Cushing syndrome and glucocorticoids: T-cell lymphopenia, apoptosis, and rescue by IL-21.

BACKGROUND: Pediatric endogenous Cushing syndrome (eCs) is mainly caused by pituitary corticotropin-producing adenomas, and most glucocorticoid-dependent effects progressively regress upon tumor removal. eCs reproduces long-term, high-dose glucocorticoid therapy, representing a clean, natural, and unbiased model in which to study glucocorticoid bona fide effects on immunity. OBJECTIVE: We performed extensive immunologic studies in otherwise healthy pediatric patients with eCs before and 6 to 13 months after tumor resection, as well as in in vitro glucocorticoid-treated control cells. METHODS: Flow cytometry, immunoblotting, enzyme-linked immunosorbent assay, real-time quantitative PCR, and RNA-Seq techniques were used to characterize patients' and in vitro glucocorticoid treated cells. RESULTS: Reduced thymic output, decreased naive T cells, diminished proliferation, and increased T-cell apoptosis were detected before surgery; all these defects eventually normalized after tumor removal in patients. In vitro studies also showed increased T-cell apoptosis, with correspondingly diminished NF-κB signaling and IL-21 levels. In this setting, IL-21 addition upregulated antiapoptotic BCL2 expression and rescued T-cell apoptosis in a PI3K pathway-dependent manner. Similar and reproducible findings were confirmed in eCs patient cells as well. CONCLUSIONS: We identified decreased thymic output and lymphocyte proliferation, together with increased apoptosis, as the underlying causes to T-cell lymphopenia in eCs patients. IL-21 was decreased in both natural and in vitro long-term, high-dose glucocorticoid environments, and in vitro addition of IL-21 counteracted the proapoptotic effects of glucocorticoid therapy. Thus, our results suggest that administration of IL-21 in patients receiving long-term, high-dose glucocorticoid therapy may contribute to ameliorate lymphopenia and the complications associated to it.

COVID-19 and Cancer: Discovery of Difference in Clinical Immune Indexes.

OBJECTIVE: This study explored the consistency and differences in the immune cells and cytokines between patients with COVID-19 or cancer. We further analyzed the correlations between the acute inflammation and cancer-related immune disorder. METHODS: This retrospective study involved 167 COVID-19 patients and 218 cancer patients. COVID-19 and cancer were each further divided into two subgroups. Quantitative and qualitative variables were measured by one-way ANOVA and chi-square test, respectively. Herein, we carried out a correlation analysis between immune cells and cytokines and used receiver operating characteristic (ROC) curves to discover the optimal diagnostic index. RESULTS: COVID-19 and cancers were associated with lymphopenia and high levels of monocytes, neutrophils, IL-6, and IL-10. IL-2 was the optimal indicator to differentiate the two diseases. Compared with respiratory cancer patients, COVID-19 patients had lower levels of IL-2 and higher levels of CD3+CD4+ T cells and CD19+ B cells. In the subgroup analysis, IL-6 was the optimal differential diagnostic parameter that had the ability to identify if COVID-19 patients would be severely affected, and severe COVID-19 patients had lower levels of lymphocyte subsets (CD3+ T cells, CD3+CD4+ T cells, CD3+CD8+T cells, and CD19+ B cells) and CD16+CD56+ NK cells and higher level of neutrophils. There were significant differences in the levels of CD3+CD4+ T cells and CD19+ B cells between T1-2 and T3-4 stages as well as IL-2 and CD19+ B cells between N0-1 and N2-3 stages while no significant differences between the metastatic and nonmetastatic cancer patients. Additionally, there were higher correlations between IL-2 and IL-4, TNF-α and IL-2, TNF-α and IL-4, TNF-α and IFN-γ, and CD16+CD56+NK cells and various subsets of T cells in COVID-19 patients. There was a higher correlation between CD3+CD4+ T cells and CD19+ B cells in cancer patients. CONCLUSION: Inflammation associated with COVID-19 or cancer had effects on patients' outcomes. Accompanied by changes in immune cells and cytokines, there were consistencies, differences, and satisfactory correlations between patients with COVID-19 and those with cancers.

Peripheral granular lymphocytopenia and dysmorphic leukocytosis as simple prognostic markers in COVID-19.

