Conceptual Development of Industrial Biotechnology for Commercial Production of Vaccines and Biopharmaceuticals

Conceptual Development of Industrial Biotechnology for Commercial Production of Biopharmaceuticals and Vaccines provides insights on how to bring sustainability into biologic drug production. The cumulative facts and figures within in the book are helpful to promoters in monitoring value chain transfer process of super quality biologics for better return in profits. In addition, this is a useful reference for students, researchers and scientists in biotechnology, pharmaceutical science, medical sciences, and the R&D division of biotechnology-based industries. Conceptual development of biotechnology has taken new avenues with the integration of medical sciences, physical science, and engineering, hence this is a timely source. The current global market for vaccines, especially COVID-19, is tremendous. Bivalent oral polio vaccine, diphtheria, tetanus-containing, and measles-containing vaccines have a high demand internationally and recombinant DNA technology and protein engineering are helpful in the production of quality bio-products. © 2023 Elsevier Inc. All rights reserved.

Docking Based Identification of Bioactive Diosmin as Potential Multi- Targeted Anti SARS-Cov-2 Agent

The pandemic COVID-19, caused by the organism severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) belongs to the family Coronoviridae has become a serious global healthcare crisis. The biggest demand of the present time is to develop efficacious medication for the treatment of SARS-CoV-2. In the present study, we performed the interaction of 50 flavonoids selected from the Pubchem database, with five efficacious protein targets for SARS-CoV-2: main protease (Mpro), spike glycoprotein-receptor binding domain (SGp-RBD), RNA-dependent RNA polymerase (RdRp), angiotensin converting enzyme-2 (ACE-2) and non-structural protein15 (NSP15, an endonuclease). All the work involve in the present study was accomplished by using Maestro 12.4 (Schrodinger Suite) to obtain the docking scores and ADME-T study result of selected ligands with the five effective target proteins of SARS-CoV-2. Molecular docking-based results indicated that diosmin has the most favorable docking scores-10.16,-11.52,-9.75,-11.25 and-10.25 kcal/mol for the Mpro, SGp-RBD, ACE-2, RdRp and NSP-15 protein targets and had acceptable drug suitability as a therapeutic agent against COVID-19. The structure of this compound can be further useful to medicinal chemists, pharmacologists, and clinicians for efficiently discovering or developing effective drugs to cure COVID-19.

Changing Gender Roles at Homes: Impact of Corona Pandemic

Women cook. They spend half of their life in the kitchen. Men can also cook, but they rarely do. This division of gender roles is ancient. With our words and acts, we comply and perpetuate such a tradition. But times are changing. Outlooks are changing. Women are more ready to pursue their dreams and aspirations. Participation of women in workforce has grown in all sectors of the economy. Women are slowly and steadily getting into roles which were hitherto reserved for men. Induction of women into combat roles in defence services in India is one such step. They have proved that they are no less than men in any job. Even in rural sector, women are forming Self Help Groups (SHG) to be economically independent. While it is a welcoming change, women are still tied to the domestic roles at their home. They attend to all household chores with almost no help from their male counterpart. But corona pandemic has disrupted gender roles at homes in its small way. Men are not shying away from doing things that normally women do. This research paper is a study into such a changing gender roles in households, post corona pandemic. © 2022, The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.

