<b><i>Background:</i></b> Although the pathophysiology of coronavirus disease 2019 (COVID-19) is not clearly defined, among the proposed mechanisms, immune system dysfunction is more likely than others. The aim of this study was to clarify the characteristics and clinical significance of dynamic changes of lymphocyte subsets in the course of COVID-19. <b><i>Methods:</i></b> In this prospective study, the levels of peripheral lymphocyte subsets including CD4<sup>+</sup>, CD8<sup>+</sup>, CD4<sup>+</sup>CD25<sup>+</sup>FOXP3<sup>+</sup>, CD38<sup>+</sup>, CD3<sup>+</sup>HLA-DR<sup>+</sup>, CD19<sup>+</sup>, CD20<sup>+</sup>, and CD16<sup>+</sup>CD56<sup>+</sup> cells were measured by flow cytometry in 52 confirmed hospitalized patients with COVID-19 at the day of admission and after 7 days of care. Clinical response was defined as improvement in symptoms (fever, dyspnea, and cough as well as blood oxygen saturation), and patients who met these criteria after 1 week of admission were classified as early responders; others who survived and finally discharged from the hospital were classified as late responders and patients who died were categorized as nonresponders. Immunophenotyping of studied cell changes on the first day of admission and 7 days after treatment were compared. Besides, the correlation between cellular subset variation and clinical response and outcome were analyzed. <b><i>Results:</i></b> Total counts of white blood cell, T cells, CD4<sup>+</sup> T cells, CD8<sup>+</sup> T cells, CD38<sup>+</sup> lymphocytes, and CD3<sup>+</sup>HLA-DR<sup>+</sup> lymphocytes were significantly increased in both early and late responders. No statistically significant difference was observed in CD4<sup>+</sup>/CD8<sup>+</sup> ratio, B cells, FOXP3<sup>+</sup><i>T</i><sub>reg</sub> lymphocytes, and FOXP3 median fluorescence intensity among studied groups. According to the multivariate analysis, an increase in CD4<sup>+</sup> T cells (<i>p</i> = 0.019), CD8<sup>+</sup> T cells (<i>p</i> = 0.001), and administration of interferon (<i>p</i> < 0.001) were independent predictors of clinical response. <b><i>Conclusion:</i></b> We found an increasing trend in total T cells, T helpers, cytotoxic T cells, activated lymphocytes, and natural killer cells among responders. This trend was not statistically significant among nonresponders. The findings of this study may enhance our knowledge about the pathogenesis of COVID-19.
Background Since the outbreak of the novel coronavirus disease-2019 (COVID-19) in December 2019, limited studies have investigated the histopathologic findings of patients infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Material and methods This study was conducted on 31 deceased patients who were hospitalized for COVID-19 in a tertiary hospital in Tehran, Iran. A total of 52 postmortem tissue biopsy samples were obtained from the lungs and liver of decedents. Clinical characteristics, laboratory data, and microscopic features were evaluated. Reverse transcription polymerase chain reaction (RT-PCR) assay for SARS-CoV-2 was performed on specimens obtained from nasopharyngeal swabs and tissue biopsies. Results The median age of deceased patients was 66 years (range, 30–87 years) and 25 decedents (81 %) were male. The average interval from symptom onset to death was 13 days (range, 6–34 days). On histopathologic examination of the lung specimens, diffuse alveolar damage and thrombotic microangiopathy were the most common findings (80 % and 60 %, respectively). Liver specimens mainly showed macrovesicular steatosis, portal lymphoplasmacytic inflammation and passive congestion. No definitive viral inclusions were observed in any of the specimens. In addition, 92 % of lung tissue samples tested positive for SARS-CoV-2 by RT-PCR. Conclusions Further studies are needed to investigate whether SARS-CoV-2 causes direct cytopathic changes in various organs of the human body.
COVID‐19, a new disease caused by the 2019‐novel coronavirus (SARS‐CoV‐2), has swept the world and challenged its culture, economy, and health infrastructure. Forced emergence to find an effective vaccine to immunize people has led scientists to design and examine vaccine candidates all over the world. Until a vaccine is developed, however, effective treatment is needed to combat this virus, which is resistant to all conventional antiviral drugs. Accordingly, more about the structure, entry mechanism, and pathogenesis of COVID‐19 is required. Angiotensin‐converting enzyme 2 (ACE2) is the gateway to SARS‐CoV and SARS‐CoV‐2, so our knowledge of SARS‐CoV‐2 can help us to complete its mechanism of interaction with ACE2 and virus endocytosis, which can be interrupted by neutralizing small molecules or proteins. ACE2 also plays a crucial role in lung injury.
