Effect of maternal post-natal Balanced Energy Protein supplementation and infant Azithromycin on infant growth outcomes- An Open-label randomized controlled trial.

BACKGROUND: Maternal undernutrition is a direct risk factor for infant growth faltering. OBJECTIVE: We evaluated the effect of postnatal Balanced Energy Protein (BEP) supplementation in lactating women and Azithromycin (AZ) in infants on infant growth outcomes. DESIGN: A randomized controlled superiority trial of lactating mother-newborn dyads was conducted in Karachi, Pakistan. Mothers intending to breastfeed their newborns with mid-upper arm circumference of less than 23 cm and live infants between 0-6 days of life were randomly assigned to one of three arms in a 1:1:1 ratio. Lactating mothers in the control arm received standard-of-care counseling on exclusive breastfeeding, nutrition, infant immunization and health promotion plus iron-folate supplementation until the infant was 6 months of age. In intervention arm 1, mothers additionally received two 75-gram sachets of BEP per day, while in intervention arm 2 along with the standard-of-care and BEP, the infant also received one dose of Azithromycin (at 20 mg per kilogram) at 42 days of life. The primary outcome was infant length velocity at 6 months. The total sample size was 957 (319 in each arm). RESULTS: From August 1, 2018 to May 19, 2020, 319 lactating mother-newborn dyads were randomized in each arm, and the last follow-up was completed on November 20, 2020. The mean difference in length velocity (cm per month) between BEP alone and control was 0.01 (95% CI: -0.03, 0.06), BEP plus AZ and control was 0.08 (95% CI:0.03,0.13) and between BEP+AZ and BEP alone was 0.06 (95% CI: 0.01, 0.11). There were 1.46% (14/957) infant deaths in the trial, and 17.9% (171/957) non-fatal events (injectable treatment and/or hospitalizations) were recorded. CONCLUSION: Postnatal maternal BEP supplementation and infant AZ administration could modestly improve infant growth outcomes at 6 months, suggesting potential benefits in simultaneously addressing maternal and infant undernutrition. CLINICAL TRIAL DATA: This trial is registered on ClinicalTrials.gov NCT03564652 on June 21, 2018.

Effect of supplementing epinephrine in maturation media on in-vitro developmental competence of cattle and buffalo oocytes.

During in-vitro maturation, the oocyte experiences stressful conditions that likely compromise its development. Epinephrine is a catecholamine that plays a vital role during cellular stress by scavenging free radicals. The hypothesis is that epinephrine addition in maturation media improves the developmental competence of oocytes in cattle and buffalo. The objectives of the experiments were to investigate the effect of epinephrine addition in maturation media on nuclear maturation, developmental competence, and oocyte mRNA abundance of genes related to antioxidants and growth pathways in cattle and buffalo. In experiment 1, cattle oocytes were matured for 24 h in maturation media supplemented with increasing concentrations of epinephrine 0, 0.01, 1.0, and 100 µM. Oocytes were cultured to assess cleavage at 48 h and blastocyst on day 7 of the culture. The cumulus-oocyte complexes (COCs) expansion, nuclear maturation, and oocyte mRNA abundance of genes (SOD1, GPX4, GDF9, CASP9) were evaluated. In experiment 2, buffalo oocytes were matured and assessed for development and mRNA abundance as described for cattle. In addition, the blastomere number was counted in the hatched blastocyst. The data were analyzed using GLIMMIX and MIXED procedures of SAS. Results revealed that the supplementation of epinephrine increased (P ≤ 0.03) the COCs expansion, nuclear maturation, and developmental competence of oocytes in cattle. Interestingly, all the responses were maximized (quadratic effect; P ≤ 0.08) at 1 µM concentrations. The mRNA abundance of genes in cattle oocytes was not affected by the treatment. The experiment in buffalo revealed that epinephrine increased blastocyst formation without affecting COCs expansion, and nuclear maturation. The higher blastocyst was achieved at 0.01 µM concentrations of epinephrine. Interestingly, the addition of epinephrine increased the mRNA abundance of genes related to antioxidant pathways (SOD1, GPX4). Moreover, supplementation of epinephrine increased the blastomere count of the hatched blastocyst in buffalo. In conclusion, epinephrine addition in maturation media benefited oocyte development in cattle and blastocyst yield in buffalo at 1 and 0.01 µM concentrations, respectively. It appears that the addition of epinephrine affected different cellular pathways, COCs expansion, and nuclear maturation in cattle and increased antioxidant genes for buffalo.

