Apolipoprotein ε in Brain and Retinal Neurodegenerative Diseases.

Alzheimer's disease (AD) is the most common form of dementia that remains incurable and has become a major medical, social, and economic challenge worldwide. AD is characterized by pathological hallmarks of senile plaques (SP) and neurofibrillary tangles (NFTs) that damage the brain up to twenty years before a clinical diagnosis is made. Interestingly these pathological features have also been observed in retinal neurodegenerative diseases including age related macular degeneration (ARMD), glaucoma and diabetic retinopathy (DR). An association of AD with these diseases has been suggested in epidemiological studies and several common pathological events and risk factors have been identified between these diseases. The E4 allele of Apolipoprotein E (APOE) is a well-established genetic risk factor for late onset AD. The ApoE ε4 allele is also associated with retinal neurodegenerative diseases however in contrast to AD, it is considered protective in AMD, likewise ApoE E2 allele, which is a protective factor for AD, has been implicated as a risk factor for AMD and glaucoma. This review summarizes the evidence on the effects of ApoE in retinal neurodegenerative diseases and discusses the overlapping molecular pathways in AD. The involvement of ApoE in regulating amyloid beta (Aß) and tau pathology, inflammation, vascular integrity, glucose metabolism and vascular endothelial growth factor (VEGF) signaling is also discussed.

COVID-19 associated acute demyelination masquerading as stroke: a case report

BackgroundDuring the recent outbreak of COVID-19, various atypical extrapulmonary manifestations are being seen, including neurological ones. Reported cases mainly include encephalopathy, myelitis, and cranial nerve involvement. This case describes uncommon neuroradiological finding in the context of COVID-19.Case presentationWe report an atypical case of COVID-19 presenting with stroke-like episode, with MRI brain showing isolated bilateral posterior internal capsule involvement. This has rarely been reported in literature.ConclusionAs the numbers of COVID-19 cases are increasing, such atypical presentations should be kept in mind.

Updated landscape of inhaled medications to combat COVID-19.

Plain language summary The COVID-19 pandemic has overwhelmed the healthcare systems worldwide. This calls for development of medicines that work effectively to decrease the death toll and severity of the infection. These medicines should be easy to administer to maintain patient compliance. Inhalation therapy is a needleless and painless route of administration that leads to fewer side effects. Various types of carriers are used for delivery of drugs via inhalation route. Vaccines can also be delivered via inhalation. Various researchers have studied vaccines via inhalation route, which have the potential to be translated into developing inhalable vaccines for COVID-19.

The COVID-19 pandemic has overwhelmed the healthcare systems worldwide. This calls for development of medicines that work effectively to decrease the death toll and severity of the infection. These medicines should be easy to administer to maintain patient compliance. Inhalation therapy is a needleless and painless route of administration that leads to fewer side effects. Various types of carriers are used for delivery of drugs via inhalation route. Vaccines can also be delivered via inhalation. Various researchers have studied vaccines via inhalation route, which have the potential to be translated into developing inhalable vaccines for COVID-19.

A New Diagnostic Criteria and Grading System of Rhino-Maxillary Mucormycosis based on Cone Beam Computed Tomographic Findings.

Background: Mucormycosis is a rare opportunistic fungal infection, which has a rapidly progressive and fulminant course with fatal outcome. It is the need of the hour to diagnose and treat the increasing cases urgently. Aim: The aim of this article is to study the common radiographic features of rhinomaxillary mucormycosis (RMM), find diagnostic criteria, and grade the disease according to the radiographic features. Settings: This study was conducted at Face Three-Dimensional Cone-Beam Computed Tomography (CBCT) Center, Aurangabad, Maharashtra. Materials and Methods: CBCT scans of 30 patients who were referred for CBCT scanning of suspected RMM were retrospectively evaluated for relevant radiological data. Results: The most common CBCT features of RMM were osteolytic lesions in alveolar bone, palate, nose and nasal cavity, and zygoma along with involvement of paranasal sinuses. About 76.66% of patients had a history of COVID-19 infection. Conclusion: According to the collected data, the scans of probable rhinomaxillary mucormycosis were graded in three groups - mild, moderate, and severe. The goal of this article is to emphasize the most overlook diagnostic entity - CBCT and its significant importance in early diagnosis, treatment, and prognosis of RMM. Early diagnosis of RMM can save the patients from the extent of morbidity and mortality.

