Examination of cord blood at birth in women with SARS-CoV-2 exposure and/or vaccination during pregnancy and relationship to fetal complete blood count, cortisol, ferritin, vitamin D, and CRP.

Background: SARS-CoV-2 is known to manifest a robust innate immune response. However, little is known about inflammatory influences from maternal SARS-CoV-2 infection or maternal mRNA vaccination upon the fetus. In addition, it is unknown if Vitamin D deficiency influences fetal homeostasis or if an anti-inflammatory mechanism to the development of possible innate cytokines or acute phase reactants by the maternal/fetal dyad, in the form of cortisol elevations, occur. In addition, effects on Complete Blood Count (CBC) are not known. Objective: To evaluate the neonatal acute phase reactants and anti-inflammatory responses after maternal SARS-CoV-2 disease or mRNA vaccination. Methods: Samples and medical records reviews from mother/baby dyads (n = 97) were collected consecutively, and were categorized into 4 groups; no SARS-CoV-2 or vaccination exposure (Control), Vaccinated mothers, maternal SARS-CoV-2 disease positive/IgG titer positive fetal blood, and maternal SARS-CoV-2 positive/IgG titer negative fetal blood. SARS-CoV-2 IgG/IgM/IgA titers, CBC, CRP, ferritin, cortisol, and Vitamin D were obtained to examine the possible development of an innate immune response and possible anti-inflammatory response. Student's t-test, Wilcoxon rank-sum, and Chi-squared with Bonferroni corrections were used to compare groups. Multiple imputations were performed for missing data. Results: Cortisol was higher in babies of both mothers who were vaccinated (p = 0.001) and SARS-CoV-2 positive/IgG positive (p = 0.009) as compared to the control group suggesting an attempt to maintain homeostasis in these groups. Measurements of ferritin, CRP, and vitamin D did not reach statistical significance. CBC showed no variation, except for the mean platelet volume (MPV), which was elevated in babies whose mothers were vaccinated (p = 0.003) and SARS-CoV-2 positive/IgG positive (p = 0.007) as compared to the control group. Conclusion: Acute phase reactant elevations were not noted in our neonates. Vitamin D levels were unchanged from homeostatic levels. Cord blood at birth, showed Cortisol and MPV higher in vaccinated and SARS-CoV-2 IgG positive mother/baby dyads as compared to the Control group, indicating that possible anti-inflammatory response was generated. The implication of possible inflammatory events and subsequent cortisol and/or MPV elevation effects upon the fetus after SARS-CoV-2 disease or vaccination is unknown and merits further investigation.

Ferritin, Serum Iron and Hemoglobin as Acute Phase Reactants in Laparoscopic and Open Surgery of Cholecystectomy: An Observational Prospective Study.

Cytokines are expressed by various cells after several stimuli such as surgical tissue damage, producing a systemic inflammatory response (SIR). C-reactive protein (CRP) is used extensively in clinical practice after operative injury, but proinflammatory cytokines, iron status, albumin, neutrophil-to-lymphocyte (N/L) ratio and hemoglobin, as acute phase reactants, have been poorly documented. This study aims to show how they behave after surgery, comparing laparoscopic (LC) versus open cholecystectomy (OC). In total, 55 patients were included in a prospective non-randomized form to undergo a cholecystectomy: 8 patients OC (50% females) and 47 patients LC (68% females). Before (A1) and 24 h after surgery (A2), blood samples were taken for an ordinary analysis and IL6, IL8 and TNFα determination. There were no differences between LC and OC groups concerning age, CRP, IL6 and TNFα at day A1. In the LC group at day A2, CRP, IL6, IL8, TNF, ferritin, leukocytes and N/L ratio increased; hemoglobin, lymphocytes, prothrombin and albumin decreased (p < 0.05). In the OC group at day A2, only IL6 (p < 0,07), ferritin, leukocytes, N/L ratio and CRP (p < 0.05) increased; serum iron, hemoglobin, lymphocytes and albumin (p < 0.05) decreased. At day A2, OC vs. LC group, higher values were observed in IL6, ferritin and CRP (p ≤ 0.05), and lesser values were observed in serum iron and prothrombin (p < 0.05). In conclusion, classic markers of inflammation are altered after surgery, in a milder way in laparoscopic surgery. Ferritin can be used as an inflammatory marker, as has been described in COVID-19 infection.

