scholarly journals Inflammatory and Immune Biomarkers in Predicting the Severity in COVID-19

2021 ◽  
pp. 1-13
Author(s):  
Shrishti Dhar Prasad ◽  
Suprava Patel ◽  
Ajoy Kumar Behera ◽  
Dibakar Sahu ◽  
Seema Shah ◽  
...  
Keyword(s):  
Serum Ferritin ◽  
Clinical Manifestations ◽  
Clinical Score ◽  
Severe Form ◽  
Clinical Severity ◽  
Close Monitoring ◽  
Complement Factor ◽  
Immune Biomarkers ◽  
Mortality Outcome ◽  
Complement Factor C3

Aims: An early diagnosis of severity can be confidently judged by monitoring the serum biomarkers in patients with COVID-19. The study was thus aimed to explore the relationship of the inflammatory and immune biomarkers in predicting the severity of the disease. Study design: It is a retrospective observational study. Methodology: The study included 79 confirmed cases of COVID-19 who had complete clinical record for the analytical variables. All cases were assigned a total clinical score as per their clinical manifestations, associated co-morbidities and mortality outcome. Laboratory inflammatory and immune biomarkers at the time of admission were noted. Results: The mean age of the study population was 55.38 (1.69) years. The percentage of admission for males (67.1%) was twice that of females (32.9%). Serum LDH (p=0.003) and ferritin (0.019) levels were remarkably raised in severe form. Total clinical score denoted a positive correlation with the inflammatory biomarkers (p<0.001). IgM exhibited a significant negative trend with increasing clinical score (p<0.001) and CRP levels (p=0.022) of the patients. The multivariate analysis reflected that the total clinical score was significantly influenced by initial SpO2 values (0.011), serum ferritin (0.027), IgM (0.001) and C3 levels (0.044) in the COVID-19 patients. Lower serum C3 values significantly influenced the hospitalization duration in moderate cases (p=0.034) and total clinical score in severe cases (p=0.01). Conclusion: The findings of the study signified that besides serum ferritin, a serial and close monitoring of serum IgM with complement factor C3 would aid in early prediction of clinical severity and thus guide physicians to start effective management strategy.

scholarly journals Complement activation in individuals with previous subclinical Lyme borreliosis and patients with previous Lyme neuroborreliosis

2019 ◽  
Vol 39 (5) ◽  
pp. 855-862
Author(s):  
Hanna Carlsson ◽  
Kerstin Sandholm ◽  
Haben Woldu Haddish ◽  
Lars Brudin ◽  
Kristina Nilsson Ekdahl ◽  
...  
Keyword(s):  
Lyme Borreliosis ◽  
Complement Activation ◽  
Clinical Manifestations ◽  
Lyme Neuroborreliosis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Complement Factor ◽  
Significant Difference ◽  
Activation Products ◽  
Study Population ◽  
Complement Factor C3

AbstractLyme borreliosis (LB) is caused by Borrelia burgdorferi and infection may lead to not only a large variety of clinical manifestations but also a subclinical outcome. The aim of the present study was to investigate if there is a constitutional difference in complement activation between individuals with previous subclinical Lyme borreliosis (SB) and patients previously diagnosed with Lyme neuroborreliosis (LNB).Lepirudin plasma for activation studies was collected from 60 SB individuals and from 22 patients pre-diagnosed with LNB. The plasma was incubated with live Borrelia spirochetes of two strains (complement sensitive B. garinii Lu59 and complement resistant B. afzelii ACA1).Complement factor C3 was measured in non-activated lepirudin plasma with immune-nephelometry and C3a and sC5b-9 generated during complement activation were measured by enzyme-linked immunosorbent assay.We found that the complement sensitive Lu59 induced higher complement activation than the complement resistant ACA1 when measuring activation products C3a and sC5b-9 in SB and LNB patients, p < 0.0001. No significant difference was found between SB and LNB patients in systemic levels of C3. Furthermore, SB individuals generated a higher activation of C3 cleavage to C3a (C3a/C3 ratio) than LNB patients after activation with ACA1, p < 0.001, but no significant differences were found in response to Lu59. In conclusion, Lu59 induced higher complement activation than ACA1 and individuals with previous SB showed increased generation of C3a compared with patients with previous LNB. In our study population, this mechanism could lead to less elimination of spirochetes in LNB patients and thereby be a factor contributing to the clinical outcome.

