Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241129EnglishN2020May4HealthcareEstimation of Reference Interval of Serum Progesterone During Three Trimesters of Normal Pregnancy in a Tertiary Care Hospital of Kolkata English0104Arpita MandalEnglish Sanchayan SinhaEnglish Soma GuptaEnglish Sanghamitra ChakrabortyEnglishAim: Hormonal milieu of pregnancy may be an important determinant of outcome in both mother & fetus. Estimation of trimester specific hormone concentrations measured may serve as a yard stick to predict feto-maternal outcome. However, the literature review suggest that the reference interval of progesterone established in western pregnant population may not be applicable in India with different reproductive profile. The primary objective of this study was to estimate trimester specific and assay-specific reference interval of progesterone in healthy pregnant females. Methodology: About 276 healthy pregnant ladies were enrolled as study participants with a distribution of 81, 111, and 84 in 1st, 2nd & 3rd trimester respectively. The study was conducted after obtaining ethical approval of Nil Ratan Sircar Medical College & subjects were collected using pre-defined inclusion and exclusion criteria. Serum of study subjects was analysed for progesterone by Enzyme linked immunesorbent assay. Results: The serum progesterone level was found to increase gradually throughout pregnancy. Conclusion: The study helped us to determine the reference interval in healthy pregnant female and the reference values markedly differ from the established reference interval in other population. EnglishProgesterone, Reference values, Pregnancy TrimesterINTRODUCTION: Human reproductive endocrine function is intricately balanced by a wide variety of hormones & their control by feedback mechanism. The menstrual cycle follows a cyclical deviation of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, and progesterone orchestrated by hypothalmic-pituitary-gonadal axis1,2. The pregnancy is also maintained an intricate regulation of placental hormones and the hormonal milieu changes with duration of pregnancy. Thus, accurate assessment of the pregnancy duration is essential to predict the feto-maternal outcome. The endocrinological changes of pregnancy is a crucial determinant of subsequent development of chronic diseases both in the mother and the offspring3,4. Estimation of trimester specific hormone concentrations measured may serve as a yard stick to predict feto-maternal outcome. Hormones estimation in early pregnancy where fetal organogenesis takes place may be helpful to assess neuro-developmental anomalies of fetus vis-à-vis hormone concentrations during late pregnancy may be helpful to assess maternal risk of breast and ovarian malignancies5,6. Progesterone is produced by the corpus luteum and regulate initial stage of pregnancy and sustain pregnancy until the luteal–placental shift takes place by 11 weeks of gestation. Thus hormone concentration in luteal phase may predict the chances of conception as well as outcome of viable pregnancy. Progesterone, C-21 steroid hormone, synthesized by ovarian granulosa cells. Progesterone promotes endometrial decidualisation and assist implantation of the blastocyst in the uterine cavity7. Progesterone retards uterine smooth muscle contraction and ameliorates immune responses involved in graft rejection7.Recent studies have suggested that First trimester progesterone concentration is the most powerful single predictor of pregnancy outcome in natural conceptions8. Thus, it is necessary to study the viability of pregnancy in women after natural conception without exogenous micronized progesterone support and its relationship with serum progesterone9,10. Since the hormonal environment during pregnancy is likely to be a predictive variable for outcome of both mother and offspring, it is important to have an understanding of the factors which can affect it. A reference interval of this hormone may help to delineate whether any deviation had occurred or not. Most of the data regarding this is obtained from western literature, where the age group of pregnancy varies a lot with respect to that of Indian population. In this instance, the reference interval of serum progesterone was established in the three trimesters of Pregnancy and evaluated to assess any deviation from western population. MATERIALS And METHODS: This study was undertaken in the Department of Biochemistry in collaboration with the Department of Obstetrics and Gynaecology, NRS Medical College and Hospital, Kolkata. The study was initiated after approval from Institutional Ethics Committee of NRS Medical College & Hospital (vide memo no NMC/6534 dated 26/12/2016). All the voluntary participants were included in the study after signing the consent form. All healthy pregnant females having no history of pre-existing disease or any complication were included in this study.  Pregnant females who had treatment for infertility, or found to have any other pregnancy associated co-morbidities were excluded in this study. The cases were selected from the pregnant females attending Antenatal clinics in the Department of Obstetrics and Gynaecology of N.R.S. Medical College & Hospital, Kolkata, according to predefined inclusion and exclusion criteria.  Proper history was taken regarding age, parity, detail history of previous pregnancy, history of hypertension, family history, history of taking any medicine, and history of whether suffering from any other medical disorders. About 4 ml blood was collected from each patient aseptically by disposable syringe using aseptic procedure in serum separation tubes. The serum sample tubes was centrifuged for 5 minutes at 2500. The serum was separated from the blood cells, analysed and was kept in aliquots and stored in deep freezer at -40°C.Serum of pregnant women collected in first trimester, second trimester and third trimester was analysed for progesterone by Enzyme linked Immunosorbant assay. RESULTS AND DATA ANALYSIS: This hospital based study incorporated 276 pregnant ladies as study subjects. The trimester wise distribution of study population was 81, 111, and 84 study participants in 1st, 2nd & 3rd trimester respectively. The values of the hormones were extrapolated in Microsoft excel sheet and calculation was done using MedCalc software (version 18.9). Table 1 shows trimester specific reference interval of progesterone. The study participants were enrolled using pre-defined inclusion and exclusion criteria, after subsequent routine clinical and investigational procedure.  It is evident that the number of study participants were less than 120 i.e. as per the IFCC recommendations. So the non-parametric method was used to assess the reference interval. Moreover, the Kolmogorov-Smirnov test showed that the reference values were in non-Gaussian distribution (i.e PEnglishhttp://ijcrr.com/abstract.php?article_id=2670http://ijcrr.com/article_html.php?did=26701. Gronowski AN, Landau-Levine ME. Reproductive endocrine function. In: Burtis CA, Ashwood ER, editors. Tietz fundamentals of clinical chemistry. Philadelphia: WB Saunders, 2001:877–97. 2. Marshall JC. Hormonal regulation of the menstrual cycle and mechanisms of ovulation. In: DeGroot LJ, Jameson JL, editors. Endocrinology. Philadelphia, PA: WB Saunders,2001:2073–85.  3.  Lukanova A, Surcel HM, Lundin E, Kaasila M, Lakso HA, Schock H, et al.Circulatingestrogens and progesterone during primiparous pregnanciesand risk of maternal breast cancer. Int J Cancer. 2012;130(4):910–20. 4. Whitaker-Azmitia PM, Lobel M, Moyer A. Low maternal progesterone may contribute to both obstetrical complications and autism. Medical hypotheses. 2014;82(3):313–8. 5. Braem MG, Onland-Moret NC, Schouten LJ, Kruitwagen RF, Lukanova A, Allen NE, et al. Multiple miscarriages are associated with the risk of ovariancancer: results from the European Prospective Investigation into Cancer and Nutrition. PloS one. 2012;7(5), e37141. 6. Beral V, Bull D, Doll R, Peto R, Reeves G. Breast cancer and abortion: collaborative reanalysis of data from 53 epidemiological studies, including83 000 women with breast cancer from 16 countries. Lancet. 2004;363(9414):1007–16. 7. Hanita O, Hanisah AH. Potential use of single measurement of serum progesterone in detecting early pregnancy failure. Malaysian J Pathol 2012; 34: 41-6. 8. Elson J, Salim R, Tailor A, Banerjee S, Zosmer N, JurkovicD. Predictionof early pregnancy viability in the absence of an ultrasonically detectable embryo. Ultrasound Obstet Gynecol 2003; 21: 57-61. 9.Vicdan K, ZekiIsik A. Luteal phase hormonal profile in prediction of pregnancy outcome after assisted reproduction. Eur J Obste Gynecol Reprod Biol 2001; 96: 98-101. 10. Zainab Ali Abdulla Al Jufairi. The value of Serum ProgesteroneMeasurement in Early Pregnancy. Bahrain Medical Bulletin, Volume22, Number 1, March 2000. 11.Hanita O, Hanisah AH. Potential use of single measurement of serum progesterone in detecting early pregnancy failure. Malaysian J Pathol 2012; 34: 41-6. 12. Elson J, Salim R, Tailor A, Banerjee S, Zosmer N, Jurkovic D. Prediction of early pregnancy viability in the absence of an ultrasonically detectable embryo. Ultrasound ObstetGynecol 2003; 21: 57-61. 13.Vicdan K, ZekiIsik A. Luteal phase hormonal profile in prediction of pregnancy outcome after assisted reproduction. Eur J Obste Gynecol Reprod Biol 2001; 96: 98-101. 14.Wuu J, Hellerstein S, Lipworth L, Wide L, Xu B, Yu GP, et al. Correlates of pregnancy oestrogen, progesterone and sex hormone-binding globulin inthe USA and China. Eur J Cancer Prev. 2002;11(3):283–93.