INTRODUCTION: Developing prognostic markers can be useful for clinical decision-making. Peripheral blood (PB) examination is simple and basic that can be performed in any facility. We aimed to investigate whether PB examination can predict prognosis in coronavirus disease (COVID-19). METHODS: Complete blood count (CBC) and PB cell morphology were examined in 38 healthy controls (HCs) and 40 patients with COVID-19. Patients with COVID-19, including 26 mild and 14 severe cases, were hospitalized in Juntendo University Hospital (Tokyo, Japan) between April 1 and August 6, 2020. PB examinations were performed using Sysmex XN-3000 automated hematology analyzer and Sysmex DI-60 employing the convolutional neural network-based automatic image-recognition system. RESULTS: Compared with mild cases, severe cases showed a significantly higher incidence of anemia, lymphopenia, and leukocytosis (P < .001). Granular lymphocyte counts were normal or higher in mild cases and persistently decreased in fatal cases. Temporary increase in granular lymphocytes was associated with survival of patients with severe infection. Red cell distribution width was significantly higher in severe cases than in mild cases (P < .001). Neutrophil dysplasia was consistently observed in COVID-19 cases, but not in HCs. Levels of giant neutrophils and toxic granulation/Döhle bodies were increased in severe cases. CONCLUSION: Basic PB examination can be useful to predict the prognosis of COVID-19, by detecting SARS-CoV-2 infection-induced multi-lineage changes in blood cell counts and morphological anomalies. These changes were dynamically correlated with disease severity and may be associated with disruption of hematopoiesis and the immunological system due to bone marrow stress in severe infection.

Antibiotic administration exacerbates acute graft vs. host disease-induced bone marrow and spleen damage in lymphopenic mice.

BACKGROUND: Hematopoietic stem cell transplantation is a potential cure for certain life-threatening malignant and nonmalignant diseases. However, experimental and clinical studies have demonstrated that pre-transplant myeloablative conditioning damages the gut leading to translocation of intestinal bacteria and the development of acute graft vs. host disease (aGVHD). The overall objective of this study was to determine whether administration of broad spectrum antibiotics (Abx) affects the onset and/or severity of aGVHD in lymphopenic mice that were not subjected to toxic, pre-transplant conditioning. RESULTS: We found that treatment of NK cell-depleted recombination activating gene-1-deficient (-NK/RAG) recipients with an Abx cocktail containing vancomycin and neomycin for 7 days prior to and 4 weeks following adoptive transfer of allogeneic CD4+ T cells, exacerbated the development of aGVHD-induced BM failure and spleen damage when compared to untreated-NK/RAG recipients engrafted with syngeneic or allogeneic T cells. Abx-treated mice exhibited severe anemia and monocytopenia as well as marked reductions in BM- and spleen-residing immune cells. Blinded histopathological analysis confirmed that Abx-treated mice engrafted with allogeneic T cells suffered significantly more damage to the BM and spleen than did untreated mice engrafted with allogeneic T cells. Abx-induced exacerbation of BM and spleen damage correlated with a dramatic reduction in fecal bacterial diversity, marked loss of anaerobic bacteria and remarkable expansion of potentially pathogenic bacteria. CONCLUSIONS: We conclude that continuous Abx treatment may aggravate aGVHD-induced tissue damage by reducing short chain fatty acid-producing anaerobes (e.g. Clostridium, Blautia) and/or by promoting the expansion of pathobionts (e.g. Akkermansia) and opportunistic pathogens (Cronobacter).

Distinct Mitochondria-Mediated T-Cell Apoptosis Responses in Children and Adults With Coronavirus Disease 2019.

BACKGROUND: Lymphopenia is a key feature for adult patients with coronavirus disease 2019 (COVID-19), although it is rarely observed in children. The underlying mechanism remains unclear. METHODS: Immunohistochemical and flow cytometric analyses were used to compare the apoptotic rate of T cells from COVID-19 adults and children and apoptotic responses of adult and child T cells to COVID-19 pooled plasma. Biological properties of caspases and reactive oxygen species were assessed in T cells treated by COVID-19 pooled plasma. RESULTS: Mitochondria apoptosis of peripheral T cells were identified in COVID-19 adult patient samples but not in the children. Furthermore, increased tumor necrosis factor-α and interleukin-6 in COVID-19 plasma induced mitochondria apoptosis and caused deoxyribonucleic acid damage by elevating reactive oxygen species levels of the adult T cells. However, the child T cells showed tolerance to mitochondrial apoptosis due to mitochondria autophagy. Activation of autophagy could decrease apoptotic sensitivity of the adult T cells to plasma from COVID-19 patients. CONCLUSIONS: Our results indicated that the mitochondrial apoptosis pathway was activated in T cells of COVID-19 adult patients specifically, which may shed light on the pathophysiological difference between adults and children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 ).

