Implications of Vitamins in COVID-19 Prevention and Treatment through Immunomodulatory and Anti-Oxidative Mechanisms

Since the appearance of the coronavirus disease 2019 (COVID-19) and its announcement as a global pandemic, the search for prophylactic and therapeutic options have become a priority for governments and the scientific community. The approval of several vaccines against SARS-CoV-2 is being crucial to overcome this situation, although the victory will not be achieved while the whole population worldwide is not protected against the virus. This is why alternatives should be studied in order to successfully support the immune system before and during a possible infection. An optimal inflammatory and oxidative stress status depends on an adequate diet. Poor levels of several nutrients could be related to an impaired immune response and, therefore, an increased susceptibility to infection and serious outcomes. Vitamins exert a number of anti-microbial, immunomodulatory, anti-inflammatory, and antioxidant activities, which can be of use to fight against this and several other diseases (especially vitamin D and C). Even though they cannot be considered as a definitive therapeutic option, in part owing to the lack of solid conclusions from well-designed clinical trials, currently available evidence from similar respiratory diseases may indicate that it would be rational to deeply explore the use of vitamins during this global pandemic.

Association of monocyte HLA-DR expression over time with secondary infection in critically ill children: a prospective observational study

An impaired immune response could play a role in the acquisition of secondary infections in critically ill children. Human leukocyte antigen-DR expression on monocytes (mHLA-DR) has been proposed as marker to detect immunosuppression, but its potential to predict secondary infections in critically ill children is unclear. We aimed to assess the association between mHLA-DR expression at several timepoints and the change of mHLA-DR expression over time with the acquisition of secondary infections in critically ill children. In this prospective observational study, children < 18 years with fever and/or suspected infection (community-acquired or hospital-acquired) were included at a paediatric intensive care unit in the Netherlands. mHLA-DR expression was determined by flow cytometry on day 1, day 2–3 and day 4–7. The association between delta-mHLA-DR expression (difference between last and first measurement) and secondary infection was assessed by multivariable regression analysis, adjusted for age and Paediatric Logistic Organ Dysfunction-2 score. We included 104 patients at the PICU (median age 1.2 years [IQR 0.3–4.2]), of whom 28 patients (27%) developed a secondary infection. Compared to 93 healthy controls, mHLA-DR expression of critically ill children was significantly lower at all timepoints. mHLA-DR expression did not differ at any of the time points between patients with and without secondary infection. In addition, delta-mHLA-DR expression was not associated with secondary infection (aOR 1.00 [95% CI 0.96–1.04]).Conclusions: Our results confirm that infectious critically ill children have significantly lower mHLA-DR expression than controls. mHLA-DR expression was not associated with the acquisition of secondary infections. What is Known:• An impaired immune response, estimated by mHLA-DR expression, could play an essential role in the acquisition of secondary infections in critically ill children.• In critically ill children, large studies on the association of mHLA-DR expression with secondary infections are scarce. What is New:• Our study confirms that critically ill children have lower mHLA-DR expression than healthy controls.• mHLA-DR expression and change in mHLA-DR was not associated with the acquisition of secondary infection.

Two oppositely-charged sf3b1 mutations cause defective development, impaired immune response, and aberrant selection of intronic branch sites in Drosophila

SF3B1 mutations occur in many cancers, and the highly conserved His662 residue is one of the hotspot mutation sites. To address effects on splicing and development, we constructed strains carrying point mutations at the corresponding residue His698 in Drosophila using the CRISPR-Cas9 technique. Two mutations, H698D and H698R, were selected due to their frequent presence in patients and notable opposite charges. Both the sf3b1-H698D and–H698R mutant flies exhibit developmental defects, including less egg-laying, decreased hatching rates, delayed morphogenesis and shorter lifespans. Interestingly, the H698D mutant has decreased resistance to fungal infection, while the H698R mutant shows impaired climbing ability. Consistent with these phenotypes, further analysis of RNA-seq data finds altered expression of immune response genes and changed alternative splicing of muscle and neural-related genes in the two mutants, respectively. Expression of Mef2-RB, an isoform of Mef2 gene that was downregulated due to splicing changes caused by H698R, partly rescues the climbing defects of the sf3b1-H698R mutant. Lariat sequencing reveals that the two sf3b1-H698 mutations cause aberrant selection of multiple intronic branch sites, with the H698R mutant using far upstream branch sites in the changed alternative splicing events. This study provides in vivo evidence from Drosophila that elucidates how these SF3B1 hotspot mutations alter splicing and their consequences in development and in the immune system.