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241129EnglishN2020May4HealthcareA Study of Platelet Parameters as a Novel Marker of Severity of Inflammation in Patients with Chronic Obstructive Pulmonary Disease English0509Dipti MohapatraEnglish Ranita SahanaEnglish Priyadarshini BeheraEnglish Manasi BeheraEnglishIntroduction: Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death worldwide, characterised by both systemic as well as pulmonary inflammation. During an acute exacerbation, the inflammatory pathways are unregulated to a greater extent and may also precipitate a critical cardiovascular event. Platelet parameters like platelet count, Mean platelet volume (MPV) and platelet distribution width (PDW) are markers of platelet activation and also has been associated with various inflammatory conditions. Aim of the Study: To find out the role of Platelet Parameters in COPD and to establish the relationship between the severity of COPD with the Platelet Parameters and to find out whether the platelet parameters can be a useful prognostic tool that will help the therapeutic target in COPD. Material and Methods: Forty COPD patients who visited Pulmonary Medicine OPD during the study period, were included in the study. COPD patients were diagnosed by spirometry and classified according to the GOLD’s criteria.The results of the Spirometry was compared with the different platelet parameters like platelet count, mean platelet volume and platelet distribution width to establish the probable role of platelets in the severity of COPD. Result and Conclusion: It was concluded from the study that as the disease worsens, the number of platelets increase and this result is associated with spirometric parameters. The MPV and PDW also increased with the severity of disease in patients with COPD.So, the platelet parameters can be used as a simple, quick, tool to predict the severity in COPD patient and help in predicting the prognosis of the disease. EnglishCOPD, Spirometry, Platelet parameters, MPV, PDWINTRODUCTION: Chronic obstructive pulmonary disease (COPD) is estimated to affect greater than 5% of the adults and with a progressively rising rate of morbidity and mortality1,2. As it is estimated, COPD will be the third leading cause of death worldwide by 20203,4. COPD is a great financial burden upon health systems, primarily because of its acute exacerbations which require hospitalization5. COPD is mainly characterized by restricted airflow, which is a result of inflammation as well as the remodelling of the airways6. COPD is characterised by both systemic as well as pulmonary inflammation. During an acute exacerbation, the inflammatory pathways areunregulated to a greater extentand may also precipitate acute cardiovascular events.COPD is also associated with low-grade systemic inflammation as obvious from increased total leucocyte count, acutephase proteins like C-reactive protein (CRP), and inflammatory cytokines7. Platelet parameters like platelet count, Mean platelet volume (MPV) and platelet distribution width (PDW)8 are markers of platelet activation.9-11 Increased MPV is associated with many vascular diseases,like peripheral, cerebrovascular disease, and coronary artery disease12,13. Biljak et al(14) reported elevated platelet count and decreased MPV in COPD patients. In contrast, Cui et al15 stated that a high MPV predicts impaired pulmonary and cardiac function in elderly COPD patients. However, only a few studies have been done showing the relationship between MPV and the severity of COPD. Hence our study aimed to establish the role of platelet parameters in patients of COPD and to find the co-relationof various platelet parameters with the severity of COPD. We also intended to find out if itcould be used as a prognostic tool in future. AIMS AND OBJECTIVES: 1. The study aimed to find out the role of Platelet Parameters in COPD and toestablish the relationship between the severity of COPD with the Platelet Parameters. 2. To find out whether the platelet parameters can be a useful prognostic tool that willhelp the therapeutic target in COPD. MATERIAL AND METHODS: The study was undertaken in the Department of Physiology of IMS and SUM Hospital, Bhubaneswar. Forty COPD patients who visited the Pulmonary Medicine OPD during the study period were included in the study. COPDpatients were diagnosed according to the GOLD’s criteria. Approval from the institutional ethic committee (IEC) was obtained, and written informed consent was taken from patients who participated in the study. Patients withother acute and chronic lung diseases, Haematological disorders, patients with any other chronic inflammatory condition or Cancer patients on Long term Oxygen Therapy were excluded from the study. In all the patients included in the study group, the following investigations were done in addition to the routine investigations: -Complete Blood Count including platelet parameters like platelet count, mean platelet volume and platelet distribution width. -Pulmonary Function Tests - Chest X-Ray The result of various tests wasrecorded independently of one another. A detail medical history was obtained,and a detail physical examination was performed. Physical examination was followed by spirometry. COPD was diagnosed on the basis of clinical examination (chronic and progressive dyspnea, cough, and sputum production) and also spirometry findings (FEV1/ FVC (forced vital capacity) Englishhttp://ijcrr.com/abstract.php?article_id=2671http://ijcrr.com/article_html.php?did=2671 Coultas DB, Mapel D, Gagnon R, Lydick E. The health impact of undiagnosed airflowobstruction in a national sample of United States adults. Am J Respir Crit Care Med.2001;164(3):372-377. Murray CJ, Lopez AD. Alternative projections of mortality and disability by cause 1990-2020: Global burden of disease study. Lancet. 1997;349(9064):1498-1504. Michaud CM, Murray CJ, Bloom BR. Burden of diseaseimplications for futureresearch. JAMA. 2001;285(5):535-539. Sullivan SD, Ramsey SD, Lee TA. The economic burden of COPD. Chest. 2000;117(suppl):5S-9S. Geitona M, Hatzikou M, Steiropoulos P, Alexopoulos EC, Bouros D. The cost ofCOPD exacerbations: a university hospital-based study in Greece. Respir Med. 2011;105(3):402-409 Global Strategy for the Diagnosis, Management and Prevention of COPD, GlobalInitiative for Chronic Obstructive Lung Disease (GOLD). Definition: Chapter 1. 2010.pp. 1–7. Vernooy H, Küçükaycan M, Jacobs A. Local and systemic inflammation in patientswith chronic obstructive pulmonary disease: soluble tumor necrosis factor receptors are increased in sputum. Am J Respir Crit Care Med 2002; 166:1218–1224. Vagdatli E, Gounari E, Lazaridou E, Katsibourlia E, Tsikopoulou F, LabrianouI. Platelet distribution width: a simple, practical and specific marker of activation of coagulation. Hippokratia. 2010; 14(1):28-32. Tsiara S, Elisaf M, Jagroop IA, Mikhailidis DP. Platelets as predictors of vascular risk:is there a practical index of platelet activity? Clin ApplThromb Hemost.2003;9(3):177-190. Jagroop IA, Clatworthy I, Lewin J, Mikhailidis DP. Shape change in human platelets: measurement with a channelyzer and visualisation by electron microscopy. Platelets.2000; 11(1):28-32.  Park Y, Schoene N, Harris W. Mean platelet volume as an indicator of plateletactivation: methodological issues. Platelets. 2002; 13(5-6):301-306. Gasparyan AY, Ayvazyan L, Mikhailidis DP, Kitas GD. Mean platelet volume: a linkbetween thrombosis and inflammation? Curr Pharm Des. 2011;17(1):47-58. Vizioli L, Muscari S, Muscari A. The relationship of mean platelet volume with therisk and prognosis of cardiovascular diseases. Int J Clin Pract. 2009;63(10):1509-1515. Biljak et al. Platelet count, mean platelet volume and smoking status in stable chronic obstructivepulmonary disease. Platelets. 2011;22(6):466-470. Sandhaus L, Meyer P. How useful are CBC and reticulocyte reports to clinicians? Am J Clin Pathol 2002; 118:787–793. Dev D, Wallace E, Sankaran R, et al, Value of C-reactive protein mea-surements in exacerbations of chronic obstructive pulmonary disease. Respir Med. 1998; 92: 664-667. Schols AM, Buurman WA, Staal van den Brekel AJ, et al, Evidence for a relationbetween metabolic derangements and increased levels of inflammatory mediators in asubgroup of patients with chronic obstructive pulmonary disease. Thorax.1996; 51:819-824. Sin DD, Wu L, Man SF. The relationship between reduced lung function andcardiovascular mortality: a population-based study and a systematic review of theliterature. Chest 2005; 127: 1952–9. Guzman-Grenfell A, Nieto-Velazquez N, Torres-Ramos Y et al., Increased platelet anderythrocyte arginase activity in chronic obstructive pulmonary disease associated withtobacco or wood smoke exposure. J. Investig. Med. 2011; 59: 587–92. Ferroni P, Basili S, Martini F et al, Soluble P-selectin as a marker of platelet hyperactivity in patients with chronic obstructive pulmonary disease. J. Investig. Med.2000; 48: 21–27. Varol E, Icli A, Kocyigit S et al, Effect of smoking cessation on mean platelet volume.Clin. Appl. Thromb. Hemost.2012; 19: 315–9. Yarlioglues M, Ardic I, Dogdu O et al, The acute effects of passive smoking on meanplatelet volume in healthy volunteers. Angiology 2011; 63: 353–357. Ulasli SS, Ozyurek BA, Yilmaz EB et al, Mean platelet volume as an inflammatorymarker in acute exacerbation of chronic obstructive pulmonary disease. Pol. Arch. Med. Wewn. 2012; 122: 284–290. Onder I, Topcu S, Dokmetas HS., Platelet aggregation size and volume in chronicobstructive pulmonary disease. Mater Med Pol 1997; 29:11–13.

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241129EnglishN2020May4HealthcareMerits and Demerits of Using Indwelling Catheter in Lower Segment Caesarean Section English1013Samina SultanaEnglish Shagufta Yasmeen RatherEnglish Iqra RehmanEnglishBackground: The reported incidence rates of urinary retention after caesarean section vary from 3.3 to 39.2%. The use of indwelling urinary catheters has been implicated as a main cause of urinary tract contamination occurring in 1.7 per 1000 of caesarean delivery patients, and accounting for greater than 80% of nosocomial UTIs and greater postoperative pain. Objectives: The aim of this study was to assess whether carrying out CS without urethral catheterization is safe in terms of intraoperative safety, prevalence of UTI, and the rate of the first voiding discomfort. Methods: A prospective case control study done at L.D. hospital, GMC Srinagar over a period of one year from December 2018 to December 2019. 200 pregnant women without any medical / surgical complication undergoing emergency / elective CS were randomly selected by use of table of random numbers and allocated to two groups. Caesarean section was done under SA by the same surgeon using conventional technique. The duration of surgery was defined as interval between skin incision to skin closure by standard clock in OT. Results: Women in both groups had no significant difference in age, parity and indication for cesarean section. They received the same pre and postoperative treatment. Time to first void was 4-8 hrs in 62 patients and more than 9 hrs in 38 patients in NC group. Discomfort at first void was seen in 34 patients of NC group and 59 of C group. Of the C group 30 had mild and 4 had severe discomfort. Among the C group, 45 had mild and 14 had severe discomfort at first void. The incidence of UTI in C/S after 48hrs was 4/100 among NC group and 17/100 among C group. Febrile morbidity was seen in 1 patient of NC group and 8 of C group. Hospital stay among NC group was 3.7 days and among C group was 4.3 days. Conclusion: Non-use of urinary catheter at caesarean section causes less pain at first void less time to ambulate and less chance of urinary tract infections with a slightly increased chance of postoperative urinary retention. EnglishCaesarean section, Voiding discomfort, Urinary tract infectionsINTRODUCTION An indwelling urinary catheter is a routine part of most surgeries including cesarean section (CS) performed today, inserted prior to surgery and remains 12 – 24 h post operation1. The rationale for catheterization is to prevent bladder injury, intra-operative dif?culties and postoperative urinary retention in the belief that an empty bladder is at less risk of damage during surgery than one that is distended2,3. The reported incidence rates of urinary retention after caesarean section vary from 3.3 to 39.2%, depending on the de?nitions used4,5 and catheterization has been consistently associated with urinary tract infections (UTIs)6,7. Bacterial access is gained to the bladder intraluminally by entering catheter system at catheter collecting tube junction or patients own gut flora may colonize the periurethral area and reach bladder via external surface of catheter8. The use of indwelling urinary catheters has been implicated as a main cause of urinary tract contamination9,10 occurring in 1.7 per 1000 of cesarean delivery patients11, and accounting for greater than 80% of nosocomial UTIs12 and greater postoperative pain13. UTIs may lead to local and systemic morbidity, as well as serious complications, such as septic shock, respiratory insuf?ciency, secondary bloodstream infection, ?uid balance disorders, chronic renal insuf?ciency and death, and related increases in healthcare costs14-18. Clinical trials have been performed comparing the safety and feasibility of urinary catheterization use and non-use during caesarean section2,19,20. OBJECTIVE To assess whether carrying out caesarean section without urethral catheterization is safe in terms of intraoperative safety, prevalence of UTI, and the rate of the first voiding discomfort. METHODS A prospective case control study done at L.D. hospital, GMC Srinagar over a period of one year from December 2018 to December 2019. 