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Since ancient times, spices such as black pepper, cinnamon, ginger, turmeric, garlic, black cumin, clove, ocimum, saffron, and nutmeg constitute an important part of foods and beverages in India. Besides, adding aroma and flavour to the food, they are also known for multiple medicinal benefits. During the COVID-19 pandemic, an interesting pattern of disease prevalence and severity was observed especially in the countries where spices are consumed regularly. It has attracted researchers worldwide to explore the therapeutic potential of spices in COVID-19 management. Various in silico studies have reported good binding affinities of spices and derived components towards structural druggable targets of SARS-CoV2. There are several compelling pieces of evidence for the role of spices in the attenuation of inflammatory cytokine storm which is the crux in the pathogenesis of COVID-19. Therefore, this review is written to provide deep insights into the role of food spices and their underlying mechanism in targeting SARS-CoV2. Based on experimentally verified data from different in-vitro, in-vivo, in-silico, and clinical studies, the information presented will certainly help in the development of promising drug therapeutics or preventive strategies to deal with SARS-CoV2. Further studies geared towards the development of drugs based on spices and derived compounds are suggested. [ABSTRACT FROM AUTHOR]

Background: The coronavirus disease (COVID-19) has spread worldwide, and the pathogenic mechanism is still under investigation. Preliminary reports suggest a link between ABO blood groups and susceptibility to severe COVID-19. Aim: The aim of this study was to confirm the link between ABO blood type, the risk of coronavirus infection, and the severity of COVID-19 disease. Setting and Design: This was a retrospective cohort study. Materials and Methods: The study was carried out at tertiary care rural hospital in Central India. The patients admitted to the COVID unit over 6 months were enrolled in the study. The data further statistically analyzed the outcome of COVID-19 disease and its relation with the patient's blood group and serum ferritin levels. Results: The data analysis observed no significant impact of blood group on the outcome of COVID-19 in terms of death and cured cases. The mortality rate was 27.2% in the AB blood group, with the highest reported serum ferritin levels (1007.78 ± 1301.25). Compared to other blood groups, A (8.1%), followed by O (13.5%), with the lowest mortality rate (P = 0.31). Alanine transferase and aspartate transferase were maximally seen in patients having blood group AB +, and lower values were observed in blood group A. Conclusions: Blood groups A and O were considered COVID-19 protective in mortality following the cytokine storm. AB blood group had high serum ferritin levels, so it can be a potential tool to predict mortality and may be considered the culprit for the triggering "cytokine storm.". [ABSTRACT FROM AUTHOR]

Infection with the SARS-CoV-2 virus results in manifestation of several clinical observations from asymptomatic to multi-organ failure. Biochemically, the serious effects are due to what is described as cytokine storm. The initial infection region for COVID-19 is the nasopharyngeal/oropharyngeal region which is the site where samples are taken to examine the presence of virus. We have now carried out detailed proteomic analysis of the nasopharyngeal/oropharyngeal swab samples collected from normal individuals and those tested positive for SARS-CoV-2, in India, during the early days of the pandemic in 2020, by RTPCR, involving high throughput quantitative proteomics analysis. Several proteins like annexins, cytokines and histones were found differentially regulated in the host human cells following SARS-CoV-2 infection. Genes for these proteins were also observed to be differentially regulated when their expression was analyzed. Majority of the cytokine proteins were found to be up regulated in the infected individuals. Cell to Cell signaling interaction, Immune cell trafficking and inflammatory response pathways were found associated with the differentially regulated proteins based on network pathway analysis. [ABSTRACT FROM AUTHOR]

There have been more than 31378143 confirmed coronavirus disease 2019 (COVID-19) cases in India. It was declared a pandemic by the World Health Organization (WHO) on March 11, 2020. Because the risk of severe COVID-19 is not consistent across all individuals, uncertainty is linked to disease development. COVID-19 results have been related to systemic inflammation as a predictor. In COVID-19, increased levels of inflammatory markers have been associated with cytokine storm, coagulopathy, and endothelial dysfunction. A significant amount of research suggests that these results have a role in the cause of death in individuals suffering from a severe form of COVID-19. We aim to show our experience of COVID-19 at GITAM Institute of Medical Sciences and Research (GIMSR), Visakhapatnam. We analyzed data on 558 patients admitted to our dedicated COVID hospital during post unlock (UL) 2.0 in India from August 2 to August 31, 2020. The mean age was 43.65 years; 69% of them were male. Using MoHFW India severity guidelines, 68.10% were mild, 18.64% were moderate, and 13.26% were severe cases. Fatigue (66.13%) was the most common complaint, followed by anosmia (63.80%), fever (57.53%), diarrhea (56.09%), shortness of breath (22.40%), and others. The most common preexisting comorbidity seen in our patients was diabetes mellitus and hypertension, respectively. Laboratory parameters revealed mean hemoglobin of 13.04±1.91 gm/dl, mean total leukocyte count of 7378.49±3229 cells/cumm, mean platelet count of 2.3±0.8 lakhs/cumm, mean erythrocyte sediment rate of 40±30 mm/hr, mean ferritin level of 335.96 ng/ml, mean D-dimer level of 794.88 ng/ml and mean CRP of 23.27 mg/l. Severity was associated with higher age, symptomatic presentation, elevated leucocytes, and elevated inflammatory markers. [ABSTRACT FROM AUTHOR]