ABO blood grouping and COVID-19: a hospital-based study in Eastern India

Background: Blood group has been stated to be one of the risk factors associated with viral diseases like dengue, hepatitis virus, Norwalk virus and even the coronavirus associated with 2003 severe acute respiratory syndrome (SARS) outbreak. In addition, anti-A antibodies in experimental models have been shown to inhibit the interaction between coronavirus and angiotensin converting enzyme (ACE) receptor of the host target cell, the major receptor involved in viral pathogenesis. Thus, several workers propose an association between ABO blood type and coronavirus disease- 2019 (COVID-19) disease in many previous studies. The present study was undertaken in the Eastern part of India in line with these authors to study the association of ABO blood group of patients with COVID susceptibility and severity. Methods: This is a retrospective study over a period of 6 months from June 2020 to November 2020 where patients who underwent quantitative real-time polymerase chain reaction (qRT-PCR) test for SARS-COV2 and having a recorded patient blood group type were considered. The qRT-PCR positive admitted cases were considered as cases, and qRT-PCR negative cases were considered as controls. Data were entered in Microsoft Excel format and analyzed by statistical method to obtain association. Results: Consecutively obtained 5000 qRT-PCR positive patients (cases) and 11,700 (controls) were included in the present study. The mean age of cases was higher (54.24 vs. 34. 67) than the controls. Among the cases, the highest number (2379;47.6%) of samples belonged to A blood group followed by B (1278;25.6%) while among the control group O blood group had the highest prevalence (4215;36%). Blood group A had a higher odd of testing positive (Odds ratio-2.552;CI 2.381–2.734;p < 0.0001) than all other blood groups. A blood group is also associated with higher risk of ICU admission (Odds ratio- 1.699;95% CI 1.515–1.905) and 65.3% of this group is also associated with high viral load which gives an indication of higher disease severity. Conclusion: Blood group A is associated with an increased susceptibility to COVID 19 infection than other blood groups. Cases of this blood group are also associated with more critical care needs and a higher viral load on testing.

Clinico-virological-epidemiological characteristics in Covid positive clusters among frontline Health care workers and non-health care workers – A Hospital based study

Background:Ample of studies have been carried out on the causative agent, pattern of illness, treatment options which mainly concern regarding the patients and general population affected from COVID -19, however few studies have fo- cused on its adverse effects on front line health care workers ( HCW ) and other employees of health care facilities. The present retrospective study was planned to analyse the clinico-viro-epidemiological profile of different covid clusters in HCWs and non-health care employees of AIIMS, Bhubaneswar. Methods:A hospital based retrospective study was carried out on the HCWs and other employees of AIIMS, Bhubanes- war, who tested positive SARS-CoV-2 infection by RT-PCR test. The clinical and demographic information were analysed with corresponding virological data of the patient. Results:Of the 671 employees of AIIMS, Bhubaneswar who tested positive for SARS-CoV-2, 92 were from eight clusters that could be traced. The eight clusters involved 4 clusters each from both the HCWs group containing 66 individuals and non-HCWs group with 32. Male to female ratio was 2.5:1. Maximum 55(59.7%) individuals belonged to 20 -30yrs age group followed by 30-40yrs 28(30.4%) and least 3(3.2%) in 50-60yrs. Asymptomatic COVID positive individuals were more as compared to symptomatic in all the age groups. All the individuals with cycle threshold value (CT) ≤ 20 were symptomatic;of the 21 persons with CT value 21-30, seven were symptomatic and 14 were asymptomatic. Majority with >30 CT value (35/44) were asymptomatic. Conclusions:Frontline HCWs are constantly at increased risk of getting infection, but the disease burden and post -covid stigma can be substantially decreased among non-HCWS if COVID appropriate behaviour are strictly implemented and followe

Inconclusives: The diagnostic dilemma of COVID-19

Background:COVID-19 RT-PCR kits of various manufacturers categorize certain samples as inconclusive and repeat testing or re-sampling is advised in those cases to ascertain positivity or a negative result. This is of paramount im- portance because a definite result helps in effective implementation of public health measures, leading to implicit con- tainment. Our study aims to ascertain criteria through which the inconclusive can be definitively categorized as either positive or negative. This will be of help in conserving manpower and resources which are utilized in re -testing of pa- tients with inconclusive RT-PCR result. Methods:Hundred samples which were inconclusive (IC) as per Q-Line Covid-19 RT-PCR kit from 1st September, 2020 to 31st October, 2020 were included in the study. These were classified into 4 groups based on Ct value of N gene;namely A (<25;3 samples), B (25-30.9;31), C (31-34;62) and D (>34;4) and were tested by NIV kit. RNA extracts of these sam- ples were run through ICMR-NIV rRT-PCR screening and confirmatory assay to ascertain a criteria with which inconclu- sives can be definitively reported as either positive or negative. Results:Majority (62%) of IC samples were in group C (Ct 31-34) followed by 31% in group B, 4% in D and 3% in group A (<25). Confirmed positivity by NIV kit was 100% in group A and 51.6%, 20.96% and 25% respectively in B, C & D groups.29% of group B and 24% group C samples remained inconclusive by NIV kit. Majority of confirmed negatives were found in group D (75%), followed by group C (54.83%). Conclusions:All inconclusive samples with Ct values of N gene less than 25 were positive with ICMR -NIV kit, whereas >50% of samples of Ct >30 became negative. Repeat sampling could be avoided in 76% cases by following strategy of repeat testing in NIV kit.

