In view of the emerging COVID-19 pandemic caused by SARS-CoV-2 virus, the search for potential protective and therapeutic antiviral strategies is of particular and urgent interest. Zinc is known to modulate antiviral and antibacterial immunity and regulate inflammatory response. Despite the lack of clinical data, certain indications suggest that modulation of zinc status may be beneficial in COVID-19. In vitro experiments demonstrate that Zn2+ possesses antiviral activity through inhibition of SARS-CoV RNA polymerase. This effect may underlie therapeutic efficiency of chloroquine known to act as zinc ionophore. Indirect evidence also indicates that Zn2+ may decrease the activity of angiotensin-converting enzyme 2 (ACE2), known to be the receptor for SARS-CoV-2. Improved antiviral immunity by zinc may also occur through up-regulation of interferon α production and increasing its antiviral activity. Zinc possesses anti-inflammatory activity by inhibiting NF-κB signaling and modulation of regulatory T-cell functions that may limit the cytokine storm in COVID-19. Improved Zn status may also reduce the risk of bacterial co-infection by improving mucociliary clearance and barrier function of the respiratory epithelium, as well as direct antibacterial effects against S. pneumoniae. Zinc status is also tightly associated with risk factors for severe COVID-19 including ageing, immune deficiency, obesity, diabetes, and atherosclerosis, since these are known risk groups for zinc deficiency. Therefore, Zn may possess protective effect as preventive and adjuvant therapy of COVID-19 through reducing inflammation, improvement of mucociliary clearance, prevention of ventilator-induced lung injury, modulation of antiviral and antibacterial immunity. However, further clinical and experimental studies are required.

https://www.spandidos-publications.com/10.3892/ijmm.2020.4575/download

Zinc and respiratory tract infections: Perspectives for COVID­19 (Review).

The importance of Zn for human health becomes obvious during Zn deficiency. Even mild insufficiencies of Zn cause alterations in haematopoiesis and immune functions, resulting in a proinflammatory phenotype and a disturbed redox metabolism. Although immune system malfunction has the most obvious effect, the functions of several tissue cell types are disturbed if Zn supply is limiting. Adhesion molecules and tight junction proteins decrease, while cell death increases, generating barrier dysfunction and possibly organ failure. Taken together, Zn deficiency both weakens the resistance of the human body towards pathogens and at the same time increases the danger of an overactive immune response that may cause tissue damage. The case numbers of Corona Virus Disease 19 (COVID-19) are still increasing, which is causing enormous problems for health systems and economies. There is an urgent need to reduce both the number of severe cases and the resulting deaths. While therapeutic options are still under investigation, and first vaccines have been approved, cost-effective ways to reduce the likelihood of or even prevent infection, and the transition from mild symptoms to more serious detrimental disease, are highly desirable. Nutritional supplementation might be an effective option to achieve these aims. In this review, we discuss known Zn deficiency effects in the context of an infection with Severe Acute Respiratory Syndrome-Coronavirus-2 and its currently known pathogenic mechanisms and elaborate on how severe pre-existing Zn deficiency may pre-dispose patients to a severe progression of COVID-19. First published clinical data on the association of Zn homoeostasis with COVID-19 and registered studies in progress are listed.

Zinc deficiency as a possible risk factor for increased susceptibility and severe progression of Corona Virus Disease 19.

Pathogenic Leptospira is the causative agent of leptospirosis, an emerging zoonotic disease affecting animals and humans worldwide. The risk of host infection following interaction with environmental sources depends on the ability of Leptospira to persist, survive, and infect the new host to continue the transmission chain. Leptospira may coexist with other pathogens, thus providing a suitable condition for the development of other pathogens, resulting in multi-pathogen infection in humans. Therefore, it is important to better understand the dynamics of transmission by these pathogens. We conducted Boolean searches of several databases, including Google Scholar, PubMed, SciELO, and ScienceDirect, to identify relevant published data on Leptospira and coinfection with other pathogenic bacteria. We review the role of the host-microbiota in determining the synanthropic interaction of Leptospira sp. with other bacteria, thus creating a suitable condition for the leptospira to survive and persist successfully. We also discuss the biotic and abiotic factors that amplify the viability of Leptospira in the environment. The coinfection of leptospira with pathogenic bacteria has rarely been reported, potentially contributing to a lack of awareness. Therefore, the occurrence of leptospirosis coinfection may complicate diagnosis, long-lasting examination, and mistreatment that could lead to mortality. Identifying the presence of leptospirosis with other bacteria through metagenomic analysis could reveal possible coinfection. In conclusion, the occurrence of leptospirosis with other diseases should be of concern and may depend on the success of the transmission and severity of individual infections. Medical practitioners may misdiagnose the presence of multiple infections and should be made aware of and receive adequate training on appropriate treatment for leptospirosis patients. Physicians could undertake a more targeted approach for leptospirosis diagnosis by considering other symptoms caused by the coinfected bacteria; thus, more specific treatment could be given.

