Arteriovenous fistula as the vascular access contributes to better survival of hemodialysis patients with COVID-19 infection.

BACKGROUND: While COVID-19 in chronic hemodialysis patients has high mortality and the pandemic will not end in the near future, effective follow up strategies should be implemented for these patients. Surgeries have been triaged according to their level of urgencies and arteriovenous fistula (AVF) operations were among elective surgeries. This study aimed to analyze the effect of vascular access on the outcomes of hemodialysis patients who had COVID-19. METHODS: One hundred four hemodialysis patients who had COVID-19 were retrospectively analyzed. Seventy-two of them had AVF as the vascular access while 32 of them had tunneled catheters. Inflammatory markers and outcomes of patients with AVFs and catheters were compared. A logistic regression analysis was performed in order to define factors that contribute to better outcomes in hemodialysis patients. RESULTS: COVID-19 had high mortality rate in hemodialysis patients (36.5%). Patients with catheters have higher peak ferritin levels (p = 0.02) and longer hospital stay (p = 0.00). Having AVF as the vascular access (OR = 3.36; 95% CI: 1.05-10.72; p = 0.041) and using medium cut-off dialyzers (OR = 7.99; 95% CI: 1.53-41.65; p = 0.014) were related to higher survival of the patients. COVID severity was inversely proportional to the survival (p = 0.000). CONCLUSIONS: AVFs contribute to higher survival of hemodialysis patients with COVID-19. Even in the pandemic era, end stage renal disease patients should be given the opportunity to have their vascular access properly created.

Diuretic-induced hypokalaemia: an updated review.

Diuretic-induced hypokalaemia is a common and potentially life-threatening adverse drug reaction in clinical practice. Previous studies revealed a prevalence of 7%-56% of hypokalaemia in patients taking thiazide diuretics. The clinical manifestations of hypokalaemia due to diuretics are non-specific, varying from asymptomatic to fatal arrhythmia. Diagnosis of hypokalaemia is based on the level of serum potassium. ECG is useful in identifying the more severe consequences. A high dosage of diuretics and concomitant use of other drugs that increase the risk of potassium depletion or cardiac arrhythmias can increase the risk of cardiovascular events and mortality. Thiazide-induced potassium depletion may cause dysglycaemia. The risk of thiazide-induced hypokalaemia is higher in women and in black people. Reducing diuretic dose and potassium supplementation are the most direct and effective therapies for hypokalaemia. Combining with a potassium-sparing diuretic or blocker of the renin-angiotensin system also reduces the risk of hypokalaemia. Lowering salt intake and increasing intake of vegetables and fruits help to reduce blood pressure as well as prevent hypokalaemia.

Blood Purification Techniques, Inflammatory Mediators and Mortality in COVID-19 Patients.

BACKGROUND: Inflammatory mediators are an important component in the pathophysiology of the coronavirus disease 2019 (COVID-19). This study aimed to assess the effects of reducing inflammatory mediators using hemoperfusion (HP) and continuous renal replacement therapy (CRRT) on the mortality of patients with COVID-19. MATERIALS AND METHODS: Twelve patients with confirmed diagnosis of COVID-19 were included. All patients had acute respiratory distress syndrome (ARDS). Patients were divided into three groups, namely, HP, CRRT and HP+CRRT. The primary outcome was mortality and the secondary outcomes were oxygenation and reduction in inflammatory mediators at the end of the study. RESULTS: Patients were not different at baseline in demographics, inflammatory cytokine levels, and the level of acute phase reactants. Half of the patients (3 out of 6) in the HP+CRRT group survived along with the survival of one patient (1 out of 2) in the HP group. All four patients in the CRRT group died. Serum creatinine (SCr), Interleukin-1 (IL1), Interleukin-6 (IL6), Interleukin-8 (IL8), partial pressure of oxygen (PaO2), O2 saturation (O2 sat), and hemodynamic parameters improved over time in HP+CRRT and CRRT groups, but no significant difference was observed in the HP group (All Ps > 0.05). CONCLUSION: Combined HP and CRRT demonstrated the best result in terms of mortality, reduction of inflammatory mediators and oxygenation. Further investigations are needed to explore the role of HP+CRRT in COVID-19 patients.