Background: Initiation of tocilizumab (TCZ) treatment in patients with coronavirus disease 2019 (COVID-19) during the early phases of cytokine storm is crucial. This study evaluated the clinical experience of TCZ use in the treatment of patients with COVID-19. Methods: This retrospective observational study included patients (>18 years) with confirmed COVID19 treated with TCZ alone/in combination with other drugs. Data related to demographics, clinical characteristics, radiological parameters, oxygen/ventilator/vasopressor support, treatment parameters, laboratory investigations pre- and post-TCZ treatment, and clinical outcomes were retrieved from medical records. Results: Out of 95 patients (mean age, 55 years), 68.4% and 31.6% of patients had moderate and severe COVID-19 disease, respectively. The mean time to TCZ administration from symptom onset was 8.7 days. At the time of admission, the mean oxygen saturation (SpO2) was 90.4% and mean concentration of fraction of inspired oxygen (FiO2) was 80.6%. The most commonly received dose of TCZ was 400 mg (84.2%) intravenously. The mean concentration of FiO2 and SpO2 improved significantly during the treatment (P < 0.001) compared to before TCZ initiation. The change in median levels of C-reactive protein (CRP) from baseline to post-treatment (63.0 vs. 4.5 mg/dL; P < 0.001) was significant. Post TCZ treatment, 73.6% of patients improved; whereas 26.4% of patients died. Acute respiratory distress syndrome (23.2%) and elevated transaminases (12.6%) were the most commonly reported adverse events. Conclusion: Tocilizumab administration during earlier phase of cytokine storm syndrome leads to reversal of abnormal SpO2 and FiO2 concentrations to normal levels and rapid decline of elevated CRP levels in patients with COVID-19. [ABSTRACT FROM AUTHOR]

Background: COVID-19 mediated immune dysregulation and cytokine storm can precipitate and aggravate Moyamoya angiopathy (MMA), influencing its disease course. This index study was undertaken to prospectively evaluate the status of neurological symptoms of MMA in relation to COVID-19 affection. Methodology and results: Follow-up MMA patients of institute's Stroke-clinic were telephonically interview from 24th March to 30th September, 2020. The first call familiarized them with COVID-19 symptoms and neurological manifestations of MMA, followed by monthly-calls with predesigned questionnaire. Patients with suggestion of COVID-19 underwent nasopharyngeal-swab-testing for COVID-19 Reverse transcription-polymerase chain reaction (RT-PCR) positive cases were subjected to antibody levels for COVID-19 Enzyme-linked immunoassay (ELISA) 8–12 weeks after recovery. During symptomatic phase till 14 days of asymptomatic, they were contacted daily/alternate day. Any new onset/worsening of neurological symptoms were noted. The baseline clinico-radiological details were obtained from stroke-clinic registery. Subsequently, all data were analyzed and compared using descriptive statistics. Seventy four of 104 MMA patients could be contacted and enrolled. The mean age, time since last follow-up and compliance to previously prescribed medication were 23.5 ± 16.1 years, 9.2 ± 1.7 months and 90.5% (n = 67), respectively. Aggravation/new onset neurological symptom were seen in 64.3% (n = 9) of COVID-19 positive MMA (n = 14), of which 8 were seen among the 11 pediatric COVID-19 positive MMA [(Transient ischemic attacks) TIA-4, TIA with headache-1, seizure-2, stroke causing mortality-1]. Conclusion: COVID-19 infection can potentiate MMA causing significant morbidity and mortality, especially in children. Providing optimal care for severe diseases (such as MMA) in developing countries during pandemic remains a challenge. [ABSTRACT FROM AUTHOR]