A Systematic Review of Radiation-Related Lymphopenia in Genito-urinary Malignancies.

BACKGROUND: The impact of radiation-related lymphopenia on clinical outcomes has been reported in various solid malignancies such as high grade gliomas, head and neck cancers, thoracic malignancies and gastro-intestinal malignancies but its impact is not clearly known in the context of common genito-urinary (GU) malignancies. METHODOLOGY: To better understand the effect of radiation-associated lymphopenia in prostate and bladder cancer, we undertook this systematic review of clinical studies that have studied radiation-related lymphopenia in GU malignancies. A systematic methodology search of PubMed, Embase, and Cochrane library resulted in 2125 abstracts. Ten studies fulfilled the inclusion criteria which included any prospective, retrospective study or cohort study of prostate, urinary bladder, kidney, ureter, urethra, penile cancer in humans, and radiation should be part of treatment and intent has to be in definitive or adjuvant settings. Finally the study should have data on radiation-related lymphopenia. RESULTS: Four studies reported on the cancer-specific outcomes related to the lymphopenia. The incidence of low lymphocyte counts were documented in all the studies. Three studies analyzed the factors associated with the Lymphocyte depletion. Pooled incidence of severe lymphopenia was 29.25% and mild to moderate lymphopenia was 60.75%. Bone marrow volume receiving 40 Gy was associated with the incidence of lymphopenia. CONCLUSION: One-third of the patients suffer from severe lymphopenia after radiation in prostate and bladder cancer. There are no clear data to support the correlation between severe lymphopenia and disease outcomes. Bone marrow dosimetry can affect the incidence and severity of lymphopenia. There is need of prospective datasets to identify the impact of radiation-related lymphopenia in GU malignancies focusing on long-term side effects, recurrence rates, and overall survival.

Analysis of Lymphocyte Subpopulations and Cytokines in COVID-19-Associated Pneumonia and Community-Acquired Pneumonia.

BACKGROUND: The 2019 novel coronavirus SARS-CoV-2 caused large outbreaks of COVID-19 worldwide. COVID-19 resembles community-acquired pneumonia (CAP). Our aim was to identify lymphocyte subpopulations to distinguish between COVID-19 and CAP. METHODS: We compared the peripheral blood lymphocytes and their subsets in 296 patients with COVID-19 and 130 patients with CAP. Parameters for independent prediction of COVID-19 were calculated by logistic regression. RESULTS: The main lymphocyte subpopulations (CD3+CD4+, CD16+CD56+, and CD4+/CD8+ ratio) and cytokines (TNF-α and IFN-γ) of COVID-19 patients were significantly different from that of CAP patients. CD16+CD56+%, CD4+/CD8+ratio, CD19+, and CD3+CD4+ were identified as predictors of COVID-19 diagnosis by logistic regression. In addition, the CD3+CD4+counts, CD3+CD8+ counts, andTNF-α are independent predictors of disease severity in patients. CONCLUSIONS: Lymphopenia is an important part of SARS-CoV-2 infection, and lymphocyte subsets and cytokines may be useful to predict the severity and clinical outcomes of the disease.

Lymphocytes screening on admission is essential for predicting in-hospital clinical outcome in COVID-19 patients: A retrospective cohort study.