Uncovering the causes and socio-demographic constructs of stillbirths and neonatal deaths in an urban slum of Karachi.

INTRODUCTION: Neonatal deaths and stillbirths are significant public health concerns in Pakistan, with an estimated stillbirth rate of 43 per 1,000 births and a neonatal mortality rate of 46 deaths per 1,000 live births. Limited access to obstetric care, poor health seeking behaviors and lack of quality healthcare are the leading root causes for stillbirths and neonatal deaths. Rehri Goth, a coastal slum in Karachi, faces even greater challenges due to extreme poverty, and inadequate infrastructure. This study aims to investigate the causes and pathways leading to stillbirths and neonatal deaths in Rehri Goth to develop effective maternal and child health interventions. METHODS: A mixed-method cohort study was nested with the implementation of large maternal, neonatal and child health program, captured all stillbirths and neonatal death during the period of May 2014 till June 2018. The Verbal and Social Autopsy (VASA) tool (WHO 2016) was used to collect primary data from all death events to determine the causes as well as the pathways. Interviews were conducted both retrospectively and prospectively with mothers and caregivers. Two trained physicians reviewed the VASA form and the medical records (if available) and coded the cause of death blinded to each other. Descriptive analysis was used to categorize stillbirth and neonatal mortality data into high- and low-mortality clusters, followed by chi-square tests to explore associations between categories, and concluded with a qualitative analysis. RESULTS: Out of 421 events captured, complete VASA interviews were conducted for 317 cases. The leading causes of antepartum stillbirths were pregnancy-induced hypertension (22.4%) and maternal infections (13.4%), while obstructed labor was the primary cause of intrapartum stillbirths (38.3%). Neonatal deaths were primarily caused by perinatal asphyxia (36.1%) and preterm birth complications (27.8%). The qualitative analysis on a subset of 40 death events showed that health system (62.5%) and community factors (37.5%) contributing to adverse outcomes, such as delayed referrals, poor triage systems, suboptimal quality of care, and delayed care-seeking behaviors. CONCLUSION: The study provides an opportunity to understand the causes of stillbirths and neonatal deaths in one of the impoverished slums of Karachi. The data segregation by clusters as well as triangulation with qualitative analysis highlight the needs of evidence-based strategies for maternal and child health interventions in disadvantaged communities.

Impact of Ebola and COVID-19 on maternal, neonatal, and child health care among populations affected by conflicts: a scoping review exploring demand and supply-side barriers and solutions.

INTRODUCTION: Armed conflicts have a severe impact on the health of women and children. Global health emergencies such as pandemics and disease outbreaks further exacerbate the challenges faced by vulnerable populations in accessing maternal, neonatal, and child healthcare (MNCH). There is a lack of evidence that summarizes the challenges faced by conflict-affected pregnant women, mothers, and children in accessing MNCH services during global health emergencies, mainly the Ebola and COVID-19 pandemics. This scoping review aimed to analyze studies evaluating and addressing barriers to accessing comprehensive MNCH services during Ebola and COVID-19 emergencies in populations affected by conflict. METHODS: The search was conducted on PubMed, Scopus, and Web of Science databases using terms related to Ebola and COVID-19, conflicts, and MNCH. Original studies published between 1990 and 2022 were retrieved. Articles addressing the challenges in accessing MNCH-related services during pandemics in conflict-affected settings were included. Thematic analysis was performed to categorize the findings and identify barriers and solutions. RESULTS: Twenty-nine studies met the inclusion criteria. Challenges were identified in various MNCH domains, including antenatal care, intrapartum care, postnatal care, vaccination, family planning, and the management of childhood illnesses. Ebola-related supply-side challenges mainly concerned accessibility issues, health workforce constraints, and the adoption of stringent protocols. COVID-19 has resulted in barriers related to access to care, challenges pertaining to the health workforce, and new service adoption. On the demand-side, Ebola- and COVID-19-related risks and apprehensions were the leading barriers in accessing MNCH care. Community constraints on utilizing services during Ebola were caused by a lack of trust and awareness. Demand-side challenges of COVID-19 included fear of disease, language barriers, and communication difficulties. Strategies such as partnerships, strengthening of health systems, service innovation, and community-based initiatives have been employed to overcome these barriers. CONCLUSION: Global health emergencies amplify the barriers to accessing MNCH services faced by conflict-affected populations. Cultural, linguistic, and supply-side factors are key challenges affecting various MNCH domains. Community-sensitive initiatives enhancing primary health care (PHC), mobile clinics, or outreach programs, and the integration of MNCH into PHC delivery should be implemented. Efforts should prioritize the well-being and empowerment of vulnerable populations. Addressing these barriers is crucial for achieving universal health coverage and the Sustainable Development Goals.

