ABSTRACT
BACKGROUND: It is widely accepted that SARS-CoV-2 causes a dysregulation of immune and coagulation processes. In severely affected patients, viral sepsis may result in life endangering multiple organ dysfunction. Furthermore, most therapies for COVID-19 patients target either the immune system or coagulation processes. As the exact mechanism causing SARS-CoV-2-induced morbidity and mortality was unknown, we started an in-depth analysis of immunologic and coagulation processes. METHODS: 127 COVID-19 patients were treated at the University Hospital Essen, Germany, between May 2020 and February 2022. Patients were divided according to their maximum COVID-19 WHO ordinal severity score (WHO 0-10) into hospitalized patients with a non-severe course of disease (WHO 4-5, n = 52) and those with a severe course of disease (WHO 6-10, n = 75). Non-infected individuals served as healthy controls (WHO 0, n = 42). Blood was analyzed with respect to cell numbers, clotting factors, as well as pro- and anti-inflammatory mediators in plasma. As functional parameters, phagocytosis and inflammatory responses to LPS and antigen-specific stimulation were determined in monocytes, granulocytes, and T cells using flow cytometry. FINDINGS: In the present study, immune and coagulation systems were analyzed simultaneously. Interestingly, many severe COVID-19 patients showed an upregulation of pro-inflammatory mediators and at the same time clear signs of immunosuppression. Furthermore, severe COVID-19 patients not only exhibited a disturbed immune system, but in addition showed a pronounced pro-coagulation phenotype with impaired fibrinolysis. Therefore, our study adds another puzzle piece to the already complex picture of COVID-19 pathology implying that therapies in COVID-19 must be individualized. CONCLUSION: Despite years of research, COVID-19 has not been understood completely and still no therapies exist, fitting all requirements and phases of COVID-19 disease. This observation is highly reminiscent to sepsis. Research in sepsis has been going on for decades, while the disease is still not completely understood and therapies fitting all patients are lacking as well. In both septic and COVID-19 patients, immune activation can be accompanied by immune paralysis, complicating therapeutic intervention. Accordingly, therapies that lower immune activation may cause detrimental effects in patients, who are immune paralyzed by viral infections or sepsis. We therefore suggest individualizing therapies and to broaden the spectrum of immunological parameters analyzed before therapy. Only if the immune status of a patient is understood, can a therapeutic intervention be successful.
ABSTRACT
-This study aims to determine spectrum of bacterial infection in patients with severe acute respiratory syndrome coronavirus-2 infection at the time of hospital admission and identify changes in hematological biomarkers of COVID19 severity. A retrospective study was conducted in blood cultures from patients suspected to have sepsis were included in the study. Patients were grouped based on SARS-CoV-2 RT-PCR result as positive, negative, or not tested. For the purposes of classifying blood cultures by SARS-CoV-2 RT-PCR status, hematological parameters were analyzed. Out off 825 blood sample, 466 samples was positive for blood culture identified by conventional and Automatic blood culture system - Vitek 2. Among these 466 patients, 211(45.2%) were positive for SARS-CoV2 virus and 255 (54.7%) were negative for SARS-CoV2 virus by RT-PCR. Regarding CRP Total number of CRP positive samples was 654, CRP negative samples was 84 and CRP was not done for 87samples. The total number of IL6 positive samples was 83 and IL6 negative samples were not evaluated for 125 patients. The concern of Bacterial sepsis in COVID-19 patients due to the above organisms based on our study over the period of one year. Consequently, it is important to pay attention to bacterial co-infections in critical patients diagnosed for COVID-19. Copyright © Global Science Publications.
ABSTRACT
Haemophilus influenzae (H. influenzae) is a facultative anaerobe, pleomorphic Gram-negative coccobacillus capable of causing various respiratory and blood stream infections. Introduction of childhood immunization against H. influenza type b has decreased its prevalence. Invasive infection with non-typeable H. influenzae is increasing specially in vulnerable population. We present a case of a 69-year-old female who developed septic shock due to H. influenzae infection. She was also found to have influenza A infection in bronchoalveolar lavage (BAL) sample although initial test with nasopharyngeal swab was negative. This case report highlights the fact that in patients with high clinical suspicion, negative nasopharyngeal swab with polymerase chain reaction may not rule out influenza infection and BAL may be necessary to confirm the diagnosis and H. influenzae can be causing bacterial superinfection in such patients. She was appropriately treated with third-generation cephalosporin for H. influenzae and with oseltamivir for influenza A. Her condition improved significantly with the treatment.