Incidence of COVID-19 infection among Asymptomatic pre-operative/ pre-procedure patients: An Experience

Background:The Coronavirus disease 2019 (COVID 19) pandemic has resulted in reduced performance of non-emergent surgeries and procedures across the nation. About four-fifth of COVID-19 infections remain asymptomatic. With an incu- bation period of 7-14 days, patients can also remain in the pre-symptomatic stage. Hence, knowledge of the prevalence of disease among the asymptomatic is important to prevent spread of disease to the health care professional as well as for patient safety. The present study sought to assess the frequency of positivity of COVID 19 among pre -procedural/pre-operative patients. Methods:A retrospective study of all asymptomatic pre-procedural cases was conducted from 10th June 2020 till 10th November 2020. Nasal swabs were collected from patients 48 hours before procedures (including elective and emer- gency surgeries, patient scheduled to receive chemotherapy, radiotherapy, patients undergoing biopsy, endoscopy). RT - PCR test was done for all samples. Case-specific data, results of all PCR tests, and answers to screening questions (about symptoms, exposure, and travel) were obtained Results: 5320 tests were conducted during the study period. Of these, data could be analysed for 2117 tests done. 51.1% were male patients and the median age group of the cohort was 46 years. 254 of 2117 (11.9%) belonged to the paediatric age group. Of 2117, 35 samples were rejected because of sample leakage or improper labelling. Out of the remaining 2082 samples;338 were positive;1606 were negative, and 138 inconclusive. We received second sample for 117 of the 138 inconclusive samples of which 18 were positive, 93 were negative and 6 remained inconclusive. Thus, the total positivity was 17.1%. Conclusions:This study confirms the high proportion of asymptomatic patients with COVID -19 positivity;and suggests the value of screening by RT-PCR during COVID-19 pandemics.

Clinico-epidemiological characteristics of COVID-19 patients in Odisha – A retrospective single centre study

Background:From the day of the detection of 1st case in India on 30th January 2020, COVID -19, has infected 8.96 mil- lion people in India, from around 128 million samples tested. The clinico -epidemiological characteristics of COVID 19 have been varied in different countries. The present study was undertaken to understand the clinico -epidemiological characteristics of COVID-19 in Odisha. Methods:This was a retrospective, single centre study. The epidemiological, demographic & clinical parameters were analysed of the samples tested in AIIMS Bhubaneswar between March 2020 to November 2020. Results:A total of 56,547 samples were tested for SARS CoV-2 by RT-PCR from March 24th 2020 till 15th November 2020. Of the total samples tested, 9754 were tested positive, with an average positivity rate of 17.25%. The mean age of the patients 38.21 years, with male to female ratio of 3:1. Among the various age groups, the majority affected were the middle ages (31-50 years) constituting around 38.77% (n = 3782) of the total cases followed by 15 -30 years (31.48%, n=3071) &> 50 years (23.64% n = 2305) & was least in children (<14years) with 6.11% (n = 596). Among the COVID -19 positives, 64.5% (n=6295) were asymptomatic & only 35.5% (n=3459) were symptomatic. Of the symptomatic patients, 81.1% (n=2805) presented with mild, 17.7 %( n=612) cases moderate, and only around 1.12% (n=39) had severe COVID - 19 disease. Of the severe cases, majority belong to the age group 31-50 (38.46%, n = 17), followed by 15-30 (15.3%, n=11). The monthly trend showed an increasing trend up to September, with maximum positivity rate of 38%, followed by a decline during October (14.7%) & November (5.8%) Conclusions: In this study of 9754 patients with confirmed COVID-19 in Odisha, the characteristic findings included younger age, male predominance, high proportion of asymptomatic patients & a declining trend in the positivity rate over the months