scholarly journals Seborrheic dermatitis prevalence in HIV patients

2015 ◽  
Vol 18 (4) ◽  
pp. 131-137
Author(s):  
Anca Răducan ◽  
◽  
Magdalena Constantin ◽  
Irina Magdalena Dumitru ◽  
Aurelia Hangan ◽  
...  
Keyword(s):  
Seborrheic Dermatitis ◽  
Clinical Manifestations ◽  
Severe Form ◽  
Clinical Severity ◽  
Prolonged Treatment ◽  
Hiv Positive ◽  
Hiv Patients ◽  
Course Of Disease ◽  
Discontinuation Of Treatment ◽  
A Prospective Study

Objective. Highlighting seborrheic dermatitis prevalence in HIV patients and evaluating clinico-therapeutical correlations. Material and methods. Between 1.10.2011 – 31.12.2014 we performed a prospective study on a group of 121 HIV-positive patients hospitalized in the HIV Adults Department in the Infectious Diseases Hospital, Constanta, to determine the prevalence, clinical particularities and treatment response of seborrheic dermatitis in HIV + patients. Results. Seborrheic dermatitis has been reported in 33.05% of patients, predominantly male (M:F = 9:1), with peak incidence in the 20-30 age group. Lesions prevalence according to the site of seborrheic dermatitis was: face (15%), scalp (22.5%), face and scalp (45%), chest (12.5%). In terms of clinical severity, 27.5% patients had mild seborrheic dermatitis, while 62.5% had moderate seborrheic dermatitis, and 10% were diagnosed with the severe form. Therapeutic response was evaluated at day 7, 14 and after 8 weeks, assessing the decrease/disappearance of erythema and flaking, and pruritus improvement/remission. After 8 weeks of treatment, complete remission was reported in 70% patients. However, HIV+ patients with seborrheic dermatitis had between 2-5 episodes per year, relapses being reported at 4 to 12 weeks after discontinuation of treatment, mean 7 weeks. Conclusions. The present study indicates a moderate prevalence of seborrheic dermatitis in hospitalized HIV+ patients. Although clinical manifestations do not differ from those of seborrheic dermatitis in seronegative patients, the clinical course of disease reveals the extensive character of seborrheic dermatitis in HIV+ patients with more severe lesions, refractory to treatment, and frequent recurrences, even in patients receiving prolonged treatment.

scholarly journals SARS-CoV-2 drives JAK1/2-dependent local complement hyperactivation

2021 ◽  
Vol 6 (58) ◽  
pp. eabg0833
Author(s):  
Bingyu Yan ◽  
Tilo Freiwald ◽  
Daniel Chauss ◽  
Luopin Wang ◽  
Erin West ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Clinical Manifestations ◽  
Lung Epithelial Cells ◽  
Complement Factor ◽  
Respiratory Epithelial Cells ◽  
Signature Genes ◽  
Wide Range ◽  
Lung Epithelial ◽  
Gene Transcripts ◽  
Respiratory Epithelial

Patients with coronavirus disease 2019 (COVID-19) present a wide range of acute clinical manifestations affecting the lungs, liver, kidneys and gut. Angiotensin converting enzyme (ACE) 2, the best-characterized entry receptor for the disease-causing virus SARS-CoV-2, is highly expressed in the aforementioned tissues. However, the pathways that underlie the disease are still poorly understood. Here, we unexpectedly found that the complement system was one of the intracellular pathways most highly induced by SARS-CoV-2 infection in lung epithelial cells. Infection of respiratory epithelial cells with SARS-CoV-2 generated activated complement component C3a and could be blocked by a cell-permeable inhibitor of complement factor B (CFBi), indicating the presence of an inducible cell-intrinsic C3 convertase in respiratory epithelial cells. Within cells of the bronchoalveolar lavage of patients, distinct signatures of complement activation in myeloid, lymphoid and epithelial cells tracked with disease severity. Genes induced by SARS-CoV-2 and the drugs that could normalize these genes both implicated the interferon-JAK1/2-STAT1 signaling system and NF-κB as the main drivers of their expression. Ruxolitinib, a JAK1/2 inhibitor, normalized interferon signature genes and all complement gene transcripts induced by SARS-CoV-2 in lung epithelial cell lines, but did not affect NF-κB-regulated genes. Ruxolitinib, alone or in combination with the antiviral remdesivir, inhibited C3a protein produced by infected cells. Together, we postulate that combination therapy with JAK inhibitors and drugs that normalize NF-κB-signaling could potentially have clinical application for severe COVID-19.