Detection of SARS-CoV-2 in a free ranging leopard (Panthera pardus fusca) in India.

We report an incidence of natural infection of SARS-CoV-2 in free-ranging Indian leopard (Panthera pardus fusca). The case was detected during routine screening. Post-mortem and laboratory examination suggested virus-induced interstitial pneumonia. Viral genome could be detected in various organs including brain, lung, spleen, and lymph nodes by real-time PCR. Whole-genome sequence analysis confirmed infection of Pango lineage B.1.617.2 of SARS-CoV-2. Till now, only Asiatic lions have been reported to be infected by SARS-CoV-2 in India. Infections in animals were detected during peak phase of pandemic and all the cases were captive with close contacts with humans, whereas the present case was observed when human cases were significantly low. No tangible evidence linked to widespread infection in the wild population and the incidence seems to be isolated case. High nucleotide sequence homology with prevailing viruses in humans suggested spillover infection to the animal. This report underlines the need for intensive screening of wild animals for keeping track of the virus evolution and development of carrier status of SARS-CoV-2 among wildlife species. Supplementary Information: The online version contains supplementary material available at 10.1007/s10344-022-01608-4.

Delta variant SARS-CoV-2 infections in pediatric cases during the second wave in India.

BACKGROUND: During October 2020, Delta variant was detected for the first time in India and rampantly spread across the globe. It also led to second wave of pandemic in India which affected millions of people. However, there is limited information pertaining to the SARS-CoV-2 strain infecting the children in India. METHODS: Here, we assessed the SARS-CoV-2 lineages circulating in the pediatric population of India during the second wave of the pandemic. Clinical and demographic details linked with the nasopharyngeal/oropharyngeal swabs (NPS/OPS) collected from SARS-CoV-2 cases (n = 583) aged 0-18 year and tested positive by real-time RT-PCR were retrieved from March to June 2021. RESULTS: Symptoms were reported among 37.2% of patients and 14.8% reported to be hospitalized. The E gene CT value had significant statistical difference at the point of sample collection when compared to that observed in the sequencing laboratory. Out of these 512 sequences 372 were VOCs, 51 were VOIs. Most common lineages observed were Delta, followed by Kappa, Alpha and B.1.36, seen in 65.82%, 9.96%, 6.83% and 4.68%, respectively in the study population. CONCLUSION: Overall, it was observed that Delta strain was the leading cause of SARS-CoV-2 infection in Indian children during the second wave of the pandemic. We emphasize on the need of continuous genomic surveillance in SARS-CoV-2 infection even amongst children.

Environmental surface sampling for SARS-CoV-2 around hospitalized patients with COVID-19 in a tertiary care hospital

Background: The contamination of patients' surroundings by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains understudied. Discordant findings of SARS-CoV-2 RNA in environmental samples were noted in many reports. Aims and Objectives: The study assessed the extent and persistence of environmental surface contamination in real-world surfaces around COVID-19 patients. Materials and Methods: We sampled the surroundings of two intensive care unit (ICU) and one ward that were occupied by laboratory-confirmed coronavirus disease 2019 (COVID-19) patients. Frequently touched environmental surfaces near patients were swabbed before and after daily environmental disinfection. Results: Of 355 environmental samples, 6 (1.69%) were positive by real-time reverse-transcription polymerase chain reaction assay. Among those, 5 of 75 ICU samples (6.67%) and 1 of 75 ward environmental samples (1.33%) in the pre-fumigation areas occupied by COVID-19 positive patients were positive. No samples obtained within the first 2 h of fumigation and surface disinfection was found to be positive. Conclusion: Surrounding environment of symptomatic COVID-19 patients can get contaminated and in cases of asymptomatic COVID-19 patients, contamination of their surroundings was an uncommon phenomenon. Strict contact barrier precaution, routine cleaning with disinfectants are mandatory hospital infection control practices in the management of patients infected with SARS-CoV-2. [ FROM AUTHOR] Copyright of Asian Journal of Medical Sciences is the property of Manipal Colleges of Medical Sciences and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Recent advances in low-cost, portable automated resuscitator systems to fight COVID-19.

