Therapeutic Potentials of Black Seeds (Nigella sativa) in the Management of COVID-19-A Review of Clinical and In-silico Studies

Background: Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), and patients with COVID-19 are managed mainly using repurposed conventional drugs, which target the viral entry and viral replication of SARS CoV-2 along with standard care and supportive therapy. Objective(s): This review article focuses on the potential benefits of black seeds (Nigella sativa) observed in clinical and in silico molecular docking studies of COVID-19. Method(s): The literature was searched using databases such as LitCOVID, Web of Science, Google Scholar, bioRxiv, medRxiv, Science Direct, EBSCO, Scopus, EMBASE, and reference lists to identify published manuscripts or preprints related to the prevention or treatment of COVID-19 with black seeds (N. sativa) or their phytoconstituents. Result(s): Various clinical studies and in silico molecular docking studies determined that black seeds (N. sativa) and their bioactive phytoconstituents have potential activity against SARS CoV-2 infection. Conclusion(s): Patients with COVID-19 could be managed using black seeds (N. sativa) along with supportive care, which would speed up the recovery and decrease the mortality rate. More randomized controlled clinical trials would further establish the safety and efficacy of N. sativa in COVID-19 patients. Copyright © 2023 Bentham Science Publishers.

Clinical Profile and Treatment Outcome of Severe Aplastic Anemia in Adults: An Experience from Tertiary Care Centre in North India

Introduction: Untreated/refractory severe aplastic anemia (SAA) is associated with very high mortality. Allogenic bone marrow transplantation or immunosuppressive therapy remains mainstay of treatment but these treatments are timely available to only a select subset of patients. Recently eltrombopag has been approved for treatment of SAA. Aims & Objectives: We aimed to describe clinical profile and treatment response in patients with SAA from a tertiary care centre. Material(s) and Method(s): A retrospective analysis of patients diagnosed with SAA over a period of 7 years from January 2015-December 2021 was performed. The details of demographic profile, laboratory features, treatment given and response were analyzed. Result(s): Ninety patients were diagnosed with SAA during this period out of which 18 patients went elsewhere for treatment. Seventy-two patients who received treatment in our hospital were included in the analysis. Sixty-two patients were SAA while 10 VSAA. PNH screening was done in 24 patients, out of which 17 (70%) had small clone. The details of treatment and response achieved is shown in Table 1. Eight patients (11.1%) received matched related donor allogenic hemopoietic cell transplant, out of which one had rejection followed by auto recovery while one died 6 months later due to covid 19 disease. Sixty-four patients received immunosuppressive therapy, forty-nine (76%) responded. Recurrence of SAA occurred in two patients who has achieved complete response to ATG therapy;one received second course of horse ATG + CSA + ETP and responded again. Conclusion(s): Timely diagnosis and appropriate treatment selection is of utmost importance to achieve optimal outcome in severe aplastic anemia. Eltrombopag has become an important addition not only in front line but also in relapsed refractory aplastic anemia. Patients lacking donor, or resources for ATG should be treated with cyclosporine and eltrombopag as early as possible. (Table Presented).

CHARACTERIZING the SCOPE and DRIVERS of the IMPACT of COVID-19 on LOCAL HIV EPIDEMICS

Background: The potential impact of COVID-19 pandemic on the US HIV epidemic remains unclear. Characterizing the scope and main drivers of the impact of COVID-19 on HIV incidence can inform future HIV policy. Methods: We characterized the impact of COVID-19 pandemic and attendant lockdowns on HIV epidemiology via reductions in sexual transmission (0-50%) from March 1st, 2020 to July 4th, 2021, plus reductions in viral suppression (0-40%), HIV testing (0-50%), and pre-exposure prophylaxis use (0-30%) from March 1st to February 4th, 2022. Using the Johns Hopkins Epidemiologic and Economic Model (JHEEM) of HIV transmission, we projected HIV infections from 2020 to 2025 across 32 high-priority US cities and compared these to projections if COVID-19 had not emerged. Results: Across all 32 cities, 80% of simulations projected a decline in HIV incidence in 2020 (median decrease of 15% from 2019), before rebounding in 2021 (96% of simulations, median increase of 13% from 2020)-see Figure, panel B. Projections of the impact of the COVID-19 pandemic on cumulative HIV incidence from 2020-2025 varied by city, ranging from a median of 3% fewer incident cases in Las Vegas to 9% more incident cases in Boston (Figure, panel A). At the MSA level, reductions in sexual transmission had the strongest impact on incidence, followed by reductions in viral suppression. Among simulations that incorporated large (>25%) reductions in viral suppression due to COVID-19, adverse impacts on HIV incidence were greater where pre-pandemic levels of viral suppression were higher (ranging from a median 1% increase in cumulative incidence 2020-25 in Chicago with 52% pre-pandemic suppression, to a 24% increase in Seattle with 86% pre-pandemic suppression-Figure, panel C). Conclusion: The effects of COVID-19 on HIV transmission remain uncertain and differ substantially at the local level. Disruptions to HIV care and viral suppression due to the COVID-19 pandemic may have greater impact in increasing HIV incidence in settings where pre-existing suppression levels are higher.