Influence of temperature, humidity on COVID positivity in Odisha

Background:The spread of COVID 19 has not been uniform across various states of India, which encounters significant spatio-temporal variations in the climatic conditions. As, seasonal cycle plays a dynamic role in spread of respiratory In- fections, we aimed to ascertain the Influence of temperature, humidity and seasonal variability on COVID positivity in a tertiary care testing hospital of Odisha Methods:Samples collected from patients attending AIIMS, Bhubaneswar and from other districts for detection of Covid-19 were tested at our lab by RTPCR. A retrospective month wise comparative analysis of the Covid -19 positivity rate of samples tested during the months of March to November 2020 was done with temperature and humidity Results:Out of 56,874 samples tested, 9,484(16.6%) were positive by real time reverse transcriptase PCR. As Odisha is a costal state it has high humidity and temperature as compared to rest of India. The mean humidity along with the mean temperature were com- pared to COVID positivity [Formula presented] Conclusions:In our study period over 9 months, Mon- soon months showed surge in positive cases peaking in August and September, and autumn months showed a downward trend.

Comparability of the Sensitivity of Different real time PCR kits Used in the Detection of SARS CoV -2

Background:COVID-19 pandemic is posing a major burden on society. Measures taken to reduce its spread critically de- pend on timely and accurate identification of virus-infected individuals by the most sensitive and specific method availa- ble, i.e. real-time reverse transcriptase PCR (RT-PCR). RT PCR can detect SARS-CoV-2 as early as day one of symptom onset. There are various RT PCR kits approved by FDA & ICMR, performance of which vary widely. Here, we assessed the performance of four PCR kits with the ICMR NIV Screening & Confirmatory assay used for diagnosis of COVID -19 in Od- isha. Methods:A total of 20 samples, which included five positives, one inconclusive & 14 negative samples by NIV assay were evaluated in the four commercially available RT-PCR kits ie;Q-line Molecular (Q-line), Allplex™ 2019-nCoV Assay (Allplex), Liferiver Novel Coronavirus (COVID-19) Multiplex RT PCR (Liferiver), LabGun™ COVID-19 kit (LabGun). Results:The sensitivity of the four PCR kits varied with the high cycle threshold (Ct) value (30-35 by NIV) & the lower Ct value (<30 by NIV). Among the negative results of NIV (n=14), LabGun, Allplex kits showed 100% concordance, while Q - line & Life river were shown to have 92.8% & 50% concordance respectively. In the inconclusive results (n=1), only All- plex Assay documented a concordance of 100% with the NIV assay, while the Q -line (n=6) & Life river (n=7) showed higher number of inconclusive results. The different kits showed lesser variations with positive results (n=5), with Life river, Allplex & LabGun showing 100% concordance for positive results with NIV assay. However, Q -line was able to de- tect only 1 positive out of all positives. Conclusions:PCR kits vary in sensitivity & it is imperial to evaluate the various kits in order to deliver accurate results at optimum time in order to detect the cases to initiate adequate treatment & control measures

A Case vignette of melioidosis pneumonia as Covid mimic: Role of microbiology laboratory in accurate diagnosis

Background:During the ongoing COVID19 pandemic period, any new cases of acute-onset respiratory illness are likely to be treated as suspected COVID-19 by default. Methods:A 42year-old lady was admitted with a 4-week history of fever and cough, followed by a 4-days history of increasing short- ness of breath. Fever was intermittent, high grade and was associated with chills and rigor. The patient had a history of uncontrolled type II diabetes mellitus and on admission HbA1C was 15.5%. On examination she had a temperature of 102° F, blood pressure (BP) of 101/67mm Hg, heart rate of 130 beats per minute, respiratory rate (RR) of 24 breaths per minute and O2 saturations of 92% in room air. On respiratory examination, there were crackles in the left infrascapular and infraaxillary area. The patient was admitted in the COVID suspect ward with an impression of moderate COVID-19 infection and nasopharyngeal swab was sent for SARS-CoV-2 on RT-PCR. The patient underwent a CECT scan of thorax, abdomen and pelvis that revealed consolidation in bilateral lung fields with a cavity in lingular lobe with presence of air-fluid level. Mediastinal and hilar lymphadenopathy were present. [Formula presented] Results: SARS-CoV-2 RT-PCR was negative. The patient’s sputum sample revealed pure growth of purple, flat, dry, wrinkled colonies on Ashdown agar after 48 hours which was identified as Burkholderia pseudomallei. The Isolate was susceptible to ceftazidime, mero- penem, co-trimoxazole, amox-clav and chloramphenicol. The patient was started on I.V Meropenem 500mg every 8hourly for 21 days and was discharged on co-trimoxazole tablet. Conclusions: The case definitions of COVID-19 such as fever, cough and shortness of breath can be associated with other infectious etiologies. The role of the microbiology laboratory is thus very crucial in COVID-19 from overshadowing other infec- tious diseases, particularly in endemic areas, hence preventing misdiagnosis and consequent adverse outcomes for patients.