World is fighting one of its greatest battle against COVID-19 (a highly infectious disease), leading to death of hundreds of thousands of people around the world, with severe patients requiring artificial breathing. To overcome the shortage of ventilators in medical infrastructure, various low-cost, easy to assemble, portable ventilators have been proposed to fight the ongoing pandemic. These mechanical ventilators are made from components that are generally readily available worldwide. Such components are already associated with day-to-day gadgets or items and which do not require specialized manufacturing processes. Various designs have been proposed, focussing on meeting basic requirements for artificial ventilation to fight the ongoing pandemic. But some people are against the usage of these mechanical ventilators in real-life situations, owing to poor reliability and inability of these designs to meet certain clinical requirements. Each design has its own merits and demerits, which need to be addressed for proper designing. Therefore, this article aims to provide readers an overview of various design parameters that needs to be considered while designing portable ventilators, by systematic analysis from available pool of proposed designs. By going through existing literature, we have recognized multiple factors influencing device performance and how these factors need to be considered for efficient device operation.

Lifestyle modification in school-going children before and after COVID-19 lockdown.

Purpose: To evaluate the impact of COVID-19 lockdown restrictions on lifestyle of school-going children. Methods: This was a questionnaire-based prospective study of 1237 school children aged 9-14 years enrolled from various private and government schools across Delhi in October-December 2020. These children were being followed-up over the previous 2 years (before pandemic) with details of their lifestyle like near/outdoor/reading activities using a questionnaire as a part of another study. The data during the COVID-19 lockdown was collected by telephonic interview. This was compared to similar information collected from this cohort in the pre-Covid period in 2019 when the students had a regular physical school curriculum. Results: A significant decline was noted in time spent on outdoor activity (from 8.5 hours/week in pre-COVID-19 time to 1.6 hours/week during COVID-19 lockdown; P < 0.001) and doing homework offline (from 15.3 hour/week to 14 hours/week; P < 0.001). A significant increase was noted in screen time spent on digital devices (from 6.2 hours/week to 19.8 hours/week; P<0.001), and watching television (from 12.2 hours/week to 13.4 hours/week; P < 0.001). The rise in the digital on-screen time was significantly more in boys (P < 0.001) and in students from private schools (P < 0.001). The rise in the duration of watching television was significantly more in girls than boys (P < 0.05). Conclusion: COVID-19 lockdown has markedly impacted the lifestyle of school children by significantly decreasing the outdoor activity and increasing the screen time, thereby pre-disposing them to ocular ill-health and myopia. This necessitates the adoption of guidelines for promoting healthy digital habits in children.

Evaluation of hematological, coagulation and inflammatory biomarker's role in predicting the severity of disease in patients with COVID-19, admitted in designated COVID-19 hospital of central India.

BACKGROUND: COVID-19 is a pandemic viral disease that has affected the Indian population very badly with more than 8.46 million cases and > 0.125 million deaths. AIM: Primary objective of the study is to establish the role of hematological, coagulation and inflammatory biomarkers in early identification of clinically severe covid-19 cases. MATERIALS AND METHODS: This study was conducted from July 2020 to August 2020 at a dedicated COVID-19 referral hospital in central India. Only RT-PCR confirmed COVID-19 positive 300 cases admitted in the hospital were included in this study. Based on the clinical assessment, patients were categorised as mild, moderate, and severe groups as per ICMR guidelines. Blood samples of all cases were tested for haematological, coagulation and inflammatory biomarkers and mean values were compared among the three groups of patients. RESULTS: 46% patients belonged to >60 years of age group. Hematological parameters like total leukocyte count, absolute neutrophil count, Neutrophil: Lymphocyte ratio, Platelet: Lymphocyte ratio significantly increased with lymphocytopenia (P=0.001). Coagulation profile(D-dimer and PT) and inflammatory biomarkers like CRP, LDH, ferritin, procalcitonin and NT- Pro BNP, all were significantly increased with severity of patients(p=0.001). ROC plotted for all the parameters between severe v/s non-severe cases showed that CRP, LDH and D-dimer had a good discriminative precision with AUC >0.8. CONCLUSION: We suggest that biochemical markers like CRP, LDH and D-dimer can be used as a screening tool to differentiate severe patients from non-severe patients of Covid-19 disease in order to identify severe disease at early stage for optimal utilization of resources & reducing further morbidity & mortality.

