Boosting the Immune System with Vitamin D: Special Focus on Prevention of COVID-19 and Complications

In addition to the classical functions of the musculoskeletal system and calcium homeostasis, the function of vitamin D as an immune modulator is well established. The vitamin D receptors and enzymes that metabolize vitamin D are ubiquitously expressed in most cells in the body, including T and B lymphocytes, antigen-presenting cells, monocytes, macrophages and natural killer cells that trigger immune and antimicrobial responses. Many in vitro and in vivo studies revealed that vitamin D promotes tolerogenic immunological action and immune modulation. Vitamin D adequacy positively influences the expression and release of antimicrobial peptides, such as cathelicidin, defensin, and anti-inflammatory cytokines, and reduces the expression of proinflammatory cytokines. Evidence suggestss that vitamin D's protective immunogenic actions reduce the risk, complications, and death from COVID-19. On the contrary, vitamin D deficiency worsened the clinical outcomes of viral respiratory diseases and the COVID-19-related cytokine storm, acute respiratory distress syndrome, and death. The study revealed the need for more preclinical studies and focused on well-designed clinical trials with adequate sizes to understand the role of vitamin D on the pathophysiology of immune disorders and mechanisms of subduing microbial infections, including COVID-19.Copyright © 2023 Bentham Science Publishers.

Comparative Study of Serum Electrolytes in Covid-19 and Healthy Patients in Tertiary Care Center, Karimnagar

Introduction- Electrolyte balance of the body is maintained by renin angiotensin aldosterone system. Some previous studies suggested that COVID-19 is associated with gastrointestinal symptoms, such as diarrhea and vomiting. This may results in electrolyte disturbances in patients. Electrolytes in body like sodium (Na), potassium (K). Chloride (Cl) plays an important physiological role in maintaining acid base and water balance of cells of the body. Aims and objectives: Our study aimed to compare some electrolyte between covid 19 and non-covid patients retrospectively. Material(s) and Method(s): This retrospective study included total 57 males and 43 females in the age group of 28 to 65 years. The results were compared with 100 age and sex matched healthy controls. Estimation of serum electrolytes was done with the collected venous blood samples using the ion selective electrode technique in an electrolyte analyzer. Analysis was done using SPSS V 25 Software. Chi-square and t-test were used to see association and difference between two variable respectively. Result(s): We have found that covid 19 is associated with low levels of electrolytes like Na, K, Cl. Chloride levels in both the groups was not statistically significant. But Hyponatremia and Hypokalemia were observed in cases group with high statical Signficance. Conclusion(s): Study found that electrolytes deterioration in these patients play a critical role in patients management. Thus a monitoring of electrolyte is essential throughout their illness to manage covid patients to improve their quality of life.Copyright © 2020 Ubiquity Press. All rights reserved.

Short-term impact of COVID-19 on health-related physical fitness in hospitalized and home-treated patients

Assessment of health-related physical fitness (PF) and body composition (BC) may yield relevant information on body function in patients who have been affected by Coronavirus disease-2019 (COVID-19). Aim of our study was to evaluate the short-term effects of COVID-19 on physical fitness in a real-life cohort of outpatients including hospitalized and home-treated patients. Sixty-four patients (M=36;mean age 56+/-13.5 yrs) previously affected by COVID-19 (25 hospitalized vs. 39 hometreated) in the 3-6 months preceding the study measurements were enrolled. PF was evaluated with the following tests: handgrip strength (HGS), gait speed (GAIT), sit-to-stand (STS), timed up and go (TUG) and Short physical performance battery (SPPB). Phase angle (PhA) was measured by bioelectrical impedance analysis (BIA) as a proxy marker of fat-free mass composition in terms of body cell mass and cell integrity. Poor PF performance was observed in 38% of subjects for HGS, 55% for GAIT, 30% for STS, 38% for TUG, and 70% for SPPB, while low values of PA were observed in 42% of the study sample in comparison with international cut-offs. The presence of 3-5 impaired values out of five was observed in 38% of patients. All PF tests (and even more the number of abnormal PF tests) consistently correlated with PhA. No differences were reported between hospitalized and home-treated patients. In the short-run, COVID-19 causes a worsening of physical fitness regardless of baseline disease severity. More research is required to systematically measure the extent of functional impairments in COVID-19 and to address whether and how rehabilitation can promote post-infection recovery.