Review of Viral Testing (Polymerase Chain Reaction) and Antibody/Serology Testing for Severe Acute Respiratory Syndrome-Coronavirus-2 for the Intensivist.

OBJECTIVE: As the severe acute respiratory syndrome-coronavirus-2 pandemic develops, assays to detect the virus and infection caused by it are needed for diagnosis and management. To describe to clinicians how each assay is performed, what each assay detects, and the benefits and limitations of each assay. DATA SOURCES: Published literature and internet. STUDY SELECTION: As well done, relevant and recent as possible. DATA EXTRACTION: Sources were read to extract data from them. DATA SYNTHESIS: Was synthesized by all coauthors. CONCLUSIONS: Available assays test for current or previous severe acute respiratory syndrome-coronavirus-2 infection. Nucleic acid assays such as quantitative, or real-time, polymerase chain reaction and loop-mediated isothermal amplification are ideal for acute diagnosis with polymerase chain reaction testing remaining the "gold standard" to diagnose acute infection by severe acute respiratory syndrome-coronavirus-2, specifically the presence of viral RNA. Assays that detect serum antibodies can theoretically diagnose both acute and remote infection but require time for the patient to develop immunity and may detect nonspecific antibodies. Antibody assays that quantitatively measure neutralizing antibodies are needed to test efficacy of convalescent plasma therapy but are more specialized.

Preliminary Data on COVID-19 in Patients with Hemoglobinopathies: A Multicentre ICET-A Study.

OBJECTIVES: This study aims to investigate, retrospectively, the epidemiological and clinical characteristics, laboratory results, radiologic findings, and outcomes of COVID-19 in patients with transfusion-dependent ß thalassemia major (TM), ß-thalassemia intermedia (TI) and sickle cell disease (SCD). DESIGN: A total of 17 Centers, from 10 countries, following 9,499 patients with hemoglobinopathies, participated in the survey. MAIN OUTCOME DATA: Clinical, laboratory, and radiologic findings and outcomes of patients with COVID-19 were collected from medical records and summarized. RESULTS: A total of 13 patients, 7 with TM, 3 with TI, and 3 with SCD, with confirmed COVID-19, were identified in 6 Centers from different countries. The overall mean age of patients was 33.7±12.3 years (range:13-66); 9/13 (69.2%) patients were females. Six patients had pneumonia, and 4 needed oxygen therapy. Increased C-reactive protein (6/10), high serum lactate dehydrogenase (LDH; 6/10), and erythrocyte sedimentation rate (ESR; 6/10) were the most common laboratory findings. 6/10 patients had an exacerbation of anemia (2 with SCD). In the majority of patients, the course of COVID-19 was moderate (6/10) and severe in 3/10 patients. A 30-year-old female with TM, developed a critical SARS-CoV-2 infection, followed by death in an Intensive Care Unit. In one Center (Oman), the majority of suspected cases were observed in patients with SCD between the age of 21 and 40 years. A rapid clinical improvement of tachypnea/dyspnea and oxygen saturation was observed, after red blood cell exchange transfusion, in a young girl with SCD and worsening of anemia (Hb level from 9.2 g/dl to 6.1g/dl). CONCLUSIONS: The data presented in this survey permit an early assessment of the clinical characteristics of COVID 19 in different countries. 70% of symptomatic patients with COVID- 19 required hospitalization. The presence of associated co-morbidities can aggravate the severity of COVID- 19, leading to a poorer prognosis irrespective of age.

Laboratory Parameters in Detection of COVID-19 Patients with Positive RT-PCR; a Diagnostic Accuracy Study.