Efficacy of two siddha polyherbal decoctions, Nilavembu Kudineer and Kaba Sura Kudineer, along with standard allopathy treatment in the management of mild to moderate symptomatic COVID-19 patients-a double-blind, placebo-controlled, clinical trial.

BACKGROUND AND AIM: Globally, the ongoing pursuit in exploring an effective drug to combat severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus has not met with significant success to date. Indian traditional medicines, especially polyherbal formulations like Nilavembu Kudineer (NVK) and Kaba Sura Kudineer (KSK) of the Siddha system of medicine, have been used as public health interventions for controlling viral epidemics like dengue and Chikungunya. These traditional therapies have been found safe, effective, and widely accepted. The current study evaluates the comparative efficacy of NVK and KSK as opposed to the placebo, in the management of mild to moderate COVID-19 disease. METHODS: The study was a double-blind, placebo-controlled comparative clinical trial, with the primary objective of determining the efficacy of KSK and NVK. Patients (n=125) diagnosed with mild to moderate COVID-19 symptoms were enrolled in the study over a period of 4 months (Aug 2020-Dec 2020). Participants were randomized into 3 arms; placebo-decaffeinated tea in Arm I, NVK in Arm II, and KSK in Arm III. Each arm received 60 ml of the respective treatment twice a day, post morning and evening meals, along with standard allopathy treatment for a maximum of 10 days. The main outcome measures of the study were the reduction in SARS-CoV-2 viral load, hospital stay, and time taken by the patients to become asymptomatic from symptomatic. Efficacy assessments included clinical symptoms (fever, cough, and breathlessness) each day and real-time reverse transcription-polymerase chain reaction (RT-PCR), liver function test (LFT), renal function test (RFT), and electrolytes and electrocardiogram (ECG) at baseline (day 0) and days 3, 6, and 10. Post-treatment, participants were followed up for 30 days via phone for adverse effects if any. Effects of drugs on inflammatory markers (IL6) at the end of treatment were also recorded. Adverse events (AE) were monitored throughout the study. RESULTS: The results revealed that when compared to patients in the placebo arm, those in NVK and KSK arms showed a statistically significant reduction in hospital stay time, reduction in viral load of SARS-CoV-2, and the time taken to become symptomatic from asymptomatic. Out of 125 COVID-19 patients recruited, 120 completed the study; two from the placebo group developed severe symptoms and were shifted to the intensive care unit (ICU) and three patients from Arms II and III withdrew from the study. The mean age of females (n=60) and males (n=60) enrolled was between 40.2 and 44.3 years, respectively. Results were more promising for all the patients in NVK and KSK arms as all enrolled participants (100%) under this group got discharged by day 6 as compared to only 42.5% (n=17) from the placebo group on that day. The hospital stay time for patients in Arm I was significantly longer (mean [SD]=8.4 [2.0] days) as compared to the Arms II and III (mean [SD]=4.7 [1.5] and 4.2 [1.5] days, respectively (Kruskal-Wallis test, P=0.0001). Patients in the three groups took a significantly different number of days to become asymptomatic. While Arm II and III patients took mean of 2.5 and 1.7 days, respectively, Arm I, patients took a mean of 4.2 days (Kruskal-Wallis test, P=0.0001). In all, two adverse events were recorded, one for vomiting and one for diarrhea lasting a day in Arm I and Arm II, respectively. The mean value of interleukin-6 (IL6) was significantly different in comparison to the placebo-decaffeinated tea arm (NVK=2.6 and KSK=2.2, placebo=4.0, P=0.02). The other blood biochemical parameters like C-reactive protein (CRP), lactate dehydrogenase (LDH), ferritin, and D-dimer that were analyzed at the baseline and at the time of discharge from the hospital, were not significantly different in the three arms. CONCLUSION: NVK and KSK arms showed a statistically significant reduction in hospital stay time, reduction in viral load of SARS-CoV-2, and time taken for patients to become asymptomatic from symptomatic, when compared to the placebo (decaffeinated tea). The primary outcome measures of the KSK arm were significantly better than those in the NVK arm.

Immune mediating molecules and pathogenesis of COVID-19-associated neurological disease.