Low Testosterone on Hospital Admission with COVID-19 Infection Is Associated with Increased Mortality

Objective: Males, despite equal sex-related susceptibility to COVID-19, appear at a greater risk of poor clinical outcomes and death. This suggests that serum testosterone could be a mediator. The aim of this retrospective study was to evaluate the association between serum total testosterone (TT), other prognostic indicators, and mortality in men with COVID-19. Methods: Of the 110 men consecutively admitted to Walsall Manor Hospital (with COVID-19 related symptoms) tested for SARS-CoV-2, 85 were positive and 27 of these men died. Serum TT was compared (rank-sum test) between men negative and positive for SARS-CoV-2, and this was followed by establishing factors associated with mortality in the latter group (rank-sum, logistic, Cox regression analyses). No patient was on testosterone therapy (TTh). Results: No significant difference (p = 0.12, rank-sum test) in serum TT between men positive [median TT (IQR) = 3.9 (1.9-7.22) nmol/L, 0 days (median) postadmission] and negative [median TT (IQR) = 5.9 (2.69-10.1) nmol/L, 2 days (median) postadmission] for SARS-CoV-2 was observed. Serum TT was lower (p = 0.0011, rank-sum test) in men with COVID-19 who died [median TT (IQR) = 2.0 (1.5-3.6) nmol/L] compared with survivors [median TT (IQR) = 5.0 (2.6-9.4) nmol/L]. Comorbidities obtained via medication history were not associated with mortality. Mortality (logistic regression) was associated with only age and serum TT (odds ratio: 0.77, 95% confidence intervals [CI]: 0.64-0.91). Survival (Cox regression) was inversely associated with serum TT (continuous variable, hazard ratio [HR]: 0.85) (95% CI: 0.74-0.98), stratified by median, TT ≥3.9 nmol/L (reference, TT <3.9 nmol/L), HR: 0.24 (95% CI: 0.089-0.63). Conclusions: Serum TT was inversely associated with mortality in men with COVID-19 and requires measurement at admission and while managing long COVID. Future research should establish whether low serum TT, possibly associated with negative acute phase response, contributes to poorer prognosis and a role for TTh. © Mark Livingston et al., 2022;Published by Mary Ann Liebert, Inc. 2022.

Exposing and Overcoming Limitations of Clinical Laboratory Tests in COVID-19 by Adding Immunological Parameters; A Retrospective Cohort Analysis and Pilot Study.

Background: Two years since the onset of the COVID-19 pandemic no predictive algorithm has been generally adopted for clinical management and in most algorithms the contribution of laboratory variables is limited. Objectives: To measure the predictive performance of currently used clinical laboratory tests alone or combined with clinical variables and explore the predictive power of immunological tests adequate for clinical laboratories. Methods: Data from 2,600 COVID-19 patients of the first wave of the pandemic in the Barcelona area (exploratory cohort of 1,579, validation cohorts of 598 and 423 patients) including clinical parameters and laboratory tests were retrospectively collected. 28-day survival and maximal severity were the main outcomes considered in the multiparametric classical and machine learning statistical analysis. A pilot study was conducted in two subgroups (n=74 and n=41) measuring 17 cytokines and 27 lymphocyte phenotypes respectively. Findings: 1) Despite a strong association of clinical and laboratory variables with the outcomes in classical pairwise analysis, the contribution of laboratory tests to the combined prediction power was limited by redundancy. Laboratory variables reflected only two types of processes: inflammation and organ damage but none reflected the immune response, one major determinant of prognosis. 2) Eight of the thirty variables: age, comorbidity index, oxygen saturation to fraction of inspired oxygen ratio, neutrophil-lymphocyte ratio, C-reactive protein, aspartate aminotransferase/alanine aminotransferase ratio, fibrinogen, and glomerular filtration rate captured most of the combined statistical predictive power. 3) The interpretation of clinical and laboratory variables was moderately improved by grouping them in two categories i.e., inflammation related biomarkers and organ damage related biomarkers; Age and organ damage-related biomarker tests were the best predictors of survival, and inflammatory-related ones were the best predictors of severity. 4) The pilot study identified immunological tests (CXCL10, IL-6, IL-1RA and CCL2), that performed better than most currently used laboratory tests. Conclusions: Laboratory tests for clinical management of COVID 19 patients are valuable but limited predictors due to redundancy; this limitation could be overcome by adding immunological tests with independent predictive power. Understanding the limitations of tests in use would improve their interpretation and simplify clinical management but a systematic search for better immunological biomarkers is urgent and feasible.