Co-infection of intestinal tuberculosis and mucormycosis in a patient with Down syndrome: a unique case report with literature review

Mucormycosis represents several unusual opportunistic infection caused by saprophytic aseptate fungi. There is a recent rise in cases of mucormycosis due to an increase in diabetic and immunodeficient patients like patients on long-term steroids, immunomodulators due to organ transplantation, malignancies, mainly haematological malignancies, and autoimmunity. Anatomically, mucormycosis can be localised most commonly as rhino-orbito-cerebral followed by pulmonary, disseminated, cutaneous and gastrointestinal, rarest being small intestinal. Patients with Down syndrome are immunodeficient due to their impaired immune response. Disseminated tuberculosis is also common in immunodeficient patients. We report a rare case of small intestinal mucormycosis in a patient with Down syndrome with coexisting intestinal tuberculosis. Due to the invasiveness of mucormycosis, the patient succumbed to death despite providing aggressive surgical debridement and medical management.

Impact of mass vaccination on SARS-CoV-2 infections among the total multiple sclerosis population receiving immunomodulatory disease-modifying therapies in England

This study aimed to understand changes in the risk of SARS-CoV-2 infection among all people with multiple sclerosis (MS) receiving immunomodulatory disease-modifying therapies (DMTs) in England, compared to the general population, following mass vaccination. Longitudinal data collected by the National Health Service (NHS) England on all MS DMT prescriptions and the UK Health Security Agency on all registered SARS-CoV-2 test results were analysed. The incidence rate ratio of SARS-CoV-2 infection among people with MS taking DMTs compared to the general population was calculated before (November 2020-January 2021) and after (July-August 2021) mass vaccination. Risk of SARS-CoV-2 infection among people on ocrelizumab or fingolimod compared to the general population increased following liberalisation of COVID-19 restrictions (during March-July 2021) despite mass vaccination. No changes were found with other DMTs. These findings converge with the impaired immune response to vaccines observed with ocrelizumab and fingolimod.

COVID19 vaccine type and humoral immune response in patients receiving dialysis

Background Patients on dialysis vaccinated with the attenuated adenovirus SARS-CoV-2 vaccine might mount an impaired response to vaccination. Methods We evaluated the humoral vaccination response among 2,099 fully vaccinated patients receiving dialysis. We used commercially available assays (Siemens) to assess prevalence of no response or diminished response to COVID-19 vaccination by vaccine type. We defined no seroconversion as lack of change from negative to positive in total RBD Ig antibody, no detectable response on semiquantitative RBD IgG antibody (index value <1) as no RBD IgG response, and a semiquantitative RBD IgG index value <10 as diminished RBD IgG response Results Of the 2,099 fully vaccinated patients on dialysis, the proportion receiving the mRNA1273, BNT162b2, and Ad26.COV2.S were 62% (n=1316), 20% (n=416) and 18% (n=367), respectively. A third (33.3%) of patients receiving the attenuated adenovirus Ad26.COV2.S vaccine failed to seroconvert and an additional 36% had no detectable or diminished IgG response even 28-60 days post vaccination. Conclusions One in three fully vaccinated patients receiving dialysis had evidence of an impaired immune response to the attenuated adenovirus Ad26.COV2.S vaccine.

COVID-19 and obesity: what is known about the features of pathogenesis and treatment?

The increasing prevalence of overweight and obesity is a public health problem worldwide. During the COVID-19 pandemic, obesity is associated with a higher risk of severe disease and adverse clinical outcome of SARS-CoV-2 infection. It may be associated with chronic systemic inflammation, impaired immune response and metabolic disturbances in obese patients. In order to establish possible pathogenetic links between obesity and COVID-19, an analysis of experimental, clinical studies, their meta-analyzes, literature reviews from the PubMed/MedLine database was carried out using the keywords «COVID-19» and «obesity». This review discusses the potential pathogenesis and treatment features of obese patients with COVID-19.

Illuminating the Role of Vitamin A in Skin Innate Immunity and the Skin Microbiome: A Narrative Review

Vitamin A is a fat-soluble vitamin that plays an important role in skin immunity. Deficiencies in Vitamin A have been linked to impaired immune response and increased susceptibility to skin infections and inflammatory skin disease. This narrative review summarizes recent primary evidence that elucidates the role of vitamin A and its derivatives on innate immune regulators through mechanisms that promote skin immunity and sustain the skin microbiome.