Role of vitamin D in COVID-19 and other viral infections

Vitamin D is a steroid hormone that is naturally produced in the body or obtained through dietary sources,primarily under the influence of UVB radiation.This essential nutrient has a vital role in numerous physiological processes,encom-passing immune function,cell growth,differentiation,insulin regulation,and cardiovascular well-being,along with its pivotal role in sustaining the delicate equilibrium of calcium and phosphate concentrations in the body.Moreover,vitamin D reinforces mucosal defense and bolsters the immune system through immunomodulation,making it a critical component of overall health.Numerous studies have unveiled the profound connection between vitamin D and the predisposition to respiratory tract infections,including well-known viruses such as influenza and the novel severe acute respiratory syndrome coronavirus 2.Vita-min D deficiency has been consistently linked to increased severity of coronavirus disease 2019(COVID-19)and a heightened risk of mortality among afflicted individuals.Retrospective observational studies have further substantiated these findings,indicating that levels of vitamin D are linked with both the occurrence and severity of COVID-19 cases.Vitamin D has its influence on viral infections th-rough a multitude of mechanisms,such as promoting the release of antimicrobial peptides and fine-tuning the responses of the immune system.Additionally,vitamin D is intertwined with the intricate network of the renin–angiotensin system,suggesting a potential impact on the development of complications related to COVID-19.While further clinical trials and extensive research are warranted,the existing body of evidence strongly hints at the possible use of vitamin D as a valuable tool in the prophylaxis and management of COVID-19 and other viral infectious diseases.

Monocyte and macrophage function in respiratory viral infections

Pulmonary macrophages,such as tissue-resident alveolar and interstitial macrophages and recruited monocyte-derived macrophages,are the major macrophages present in the lungs during homeostasis and diseased conditions.While tissue-resident macrophages act as sentinels of the alveolar space and play an important role in maintaining homeostasis and immune regulation,recruited macrophages accumulate in the respiratory tract after acute viral infections.Despite sharing similar anatomical niches,these macrophages are distinct in terms of their origins,surface marker expression,and transcriptional profiles,which impart macrophages with distinguished characteristics in physi-ological and pathophysiological conditions.In this review,we summarize the current view on these macrophage populations,their shared functions,and what makes them distinct from each other in the context of homeostasis andrespiratoryviral infections.

Management strategies for common viral infections in pediatric renal transplant recipients

Viral infections have been considered as a major cause of morbidity and mortality after kidney transplantation in pediatric cohort.Children are at high risk of acquiring virus-related complications due to immunological immaturity and the enhanced alloreactivity risk that led to maintenance of high immunosuppressive regimes.Hence,prevention,early detection,and prompt treatment of such infections are of paramount importance.Among all viral infections,herpes viruses(herpes simplex virus,varicella zoster virus,Epstein-Barr virus,cytomegalovirus),hepatitis B and C viruses,BK polyomavirus,and respiratory viruses(respiratory syncytial virus,parainfluenza virus,influenza virus and adenovirus)are common in kidney transplant recipients.These viruses can cause systemic disease or allograft dysfunction affecting the clinical outcome.Recent advances in technology and antiviral therapy have improved management strategies in screening,monitoring,adoption of prophylactic or preemptive therapy and precise treatment in the immunocompromised host,with significant impact on the outcome.This review discusses the etiology,screening and monitoring,diagnosis,prevention,and treatment of common viral infections in pediatric renal transplant recipients.

Factors Associated with HIV/Tuberculosis Coinfection among People Living with HIV after Initiation of Antiretroviral Treatment in Lingwala Health Zone from 2021 to 2023