Ophthalmic Manifestation of COVID-19 disease

A coronavirus is the novel coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). It's a nonsegmented enveloped positive sense RNA virus with 82 percent genetic similarity to the SARS coronavirus (SARSCoV), which sparked an outbreak in early 2003. Respiratory droplets are assumed to be the primary mechanism of transmission because the virus is found in respiratory secretions. Conjunctival transmission and aerosol transmission have also been proposed, however they are also problematic. Fever, tiredness, and dry mouth are the three most prevalent COVID19 clinical symptoms. In several patients, however, conjunctivitis was the initial symptom. The disease's respiratory complications have been the focus of diagnostic and therapeutic efforts, However, a number of ocular concerns have surfaced. Infected patients' tears have been confirmed to contain SARSCov2 RNA, and studies indicate that the virus is spreading. For viral transmission, the ocular surface could serve as both an entry point and a reservoir. COVID19 has been linked to mild conjunctivitis, which can be the disease's first and only symptom. Ocular symptoms can be treated with observation without therapy, antibacterial eye drops, antiviral eye drops, and antiallergic eye drops, according to clinical trials..As a result, the only recommended treatment for COVID19related ocular manifestations is close observation cough. The motivation behind this examination was to investigate the event of visual appearances in patients who had been determined to have Covid illness 2019 (Coronavirus) because of serious intense respiratory condition. 2(SARS-CoV-2). © The Electrochemical Society

Analysis of Patients with Major Fractures with and without COVID-19 Infection

PURPOSE OF THE STUDY As in orthopedic trauma patients, a hyperinflammatory response due to cytokine release occurs in patients with moderate and severe COVID-19 infection. In these patients, untimely surgical intervention can create more destructive situations in the postoperative period. Our aim in this study was to investigate the effect of COVID-19, trauma and surgical intervention on acute phase reactants' levels in patients with and without COVID-19 infection. MATERIAL AND METHODS Twenty-four patients diagnosed with COVID-19 infection and major fractures requiring surgical treatment were evaluated retrospectively (Group 1). Twenty-four COVID-19 negative patients with similar trauma were included in the study as a control group (Group 2). These two groups were compared in terms of demographic data, time to surgery, total hospitalization time, and preoperative and postoperative acute phase reactants' [C-reactive protein (CRP), D-dimer, ferritin, fibrinogen and white blood cell (WBC)] values. RESULTS Time to surgery was 8.3 +/- 0.7 days and the total hospital stay was 15.2 +/- 0.8 days, in Group 1. These values were determined as 3.3 +/- 0.4 and 6.5 +/- 0.6 days, respectively for the patients in Group 2 (p < 0.001 and p < 0.001, respectively). When the acute phase reactant values studied during admission were examined, a significant difference was found between the two groups in terms of CRP, D-dimer, ferritin and WBC (p = 0009, p = 0.002, p < 0.001 and p < 0.001, respectively). In the preoperative period, a significant difference was observed between the groups in terms of CRP and ferritin (p = 0.011, p < 0.001, respectively). A significant difference was found only in terms of ferritin from the laboratory values studied in the postoperative period (p < 0.001). DISCUSSION To our knowledge, the present study is the first study which compares and investigates the effects of COVID-19 infection, major fracture and surgical intervention on acute phase reactants' values. Surgical treatment is generally recommended as soon as possible in daily orthopedic practice. However, in patients with asymptomatic or mildly symptomatic COVID-19 infection, it remains unclear how long surgical intervention will be delayed after admission and clinical stabilization of patients with a fracture that requires surgical fixation. In a meta-analysis, patients with COVID-19 infection accompanying hip fracture had a mortality rate of 32.6% in the early postoperative period, and the mortality risk of these patients was found to be 5.66 times higher compared to patients without COVID-19 infection. In our study, one patient (4.2%) with COVID-19 infection who underwent partial hip arthroplasty due to femoral neck fracture. CONCLUSIONS The follow-up and treatment of patients with COVID-19 infection with accompanying a major fracture requiring orthopedic surgery is a complex situation. We recommend that acute phase reactants such as CRP, D-dimer, erythrocyte sedimentation rate (ESR), and ferritin should be closely monitored in these patients during the period from admission to surgery, and surgical intervention should be performed while these values are in remission or decline.