scholarly journals Variable immunodeficiency score upfront analytical link (VISUAL), a proposal for combined prognostic score at diagnosis of common variable immunodeficiency

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kissy Guevara-Hoyer ◽  
Adolfo Jiménez-Huete ◽  
Julia Vasconcelos ◽  
Esmeralda Neves ◽  
Silvia Sánchez-Ramón
Keyword(s):  
Common Variable Immunodeficiency ◽  
Severity Score ◽  
Prognostic Score ◽  
Clinical Severity ◽  
Risk Category ◽  
Close Monitoring ◽  
Accurate Identification ◽  
Visual Score ◽  
Severity Scores ◽  
Common Variable

AbstractThe broad and heterogeneous clinical spectrum that characterizes common variable immunodeficiency (CVID) is associated with quite different disease course and prognosis, highlighting the need to develop tools that predict complications. We developed a multianalyte VISUAL score (variable immunodeficiency score upfront analytical link) aimed to predict severity using individual CVID patient data at baseline of a cohort of 50 CVID patients from two different centers in Portugal and Spain. We retrospectively applied VISUAL to the CVID clinical severity scores proposed by Ameratunga and Grimbacher after 15 years follow-up of our cohort. VISUAL score at CVID diagnosis showed adequate performance for predicting infectious and non-infectious severe complications (Cluster B). Compared to switched memory B lymphocyte phenotype alone, VISUAL provided a more accurate identification of clinically meaningful outcome, with significantly higher sensitivity (85% vs 55%, p = 0.01), and negative predictive value (77% vs 58%) and AUC of the ROC curves (0.72 vs 0.64), with optimal cut-off level of 10. For every increase of 1 point in the VISUAL scale, the odds of being in the higher risk category (Cluster B) increased in 1.3 (p = 0.005) for Ameratunga’s severity score and 1.26 (p = 0.004) for Grimbacher’s severity score. At diagnosis of CVID, VISUAL score ≥ 10 showed 8.94-fold higher odds of severe prognosis than below this threshold. Kaplan–Meier estimates for the VISUAL ≥ 10 points showed significantly earlier progression to Cluster B than those with VISUAL < 10 (p = 0.0002). This prognostic laboratory score might allow close monitoring and more aggressive treatment in patients with scores ≥ 10 on a personalized basis approach. Further studies are needed to prospectively validate VISUAL score.

scholarly journals Evidence for non-traditional activation of complement factor C3 during murine liver regeneration

2008 ◽  
Vol 45 (11) ◽  
pp. 3125-3132 ◽  
Author(s):  
Amelia Clark ◽  
Alexander Weymann ◽  
Eric Hartman ◽  
Yumirle Turmelle ◽  
Michael Carroll ◽  
...  
Keyword(s):  
Liver Regeneration ◽  
Complement Factor ◽  
Murine Liver ◽  
Complement Factor C3

scholarly journals Clinical Manifestations of Hemochromatosis inHFEC282Y Homozygotes Identified by Screening

2008 ◽  
Vol 22 (11) ◽  
pp. 923-930 ◽  
Author(s):  
Gordon D McLaren ◽  
Christine E McLaren ◽  
Paul C Adams ◽  
James C Barton ◽  
David M Reboussin ◽  
...  
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Elevated Serum ◽  
Clinical Signs ◽  
Clinical Manifestations ◽  
Joint Stiffness ◽  
Chronic Fatigue ◽  
Newly Diagnosed ◽  
Wild Type ◽  
Control Subjects