INTRODUCTION: We aimed to identify the associations between the lymphocytes (LYM) absolute count on admission and clinical outcomes in COVID-19 patients. METHODS: In this retrospective study, 224 COVID-19 patients who were admitted to General Hospital of Central Theater Command of the PLA from January 22 to April 4, 2020, were consecutively included. These patients were divided into the lymphopenia group and the nonlymphopenia group according to whether the LYM count on admission was below the normal range. RESULTS: During hospitalization, patients in the lymphopenia group have a much higher all-cause mortality (14.5% vs 0.0%; P < .001) and an evidently longer length of hospital stay (24.0 vs 17.5 days; P < .001) than patients in the nonlymphopenia group. The correlation analysis results indicated that the LYM count was negatively correlated with the values of NEU (R = -.2886, P < .001), PT (R = -.2312, P < .001), FIB (R = -.2954, P < .001), D-D (R = -.3554, P < .001), CRP (R = -.4899, P < .001), IL-6 (R = -.5459, P < .001), AST (R = -.2044, P < .01), Cr (R = -.1350, P < .05), CPK (R = -.2119, P < .01), CK-Mb (R = -.1760, P < .01), and LDH (R = -.4330, P < .001), and was positively correlated with the count of PLT (R = .2679, P < .001). In addition, LYM as a continuous variable was associated with 97% decreased risk of in-hospital mortality in the fully adjusted models (OR = 0.03, 95%CI, 0.00-0.37, P < .001). DISCUSSION: LYM screening on admission is a critical predictor for assessment of disease severity and clinical outcomes in patients with COVID-19, and lymphopenia substantially correlates with poor clinical outcomes.

Cytokine storm in severe COVID-19 pneumonia.

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.

A systematic review of clinical and laboratory parameters associated with increased severity among COVID-19 patients.

BACKGROUND AND AIMS: Corona virus disease 2019 (COVID-19) has been an extremely difficult pandemic to contain and it has affected more than 148 countries worldwide. The main aim of this systematic review is to provide a comprehensive summary of clinical and laboratory parameters that are associated with and indicative of increased severity among COVID-19 patients. MATERIAL AND METHODS: All the available data from high-quality research articles relevant to the epidemiology, demographics, trends in hospitalization and outcomes, clinical signs and symptoms, diagnostic methods and treatment methods of COVID-19 were retrieved and evaluated for inclusion. RESULTS: As per our review, the mean age of patients in the severe group was 59.3 years compared to 46.5 years in non severe group. COVID-19 was more severe among men than women. Clinical presentation was variable among different studies. and dyspnea was the factor indicating severe disease. Laboratory parameters associated with increased severity were lymphopenia <0.8 × 109/L, thrombocytopenia 100 × 109/L, leucocytosis TC > 11 × 109/L, procalcitonin >0.5 ng/mL, d dimer >2 mcg/mL, aspartate transaminase elevation >150U/L, LDH >250U/L. CONCLUSION: This systematic review suggests that COVID-19 is a disease with varied clinical presentation and laboratory parameters. The commonest clinical symptoms were fever, cough and dyspnea. The laboratory parameters associated with severe disease were lymphopenia, elevated LDH, D dimer and Procalcitonin.

Role of Interleukin-7 in the Development of and Recovery from Radiation-Induced Lymphopenia: A Post-hoc Analysis of a Prospective Cohort.

PURPOSE: Radiation-induced lymphopenia is associated with worse outcomes in solid tumors. We assessed the impact of interleukin-7 (IL-7), a key cytokine in lymphocyte homeostasis, on radiation-induced lymphopenia. MATERIALS AND METHODS: A post-hoc analysis was performed in a prospective cohort of 98 patients with hepatocellular carcinoma who were treated with radiotherapy in 2016-2018. Blood IL-7 levels were assayed before and at the end of radiotherapy. Acute severe lymphopenia (ASL) was defined as a total lymphocyte count of < 200/µL during radiotherapy. Cox and logistic regression analyses were performed to identify predictors of survival and ASL development, respectively. RESULTS: Patients with ASL (n=41) had significantly poorer overall survival than those without (12.0 months vs. 25.3 months, p=0.001). Patients with lymphocyte recovery showed significantly longer overall survival than those without (21.8 months vs. 10.3 months, p=0.042). ASL was an independent predictor of poor survival (hazard ratio, 2.07; p=0.015). Patients with ASL had significantly lower pre-radiotherapy IL-7 levels (2.07 pg/mL vs. 3.01 pg/mL, p=0.010). A high pre-radiotherapy IL-7 level was an independent predictor of a reduced risk of ASL development (hazard ratio, 0.40; p=0.004). IL-7 levels reflected a feedback response to ASL, with a higher ΔIL-7 in patients with ASL and a lower ΔIL-7 in those without ASL (0.48 pg/mL vs. -0.66 pg/mL, p < 0.001). Post-radiotherapy IL-7 levels were significantly positively correlated with the total lymphocyte counts at 2 months. CONCLUSION: IL-7 is associated with the development of and recovery from ASL, which may impact survival. To overcome radiation-induced lymphopenia, a novel strategy using IL-7 may be considered.