Extracellular Oxidative Stress Markers in COVID-19 Patients with Diabetes as Co-Morbidity.

COVID-19 patients have a higher risk of developing inflammatory responses associated with serious and even fatal respiratory diseases. The role of oxidative stress in exacerbating manifestations in COVID-19 pathogenesis is under-reported.This study aimed touseserum levels of superoxide dismutase (SOD3) and glutathione-S-transferase (GSTp1) by ELISA, zinc (ErbaChem5), ferritin and free iron (VitrosChemistry, Ortho Clinical Diagnosis, Raritan, NJ, USA) at the first encounter of randomly selected RT-PCR-positive COVID-19 patients, for assessing disease severity. The parameters which helped in identifying the severity, leading to poor prognosis, were neutrophil:lymphocyte higher than 4, high CRP, low SOD3 values and high GSTp1 values, and diabetes mellitus as a co-morbidity. Higher zinc levels correlated with high GSTp1 and low SOD3, indicating the protective effect of zinc on ROS. The increased high GSTp1 shows an anticipated protective biochemical response, to mitigate the low SOD3 values due to ROS consumption. Decreased SOD3 levels indicate a state of high oxidative stress at cellular levels, and an anticipated increase in GSTp1 levels points to the pathophysiological bases of increasing severity with age, sex, and co-morbidities, such asdiabetes. High levels of initial GSTp1 and zinc levels possibly offer protection to redox reactions at the cellular level in severe COVID-19 infection, preventing deterioration.

Effect of a single high dose of vitamin D3 on cytokines, chemokines, and growth factor in patients with moderate to severe COVID-19.

BACKGROUND: The modulating effect of vitamin D on cytokine concentrations in severe coronavirus disease 2019 (COVID-19) remains unknown. OBJECTIVES: We aimed to investigate the effect of a single high dose of vitamin D3 on cytokines, chemokines, and growth factor in hospitalized patients with moderate to severe COVID-19. METHODS: This is a post hoc, ancillary, and exploratory analysis from a multicenter, double-blind, placebo-controlled, randomized clinical trial. Patients with moderate to severe COVID-19 were recruited from 2 hospitals in São Paulo, Brazil. Of 240 randomly assigned patients, 200 were assessed in this study and randomly assigned to receive a single oral dose of 200,000 IU vitamin D3 (n = 101) or placebo (n = 99). The primary outcome was hospital length of stay, which has been published in our previous study. The prespecified secondary outcomes were serum concentrations of IL-1ß, IL-6, IL-10, TNF-α, and 25-hydroxyvitamin D. The post hoc exploratory secondary outcomes were IL-4, IL-12p70, IL-17A, IFN-γ, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-8, IFN-inducible protein-10 (IP-10), macrophage inflammatory protein-1ß (MIP-1ß), monocyte chemoattractant protein-1 (MCP-1), vascular endothelial growth factor (VEGF), and leukocyte count. Generalized estimating equations for repeated measures, with Bonferroni's adjustment, were used for testing all outcomes. RESULTS: The study included 200 patients with a mean ± SD age of 55.5 ± 14.3 y and BMI of 32.2 ± 7.1 kg/m2, of which 109 (54.5%) were male. GM-CSF concentrations showed a significant group-by-time interaction effect (P = 0.04), although the between-group difference at postintervention after Bonferroni's adjustment was not significant. No significant effects were observed for the other outcomes. CONCLUSIONS: The findings do not support the use of a single dose of 200,000 IU vitamin D3, compared with placebo, for the improvement of cytokines, chemokines, and growth factor in hospitalized patients with moderate to severe COVID-19.This trial was registered at clinicaltrials.gov as NCT04449718.