INTRODUCTION: The role of laboratory parameters in screening of COVID-19 cases has not been definitely established. This study aimed to evaluate the accuracy of laboratory parameters in predicting cases with positive RT-PCR for COVID-19. METHODS: This diagnostic accuracy study was conducted on suspected COVID-19 patients, who presented to Behpooyan Clinic Medical center in Tehran (Iran) from 22 February to 14 March, 2020. Patients were divided into two groups based on the results of real time reverse transcriptase-polymerase chain reaction (RT-PCR) for COVID-19, and the accuracy of different laboratory parameters in predicting cases with positive RT-PCR was evaluated using area under the ROC curve (AUC). RESULTS: Two hundred cases with the mean age of 41.3± 14.6 (range: 19-78) years were studied (0.53% male). The result of RT-PCR for COVID-19 was positive in 70 (35%) cases. Patients with positive RT-PCR had significantly higher neutrophil (NEU) count (p = 0.0001), and C-reactive protein (CRP) (p = 0.04), lactate dehydrogenase (LDH) (p = 0.0001), aspartate aminotransferase (AST) (p = 0.001), alanine aminotransferase (ALT) (p = 0.0001), and Urea (p = 0.001) levels in serum. In addition, patients with positive RT-PCR had lower white blood cell (WBC) count (p = 0.0001) and serum albumin level (p = 0.0001) compared to others. ALT (AUC = 0.879), CRP (AUC = 0.870), NEU (AUC = 0.858), LDH (AUC = 0.835), and Urea (AUC = 0.835) had very good accuracy in predicting cases with positive RT-PCR for COVID-19, respectively. CONCLUSION: Our findings suggest that level of LDH, CRP, ALT and NEU can be used to predict the result of COVID-19 test. They can help in detection of COVID-19 patients.

Antibody Responses to Severe Acute Respiratory Syndrome Coronavirus 2 in the Serum and Cerebrospinal Fluid of Patients With Coronavirus Disease 2019 and Neurological Symptoms.

Antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in serum and cerebrospinal fluid (CSF) samples from 16 patients with coronavirus disease 2019 and neurological symptoms were assessed using 2 independent methods. Immunoglobulin G (IgG) specific for the virus spike protein was found in 81% of patients in serum and in 56% in CSF. SARS-CoV-2 IgG in CSF was observed in 2 patients with negative serological findings. Levels of IgG in both serum and CSF were associated with disease severity (P < .05). All patients with elevated markers of central nervous system damage in CSF also had CSF antibodies (P = .002), and CSF antibodies had the highest predictive value for neuronal damage markers of all tested clinical variables.

Systematic review of cases of acute myelitis in individuals with COVID-19.

BACKGROUND AND PURPOSE: An incremental number of cases of acute transverse myelitis (ATM) in individuals with ongoing or recent coronavirus disease 2019 (COVID-19) have been reported. METHODS: A systematic review was performed of cases of ATM described in the context of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by screening both articles published and in preprint. RESULTS: Twenty cases were identified. There was a slight male predominance (60.0%) and the median age was 56 years. Neurological symptoms first manifested after a mean of 10.3 days from the first onset of classical, mostly respiratory symptoms of COVID-19. Overall, COVID-19 severity was relatively mild. Polymerase chain reaction of cerebrospinal fluid for SARS-CoV-2 was negative in all 14 cases examined. Cerebrospinal fluid findings reflected an inflammatory process in most instances (77.8%). Aquaporin-4 and myelin oligodendrocyte protein antibodies in serum (tested in 10 and nine cases, respectively) were negative. On magnetic resonance imaging, the spinal cord lesions spanned a mean of 9.8 vertebral segments, necrotic-hemorrhagic transformation was present in three cases and two individuals had additional acute motor axonal neuropathy. More than half of the patients received a second immunotherapy regimen. Over a limited follow-up period of several weeks, 90% of individuals recovered either partially or near fully. CONCLUSION: Although causality cannot readily be inferred, it is possible that cases of ATM occur para- or post-infectiously in COVID-19. All identified reports are anecdotal and case descriptions are heterogeneous. Whether the condition and the observed radiological characteristics are specific to SARS-CoV-2 infection needs to be clarified.

