Tocilizumab treatment in COVID-19: A single center experience

Tocilizumab (TCZ), a monoclonal antibody against interleukin-6 (IL-6), emerged as an alternative treatment for COVID-19 patients with a risk of cytokine storms recently. In the present study, we aimed to discuss the treatment response of TCZ therapy in COVID-19 infected patients. The demographic, treatment, laboratory parameters of C-reactive protein (CRP) and IL-6 before and after TCZ therapy and clinical outcome in the 15 COVID-19 patients were retrospectively assessed. Totally 15 patients with COVID-19 were included in this study. Two of them were moderately ill, six were seriously ill and seven were critically ill. The TCZ was used in combination with methylprednisolone in eight patients. Five patients received the TCZ administration twice or more. Although TCZ treatment ameliorated the increased CRP in all patients rapidly, for the four critically ill patients who received an only single dose of TCZ, three of them (No. 1, 2, and 3) still dead and the CRP level in the rest one patient (No. 7) failed to return to normal range with a clinical outcome of disease aggravation. Serum IL-6 level tended to further spiked firstly and then decreased after TCZ therapy in 10 patients. A persistent and dramatic increase of IL-6 was observed in these four patients who failed treatment. TCZ appears to be an effective treatment option in COVID-19 patients with a risk of cytokine storms. And for these critically ill patients with elevated IL-6, the repeated dose of the TCZ is recommended.     

Featuring COVID-19 cases via screening symptomatic patients with epidemiologic link during flu season in a medical center of central Taiwan

BackgroundCoronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CO-V-2), was first reported in Wuhan, Hubei province, China has now rapidly spread over 50 countries. For the prevention and control of infection, Taiwan Centers for Disease Control initiated testing of SARS-CoV-2 on January 24th 2020 for persons suspected with this disease. Until February 28th, 43 flu-like symptomatic patients were screened in China Medical University Hospital.MethodsTwo patients were confirmed positive for SARS-CoV-2 infection by rRT-PCR as COVID-19 patients A and B. Causative pathogens for included patients were detected using FilmArray™ Respiratory Panel. We retrospectively analyzed the clinical presentations, laboratory data, radiologic findings, and travel and exposure contact histories, of the COVID-19 patients in comparison to those with other respiratory infections.ResultsThrough contact with Taiwan No. 19 case patient on 27th January, COVID-19 patients A and B were infected. Both patients had no identified comorbidities and developed mild illness with temporal fever, persistent cough, and lung interstitial infiltrates. Owing to the persistence of positive SARS-CoV-2 in respiratory specimen, the two COVID-19 patients are still in the isolation rooms despite recovery until 10th of March. The results of FilmArrayTM Respiratory Panel revealed 22 of the 41 non-COVID-19 patients were infected by particular pathogens. In general, seasonal respiratory pathogens are more prevalent than SARS-CoV-2 in symptomatic patients in non- COVID-19 endemic area during the flu season. Since all patients shared similar clinical and laboratory findings, expanded surveillance of detailed exposure history for suspected patients and application of rapid detection tools are highly recommended.     