Context and objective: Around 8% of incident cases of tuberculosis (TB) were reported among people living with HIV worldwide in 2022. Tuberculosis is the leading cause of death among people living with HIV. Africa accounts for the majority of co-infection episodes, with over 50% of cases in some parts of southern Africa. In the Democratic Republic of Congo (DRC), around 9% of persons living with HIV (PLHIV) develop TB and 11% of TB patients are infected with HIV. The DRC is one of the 30 countries in the world bearing the brunt of co-infection. Despite the efforts made by countries to improve access to antiretroviral traitement (ART), TB remains a major problem among people living with HIV. The Lingwala Health Zone in the provincial city of Kinshasa recorded a large number of cases of HIV/TB co-infection during the study period. The aim of this study was to determine the factors associated with HIV/TB co-infection among PLHIV on ART in the Lingwala health zone (HZ) in Kinshasa. Methods: This was a case-control study conducted in the state-run HIV care facilities in the Lingwala health district among PLHIV who had visited the health facilities during the period 2021-2023. Cases were coinfected patients and controls were PLHIV who had not developed tuberculosis during the study period. Results: A total of 281 PLHIV were enrolled in the study, with 70 cases and 211 controls. Factors associated with HIV/TB co-infection after multivariate analysis were viral load (OR = 5.34;95% CI;1.8-15.8, p = 0.005). History of tuberculosis (OR = 20.84;95% CI;8.6-50.3, p -85.0, p = 0.005) and BMI Conclusion: The results of this study indicate that the detection of these enumerated factors should prompt providers to actively search for tuberculosis with a view to organising early management.

Role of nutrition in diabetes mellitus and infections

In this editorial,we have commented on the article that has been published in the recent issue of World Journal of Clinical Cases.The authors have described a case of unilateral thyroid cyst and have opined that the acute onset of infection may be linked to diabetes mellitus(DM).We have focused on the role of nutrition in the association between DM and infection.Patients with DM are at a high risk of infection,which could also be attributed to nutrition-related factors.Nutritional interventions for patients with diabetes are mainly based on a low-calorie diet,which can be achieved by adhering to a low-carbohydrate diet.However,dietary fiber supplementation is recommended to maintain the diversity of the gut microbiota.Furthermore,high-quality protein can prevent the increased risk of infection due to malnutrition.Supplementation of vitamins C,vitamins A,vitamins D,and folic acid improves blood sugar control and facilitates immune regulation.Mineral deficiencies augment the risk of infection,but the relationship with diabetes is mostly U-shaped and a good intake should be maintained.

Effects of viral infection and microbial diversity on patients with sepsis:A retrospective study based on metagenomic next-generation sequencing

BACKGROUND: The study aims to investigate the performance of a metagenomic next-generationsequencing (NGS)-based diagnostic technique for the identifi cation of potential bacterial and viral infectionsand eff ects of concomitant viral infection on the survival rate of intensive care unit (ICU) sepsis patients.METHODS: A total of 74 ICU patients with sepsis who were admitted to our institution from February1, 2018 to June 30, 2019 were enrolled. Separate blood samples were collected from patients for bloodcultures and metagenomic NGS when the patients’ body temperature was higher than 38 °C. Patients’demographic data, including gender, age, ICU duration, ICU scores, and laboratory results, were recorded.The correlations between pathogen types and sepsis severity and survival rate were evaluated.RESULTS: NGS produced higher positive results (105 of 118;88.98%) than blood cultures(18 of 118;15.25%) over the whole study period. Concomitant viral infection correlated closelywith sepsis severity and had the negative effect on the survival of patients with sepsis. However,correlation analysis indicated that the bacterial variety did not correlate with the severity of sepsis.CONCLUSIONS: Concurrent viral load correlates closely with the severity of sepsis and thesurvival rate of the ICU sepsis patients. This suggests that prophylactic administration of antiviraldrugs combined with antibiotics may be benefi cial to ICU sepsis patients.

RNAi,a new therapeutic strategy against viral infection

RNA interference (RNAi) is an adaptive defense mechanism triggered by double-stranded RNA (dsRNA). It is a powerful reverse genetic tool that has been widely employed to silence gene expression in mammalian and human cells.RNAi-based gene therapies, especially in viral diseases have become more and more interesting and promising. Recently,small interfering RNA (siRNA) can be used to protect host from viral infection, inhibit the expression of viral antigen and accessory genes, control the transcription and replication of viral genome, hinder the assembly of viral particles, and display influences in virus-host interactions. In this review, we attempt to present recent progresses of this breakthrough technology in the above fields and summarize the possibilities of siRNA-based drugs.