Development and validation of a predictive model of in-hospital mortality in COVID-19 patients.

We retrospectively evaluated 2879 hospitalized COVID-19 patients from four hospitals to evaluate the ability of demographic data, medical history, and on-admission laboratory parameters to predict in-hospital mortality. Association of previously published risk factors (age, gender, arterial hypertension, diabetes mellitus, smoking habit, obesity, renal failure, cardiovascular/ pulmonary diseases, serum ferritin, lymphocyte count, APTT, PT, fibrinogen, D-dimer, and platelet count) with death was tested by a multivariate logistic regression, and a predictive model was created, with further validation in an independent sample. A total of 2070 hospitalized COVID-19 patients were finally included in the multivariable analysis. Age 61-70 years (p<0.001; OR: 7.69; 95%CI: 2.93 to 20.14), age 71-80 years (p<0.001; OR: 14.99; 95%CI: 5.88 to 38.22), age >80 years (p<0.001; OR: 36.78; 95%CI: 14.42 to 93.85), male gender (p<0.001; OR: 1.84; 95%CI: 1.31 to 2.58), D-dimer levels >2 ULN (p = 0.003; OR: 1.79; 95%CI: 1.22 to 2.62), and prolonged PT (p<0.001; OR: 2.18; 95%CI: 1.49 to 3.18) were independently associated with increased in-hospital mortality. A predictive model performed with these parameters showed an AUC of 0.81 in the development cohort (n = 1270) [sensitivity of 95.83%, specificity of 41.46%, negative predictive value of 98.01%, and positive predictive value of 24.85%]. These results were then validated in an independent data sample (n = 800). Our predictive model of in-hospital mortality of COVID-19 patients has been developed, calibrated and validated. The model (MRS-COVID) included age, male gender, and on-admission coagulopathy markers as positively correlated factors with fatal outcome.

A propensity score-matched analysis of mortality in solid organ transplant patients with COVID-19 compared to non-solid organ transplant patients.

In the context of COVID-19 pandemic, we aimed to analyze the epidemiology, clinical characteristics, risk factors for mortality and impact of COVID-19 on outcomes of solid organ transplant (SOT) recipients compared to a cohort of non transplant patients, evaluating if transplantation could be considered a risk factor for mortality. From March to May 2020, 261 hospitalized patients with COVID-19 pneumonia were evaluated, including 41 SOT recipients. Of these, thirty-two were kidney recipients, 4 liver, 3 heart and 2 combined kidney-liver transplants. Median time from transplantation to COVID-19 diagnosis was 6 years. Thirteen SOT recipients (32%) required Intensive Care Unit (ICU) admission and 5 patients died (12%). Using a propensity score match analysis, we found no significant differences between SOT recipients and non-transplant patients. Older age (OR 1.142; 95% [CI 1.08-1.197]) higher levels of C-reactive protein (OR 3.068; 95% [CI 1.22-7.71]) and levels of serum creatinine on admission (OR 3.048 95% [CI 1.22-7.57]) were associated with higher mortality. The clinical outcomes of SARS-CoV-2 infection in our cohort of SOT recipients appear to be similar to that observed in the non-transplant population. Older age, higher levels of C-reactive protein and serum creatinine were associated with higher mortality, whereas SOT was not associated with worse outcomes.

T-Helper Cell Subset Response Is a Determining Factor in COVID-19 Progression.

