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J Med Virol ; 93(9): 5474-5480, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1219314


In this study, laboratorial parameters of hospitalized novel coronavirus (COVID-19) patients, who were complicated with severe pneumonia, were compared with the findings of cytokine storm developing in macrophage activation syndrome (MAS)/secondary hemophagocytic lymphohistiocytosis (sHLH). Severe pneumonia occurred as a result of cytokine storm in some patients who needed intensive care unit (ICU), and it is aimed to determine the precursive parameters in this situation. Also in this study, the aim is to identify laboratory criteria that predict worsening disease and ICU intensification, as well as the development of cytokine storm. This article comprises a retrospective cohort study of patients admitted to a single institution with COVID-19 pneumonia. This study includes 150 confirmed COVID-19 patients with severe pneumonia. When they were considered as severe pneumonia patients, the clinic and laboratory parameters of this group are compared with H-score criteria. Patients are divided into two subgroups; patients with worsened symptoms who were transferred into tertiary ICU, and patients with stable symptoms followed in the clinic. For the patients with confirmed COVID-19 infection, after they become complicated with severe pneumonia, lymphocytopenia (55.3%), anemia (12.0%), thrombocytopenia (19.3%), hyperferritinemia (72.5%), hyperfibrinogenemia (63.7%) and elevated lactate dehydrogenase (LDH) (90.8%), aspartate aminotransaminase (AST) (31.3%), alanine aminotransaminase (ALT) (20.7%) are detected. There were no significant changes in other parameters. Blood parameters between the pre-ICU period and the ICU period (in which their situation had been worsened and acute respiratory distress syndrome [ARDS] was developed) were also compared. In the latter group lymphocyte levels were found significantly reduced (p = 0.01), and LDH, highly sensitive troponin (hs-troponin), procalcitonin, and triglyceride levels were significantly increased (p < 0.05). In addition, there was no change in hemoglobin, leukocyte, platelet, ferritin, and liver function test levels, including patients who developed ARDS, similar to the cytokine storm developed in MAS/sHLH. COVID-19 pneumonia has similar findings as hyperinflammatory syndromes but does not seem to have typical features as in cytokine storm developed in MAS/sHLH. In the severe patient group who has started to develop ARDS signs, a decrease in lymphocyte level in addition to the elevated LDH, hs-troponin, procalcitonin, and triglyceride levels can be a predictor in progression to ICU admission and could help in the planning of anti-cytokine therapy.

COVID-19/pathology , Cytokine Release Syndrome/pathology , Lymphohistiocytosis, Hemophagocytic/pathology , Macrophage Activation Syndrome/pathology , SARS-CoV-2/pathogenicity , Aged , Alanine Transaminase/blood , Anemia/blood , Anemia/diagnosis , Anemia/immunology , Anemia/pathology , Aspartate Aminotransferases/blood , Biomarkers/blood , COVID-19/blood , COVID-19/diagnosis , COVID-19/immunology , Cytokine Release Syndrome/blood , Cytokine Release Syndrome/diagnosis , Cytokine Release Syndrome/immunology , Diagnosis, Differential , Disease Progression , Female , Fibrinogen/metabolism , Humans , Hyperferritinemia/blood , Hyperferritinemia/diagnosis , Hyperferritinemia/immunology , Hyperferritinemia/pathology , Intensive Care Units , L-Lactate Dehydrogenase/blood , Lymphohistiocytosis, Hemophagocytic/blood , Lymphohistiocytosis, Hemophagocytic/diagnosis , Lymphohistiocytosis, Hemophagocytic/immunology , Lymphopenia/blood , Lymphopenia/diagnosis , Lymphopenia/immunology , Lymphopenia/pathology , Macrophage Activation Syndrome/blood , Macrophage Activation Syndrome/diagnosis , Macrophage Activation Syndrome/immunology , Male , Middle Aged , Procalcitonin/blood , Retrospective Studies , Thrombocytopenia/blood , Thrombocytopenia/diagnosis , Thrombocytopenia/immunology , Thrombocytopenia/pathology , Triglycerides/blood , Troponin/blood
Placenta ; 105: 7-13, 2021 02.
Article in English | MEDLINE | ID: covidwho-1047776