New animal models for hepatitis C viral infection and pathogenesis studies

Hepatitis C virus （HCV） is a major cause of chronic liver disease, cirrhosis and hepatocellular carcinoma （HCC）. In man, the pathobiological changes associated with HCV infection have been attributed to both the immune system and direct viral cytopathic effects. Until now, the lack of simple culture systems to infect and propagate the virus has hampered progress in understanding the viral life cycle and pathogenesis of HCV infection, including the molecular mechanisms implicated in HCV-induced HCC. This clearly demonstrates the need to develop small animal models for the study of HCV-associated pathogenesis. This review describes and discusses the development of new HCV animal models to study viral infection and investigate the direct effects of viral protein expression on liver disease.

TT viral infection through blood transfusion:retrospective investigation on patients in a prospective study of post-transfusion hepatitis

AIM To investigate the role of bloodtransfusion in TT viral infection(TTV).METHODS We retrospectively studied serumsamples from 192 transfusion recipients whounderwent cardiovascular surgery and bloodtransfusion between July 1991 and June 1992.Allpatients had a follow-up every other week for atleast 6 months after transfusion.Eightyrecipients received blood before screeningdonors for hepatitis C antibody(anti-HCV),and112 recipients received screened blood.Recipients with alanine aminotransferase level】2.5 times the upper normal limit were testedfor serological markers for viral hepatitis A,B,C,G,Epstein-Barr virus and cytomegalovirus.TTV infection was defined by the positivity forserum TTV DNA using the polymerase chainreaction method.RESULTS Eleven and three patients,whoreceived anti-HCV unscreened and screened'blood,respectively,had serum ALT levels】90 IU/L.Five patients(HCV and TTV:1;HCV,HGV,and TTV:1;TTV:2;and CMV and TTV:1)were positive for TTV DNA,and four of them hadsero-conversion of TTV DNA.CONCLUSION TTV can be transmitted viablood transfusion.Two recipients infected byTTV alone may be associated with the hepatitis.However,whether TTV was the causal agentremains unsettled,and further studies arenecessary to define the role of TTV infection inchronic hepatitis.

Memory CD8+ T cell differentiation in viral infection: A cell for all seasons

Chronic viral infections such as hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) are major global health problems affecting more than 500 million people worldwide. Virus-specific CD8+ T cells play an important role in the course and outcome of these viral infections and it is hypothesized that altered or impaired differentiation of virus- specific CD8+ T cells contributes to the development of persistence and/or disease progression. A deeper understanding of the mechanisms responsible for functional differentiation of CD8+ T cells is essential for the generation of successful therapies aiming to strengthen the adaptive component of the immune system.

Viral infections and cell cycle G2/M regulation

Progression of cells from G2 phase of the cell cycle to mitosis is a tightly regulated cellular process that requires activation of the Cdc2 kinase, which determines onset of mitosis in all eukaryotic cells. In both human and fission yeast (Schizosaccharomyces pombe) cells, the activity of Cdc2 is regulated in part by the phosphorylation status of tyrosine 15 (Tyr15) on Cdc2, which is phosphorylated by Wee1 kinase during late G2 and is rapidly dephosphorylated by the Cdc25 tyrosine phosphatase to trigger entry into mitosis. These Cdc2 regulators are the downstream targets of two well- characterized G2/M checkpoint pathways which prevent cells from entering mitosis when cellular DNA is damaged or when DNA replication is inhibited. Increasing evidence suggests that Cdc2 is also commonly targeted by viral proteins, which modulate host cell cycle machinery to benefit viral survival or replication. In this review, we describe the effect of viral protein R (Vpr) encoded by human immunodeficiency virus type 1 (HIV-1) on cell cycle G2/M regulation. Based on our current knowledge about this viral effect, we hypothesize that Vpr induces cell cycle G2 arrest through a mechanism that is to some extent different from the classic G2/M checkpoints. One the unique features distinguishing Vpr-induced G2 arrest from the classic checkpoints is the role of phosphatase 2A (PP2A) in Vpr-induced G2 arrest. Interestingly, PP2A is targeted by a number of other viral proteins including SV40 small T antigen, polyomavirus T antigen, HTLV Tax and adenovirus E4orf4. Thus an in-depth understanding of the molecular mechanisms underlying Vpr-induced G2 arrest will provide additional insights into the basic biology of cell cycle G2/M regulation and into the biological significance of this effect during host-pathogen interactions.