BACKGROUND: Patients with hemochromatosis may suffer organ damage from iron overload, often with serious clinical consequences.OBJECTIVE: To assess prevalences of self-reported symptoms and clinical signs and conditions in persons homozygous for the hemochromatosis gene (HFE)mutation (C282Y) identified by screening.METHODS: Participants were adults 25 years of age or older enrolled in the Hemochromatosis and Iron Overload Screening (HEIRS) Study. C282Y homozygotes (n=282) were compared with control participants without theHFEC282Y or H63D alleles (ie, wild type/wild type; n=364).RESULTS: Previously diagnosed C282Y homozygotes and newly diagnosed homozygotes with elevated serum ferritin levels had higher prevalences of certain symptoms such as chronic fatigue (OR 2.8; 95% CI 1.34 to 5.95, and OR 2.0; 95% CI 1.07 to 3.75, respectively), and had more hyperpigmentation on physical examination (OR 4.7; 95% CI 1.50 to 15.06, and OR 3.7; 95% CI 1.10 to 12.16, respectively) and swelling or tenderness of the second and third metacarpophalangeal joints (OR 4.2; 95% CI 1.37 to 13.03, and OR 3.3; 95% CI 1.17 to 9.49, respectively) than control subjects. Joint stiffness was also more common among newly diagnosed C282Y homozygotes with elevated serum ferritin than among control subjects (OR 2.7; 95% CI 1.38 to 5.30). However, the sex- and age-adjusted prevalences of self-reported symptoms and signs of liver disease, heart disease, diabetes and most other major clinical manifestations of hemochromatosis were similar in C282Y homozygotes and control subjects.CONCLUSIONS: Some symptoms and conditions associated with hemochromatosis were more prevalent among C282Y homozygotes identified by screening than among control subjects, but prevalences of most outcomes were similar in C282Y homozygotes and controls in this primary care-based study.

A case of Graves’ disease associated with membranoproliferative glomerulonephritis and leukocytoclastic vasculitis

2018 ◽  
Vol 31 (10) ◽  
pp. 1165-1168 ◽  
Author(s):  
Werner Keenswijk ◽  
Eva Degraeuwe ◽  
Anne Hoorens ◽  
Jo Van Dorpe ◽  
Johan Vande Walle
Keyword(s):  
Renal Function ◽  
Membranoproliferative Glomerulonephritis ◽  
Leukocytoclastic Vasculitis ◽  
White Cell Count ◽  
Gastrointestinal Symptoms ◽  
Thyroid Stimulating Hormone ◽  
Graves Disease ◽  
Complement Factor ◽  
Gradual Improvement ◽  
Complement Factor C3

Abstract Background The association of hyperthyroidism with renal disease is very rare and the importance of timely clinical recognition cannot be overemphasized. Case presentation An 11-year-old girl presented with gastrointestinal symptoms while hypertension, edema and abdominal pain were noticed on clinical examination. Laboratory investigation revealed: hemoglobin 9.4 (11.5–15.5) g/dL, total white cell count 16 (4.5–12)×109/L, platelets 247 (150–450)×109/L, C-reactive protein (CRP) 31.8 (<5) mg/L, blood urea nitrogen (BUN) 126 (13–43) mg/dL, creatinine 0.98 (0.53–0.79) mg/dL, albumin 25 (35–52) g/dL, complement factor C3 0.7 (0.9–1.8) g/L, complement factor C4 0.1 (0.1–0.4) g/L, tri-iodothyronine 6.5 (2.5–5.2) pg/mL, free thyroxine 2.4 (1–1.7) ng/dL, thyroid stimulating hormone (TSH) <0.02 (0.5–4.3) mU/L. Urinalysis showed nephrotic range proteinuria. Renal function deteriorated necessitating hemodialysis (HD). A renal biopsy revealed an immune complex-mediated membranoproliferative glomerulonephritis (MPGN). Elevated thyroid hormones and suppressed TSH levels with elevated thyroperoxidase antibodies and thyroid stimulating immunoglobulins confirmed the diagnosis of Graves’ disease. Corticosteroids were commenced and eventually thiamazole was added with gradual improvement of renal function, cessation of HD and discharge from the hospital. Conclusions Graves’ disease complicated by MPGN is extremely rare, but can cause life-threatening complications.

