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1.
Journal of the Endocrine Society ; 5(Supplement_1):A835-A836, 2021.
Article in English | PMC | ID: covidwho-1221835

ABSTRACT

Background: Lymphopenia is a key feature of immune dysfunction in bacterial sepsis and COVID-19 patients and is associated with poor clinical outcomes, but the cause is largely unknown. These severely ill patients may also present with thyroid function abnormalities, so-called non-thyroidal illness syndrome (NTIS), and several studies have suggested that TSH, thyroxin (T4) and triiodothyronine (T3) play a crucial role in the homeostatic regulation and function of lymphocyte populations.

2.
Eur J Intern Med ; 88: 52-62, 2021 06.
Article in English | MEDLINE | ID: covidwho-1157261

ABSTRACT

Aims Infection by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) may lead to the development of severe respiratory failure. In hospitalized-patients, prompt interruption of the virus-driven inflammatory process by using combination treatments seems theoretically of outmost importance. Our aim was to investigate the hypothesis of multifaceted management of these patients. Methods A treatment algorithm based on ferritin was applied in 311 patients (67.2% males; median age 63-years; moderate disease, n=101; severe, n=210). Patients with ferritin <500ng/ml received anakinra 2-4mg/kg/day ± corticosteroids (Arm A, n=142) while those with ≥500ng/ml received anakinra 5-8mg/kg/day with corticosteroids and γ-globulins (Arm B, n=169). In case of no improvement a single dose of tocilizumab (8mg/kg; maximum 800mg) was administered with the potential of additional second and/or third pulses. Treatment endpoints were the rate of the development of respiratory failure necessitating intubation and the SARS-CoV-2-related mortality. The proposed algorithm was also validated in matched hospitalized-patients treated with standard-of-care during the same period. Results In overall, intubation and mortality rates were 5.8% and 5.1% (0% in moderate; 8.6% and 7.6% in severe). Low baseline pO2/FiO2 and older age were independent risk factors. Comparators had significantly higher intubation (HR=7.4; 95%CI: 4.1-13.4; p<0.001) and death rates (HR=4.5, 95%CI: 2.1-9.4, p<0.001). Significant adverse events were rare, including severe secondary infections in only 7/311 (2.3%). Conclusions Early administration of personalized combinations of immunomodulatory agents may be life-saving in hospitalized-patients with COVID-19. An immediate intervention (the sooner the better) could be helpful to avoid development of full-blown acute respiratory distress syndrome and improve survival.


Subject(s)
COVID-19 , Respiratory Distress Syndrome , Respiratory Insufficiency , Aged , Female , Humans , Interleukin 1 Receptor Antagonist Protein , Male , Middle Aged , Respiratory Insufficiency/therapy , SARS-CoV-2 , Treatment Outcome
3.
J Clin Endocrinol Metab ; 106(7): 1994-2009, 2021 06 16.
Article in English | MEDLINE | ID: covidwho-1133638

ABSTRACT

CONTEXT: Lymphopenia is a key feature of immune dysfunction in patients with bacterial sepsis and coronavirus disease 2019 (COVID-19) and is associated with poor clinical outcomes, but the cause is largely unknown. Severely ill patients may present with thyroid function abnormalities, so-called nonthyroidal illness syndrome, and several studies have linked thyrotropin (thyroid stimulating hormone, TSH) and the thyroid hormones thyroxine (T4) and 3,5,3'-triiodothyronine (T3) to homeostatic regulation and function of lymphocyte populations. OBJECTIVE: This work aimed to test the hypothesis that abnormal thyroid function correlates with lymphopenia in patients with severe infections. METHODS: A retrospective analysis of absolute lymphocyte counts, circulating TSH, T4, free T4 (FT4), T3, albumin, and inflammatory biomarkers was performed in 2 independent hospitalized study populations: bacterial sepsis (n = 224) and COVID-19 patients (n = 161). A subgroup analysis was performed in patients with severe lymphopenia and normal lymphocyte counts. RESULTS: Only T3 significantly correlated (ρ = 0.252) with lymphocyte counts in patients with bacterial sepsis, and lower concentrations were found in severe lymphopenic compared to nonlymphopenic patients (n = 56 per group). Severe lymphopenic COVID-19 patients (n = 17) showed significantly lower plasma concentrations of TSH, T4, FT4, and T3 compared to patients without lymphopenia (n = 18), and demonstrated significantly increased values of the inflammatory markers interleukin-6, C-reactive protein, and ferritin. Remarkably, after 1 week of follow-up, the majority (12 of 15) of COVID-19 patients showed quantitative recovery of their lymphocyte numbers, whereas TSH and thyroid hormones remained mainly disturbed. CONCLUSION: Abnormal thyroid function correlates with lymphopenia in patients with severe infections, like bacterial sepsis and COVID-19, but future studies need to establish whether a causal relationship is involved.