Viral infections in inflammatory bowel disease:Tips and tricks for correct management

Over the past decades,the treatment of inflammatory bowel diseases(IBD)has become more targeted,anticipating the use of immune-modifying therapies at an earlier stage.This top-down approach has been correlated with favorable short and long-term outcomes,but it has also brought with it concerns regarding potential infectious complications.This large IBD population treated with immunemodifying therapies,especially if combined,has an increased risk of severe infections,including opportunistic infections that are sustained by viral,bacterial,parasitic,and fungal agents.Viral infections have emerged as a focal safety concern in patients with IBD,representing a challenge for the clinician:they are often difficult to diagnose and are associated with significant morbidity and mortality.The first step is to improve effective preventive strategies,such as applying vaccination protocols,adopt adequate prophylaxis and educate patients about potential risk factors.Since viral infections in immunosuppressed patients may present atypical signs and symptoms,the challenges for the gastroenterologist are to suspect,recognize and diagnose such complications.Appropriate treatment of common viral infections allows us to minimize their impact on disease outcomes and patients’lives.This practical review supports this standard of care to improve knowledge in this subject area.

HCV-RNA positivity in peripheral blood mononuclear cells of patients with chronic HCV-infection: does it really mean viral replication?

AIM: To analyze the association of HCV-RNA with peripheral blood mononuclear cells (PBMC) and to answer the question whether HCV-RNA positivity in PBMC is due to viral replication. METHODS: HCV-RNA was monitored in serum and PBMC preparations from 15 patients with chronic HCV infection before, during and after an IFN-alpha therapy using a nested RT/PCR technique. In a second approach, PBMC from healthy donors were incubated in HCV positive plasma. RESULTS: In the IFN-alpha responding patients,HCV-RNA disappeared first from total RNA preparations of PBMC and then from serum. In contrast, in relapsing patients, HCV-RNA reappeared first in serum and then in PBMC. A quantitative analysis of the HCV-RNA concentration in serum was performed before and after transition from detectable to non detectable HCV-RNA in PBMC-RNA and vice versa. When HCV-RNA was detectable in PBMC preparations, the HCV concentration in serum was significantly higher than the serum HCV-RNA concentration when HCV-RNA in PBMC was not detectable. Furthermore, at no time during the observation period was HCV specific RNA observed in PBMC, if HCV-RNA in serum was under the detection limit. Incubation of PBMC from healthy donors with several dilutions of HCV positive plasma for two hours showed a concentration dependent PCR positivity for HCV-RNA in reisolated PBMC. CONCLUSION: The detectability of HCV-RNA in total RNA from PBMC seems to depend on the HCV concentration in serum. Contamination or passive adsorption by circulating virus could be the reason for detection of HCV-RNA in PBMC preparations of chronically infected patients.

Viral exploitation of actin: force-generation and scaffolding functions in viral infection

As a fundamental component of the host cellular cytoskeleton, actin is routinely engaged by infecting viruses. Furthermore, viruses from diverse groups, and infecting diverse hosts, have convergently evolved an array of mechanisms for manipulating the actin cytoskeleton for efficacious infection. An ongoing chorus of research now indicates that the actin cytoskeleton is critical for viral replication at many stages of the viral life cycle, including binding, entry, nuclear localization, genomic transcription and reverse transcription, assembly, and egress/dissemination. Specifically, viruses subvert the force-generating and macromolecular scaffolding properties of the actin cytoskeleton to propel viral surfing, internalization, and migration within the cell. Additionally, viruses utilize the actin cytoskeleton to support and organize assembly sites, and eject budding virions for cell-to-cell transmission. It is the purpose of this review to provide an overview of current research, focusing on the various mechanisms and themes of virus-mediated actin modulation described therein.