7例儿童新型冠状病毒肺炎病例的临床特征

目的回顾性分析新型冠状病毒肺炎(COVID-19)儿童确诊病例的流行病学及临床特征,为儿童感染新型冠状病毒(2019-nCoV)的临床诊疗提供建议。方法选取2020年1~2月在襄阳市中心医院发热病房收治的7例COVID-19儿童患者为研究对象,收集临床资料,分析一般情况、临床症状、血液学检验及CT影像学等特征。结果7例儿童患者中,男性3例,女性4例;年龄中位数为8(2.6-14.0)岁;有基础疾病患者2例,有家族聚集史患者4例,其中有2人为亲兄妹;7例患儿均具有高危流行病学史。COVID-19儿童患者的主要临床症状为发热(4例),咳嗽咳痰(5例),其余为无症状患者(2例)。患者外周血表现为:白细胞总数减少患者1例,中性粒细胞减少患者2例,C反应蛋白轻度升高1例,血清中乳酸脱氢酶(LDH)水平增高3例。7例COVID-19患者淋巴细胞计数均为正常,降钙素原均为正常。儿童患者血清中白蛋白、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、肌酸激酶(CK)、血肌酐(Scr)等指标无明显异常。儿童胸部CT结果多以肺叶高密度灶(5例)为典型表现,部分有典型的磨玻璃密度影(2例)。7例儿童患者临床分型:普通型5例,亚临床型2例。患者经抗病毒药物(阿比多尔)联合中药方剂对症治疗均痊愈。结论儿童COVID-19以轻型和普通型病例为主,多为家庭聚集性发病,且实验室检查无特异性,预后较好。     

Risk factors for mortality of critically ill patients with COVID-19 receiving invasive ventilation

Rationale: Early invasive ventilation may improve outcomes for critically ill patients with COVID-19. The objective of this study is to explore risk factors for 28-day mortality of COVID-19 patients receiving invasive ventilation.Methods: 74 consecutive adult invasively ventilated COVID-19 patients were included in this retrospective study. The demographic and clinical data were compared between survivors and non-survivors, and Cox regression analysis was used to explore risk factors for 28-day mortality. The primary outcome was 28-day mortality after initiation of invasive ventilation. Secondary outcome was the time from admission to intubation.Results: Of 74 patients with COVID-19, the median age was 68.0 years, 53 (71.6%) were male, 47 (63.5%) had comorbidities with hypertension, and diabetes commonly presented. The most frequent symptoms were fever and dyspnea. The median time from hospital admission to intubation was similar in survivors and non-survivors (6.5 days vs. 5.0 days). The 28-day mortality was 81.1%. High Sequential Organ Failure Assessment (SOFA) score (hazard ratio [HR], 1.54; 95% confidence interval [CI], 1.23-1.92; p < 0.001) and longer time from hospital admission to intubation (HR, 2.41; 95% CI, 1.15-5.07; p = 0.020) were associated with 28-day mortality in invasively ventilated COVID-19 patients.Conclusions: The mortality of invasively ventilated COVID-19 patients was particularly striking. Patients with high SOFA score and receiving delayed invasive ventilation were at high risk of mortality.     

采用HA130型树脂灌流器血液灌流对维持性血液透析患者微炎症的影响

背景：研究发现维持性血液透析的尿毒症患者体内存在“微炎症状态”。 目的：观察采用HA130型树脂灌流器行血液灌流对维持性血液透析患者微炎症的影响。 方法：选取维持性血液透析治疗的尿毒症患者60例,随机分为2组,灌流组采用HA130型树脂灌流器串联血液透析器进行血液灌流加血液透析治疗;透析组行单纯血液透析治疗。采集治疗前后两组患者的血清,检测高敏C-反应蛋白、肿瘤坏死因子α和白细胞介素6水平。 结果与结论：灌流组血清高敏C-反应蛋白、白细胞介素6和肿瘤坏死因子α水平治疗后较治疗前显著降低(P < 0.05);透析组治疗后上述指标较治疗前略升高,差异无显著性意义。提示血液灌流可以降低维持性血液透析患者血清高敏C-反应蛋白、白细胞介素6和肿瘤坏死因子α水平,有利于减轻其微炎症反应。     

