Acute kidney injury in COVID 19 - an update on pathophysiology and management modalities.

Acute kidney injury (AKI), characterised by fluid imbalance and overload, is prevalent in severe disease phenotypes of coronavirus disease 2019 (COVID-19). The elderly immunocompromised patients with pre-existing comorbidities being more risk-prone to severe COVID-19, the importance of early diagnosis and intervention in AKI is imperative. Histopathological examination of COVID-19 patients with AKI reveals viral invasion of the renal parenchyma and evidence of AKI. The definitive treatment for AKI includes renal replacement therapy and renal transplant. Immunosuppressant regimens and its interactions with COVID-19 have to be further explored to devise effective treatment strategies in COVID-19 transplant patients. Other supportive strategies for AKI patients include hemodynamic monitoring and maintenance of fluid balance. Antiviral drugs should be meticulously monitored in the management of these high-risk patients. We have focussed on the development of renal injury provoked by the SARS-CoV-2, the varying clinical characteristics, and employment of different management strategies, including renal replacement therapy, alongside the emerging cytokine lowering approaches.

Comparative Analysis of Serum Zinc, Copper and Magnesium Level and Their Relations in Association with Severity and Mortality in SARS-CoV-2 Patients.

The deficiencies of trace elements and infectious diseases often coexist and exhibit complex interactions. Several trace elements such as zinc (Zn), copper (Cu) and magnesium (Mg) have immunomodulatory functions and thus influence the susceptibility to the course and outcome of a variety of viral infections. So, this present study was aimed to study relations of trace metals in association with severity and mortality in SARS-CoV-2 patients. A total of 150 individuals infected with COVID-19 and 50 healthy individuals were recruited. Cases were divided based on severity (mild, moderate and severe) and outcome (discharged or deceased). Serum Zn, Mg and Cu levels were analysed by direct colourimetric method. Both serum Cu and Zn levels were significantly decreased in cases when compared to those in controls (p < 0.005 and p < 0.0001). Serum magnesium levels although not significant were found to be slightly decreased in controls. On comparing the trace elements between the deceased and discharged cases, a significant difference was found between serum copper and zinc levels, but for magnesium, both groups have similar levels. The receiver operating characteristic (ROC) curve results indicate that a serum Cu/Zn ratio along with the age of patient provides some reliable information on COVID-19 course and survival odds by yielding an AUC of 95.1% with a sensitivity of 93.8% and specificity of 89.8%. Therefore, we would like to emphasize that measuring the serum copper and zinc along with their ratio can be used as routine investigations for COVID-19 patients in proper identification and management of severe cases in upcoming new waves of COVID-19.

Association of iron-related biomarkers with severity and mortality in COVID-19 patients.

BACKGROUND: Nutritional deficiency is associated with weaken immune system and increased susceptibility to infection. Among other nutrients, several trace elements have been shown to regulate immune responses. Iron is one of the most abundant trace elements present in our body, which is required in various biological processes. Iron has an immunomodulatory function and thus influence the susceptibility to the course and outcome of a variety of viral infections. So, this present study was aimed to study relations of different iron-related biomarkers in association to severity and mortality in SARS-CoV-2 patients. MATERIALS AND METHODS: A total of 150 individuals infected with COVID-19 and 50 healthy individuals were recruited. Cases were divided based on severity (mild, moderate, and severe) and outcome (discharged or deceased). Serum iron, TIBC, ferritin, transferrin, transferrin saturation levels were analyzed by the direct colourimetric method. RESULTS: In cases the median levels of serum iron, TIBC, transferrin, transferrin saturation and ferritin are 29 µg/dL, 132.53 µg/dL, 106.3 mg/dL, 17.74 % and 702.9 ng/dL respectively. Similarly, in controls the median levels of serum iron, TIBC, transferrin, transferrin saturation and ferritin are 53 µg/dL, 391.88 µg/dL, 313.51 mg/dL, 12.81 % and 13.52 ng/dL respectively. On comparing the cases with the controls, a significant lower level of iron, TIBC, and transferrin were found in the cases along with the significant higher levels of ferritin and transferrin saturation. On comparing the Receiver operating characteristic (ROC) curves of Iron, Ferritin, Transferrin, Transferrin sat % and TIBC in relation to survival in COVID-19 patients it was found that iron, followed by transferrin and ferritin has the highest area under the curve (AUC) with 74 %, 63 % and 61 % respectively. Further, in pairwise analysis of ROC curve, a significant difference was found between the Iron-transferrin (p < 0.01), iron-TIBC (p < 0.001) and transferrin-ferritin (P < 0.01). The multiple regression model based on Iron and transferrin outperformed any other combination of variables via stepwise AIC selection with an AUC of 98.2 %. The cutoff point according to Youden's J index is characterized with a sensitivity of 98 % and a specificity of 96.8 %, indicating that iron along with transferrin can be a useful marker that may contribute to a better assessment of survival chances in COVID-19. CONCLUSION: Our study demonstrated a significantly decreased levels of iron, TIBC, & transferrin and a significantly increased levels of ferritin and transferrin saturation in COVID-19 patients when compared with controls. Further, Iron and transferrin were observed to be a good predictor of mortality in patients with COVID-19. From the above analysis we confirm that iron-related biomarkers play an important role in the development of oxidative stress and further lead to activation of the cytokine storm. So, continuous monitoring of these parameters could be helpful in the early detection of individuals developing the severe disease and can be used to decrease mortality in upcoming new waves of COVID-19.