INTRODUCTION: Recent reports suggest SARS-CoV-2, the virus causing COVID-19, may be transmittable from pregnant mother to placenta and fetus, albeit rarely. The efficacy of vertical transmission of SARS-CoV-2 critically depends on the availability of its receptor, ACE2, in the placenta. In the present study, we tested the hypothesis that placental ACE2 expression is oxygenation-dependent by studying the expression of ACE2 and associated cell entry regulators in the monochorionic twin anemia-polycythemia (TAPS) placenta, a model of discordant placental oxygenation. METHODS: We performed a retrospective comparative immunohistochemical, immunofluorescence and Western blot analysis of ACE2, TMPRSS2 and Cathepsin B expression in anemic and polycythemic territories of TAPS placentas (N = 14). RESULTS: ACE2 protein levels were significantly higher in the anemic twin territories than in the corresponding polycythemic territories, associated with upregulation of the key ACE2-related cell entry regulators, TMPRSS2 and Cathepsin B, immunolocalized to villous trophoblastic and stromal cells. Cellular colocalization of ACE2 and TMPRSS2, suggestive of functionality of this cell entry axis, was demonstrated by double immunofluorescence studies. DISCUSSION: Placental hypoxia is associated with upregulation of ACE2 expression, concomitant with increased expression of its key cell entry proteases. ACE2-regulated placental functions, both infection- and non-infection related, may be highly oxygenation-dependent.

Anemia/metabolism , Angiotensin-Converting Enzyme 2/metabolism , Fetal Diseases/metabolism , Hypoxia/metabolism , Placenta/metabolism , Polycythemia/metabolism , Pregnancy, Twin , Adult , Anemia/complications , Anemia/pathology , Case-Control Studies , Cohort Studies , Diseases in Twins/metabolism , Diseases in Twins/pathology , Female , Fetal Diseases/pathology , Humans , Hypoxia/complications , Hypoxia/pathology , Immunohistochemistry , Infant, Newborn , Male , Placenta/pathology , Polycythemia/complications , Polycythemia/pathology , Pregnancy , Pregnancy, Twin/metabolism , Retrospective Studies , SARS-CoV-2/metabolism , Serine Endopeptidases/metabolism , Up-Regulation
Clin Exp Med ; 21(2): 239-246, 2021 May.
Article in English | MEDLINE | ID: covidwho-1014153


COVID-19 patients typically present with lower airway disease, although involvement of other organ systems is usually the rule. Hematological manifestations such as thrombocytopenia and reduced lymphocyte and eosinophil numbers are highly prevalent in COVID-19 and have prognostic significance. Few data, however, are available about the prevalence and significance of anemia in COVID-19. In an observational study, we investigated the prevalence, pathogenesis and clinical significance of anemia among 206 patients with COVID-19 at the time of their hospitalization in an Internal Medicine unit. The prevalence of anemia was 61% in COVID-19, compared with 45% in a control group of 71 patients with clinical and laboratory findings suggestive of COVID-19, but nasopharyngeal swab tests negative for SARS-CoV-2 RNA (p = 0.022). Mortality was higher in SARS-CoV-2 positive patients. In COVID-19, females had lower hemoglobin concentration than males and a higher prevalence of moderate/severe anemia (25% versus 13%, p = 0.032). In most cases, anemia was mild and due to inflammation, sometimes associated with iron and/or vitamin deficiencies. Determinants of hemoglobin concentration included: erythrocyte sedimentation rate, serum cholinesterase, ferritin and protein concentrations and number of chronic diseases affecting each patient. Hemoglobin concentration was not related to overall survival that was, on the contrary, influenced by red blood cell distribution width, age, lactate dehydrogenase and the ratio of arterial partial oxygen pressure to inspired oxygen fraction. In conclusion, our results highlight anemia as a common manifestation in COVID-19. Although anemia does not directly influence mortality, it usually affects elderly, frail patients and can negatively influence their quality of life.

Anemia, Iron-Deficiency/blood , COVID-19/blood , COVID-19/pathology , Erythrocyte Count , Hemoglobins/analysis , Adult , Aged , Anemia/blood , Anemia/pathology , Anemia, Iron-Deficiency/pathology , Anemia, Iron-Deficiency/therapy , Blood Gas Monitoring, Transcutaneous , Blood Sedimentation , C-Reactive Protein/analysis , COVID-19/mortality , Cholinesterases/blood , Comorbidity , Female , Ferritins/blood , Humans , L-Lactate Dehydrogenase/blood , Male , Middle Aged , Oxygen/blood , SARS-CoV-2