COVID-19 and Sepsis

The COVID-19 pandemic has created a major alteration in the medical literature including the sepsis discussion. From the outset of the pandemic, various reports have indicated that although there are some unique features pertinent to COVID-19, many of its acute manifestations are similar to sepsis caused by other pathogens. As a consequence, the old definitions now require consideration of this new etiologic agent, namely SARS-CoV-2. Although the pathogenesis of COVID-19 has not been fully explained, the data obtained so far in hospitalized patients has revealed that serum cytokine and chemokine levels are high in severe COVID-19 patients, similar to those found with sepsis. COVID-19 may involve multiple organ systems. In addition to the lungs, the virus has been isolated from blood, urine, faeces, liver, and gallbladder. Results from autopsy series in COVID-19 patients have demonstrated a wide range of findings, including vascular involvement, congestion, consolidation, and hemorrhage as well as diffuse alveolar damage in lung tissue consistent with acute respiratory distress syndrome (ARDS). The presence of viral cytopathic-like changes, infiltration of inflammatory cells (mononuclear cells and macrophages), and viral particles in histopathological samples are considered a consequence of both direct viral infection and immune hyperactivation. Thromboembolism and hyper-coagulopathy are other components in the pathogenesis of severe COVID-19. Although the pathogenesis of hypercoagulability is not fully understood, it has been pointed out that all three components of Virchow’s triad (endothelial injury, stasis, and hypercoagulable state) play a major role in contributing to clot formation in severe COVID-19 infection. In severe COVID-19 cases, laboratory parameters such as hematological findings, coagulation tests, liver function tests, D-dimer, ferritin, and acute phase reactants such as CRP show marked alterations, which are suggestive of a cytokine storm. Another key element of COVID-19 pathogenesis in severe cases is its similarity or association with hemophagocytic lymphohistiocytosis (HLH). SARS-CoV-2 induced cytokine storm has significant clinical and laboratory findings overlapping with HLH. Viral sepsis has some similarities but also some differences when compared to bacterial sepsis. In bacterial sepsis, systemic inflammation affecting multiple organs is more dominant than in COVID-19 sepsis. While bacterial sepsis causes an early and sudden onset clinical deterioration, viral diseases may exhibit a relatively late onset and chronic course. Consideration of severe COVID-19 disease as a sepsis syndrome has relevance and may assist in terms of determining treatments that will modulate the immune response, limit intrinsic damage to tissue and organs, and potentially improve outcome.     

Can steroids reverse the severe COVID-19 induced “cytokine storm”?

Severe coronavirus disease (COVID-19) is characterized by an excessive proinflammatory cytokine storm, resulting in acute lung injury and development of acute respiratory distress syndrome (ARDS). The role of corticosteroids is controversial in severe COVID-19 pneumonia and associated hyper-inflammatory syndrome. We reported a case series of six consecutive COVID-19 patients with severe pneumonia, ARDS and laboratory indices of hyper-inflammatory syndrome. All patients were treated early with a short course of corticosteroids, and clinical outcomes were compared before and after corticosteroids administration. All patients evaded intubation and intensive care admission, ARDS resolved within 11.8 days (median), viral clearance was achieved in four patients within 17.2 days (median), and all patients were discharged from the hospital in 16.8 days (median). Early administration of short course corticosteroids improves clinical outcome of patients with severe COVID-19 pneumonia and evidence of immune hyperreactivity.     

The significance of antiglobulin (Coombs) test reactivity in patients with COVID-19

Previous case reports have described patients with COVID-19-associated autoimmune hemolytic anemia (AIHA), and cold agglutinin disease (CAD) which is characterized by a positive direct antiglobulin (DAT) or “Coombs” test, yet the mechanism is not well understood. To investigate the significance of Coombs test reactivity among COVID-19 patients, we conducted a retrospective study on hospitalized COVID-19 patients treated at NMC Royal Hospital between 15 April and 30 May 2020. There were 27 (20%) patients in the Coombs-positive group and 108 (80%) in the Coombs-negative group. The cold agglutinin titer was examined in 22 patients due to symptoms suggestive of cold agglutinin disease, and all tested negative. We demonstrated a significant association with reactive Coombs test results in univariate analysis through clinical findings such as ICU admission rate, the severity of COVID-19, and several laboratory findings such as CRP, D-dimer, and hemoglobin levels lactate dehydrogenase, and RDW-CV. However, only hemoglobin levels and disease severity had a statistically significant association in multivariate analysis. A possible explanation of COVID-19-associated positive Coombs is cytokine storm-induced hyperinflammation, complement system activation, alterations of RBCs, binding of SARS-CoV-2 proteins to hemoglobin or its metabolites, and autoantibody production. Coombs-positive patients were tested for hemolysis using indirect bilirubin, consumed haptoglobin, and/or peripheral smear that ruled out any evidence of hemolysis. Understanding this etiology sheds new light on RBC involvement as a pathophysiological target for SARS-CoV-2 by interfering with their function; consequently, therapies capable of restoring RBC function, such as erythrocytapheresis, could be repurposed for the treatment of worsening severe and critical COVID-19.     