Subject(s)
COVID-19/complications , Euthyroid Sick Syndromes/diagnosis , Lymphopenia/immunology , Sepsis/complications , Aged , Aged, 80 and over , COVID-19/blood , COVID-19/immunology , Euthyroid Sick Syndromes/blood , Euthyroid Sick Syndromes/immunology , Female , Greece , Humans , Lymphocyte Count , Lymphopenia/blood , Lymphopenia/diagnosis , Male , Netherlands , Retrospective Studies , SARS-CoV-2/immunology , Sepsis/blood , Sepsis/immunology , Thyroid Hormones/blood , Thyroid Hormones/immunology , Thyrotropin/blood , Thyrotropin/immunology
4.
BMC Infect Dis ; 20(1): 860, 2020 Nov 19.
Article in English | MEDLINE | ID: covidwho-934260

ABSTRACT

BACKGROUND: The accuracy of a new optical biosensor (OB) point-of-care device for the detection of severe infections is studied. METHODS: The OB emits different wavelengths and outputs information associated with heart rate, pulse oximetry, levels of nitric oxide and kidney function. At the first phase, recordings were done every two hours for three consecutive days after hospital admission in 142 patients at high-risk for sepsis by placing the OB on the forefinger. At the second phase, single recordings were done in 54 patients with symptoms of viral infection; 38 were diagnosed with COVID-19. RESULTS: At the first phase, the cutoff value of positive likelihood of 18 provided 100% specificity and 100% positive predictive value for the diagnosis of sepsis. These were 87.5 and 91.7% respectively at the second phase. OB diagnosed severe COVID-19 with 83.3% sensitivity and 87.5% negative predictive value. CONCLUSIONS: The studied OB seems valuable for the discrimination of infection severity.


Subject(s)
Biosensing Techniques/methods , Coronavirus Infections/diagnosis , Pneumonia, Viral/diagnosis , Sepsis/diagnosis , Aged , Aged, 80 and over , Algorithms , Area Under Curve , Betacoronavirus/isolation & purification , COVID-19 , COVID-19 Testing , Clinical Laboratory Techniques , Coronavirus Infections/pathology , Coronavirus Infections/virology , Early Diagnosis , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , ROC Curve , SARS-CoV-2 , Sensitivity and Specificity , Severity of Illness Index
5.
Crit Care Med ; 49(2): e170-e178, 2021 02 01.
Article in English | MEDLINE | ID: covidwho-930107

ABSTRACT

OBJECTIVES: Complex critical syndromes like sepsis and coronavirus disease 2019 may be composed of underling "endotypes," which may respond differently to treatment. The aim of this study was to test whether a previously defined bacterial sepsis endotypes classifier recapitulates the same clinical and immunological endotypes in coronavirus disease 2019. DESIGN: Prospective single-center observational cohort study. SETTING: Patients were enrolled in Athens, Greece, and blood was shipped to Inflammatix (Burlingame, CA) for analysis. PATIENTS: Adult patients within 24 hours of hospital admission with coronavirus disease 2019 confirmed by polymerase chain reaction and chest radiography. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We studied 97 patients with coronavirus disease 2019, of which 50 went on to severe respiratory failure (SRF) and 16 died. We applied a previously defined 33-messenger RNA classifier to assign endotype (Inflammopathic, Adaptive, or Coagulopathic) to each patient. We tested endotype status against other clinical parameters including laboratory values, severity scores, and outcomes. Patients were assigned as Inflammopathic (29%), Adaptive (44%), or Coagulopathic (27%), similar to our prior study in bacterial sepsis. Adaptive patients had lower rates of SRF and no deaths. Coagulopathic and Inflammopathic endotypes had 42% and 18% mortality rates, respectively. The Coagulopathic group showed highest d-dimers, and the Inflammopathic group showed highest C-reactive protein and interleukin-6 levels. CONCLUSIONS: Our predefined 33-messenger RNA endotypes classifier recapitulated immune phenotypes in viral sepsis (coronavirus disease 2019) despite its prior training and validation only in bacterial sepsis. Further work should focus on continued validation of the endotypes and their interaction with immunomodulatory therapy.


Subject(s)
COVID-19/diagnosis , SARS-CoV-2/isolation & purification , Sepsis/classification , Sepsis/genetics , Adult , COVID-19/complications , Female , Gene Expression Profiling , Humans , Male , Middle Aged , Respiratory Insufficiency , Severity of Illness Index
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