200 pregnant women without any medical /surgical complication undergoing emergency/elective CS were randomly selected by use of table of random numbers and allocated to two groups. Group 1 (NC): Non Catheterized (NC) Group 2 (C): Catheterised for 24hrs postoperative. The groups were comparable in terms of age, parity, indication of CS, type of CS, anaesthesia and same operating surgeon. Exclusion criteria Medical disorders associated with pregnancy e.g. GDM, PIH, CKD etc.  Previous LSCS/ surgical complication. Rupture of membranes > 4hrs Pre-existing UTI All patients received a single dose of antibiotics before surgery after cord clamping which as per hospital protocol was continued for 2 days postoperatively. Parameters noted were; Duration of surgery. Time to ambulation Postop retention Time of first void Discomfort at first void UTI [urine routine / morning (U-R/M), urine culture sensitivity (U – C/S) done on urine sample at end of 24hrs post op in both groups. Duration of hospital stay. Caesarean section was done under SA by the same surgeon using conventional technique. The duration of surgery was defined as interval between skin incision to skin closure by standard clock in OT. Postoperatively patients were monitored closely and were kept fasting for a minimum of 8 hrs and received tramadol as analgesia for first 24 hrs. Discomfort at first void was defined as burning, urging, and painful voiding. For assessing level of discomfort visual analog scale (VAS) was used. VAS uses numerical rating of 0-10 as was explained to each patient. The patient chooses a number from 0-10 that best described her pain intensity. Accordingly, three categories were divided (i) No discomfort VAS -0, Mild discomfort (VAS: 1-3) and Moderate discomfort (VAS: 4-10).  Time of first void was defined as time interval between removal of urinary catheter and first spontaneous void. The time of first ambulation was defined as interval between onset of surgery and time patient first ambulated. Urine of all patients was sampled immediately before and 24 hrs post-surgery and subjected to routine and microscopy exam and culture and sensitivity. Antibiotics were changed according to culture report. Criteria for discharge were: (i) Patient afebrile for 24hrs, (ii) On oral medications, (iii) Accepting orally well     (iv) bowel and bladder function normal. Statistical Method: The recorded data was compiled and entered in a spreadsheet (Microsoft Excel) and then exported to data editor of SPSS Version 20.0 (SPSS Inc., Chicago, Illinois, USA). Continuous variables were expressed as Mean±SD and categorical variables were summarized as frequencies and percentages. Chi-square test was applied for comparing categorical variables and continuous variables were compared by Student’s independent t-test. A P-value of less than 0.05 was considered statistically significant. All P-values were two tailed. RESULTS 200 women enrolled in the study were assigned to two groups. Women in both groups had no significant difference in age, parity and indication for cesarean section. They received the same pre and postoperative treatment. Duration of surgery was almost similar in both groups. Initiation of ambulation was 9 hrs in NC group and 15 hrs in C group. This was statistically significant with a p value of < 0.001.  Postoperative retention was seen in 2 women among the NC group for which catheterization was done on the first postoperative day. Time to first void was 4-8 hrs in 62 patients and more than 9 hrs in 38 patients in NC group. Discomfort at first void was seen in 34 patients of NC group and 59 of C group. Of the C group 30 had mild and 4 had severe discomfort. Among the C group, 45 had mild and 14 had severe discomfort at first void. The difference was statistically significant with a p value of < 0.001. The incidence of UTI in C/S after 48 hrs was 4/100 among NC group and 17/100 among C group. Febrile morbidity was seen in 1 patient of NC group and 8 of C group. Hospital stay among NC group was 3.7 days and among C group was 4.3 days. DISCUSSION The study confirms that catheterisation during cesarean section is not necessary. We found that non placement of indwelling catheter during LSCS was associated with significantly fewer UTIs, a lower rate of discomfort at first voiding, less time until first voiding and ambulation and shorter duration of hospital stay. Duration of surgery was comparable in both groups. The patients in NC group ambulated early. This was due to restriction of mobility with the indwelling catheter because of pain and fear of accidental expulsion in the C group21. The C group had a longer hospital stay because of post op UTI and associated fever. Discomfort at first void was seen more in group C patients (59%) with 14% patients experiencing moderate to severe discomfort. Majority of patients in group NC had mild discomfort at first void. In a study by Arlyn et al 83% of group C patients had discomfort at first void of which 28% had severe discomfort22. The urethral catheter as a cause of UTI in pregnancy and puerperium is well known. Bacteriuria associated with indwelling catheter in the postoperative period has been found to be an important cause of hospital acquired UTI. It was seen in 14% of patients of group C and the results were significant. Febrile morbidity was seen in 1% of patients in NC group as compared to 8% patients in group C. A major rationale for catheterisating urinary bladder was to avoid postoperative retention. However in our study non-use of urinary catheterisation during cesarean section was not associated with an increase in urinary retention. Urinary retention was seen in 2% patients in group NC and was probably due to inadequate analgesia and fear of early ambulation. Hence indwelling catheterisation leads to increased incidence of UTI. More discomfort at first void and delayed ambulation. In cases where required, proper aseptic catheter insertion technique, closed drainage maintenance, avoiding prolonged catheterisation and proper catheter care can reduce the risk of acquiring UTIs. CONCLUSION             Routine use of indwelling catheter for cesarean section in haemodynamically stable patients is not necessary. Use of catheter is associated with increased incidence of urinary infection, more discomfort at first voiding, immobility and increased cost of healthcare delivery services. Acknowledgement We acknowledge the help and support of the Head of the Department of Obstetrics and Gynaecology. We extend our gratitude to all the participating patients. Conflict of interest: None Financial support: None Englishhttp://ijcrr.com/abstract.php?article_id=2672http://ijcrr.com/article_html.php?did=2672 Lang JF, Bowen JC, Strong P., Use of indwelling urinary catheter at cesarean delivery, Obstetrics & Gynecology. 2001; 97(4): S 66. Senanayake H., Elective cesarean section without urethral catheterization.             J ObstetGynaecol Res 2005;31:32–37. Arulkumaran S, Cheng S, Ingemarsson I, Ratnam SS, Low SH, Is there a need for routine indwelling catheter after caesarean section? Singapore Med J 1986;27:54–57. Tangtrakul S, Taechaiya S, Suthutvoravut S, Linasmita V., Post-caesarean section urinary tract infection: a comparison between intermittent and indwelling catheterization. J Med Assoc Thai 1994;77: 244–48. Humburg J., Postpartum urinary retention – without clinical impact? Ther Umsch 2008;65:681–85. Schwartz MA, Wang CC, Eckert LO, Critchlow CW, Risk factors for urinary tract infection in the postpartum period. Am J Obstet Gynecol 1999;181:547–53. Barnes JS, Is it better to avoid urethral catheterization at hysterectomy and caesarean section? Aust NZ J Obstet Gynaecol 1998; 38:315–16. Pandey D, Mehta S, Grover A, Goel N. Indwelling Catheterization in Caesarean Section: Time To Retire It! J Clin Diagn Res. 2015;9(9):QC01–QC4. Hemsell DL, Infections after gynecologic surgery. Obstet Gynecol Clin North Am 1989; 16: 381–85. Kunin CM, Urinary tract infections in females, Clin Infect Dis 1994; 18(1): 1–10. Rochelle L In: Cunningham FG, MacDonald PC, Gant NF (eds). Williams Obstetrics. 22nd edn. Vol 23 McGraw-Hill: New York, 2005, pp 523. Sedor J, Mulholland SG. Hospital-acquired urinary tract infections associated with the indwelling catheter. UrolClin North Am 1999; 26(4): 821–28. Leksawasdi N, Chanchai N, Wongkolkijsin N. Patient’s Pain Level During Indwelling Urinary Catheter. Faculty of Nursing, Chiang Mai University, Thailand, 1995. Saint S, Chenoweth CE. Bio?lms and catheter-associated urinary tract infections. Infect Dis Clin North Am 2003;17:411–32. Warren JW. The catheter and urinary tract infection. Med Clin North Am 1991; 75: 481–93. Maki DG, Tambyah PA, Engineering out the risk for infection with urinary catheters. Emerg Infect Dis 2001;7:342–47. Saint S, Lipsky BA, Goold SD, Indwelling urinary catheters: aonepoint restraint? Ann Intern Med 2002;137:125–57. Plowman R, Graves N, Grif?n MA, Roberts JA, Swan AV, Cookson B, et al. The rate and cost of hospital-acquired infections occurring in patients admitted to selected specialties of a district general hospital in England and the national burden imposed. J Hosp Infect 2001;47:198–209. Nasr AM, El-Bigawy AF, Abdelamid AE, Al-Khulaidi S, Al-Inany HG, Sayed EH. Evaluation of the use vs nonuse of urinary catheterization during cesarean delivery: a prospective, multicenter, randomized controlled trial. J Perinatol 2009;29:416–21. Ghoreishi J., Indwelling urinary catheters in cesarean delivery. Int J Gynaecol Obstet 2003;83:267–70. Beeson PB, The case against the catheter. Am J Med.2000;24:1-6. Arlyn E, Antonia E, et al. Early removal of urinary catheter in CS in a tertiary       training hospital. Philippine Journal of Obs & Gynae.2007;31(2):69-74.

Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241129EnglishN2020May4HealthcareOptimization of the Response to nCOVID-19 Pandemic in Pregnant Women – An Urgent Appeal in Indian Scenario English1418Neha GargEnglish Keerthana KothandaramanEnglish Madhan JeyaramanEnglishCorona virus Disease 2019 (nCOVID-19), the novel corona virus infection caused by SARS-CoV-2 is a global pandemic with an estimated global mortality rate of 3.4%. SARS-CoV-2, the seventh human corona virus after SARS-CoV and MERS-CoV. The disease presentation can range from no symptoms (asymptomatic) to severe pneumonia and death. As of now, the Indian experience is limited. There is even less to draw from in terms of experience in pregnant women and neonates. Pregnancy is a physiological state with changes that predisposes to respiratory complications of viral infection. Limited knowledge available on Corona virus infections during pregnancy is attributable to the findings in SARS and MERS epidemics. Clinical manifestations in pregnancy were found to be similar to those of non-pregnant adults with nCOVID-19 that have been reported in the literature without increased susceptibility.Recent evidences have shown the absence of vertical transmission of the SARS-CoV-2 virus from mother to infant. In India, cost effective and readily available drugs such as hydroxychloroquine and azithromycin are used for nCOVID-19 infection as per guidelines given by Federation of Obstetric and Gynaecological Societies of India (FOGSI). All the patients with nCOVID-19 in labour universally delivered by caesarean section. Initiation of breastfeeding is controversial. The isolation, quarantine, case, contact definition, notification and testing guidelines are same as that of the general public. EnglishnCOVID-19, Pregnancy, SARS CoV-2, PandemicIntroduction Corona virus Disease 2019 (nCOVID?19), the novel corona virus infection caused bySARS-CoV-2 is a global pandemic as declared by WHO on March 11, 2020.1 Since the time the first case of nCOVID-19 pneumonia was reported in Wuhan, Hubei Province, China, in December 2019, the infection has rapidly spread world over.2,3,4 Currently, it has affected 208 countries and territories around the world with 32,49,022 total cases and 2,30,804 deaths (As on 1st May, 2020).5 The Report of the World Health Organization (WHO) estimated a high R0 (reproduction number) of 2–2.56 and an estimated global mortality rate of 3.4%.7India reported its first case on 30th January, 2020. There was a travel history from Wuhan, China. Since then (as on 1st May, 2020), 35,043 confirmed cases and 1075 deaths have been reported from 27 States/UTs.8 As of now, the Indian experience is limited. There is even less to draw from in terms of experience in pregnant women and neonates. Corona Virology Corona viruses are enveloped, non segmented, positive sense ribonucleic acid (RNA) viruses belonging to the family Coronaviridae, order Nidovirales with three approved genera (alpha, beta and gamma). Around the world, corona viruses are found widespread in bats with many other species including birds, cats, dogs, pigs, mice, horses, whales, and humans being the host to a lesser extent. There is a huge diversity of these viruses which can be explained by their unusually large genomes, infidelity of the RNA-dependent RNA polymerase and the high frequency of RNA recombination.9,10 This has enabled the emergence of new viruses with traits that allow them to adapt to new hosts and ecologic niches, sometimes leading to zoonotic events. In humans, four respiratory corona viruses (human corona viruses (HCoV) 229E, OC43, NL63, and HKU1) are known to be endemic.10 Other corona viruses such as severe acute respiratory syndrome corona virus (SARS-CoV) and Middle East respiratory syndrome corona virus (MERS-CoV)have caused large scale epidemics in 2002 and 2012 respectively, with more than 10 000 cumulative cases in the past two decades, and mortality rates of 10% for SARS-CoV and 37% for MERS?CoV.11,12,13 Pathogenesis SARS-CoV-2, the seventh human corona virusbelongs to the same β-corona virus genus and has genome similarity of about 79% and 50% with SARS-CoV and MERS-CoV, respectively. It has structural similarity of the receptor-binding domains with SARS-CoV and usesACE-2 as the receptor for host cellular binding.14,15 nCOVID-19 is spread by respiratory droplets and direct contact. Fecal shedding has been demonstrated from some patients. Airborne spread and fecal-oral route does not appear to be a major driver of transmission based on available evidence. The natural symptomatology of the disease can range from no symptoms (asymptomatic) to severe pneumonia and death.2Typical signs and symptoms include fever (87.9%), dry cough (67.7%), fatigue (38.1%), sputum production (33.4%), shortness of breath (18.6%), sore throat (13.9%), headache (13.6%), myalgia or arthralgia (14.8%), chills (11.4%), nausea or vomiting (5.0%), nasal congestion (4.8%), diarrhoea (3.7%), and hemoptysis (0.9%), and conjunctival congestion (0.8%). Approximately 80% of confirmed cases have mild to moderate disease, which includes non-pneumonia and pneumonia cases, 13.8% have severe disease (dyspnea, respiratory rate ≥30/minute, blood oxygen saturation ≤93%, PaO2/FiO2 ratio 50% of the lung field within 24-48 hours) and 6.1% are critical (respiratory failure, septic shock, and/or multiple organ dysfunction/failure).1,6,16,17 Pregnancy with nCOVID-19 infection On extensive review of scientific literature, it was found that out of a total of 1794 articles on the Corona virus infection, only 36 addressed the issue in pregnant women. A total of eight studies (10 case series/reports and 1 retrospective cohort study) reported outcome in 73 pregnant women with corona virus infection.19 There is a dearth of studies in this area as highlighted by the Indian obstetric and neonatology forums.18,19 Analysis in the Indian context is lacking. No clinical trials have compared specific care including isolation strategies in pregnant women. Due to absence of comparative group it is not possible to assess the effect of nCOVID-19 infection in pregnancy. Pregnancy is a physiological state with changes in the immune and cardiopulmonary systems that predisposes the women to respiratory complications of viral infection. During previous influenza pandemics (1918-2010), pregnant women were at higher risk for hospitalization than non-pregnant women a year before pregnancy20 or those 6 months after delivery 21 and mortality rates were also higher among antenatal women.22-26 Infection with SARS-CoV in pregnancy was associated with adverse pregnancy outcomes. High incidences of spontaneous miscarriage (57%), preterm delivery (80%), and intrauterine growth restriction (16.67%) was seen. There is no evidence of perinatal SARS infection among infants born to these mothers. The case fatality rate of such pregnant women is up to 25%.27 MERS-CoV is known to be responsible for severe complications during pregnancy, including the need for endotracheal intubation, admission to an intensive care unit (ICU) (54%), renal failure and death (27%). All the reported cases were symptomatic with the case fatality rate of 35%. The infant death rate was 27%.28 Currently, however, the impact of nCOVID-19 infection on pregnant woman is not fully elucidated. There are concerns relating to the potential effect on fetal and neonatal outcome. Therefore, pregnant women require special attention in terms of prevention, diagnosis and management of nCOVID -19 infection. Maternal symptomatology The mean incubation period is 5 to 7 days with maximum infection seen by 11 days of exposure.29 The evidence and the limited knowledge available on Corona virus infections during pregnancy is attributable to the findings in SARS and MERS epidemics. They are responsible for serious maternal and neonatal outcomes, both in terms of morbidity and mortality as previously mentioned. But the findings with SARS-CoV-2 follows a different milder trajectory. Nan Yu et al30 studied seven infected pregnant patients in late pregnancy (mean = 39 weeks plus 1 day) admitted at a Chinese Hospital from 1st Jan to 8th Feb, 2020.Clinical manifestations were found to be similar to those of non-pregnant adults with nCOVID-19 that have been reported in the literature which ranged from fever (86%), cough (14%), shortness of breath (14%), to diarrhoea (14%). The pregnancy and neonatal outcomes were good which was achieved with intensive and active management that might be the best practice in the absence of more robust data. Chen H et al31 retrospectively studied 9 infected pregnant Chinese females admitted from January 20th to 31st, 2020. Cases presented with low-grade fever without chills (77.8%), cough (44.4%), myalgia (33.3%), sore throat (22.2%), malaise (22.2%) and obvious gastrointestinal symptoms (11.1%), shortness of breath and pre-eclampsia (11.1%). However, none of the nine patients developed severe pneumonia, requiring mechanical ventilation, or died of COVID-19 pneumonia, as of Feb 4, 2020. In a detailed report of 38 infected pregnant Chinese women, of whom 37 were confirmed cases, there were no cases of either severe pneumonia or maternal deaths. Although there were co-morbid conditions (like gestational hypertension, pre-eclampsia, hypothyroidism and influenza infection) present in some of the women, mostly obstetrical in etiology, they apparently did not result in life-threatening maternal SARS-CoV 2 disease.32 Similarly, two case reports of a Chinese infected pregnant woman showed a two-day history of dry cough, chills without fever, or shortness of breath33 and fever without cough or sputum34 respectively. Royal College of Obstetricians and Gynaecologists (RCOG) has also postulated that pregnant women don&#39;t appear to be more susceptible to consequences of infection of nCOVID-19 than general population.35 Maternal-fetal transmission and neonatal cases  Nan Yu et al30 reported that 33.33% of the neonates were infected with SARS-CoV-2 36 hours after birth. Similarly, a Chinese case report by Wang Set al34 described a positive neonatal case at 36 hours of birth. The babies had no contact with their mothers after birth. Both cases were discharged after 12-14 days of birth following two consecutive negative nucleic acid test results. The suspected vertical transmission of the SARS-CoV-2 infection could not be confirmed because of the late collection of the neonatal oropharyngeal swab, performed 36 hours after birth.  Whereas other studies were able to prove conclusively that no vertical transmission of the infection to the neonates occurred. A retrospective study of 9confirmed pregnant cases confirmed negative detection of the virus in amniotic fluid, umbilical cord blood and nasopharyngeal swab of newborns.31 Another case report showed negative vertical transmission.33Schwartz et al described a series of 30 neonates with no confirmed SARS-CoV-2 infection cases, despite the existence of perinatal complications in some of the infants. The virus was not identified in the amniotic fluid, placenta, breast milk of 6 mothers or in the nasal secretions of their neonates tested so far.32Similar to the previous SARS and MERS epidemics, all these studies show no evident vertical transmission with the current SARS-CoV-2.36 Thus, the evidence to support the absence of vertical transmission of the SARS-CoV-2 virus from mother to infant is continuously increasing.  