Assessment of DHEAS, cortisol, and DHEAS/cortisol ratio in patients with COVID-19: a pilot study.

PURPOSE: Dehydroepiandrosterone sulfate (DHEAS) is observed to be decreased in sepsis and inflammatory conditions. In the present study, we assessed the levels of DHEAS and cortisol and the DHEAS/cortisol ratio and their association with inflammatory markers in patients with COVID-19. METHODS: The study recruited 76 RT-PCR-positive COVID-19-positive patients and 79 healthy controls. The blood samples were collected and were analyzed for cortisol and DHEAS. RESULTS: We observed decreased levels of DHEAS and DHEAS/cortisol ratio and increased levels of cortisol in cases when compared with controls. DHEAS and DHEAS/cortisol ratio showed a decreasing trend with the increase in disease severity. CONCLUSION: The present study is the first of its kind comparing DHEAS levels and DHEAS/cortisol ratio in COVID-19 patients and control subjects. DHEAS, with its inhibitory effect on IL6 and activation of Tregs, may play a crucial role in immune defense mechanisms against COVID-19.

Selenium to selenoproteins - role in COVID-19.

The disruption of antioxidant defense has been demonstrated in severe acute respiratory syndrome due to SARS-CoV infection. Selenium plays a major role in decreasing the ROS produced in response to various viral infections. Selenoprotein enzymes are essential in combating oxidative stress caused due to excessive generation of ROS. Selenium also has a role in inhibiting the activation of NF-κB, thus alleviating inflammation. In viral infections, selenoproteins have also been found to inhibit type I interferon responses, modulate T cell proliferation and oxidative burst in macrophages, and inhibit viral transcriptional activators. Potential virally encoded selenoproteins have been identified by computational analysis in different viral genomes like HIV-1, Japanese encephalitis virus (JEV), and hepatitis C virus. This review discusses the role and the possible mechanisms of selenium, selenoproteins, and virally encoded selenoproteins in the pathogenicity of viral infections. Identification of potential selenoproteins in the COVID 19 genome by computational tools will give insights further into their role in the pathogenesis of viral infections.

MicroRNAs based regulation of cytokine regulating immune expressed genes and their transcription factors in COVID-19.

BACKGROUND: Coronavirus disease 2019 is characterized by the elevation of a broad spectrum of inflammatory mediators associated with poor disease outcomes. We aimed at an in-silico analysis of regulatory microRNA and their transcription factors (TF) for these inflammatory genes that may help to devise potential therapeutic strategies in the future. METHODS: The cytokine regulating immune-expressed genes (CRIEG) were sorted from literature and the GEO microarray dataset. Their co-differentially expressed miRNA and transcription factors were predicted from publicly available databases. Enrichment analysis was done through mienturnet, MiEAA, Gene Ontology, and pathways predicted by KEGG and Reactome pathways. Finally, the functional and regulatory features were analyzed and visualized through Cytoscape. RESULTS: Sixteen CRIEG were observed to have a significant protein-protein interaction network. The ontological analysis revealed significantly enriched pathways for biological processes, molecular functions, and cellular components. The search performed in the miRNA database yielded ten miRNAs that are significantly involved in regulating these genes and their transcription factors. CONCLUSION: An in-silico representation of a network involving miRNAs, CRIEGs, and TF, which take part in the inflammatory response in COVID-19, has been elucidated. Thus, these regulatory factors may have potentially critical roles in the inflammatory response in COVID-19 and may be explored further to develop targeted therapeutic strategies and mechanistic validation.

Does dehydroepiandrosterone sulfate have a role in COVID-19 prognosis and treatment?

The pathophysiology of COVID comprises an exaggerated pro-inflammatory response. Hypothalamic-pituitary-adrenal (HPA) axis has a crucial role in various inflammatory conditions and modulated immunological response. Limited evidence is available regarding the incidence and the effect of HPA dysfunction in COVID-19. Although the cortisol levels have only been estimated in a few studies, the dehydroepiandrosterone sulfate (DHEAS) release from the adrenal gland has not been explored yet. In this mini review, the authors discuss the role of dehydroepiandrosterone (DHEA) and DHEAS in the acute stress response and immunological modulation. Various effects of DHEAS have been demonstrated in different diseases. The specific inhibitory effect of DHEA on interleukin 6 (IL-6) could be of paramount importance in COVID-19. Further, DHEA supplementation has already been proposed in inflammatory conditions, like rheumatoid arthritis. DHEAS levels in COVID-19 may help to understand the HPA axis dysfunction as well as the possibility of repurposing DHEA as a drug for mitigating the pro-inflammatory COVID-19.