Characteristics of Vaccinated Kidney Transplant Recipients Requiring Hospitalization for COVID-19 Infection

Background: Studies have shown suboptimal immunological response to COVID-19 vaccination in kidney transplant recipients (KTRs). We aimed to describe specific characteristics of vaccinated KTRs who required hospitalization for COVID-19 infection. Method(s): In this descriptive study utilizing chart review, we identified KTRs who were hospitalized for COVID-19 infection between March 2020 and January 2022 within our integrated health network. Demographic characteristics were identified for KTRs who received >=2 COVID-19 vaccine doses prior to hospitalization. Result(s): Among 114 KTRs admitted to the hospital with COVID-19 infection, 44 (39%) had received 2 or more vaccine doses prior to hospitalization including 35 patients who received 2 vaccines and 9 who received >2 vaccines. Vaccinated patients requiring hospitalization were generally older with male predominance. Prevalent comorbidities included overweight/obesity, hypertension, and diabetes. Among these patients, 18% required dialysis and 90-day mortality was 20% (Table). Conclusion(s): Despite receiving at least 2 doses of preventative vaccination, many KTRs developed COVID-19 infection requiring hospitalization. Our findings are consistent with studies showing reduced antibody and cell mediated response to vaccination in KTRs. Every effort should be made to educate and encourage this vulnerable population about measures to prevent infection, especially vaccination with subsequent booster doses.

Retinas of human donors with COVID-19 disease show morphological alterations and signs of inflammation including glial activation

Purpose : Different signs of inflammation have been described in the brains of COVID-19 patients. In the retina, the fundus eye exam of these patients shows cotton wool spots, microhemorrhages, and a decrease in vascular density. However, morphological alterations of retinal cells in these patients are unknown. Thus, the aim was to analyze the morphological changes of the retinal cells from human donors with COVID-19 to establish several stages of response to damage in these cells and to define correlations with clinical parameters. Methods : The retinas of human donors with COVID-19 (n = 16) and control subjects (n = 12) obtained from the General University Hospital Consortium of Valencia were analyzed. Immunohistochemical stainings were performed on transversal sections or flat-mount retinas to study photoreceptors, microglial cells, Müller cells, astrocytes, and the presence of ACE2. TUNEL assays and confocal microscopy imaging were carried out. Correlations were calculated between retinal and clinical parameters. Results : Mean age of COVID-19 and control group were 80±10 and 70±8 years respectively. Müller cells, outer segment of cones and retinal pigment epithelium presented ACE2 staining. Larger staining of ACE2 and CRALBP was observed in cell bodies of Müller cells in COVID group. Disorganization of honeycomb-like pattern formed by Müller cells in the outer nuclear layer and disruption of external limiting membrane was found in the 81.3% of COVID patients. The 56.3% of COVID patients showed gliosis compared to controls (40%). COVID-19 retinas also presented epiretinal membranes and astrocytes protruding to vitreous humor. The 93.8% of COVID-19 patients had activated or ameboid-shape microglia. Microglial nodules around vessels and a reduction of the area occupied by microglia in these retinas were observed. COVID-19 group showed a more severe degeneration of cones. Cone degeneration correlated with Müller cell activation. Age of COVID patients correlated inversely with total retinal degeneration. Conclusions : Morphological alterations in the cone photoreceptors as well as glial activation showing an inflammatory state of the retina were observed in COVID-19 patients.