Spectrum of Bacterial Pathogens in Critical COVID-19 Patients Admitted in Intensive Care Units of a Tertiary Care Hospital during the First and Second Wave of the Pandemic

Objective: This study intends to compare the clinical characteristics and the prevalence and spectrum of bacterial pathogens in COVID-19 patients admitted to ICU during the first and second waves at a tertiary care, teaching and referral hospital of eastern India. Method: This is a hospital-based retrospective study which analysed demographic details, clinical profile and bacterial culture results of severe and critically ill COVID-19 patients admitted in intensive care units (ICU) during April -Oct 2020 (1stwave) and April -July 2021 (2ndwave). Result: The patients admitted during the 2ndwave were comparatively older and had multiple comorbidities compared to the 1stwave. (23.8%) (45/189) and 50% (173/346) of the COVID-19 patients admitted to ICU developed bacterial infection during the 1stand 2ndwave respectively. Overall, there was predominance of multidrug resistant Gram negative bacilli in both the waves. There was increased isolation of intrinsic colistin resistant microorganisms. Conclusion: Multidrug resistant Gram negative bacterial infections, remain a dreaded complication in severe and critically ill hospitalised COVID-19 patients requiring ICU care and high usage of colistin spirals the emergence and spread of pathogens intrinsically resistant to colistin. © 2022 Journal of Association of Physicians of India. All rights reserved.

Evaluation of hospital environment for presence of Mucorales during COVID-19-associated mucormycosis outbreak in India - a multi-centre study.

BACKGROUND: An unprecedented rise in the number of COVID-19-associated mucormycosis (CAM) cases has been reported in India. Myriad hypotheses are proposed for the outbreak. We recently reported uncontrolled diabetes and inappropriate steroid therapy as significant risk factors for the outbreak. However, Mucorales contamination of hospital environment was not studied. AIM: To perform a multi-centre study across India to determine possible Mucorales contamination of hospital environment during the outbreak. METHODS: Eleven hospitals from four zones of India representing high to low incidence for mucormycosis cases were included in the study. Samples from a variety of equipment used by the patients and ambient air were collected during May 19th, 2021 through August 25th, 2021. FINDINGS: None of the hospital equipment sampled was contaminated with Mucorales. However, Mucorales were isolated from 11.1% air-conditioning vents and 1.7% of patients' used masks. Other fungi were isolated from 18% of hospital equipment and surfaces, and 8.1% of used masks. Mucorales grew from 21.7% indoor and 53.8% outdoor air samples. Spore counts of Mucorales in air were significantly higher in the hospitals of North and South zones compared to West and East zones (P < 0.0001). Among Mucorales isolated from the environment, Rhizopus spp. were the most frequent genus. CONCLUSION: Contamination of air-conditioning vents and hospital air by Mucorales was found. Presence of Mucorales in these areas demands regular surveillance and improvement of hospital environment, as contamination may contribute to healthcare-associated mucormycosis outbreaks, especially among immunocompromised patients.

Tailoring magnetism in spinel vanadate CoV2O4epitaxial thin films.