Scan to discover online Background & Objective: Although the antigen expression patterns of acute lymphoblastic leukemia (ALL) are well known, this study attempted to evaluate commonly used immune markers for immunophenotyping of acute leukemia to set the minimum of necessary diagnostic panels by flow cytometry. Methods: This study evaluated 89 patients referred from all over the country to the Iranian Blood Transfusion Organization (IBTO) in Tehran from 2013 to 2015. We compared the immunophenotype patterns of childhood and adult ALLs including 69(77.5%) B-cell lymphoblastic lymphoma (B-LBL), 2(2.2%) Burkitt's lymphoma (BL), and 18(20.2%) T-cell lymphoblastic lymphoma (T-LBL) cases using flowcytometry with broad antibody panel. Results: CD19 and CD79a were the most frequent markers for B-LBL while CD7 was the most sensitive marker in T-LBL; the frequency of CD7, CD3, and CD5 antigens were 100%, 38.9%, and 88.9%, respectively. TdT+/CD34+ was significantly higher in adult B-LBLs than children, which indicates blast cells are more immature in adults. In addition, CD10 and cCD79a were significantly higher in children with B-LBL like as CD5 and CD8 in children with T-LBL. Aberrant phenotypes including CD13, CD33, CD7, and CD117 were found in 7(10.1%) cases of B-LBL. These phenotypes were CD117, HLA-DR, and CD33 in 7(38/9%) cases of T-LBL. Expression of CD117 aberrant myeloid antigen was significantly more associated with T-LBL than with Blineage ALL. Conclusion: Significant differences were observed in antigen-expression patterns between adult and childhood ALLs. Further studies are needed to correlate specific markers with recurrent cytogenetic abnormalities and prognosis with therapeutic response.
Background Although there are a growing number of studies on evaluating lymphocyte subset counts as prognostic factors for COVID-19 disease severity, the lymphocyte subsets’ analyses of both IgM and IgG responders and non-responders during the periods after onset of symptoms, have not been conducted yet. So, this study aimed to evaluate immune cell profiling of COVID-19 patients with and without antibody responses. Methods In this cross-sectional study, the levels of peripheral lymphocyte subsets were measured using flow cytometry in 53 patients with positive SARS-CoV-2 RT-PCR, for whom antibody testing of COVID-19 was performed. Results The white blood cell, neutrophil, and lymphocyte counts consistently decreased in the IgM and IgG non-responder group, while the differences in the median value between the two study groups were found to be statistically significant only in terms of neutrophil counts (P = 0.024 for IgM response and p-value = 0.046 for IgG response, respectively). Moreover, the level of neutrophil-to-lymphocyte ratio was observed to be significantly lower in the IgM or IgG non-responder group compared to the IgM or IgG responder group (3.6 ± 3.1 vs. 6.3 ± 4.2; p-value = 0.021). The patients with IgM antibody response had a significantly lower CD20+ lymphocytes (11% versus 15% in the groups without IgM antibody response, p-value = 0.031), The percentages of NK cells and CD4+ T cells significantly increased in the patients with IgG antibody response compared to those without IgG antibody response (13% versus 10%, p-value = 0.028, and 41.5% versus 34%; p-value = 0.03, respectively). Moreover, the patients who produced IgM or IgG antibody had significantly higher percentages of total T lymphocytes (64% versus 54%; p-value = 0.017), CD4+ T cells (41% versus 34%; p-value = 0.038), and NK cells (13% versus 9%, p-value = 0.023) compared to the group with no serological response. No significant difference was observed in the percentage of other lymphocyte subsets, including CD8+ T cells, Treg cells, and CD19+ B cells. Conclusion Our results suggest that the total T cells, CD4+ T cells, and NK cells percentages are linked to serological response. Moreover, our findings suggested that neutrophil absolute counts and neutrophil-to-lymphocyte ratio may be valuable predictors of IgM or IgG antibody response.
We aimed to determine the characteristics of coronavirus disease-2019 among the Iranian population. In this study, we collected and analyzed the demographics, laboratory findings and outcomes of patients with COVID-19 who were admitted to Masih Daneshvari Hospital in Tehran, Iran between February 20, 2020 and April 2, 2020. Of 1061 patients, the median age was 55 years (interquartile range [IQR], 44-66 years) and 692 (65.2%) were male. Among these, 129 (12.2%) patients died at some point during hospitalization in the ward or intensive care unit (ICU). From the remaining 932 survivors, 46 (5.0%) patients were admitted to the ICU and 886 (95.0%) patients were hospitalized in the ward. Patients who died were significantly older than those hospitalized in the ward (p<0.001). The median absolute number of lymphocytes was 1.2 × 10 3 per microliter (IQR, 0.9-1.6 × 10 3 per microliter) and 708 (66.7%) patients had lymphopenia (absolute lymphocyte count <1500 per microliter). Among the laboratory tests, D-dimer, serum ferritin and albumin had the strongest correlation with mortality (r = 0.455, r = 0.412, r = -0.406, respectively; p-values <0.001). Conclusively, laboratory findings could provide useful information in regard to the management of patients with COVID-19.
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