Role of chemokines and their receptors in viral persistence and liver damage during chronic hepatitis C virus infection

Chemokines produced in the liver during hepatitis C virus(HCV) infection induce migration of activated T cells from the periphery to infected parenchyma.The milieu of chemokines secreted by infected hepatocytes is predominantly associated with the T-helper cell/Tc1 T cell(Th1/Tc1) response.These chemokines consist of CCL3(macrophage inflammatory protein-1α;MIP-1α),CCL4(MIP-1β),CCL5(regulated on activation normal T cell expressed and secreted;RANTES),CXCL10(interferon-γ-inducible protein-10;IP-10),CXCL11(interferon-inducible T-cell α chemoattractant;I-TAC),and CXCL9(monokine induced by interferon γ;Mig) and they recruit T cells expressing either CCR5 or CXCR3 chemokine receptors.Intrahepatic and peripheral blood levels of these chemokines are increased during chronic hepatitis C.The interaction between chemokines and their receptors is essential in recruiting HCV-specific T cells to control the infection.When the adaptive immune response fails in this task,non-specific T cells without the capacity to control the infection are also recruited to the liver,and these are ultimately responsible for the persistent hepatic damage.The modulation of chemokine receptor expression and chemokine secretion could be a viral escape mechanism to avoid specific T cell migration to the liver during the early phase of infection,and to maintain liver viability during the chronic phase,by impairing non-specific T cell migration.Some chemokines and their receptors correlate with liver damage,and CXCL10(IP-10) and CXCR3 levels have shown a clinical utility as predictors of treatment response outcome.The regulation of chemokines and their receptors could be a future potential therapeutic target to decrease liver inflammation and to increase specific T cell migration to the infected liver.

Antiviral treatment of hepatitis C virus infection and factors affecting efficacy

Hepatitis C virus(HCV)infection is the leading cause of chronic liver-related diseases,including cirrhosis,liver failure,and hepatocellular carcinoma.Currently,no effective vaccine is available for HCV infection.Polyethylene glycol interferon-α(PegIFN-α)in combination with ribavirin(RBV)is the standard of care(SOC)for chronic hepatitis C.However,the efficacy of PegIFN-αand RBV combination therapy is less than 50%for genotype 1HCV,which is the dominant virus in humans.In addition,IFN and RBV have several severe side effects.Therefore,strategies to improve sustained virological response(SVR)rates have been an important focus for clinical physicians.The serine protease inhibitors telaprevir and boceprevir were approved by the United States Food and Drug Administration in 2011.The addition of HCV protease inhibitors to the SOC has significantly improved the efficacy of treatments for HCV infection.Several direct-acting antiviral drugs currently in late-stage clinical trials,both with and without pegIFN and RBV,have several advantages over the previous SOC,including higher specificity and efficacy,fewer side effects,and the ability to be administered orally,and might be optimal regimens in the future.Factors affecting the efficacy of anti-HCV treatments based on IFN-αinclude the HCV genotype,baseline viral load,virological response during treatment,host IL28B gene polymorphisms and hepatic steatosis.However,determining the effect of the above factors on DAA therapy is necessary.In this review,we summarize the development of antiHCV agents and assess the main factors affecting the efficacy of antiviral treatments.

COVID-19 Pandemic, Part I: What to Do and Who to Blame? Susceptibility to Viral Infection via Jeopardized Immunity

When this tragedy ends, it will become clear whether it is a pandemic, epidemic, mass infection, or mass psychosis (initiated by mass media with heavy engagement from political and economic establishments). The USA and other countries are raining accusations upon China, and vice versa. This problem will have future impacts on human society and civilization will be quite different following the “Pandemic of COVID-19”. Although this series of papers will discuss a broad array of related problems, the author contends that the most important priorities are developing medications against diseases and improving our scientific understanding of the social situations and substances that jeopardize human health and increase our susceptibility to viral infection. Later papers in this series will provide support for the Chinese claim that chloroquine may be a useful medication for patients with viral infection.

