Severity in Elderly Patients With COVID-19

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Brief Title

Study of Lymphopenia as a Specific Biomarker or Prognostic Risk Factor for Disease Severity in Elderly Patients With COVID-19

Official Title

Study of Lymphopenia as a Specific Biomarker or Prognostic Risk Factor for Disease Severity in Elderly Patients With COVID-19.

Brief Summary

      Background: Lymphopenia is reported to be associated with the severity of disease progression
      in COVID-19. Low lymphocyte count is also associated with increasing age. No study has yet
      investigated the effects of lymphopenia in this disease on the outcome in elderly people.

      Objectives: To assess the outcome of lymphopenia in elderly patients having COVID-19 and its
      usefulness as prognostic factor in elderly people.

      Methods: Retrospective cohort study. Clinical data (medical history, comorbidities,
      treatments, geriatric syndromes) and biological parameters will be collected from 100
      hospitalized geriatric COVID-19 patients (> 70 yrs.) (Group 1) and 100 hospitalized geriatric
      patients (> 70 yrs.) presenting with acute infection other than COVID-19 (Group 2) and will
      be compared according to the presence/absence of lymphopenia. A third Group (3) will be
      studied to assess the influence of comorbidities on lymphopenia consisting of healthy aged
      elderly (> 70 yrs.).
    

Detailed Description

      Introduction In December 2019 a cluster of viral pneumonia cases in Wuhan, a city in the
      Hubei Province of China, led to the discovery of a novel pathogen that was later named Severe
      Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) (1). SARS-CoV-2 rapidly spread
      throughout the population of China and subsequently to all continents of the world (except
      for Antarctica). On 11 March 2020 the outbreak was declared a pandemic by the World Health
      Organisation (WHO) (2). In September confirmed cases have been reported from 217 different
      countries and has resulted in over 27 million infected individuals and as near as 900.000
      deadly cases reported to the WHO (3, 4). SARS-CoV-2 does not discriminate between social
      status, age or ethnicity and an effective treatment remains absent until so far. However,
      risk factors associated with severity of disease progression have been identified and include
      advanced age (>65y), comorbidities with inclusion of arterial hypertension, cardiovascular
      disease, cerebrovascular disease, respiratory disease and laboratory parameters such as low
      CD3+CD8+ T cells (<75 cells.µL-1), low lymphocyte count, neutrophil to lymphocyte ratio (N/L)
      (N/L ratio >3.13) and increased cardiac troponin I (≥0.05ng.mL-1) (5-9).

      It has been demonstrated that both age and lymphopenia are risk factors associated with
      severity of disease progression in COVID-19 patients. A low lymphocyte count, however, is
      also known to be associated with increasing age in healthy individuals (10). Another study
      has also shown that a high CRP was associated with lymphopenia in a geriatric hospitalized
      population before the apparition of COVID-19 (11). This observation raises the question
      whether or not lymphopenia is a specific prognostic marker for the COVID-19 illness in
      elderly patients.

      The aims of this study are:

        1. to assess the specificity of lymphopenia in COVID-19 cases in elderly people thanks to
           the comparison of 3 Groups:

             1. Group 1 consists of COVID-19 cases

             2. Group 2 consists of patients with an acute infection other than COVID-19

             3. Group 3 consists of healthy aged people defined as in the modified SENIEUR protocol

        2. to assess the correlation of lymphopenia in COVID-19 cases and the outcome

        3. to assess the relationship between other morbidities (such as CV diseases / risk
           factors) and lymphopenia in elderly people.

      Patients and methods

      Patients:

      To assess the outcome of lymphopenia in COVID-19 infections in elderly patients, three Groups
      will be studied:

      Group 1 will consist of 100 patients COVID-19 positive patients older than 70 years old
      hospitalized in UZ Brussel from February 2020 until September 2020 with a positive RT-PCR
      test for SARS-CoV-2.

      Group 2 will consist of 100 patients older than 70 years old hospitalized in UZ Brussel for
      acute infections other than COVID-19. To avoid including false negative patients, these
      patients will be selected from January 2019 until December 2019, before the first COVID-19
      cases were documented in Belgium. An acute infection other than COVID-19 will be defined as
      1) viral infection confirmed by nasopharynx swab for: influenza, RSV, parainfluenza,
      rhinoviruses, coronaviruses or 2) bacterial infection confirmed with positive blood culture,
      positive articular punction, positive expectorations, pneumonia on chest radiograph, or
      infection documented by abdominal imagery (CT or echo), a positive urine culture with a
      confirmed pyelonephritis with a renal echography or a DMSA scintigraphy or specific clinical
      symptoms for pyelonephritis and positive hemoculture. A positive urine culture alone is not
      considered as urine infection because of the high prevalence of asymptomatic bacteriuria in
      geriatric patients.

      To assess the influence of comorbidities on lymphopenia in elderly people, the Groups 1 and 2
      will be compared to a well-defined historical group (Group 3):

      Group 3 will consist of healthy aged people defined as in the modified SENIEUR protocol (12,
      13). This group is recruited from a previously conducted study. These are community dwelling
      individuals above the age of 70 and considered as almost healthy with some conditions that
      are present in the majority of old people such as osteoporosis, osteoarthritis or
      atherosclerosis.

      Inclusion criteria Cfr definition of the three groups Exclusion criteria Patients receiving
      immunosuppressive therapy, patients with known active cancer or hematologic disorders,
      patients undergoing radio- or chemotherapy or with known autoimmune diseases will not be
      included since these underlying conditions or therapies can interfere with white blood cell
      count in a way that is beyond the scope of this research.