Temporal changes of haematological and radiological findings of the COVID-19 infection-a review of literature.

BACKGROUND: COVID-19 is a systemic viral infection which mainly targets the human respiratory system with many secondary clinical manifestations especially affecting the hematopoietic system and haemostasis. Few studies have highlighted the prognostic value of blood findings such as lymphopenia, neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, LDH, CRP, cardiac troponin, low-density lipoproteins and chest radiographic abnormality. A study of progressions of blood and radiological results may help to identify patients at high risk of severe outcomes. This systematic review aimed to assess the temporal progression of blood and radiology findings of patients with COVID-19. METHODS: Comprehensive systematic literature search was conducted on Medline, Embase and Cochrane databases to identify articles published for peripheral blood investigation and radiological results of COVID-19 patients. RESULTS: A total of 27 studies were included in this review. The common laboratory features reported include lymphopenia, elevated levels of C-reactive proteins and lactate dehydrogenase. For radiological signs, ground-glass opacifications, consolidations, and crazy paving patterns were frequently reported. There is a correlation between lymphocyte count, neutrophil count and biomarkers such as C-reactive proteins and lactate dehydrogenase; at a later phase of the disease (more than 7 days since onset of symptoms), lymphopenia worsens while neutrophil count, C-reactive protein levels and lactate dehydrogenase levels increase. Frequencies of ground-glass opacifications and ground-glass opacifications with consolidations decrease at a later phase of the disease while that of consolidation and crazy paving pattern rises as the disease progresses. More extensive lung involvement was also seen more frequently in the later phases. CONCLUSION: The correlation between temporal progression and the reported blood and radiological results may be helpful to monitor and evaluate disease progression and severity.

Coronavirus Disease 2019 (COVID-19): A Haematologist's Perspective.

Coronavirus disease 2019 (COVID-19) is affecting millions of patients worldwide. It is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which belongs to the family Coronaviridae, with 80% genomic similarities to SARS-CoV. Lymphopenia was commonly seen in infected patients and has a correlation to disease severity. Thrombocytopenia, coagulation abnormalities, and disseminated intravascular coagulation were observed in COVID-19 patients, especially those with critical illness and non-survivors. This pandemic has caused disruption in communities and hospital services, as well as straining blood product supply, affecting chemotherapy treatment and haematopoietic stem cell transplantation schedule. In this article, we review the haematological manifestations of the disease and its implication on the management of patients with haematological disorders.

Prognostic implications of neutrophil-lymphocyte ratio in COVID-19.

BACKGROUND: The clinical presentation of COVID-19 ranges from a mild, self-limiting disease, to multiple organ failure and death. Most severe COVID-19 cases present low lymphocytes counts and high leukocytes counts, and accumulated evidence suggests that in a subgroup of patients presenting severe COVID-19, there may be a hyperinflammatory response driving a severe hypercytokinaemia which may be, at least in part, signalling the presence of an underlying endothelial dysfunction. In this context, available data suggest a prognostic role of neutrophil-lymphocyte ratio (NLR) in various inflammatory diseases and oncological processes. Following this rationale, we hypothesized that NLR, as a marker of endothelial dysfunction, may be useful in identifying patients with a poor prognosis in hospitalized COVID-19 cases. DESIGN: A retrospective observational study performed at Hospital Universitario HM Puerta del Sur, Madrid, Spain, which included 119 patients with COVID-19 from 1 March to 31 March 2020. Patients were categorized according to WHO R&D Expert Group. RESULTS: Forty-five (12.1%) patients experienced severe acute respiratory failure requiring respiratory support. Forty-seven (12.6%) patients died. Those with worse outcomes were older (P = .002) and presented significantly higher NLR at admission (P = .001), greater increase in Peak NLR (P < .001) and higher increasing speed of NLR (P = .003) compared with follow-up patients. In a multivariable logistic regression, age, cardiovascular disease and C-reactive protein at admission and Peak NLR were significantly associated with death. CONCLUSIONS: NLR is an easily measurable, available, cost-effective and reliable parameter, which continuous monitoring could be useful for the diagnosis and treatment of COVID-19.