Impact of COVID-19 and malaria coinfection on clinical outcomes: a retrospective cohort study

ObjectivesDespite the possibility of concurrent infection with COVID-19 and malaria, little is known about the clinical course of coinfected patients. We analysed the clinical outcomes of patients with concurrent COVID-19 and malaria infection.MethodsWe conducted a retrospective cohort study that assessed prospectively collected data of all patients who were admitted between May and December 2020 to the Universal COVID-19 treatment center (UCTC), Khartoum, Sudan. UCTC compiled demographic, clinical, laboratory (including testing for malaria), and outcome data in all patients with confirmed COVID-19 hospitalized at that clinic. The primary outcome was all-cause mortality during the hospital stay. We built proportional hazard Cox models with malaria status as the main exposure and stepwise adjustment for age, sex, cardiovascular comorbidities, diabetes, and hypertension.ResultsWe included 591 patients with confirmed COVID-19 diagnosis who were also tested for malaria. Mean (SD) age was 58 (16.2) years, 446/591 (75.5%) were males. Malaria was diagnosed in 270/591 (45.7%) patients. Most malaria patients were infected by Plasmodium falciparum (140/270; 51.9%), while 121/270 (44.8%) were coinfected with Plasmodium falciparum and Plasmodium vivax. Median follow-up was 29 days. Crude mortality rates were 10.71 and 5.87 per 1000 person-days for patients with and without concurrent malaria, respectively. In the fully adjusted Cox model, patients with concurrent malaria and COVID-19 had a greater mortality risk (hazard ratio 1.43, 95% confidence interval 1.21-1.69).DiscussionCoinfection with COVID-19 and malaria is associated with increased all-cause in-hospital mortality compared to monoinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).     

Tocilizumab challenge: A series of cytokine storm therapy experiences in hospitalized COVID-19 pneumonia patients

To recognize the period of exaggerated cytokine response in patients with coronavirus disease 2019 (COVID-19) pneumonia, and to describe the clinical outcomes of using tocilizumab as a treatment option. The data of 12 adult COVID-19 pneumonia patients who were followed in the inpatient clinics of Biruni University Medical Faculty Hospital (Istanbul, Turkey) were retrospectively analyzed. Diagnostic tests, laboratory examinations, clinical findings, and computed tomography of the thorax imaging results were evaluated. A dramatic laboratory and clinical improvement was observed in 83% (10 out of 12) of patients after tocilizumab. In 17% (2 out of 12) of our patients, short-term ventilator support was required in the intensive care unit. The longest hospital stay was 18 days. However, in the end, all of our patients were discharged home with good health. Although arterial oxygen saturations (87.58 ± 3.12%) dropped in room air in the pre-tocilizumab period, post-tocilizumab they normalized in all patients (94.42 ± 1%). None of them had fever after tocilizumab treatment and the levels of C-reactive protein (13.08 ± 12.89) were almost within normal limits. Eosinophil values were quite low at the time of diagnosis (10 ± 17.06), but increased significantly post-tocilizumab (155.33 ± 192.69). There is currently no proven treatment for COVID-19 induced by novel coronavirus SARS-CoV-2. Based on our experience with twelve adult COVID-19 pneumonia patients, we can say that tocilizumab, an IL-6 inhibitor, is more beneficial in preventing the damage caused by excessive cytokine response in the body if administered at the right time and provides clinical and radiological recovery.     