Treatment protocols followed All the patients with nCOVID-19 in labour had caesarean section after consultation with a multidisciplinary team within a few days of the admission to the hospital.30-34 There is no proven scientific rationale for this. It could reflect local preference and practices. Another reason could be lack of knowledge about the intrapartum course with its possible complications such as prolonged labour, or chorioamnionitis with suspected fetal jeopardy. Because nCOVID-19 is an emerging infectious disease, the optimal treatment for affected individuals has not yet been established. In a study by Nan Yu et al30 all patients received oxygen therapy, via nasal catheter, in isolation. Antiviral treatment included oseltamivir (75 mg every 12 horally), ganciclovir (0·25 g every 12 h, intravenously), and interferon (40 μg daily, atomisation inhalation) and arbidol tablets (200 mg three times daily, orally). Traditional chinese medicines, such as Jinyebaidu granules and Lianhuaqingwen capsules were also used. Antibiotic treatment (cephalosporins, quinolones, and macrolides) was given for all with 29% patients given single antibiotic and 71% patients given combination therapy. Methylprednisolone was given after caesarean section in 71% cases. Wang S et al34 in Tongji Hospital, Wuhan, China used antiviral treatment (40 μg of recombinant human interferon α1b atomized inhalation and ganciclovir, 0·25 g every 12 h, intravenously), methylprednisolone?20mg intravenously) and antibiotics (Abipenem, 0.3g every 12h, intravenously and moxifloxacin, 0.4g q.d, intravenously) for treatment for nCOVID-19 infection. General measures for nCOVID-19 infections should include rest, oxygen supplementation, fluid management and nutritional care as needed. According to Federation of Obstetric and Gynecological Societies of India (FOGSI), its treatment can be attempted by two approaches. The first being the use of a combination of Hydroxychloroquine and Azithromycin which are cost effective and readily available in India. The other approach being the use of antiviral drugs, some of which are not yet available in India.19 Outcomes and discharge The outcomes of the pregnant women were good among the various institutions observed.30-34 There were no intensive care unit admissions for mothers throughout the study period, including before and after delivery. All patients were discharged from the hospital after adequate care. Body temperature returned to normal for more than 3 days; respiratory symptoms improved significantly; pulmonary imaging showed a significant improvement in acute exudative lesions; and nucleic acid test of respiratory specimens such as results of sputum and nasopharyngeal swabs were negative twice in a row (sampling interval ≥24 h).30-34 The mother’s breast milk sample was negative for SARS-CoV-231,32,34 and therefore breastfeeding is not a contraindication. The main risk for infants of breastfeeding is the close contact with the mother, who is likely to share infective airborne droplets. Whether it could be allowed with proper hygienic practices and keeping in mind the risk-benefit ratio, is still controversial.37 This should be discussed with the parents before a decision is made. In accordance with RCOG and FOGSI guidelines hand hygiene and respiratory hygiene (wearing a mask and not sneezing in front of a baby) should be strictly followed during breast feeding. Milk can be expressed with a manual or electric breast pump after adequately washing of hands and according to recommendations for proper pump cleaning after each use. This could later be fed to the baby by someone well.19,35 Discussion and Implications Due to the rapid outbreak and want of time for evaluation and follow up, the long-term outcomes of the neonates and whether in-utero or vertical transmission is possible has not been demonstrated so far. Postnatal transmission from infected mother or care givers to the neonate is definitely possible. A delay in testing can make it difficult to differentiate a mother to fetal transmission (or at birth) from postnatal (contact/droplet) transmission. Lastly, fetal effect of maternal infection during first and second trimester of pregnancy is not known. It must be emphasized that as vaccine development is currently under progress for nCOVID-19, pregnant women should be considered for inclusion in the clinical trials as well as the eventual distribution of the vaccine unless the risks outweigh the potential benefits.38 Transparent and comprehensive reporting of all cases of nCOVID-19 pregnancies is very essential to get concrete results helping in generating evidence and guiding clinical management. Government of India guidelines39 should be followed for the same. The isolation, quarantine, case, contact definition, notification and testing guidelines are same as that of the general public. Conclusion This review article of the presentation of nCOVID-19 infection in pregnant women provides a scaffold on which further investigations and studies can be added, to its ever-evolving knowledge to equip us in fighting this global crisis better. Acknowledgement: Authors acknowledge the immense help received from the scholars whose articles are cited and included in references of this manuscript. The authors are also grateful to authors / editors / publishers of all those articles, journals and books from where the literature for this article has been reviewed and discussed. Financial support: Nil Conflicts of interest: Nil Englishhttp://ijcrr.com/abstract.php?article_id=2673http://ijcrr.com/article_html.php?did=2673 World Health Organization. https://www.who.int/dg/speeches/detail/whodirector-general-s-opening-remarks-at-the-media-briefing-on-covid-19---11-march-2020. [Cited: 1st May, 2020] Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y et al. Clinical features of patients infected with 2019 novel corona virus in Wuhan, China. Lancet 2020; 395: 497– 506. World Health Organization. Novel corona virus - China. Disease outbreak news: Update. 12 January 2020. https://www.who.int/csr/don/12-january-2020-novel-corona virus?china/en/ [Accessed 7 March 2020]. Corona virus COVID?19 Global Cases by the Center for Systems Science and Engineering (CSSE) at Johns HopkinsUniversity.  https://www.arcgis.com/apps/opsdashboard/index.html#/bda7594740fd40299423467b48e9ecf6. Worldometers. https://www.worldometers.info/corona virus/.[Cited: May 1, 2020] Report of the WHO-China Joint Mission on Corona virus Disease 2019 (COVID?19). 16-24 February 2020. https://www.who.int/docs/default-source/corona viruse/who.china.joint-mission-on-covid-19-final-report.pdf WHO Director?General&#39;s opening remarks at the media briefing on COVID-1 - 3 March 2020. https://www.who.int/dg/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19- -3-march-2020 Ministry of Health and Family Welfare, Government of India. https://www.mohfw.gov.in/. [Cited: March 30, 2020] Virus taxonomy, classification and nomenclature of viruses: ninth report of the International Committee on Taxonomy of Viruses. San Diego, CA: Academic Press, 2012. Su S, Wong G, Shi W, Liu J, Lai ACK, Zhou J et al. Epidemiology, genetic recombination, and pathogenesis of corona viruses. Trends Microbiol 2016 ;24: 490– 502. World Health Organization. Emergencies preparedness, response. Summary of probable SARS cases with onset of illness from 1 November 2002 to 31 July 2003. https://www.who.int/csr/sars/country/table2004_04_21/en/. World Health Organization. Middle East respiratory syndrome corona virus (MERS-CoV). MERS Monthly Summary, November 2019. http://www.who.int/emergencies/mers-cov/en/. Zaki AM, van Boheemen S, Bestebroer TM, Osterhaus AD, Fouchier RA. Isolation of a novel corona virus from a man with pneumonia in Saudi Arabia. N Engl J Med 2012; 367: 1814– 1820. Lu R, Zhao X, Li J, Niu P, Yang B, Wu Het al. Genomic characterisation and epidemiology of 2019 novel corona virus: implications for virus origins and receptor binding. Lancet 2020; 395: 565– 574. Zhou P, Yang X-L, Wang X-G et al. Discovery of a novel corona virus associated with the recent pneumonia outbreak in humans and its potential bat origin. bioRxiv. 2020. Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J et al. Clinical characteristics of 138 hospitalized patients with 2019 novel corona virus infected pneumonia in Wuhan, China. JAMA 2020. Guan W, Ni Z, Hu Y, Liang W, Ou C, He J et al. Clinical characteristics of 2019 novel corona virus infection in China.  medRxiv 2020. FOGSI NNF India IAP. Perinatal Neonatal Management of COVID-19 Infection. New Delhi: 2020. FOGSI. Pregnancy with COVID-19 infection. New Delhi: 2020. Dodds L, McNeil SA, Fell DB, et al. Impact of influenza exposure on rates of hospital admissions and physician visits because of respiratory illness among pregnant women. CMAJ. 2007;176(4):463–468. Neuzil KM, Reed GW, Mitchel EF, Simonsen L, Griffin MR. Impact of influenza on acute cardiopulmonary hospitalizations in pregnant women. Am J Epidemiol. 1998;148(11):1094–1102. Nuzum JW, Pilot I, Stangl FH, Bonar BE. Pandemic influenza and pneumonia in a large civilian hospital. JAMA. 1918; 71:1562–1565. Freeman DW, Barno A. Deaths from Asian influenza associated with pregnancy. Am J Obstet Gynecol. 1959; 78:1172–1175. Harris JW. Influenza occurring in pregnant women. JAMA. 1919; 72:978–980. Woolston WJ, Conley DO. Epidemic pneumonia (Spanish influenza) in pregnancy. JAMA. 1918; 71:1898–1899. Siston AM, Rasmussen SA, Honein MA, Fry AM, Seib K, Callaghan WM et al. Pandemic H1N1 Influenza in Pregnancy Working Group. Pandemic 2009 influenza A(H1N1) virus illness among pregnant women in the United States. JAMA 2010; 303: 1517–1525. Wong SF, Chow KM, Leung TN, Ng WF, Ng TK, Shek CC et al. Pregnancy and perinatal outcomes of women with severe acute respiratory syndrome. Am J Obstet Gynecol 2004; 191: 292–297. Alfaraj SH, Al-Tawfiq JA, Memish ZA. Middle East respiratory syndrome corona virus (MERS-CoV) infection during pregnancy: report of two cases and review of the literature. J Microbiol Immunol Infect 2019; 52: 501–503. 