Is COVID-19 a New Hematologic Disease?

SARS-CoV-2 viruses are positive single-stranded RNA viruses, whose infection can be asymptomatic or lead to the coronavirus disease 2019 (Covid-19). Covid-19 is a respiratory infection with a significant impact on the hematopoietic system and hemostasis leading to several cardiovascular complications. Hematologic consequences of this new infection allowed medical community to start new treatment approaches concerning infection going from targeted anti-inflammatory drugs to anticoagulation or stem cell therapies. A better understanding of Covid-19 pathophysiology, in particular hematological disorders, will help to choose appropriate treatment strategies.

Meta-analysis investigating the relationship between clinical features, outcomes, and severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia.

OBJECTIVE: We aimed to investigate the relationship between clinical characteristics, outcomes and the severity of severe acute respiratory syndrome coronavirus 2 pneumonia. METHODS: We performed a systematic review and meta-analysis using PubMed, Embase, and Cochrane Library databases to assess the clinical characteristics and outcomes of confirmed COVID-19 cases and compared severe (ICU) and nonsevere (non-ICU) groups. RESULTS: We included 12 cohort studies including 2,445 patients with COVID-19. Compared with nonsevere (non-ICU) patients, severe (ICU) disease was associated with a smoking history (P = .003) and comorbidities including chronic obstructive pulmonary disease (OR = 5.08, P < .001), diabetes (OR = 3.17, P < .001), hypertension (OR = 2.40, P < .001), coronary heart disease (OR = 2.66, P < .001), cerebrovascular diseases (OR = 2.68, P = .008), and malignancy (OR=2.21, P = .040). We found significant differences between the 2 groups for fever, dyspnea, decreased lymphocyte and platelet counts, and increased leukocyte count, C-creative protein, procalcitonin, lactose dehydrogenase, aspartate aminotransferase, alanine aminotransferase, creatinine kinase, and creatinine levels (P < .05). Significant differences were also observed for multiple treatments (P < .05). Patients in the severe (ICU) group were more likely to have complications and had a much higher mortality rate and lower discharge rate than those with nonsevere (non-ICU) disease (P < .05). CONCLUSIONS: Investigation of clinical characteristics and outcomes of severe cases of COVID-19 will contribute to early prediction, accurate diagnosis, and treatment to improve the prognosis of patients with severe illness.

Characteristics and outcomes of critically ill patients with covid-19 in Sakarya, Turkey: a single centre cohort study

Background/aim: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Turkey on March 10, 2020 and the number of the patients are increasing day by day. Coronavirus disease 2019 (Covid-19) has high mortality rates in intensive care units (ICUs). We aimed to describe the demographic characteristics, comorbidities, treatment protocols, and clinical outcomes among the critically ill patients admitted to the ICU of our hospital. Materials and methods: This cohort study included 103 consecutive patients who had laboratory confirmed Covid-19 and admitted to ICU of Sakarya University Training and Research Hospital between March 19 and April 13, 2020. The final date of the follow-up was April 18. Results: The mean age of the patients was 69.6 ± 14.1 years. Most of the patients had increased CRP (99%), serum ferritin (73.8%), d-dimer (82.5%), and hs-troponin levels (38.8%). 34 patients (33%) had lymphocytopenia, 24 patients (23.3%) had thrombocytopenia. 63 patients (61.2%) developed acute respiratory distress syndrome (ARDS), 31 patients (30.1%) had acute kidney injury, and 52 patients (50.5%) had multiple organ dysfunction syndrome (MODS) during follow-up. Sixty-two patients (60.2%) received mechanical ventilation. As of April 18, of the 103 patients, 52 (50.5%) had died, 30 (29.1%) had been discharged from the ICU, 21 (20.4%) were still in the ICU. Conclusions: Covid-19 has high mortality rates in ICU. Patients with elevated procalcitonin, hs-troponin, d-dimer, and CRP levels and lower platelet count at admission have higher mortality.