Diagnostic utility of clinical laboratory data determinations for patients with the severe COVID-19

The role of clinical laboratory data in the differential diagnosis of the severe forms of COVID-19 has not been definitely established. The aim of this study was to look for the warning index in severe COVID-19 patients. We investigated 43 adult patients with COVID-19. The patients were classified into mild group (28 patients) and severe group (15 patients). A comparison of the hematological parameters between the mild and severe groups showed significant differences in interleukin-6 (IL-6), d -dimer (d -D), glucose, thrombin time, fibrinogen, and C-reactive protein (P < .05). The optimal threshold and area under the receiver operator characteristic curve (ROC) of IL-6 were 24.3 and 0.795 µg/L, respectively, while those of d -D were 0.28 and 0.750 µg/L, respectively. The area under the ROC curve of IL-6 combined with d -D was 0.840. The specificity of predicting the severity of COVID-19 during IL-6 and d -D tandem testing was up to 93.3%, while the sensitivity of IL-6 and d -D by parallel test in the severe COVID-19 was 96.4%. IL-6 and d -D were closely related to the occurrence of severe COVID-19 in the adult patients, and their combined detection had the highest specificity and sensitivity for early prediction of the severity of COVID-19 patients, which has important clinical value.     

Incidence of co-infections and superinfections in hospitalized patients with COVID-19: a retrospective cohort study

ObjectivesTo describe the burden, epidemiology and outcomes of co-infections and superinfections occurring in hospitalized patients with coronavirus disease 2019 (COVID-19).MethodsWe performed an observational cohort study of all consecutive patients admitted for ≥48 hours to the Hospital Clinic of Barcelona for COVID-19 (28 February to 22 April 2020) who were discharged or dead. We describe demographic, epidemiologic, laboratory and microbiologic results, as well as outcome data retrieved from electronic health records.ResultsOf a total of 989 consecutive patients with COVID-19, 72 (7.2%) had 88 other microbiologically confirmed infections: 74 were bacterial, seven fungal and seven viral. Community-acquired co-infection at COVID-19 diagnosis was uncommon (31/989, 3.1%) and mainly caused by Streptococcus pneumoniae and Staphylococcus aureus. A total of 51 hospital-acquired bacterial superinfections, mostly caused by Pseudomonas aeruginosa and Escherichia coli, were diagnosed in 43 patients (4.7%), with a mean (SD) time from hospital admission to superinfection diagnosis of 10.6 (6.6) days. Overall mortality was 9.8% (97/989). Patients with community-acquired co-infections and hospital-acquired superinfections had worse outcomes.ConclusionsCo-infection at COVID-19 diagnosis is uncommon. Few patients developed superinfections during hospitalization. These findings are different compared to those of other viral pandemics. As it relates to hospitalized patients with COVID-19, such findings could prove essential in defining the role of empiric antimicrobial therapy or stewardship strategies.     

Relationship between Cognitive Impairment and Depression in Dialysis Patients

Purpose

Patients with chronic kidney disease frequently show cognitive dysfunction. The association of depression and cognitive function is not well known in maintenance dialysis patients. We evaluated cognitive impairment and depression, as well as their relationship in regards to methods of dialysis, maintenance hemodialysis (MHD) and chronic peritoneal dialysis (CPD).

Materials and Methods

Fifty-six maintenance dialysis patients were recruited and their clinical and laboratory data were collected. The Korean version of the mini-mental state exam (K-MMSE) was applied to screen the patient''s cognitive function, while the Korean version of the Beck Depression Inventory (K-BDI) was used for depression screening.

