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.

Co-infections in Hospitalized COVID-19 Patients- A Prospective Observational Study.

INTRODUCTION: SARS -CoV-2 was first reported in Wuhan and declared a pandemic in March 2020. Co-infections during other pandemics have been associated with severe outcomes, but data are scarce regarding co-infections in COVID-19 patients. Our study evaluated co-infections prevalence and its impact on morbidity and mortality in hospitalized COVID -19 patients. METHODS: This prospective observational study included 100 patients admitted to a high-dependency unit at a tertiary care hospital in India. Prevalence of co-infections and clinical outcome-related data were analyzed in COVID-19 patients satisfying the inclusion criteria. RESULTS: 14% of patients had co-infections, out of which urinary tract infection was found in 9%. Patients with co-infections had a higher mortality rate (p<0.0004). Urinary co-infection emerged as an independent risk factor for mortality (p <0.001). CONCLUSION: Co-infections associated with COVID-19 infections are an essential risk factor for morbidity and mortality. Early identification and timely treatment of co-infections may help in improving clinical outcomes.

Comparison of clinical characteristics and outcome in RT-PCR positive and false-negative RT-PCR for COVID-19: A Retrospective analysis.

Cases with SARS-CoV-2 RT-PCR negative pneumonia are an understudied group with uncertainty remaining regarding their treatment approach. We aimed to compare the clinical and radiological characteristics of RT-PCR positive and clinically diagnosed RT-PCR negative COVID-19. This was a single-centre retrospective study conducted at a tertiary care hospital in Western India. All patients (age ≥18 years) with suspicion of COVID-19 with SARI (severe acute respiratory infections) who were subjected to RT-PCR testing (nasal/oropharyngeal swab) were included. Based on RTPCR results, patients were categorized and compared for demographic, clinical, and biochemical characteristics and outcomes. Out of 500 patients, 339 (67.8%) found RT-PCR positive. Except for the radiological findings, both groups differ in clinical presentation, disease severity (inflammatory markers), and outcome. RT-PCR-positive patients had raised ferritin, NLR (Neutrophil-Lymphocyte ratio), LDH, and high mortality compared to the swab-negative group. In-hospital mortality was also significantly high in RT-PCR positive group (HR=1.9, 95% CI=1.4-2.5, p=0.001). On multivariate analysis, NLR, ferritin, and d-dimer were the independent predictors of mortality in RT-PCR-positive (p=0.038, 0.054, and 0.023). At the same time, raised TLC (total leukocyte count) and procalcitonin were the risk factors for poor outcomes in RT-PCR-negative patients (p=0.041 and 0.038). We found significantly raised ferritin, NLR, and LDH levels and increased mortality in RT-PCR positive patients compared to RT-PCR negative. Incorporating clinical features, radiological, and biochemical parameters could be prudent while managing the RT-PCR-negative patients.

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.

Role of Breath Biopsy in COVID-19.

BACKGROUND: COVID-19 is a highly contagious respiratory disease that can be transmitted through human exhaled breath. It has caused immense loss and has challenged the healthcare sector. It has affected the economy of countries and thereby affected numerous sectors. Analysis of human breath samples is an attractive strategy for rapid diagnosis of COVID-19 by monitoring breath biomarkers. CONTENT: Breath collection is a noninvasive process. Various technologies are employed for detection of breath biomarkers like mass spectrometry, biosensors, artificial learning, and machine learning. These tools have low turnaround time, robustness, and provide onsite results. Also, MS-based approaches are promising tools with high speed, specificity, sensitivity, reproducibility, and broader coverage, as well as its coupling with various chromatographic separation techniques providing better clinical and biochemical understanding of COVID-19 using breath samples. SUMMARY: Herein, we have tried to review the MS-based approaches as well as other techniques used for the analysis of breath samples for COVID-19 diagnosis. We have also highlighted the different breath analyzers being developed for COVID-19 detection.

SARS-CoV-2 IgG Antibody and its Clinical Correlates in Convalescent Plasma Donors: An Indian Experience.