Trace Elements as Immunoregulators in SARS-CoV-2 and Other Viral Infections.

Nutritional deficiency is associated with impaired immunity and increased susceptibility to infections. The complex interactions of trace elements with the macromolecules trigger the effective immune response against the viral diseases. The outcome of various viral infections along with susceptibility is affected by trace elements such as zinc, selenium, iron, copper, etc. due to their immuno-modulatory effects. Available electronic databases have been comprehensively searched for articles published with full text available and with the key words "Trace elements", "COVID-19", "Viral Infections" and "Immune Response" (i.e. separately Zn, Se, Fe, Cu, Mn, Mo, Cr, Li, Ni, Co) appearing in the title and abstract. On the basis of available articles we have explored the role of trace elements in viral infections with special reference to COVID-19 and their interactions with the immune system. Zinc, selenium and other trace elements are vital to triggerTH1 cells and cytokine-mediated immune response for substantial production of proinflammatory cytokines. The antiviral activity of some trace elements is attributed to their inhibitory effect on viral entry, replication and other downstream processes. Trace elements having antioxidants activity not only regulate host immune responses, but also modify the viral genome. Adequate dietary intake of trace elements is essential for activation, development, differentiation and numerous functions.

Association of Vitamin D Status with COVID-19 Infection and Mortality in the Asia Pacific region: A Cross-Sectional Study.

COVID-19 has been declared a global pandemic by WHO on 11 March 2020. Still, very little is known about the potential protective dietary factors for the prevention of infection and mortality due to COVID-19. Keeping in view the scarcity of literature/studies available, in this regards present study was undertaken to assess if there is any correlation between mean levels of Vitamin D in various Asia Pacific countries with the infection and mortality caused by COVID-19. We collected data for mean levels of Vitamin D for 37 Asia Pacific countries for which we have also got the data regarding the morbidity and mortality of COVID-19. The mean levels of Vitamin D were found to have a significant association with the number of cases/million(r = - 0.394, p value = 0.016) and a weak association with the number of deaths/ million (r = - 0.280, p value = 0.093) due to COVID-19. In conclusion, we found a significant relationship between Vitamin D levels with the number of COVID-19 cases. So further clinical trial/study with a large sample size is needed to elucidate the protective role of Vitamin D in COVID-19.

Complement activation and coagulopathy - an ominous duo in COVID19.

INTRODUCTION: COVID-19 has similarities to the Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) outbreaks, as severe patients and non-survivors have frequently shown abnormal coagulation profiles. Immune-mediated pathology is a key player in this disease; hence, the role of the complement system needs assessment. The complement system and the coagulation cascade share an intricate network, where multiple mediators maintain a balance between both pathways. Coagulopathy in COVID-19, showing mixed features of complement-mediated and consumption coagulopathy, creates a dilemma in diagnosis and management. AREAS COVERED: Pathophysiology of coagulopathy in COVID-19 patients, with a particular focus on D-dimer and its role in predicting the severity of COVID-19 has been discussed. A comprehensive search of the medical literature on PubMed was done till May 30th, 2020 with the keywords 'COVID-19', 'SARS-CoV-2', 'Coronavirus', 'Coagulopathy', and 'D-dimer'. Twenty-two studies were taken for weighted pooled analysis of D-dimer. EXPERT OPINION: A tailored anticoagulant regimen, including intensification of standard prophylactic regimens with low-molecular-weight heparin is advisable for COVID-19 patients. Atypical manifestations and varying D-dimer levels seen in different populations bring forth the futility of uniform recommendations for anticoagulant therapy. Further, direct thrombin inhibitors and platelet inhibitors in a patient-specific manner should also be considered.

The Clinical Laboratory: A Key Player in Diagnosis and Management of COVID-19.

The Coronavirus disease 2019 (COVID-19) outbreak, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), had emerged as a pandemic affecting almost all countries in the world in a short span after it was first reported in December. Clinical laboratory have a crucial role in mitigating this new pandemic. Timely and accurate diagnosis of COVID-19 is of paramount importance for detecting cases early and to prevent transmission. Clinical Laboratories have adopted different test modalities and processes to tackle this unprecedented situation with directives from regulatory bodies such as the WHO. The varying presentations, as well as complications attributed to comorbidities in COVID-19, have created hurdles in the management of these patients. Various clinical laboratory parameters have been investigated for their potential for diagnosis and prognosis of the disease, prediction of complications and monitoring of treatment response. Different routine and uncommon parameters have been shown to have the diagnostic and prognostic capacity. This update discusses the role of the laboratory in diagnosis, prognosis and monitoring of treatment response. Different methodologies for diagnostic testing as well as various clinical laboratory parameters having diagnostic and predictive powers have been discussed. This compilation organises relevant available information on various clinical laboratory parameters and their role in COVID-19 mitigating pandemic.