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.

[Cough in times of coronavirus]. / Husten in Corona-Zeiten.

The article describes the case of a hospitalized 58-year-old female patient with a chronic dry cough and increased inflammation values. Before hospital admission, the presence of coronavirus disease 2019 (COVID-19) was excluded by a normal chest X­ray and two negative PCR tests on throat swabs. On admission the only symptom was a dry cough with clinically inconspicuous auscultation findings. The laboratory investigations revealed anemia and increased inflammation parameters, e.g. C­reactive protein (CRP) 92.4 mg/l and erythrocyte sedimentation rate (ESR) 102 mm/h (according to Westergren). A large vessel vasculitis was demonstrated on magnetic resonance angiography (MRA). After the diagnosis of a giant cell arteritis, treatment with an oral glucocorticoid and subcutaneous methotrexate (MTX) was initiated, with good clinical and laboratory parameter responses. Dry cough has been described in rare cases in the literature as the first sign of large vessel vasculitis.

Association Between Severity Grading Score And Acute Phase Reactants In Patients With Crimean Congo Hemorrhagic Fever.

As the COVID-19 pandemic continues, countries still have to struggle with their endemic diseases such as Crimean-Congo hemorrhagic fever (CCHF). Severity grading score (SGS) is a practical approach and may shed light on the course of the CCHF, whose pathogenesis is not clearly understood, and have no effective treatments. It is aimed to assess the association between SGS and acute phase reactants (APR). Laboratory-confirmed patients were categorized by severity scores, and the relationship between APR and SGS was evaluated. A significant correlation between SGS and C-reactive protein (CRP) was found (p < 0.001). High SGS was associated with mortality and high CRP levels were used to predict the mortality at the beginning of the hospital admission. To predict the outcome of the disease and for appropriate patient management, SGS and APR can be used simultaneously.

Ocular manifestations of coronavirus disease 2019.

PURPOSE: Coronavirus disease 2019 (COVID-19) is an ongoing global public health problem, and most of the COVID-19 research is focused mainly on the respiratory system because of life-threatening results. However, manifestations in other organs should not be ignored since they can also be a mode of transmission. We sought to describe the ocular manifestations of COVID-19 and investigate the association between ocular involvement and clinical presentation and laboratory outcomes. METHODS: This cross-sectional study was conducted between March 1, 2020, and April 30, 2020. Ninety-three sequentially hospitalized and clinically confirmed COVID-19 patients were included in the study. The systemic and ocular symptoms, clinical findings, and laboratory outcomes were recorded. RESULTS: Of the 93 COVID-19 patients, 54 (58.1%) were male, and 39 (41.9%) were female. Mean age of the patients was 39.4 ± 21.9 (min 7, max 88) years. Twenty patients (n 21.5%) had at least one ocular abnormality. Most common findings included hyperemia (n = 20), epiphora (n = 9), increased secretion (n = 6), chemosis (n = 3), follicular conjunctivitis (n = 2), and episcleritis (n = 2). The most common symptom was photophobia (n 15). Patients with ocular involvement were more likely to have higher neutrophil counts (p = 0.001), and increased CRP (p < 0.001), PCT (p = 0.001), and ESR levels (p < 0.001). Mean lymphocyte count was statistically lower in patients with ocular manifestations (p = 0.001). Mean age and number of patients with fever over 37.3 °C in the ocular involvement group was found to be higher (p < 0.001, p = 0.006, respectively). CONCLUSION: Older age, high fever, increased neutrophil/lymphocyte ratio, and high levels of acute phase reactants seemed to be risk factors for ocular involvement.