Results

The average age of the participants was 54.2±10.2 years; 29 (51.8%) were female. The average dialysis vintage was 4.2±3.8 years. The CPD group showed significantly higher K-MMSE score (27.8±2.9 vs. 26.1±3.1, p=0.010) and lower K-BDI score (12.0±8.4 vs. 20.2±10.4, p=0.003) compared with the MHD group. The percentage of patients with depression symptoms was higher in the MHD group (51.7% vs. 18.5%). There was a negative correlation between cognitive function and prevalence of depressive symptoms. Depression and education level were shown to be independent predictors for cognitive impairment in multivariate analysis.

Conclusion

Cognitive impairment was closely correlated with depression. It is important to detect cognitive impairment and depression early in maintenance dialysis patients with simple bedside screening tools.     

Using IL-2R/lymphocytes for predicting the clinical progression of patients with COVID-19

Effective laboratory markers for the estimation of disease severity and predicting the clinical progression of coronavirus disease-2019 (COVID-19) is urgently needed. Laboratory tests, including blood routine, cytokine profiles and infection markers, were collected from 389 confirmed COVID-19 patients. The included patients were classified into mild (n = 168), severe (n = 169) and critical groups (n = 52). The leukocytes, neutrophils, infection biomarkers [such as C-reactive protein (CRP), procalcitonin (PCT) and ferritin] and the concentrations of cytokines [interleukin (IL)-2R, IL-6, IL-8, IL-10 and tumor necrosis factor (TNF)-α] were significantly increased, while lymphocytes were significantly decreased with increased severity of illness. The amount of IL-2R was positively correlated with the other cytokines and negatively correlated with lymphocyte number. The ratio of IL-2R to lymphocytes was found to be remarkably increased in severe and critical patients. IL-2R/lymphocytes were superior compared with other markers for the identification of COVID-19 with critical illness, not only from mild but also from severe illness. Moreover, the cytokine profiles and IL-2R/lymphocytes were significantly decreased in recovered patients, but further increased in disease-deteriorated patients, which might be correlated with the outcome of COVID-19. Lymphopenia and increased levels of cytokines were closely associated with disease severity. The IL-2R/lymphocyte was a prominent biomarker for early identification of severe COVID-19 and predicting the clinical progression of the disease.     

Immune repertoire sequencing reveals an abnormal adaptive immune system in COVID-19 survivors

Accumulating evidence suggests that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) impairs the adaptive immune system during acute infection. Still, it remains largely unclear whether the frequency and functions of T and B cells return to normal after the recovery of Coronavirus Disease 2019 (COVID-19). Here, we analyzed immune repertoires and SARS-CoV-2-specific neutralization antibodies in a prospective cohort of 40 COVID-19 survivors with a 6-month follow-up after hospital discharge. Immune repertoire sequencing revealed abnormal T- and B-cell expression and function with large T cell receptor/B cell receptor clones, decreased diversity, abnormal class-switch recombination, and somatic hypermutation. A decreased number of B cells but an increased proportion of CD19⁺CD138⁺ B cells were found in COVID-19 survivors. The proportion of CD4⁺ T cells, especially circulating follicular helper T (cTfh) cells, was increased, whereas the frequency of CD3⁺CD4⁻ T cells was decreased. SARS-CoV-2-specific neutralization IgG and IgM antibodies were identified in all survivors, especially those recorded with severe COVID-19 who showed a higher inhibition rate of neutralization antibodies. All severe cases complained of more than one COVID-19 sequelae after 6 months of recovery. Overall, our findings indicate that SARS-CoV-2-specific antibodies remain detectable even after 6 months of recovery. Because of their abnormal adaptive immune system with a low number of CD3⁺CD4⁻ T cells and high susceptibility to infections, COVID-19 patients might need more time and medical care to fully recover from immune abnormalities and tissue damage.     