BACKGROUND: Long period of SARS-CoV-2 infection has been associated with psychiatric and cognitive disorders in adolescents and children. SARS-CoV-2 remains dormant in the CNS leading to neurological complications. The wide expression of ACE2 in the brain raises concern for its involvement in SARS-CoV-2 infection. Though, the mechanistic insights about blood-brain barriers (BBB) crossing by SARS-CoV-2 and further brain infection are still not clear. Moreover, the mechanism behind dormant SARS-CoV-2 infections leading to chronic neurological disorders needs to be unveiled. There is an urgent need to find out the risk factor involved in COVID-19-associated neurological disease. Therefore, the role of immune-associated genes in the pathogenesis of COVID-19 associated neurological diseases is presented which could contribute to finding associated genetic risk factors. METHOD: The search utilizing multiple databases, specifically, EMBASE, PubMed (Medline), and Google Scholar was performed. Moreover, the literature survey on the involvement of COVID-19, neuropathogenesis, and its consequences was done. DESCRIPTION: Persistent inflammatory stimuli may promote the progression of neurodegenerative diseases. An increased expression level of cytokine, chemokine, and decreased expression level of immune cells has been associated with the COVID-19 patient. Cytokine storm was observed in severe COVID-19 patients. The nature of SARS-CoV-2 infection can be neuroinflammatory. Genes of immune response could be associated with neurodegenerative diseases. CONCLUSION: The present review will provide a useful framework and help in understanding COVID-19-associated neuropathogenesis. Experimental studies on immune-associated genes in COVID-19 patients with neurological manifestations could be helpful to establish its neuropathogenesis.

Turning a New Chapter in Neurosurgery Outpatient Services: Telemedicine A "Savior" in this Pandemic.

BACKGROUND: Teleconsultation services in India, especially in neurosurgery, are relatively new. Despite its large-scale adoption during the COVID-19 pandemic, comprehensive analyses of patients' perspectives and hurdles are lacking. MATERIALS AND METHODS: We conducted an anonymized telephonic survey of consecutive neurosurgical patients who availed telemedicine services at our institute, using a validated, structured questionnaire. To prevent bias, interviewers were not involved in the study design/analyses. Patients' perception of usefulness and performance of teleconsultation was graded on a 5-point Likert scale. RESULTS: Of the 330 patients who availed teleconsultation services, 231 (70%) completed the survey. Even though 91% of the respondents had access to a smartphone, only 10% received a video-based teleconsult. As per respondents, the challenges included poor network (7%), suboptimal communication/discussion (5.6%), lack of physical examination (6%), and misinterpretation of prescription by pharmacists/patients (6%). The majority of the respondents (58%) either agreed/strongly agreed that teleconsultation helped them tide over the medical exigency during the lockdown; however, the clinical diagnosis did not influence this response (P = 0.21). The vast majority of the respondents felt that teleconsultation is beneficial (97%), as it minimizes their exposure to COVID-19. One-third of the patients preferred this service over physical visits and 60% agreed to its continuation till resumption of routine care. Access to video-teleconsultation was the chief suggestion in 39 of 74 suggestions received. CONCLUSIONS: Telemedicine in neurosurgery offers favorable patient satisfaction during this pandemic and may be a satisfactory alternative to physical outpatient services in the future. Video-based teleconsults should be the preferred modality of communication for neurosurgery patients.

Knowledge of COVID-19 and its implications in dental treatment, and practices of personal protective equipment among dentists: A survey-based assessment.

BACKGROUND: Oral health-care providers are always at a risk of transmitting or acquiring airborne, saliva-borne, or blood-borne infections due to their proximity to the patient's mouth, contact with saliva, and handling of sharp instruments. the aim this study was to evaluate the knowledge of the dentists regarding COVID-19, methods to prevent its transmission, and implications of COVID-19 in dental treatment. MATERIALS AND METHODS: It was a cross-sectional online survey. There were 35 questions in total, divided into sections of knowledge of COVID-19, practices of personal protective equipment (PPE), and knowledge of implications of COVID-19 in dental treatment. Both convenience sampling and snowball sampling were used, so that maximal participation could be ensured. The results were analyzed using descriptive statistics and making comparisons among various groups. The data were summarized as proportions and percentages (%). All the associations were tested using the Chi-square test, ANOVA, and Pearson's correlation coefficient. Statistical analyses were performed using SPSS version 19.0. RESULTS: 26.8% of respondents had a high knowledge, 61.5% had good knowledge, 10.1% had low knowledge, and 6 (1.5%) had nil knowledge about COVID-19. No significant association was found between qualification and knowledge level among the respondents (P = 0.053). Both graduates and postgraduates had low knowledge regarding effective PPE components (P = 0.053), donning (P = 0.888), and doffing (P = 0.745). Only 52.9% of postgraduates and 43.7% graduates answered correctly about the sequence of donning, and 47.9% of postgraduates and 46.1% of graduates had knowledge regarding correct doffing sequence of PPE. Furthermore, knowledge was low regarding the implications of COVID-19 in dental treatment. CONCLUSION: Although the dentists were found to have high/good knowledge scores regarding COVID-19, there was a lack of knowledge regarding hand hygiene, proper use of PPE, and implications of COVID-19 in dental treatment. Thus, they need to be trained and sensitized regarding the same.