SARS-CoV-2, a novel coronavirus, emerged a year ago in Wuhan, China causing a new pandemic. Convalescent plasma therapy has been applied previously to many infectious diseases and has shown a successful result. This study was planned to assess the Anti-SARS-CoV-2 IgG antibody levels in convalescent COVID-19 patients. In this study, serum samples from 210 persons infected by SARS-CoV-2, treated and discharged from the hospital were collected. Anti-SARS-CoV-2 IgG antibody levels were detected using a chemiluminescence assay. A directory of convalescent plasma donors was created. Anti-SARS-CoV-2 IgG antibody levels vary substantially in the study population with a mean of 51.2 AU/ml. On comparing the serum anti-SARS-CoV-2 IgG antibody levels, a significant difference was observed between the subjects who had cough and those who did not (p = 0.0004). Similar significant findings were found with total protein and globulin levels on comparing the individuals with different antibody status (positive, negative and equivocal). The middle-aged and old age people had high Ab titres compared to younger individuals and the duration of the hospital stay was found to be positively correlated with the anti-SARS-CoV-2 IgG antibody. Cough, age and duration of the hospital stay was found to play a significant role in the development of Anti-SARS-CoV-2 IgG levels. Further, the data suggests that blood groups have a lesser impact on the severity of disease and the development of antibodies. Patients who present with the cough are more likely to develop antibodies.

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.

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.

Prediction of potential drug interactions between repurposed COVID-19 and antitubercular drugs: an integrational approach of drug information software and computational techniques data.

INTRODUCTION: Tuberculosis is a major respiratory disease globally with a higher prevalence in Asian and African countries than rest of the world. With a larger population of tuberculosis patients anticipated to be co-infected with COVID-19 infection, an ongoing pandemic, identifying, preventing and managing drug-drug interactions is inevitable for maximizing patient benefits for the current repurposed COVID-19 and antitubercular drugs. METHODS: We assessed the potential drug-drug interactions between repurposed COVID-19 drugs and antitubercular drugs using the drug interaction checker of IBM Micromedex®. Extensive computational studies were performed at a molecular level to validate and understand the drug-drug interactions found from the Micromedex drug interaction checker database at a molecular level. The integrated knowledge derived from Micromedex and computational data was collated and curated for predicting potential drug-drug interactions between repurposed COVID-19 and antitubercular drugs. RESULTS: A total of 91 potential drug-drug interactions along with their severity and level of documentation were identified from Micromedex between repurposed COVID-19 drugs and antitubercular drugs. We identified 47 pharmacodynamic, 42 pharmacokinetic and 2 unknown DDIs. The majority of our molecular modelling results were in line with drug-drug interaction data obtained from the drug information software. QT prolongation was identified as the most common type of pharmacodynamic drug-drug interaction, whereas drug-drug interactions associated with cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp) inhibition and induction were identified as the frequent pharmacokinetic drug-drug interactions. The results suggest antitubercular drugs, particularly rifampin and second-line agents, warrant high alert and monitoring while prescribing with the repurposed COVID-19 drugs. CONCLUSION: Predicting these potential drug-drug interactions, particularly related to CYP3A4, P-gp and the human Ether-à-go-go-Related Gene proteins, could be used in clinical settings for screening and management of drug-drug interactions for delivering safer chemotherapeutic tuberculosis and COVID-19 care. The current study provides an initial propulsion for further well-designed pharmacokinetic-pharmacodynamic-based drug-drug interaction studies. PLAIN LANGUAGE SUMMARY: Introduction:: Tuberculosis is a major respiratory disease globally with a higher prevalence in Asian and African countries than rest of the world. With a larger population of tuberculosis patients predicted to be infected with COVID-19 during this period, there is a higher risk for the occurrence of medication interactions between the medicines used for COVID-19 and tuberculosis. Hence, identifying and managing these interactions is vital to ensure the safety of patients undergoing COVID-19 and tuberculosis treatment simultaneously.Methods:: We studied the major medication interactions that could likely happen between the various medicines that are currently given for COVID-19 and tuberculosis treatment using the medication interaction checker of a drug information software (Micromedex®). In addition, thorough molecular modelling was done to confirm and understand the interactions found from the medication interaction checker database using specific docking software. Molecular docking is a method that predicts the preferred orientation of one medicine molecule to a second molecule, when bound to each other to form a stable complex. Knowledge of the preferred orientation may be used to determine the strength of association or binding affinity between two medicines using scoring functions to determine the extent of the interactions between medicines. The combined knowledge from Micromedex and molecular modelling data was used to properly predict the potential medicine interactions between currently used COVID-19 and antitubercular medicines.Results:: We found a total of 91 medication interactions from Micromedex. Majority of our molecular modelling findings matched with the interaction information obtained from the drug information software. QT prolongation, an abnormal heartbeat, was identified as one of the most common interactions. Our findings suggest that antitubercular medicines, mainly rifampin and second-line agents, suggest high alert and scrutiny while prescribing with the repurposed COVID-19 medicines.Conclusion:: Our current study highlights the need for further well-designed studies confirming the current information for recommending safe prescribing in patients with both infections.