Serosurvey for Nipah virus in bat population of southern part of India.

Nipah virus (NiV) is one of the priority pathogens with pandemic potential. Though the spread is far slower than SARS-CoV-2, case fatality is the biggest concern. Fruit bats belonging to genus Pteropus are identified to be the main reservoir of the virus causing sporadic cases and outbreaks in Malaysia, Bangladesh and India. The sudden emergence of Nipah in Kerala, India during 2018-2019 has been astonishing with respect to its introduction in the unaffected areas. With this, active Nipah virus surveillance was conducted among bat populations in Southern part of India viz., Karnataka, Kerala, Tamil Nadu, Telangana, Puducherry and Odisha during January-November 2019. Throat swabs/rectal swabs (n = 573) collected from Pteropus medius and Rousettus leschenaultii bat species and sera of Pteropus medius bats (n = 255) were screened to detect the presence of Nipah viral RNA and anti-Nipah IgG antibodies respectively. Of 255 P. medius bats sera samples, 51 bats (20%) captured from Karnataka, Kerala, Tamil Nadu and Puducherry demonstrated presence of anti-Nipah IgG antibodies. However, the presence of virus couldn't be detected in any of the bat specimens. The recent emergence of Nipah virus in Kerala in September 2021 warrants further surveillance of Nipah virus among bat populations from the affected and remaining states of India.

Nipah Virus Outbreak in Kerala State, India Amidst of COVID-19 Pandemic.

We report here a Nipah virus (NiV) outbreak in Kozhikode district of Kerala state, India, which had caused fatal encephalitis in a 12-year-old boy and the outbreak response, which led to the successful containment of the disease and the related investigations. Quantitative real-time reverse transcription (RT)-PCR, ELISA-based antibody detection, and whole genome sequencing (WGS) were performed to confirm the NiV infection. Contacts of the index case were traced and isolated based on risk categorization. Bats from the areas near the epicenter of the outbreak were sampled for throat swabs, rectal swabs, and blood samples for NiV screening by real-time RT-PCR and anti-NiV bat immunoglobulin G (IgG) ELISA. A plaque reduction neutralization test was performed for the detection of neutralizing antibodies. Nipah viral RNA could be detected from blood, bronchial wash, endotracheal (ET) secretion, and cerebrospinal fluid (CSF) and anti-NiV immunoglobulin M (IgM) antibodies from the serum sample of the index case. Rapid establishment of an onsite NiV diagnostic facility and contact tracing helped in quick containment of the outbreak. NiV sequences retrieved from the clinical specimen of the index case formed a sub-cluster with the earlier reported Nipah I genotype sequences from India with more than 95% similarity. Anti-NiV IgG positivity could be detected in 21% of Pteropus medius (P. medius) and 37.73% of Rousettus leschenaultia (R. leschenaultia). Neutralizing antibodies against NiV could be detected in P. medius. Stringent surveillance and awareness campaigns need to be implemented in the area to reduce human-bat interactions and minimize spillover events, which can lead to sporadic outbreaks of NiV.