The immune response type organized against viral infection is determinant in the prognosis of some infections. This work has aimed to study Th polarization in acute COVID-19 and its possible association with the outcome through an observational prospective study. Fifty-eight COVID-19 patients were recruited in the Medicine Department of the hospital "12 de Octubre," 55 patients remaining after losses to follow-up. Four groups were established according to maximum degree of disease progression. T-helper cell percentages and phenotypes, analyzed by flow cytometer, and serum cytokines levels, analyzed by Luminex, were evaluated when the microbiological diagnosis (acute phase) of the disease was obtained. Our study found a significant reduction of %Th1 and %Th17 cells with higher activated %Th2 cells in the COVID-19 patients compared with reference population. A higher percent of senescent Th2 cells was found in the patients who died than in those who survived. Senescent Th2 cell percentage was an independent risk factor for death (OR: 13.88) accompanied by the numbers of total lymphocytes (OR: 0.15) with an AUC of 0.879. COVID-19 patients showed a profile of pro-inflammatory serum cytokines compared to controls, with higher levels of IL-2, IL-6, IL-15, and IP-10. IL-10 and IL-13 were also elevated in patients compared to controls. Patients who did not survive presented significantly higher levels of IL-15 than those who recovered. No significant differences were observed according to disease progression groups. The study has shown that increased levels of IL-15 and a high Th2 response are associated with a fatal outcome of the disease.

A Machine Learning Prediction Model of Respiratory Failure Within 48 Hours of Patient Admission for COVID-19: Model Development and Validation.

BACKGROUND: Predicting early respiratory failure due to COVID-19 can help triage patients to higher levels of care, allocate scarce resources, and reduce morbidity and mortality by appropriately monitoring and treating the patients at greatest risk for deterioration. Given the complexity of COVID-19, machine learning approaches may support clinical decision making for patients with this disease. OBJECTIVE: Our objective is to derive a machine learning model that predicts respiratory failure within 48 hours of admission based on data from the emergency department. METHODS: Data were collected from patients with COVID-19 who were admitted to Northwell Health acute care hospitals and were discharged, died, or spent a minimum of 48 hours in the hospital between March 1 and May 11, 2020. Of 11,525 patients, 933 (8.1%) were placed on invasive mechanical ventilation within 48 hours of admission. Variables used by the models included clinical and laboratory data commonly collected in the emergency department. We trained and validated three predictive models (two based on XGBoost and one that used logistic regression) using cross-hospital validation. We compared model performance among all three models as well as an established early warning score (Modified Early Warning Score) using receiver operating characteristic curves, precision-recall curves, and other metrics. RESULTS: The XGBoost model had the highest mean accuracy (0.919; area under the curve=0.77), outperforming the other two models as well as the Modified Early Warning Score. Important predictor variables included the type of oxygen delivery used in the emergency department, patient age, Emergency Severity Index level, respiratory rate, serum lactate, and demographic characteristics. CONCLUSIONS: The XGBoost model had high predictive accuracy, outperforming other early warning scores. The clinical plausibility and predictive ability of XGBoost suggest that the model could be used to predict 48-hour respiratory failure in admitted patients with COVID-19.

Assessment of Galectin-1, Galectin-3, and Prostaglandin E2 Levels in Patients with COVID-19.

It is important to determine the inflammatory biomarkers in the severity of coronavirus disease 2019 (COVID-19) with the emergence of the pandemic. Galectins and prostaglandins play important roles in the regulation of immune and inflammatory responses. Therefore, this study aimed to investigate Galectin-1 (Gal-1), Galectin-3 (Gal-3), and prostaglandin E2 (PGE2) levels in patients with COVID-19. Serum concentrations of Gal-1, Gal-3, and PGE2 were measured using enzyme-linked immunosorbent assay on 84 patients with COVID-19 (severe = 29 and nonsevere = 55) and 56 healthy controls. In this study, increased levels of Gal-1 (median, 9.86, 6.35, and 3.67 ng/mL), Gal-3 (median, 415.31, 326.33, and 243.13 pg/mL), and PGE2 (median, 193.17, 192.58, and 124.62 pg/mL) levels were found in patients with COVID-19 than in healthy controls (P < 0.001 for all). In the severe disease group, Gal-3 levels were higher, while no differences were noted in Gal-1 and PGE2 levels (P = 0.011, P = 0.263, and P = 0.921, respectively). Serum levels of Gal-1 were positively correlated with those of Gal-3 (P = 0.871 and P < 0.001). Gal-3, C-reactive protein, lymphocyte count, and age were found as independent predictors of disease severity (P = 0.002, P = 0.001, P = 0.007, and P = 0.003, respectively). With the emergence of effective drug needs in the COVID-19 pandemic, differentiation of severe disease is important. Therefore, Gal-3 could be a potential prognostic biomarker of COVID-19.