      Methods:

      Determination of clinical characteristics All subjects will be assessed for underlying
      illnesses by medical archives and blood sampling. Social evaluation included determination of
      age, gender and home (private versus institution). Clinical data included smoking and alcohol
      habits, body mass index (BMI), medical history, current treatment and reasons for
      hospitalization. Cardiovascular (CV) diseases are defined as a history of stroke, myocardial
      infarct, cardiac insufficiency (assessed by anterior cardiac echography and clinical
      symptoms), cerebral vascular disease or atheromatosis assessed by carotid or leg Doppler
      ultrasonography and ischemic symptoms. CV risk factors will be defined by the presence in the
      medical history of arterial hypertension (AHT), type 2 diabetes mellitus (DM 2),
      hypercholesterolemia or statin intake, infarct history or smoking.

      Comprehensive geriatric assessment When possible, we will obtain a comprehensive geriatric
      assessment: The comorbidities and the severity of the medical problems were scored using the
      "Cumulative Illness Rating Scale-Geriatric" (CIRS-G), which is an instrument to quantify
      disease burden. It differentiates older adults with the highest risk and severity of
      infection with a markedly impaired vaccine response (14). It comprises a comprehensive review
      of medical problems of 14 organ systems. It is based on a 0 to 4 rating of each organ system
      (15). The "Geriatric Depression Scale" was used to assess the risk of depression (GDS-15) in
      15 questions (16). The assessment of "Activities of Daily Living" (ADL) was made using Katz's
      scale. It includes the following items: bathing, dressing, transfer, toilet, continence and
      eating. Each task is graded on a 4-level scale (1 to 4 for Katz's scale), where lower levels
      represent the absence of dependence and upper levels the maximal dependence for the task
      (17). Cognitive functions were assessed using the "Mini Mental State Examination" (MMSE).
      Possible scores range from 0 to 30 points, with scores<24/30 indicating impaired cognitive
      function (18). Nutritional status was assessed using the "Malnutrition Universal Screening
      Tool" (MUST) (19). Social complexity was defined by the need for an intervention with a
      social worker (need for home care, rehabilitation nursing home or financial help). The sum of
      geriatric syndrome includes the following: fall, social complexity, delirium, undernutrition,
      dependence, depression, dysphagia, incontinence, orthostatic hypotension, inappropriate
      prescription, and cognitive dysfunction.

      Biological parameters Data from the routine biochemical assessment performed in the first 24
      hrs and after 3 to 5 days after admission to a geriatric unit will be collected (total and
      differential white blood cell counts, hemoglobin and hematocrit, renal function and
      electrolytes CRP, albumin, prealbumin, vitamin B12, and folic acid levels).

      Outcome:

      To assess the outcome of patients with or without lymphopenia, the number of
      rehospitalisation's, the admissions to an intensive care unit, the complications such as lung
      embolism, the duration of the hospital stay, the mortality, the place of the discharge and
      the severity score of the CT scan of the thorax in COVID-19 + patients will be collected.

      Procedures This is a retrospective study. No interventions will be performed.

      Flowchart

      Study analysis Statistical analysis IBM SPSS version 25 will be used for statistical
      analyses. The Kolmogorov-Smirnov test will be used to determine the normality of the data.

      Mann Whitney rank sum test for non-parametric data or a student T-test for parametric data
      will be performed to compare patients with and without lymphopenia for COVID-19, other
      infections, comorbidities, complications, geriatric assessment, duration of hospitalisation,
      rehospitalisation, mortality, place of discharge.

      In order to identify clinical and biological factors that could be significantly associated
      with lymphopenia, we performed univariate analyses (depicted by Pearson's coefficient). For
      all volunteers, these parameters comprised CV diseases and risk factors (smoking, arterial
      hypertension, type 2 diabetes, cholesterol levels, BMI), COVID-19, other infections,
      comorbidities, complications, geriatric assessment, duration of hospitalisation,
      rehospitalisation, mortality, place of discharge.

      In order to define independent predictive factors of lymphopenia, we tested several models by
      stepwise backward multi-linear regression analyses.
    


Study Type

Observational


Primary Outcome

assess the specificity of lymphopenia in COVID-19 cases in elderly people

Secondary Outcome

 to assess the correlation of lymphopenia in COVID-19 cases and the outcome

Condition

Lymphopenia

Intervention

observation no intervention

Study Arms / Comparison Groups

 Group 1
Description:  Group 1 will consist of 100 patients COVID-19 positive patients older than 70 years old hospitalized in UZ Brussel from February 2020 until September 2020 with a positive RT-PCR test for SARS-CoV-2.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Other

Estimated Enrollment

300

Start Date

June 30, 2021

Completion Date

December 31, 2023

Primary Completion Date

December 31, 2023

Eligibility Criteria

        Inclusion Criteria:

        Cfr definition of the three groups

        Exclusion Criteria:

          -  Patients receiving immunosuppressive therapy, patients with known active cancer or
             hematologic disorders, patients undergoing radio- or chemotherapy or with known
             autoimmune diseases will not be included since these underlying conditions or
             therapies can interfere with white blood cell count in a way that is beyond the scope
             of this research.
      

Gender

All

Ages

70 Years - N/A

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

, , 

Location Countries

Belgium

Location Countries

Belgium

Administrative Informations


NCT ID

NCT04800731

Organization ID

Lymfopenia


Responsible Party

Principal Investigator

Study Sponsor

Universitair Ziekenhuis Brussel


Study Sponsor

, , 


Verification Date

August 2021