Today, we are living in the era of Coronavirus Disease-2019 (COVID-19), a pandemic that has affected almost the whole globe. It has rightly been called as the 'twenty-first-century plague' which has garnered considerable attention from researchers, pharma companies, policymakers, and media. Though vaccines are being deployed and people are eagerly receiving vaccination; the duration of conferred immunity, the possibility of re-infection of recovered/vaccinated individuals, the consequence of the new mutation in SARS-CoV-2 and its impact and challenge for the efficacy and degree of protection that a potential vaccine could provide is under question. In the absence of any definite answer, people are turning towards natural remedies and spices. India is known globally as the land of spices. Spices like ginger, garlic, black pepper, cardamom, turmeric, clove, cinnamon, etc., are known for their rich aroma, texture, and immunity boosting ingredients. These are rich sources of antioxidants such as flavonoids and alkaloids. The antioxidants present in them, neutralise the free radicals generated inside the body during viral infections and also prevent cellular damage. These exhibit anti-inflammatory activity and have the potential to combat "cytokine storm" in severe COVID-19 infection. Their potential has been realized by the public and has led to a tremendous increase in global demand and consumption. The present review enlists the active ingredients present in important spices and addresses their antioxidants, antiinflammatory, and anti-viral action. Traditional Indian spices that are not only a cardinal part of the diet but are affordable, easily available can be viewed as the light at the end of the tunnel to combat the current COVID-19 conditions as a preventive measure. [ABSTRACT FROM AUTHOR]

• Haploidentical stem cell transplantation with post-transplant cyclophosphamide can be considered a viable option in children with Fanconi anemia, particularly in resource-limited settings given the high costs of hematopoietic stem cell transplantations, with an overall survival of 68.4%. • Peripheral blood stem cells provide early engraftment, decreasing the risk of prolonged neutropenia and sepsis, with a focus on maintaining CD34 and CD3 dose of a minimum of 5 × 106/kg and 1.5 × 108/kg recipient body weight, respectively, in the infused graft. • Supportive care measures, including N -acetyl cysteine infused concomitantly with cyclophosphamide on day +3 and day +4, can help decrease the incidence of severe mucositis and transaminitis and thereby reduce regimen-related toxicity. • Monitoring ferritin as a surrogate marker for IL-6 levels and cytokine release syndrome with log increases combined with clinical features as the basis for instituting early steroids can decrease the mortality associated with cytokine release syndrome. • Ruxolitinib can be a useful second-line agent for chronic graft-versus-host disease (GVHD) with good responses in those with skin and mouth GVHD. Fanconi anemia is the most common inherited bone marrow failure syndrome, and hematopoietic stem cell transplantation (HSCT) is the only curative option. Post-transplant cyclophosphamide (PTCy) is challenging in this group of children, given their increased sensitivity to chemotherapy. We performed a retrospective analysis of the data on children diagnosed with Fanconi anemia who underwent a haploidentical HSCT with PTCy from January 2014 to December 2019. Nineteen children (male/female, 0.75:1) underwent 21 haplo-HSCTs with PTCy. Fludarabine, low-dose cyclophosphamide, and 200 centi-gray total body irradiation were included in the conditioning regimen with 25 mg/kg PTCy on days +3 and +4. Haplo-graft was from a sibling in 38% and father in 57% of transplants. The source of stem cells was peripheral blood stem cells in 81% and bone marrow in 19% of transplants, with a median CD34 dose of 5.0 × 106/kg. We documented engraftment in 84% and primary graft failure in 10% of transplants. N -acetylcysteine (NAC) was infused concomitantly during cyclophosphamide in 13 children. Grade 2 and 3 mucositis was lower among those who received NAC as compared to those who did not (30% and 15% versus 33% and 50%), while transaminitis was higher among those who did not receive the infusion. The incidence of acute graft-versus-host disease (GVHD) was 68%, and 81% of these were steroid responsive (grade I/II). We documented chronic GVHD in 25% children, predominantly involving the skin and mouth, which responded to low-dose steroids and ruxolitinib. Serum ferritin was monitored twice weekly as a surrogate marker for cytokine release syndrome due to nonavailability of IL-6 levels. A 1- or 2-log increase in the titers of ferritin associated with clinical features guided the early addition of steroids in the periengraftment period. The mean survival was found to be less among those with high serum ferritin (>10,000 ng/dL) in the periengraftment period as compared to those with ferritin <10,000 ng/dL (mean survival of 25 ± 10 months versus 50 ± 6 months, respectively). The overall survival in our cohort was 68.4%, with a mean survival time of 41.5 months (95% confidence interval, 29.3 to 53.8 months), with a statistically significant correlation between inferior outcome and having received over 15 transfusions before HSCT (P =.01). PTCy can be considered a viable option in children with Fanconi anemia, particularly in resource-limited settings given the high costs of HSCTs. Focused interventions in this subset of children help improve survival outcomes. Early identification of cytokine release syndrome and risk-adapted steroid therapy during engraftment helps prevent mortality. The concomitant use of NAC during cyclophosphamide infusion helps reduce oxygen free radical related tissue damage and regimen-related toxicity. [ABSTRACT FROM AUTHOR]