Increased Glucocorticoid Receptor Alpha Expression and Signaling in Critically Ill Coronavirus Disease 2019 Patients.

OBJECTIVES: Critical illness is characterized by increased serum cortisol concentrations and bioavailability resulting from the activation of the hypothalamic-pituitary-adrenal axis, which constitutes an essential part of the stress response. The actions of glucocorticoids are mediated by a ubiquitous intracellular receptor protein, the glucocorticoid receptor. So far, data on coronavirus disease 2019 and glucocorticoid receptor alpha expression are lacking. DESIGN: Prospective observational study. SETTING: One academic multidisciplinary ICU. SUBJECTS: Twenty-six adult coronavirus disease 2019 patients; 33 adult noncoronavirus disease 2019 patients, matched for age, sex, and disease severity, constituted the control group. All patients were steroid-free. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Glucocorticoid receptor alpha, glucocorticoid-inducible leucine zipper expression, and serum cortisol were measured on ICU admission. In coronavirus disease 2019 patients, glucocorticoid receptor alpha and glucocorticoid-inducible leucine zipper messenger RNA expression were upregulated (4.7-fold, p < 0.01 and 14-fold, p < 0.0001, respectively), and cortisol was higher (20.3 vs 14.3 µg/dL, p < 0.01) compared with the control group. CONCLUSIONS: ICU coronavirus disease 2019 patients showed upregulated glucocorticoid receptor alpha and glucocorticoid-inducible leucine zipper expression, along with cortisol levels, compared with ICU noncoronavirus disease 2019 patients. Thus, on ICU admission, critical coronavirus disease 2019 appears to be associated with hypercortisolemia, and increased synthesis of glucocorticoid receptor alpha and induced proteins.

Pharmacokinetic/Pharmacodynamic Dosage Individualization of Cefepime in Critically Ill Patients: A Case Study.

OBJECTIVE: The authors report on a case of a 59-year-old man hospitalized in the intensive care unit because of severe SARS-COV-2 infection (COVID-19). BACKGROUND: The patient had several comorbidities, including liver cirrhosis. He developed ventilation-associated bacterial pneumonia for which he was administered cefepime at an initial dose of 2 g/8 hours. Therapeutic drug monitoring was performed, showing overexposure with an initial trough concentration of >60 mg/L. METHODS: Analysis of pharmacokinetic data and model-based dose adjustment was performed using BestDose software. RESULTS: The patient had unexpected pharmacokinetic parameter values. Serum creatinine was only moderately increased, whereas measured creatinine clearance based on urine collection showed impaired renal function. Bacterial minimum inhibitory concentration was also considered in the dosing decisions. After dose reduction to 0.5 g/8 hours, the cefepime trough concentration progressively declined and reached the target values by the end of the therapy. A post-hoc analysis provided a different interpretation of drug overexposure. CONCLUSION: This case report illustrates how physiological, microbiological, and drug concentration data can be used for model-based dosage individualization of cefepime in intensive care unit patients.

Symptomatic Severe Acute Respiratory Syndrome Coronavirus 2 Reinfection of a Healthcare Worker in a Belgian Nosocomial Outbreak Despite Primary Neutralizing Antibody Response.