Antibodies and cell immunity after vaccination with tozinameran (BNT162b2) in workers of National Comprehensive Cancer Center (NCCC) in Slovakia

Background: Vaccination remains the leading strategy against Covid-19 worldwide. BNT 162b2 (tozinameran) belongs among first licensed vaccines with good efficacy. However, the role of monitoring both, antibodies and cell immunity after vaccination remains unclear. Methods: We conducted a 6-month prospective study involving vaccinated workers of NCCC in Slovakia who were tested for the presence of neutralizing antibodies and cell immunity after second dose of tozinameran. SARS-CoV-2 IgG antibodies were detected by the Atellica IM sCOVG, a fully automated 2-step sandwich immunoassay using indirect chemiluminescent technology. Blood samples were tested by two IGRA tests (Quantiferon RUO and CoviFeron) to assess interferon-γ (IFN-γ) responses to SARS CoV-2 spike protein antigen and nucleocapsid protein antigen. Results were stratified by gender and body mass index. P values for categorical variables were calculated using χ2 or Fishers exact test. P values for continuous variables were calculated using T test and Wilcoxon-Mann-Whitney test. Value of statistical significance was set to 0.05. Data were analyzed using SAS 9.4 software. Results: Medical records of 94 respondents (71 females) were analyzed. Mean age was 40.2 years (23 - 62 years) and mean body mass index (BMI) ± standard error of mean (SEM) was 26.4±2.7 (21.3 - 31.7). Twenty-two (23.4 %) respondents had Covid-19 before first, 5 (5.3 %) before second, and 2 (2.15 %) after second dose of vaccine (P < 0.0001). IgG were tested 24.4±5.0, 50.2±12.1, and 187.9±12.8 days after second vaccination. IgG index progressively decline with corresponding values 126.81±40.34, 93.55±51.29, and 17.68±29.07 (P < 0.0001). Mean time from second vaccination to cell immunity testing was 157.2±101.3 days. Forty-eight (51.1 %) of respondents had negative, 6 (6.4 %) border line, and 40 (42.6 %) positive cell immunity (P < 0.0001). Conclusions: Our study confirmed the efficacy of tozinameran despite both, rapid decline of antibodies and absence of cell immunity in majority of subjects.

GLOMERULAR HYPERFILTRATION MAY CONTRIBUTE TO RENAL TROPISM AND KIDNEY INJURY IN COVID-19 BY UPREGULATING ACE2 IN HUMAN PODOCYTES

Objective: Apart from the respiratory system, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can potentially infect multiple other organs including podocytes in the kidney. The latter play a crucial role in glomerular filtration. Podocytes can be damaged by increased fluid flow shear stress (FFSS) of the ultrafiltrate in Bowman's space in the setting of glomerular hyperfiltration that occurs in disease states such as hypertension, diabetes or in several forms of chronic kidney disease. These conditions are associated with an increased risk of a more severe course of coronavirus disease 2019 (COVID-19) and mortality. Design and method: To assess the susceptibility of human podocytes (hPC) for SARS-CoV-2 infection in the context of hyperfiltration in vitro, we used a recently established model system (Streamer Shear Stress Device)) to mimic hyperfiltration by exposing hPC to increased FFSS of 1 dyne/cm2 for 2 h. In this setting we nalysed the effects of FFSS on mRNA expression of angiotensin I-converting enzyme 2 (ACE2) as the pivotal entry receptor for SARS-CoV-2 infection in hPC. Moreover, other potential critical host cell factors including transmembrane serine protease 2 (TMPRSS2), furin (FURIN), and neuropilin 1 (NRP1) were also assessed in parallel with changes of the F-actin fiber structure, i.e. an important cytoskeletal marker in hPC. Results: Under control conditions, hPC displayed long, parallel F-actin fibers crossing the entire cell body. After FFSS, an enrichment of cells that express F-actin in a cortically condensed pattern near the cell membrane was observed. FFSS induced a significant upregulation of ACE2 expression (about twofold) and of all other nalysed SARS-CoV-2 entry factors in hPC (p < 0.05, respectively compared to control conditions, Figure 1 with data plotted as log2fold change [FC]). Conclusions: Our data support a potential link between glomerular hyperfiltration, podocyte damage and renal tropism of SARS-CoV-2 that may contribute to kidney damage including albuminuria development in COVID-19 patients.