Endocrine Dysfunction among Patients with COVID-19: A Single-center Experience from a Tertiary Hospital in India.

OBJECTIVE: COVID-19 has emerged as a multi-system disease with the potential for endocrine dysfunction. We aimed to study the hormonal profile of hospitalized patients with COVID-19 at a tertiary care referral hospital at Jodhpur, India. DESIGN: A hospital-based clinical study of endocrine profile of COVID-19 patients conducted from 15th May to 30th June 2020 after ethical approval. MEASUREMENTS: Fasting blood samples for free thyroxine (T4), free tri-iodothyronine (T3), thyroid stimulating Hormone (TSH), serum prolactin; basal and 1 h post-intramuscular adrenocorticotropic hormone (ACTH) stimulated cortisol, interleukin-6 (IL-6), and high sensitivity C-reactive protein (hsCRP) were collected within 24 h of admission after written informed consent. All hormones and IL-6 were analyzed by chemiluminescent immunoassay. hsCRP was measured by immune-turbidimetric assay. RESULTS: Of 235 patients studied, 14% had severe disease and 5.5% died. Adrenal insufficiency was present in 14%, most of whom had mild disease. A robust adrenal response was observed in those with severe disease. Basal and post-ACTH serum cortisol were significantly increased in severe disease or those who died compared to those who were mild or asymptomatic. Basal and post-ACTH serum cortisol showed a significant positive correlation with hsCRP but not with IL-6. Low T3 and low T4 syndrome were documented in 25% and 5%, respectively. Serum TSH and FT3 levels declined significantly from asymptomatic to severe category. Hyperprolactinemia was found in 21 patients. hsCRP showed a rising trend with disease severity while IL-6 did not. CONCLUSIONS: Endocrine dysfunction in the form of adrenal insufficiency, low T3, and low TSH syndrome and hyperprolactinemia were common COVID-19 hospitalized patients.

Predictors of Clinical Outcomes in Adult COVID-19 Patients Admitted to a Tertiary Care Hospital in India: an analytical cross-sectional study.

BACKGROUND: The outbreak ofsevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has resulted inexponential rise in the number of patients getting hospitalised with corona virus disease 2019 (COVID-19). There is a paucity of data from South East Asian Region related to the predictors of clinical outcomes in these patients. This formed the basis of conducting our study. METHODS: This was an analytical cross-sectional study. Demographic, clinical, radiological and laboratory data of 125 patients was collected on admission. The study outcome was death or discharge after recovery. For univariate analysis, unpaired t-test, Chi-square and Fisher's Exact test were used. Receiver operating characteristic (ROC) curves were plotted for Sequential Organ Failure Assessment (SOFA) score and few laboratory parameters. Logistic regression was applied for multivariate analysis. RESULTS: Elderly age, ischemic heart disease and smoking were significantly associated with mortality. Elevated levels of D-dimer and lactate dehydrogenase (LDH) and reduced lymphocyte counts were the predictors of mortality. The ROCs for SOFA score curve showed a cut-off value ≥ 3.5 (sensitivity- 91.7% and specificity- 87.5%), for IL-6 the cut-off value was ≥ 37.9 (sensitivity- 96% and specificity- 78%) and for lymphocyte counts, a cut off was calculated to be less than and equal to 1.46 x 109per litre (sensitivity-75.2%and specificity- 83.3%). CONCLUSION: Old age, smoking history, ischemic heart disease and laboratory parameters including elevated D-dimer, raised LDH and low lymphocyte counts at baseline are associated with COVID-19 mortality. A higher SOFA score at admission is a poor prognosticator in COVID-19 patients.

Interleukin-6 Perpetrator of the COVID-19 Cytokine Storm.