An overview of COVID-19 for diagnostic pathologists: clinicopathological correlation and diagnostic techniques

The emergence of COVID-19 as a global pandemic has led to a rapid focus on understanding its pathobiology. The constellation of clinical, histological and laboratory findings seen in these patients is similar to other forms of viral pneumonia, but somewhat distinctive aspects exist which may raise the index of suspicion for this disease. The pathological findings are not limited to the respiratory system; cardiovascular, gastrointestinal and renal abnormalities have also been described. Establishing a link between the clinical features and macroscopic and microscopic findings is not only important for the practicing autopsy pathologist, but also for understanding of the disease as a whole. Furthermore, context-sensitive interpretation of diagnostic tests is essential. This article aims to review understanding of clinicopathological correlation in COVID-19, as well as clarifying the role of current diagnostic techniques.     

Vascular thrombosis and vasculitis in the gastrointestinal tract are associated with poor prognosis in patients with COVID-19

Aim: To report pathologic findings in the gastrointestinal (GI) tract of coronavirus disease 2019 (COVID-19) patients. Material and Methods: we evaluated clinical and GI tract histologic findings in six COVID-19 patients that presented with GI symptoms like diarrhea, and abdominal pain. This study includes surgical resection specimens from five patients and two sets of biopsy specimens from one patient. Results: Idiopathic inflammatory bowel disease was considered in three of six cases based on clinical, radiologic, and endoscopic presentation. Histologically, the enteric mucosa had a spectrum of histologic changes, including active enteritis, chronic active enteritis, and transmural necrosis. Extensive thrombi in vessels and/or vasculitis were identified in three out of the six cases. The presence of extensive vascular thrombi is associated with poor prognosis, and the three patients deceased in a short period of time (ranges from 7-67 days, median 14 days) after admission for GI symptoms. Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) RNA was detected in bowel tissue of one case. The other three patients recovered and were discharged and free of GI symptoms (follow-up period ranges from 235 days to 270 days, median 237 days). Conclusion: COVID-19 associated enteritis may mimic Crohn’s disease clinically, radiologically and endoscopically, and these two entities can be differentiated by pathologic findings. COVID-19 patients with GI symptoms may warrant a workup to evaluate for pathologic changes, as the presence of vasculitis and microthrombi may predict poor clinical outcome.     

Correlation of myeloid-derived suppressor cells with C-reactive protein,ferritin and lactate dehydrogenase levels in patients with severe COVID-19

The novel coronavirus disease 2019 (COVID-19) remains a global health emergency, and understanding the interactions between the virus and host immune responses is crucial to preventing its lethal effects. The expansion of myeloid-derived suppressor cells (MDSCs) in COVID-19, thereby suppressing immune responses, has been described as responsible for the severity of the disease, but the correlation between MDSC subsets and COVID-19 severity remains elusive. Therefore, we classified patients according to clinical and laboratory findings—aiming to investigate the relationship between MDSC subsets and laboratory findings such as high C-reactive protein, ferritin and lactate dehydrogenase levels, which indicate the severity of the disease. Forty-one patients with COVID-19 (26 mild and 15 severe; mean age of 49.7 ± 15 years) and 26 healthy controls were included in this study. MDSCs were grouped into two major subsets—polymorphonuclear MDSCs (PMN-MDSCs) and monocytic MDSCs—by flow cytometric immunophenotyping, and PMN-MDSCs were defined as mature and immature, according to CD16 expressions, for the first time in COVID-19. Total MDSCs, PMN-MDSCs, mature PMN-MDSCs and monocytic MDSCs were significantly higher in patients with COVID-19 compared with the healthy controls (P < .05). Only PMN-MDSCs and their immature PMN-MDSC subsets were higher in the severe subgroup than in the mild subgroup. In addition, a significant correlation was found between C-reactive protein, ferritin and lactate dehydrogenase levels and MDSCs in patients with COVID-19. These findings suggest that MDSCs play a role in the pathogenesis of COVID-19, while PMN-MDSCs, especially immature PMN-MDSCs, are associated with the severity of the disease.