ABSTRACT
BACKGROUND: Coronavirus disease 2019 (COVID-19) has caused more than 2 million deaths worldwide. Viral sepsis has been proposed as a description for severe COVID-19, and numerous therapies have been on trials based upon this hypothesis. However, whether the clinical characteristics of severe COVID-19 are similar to those of bacterial sepsis has not been elucidated. METHODS: We retrospectively compared the clinical data of non-surviving COVID-19 patients who were admitted to a 30-bed intensive care unit (ICU) in Wuhan Infectious Diseases Hospital (Wuhan, China) from 22 January 2020, to 28 February 2020, with those of non-surviving patients with bacterial sepsis who were admitted to the ICU in Zhongshan Hospital, Fudan University (Shanghai, China) from 3 July 2018, to 30 June 2020. RESULTS: A total of 53 COVID-19 patients and 26 septic patients were included in the analysis. The mean ages were 65.6 [standard deviation (SD): 11.1] and 70.4 (SD: 14.3) years in the COVID-19 cohort and sepsis cohort, respectively. The proportion of participants with hypertension was higher in non-survivors with COVID-19 than in non-survivors with sepsis (41.5% vs. 15.4%, P=0.020). The Sequential Organ Failure Assessment (SOFA) score of non-survivors with COVID-19 was lower than that of non-survivors with sepsis at ICU admission {4.0 [interquartile range (IQR): 3.0-6.0] vs. 7.5 [IQR: 5.8-11.0], P<0.001}. The clinical parameters at ICU admission assessed with principal component analysis and hierarchical cluster analysis showed that COVID-19 patients were distinct from bacterial septic patients. Compared with non-survivors with sepsis, non-survivors with COVID-19 had a higher neutrophil/lymphocyte ratio, total protein, globulin, lactate dehydrogenase (LDH), and D-dimer; a lower eosinophil count, procalcitonin, interleukin-6 (IL-6), total bilirubin, direct bilirubin, myohemoglobin, albumin/globulin ratio, activated partial thromboplastin time (APTT), prothrombin time (PT), and international normalization ratio (INR) at ICU admission. In addition, the levels of total protein, globulin, LDH, D-dimer, and IL-6 were significantly different between the two groups during the ICU stay. CONCLUSIONS: Patients with critical COVID-19 have a phenotype distinct from that of patients with bacterial sepsis. Therefore, caution should be used when applying the previous experience of bacterial sepsis to patients with severe COVID-19.
ABSTRACT
BACKGROUND: The mechanisms driving acute kidney injury (AKI) in critically ill COVID-19 patients are unclear. We collected kidney biopsies from COVID-19 AKI patients within 30 min after death in order to examine the histopathology and perform mRNA expression analysis of genes associated with renal injury. METHODS: This study involved histopathology and mRNA analyses of postmortem kidney biopsies collected from patients with COVID-19 (n = 6) and bacterial sepsis (n = 27). Normal control renal tissue was obtained from patients undergoing total nephrectomy (n = 12). The mean length of ICU admission-to-biopsy was 30 days for COVID-19 and 3-4 days for bacterial sepsis patients. RESULTS: We did not detect SARS-CoV-2 RNA in kidney biopsies from COVID-19-AKI patients yet lung tissue from the same patients was PCR positive. Extensive acute tubular necrosis (ATN) and peritubular thrombi were distinct histopathology features of COVID-19-AKI compared to bacterial sepsis-AKI. ACE2 mRNA levels in both COVID-19 (fold change 0.42, p = 0.0002) and bacterial sepsis patients (fold change 0.24, p < 0.0001) were low compared to control. The mRNA levels of injury markers NGAL and KIM-1 were unaltered compared to control tissue but increased in sepsis-AKI patients. Markers for inflammation and endothelial activation were unaltered in COVID-19 suggesting a lack of renal inflammation. Renal mRNA levels of endothelial integrity markers CD31, PV-1 and VE-Cadherin did not differ from control individuals yet were increased in bacterial sepsis patients (CD31 fold change 2.3, p = 0.0006, PV-1 fold change 1.5, p = 0.008). Angiopoietin-1 mRNA levels were downregulated in renal tissue from both COVID-19 (fold change 0.27, p < 0.0001) and bacterial sepsis patients (fold change 0.67, p < 0.0001) compared to controls. Moreover, low Tie2 mRNA expression (fold change 0.33, p = 0.037) and a disturbed VEGFR2/VEGFR3 ratio (fold change 0.09, p < 0.0001) suggest decreased microvascular flow in COVID-19. CONCLUSIONS: In a small cohort of postmortem kidney biopsies from COVID-19 patients, we observed distinct histopathological and gene expression profiles between COVID-19-AKI and bacterial sepsis-AKI. COVID-19 was associated with more severe ATN and microvascular thrombosis coupled with decreased microvascular flow, yet minimal inflammation. Further studies are required to determine whether these observations are a result of true pathophysiological differences or related to the timing of biopsy after disease onset.