Leptospirosis and Coinfection: Should We Be Concerned?

Macrophage Activation Syndrome (MAS) is a very severe complication of different rheumatic diseases, including pediatric Systemic Lupus Erythematosus (pSLE). MAS is not considered as a frequent complication of pSLE; however, its occurrence could be under-estimated and the diagnosis can be challenging. In order to address this issue, we performed a systematic review of the available medical literature, aiming to retrieve all those papers providing diagnostic (clinical/laboratory) data on patients with pSLE-related MAS, in individual or aggregated form. The selected case reports and series provided a pool of 46 patients, accounting for 48 episodes of MAS in total. We re-analyzed these patients in light of the diagnostic criteria for MAS validated in systemic Juvenile Idiopathic Arthritis (sJIA) patients and the preliminary diagnostic criteria for MAS in pSLE, respectively. Five clinical studies were also selected and used to support this analysis. This systematic review confirms that MAS diagnosis in pSLE patients is characterized by several diagnostic challenges, which could lead to delayed diagnosis and/or under-estimation of this complication. Specific criteria should be considered to diagnose MAS in different rheumatic diseases; as regards pSLE, the aforementioned preliminary criteria for MAS in pSLE seem to perform better than the sJIA-related MAS criteria, because of a lower ferritin cut-off.

/pdf/macrophage-activation-syndrome-in-pediatric-systemic-lupus-5a5lg4jqu4.pdf

Macrophage Activation Syndrome in Pediatric Systemic Lupus Erythematosus: A Systematic Review of the Diagnostic Aspects

Hemophagocytic lymphohistiocytosis (HLH) is a rare and potentially fatal disease primarily of children, characterized by a severe hyperinflammatory state. We describe a case of adult onset familial HLH with a novel exon 19, c.1607G>T (p.Arg536Leu) heterozygous mutation of the UNC13D gene in a 40-year-old woman who developed HLH during her first and second pregnancies, both episodes occurring during the first trimester. Our patient was treated successfully both times with HLH-94 protocol following spontaneous abortions and is currently in the process of getting a bone marrow transplant. We also discuss pregnancy as a potential trigger for late onset familial HLH.

/pdf/a-case-of-recurrent-pregnancy-induced-adult-onset-familial-3tgle4tog1.pdf

A Case of Recurrent Pregnancy-Induced Adult Onset Familial Hemophagocytic Lymphohistiocytosis

Melioidosis is a tropical infectious disease with diverse clinical presentations. We aimed to investigate the characteristics and mortality risk factors of patients diagnosed with melioidosis in the past 10 years. This was a retrospective cohort study conducted at a quaternary care centre in South India. Clinical, demographic, and biochemical data in patients diagnosed with melioidosis with cultures were collected between January 2011 and December 2020 from medical records. Logistic regression analysis was performed to screen mortality risk factors of melioidosis in addition to descriptive statistics and chi-square analysis. Seventy-three melioidosis patients' records were analysed, and the most common comorbidity was type 2 diabetes mellitus (n = 53, 72.6%). The patients showed diverse presentations: pulmonary involvement, 30 (41.1%); splenomegaly, 29 (39.7%); abscesses and cutaneous involvement, 18 (24.7%); lymph node, 10 (13.7%); arthritis and osteomyelitis, 9 (12.3%); and genitourinary infection, 4 (5.4%). The mortality was noted to be 15 (20.5%). Logistic regression analysis indicated that chronic kidney disease (OR = 14.0), CRP >100 IU/L (OR = 6.964), and S. albumin <3 gm/dl (OR = 8.0) were risk factors associated with mortality and can guide in risk stratification. Hypoalbuminemia is a novel mortality risk factor, detected in this study, and requires further investigation to validate its utility as a prognostic marker and reveal possible therapeutic benefits in clinical correction.

/pdf/risk-factors-for-mortality-in-melioidosis-a-single-centre-10-1x5683641j.pdf

Risk Factors for Mortality in Melioidosis: A Single-Centre, 10-Year Retrospective Cohort Study.