BACKGROUND: It is currently unclear whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection will remain a rare event, only occurring in individuals who fail to mount an effective immune response, or whether it will occur more frequently when humoral immunity wanes following primary infection. METHODS: A case of reinfection was observed in a Belgian nosocomial outbreak involving 3 patients and 2 healthcare workers. To distinguish reinfection from persistent infection and detect potential transmission clusters, whole genome sequencing was performed on nasopharyngeal swabs of all individuals including the reinfection case's first episode. Immunoglobulin A, immunoglobulin M, and immunoglobulin G (IgG) and neutralizing antibody responses were quantified in serum of all individuals, and viral infectiousness was measured in the swabs of the reinfection case. RESULTS: Reinfection was confirmed in a young, immunocompetent healthcare worker as viral genomes derived from the first and second episode belonged to different SARS-CoV-2 clades. The symptomatic reinfection occurred after an interval of 185 days, despite the development of an effective humoral immune response following symptomatic primary infection. The second episode, however, was milder and characterized by a fast rise in serum IgG and neutralizing antibodies. Although contact tracing and viral culture remained inconclusive, the healthcare worker formed a transmission cluster with 3 patients and showed evidence of virus replication but not of neutralizing antibodies in her nasopharyngeal swabs. CONCLUSIONS: If this case is representative of most patients with coronavirus disease 2019, long-lived protective immunity against SARS-CoV-2 after primary infection might not be likely.

Changes of serum IL-10, IL-1ß, IL-6, MCP-1, TNF-α, IP-10 and IL-4 in COVID-19 patients.

BACKGROUND AND PURPOSE: Studies have shown that some cytokines in COVID-19 patients were elevated. This study aims to assess whether IL-10, IL-1ß, IL-6, MCP-1, TNF-α, IP-10 and IL-4 serve as potential diagnostic biomarkers of COVID-19. METHODS: The above serum cytokines in COVID-19 patients and non-COVID-19 patients were detected by ELISA and SARS-CoV-2 IgM and IgG were detected by the chemiluminescence method. The independent-sample Mann-Whitney U test was utilised to compare cytokine levels in different groups and courses, the Levene T-test and T'-test were utilised to compare they in different genders and the Spearman correlation test was utilised to analyse the correlation between the cytokine levels with ages and SARS-CoV-2 IgG and IgM. RESULTS: Serum levels of IL-10, IL-1ß, MCP-1, TNF-α and IL-4 in COVID-19 patients were significantly higher than those in non-COVID-19 patients, while IL-6 were only significantly higher than in healthy people, IP-10 were significantly lower than in other diseases patients. AUCs of COVID-19 diagnosed by IL-10, IL-1ß, IL-6, MCP-1, TNF-α, IP-10 and IL-4 were 0.735, 0.775, 0.595, 0.821, 0.848, 0.38 and 0.682, respectively. In the COVID-19 patients' serum, the levels of IL-10 and MCP-1 of male were noticeably higher than those of female, and all cytokines were significantly positively correlated with age, IL-1ß and IL-4 were significantly negatively correlated with SARS-CoV-2 IgM, while IL-10, IL-1ß, IL-6, TNF- and IP-10 were significantly negatively correlated with SARS-CoV-2 IgG. IL-10 on 43-56 days was significantly lower than at 29-42 days, TNF-α at 15-42 days was significantly higher than at 0-14 days, IP-10 at 0-14 days was the highest and IL-4 at 29-42 days was significantly higher than at 0-14 days. CONCLUSIONS: The detection of IL-10, IL-1 ß, IL-6, MCP-1, TNF-α and IL-4 would assist the clinical study of COVID-19, and IP-10 may be the cytokine of early elevation in COVID-19 patients.

7-Ketocholesterol: Effects on viral infections and hypothetical contribution in COVID-19.