Tele-rehabilitation for visually challenged students during COVID-19 pandemic: Lesson learned.

PURPOSE: The COVID-19 outbreak poses a global crisis in health care delivery system, including habilitation and rehabilitation services. In this study, we shared our experiences on telerehabilitation services established primarily for students with visual disabilities (SwVD) amidst COVID-19 pandemic and its outputs. METHODS: Following the lockdown declared on March 23, 2020, the rehabilitative team of a tertiary eye center in north India received information that many visually challenged students (VCS) were stranded in schools for the blind in Delhi, and feeling with anxiety and panic in absence of teachers. Shortly, the room for vision rehabilitation clinic was set-up for telefacilities. The intended services were explained while disseminating the mobile numbers. A semi-structured questionnaire consisting of closed and open-ended was developed to record COVID-19 knowledge and concerns. Inductive content analysis was used to report the qualitative information. RESULTS: As of June 30, 2020, a total of 492 clients contacted the team, with maximum from Delhi (41.5%), and predominantly males (78.8%). Around 80.3% of callers were VCS with age range of 11 to 30 years. The two most frequently encountered health needs were itching in eyes (36.1%) and headache (29%). Television news was the most used medium among callers to get COVID-19 information. Cough is a less frequently known mode of transmission (28%), similarly handwashing as a less known for prevention (17.2%). Eight concerns were recorded based on qualitative data analysis. CONCLUSION: Telerehabilitation provides valuable insights and has the potential to address various concerns, uncertainty, anxiety, and fear among VCS during the pandemic.

A double blinded placebo controlled comparative clinical trial to evaluate the effectiveness of Siddha medicines, Kaba Sura Kudineer (KSK) & Nilavembu Kudineer (NVK) along with standard Allopathy treatment in the management of symptomatic COVID 19 patients - a structured summary of a study protocol for a randomized controlled trial.