Background: While many factors are known to play a role in outcomes of sepsis, the role of micronutrients such as zinc remains a gray area. This study assesses the correlation of plasma zinc levels with mortality and severity of sepsis. Objective was to study the association between plasma zinc levels with mortality and severity of sepsis. Methods: Comparative prospective observational study which included 89 patients with proven sepsis according to the society of critical care medicine (SCCM) guidelines. The study was conducted at a tertiary care centre in South India. A total of 89 patients who were admitted into the medical ICU directly from ER, from December 2014 to August 2015 were chosen for the study after satisfying specific inclusion criteria and divided into 2 outcome groups based on mortality. Results: There was a significant association between plasma zinc (categorized as low, normal and high plasma zinc) and outcome. While the severity of sepsis as per SOFA score on admission did not have an association, there was a significant association between plasma zinc and the 48-hour SOFA score. Conclusions: Higher plasma zinc values had lower mortality and lower 48 hours SOFA score, strengthening the hypothesis regarding the role of zinc in the immune response to sepsis. More research is needed regarding the role of zinc in assessing the severity and predicting the mortality of patients with sepsis.

Could plasma zinc be a predictor for mortality and severity in sepsis syndrome

BACKGROUND In autoimmune inflammatory rheumatological diseases, routine cardiovascular risk assessment is becoming more important. As an increased cardiovascular disease (CVD) risk is recognized in patients with fibromyalgia (FM), a combination of traditional CVD risk assessment tool with Machine Learning (ML) predictive model could help to identify non-traditional CVD risk factors. METHODS This study was a retrospective case-control study conducted at a quaternary care center in India. Female patients diagnosed with FM as per 2016 modified American College of Rheumatology 2010/2011 diagnostic criteria were enrolled; healthy age and gender-matched controls were obtained from Non-communicable disease Initiatives and Research at AMrita (NIRAM) study database. Firstly, FM cases and healthy controls were age-stratified into three categories of 18-39 years, 40-59 years, and ≥ 60 years. A 10 year and lifetime CVD risk was calculated in both cases and controls using the ASCVD calculator. Pearson chi-square test and Fisher's exact were used to compare the ASCVD risk scores of FM patients and controls across the age categories. Secondly, ML predictive models of CVD risk in FM patients were developed. A random forest algorithm was used to develop the predictive models with ASCVD 10 years and lifetime risk as target measures. Model predictive accuracy of the ML models was assessed by accuracy, f1-score, and Area Under 'receiver operating Curve' (AUC). From the final predictive models, we assessed risk factors that had the highest weightage for CVD risk in FM. RESULTS A total of 139 FM cases and 1820 controls were enrolled in the study. FM patients in the age group 40-59 years had increased lifetime CVD risk compared to the control group (OR = 1.56, p = 0.043). However, CVD risk was not associated with FM disease severity and disease duration as per the conventional statistical analysis. ML model for 10-year ASCVD risk had an accuracy of 95% with an f1-score of 0.67 and AUC of 0.825. ML model for the lifetime ASCVD risk had an accuracy of 72% with an f1-score of 0.79 and AUC of 0.713. In addition to the traditional risk factors for CVD, FM disease severity parameters were important contributors in the ML predictive models. CONCLUSION FM patients of the 40-59 years age group had increased lifetime CVD risk in our study. Although FM disease severity was not associated with high CVD risk as per the conventional statistical analysis of the data, it was among the highest contributor to ML predictive model for CVD risk in FM patients. This also highlights that ML can potentially help to bridge the gap of non-linear risk factor identification.

Cardiovascular risk assessment using ASCVD risk score in fibromyalgia: a single-centre, retrospective study using "traditional" case control methodology and "novel" machine learning.

Triple threat: pregnancy, SLE, EBV as potential triggers in secondary hemophagocytic lymphohistiocytosis

We report a case of a 12-year-old male who initially presented with active systemic lupus erythematosus (SLE) with lupus nephritis and secondary macrophage activation syndrome (MAS). He went on to develop left-sided upper motor neuron (UMN) facial palsy secondary to lupus-related tumefactive demyelination. Tumefactive lesions secondary to demyelination are a very rare manifestation in neuropsychiatric SLE. This child responded to aggressive immunosuppression with steroids and cyclophosphamide.

Sandeep Surendran

Papers

Risk Factors for Mortality in Melioidosis: A Single-Centre, 10-Year Retrospective Cohort Study.

Could plasma zinc be a predictor for mortality and severity in sepsis syndrome

Cardiovascular risk assessment using ASCVD risk score in fibromyalgia: a single-centre, retrospective study using "traditional" case control methodology and "novel" machine learning.

Triple threat: pregnancy, SLE, EBV as potential triggers in secondary hemophagocytic lymphohistiocytosis

Staring at an abscess, but lupus stares back….