Viral respiratory infections among Hajj pilgrims in 2013

Middle East respiratory syndrome coronavirus(MERS-Co V) has emerged in the Arabian Gulf region, with its epicentre in Saudi Arabia, the host of the ‘Hajj' which is the world's the largest mass gathering. Transmission of MERS-Co V at such an event could lead to its rapid worldwide dissemination. Therefore, we studied the frequency of viruses causing influenza-like illnesses(ILI) among participants in a randomised controlled trial at the Hajj 2013. We recruited 1038 pilgrims from Saudi Arabia, Australia and Qatar during the first day of Hajj and followed them closely for four days. A nasal swab was collected from each pilgrim who developed ILI. Respiratory viruses were detected using multiplex RT-PCR. ILI occurred in 112/1038(11%) pilgrims. Their mean age was 35 years, 49(44%) were male and 35(31%) had received the influenza vaccine pre-Hajj. Forty two(38%) pilgrims had laboratory-confirmed viral infections; 28(25%) rhinovirus, 5(4%) influenza A, 2(2%) adenovirus, 2(2%) human coronavirus OC43/229 E, 2(2%) parainfluenza virus 3, 1(1%) parainfluenza virus 1, and 2(2%) dual infections. No MERS-Co V was detected in any sample. Rhinovirus was the commonest cause of ILI among Hajj pilgrims in 2013. Infection control and appropriate vaccination are necessary to prevent transmission of respiratory viruses at Hajj and other mass gatherings.

Comparison on Serum Levels of Procalcitonin of Children with Viral and Bacterial Infection

Objective To compare and analyze serum levels of procalcitonin (PCT) of children with viral and bacterial infection and probe into the importance of determining the level of serum PCT in the diagnosis of bacterial infection in order to provide evidences of the clinical use of antibiotics. Methods A total of 85 cases of children with an average age of 8.9 years (10 months-12 years) were enrolled in this study, 53 cases were with viral infection and 32 cases with bacterial infection. We determined serum levels of PCT by semi-quantitative solid phase immunoassay, and the serum levels of PCT were divided into four grades as<0.5μg/L,≥ 0.5μg/L,≥2.0μg/L and≥10μg/L forχ2 test and Ridit analysis. Results The serum level of PCT of the group with bacterial infection were signiifcantly higher than that of the group with viral infection (P<0.001). The sensitivity of diagnosis of bacterial infection in children with determination of serum levels of PCT was 87.50%while the speciifcity was 92.13%, and positive predictive value was 73.68%while negative predictive value was 91.49%, and positive likelihood ratio was 4.65 while negative likelihood ratio was 0.15, and the diagnostic accuracy was 83.53%. Conclusions Serum PCT is a bacterial sensitive marker of bacterial infection in children, and the determination of the level of serum PCT is helpful for the diagnosis of bacterial infection, which can also be a basis for the use of antibiotics.

Human bocavirus infection in children hospitalized with lower respiratory tract infections:Does viral load affect disease course?

Objective:To examine the effects of human bocavirus type 1(HBoV1)on the course of lower respiratory tract infections in cases of monoinfection and coinfection,and the effects of HBoV1 viral load on the disease in children under six years old hospitalized with a diagnosis of HBoV1-associated lower respiratory tract infections.Methods:Children under six years of age,who were hospitalized with the diagnosis of lower respiratory tract infection due to HBoV1 between 1 January 2021 and 1 January 2022 were included in the study.Laboratory confirmation of the respiratory pathogens was performed using polymerase chain reaction(PCR).Results:Fifty-four(16.4%)children with HBoV1 among 329 children whose PCR was positive with bacterial/viral agent in nasopharyngeal swab samples were included in the study.There were 28(51.9%)males and 26(48.1%)females with a median age 23.4 months[interquartile range(IQR):13.2,30.0 months](min-max:1 month-68 months).HBoV1 was detected as a monoinfecton in 26(48.1%)children,and as a coinfection with other respiratory agents in 28 children(51.9%).In multiple regression analysis,coinfection(P=0.032)was associated with the length of hospitalization(P<0.001;R^(2)=0.166).There was a negative correlation(r=−0.281,P=0.040)between cough and cycle threshold.Fever was found to be positively correlated with C-reactive protein(r=0.568,P<0.001)and procalcitonin(r=0.472;P=0.001).Conclusions:Although we found a higher HBoV1 viral load in children with more cough symptoms in our study,it had no effect on the severity of the disease,such as length of hospital stay and need for intensive care.Coinfection was found to affect the length of hospitalization.