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Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241129EnglishN2020May4HealthcareVitamin-D an Immune Shield Against nCOVID-19 English1925Madhan JeyaramanEnglish Arun GulatiEnglish Talagavadi Channaiah AnudeepEnglish Dharma U ShettyEnglish Latha SEnglish Ajay SSEnglish Rashmi JainEnglish Madhurya SantoshEnglishPresently the world is battling a deadly pandemic without any effective licenced drugs or biologics to vanquish SARS-CoV-2. The experience of managing the past viral aetiological outbreaks has been extrapolated to nCOVID-19, yet its effectiveness is uncertain. This connotation invokes a potential insight to focus upon those elements and etiquettes which are an integral part of our life and expound for nCOVID-19 treatment. This further impels us to consider our food as a time-tested medicine. In a study, a decrease in vitamin D levels accounted for the bovine coronavirus infection in calves. Interestingly it paves the way for exploring the role of Vitamin-D as accessible ‘magic bullets’ against nCOVID-19. Currently, its metabolism and immuno-modulatory characterization are well-established. In fact, the studies have described an inverse relationship between Vitamin-D level and respiratory infections. This further substantiates for understanding its shielding effect against nCOVID-19. Few researchers have recommended dosage of Vitamin-D intake among adult and high-risk individuals including front-liners. However, the enforcement of this potent nutritional ergogenic calls for dose rationalisation with due effectivity and safety based on large randomized control trials. EnglishCoronavirus, nCOVID-19, Vitamin D, Pandemic, ImmunomodulatorIntroduction The world is witnessing the tight grip of the deadly pandemic caused by the newly identified strain of Coronavirus (SARS-CoV-2/nCOVID-19).1 Currently, no specific drugs or biologics are available against nCOVID-19. However, the evidence from past viral outbreaks (SARS-CoV-1, MERS-CoV, EBOV and Influenza) have been extrapolated to combat SARS-CoV-2; yet the efficacy remains uncertain.2 It was found that  a decrease in vitamin D in calves accounted as the prime cause of bovine coronavirus infection previously. This leads to plausible insight for exploring and understanding the role of vitamin D against SARS-CoV-2 in order to optimize it as a potent nutritional ergogenic for the same. Vitamin D is a steroid hormone (also called sunshine hormone) synthesized endogenously from UV-B radiation to the skin or as exogenous supplements from an animal source or fortified food. The complex synthesis and its metabolism is well established which confers essential benefits in bone and muscle health, helps in immune functioning by defying inflammation and prevents respiratory infection.1 Various studies and researches provide us with the evidence of immunogenic and anti-microbial properties of Vitamin D.3,4 Vitamin D deficiency is seen in those who get less exposure to sunlight or inadequate intake of vitamin D and other high-risk group includes individuals with chronic lung disease and obese or physically inactive. Studies have shown an inverse relationship between Vitamin D level and respiratory infection. This article provides an insight into how Vitamin D can act as an immune shield in respiratory infection like nCOVID-19 and substantiate for supplementary benefits for the front line warriors, high-risk population and general adult population. Vitamin D – Metabolism and Absorption Vitamin D was first characterized as a vitamin in the 20th century and now it is recognized as a prohormone. The two important forms of vitamin D are vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol) respectively.1 Sources: Vitamin D3 is synthesized endogenously in the skin by epidermis and dermis containing 7-dehydrocholesterol (DHC). When UV-B radiation (280–310 nm) passes through these skin layers, 7 dehydrocholesterol absorbs UV-B photons and gets converted to pre vitamin D3 (precalciferol). This photoisomerization is followed by thermal-dependent isomerization of the pre-vitamin D3, leading to formation of the vitamin D3 molecule, also known as cholecalciferol. Once formed, vitamin D3 is bound preferentially to the vitamin D binding protein (DBP), which allows its translocation into the general circulation.5 The exogenous source of vitamin D includes dietary supplementation through animal-based food (mainly fish oils contain vitamin D3) or fortified food. On the other hand, plant derivatives contain vitamin D2. Moreover, fungi and mushrooms irradiated with UV-B also contain vitamin D2.6 Metabolism: The complex process of Vitamin-D synthesis, mechanism of action and absorption is explicably depicted in figure 1. The ‘hydroxylation reaction’ is the key biochemical process involved in conversion into active form; calcitriol (1,25-dihydroxycholecalciferol). This hydroxylation is mediated via cytochrome P450 mixed-function oxidases (CYPs) located either in the endoplasmic reticulum (ER) (e.g. CYP2R1) or in the mitochondria (e.g., CYP27A1, CYP27B1, and CYP24A1).7 Figure 1: Metabolism and effects of Vitamin D in target organs. (Pic courtesy: Michael F. Holick. Resurrection of vitamin D deficiency and rickets. J Clin Invest. 2006;116(8):2062-20728) Calcitriol acts through the vitamin D receptor (VDR), belonging to the nuclear receptor superfamily.7 The absorption of dietary Vitamin-D2 or D3 usually occurs in the small intestine with other dietary fats wherein the following subsets of processes for packaging exogenous Vitamin-D into chylomicrons occurs, and thereafter they are transported to the liver. A fraction of the vitamin D contained in the chylomicron can be taken up by the adipose tissue and skeletal muscle and the remaining chylomicrons reach theliver via specific carrier protein i.e. vitamin D binding protein (DBP) which in turn also facilitates their transport to different tissues as per requirement.6 Calcitriol is mainly involved in the regulation of plasma calcium and phosphate levels along with PTH by acting on three major organs i.e, intestine, kidney, and bone (as shown in figure 1).6,7,8 Vitamin D – An Immune Shield Vitamin D prevents respiratory infection by strengthening and regularizing physical barrier, cellular innate immunity and adaptive immunity (as shown in figure 2). Figure 2: Vitamin D as Immune Shield. (Pic courtesy: MirentxuIruretagoyena, Daniela Hirigoyen, Rodrigo Naves and Paula Isabel Burgos. Immune response modulation by vitamin D: role in systemic lupus erythematosus. Frontiers in Immunology. 2015;6:5139) Physical barrier: Vitamin D acts as a physical barrier by maintaining the integrity of the skin epithelium. It upregulates genes via the 1a-hydroxylase enzyme, which helps in the maintenance of tight junctions (occludins), gap junctions (connexion 43), and adherens junctions (E-cadherin) (as shown in figure 3). There is well documentation of viral infections resulting in subsequent bacterial superinfections. The upregulated molecules by viral pathogen may serve as receptors for bacteria and may result in this superinfection. Influenza and parainfluenza viruses possess neuraminidase (NA) activity, which appears to increase bacterial adherence after viral preincubation.10 Tight junctions and adherens junctions also prevent viruses from crossing the epithelial barrier. However, viruses have adopted multiple strategies wherein they utilize components of cell–cell adhesion structures as receptors and blazing their path through the epithelium.Viruses takeadvantage of the apical junction complex to spread. Whereas some viruses quickly disrupt epithelial integrity, others carefully preserve it and use cell adhesion proteins and their cytoskeletal connections to rapidly spread laterally. This is exemplified by the hidden transmission of enveloped viruses that use nectins as receptors (as shown in figure 4).11 Cellular immunity: Vitamin D potentiates cellular innate immunity through the induction of antimicrobial peptides, including human cathelicidin LL-37 and β defensin which exist in neutrophils, monocytes, natural killer (NK) cells and epithelial cells lining the respiratory tract.12Cathelicidins possess direct antimicrobial activities against a spectrum of microbes, (gram-positive & negative bacteria, mycobacteria, enveloped & non-enveloped viruses, protozoa and fungi) which percolate cell membrane and also neutralizes the activities of microbial endotoxins (as shown in figure 5).13,14 Jeng et al., demonstrated that systemic LL-37 levels may be regulated by vitamin D status in acutely ill patients.15 Vitamin D enhances chemotaxis and phagocytic ability of innate immune regulatory cells.16 Figure 4: Viruses use junctional proteins as receptors. (Pic courtesy: Mateo M, Generous A, Sinn PL, Cattaneo R. Connections matter− how viruses use cell–cell adhesion components. Journal of cell science. 2015;128(3):431-911)   Vitamin D mediates antioxidant property by enhancing the upregulation of glutathione reductase genes and glutamate–cysteine ligase modifier subunit genes which prevent the microbial infection.17 Jain et al reported that glutathione upregulates vitamin D regulatory genes and lowers oxidative stress & inflammation.18 Vitamin D enhances the innate cellular immunity by reducing the cytokine storm wherein it  decreases  the expression of pro-inflammatory cytokines and increases the expression of anti-inflammatory cytokines mediated by macrophages.19 Adaptive immunity: Vitamin D acts as a “Magic Bullet” in modulating the adaptive immunity.20 VitaminD3 (a) suppresses T helper type 1 (Th1) cell-mediated responses by primarily repressing production of IL-2 and INF-γ, (b) upregulates T helper type 2 (Th2) cells, which indirectly suppresses Th1 cells and (c) promotes induction of the T regulatory cells, thereby inhibiting inflammatory processes.20 The immunomodulatory activities of vitamin D are depicted in figure 6.   Dendritic cells (DCs) are the chief antigen-presenting cells (APCs). They help in maintaining peripheral tolerance by preventing self-reactive T cells from causing autoimmune damage through an adaptive immune response. That&#39;s how DCs play a critical role against infectious agents and tumours. DCs have a role in peripheral T cell tolerance, by inducing T cell anergy or unresponsiveness to self- antigens. Calcitriol suppresses DC differentiation and maturation in-vitro.21 Due to the central tolerogenic activity of DCs, when there is low serum Vitamin D concentration, there is a risk of development of autoimmune diseases.22 Relationship between vitamin D and viral diseases Seasonal influenza, which peaks in the winter, has a high health impact on the population and pose a public health problem. According to GLaMOR Project (2019), 389,000 (uncertainty range 294,000–518,000) respiratory deaths were associated with influenza during the period 2002–2011.23Cannell et al. hypothesized that the winter peak of infection was due to the seasonal changes as the solar UV-B doses are less in the winter and leading to lesser vitamin D concentration, in most mid and high latitude countries.24 Gruber-Bzura BM (2018) suggested that vitamin D should reduce the risk of influenza, butmore studies are required to evaluate this plausibility.25 An observational study conducted in Connecticut on 198 healthy adults concluded that concentrations of 38 ng/mL or more were associated with a significant (p < 0.0001) two-fold reduction in the risk of developing ARTIs and with a marked reduction in the percentage of days ill.26 Evidence from the effects of vitamin D concentration among viral agents were shown in the following table 1. Postmenopausal women residing in Long Island, NY with mean baseline 25(OH)D3concentration 19 ± 8 ng/mL were included in a clinical trial wherein it was reported that supplementation with 2000 IU/day accounted for lesser number of cases of upper respiratory tract infections, including influenza, than a placebo or supplementation with 800 IU/day.31 Martineau AR et al reported that 25(OH)D3 concentrations of 20–30 ng/mL reduced the risk of ARTIs.3 Sabetta JR et al, conducted an observational study wherein they found 38 ng/mL as the appropriate concentration for reducing the risk of Community-Acquired Pneumonia.26 Vitamin D supplementation for raising serum 25(OH)D3 concentrations can help in the reduction of hospital-associated infections (HAIs).32 Albeit the level of protection generally spikes with spiking of 25(OH)D3 concentration. The optimal range appears to be 40–60 ng/mL (100–150 nmol/l) for the same. In order to achieve those levels, a study reported that it calls for