COVID-19 has emerged as a global pandemic. It is mainly manifested as pneumonia which may deteriorate into severe respiratory failure. The major hallmark of the disease is the systemic inflammatory immune response characterized by Cytokine Storm (CS). CS is marked by elevated levels of inflammatory cytokines, mainly interleukin-6 (IL-6), IL-8, IL-10, tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). Of these, IL-6 is found to be significantly associated with higher mortality. IL-6 is also a robust marker for predicting disease prognosis and deterioration of clinical profile. In this review, the pivotal role played by IL-6 in the immuno-pathology of COVID-19 has been illustrated. The role of IL-6 as a pleiotropic cytokine executing both pro and anti-inflammatory activities has been reviewed. ADAM 10, a metalloproteinase switches the anti-inflammatory pathway of IL-6 to pro inflammatory hence blocking the action of ADAM 10 could be a new therapeutic strategy to mitigate the proinflammatory action of IL-6. Furthermore, we explore the role of anti-IL6 agents, IL-6 receptor antibodies which were being used for autoimmune diseases but now are being repurposed for the therapy of COVID-19.

Rational use of PPE and preventing PPE related skin damage.

On 31st December, 2019, an outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was declared in Wuhan, China. On 24 March 2020, there was a nationwide lockdown for 21 days, followed by Janata curfew on 22nd March. As the pandemic has developed and spread across continents, everyone including policy makers have realized shortage of personal protective equipment (PPE) such as N95 respirators, coverall, and face shields. This is one of the major factors putting healthcare workers not only at risk of infection but also to various side effects of prolonged use of PPE. Based on international experiences, new ideas in procuring and mass manufacturing, rational use of PPE equipment is the need of hour, especially for developing nations which lack adequate resources and infrastructure for manufacturing PPEs.

Probiotics in Prevention and Treatment of COVID-19: Current Perspective and Future Prospects.

Saving lives and flattening the curve are the foremost priorities during the ongoing pandemic spread of SARS-CoV-2. Developing cutting-edge technology and collating available evidence would support frontline health teams. Nutritional adequacy improves general health and immunity to prevent and assuage infections. This review aims to outline the potential role of probiotics in fighting the COVID-19 by covering recent evidence on the association between microbiota, probiotics, and COVID-19, the role of probiotics as an immune-modulator and antiviral agent. The high basic reproduction number (R0) of SARS-CoV-2, absence of conclusive remedies, and the pleiotropic effect of probiotics in fighting influenza and other coronaviruses together favour probiotics supplements. However, further support from preclinical and clinical studies and reviews outlining the role of probiotics in COVID-19 are critical. Results are awaited from many ongoing clinical trials investigating the benefits of probiotics in COVID-19.

Clinical outcome, viral response and safety profile of chloroquine in COVID-19 patients - initial experience.

INTRODUCTION: Chloroquine and its analogues are currently being investigated for the treatment and post exposure prophylaxis of COVID-19 due to its antiviral activity and immunomodulatory activity. MATERIAL AND METHODS: Confirmed symptomatic cases of COVID-19 were included in the study. Patients were supposed to receive chloroquine (CQ) 500 mg twice daily for 7 days. Due to a change in institutional protocol, initial patients received chloroquine and subsequent patients who did not receive chloroquine served as negative controls. Clinical effectiveness was determined in terms of timing of symptom resolution and conversion rate of reverse transcriptase polymerase chain reaction (RT-PCR) on day 14 and day 15 of admission. RESULTS: Twelve COVID-19 patients formed the treatment arm and 17 patients were included in the control arm. The duration of symptoms among the CQ treated group (6.3 ± 2.7 days) was significantly (p-value = 0.009) lower than that of the control group (8.9 ± 2.2 days). There was no significant difference in the rate of RT-PCR negativity in both groups. 2 patients out of 12 developed diarrhea in the CQ therapy arm. CONCLUSION: The duration of symptoms among the treated group (with chloroquine) was significantly lower than that of the control group. RT-PCR conversion was not significantly different between the 2 groups.

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.

Obesity and COVID-19: A Fatal Alliance.

Most people infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV2) are mildly symptomatic while few progress to critical illness and succumb to the infection. The disease severity is seen to be associated with increasing age and underlying comorbid conditions. Obesity, responsible for various metabolic disorders, appears to be a risk factor in determining the severity of infection despite any age group. Though this association is clinically relevant, the mechanisms underlying are not fully elucidated. SARS CoV2 enters host cell via Angiotensin Converting Enzyme 2 receptor, expression of which is upregulated in visceral fat tissue in obese people, underscoring the fact that adipose tissue is a potential reservoir for virus. Adipose tissue is also a source of many proinflammatory mediators and adipokines. High baseline C-Reactive Protein, interleukin 6, hyperleptinemia with Leptin resistance and hypoadiponectinemia associated with obesity explains the preexisting inflammatory state in obese individuals which predisposes them to worse outcomes and fatality.