7-Ketocholesterol, which is one of the earliest cholesterol oxidization products identified, is essentially formed by the auto-oxidation of cholesterol. In the body, 7-ketocholesterol is both provided by food and produced endogenously. This pro-oxidant and pro-inflammatory molecule, which can activate apoptosis and autophagy at high concentrations, is an abundant component of oxidized Low Density Lipoproteins. 7-Ketocholesterol appears to significantly contribute to the development of age-related diseases (cardiovascular diseases, age-related macular degeneration, and Alzheimer's disease), chronic inflammatory bowel diseases and to certain cancers. Recent studies have also shown that 7-ketocholesterol has anti-viral activities, including on SARS-CoV-2, which are, however, lower than those of oxysterols resulting from the oxidation of cholesterol on the side chain. Furthermore, 7-ketocholesterol is increased in the serum of moderately and severely affected COVID-19 patients. In the case of COVID-19, it can be assumed that the antiviral activity of 7-ketocholesterol could be counterbalanced by its toxic effects, including pro-oxidant, pro-inflammatory and pro-coagulant activities that might promote the induction of cell death in alveolar cells. It is therefore suggested that this oxysterol might be involved in the pathophysiology of COVID-19 by contributing to the acute respiratory distress syndrome and promoting a deleterious, even fatal outcome. Thus, 7-ketocholesterol could possibly constitute a lipid biomarker of COVID-19 outcome and counteracting its toxic effects with adjuvant therapies might have beneficial effects in COVID-19 patients.

The Significance of COVID-19 Immunological Status in Severe Neurological Complications and Multiple Sclerosis-A Literature Review.

SARS-CoV-2/Coronavirus 2019 (COVID-19) is responsible for the pandemic, which started in December 2019. In addition to the typical respiratory symptoms, this virus also causes other severe complications, including neurological ones. In diagnostics, serological and polymerase chain reaction tests are useful not only in detecting past infections but can also predict the response to vaccination. It is now believed that an immune mechanism rather than direct viral neuroinvasion is responsible for neurological symptoms. For this reason, it is important to assess the presence of antibodies not only in the serum but also in the cerebrospinal fluid (CSF), especially in the case of neuro-COVID. A particular group of patients are people with multiple sclerosis (MS) whose disease-modifying drugs weaken the immune system and lead to an unpredictable serological response to SARS-CoV-2 infection. Based on available data, the article summarizes the current serological information concerning COVID-19 in CSF in patients with severe neurological complications and in those with MS.

Serum sodium alterations in SARS CoV-2 (COVID-19) infection: impact on patient outcome.

OBJECTIVE: Hyponatremia is the most common electrolyte disorder in hospitalized patients and occurs in about 30% of patients with pneumonia. Hyponatremia has been associated with a worse outcome in several pathologic conditions The main objective of this study was to determine whether serum sodium alterations may be independent predictors of the outcome of hospitalized COVID-19 patients. DESIGN AND METHODS: In this observational study, data from 441 laboratory-confirmed COVID-19 patients admitted to a University Hospital were collected. After excluding 61 patients (no serum sodium at admission available, saline solution infusion before sodium assessment, transfer from another hospital), data from 380 patients were analyzed. RESULTS: 274 (72.1%) patients had normonatremia at admission, 87 (22.9%) patients had hyponatremia and 19 (5%) patients had hypernatremia. We found an inverse correlation between serum sodium and IL-6, whereas a direct correlation between serum sodium and PaO2/FiO2 ratio was observed. Patients with hyponatremia had a higher prevalence of non-invasive ventilation and ICU transfer than those with normonatremia or hypernatremia. Hyponatremia was an independent predictor of in-hospital mortality (2.7-fold increase vs normonatremia) and each mEq/L of serum sodium reduction was associated with a 14.4% increased risk of death. CONCLUSIONS: These results suggest that serum sodium at admission may be considered as an early prognostic marker of disease severity in hospitalized COVID-19 patients.