Typically ''atypical'': A case series of atypical chronic myeloid leukemia

Aims & Objectives: Atypical Chronic myeloid leukemia (aCML) is a rare subtype of MDS/MPN. The diagnosis of aCML has evolved over years with more evidence from cytogenetic and molecular studies. We report here a case series of three patients with aCML that was picked up based on morphology and molecular workup. Patients/Materials & Methods: Case 1: A 68-year male with incidental detection of leukocytosis on routine hemogram without organomegaly with Hb11.6 g/dL,TLC 35X103/μl,platelets 41X103/ ll,DLC My30MM5N53L8E3Baso1%. Bone marrow was hypercellular with M:E ratio7.7:1, severe dysgranulopoiesis, 07% blasts,and dysmegakaryopoiesis (>50%). His extended MPN reflex panel (BCR-ABL1, JAK2, CALR, MPL) was negative. Provisional diagnosis of aCML was made. NGS panel revealed multiple mutations in ZRSR2, ASXL1, RUNX1, SF3B1, EZH2, TET2 genes. He has completed 6 cycles of Azacytidine and remains stable for 8 months since the diagnosis. Case 2: A 76-year old male with suspected CML presented with mild hepatosplenomegaly with Hb 8.9 g/dL,TLC 46X103/μl, platelets 75X103/μl, DLC Blast3My12MM8 N66Ly8 Mono2Baso1% and 2nRBC/100 WBCs. Bone marrow was hypercellular with M:E 6.3:1, significant dysgranulopoiesis 03% blasts, and dysmegakaryopoiesis. His extended MPN reflex panel was negative. NGS revealed mutations in ASXL1 and KRAS genes. After diagnosing aCML he was started on hydroxyurea and remains stable after 6 months of diagnosis. Case 3: A 71-year old female with suspected CML based on moderate splenomegaly and hemogram showed Hb 8.9 g/dL,TLC 65.94X103/μl, Platelets 45X103/μl with DLC Blast1My29MM22N38Ly5Eo4Baso2% Bone marrow was hypercellular with M:E 5.8:1, prominent left shift in granulocytic series, 01% blasts, no dysgranulopoiesis. There was significant dysmegakaryopoiesis. A provisional diagnosis of CML vs MDS/MPN was kept and was advised molecular workup. BCR-ABL1 and JAK2 mutation were negative. NGS panel revealed ASXL1 and SF3B1 gene mutations. Finally diagnosed as aCML and treated with Hydroxyurea. She developed undiagnosed fever during COVID19 lockdown and succumbed to her illness. Discussion & Conclusion: Atypical CML is a very rare entity with close differential diagnoses of accelerated phase of CML or MDS/ MPN-U. However as more awareness of this entity has emerged, more patients are subjected to NGS evaluation, thus contributing to the knowledge about this under-reported diagnosis from the third world.

Detection of coronaviruses in Pteropus & Rousettus species of bats from different States of India.

Background & objectives: Bats are considered to be the natural reservoir for many viruses, of which some are potential human pathogens. In India, an association of Pteropus medius bats with the Nipah virus was reported in the past. It is suspected that the recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) also has its association with bats. To assess the presence of CoVs in bats, we performed identification and characterization of bat CoV (BtCoV) in P. medius and Rousettus species from representative States in India, collected during 2018 and 2019. Methods: Representative rectal swab (RS) and throat swab specimens of Pteropus and Rousettus spp. bats were screened for CoVs using a pan-CoV reverse transcription-polymerase chain reaction (RT-PCR) targeting the RNA-dependent RNA polymerase (RdRp) gene. A single-step RT-PCR was performed on the RNA extracted from the bat specimens. Next-generation sequencing (NGS) was performed on a few representative bat specimens that were tested positive. Phylogenetic analysis was carried out on the partial sequences of RdRp gene sequences retrieved from both the bat species and complete viral genomes recovered from Rousettus spp. Results: Bat samples from the seven States were screened, and the RS specimens of eight Rousettus spp. and 21 Pteropus spp. were found positive for CoV RdRp gene. Among these, by Sanger sequencing, partial RdRp sequences could be retrieved from three Rousettus and eight Pteropus bat specimens. Phylogenetic analysis of the partial RdRp region demonstrated distinct subclustering of the BtCoV sequences retrieved from these Rousettus and Pteropus spp. bats. NGS led to the recovery of four sequences covering approximately 94.3 per cent of the whole genome of the BtCoVs from Rousettus bats. Three BtCoV sequences had 93.69 per cent identity to CoV BtRt-BetaCoV/GX2018. The fourth BtCoV sequence was 96.8 per cent identical to BtCoV HKU9-1. Interpretation & conclusions: This study was a step towards understanding the CoV circulation in Indian bats. Detection of potentially pathogenic CoVs in Indian bats stresses the need for enhanced screening for novel viruses in them. One Health approach with collaborative activities by the animal health and human health sectors in these surveillance activities shall be of use to public health. This would help in the development of diagnostic assays for novel viruses with outbreak potential and be useful in disease interventions. Proactive surveillance remains crucial for identifying the emerging novel viruses with epidemic potential and measures for risk mitigation.