Itolizumab is a first-in-class anti-CD6 monoclonal antibody that was initially developed for various cancers and was later developed and approved in India for treatment of moderate to severe chronic plaque psoriasis in 2013. This drug is now being re-purposed for COVID-19. The potential utility of itolizumab in COVID-19, based on its unique mechanism of action in ameliorating cytokine release syndrome (CRS), was proposed first in Cuba with approval of a single-arm clinical trial and expanded access use. Subsequently, a phase II, open-label, randomized, placebo-controlled trial has been conducted in 30 COVID-19 patients in India after receiving regulatory permission. Based on the results, the Indian drug regulatory agency recently approved itolizumab in July 2020 for 'restricted emergency use' for the treatment of CRS in moderate to severe acute respiratory distress syndrome (ARDS) due to COVID-19. This has drawn sharp criticism within the scientific community, with the approval being granted on the basis of a relatively small phase II trial, without conduct of a conventional phase III trial, and lacking availability of the claimed supportive real-world evidence in the public domain to date. In a global scenario where finding a successful treatment for COVID-19 is of utmost priority, a biologic agent has been re-purposed and approved with a successfully completed RCT, in a country where cases and mortality due to COVID-19 are growing exponentially. However, instead of welcoming the approval with open arms, many doubts are being raised. This is an issue that needs to be considered and dealt with sensitively, as well as scientifically. [ABSTRACT FROM AUTHOR]

Covid-19 worldwide pandemic struck India when 1st case was reported on Jan30th 2020. Amidst the great challenge faced by treating physicians, to cure their patients, with continuously evolving management strategies, some also got infected, despite of all preventive measures taken. We present here two such cases where the doctors themselves have narrated their course of disease and management plus back up support. Proper strategic management of the illness according to WHO and ICMR protocols, along with good physicians' cover 24/7 was the hallmark of good outcome. Timely identification and immediate treatment of cytokine storm helped in allaying the worsening of pulmonary and other systemic effects of the disease. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 has affected millions of people worldwide. This pandemic requires newer medical management strategies to control the morbidity and mortality associated with the disease. Several approaches, including global targeting of inflammation or neutralizing a single key inflammatory mediator, are being employed to cope with cytokine storms in coronavirus disease-2019 (COVID-19). The role of anti-inflammatory biologics, such as acalabrutinib, tocilizumab, anakinra, and itolizumab can become relevant. Itolizumab is a humanized recombinant immunoglobulin G1 monoclonal antibody. It targets the extracellular, scavenger receptor cysteine-rich (SRCR) distal domain 1 of CD6 and is responsible for priming, activation, and differentiation of T-cells. Itolizumab has been approved by the Drug Controller General of India for the treatment of COVID-19 in India. Here, we shared our clinical experience of 20 patients having moderate acute respiratory distress syndrome (ARDS) due to COVID-19 on treatment with itolizumab. We observed the mortality benefit with single-dose itolizumab (1.6 mg/kg) in patients having moderate COVID-19 ARDS. [ABSTRACT FROM AUTHOR]

Cytokine storm is the exaggerated immune response often observed in viral infections. It is also intimately linked with the progression of COVID-19 disease as well as associated complications and mortality. Therefore, targeting the cytokine storm might help in reducing COVID-19-associated health complications. The number of COVID-19 associated deaths (as of January 15, 2021; https://www.worldometers.info/coronavirus/) in the USA is high (1199/million) as compared to countries like India (110/million). Although the reason behind this is not clear, spices may have some role in explaining this difference. Spices and herbs are used in different traditional medicines, especially in countries such as India to treat various chronic diseases due to their potent antioxidant and anti-inflammatory properties. To evaluate the literature available on the anti-inflammatory properties of spices which might prove beneficial in the prevention and treatment of COVID-19 associated cytokine storm. A detailed literature search has been conducted on PubMed for collecting information pertaining to the COVID-19; the history, origin, key structural features, and mechanism of infection of SARS-CoV-2; the repurposed drugs in use for the management of COVID-19, and the anti-inflammatory role of spices to combat COVID-19 associated cytokine storm. The literature search resulted in numerous in vitro , in vivo and clinical trials that have reported the potency of spices to exert anti-inflammatory effects by regulating crucial molecular targets for inflammation. As spices are derived from Mother Nature and are inexpensive, they are relatively safer to consume. Therefore, their anti-inflammatory property can be exploited to combat the cytokine storm in COVID-19 patients. This review thus focuses on the current knowledge on the role of spices for the treatment of COVID-19 through suppression of inflammation-linked cytokine storm. [Display omitted] [ABSTRACT FROM AUTHOR]