OBJECTIVES: The primary objectives of the study are to determine the effectiveness of the Kaba Sura Kudineer (KSK) & Nilavembu Kudineer (NVK) along with standard Allopathy Treatment to compared with Placebo (Decaffeinated Tea) with standard Allopathy Treatment in the management of Symptomatic COVID 19 patients and also in reduction of Hospital Stay Time & Changes in Immunological (IL6) and Bio Chemical Markers (Ferritin, CRP, D-Dimer and LDH). The secondary objectives are to evaluate the safety of the trial medicines and their effects in the reduce the risks of the disease. In addition, to document the profile of Symptomatic COVID 19 patients as per Siddha Principles. TRIAL DESIGN: A Double Blinded, Three arm, Single Centre, Placebo Controlled, Exploratory and comparative Randomized Controlled Trial PARTICIPANTS: Patients who were admitted to the COVID Care Centre at Govt. Institute of Medical Sciences. Noida in India will be recruited. These will be patients with Mild and Moderate symptoms with laboratory confirmed COVID 19 (RT - PCR Tested Positive) aged 18-65, willing and consenting to participate. INTERVENTION AND COMPARATOR: Arm I: Decaffeinated Tea (Placebo - similar in taste and appearance to the other Two Decoctions), 60 Ml Morning and Night after Food, along with standard Allopathy Treatment for 10 days. Arm II: Nilavembu Kudineer (The Siddha Medicines which is used as a standard Anti-Viral drug for the past Pandemics by Siddha Physicians) 60 Ml Morning and Night after Food, along with standard Allopathy Treatment for 10 days. Arm III: Kaba Sura Kudineer (The Siddha Medicine which is proposed to be used as a Treatment for COVID 19 based on Siddha Literature) 60 Ml Morning and Night after Food, along with standard Allopathy Treatment for 10 days. The investigational drugs are registered products under the Govt.of India and bought from GMP Certified Manufacturing Units. MAIN OUTCOMES: Primary outcomes: 1. Reduction in Viral load of SARS-CoV-2 at the end of treatment (10 days). 2. Time taken to convert Patient from symptomatic to Asymptomatic based on Reduction in clinical symptoms (10 days). 3. Effect of drugs inflammatory markers (IL6,) at the end of treatment (10 days). 4. Reduction in hospital stay time (20 days follow up). (Based on RT PCR CT Value 3rd, 6th if needed 10th day). (Based on IL 6 Value needed 10th day or IL6 value on turning negative. (entry level/exit level). Secondary outcomes (10 days): 1. Reduction in use of Intensive Supportive Care. 2. Reduction in incidence of complications (Acute Respiratory Distress Syndrome, other systemic complications). 3. MuLBSTA score for viral pneumonia (multinodular infiltration, hypo-lymphocytosis, bacterial co infection, Total Leucocyte Count (TLC ≤ 0.8 x 109/L), smoking history, hyper-tension and age) score. 4. Laboratory markers (Haematological & Biochemical Markers). 5. Adverse events/effects Siddha-based measurements. 6. Siddha Udaliyal assessment by using Yakkai Ilakkanam (YI) Tool to diagnose body condition for covid-19 patients. RANDOMISATION: The assignment of the participants into 3 Groups will be allocated in 1:1:1 Ratio through randomization Blocks in Microsoft Excel by a Statistician who is not involved in the study. The allocation scheme will be made by another statistician by using a closed envelope after the assessment of eligibility and Informed consent procedures. The groups will be balanced for age and sex with 3:1 Ratio in each group for mild: severe COVID-19 symptoms. BLINDING: The Study is Double Blinded. Participants and Investigators were blinded. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): Sample size could not be calculated, Since there are no prior trials on KSK and NVK as a comparative trial. In addition, there are no prior trials on KSK and NVK in this region. A total Number of 120 Patients, 40 each in 3 groups will be recruited in 1:1:1 Ratio. TRIAL STATUS: Protocol Number : SCRUND GIMS Noida Study 1,Version: 2.0 Protocol Date : 20.08.2020 The recruitment period is completed for the trial. The Trial started its recruitment on 22.8.2020. We anticipate study including data analysis will finish in January 2021. This is to state that it was a late submission from authors for publication of the protocol to the BMC, after enrolment in the study was over. TRIAL REGISTRATION: The trial protocol was registered with CTRI (Clinical Trial Registry of India) and number is CTRI/2020/08/027286 on 21.08.2020 FULL PROTOCOL: The full Protocol is attached as an additional file, Accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated. This letter serves as a summary of the key elements of the full protocol. The Study protocol has been reported in accordance with the SPIRIT guidelines.

Can Host Cell Proteins Like ACE2, ADAM17, TMPRSS2, Androgen Receptor be the Efficient Targets in SARS-CoV-2 Infection?

A novel betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV- -2), which caused a large disease outbreak in Wuhan, China in December 2019, is currently spreading across the world. Along with binding of the virus spike with the host cell receptor, fusion of the viral envelope with host cell membranes is a critical step in establishing successful infection of SARS-CoV-2. In this entry process, a diversity of host cell proteases and androgen receptor play a very important role directly or indirectly. These features of SARS-CoV-2 entry contribute to its rapid spread and severe symptoms, high fatality rates among infected patients. This review is based on the latest published literature including review articles, research articles, hypothetical manuscript, preprint articles and official documents. The literature search was made from various published papers on physiological aspects relevant to SARS-CoV and SARS-CoV-2. In this report, we focus on the role of host cell proteases (ACE2, ADAM17, TMPRSS2) and androgen receptor (AR) in SARS-CoV-2 infection. The hypotheses put forth by us are based on the role played by the proteases ACE2, ADAM17, TMPRSS2 and AR in SARS-CoV-2 infection, which were deduced based on various studies. We have also summarized how these host proteins increase the pathology and the infective ability of SARS-CoV-2 and we posit that their inhibition may be a therapeutic option for preventing SARS-CoV-2 infection.