Coronavirus 2019:clinical and neuropathological aspects

Objective: To describe the clinicopathological correlations of 141 confirmed postmortem cases of coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome-coronavirus -2 (SARS-CoV-2). Background: Analysis of 50 cases of COVID-19 with available neuropathology revealed three CNS findings. First, hypoxia-ischemia does not account for all relevant neuropathological features. Second, elevated levels of circulating cytokines suggest activation of post-infectious immunity indicative of a cytokine storm, with increased hypercoagulability leading to a risk for thrombotic and hemorrhagic parenchymal tissue infarction. Third, a minority of cases have acute demyelinating encephalomyelitis-(ADEM) like features or indolent brainstem encephalitis. Such cases may present with early altered sensorium and brainstem signs. Fourth, SARS-CoV-2 staining could not be confirmed due to paucity of available tissue specimens. Design/Methods: Ninety-four additional cases with available postmortem CNS neuropathology showed four additional findings. Results: First, positive SARS-CoV-2 genome by PCR testing is present in brain tissues especially in olfactory bulb neurons and glial cells lending support to a route of entry into the CNS and the importance of early anosmia. Second, SARS-CoV-2-positive neurons appear to be TUNEL positive and caspase-positive, displaying reversible pT231 Tau localization in some cell soma that may be highly neurotoxic and a driver of tauopathy. Third, expression of ACE2 in oligodendrocytes is associated with viral entry, while TMPRSS2 and TMPRSS4 staining is implicated in pruning of viral-decorating spikes. Fourth, meningeal and interstitial brainstem inflammation by cytotoxic T-cells coincides with the localization of SARS-CoV-2 viral proteins in cranial nerves and interstitial areas of lower brainstem encephalitis. The detection of brain microglial activation and sparse perivascular and leptomeningeal T-cell infiltrates correlates with critical illness encephalopathy. Conclusions: Genetic diversity, recombination, and viral mutation carries the foreseeable risk of continued fatality due to the direct and indirect effects of SARS-CoV-2 that include inflammatory vasculopathy, encephalitis, silent infarctions, and critical illness encephalopathy.

SARS-CoV-2 SPIKE EXPRESSION at the SURFACE of INFECTED HUMAN AIRWAY EPITHELIAL CELLS

Background: Emerging evidence points out to potential benefits from Fc-mediated effector functions in SARS-CoV-2 infection. Some Fc-mediated effector functions such as antibody-dependent cellular cytotoxicity (ADCC) or antibody-dependent cellular phagocytosis (ADCP) require recognition of the antigen at the surface of infected cells. Methods: To evaluate the expression levels of SARS-CoV-2 Spike at the surface of infected airway epithelial cells, we developed an intracellular staining against SARS-CoV-2 nucleocapsid (N). This assay allows the distinction between infected versus uninfected cells. Human primary airway epithelial cells (pAECs) were infected with authentic SARS-CoV-2 D614G or Alpha variants. Infected cells were identified with an anti-N antibody and cell surface expression of Spike measured with the conformational-independent anti-S2 CV3-25 antibody. Results: We found robust SARS-CoV-2 Spike expression at the cell surface of pAECs. Infected cells were readily recognized with plasma from convalescent and vaccinated individuals. Importantly, recognition of SARS-CoV-2 infected cells strongly correlated with Fc-mediated effector functions measured in a cohort of vaccinated naïve and previously-infected individuals. Conclusion: Altogether, our findings further support the importance of measuring Fc-mediated effector function in infection and vaccination settings for SARS-CoV-2.