Near itinerant cubic bulk CoV2O4is at variance with other spinel vanadates by not showing orbital ordering down to low temperature, albeit it displays fragile anomalies related to spin, and lattice structure, signaling a spin/orbital glass transition around 95 K. We investigate tetragonal-like epitaxial CoV2O4films on SrTiO3and (La0.3Sr0.7)(Al0.65Ta0.35)O3substrates that exhibit pronounced signature of spin reorientation transition from toa/bplane around 90 K unlike its bulk counterpart. Using in-plane and out-of-plane magnetic measurements, we demonstrate the intricate link between Co2+and V3+sublattice magnetizations that give rise to anisotropic magnetic switching. In-plane magnetic measurements reveal a wasp-waist shapedM(H) loop below reorientation transition temperature, while the out-of-plane follows antiferromagnet-likeM(H) response. The wasp-waist shaped feature could be linked to in-plane spin-canted (anti)ferromagnetism induced by canting away of V-spins away from antiferromagnetically coupled Co-spin direction below reorientation transition temperature. Further, we uncover the evidence for slow relaxation over a period of ∼104 s at 20 K and memory effect that indicates the possible existence for magnetic glassy phase in the low temperature regime. Using epitaxial strain as a control knob, our results inspire future study to manipulate orbital states, spin texture and itinerant electron character in tailored CoV2O4films away from cubic lattice symmetry.

P09.48 Experience and Outcome of COVID-19-Positive Lung Cancer Patients from a Eastern Indian Hospital

Introduction: The COVID-19 pandemic has caused unprecedented crisis in the care of non-Covid patients all across the globe and care for lung cancer patients is no exception. Lung Cancer patients are at increased risks of COVID due to increased mortality from dual aggressive pathology in the lungs. Our aim was to examine the impact of COVID-19 on lung cancer therapy and factors responsible delay in optimal care during the pandemic. Methods: This study included all patients with a diagnosis of lung cancer being treated at our Institute, a tertiary level referral hospital in eastern part of India during on going pandemic. Seven developed COVID-19, confirmed by RT-PCR method (Table 1). Results: The mean age of the patients was 49 years. All the patients had metastatic lung cancer. All males had history of smoking. Hypertension was present in only one patient. Four patients (57%) died from concomitant COVID-19 at our institution.Three patients who recovered from COVID were stable. One of them (positive for ROS1) was switched over to Crizotinib and other patient resumed chemotherapy only after he had recovered from COVID-19. Most of the patients acquired COVID-19 infection during the process of evaluatio/chemotherapy and that further delayed the treatment. [Formula presented] Conclusion: The results were disappointing because more than half of lung cancer patients died due to COVID-19. The disease course of COVID-19 has been more severe in patients with lung cancers with Chemotherapy. There have been delay in resuming treatment among survivors by few weeks. Fear of aggressiveness of disease was the key factor for interruption or delay in chemotherapy. Other variable factors like stage of cancer, palliative intent of chemotherapy, ECOG status were key determinants for interruption of treatment. The decision to temporarily suspend chemotherapy while waiting for recovery from SARS-CoV-2 and then restart, was not easy due to the risk of cancer progression. The findings amplify the importance of optimizing of lung cancer care in the context of the COVID-19 prevalence. The decisions need to be taken on the basis of individual cases rather than rely on a generalized approach. In resource limited country like India diverting the existing resources to an emergency leads to compromise of routine outpatient care, especially patients with chronic illness. We need to be flexible in restarting of services guided by local COVID prevalence, while awaiting a definite management plan for COVID-19. Keywords: lung cancer, India, COVID-19, SARS-CoV-2

The Emergence of novel SARS-CoV-2 (COVID-19) a triple reassortant corona virus immunogenicity and reactogenicity in human

Presently, the emergence of a novel human corona virus, Severe Acute Respiratory Syndrome (SARS)-CoV-2, has lead to a global health concern. It causes severe respiratory tract infections in humans. WHO on March 11, 2020, declared COVID-19 (Corona Virus) as a pandemic. There have been more than 3,842,000 confirmed COVID-19 cases in the world. The reports have shown sharp increase in the number of infections reported in recent days from Italy, Iran, South Korea, Spain, Germany, United States, and other parts of the world, with the most dramatic increase recorded in China where more than 80,000 cases were reported in a very short duration. Since no potential medication nor vaccines are available in the market and the presence of corona virus in different form both in symptomatic and asymptomtic in human system makes the chances of cure less effective. This article enlightens about the Corona virus, its modes of infection, and prevention measures.