administering approximately half of the population with at least 2000–5000 IU/day of vitamin D3respectively.33 Relationship between Vitamin D and nCOVID-19 The world distribution of nCOVID-19 fatalities appears to overlap with that of the vitamin D lacking population.34 Epidemiological studies have shown people with low vitamin D levels have a higher risk of acute respiratory tract infection and community-acquired pneumonia.3 Grant WB et al recommended that people at risk of influenza and/or nCOVID-19 should consider taking 10,000 IU/day of vitamin D3 for a few weeks to rapidly raise 25(OH)D3 concentrations, followed by 5000 IU/day. “The goal should be to raise 25(OH)D3 concentrations above 40–60 ng/mL (100–150 nmol/L),” the team adds. “For treatment of people who become infected with nCOVID-19, higher vitamin D3 doses might be useful.”4 The correction of vitamin D deficiency is thought to suppress CD26, a putative adhesion molecule for nCOVID-19 host cell invasion. Vitamin D may also attenuate interferon gamma (IFNγ) and interleukin-6 (IL-6) inflammatory responses, both potent predictors of poorer outcome in critically-ill ventilated patients including those with nCOVID-19.35-37 In the expanding  face of the nCOVID-19 pandemic, and in the absence of a vaccine or any effective anti-viral drug therapy to treat those infected, these findings call for the prioritized supplementation of all hospital inpatients, nursing home residents and community-dwelling older adults with vitamin D at a minimum daily dose of 20 micrograms per day. It is further recommended that supplementation be targeted at other vulnerable constituencies (e.g. those with diabetes mellitus or compromised immune function, those with darker skin, vegetarians and vegans, those who are overweight or obese, smokers and healthcare workers), and ultimately extended to rest of the population in order to mitigate the grave public health risks associated with nCOVID-19 infection.38 Discussion Our life has come to a standstill due to the rampant spread of the novel coronavirus. The ever-pacing life of each and every individual has now been turned up-side-down. What is more saddening is that  till date we haven’t been  able to direct our specific medical armours (drugs & biologics) effectively and also we are striving hard to address the efficacy and safety concerns rationalised for curbing this contagion. This gives us an opportunity to expand our insight to focus upon those elements and etiquettes which are an integral part of our life and expound for nCOVID-19 treatment. We, the authors of this article staunchly agree with this famous quotation “Let your food be your medicine” by Hippocrates, the father of Medicine. The food we eat, contributes a substantial amount to our body’s healthy functioning. The food rich in all the nutrients, what we call as balanced diet adjuncts for being an ever-green medicine. And this framework made us inquire into how the most deficit reported vitamin i.e. Vitamin-D can boost our fight against nCOVID-19. Can this act as an easily accessible “magic bullet”? If it has any role in conferring immunity? Is there any specific role of Vitamin D in combating respiratory infections? To add, if we can extrapolatethis as a prophylaxis or treatment against nCOVID-19. And finally, if it will be   beneficial for any specific population, and if it is, to tabulate the optimum dose.   These are some potential questions which we have explicably addressed in this review article. Vitamin-D, also known as the sunshine vitamin is readily accessible from 10-15 minutes of exposure to sunlight, whereby upon absorption it undergoes a complex metabolic procedure relayed at liver and kidney for making it available in the active form (Calcitriol; 1,25-dihydroxycholecalciferol). It can also be exogenously supplemented from an animal source or fortified food. This vitamin is further known to regulate calcium metabolism and plays an important role in strengthening the skeletal system. Some research analysis also accounts that its deficiency during pregnancy can result in preterm delivery. The individuals who are deficient in Vitamin-D are susceptible to infections and it has been proved that it is more so in the elderly in whom this deficiency is more common.  Recent research has highlighted that it may have an important role in regulating the immune system. The immune response with advancing age swiftly inclines towards pro-inflammatory state accentuating chronic low-level inflammation with the progression of the disease. This age- associated state is regarded as ‘inflamm-aging’. Notably, this also plays a crucial role in preventing respiratory infections as per recent research. The mechanism recognised involves the interplay of physical barrier, innate cellular immunity and adaptive immunity respectively. In conjunction, these function to downregulate the inflammatory factors and further attenuate the cytokine storm phenomenon. This storming phenomenon of cytokines accounts for morbidity and mortality in the underlying infective condition which has been discussed in detail in this review. SARS-CoV-2 emerged as ‘pneumonia of unknown aetiology’; later mechanism of entry into the host cell portrays it as respiratory virus primarily. Serum vitamin D concentrations tend to decrease with age, which may be important for nCOVID-19 as case-fatality rates (CFRs) increase with age. By increasing the upregulation of glutathione, vitamin D is being hypothesized to prevent and treat nCOVID-19. In view of this, several clinical trials are afoot for optimising Vitamin-D as a potential option.A recent study from Ireland identified Vitamin-D as the potent immuno-modifier which can be used in 70+ and older individuals who are ‘cocooning’ during this outbreak. The recommendations include 10ug/day (400 IU) from diet during winters. But since the level in diet is lower than this, so 10ug/ day supplementation can be taken and for those who are housebound due to quarantine an additional supplement of 15-20ug/ day (600-800 IU) to be taken. Persons over 70 years are recommended to take 20-25ug/day (800-1000 IU) respectively.4 In another study, a team from the US recommended taking 10,000 IU/d of vitamin D3 for a few weeks to raise 25(OH)D3 concentrations rapidly and followed by 5000 IU/d respectively. They defined that the purpose should be to raise 25(OH)D3 concentrations to 40–60 ng/mL (100–150 nmol/L), and recommended higher doses for individuals who are infected with COVID-19.39 With this background, considering all the evidence-based literature reviewed above, we postulate that Vitamin-D may be administered as chemoprophylaxis to all the front-liners and can also be considered as an add-on supplement in hospitalised nCOVID-19 patients after dose optimization. Conclusion The world is witnessing the tremendous contagiosity of nCOVID-19 wherein the greatest challenge is being confronted by the medical fraternity. Clinical evaluation and trials are pacing globally to come-up with specific drugs or biologics for nCOVID-19 treatment. Amidst all, it is equivalently significant to understand and practice healthy eating habits. The available literature beautifully enlightens us with the imperative role of diet and how these biochemical molecules boost up an individual&#39;s immunity; further render shielding effect against infections. In this connotation, Vitamin-D has been studied and further extrapolated for nCOVID-19 treatment. The immuno-modulatory property has been outlined with a positive outlook for chemoprophylaxis and combination therapy. This surely will be beneficial for high-risk candidates; however, the dose optimization for the optimum benefits and efficacy should be re-enforced based on large randomized control trials. Some clinical trials are underway; in the interim the recommended daily allowance can be regarded as a safe play. Clinicians should thus advocate wisely in relation to the rapidly emerging views on nCOVID-19 treatment. Acknowledgements: All the authors have equally contributed in framing and reviewing the manuscript. Authors acknowledge the immense help received from the scholars whose articles are cited and included in references of this manuscript. The authors are also grateful to authors / editors / publishers of all those articles, journals and books from where the literature for this article has been reviewed and discussed. We thank Dr. Naveen Jeyaraman, Junior Resident of Orthopedics, Kasturba Medical College, Manipal, Karnataka, India, Dr. Shirodkar Jaswandi Dilip, Medical Officer, ESIS hospital (Worli), Mumbai, Maharashtra, India and Dr.Prajwal GS, Junior Resident of Orthopedics, JJM Medical College, Davangere, Karnataka, India for literature search regarding nCOVID-19. Conflicts of interest:Nil Funding sources: Nil Abbreviation: APC – Antigen Presenting Cells; DC – Dendritic Cells; DHC – Dehydrocholesterol; DBP – vitamin D-Binding Protein; EBOV – Ebola Virus; NA – Neuraminidase; NK cells – Natural Killer cells; UV-B – Ultraviolet – B; VDR – Vitamin D Receptor Englishhttp://ijcrr.com/abstract.php?article_id=2674http://ijcrr.com/article_html.php?did=2674 Kristian G. Anderson, Andrew Rambaut, W. Ian Lipkin, Edward C Holmes and Robert F. Garry. The proximal origin of SARS-CoV-2. Nature Medicine. 2020. Available from March 17th, 2020. Anudeep TC, Madhan Jeyaraman, Dharma U. Shetty, Hemmanth Raj, Ajay SS, RajeswariSomasundaram, Vinodh Kumar V, Rashmi Jain. Convalescent Plasma as a plausible therapeutic option in nCOVID-19 – A Review. J Clin Trials. 2020;10(3):1000409. Adrian R Martineau, David A Jolliffe, Richard L Hooper, Lauren Greenberg, John F Aloia, Peter Bergman et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ. 2017;356, i6583. Grant WB, Lahore H, McDonell SL, Baggerly CA, French CB, Aliano JL and Bhattoa HP. Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths. Nutrients. 2020;12:988. Battault S, Whiting SJ, Peltier SL, Sadrin S, Gerber G, Maixent JM. Vitamin D metabolism, functions and needs: from science to health claims. European journal of nutrition. 2013.;52(2):429-41. Gil A, Plaza-Diaz J, Mesa MD. Vitamin D: classic and novel actions. Annals of Nutrition and Metabolism. 2018;72(2):87-95. Bikle DD. Vitamin D metabolism, mechanism of action, and clinical applications. Chem Biol. 2014;21(3):319–329. Jacquillet G, Unwin RJ. Physiological regulation of phosphate by vitamin D, parathyroid hormone (PTH) and phosphate (Pi). Pflügers Archiv-European Journal of Physiology. 2019;471(1):83-98. Mirentxu Iruretagoyena, Daniela Hirigoyen, Rodrigo Naves and Paula Isabel Burgos. Immune response modulation by vitamin D: role in systemic lupus erythematosus. Frontiers in Immunology. 2015;6:51. Peltola VT, McCullers JA. Respiratory viruses predisposing to bacterial infections: role of neuraminidase. The Paediatric infectious disease journal. 2004;23(1):S87-97. Mateo M, Generous A, Sinn PL, Cattaneo R. Connections matter− how viruses use cell–cell adhesion components. Journal of cell science. 2015;128(3):431-9. Bartley J. Vitamin D: emerging roles in infection and immunity. Expert Rev Anti Infect Ther. 2010;8:1359–1369. Youssef DA, Miller CW, El-Abbassi AM, et al. Antimicrobial implications of vitamin D. Dermatoendocrinol. 