Clinical characteristics and mortality of patients with hematologic malignancies and COVID-19: a systematic review.

OBJECTIVE: Hematologic cancer patients with Coronavirus Disease 2019 (COVID-19) tend to have a more serious disease course than observed in the general population. Herein, we comprehensively reviewed existing literature and analyzed clinical characteristics and mortality of patients with hematologic malignancies and COVID-19. MATERIALS AND METHODS: Through searching PubMed until June 03, 2020, we identified 16 relevant case studies (33 cases) from a total of 45 studies that have reported on patients with COVID-19 and hematologic malignancies. We investigated the clinical and laboratory characteristics including type of hematologic malignancies, initial symptoms, laboratory findings, and clinical outcomes. Then, we compared those characteristics and outcomes of patients with hematologic malignancies and COVID-19 to the general population infected with COVID-19. RESULTS: The median age was 66-year-old. Chronic lymphocytic leukemia was the most common type of hematologic malignancy (39.4%). Fever was the most common symptom (75.9%). Most patients had normal leukocyte counts (55.6%), lymphocytosis (45.4%), and normal platelet counts (68.8%). In comparison to patients with COVID-19 without underlying hematologic malignancies, dyspnea was more prevalent (45.0 vs. 24.9%, p=0.025). Leukocytosis (38.9 vs. 9.8%, p=0.001), lymphocytosis (45.4 vs. 8.2%, p=0.001), and thrombocytopenia (31.3 vs. 11.4%, p=0.036) were significantly more prevalent and lymphopenia (18.2 vs. 57.4%, p=0.012) less prevalent in patients with hematologic malignancies. There were no clinical and laboratory characteristics predicting mortality in patients with hematologic malignancies. Mortality was much higher in patients with hematologic malignancies compared to those without this condition (40.0 vs. 3.6%, p<0.001). CONCLUSIONS: Co-occurrence of hematologic malignancies and COVID-19 is rare. However, due to the high mortality rate from COVID-19 in this vulnerable population, further investigation on tailored treatment and management is required.

Hematological manifestations of SARS-CoV-2 in children.

Infection from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), though mainly a respiratory disease, can impair many systems, including causing hematological complications. Lymphopenia and hypercoagulability have been reported in adults with coronavirus disease 2019 (COVID-19) and are considered markers of poor prognosis. This review summarizes the hematological findings in children with SARS-CoV-2 infection. The majority of infected children had a normal leukocyte count, while the most common white blood cell abnormality was leukopenia. Lymphopenia, which may be a marker of severe disease, was rarer in children than in adults, possibly due to their immature immune system or due to the less severe manifestation of COVID-19 in this age group. Age may have an impact, and in neonates and infants the most common abnormality was lymphocytosis. Abnormalities of red blood cells and platelets were uncommon. Anemia and hypercoagulability were reported mainly in children presenting the novel multisystem inflammatory syndrome (MIS) associated with SARS-CoV-2.

Clinical Characteristics of 3 Patients Infected with COVID-19: Age, Interleukin 6 (IL-6), Lymphopenia, and Variations in Chest Computed Tomography (CT).

BACKGROUND COVID-19 has been identified as the cause of the large outbreak of pneumonia in patients in Wuhan with shared history of exposure to the Huanan seafood market; however, there is more to learn about this disease. Some experts report that the virus may have reduced toxicity during transmission, but others say that toxicity does not change during transmission. CASE REPORT In this case series, we report clinical and imaging characteristics of 3 patients (A, B, and C) infected with COVID-19. In an exposure-tracking epidemiological investigation, we found that it is possible that Patient A transmitted the infection to her treating physician, Patient B. Patient B then likely transmitted the infection to her family member, Patient C. From the chest CT studies and clinical characteristics, we postulate that the virulence did not decrease during human-to-human transmission. In previous studies, patients with the virus infection had changes in chest CT; however, we found that during the early stages of this disease, some patients (Patient C) may have normal chest CT scans and laboratory studies. Most importantly, we found that IL-6 levels were highest and lymphocyte count was lowest in those with more severe infection. CONCLUSIONS In this case series, we report the exposure relationship of the 3 patients and found that chest CT scans may not have any changes at the beginning of this disease. Lymphopenia and elevated levels of IL-6 can be found after infection.