scholarly journals Discrete viral E2 lysine residues and scavenger receptor MARCO are required for clearance of circulating alphaviruses

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Kathryn S Carpentier ◽  
Bennett J Davenport ◽  
Kelsey C Haist ◽  
Mary K McCarthy ◽  
Nicholas A May ◽  
...  
Keyword(s):  
Disease Severity ◽  
Mutational Analysis ◽  
Scavenger Receptor ◽  
Transmission Efficiency ◽  
Complement Factor ◽  
Critical Determinant ◽  
Lysine Residues ◽  
Complement Factor C3 ◽  
Immune Pathway ◽  
Innate Immune Pathway

The magnitude and duration of vertebrate viremia is a critical determinant of arbovirus transmission, geographic spread, and disease severity. We find that multiple alphaviruses, including chikungunya (CHIKV), Ross River (RRV), and o’nyong ‘nyong (ONNV) viruses, are cleared from the circulation of mice by liver Kupffer cells, impeding viral dissemination. Clearance from the circulation was independent of natural antibodies or complement factor C3, and instead relied on scavenger receptor SR-A6 (MARCO). Remarkably, lysine to arginine substitutions at distinct residues within the E2 glycoproteins of CHIKV and ONNV (E2 K200R) as well as RRV (E2 K251R) allowed for escape from clearance and enhanced viremia and dissemination. Mutational analysis revealed that viral clearance from the circulation is strictly dependent on the presence of lysine at these positions. These findings reveal a previously unrecognized innate immune pathway that controls alphavirus viremia and dissemination in vertebrate hosts, ultimately influencing disease severity and likely transmission efficiency.

Evaluation of serum electrolyte levels in iron deficiency anemia patients.

2021 ◽  
Vol 28 (05) ◽  
pp. 691-696
Author(s):  
Maryam Rafiq ◽  
Amna Arooj ◽  
Qurrat-ul-Ain Tahir ◽  
Nudrat Fayyaz ◽  
Afra Samad ◽  
...  
Keyword(s):  
Iron Deficiency ◽  
Iron Deficiency Anemia ◽  
Serum Ferritin ◽  
Cross Sectional Study ◽  
Deficiency Anemia ◽  
Close Monitoring ◽  
Cross Sectional ◽  
Mean Values ◽  
Medical College ◽  
Complete Blood Counts

Objectives: To evaluate electrolytes levels in patients suffering from iron deficiency anemia and to compare it with patients without anemia. Study Design: Descriptive Cross Sectional study. Setting: Department of Pathology, Sahiwal Medical College Sahiwal. Period: November, 2019 to May, 2020. Material & Methods: After taking informed consent, five milliliter of blood was drawn from each patient. Blood sample was analyzed for electrolytes, complete blood counts and serum ferritin levels. Results were compared in normal and iron deficiency anemic groups. Results: A total of 287 clinically anemic suspects including 181 (63.0%) female and 106 (37.0%) male with mean age of patients as 36.11±12.23 were included in this study. A total of 205 (71.4%) of the suspects had anemia whereas frequency of anemia remained higher among females (78.5%) as compared to males (59.5%) in this study. On the basis of serum ferritin levels a total of 178 (62.0%) patients had iron deficiency. Mean values of Sodium (130.41±0.59) and Bicarbonate (24.10±0.31) remained low while mean Potassium (4.33±0.07) and Chloride (103.93±0.47) levels of Iron Deficiency Anemia (IDA) group remained high as compared to non-anemic group. Conclusion: Levels of sodium and bicarbonate are found to be on the lower side while potassium and chloride remained on higher side in patients with Iron deficiency Anemia in this study. Thus these findings indicate close monitoring of electrolytes to evade impediments during management of patients.

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