2011;3(4):220–229. Grant WB. Solar ultraviolet-B irradiance and vitamin D may reduce the risk of septicemia. Dermatoendocrinol. 2009;1:37–42. Jeng L, Yamshchikov AV, Judd SE, Blumberg HM, Martin GS, Ziegler TR, et al. Alterations in vitamin D status and anti-microbial peptide levels in patients in the intensive care unit with sepsis. J Transl Med. 2009;7:28. Scherberich JE, Kellermeyer M, Ried C, HartingerA. 1-Alpha-calcidol modulates major human monocyte antigens and toll-like receptors TLR2 and TLR4 in vitro. Eur J Med Res. 2005;10(4):179–82. Lei, G.S.; Zhang, C.; Cheng, B.H.; Lee, C.H. Mechanisms of Action of Vitamin D as Supplemental Therapy for Pneumocystis Pneumonia. Antimicrob. Agents Chemother. 2017, 61. 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Paget, J.; Spreeuwenberg, P.; Charu, V.; Taylor, R.J.; Iuliano, A.D.; Bresee, J.; Simonsen, L.; Viboud, C. Global mortality associated with seasonal influenza epidemics: New burden estimates and predictors from the GLaMOR Project. J. Glob. Health 2019, 9, 020421. Cannell, J.J.; Vieth, R.; Umhau, J.C.; Holick, M.F.; Grant, W.B.; Madronich, S.; Garland, C.F.; Giovannucci, E. Epidemic influenza and vitamin D. Epidemiol. Infect. 2006, 134, 1129–1140. Gruber-Bzura, B.M. Vitamin D and Influenza-Prevention or Therapy? Int. J. Mol. Sci. 2018, 19, 2419. Sabetta, J.R.; DePetrillo, P.; Cipriani, R.J.; Smardin, J.; Burns, L.A.; Landry, M.L. Serum 25-hydroxyvitamin d and the incidence of acute viral respiratory tract infections in healthy adults. PLoS ONE 2010, 5, e11088. Villamor, E.; Villar, L.A.; Lozano, A.; Herrera, V.M.; Herran, O.F. Vitamin D serostatus and dengue fever progression to dengue hemorrhagic fever/dengue shock syndrome. Epidemiol. Infect. 2017, 145, 2961–2970. 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Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241129EnglishN2020May4HealthcareCurrent Consensus on Drugs and Biologics against nCOVID-19 — – A Systematic Review English2635Rashmi JainEnglish Ajay SSEnglish Talagavadi Channaiah AnudeepEnglish Dharma U ShettyEnglish Madhan JeyaramanEnglish Aditi ChawlaEnglish Shivam MahajanEnglish Trisha TarunitaEnglishThe deadly pandemic caused by the novel coronavirus continues to jeopardize humanity. The current situation report published by the World Health Organization (on1st May, 2020) confirms32,49,022 nCOVID-19 cases with 2,30,804 toll of human lives. This global statistical data reflects the contagiosity of SARS-CoV-2 across the world. This newly emerged strain has presented an unequalled challenge for identifying effective drugs & biologics. Till date, no proven effective therapy exists for SARS-CoV-2 infection. The past experience of managing viral aetiological outbreaks renders background for extrapolation to nCOVID-19, yet effectivity remains uncertain. This dire scenario has been addressed with an escalation in the number of clinical trials in order to comeup with specific treatment. Repurposed drugs, Antibodies and Vaccines are under various stages of clinical trials currently. In the interim, supportive care, infection prevention measures and extended psychological assistance concords the core strategy to battle against this virus. EnglishPandemic, World Health Organization, nCOVID-19, SARS-CoV-2, EffectivityIntroduction Humanity is being jeopardized under the grip of the newly emerged strain of coronavirus (SARS-CoV-2).It was declared as a pandemic by the World Health Organization on 11th March 2020. Since its inception, nCOVID-19 is spreading like a global wildfire. The ongoing pandemic has challenged the solidarity of rapidly progressing medical sciences and technologies. The genomic studies render natural selection process as the plausible explanation of the emergence of SARS-CoV-2 and rules out the view of it as a product of laboratory manipulation1. The epidemiological studies have described bats as the reservoir host and Malayan pangolins as intermediate host2. The transmission occurs either by direct contact or indirect contact. Understanding of the pathogenesis has rendered insight into the potential target sitesfor therapeutics; however those identified are in trial and not specifically approved. The global statistical data confirms 32,49,022 nCOVID-19 cases with 2,30,804 toll of human lives (on 1st May2020)(3). The incidence and mortality reported are subject to geographic variation3. The past experience of managing outbreaks of viral aetiology (SARS-CoV-1, Influenza, MERS-CoV and EBOV) paves the ground for extrapolation to SARS-CoV-2 pandemic.  Yet no proven therapies to vanquish the virus are rationally validated. The data as on 15th April 2020 at ClinicalTrials.gov with the searched terms- nCOVID-19, SARS-CoV-2, 2019-nCoV, 2019 novel coronavirus, severe acute respiratory distress syndrome, coronavirus-2 shows 833 enrolled studies and of all 541 are interventionalstudies4. This shows the glimpse of the global pace in the quest to find specific therapy with proven efficacy and rationality. Numerous authorities have collaborated for active clinical trials and these are underway. One such multinational megatrial launched by the WHO is ‘Solidarity’ which is directed to find the effectiveness of four subsets of drugs- Remdesivir;  Lopinavir/Ritonavir; Lopinavir/Ritonavir with Interferon β-1a and Chloroquine or Hydroxychloroquine (selection based on evidence from laboratory, animal and clinical studies)5. In addition, few therapies which emerged as a result of divergent thought processincludes vitamin-D supplementation, the role of mesenchymal stem cells, monoclonal antibodies and convalescent plasma are also under clinical evaluation. As of now, supportive care, strict implementation of infection control measures and extended psychological assistance are the concordant principles to deterrence. This review article adduces current consensus regarding proposed treatment, repurposed or experimental drugs and biologicsfor nCOVID-19 with a brief outline of preventive strategies advocated currently.   Figure 1: Simplified Representation ofMolecular Pathogenesis of SARS-CoV-2 with Potential Target Site of Selected Repurposed and Investigational Drugs & Biologics1 [(1)Binding of spike protein to ACE-2 and TMPRSS-2 facilitates virion entry; (2) Release of RNA by virion; (3) Translation of RNA into proteins by protein making machinery; (4)Formation of Replication Complex to produce more RNA; (5) Assembling of protein & RNA in golgi apparatus; (6)Virion Released] SARS-CoV-2 is a single-stranded positive sensed, RNA enveloped virus belonging to the beta subfamily of Coronaviridae family1. The virus glycoprotein- (S) spike protein targets angiotensin converting enzyme 2 (ACE-2) receptors, which are widely distributed over the alveolar type II (AT2) cells and endothelium and bind to it6. Another host type 2 transmembrane serine protease (TMPRSS-2) facilitates the entry mechanism via S protein7. The complex procedure of the replication of SARS-CoV-2 following a series of steps has been depicted in figure1. The understanding of viral life-cycle renders selection of a potential site for optimizing drug targets. Remdesivir is the most promising drug currently. However, the FDA has categorised it as an Investigational Agent (IND)8. The Pipeline of Drugs & Biologics for nCOVID-19 Antiviral Drugs A. REMDESIVIR (formally GS-5734) Remdesivir is an investigational nucleoside analogue of Remdesivir triphosphate (RDV-TP) discovered amidst a screening procedure against RNA viruses such as Flaviviridae and Coronaviridae. During the outbreak of EBOV, this was found to be a ‘promising agent’ due to its low EC50 with host polymerase selectivity against EBOV9. It acts as an inhibitor of RNA-dependent RNA polymerase (RdRps). Remdesivir was found to prevent haemorrhage in the lungs with a reduction in viral lung titres more than comparator agents in a murine lung infection model with MERS-CoV10. It is currently a promising potential drug due to its broad-spectrum effect with potent in-vitro activity against several coronaviruses including SARS-CoV-2 with EC50 and EC90 values found to be 0.77µM and 1.76µM respectively11 12. Single and multiple-dose phase-1 clinical trials evaluated the safety and pharmacokinetics of this drug where intravenous infusions ranging 3-225mg demonstrated to be well-tolerated without any substantiation of hepatic and renal toxicity. However, multiple dosing showed a rise in reversible aspartate aminotransferase and alanine transaminase levels 13. Notably, it is not approved by the FDA at present and can be obtained via expanded access, enrolling in a clinical trial or for compassionate use only for children who are Englishhttp://ijcrr.com/abstract.php?article_id=2675http://ijcrr.com/article_html.php?did=2675 Andersen, K.G., Rambaut, A.,Lipkin,W.I. et al. The proximal origin of SARS-CoV-2. Nat Med. 2020;26:450–452. Lam, T.T, Shum, M.H., Zhu, H. et al. Identifying SARS-CoV-2 related coronaviruses in Malayan pangolins. Nature. 2020. Coronavirus disease 2019 (COVID-19). 2020. Situation Report-82.https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200411-sitrep-82-covid-19.pdf?sfvrsn=74a5d15_2 [Cited: 1st May, 2020]. Search result for a keyword ‘COVID-19’ on ClinicalTrials.govhttps://www.clinicaltrials.gov/ct2/results/details?=Intr&Covid-19.[Cited: 1st May, 2020]. WorldHealth Organization. 2020. https://www.who.int/emergencies/diseases/novel-coronavirus-2019/global-research-on-novel-coronavirus-2019-ncov/solidarity-clinical-trial-for-covid-19-treatments.[Cited: 1st May, 2020]. ZikuanLeng, Rongjia Zhu, Wei Hou, Yingmei Feng, Yanlei Yang, Qin Han et al. Transplantation of ACE2- mesenchymal stem cells improves the outcome of patients with COVID-19 pneumonia. Aging and Disease. 2020;11(2):216-228. Iwata-Yoshikawa N, Okamura T, Shimizu Y, Hasegawa H, Takeda M, Nagata N. TMPRSS2 Contributes to Virus Spread and Immunopathology in the Airways of Murine Models after Coronavirus Infection. J Virol. 2019;93(6): e01815-18. Remdesivir Approval Status. https://www.drugs.com/history/remdesivir.html. [Cited: 15th April, 2020]. Siegel D, Hui HC, Doerffler E, et al. Discovery and synthesis of a phosphoramidate prodrug of a pyrrolo[2,1-f][triazin-4-amino] adenine C-nucleoside (GS-5734) for the treatment of Ebola and emerging viruses. J Med Chem. 2017;60(5):1648-1661. Sheahan TP, Sims AC, Leist SR, et al. Comparative therapeutic efficacy of remdesivir and combination lopinavir,ritonavir, and interferon beta against MERS-CoV. Nat Commun. 2020;11(1):222. Al-Tawfiq JA, Al-Homoud AH, Memish ZA. Remdesivir as a possible therapeutic option for the COVID-19. Travel Med Infect Dis.2020: 101615. Wang M, Cao R, Zhang L, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020;30(3):269-271. WHO R&D blueprint: ad-hoc expert consultation on clinical trials for Ebola therapeutics. Organization, World Health. October 2018.https://www.who.int/ebola/drc-2018/treatments-approved-for-compassionate-use-update/en/ [Cited: 1st May, 2020]. Search result for a keyword ‘Remdesevir’ on https://www.clinicaltrials.gov.https://clinicaltrials.gov/ct2/results?cond=remdesivir[Cited: 15th April, 2020] Chen F, Chan KH, Jiang Y et al. 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