Structural Changes in the Brain on Magnetic Resonance Imaging in Malnourished Children: A Scoping Review of the Literature.

BACKGROUND: This review was conducted to summarize the current evidence on the structural findings seen in brain magnetic resonance imaging (MRI) in malnourished children and the effect of optimized nutritional supplementation on brain development as studied through MRI. METHODS: A systematic search was carried out in PubMed, Embase, The Cochrane Library, Web of Science (Clarivate Analytics), WHO ICTRP Clinical Trials in Children, and ClinicalTrials.gov using a predefined search criterion for relevant literature from inception to January 2022. The primary outcome of the study was structural changes observed in the brain on MRI. RESULTS: The most common abnormal findings on MRI in malnourished infants were cerebral atrophy and dilated ventricles. Furthermore, a higher proportion of breast milk, calorie, and lipid intake in the diet was significantly associated with increased brain volumes; this also increased the likelihood of normal MRI scores at term. When followed till adolescence, it was observed that these infants had increased neonatal weight gain and a higher intelligence quotient when compared with the group. CONCLUSIONS: In conclusion, most children with moderate/severe malnutrition had abnormal MRI findings, mostly cerebral atrophy with or without ventricular dilatation. Since none of the studies measured the degree of atrophy or ventricular dilatation, it was not possible to assess the effect of the severity of malnutrition on brain atrophy. A universal measurement or scoring system for assessing the degree of brain atrophy is needed to help correlate the severity of malnutrition with the degree of brain atrophy and monitor the effects of nutritional rehabilitation over time.

Client-centered counseling and facilitation in improving modern contraceptive uptake in urban slum of Karachi Pakistan.

BACKGROUND: Population growth in Pakistan necessitates the implementation of comprehensive family planning (FP) initiatives. The adoption of modern contraceptives, especially long-acting reversible contraceptives (LARC), and permanent family planning methods in the country is challenging and has yet to reach an optimal level. These challenges are deeply rooted in the lack of informed decision-making, as well as demographic and maternal obstetric history. Interventions tailored according to women's needs can address the challenges faced by FP programs. This paper presents the findings of the implementation of a client-centered counseling and facilitation approach in an urban slum in Karachi, Pakistan. Such an approach has the potential to inform women and help them make better decisions regarding their health. METHODS: In Rehri Goth, a slum located in Karachi, client-centered counseling along with facilitation at the facility was implemented to encourage the adoption of any modern contraceptive methods, with a specific emphasis on promoting the use of LARCs and permanent methods (where needed) among married women of reproductive age (MWRA). This approach was integrated into the existing Maternal, Neonatal, and Child Health (MNCH) services established in 2014. During the routine delivery of services, data were collected on various aspects including demographic characteristics, obstetric history, motivation to adopt LARCs, and reasons for refusal. RESULTS: A total of N = 3079 eligible MWRA received client-centered counseling, and 60.3% accepted modern contraceptive methods after counseling. Furthermore, 32.5% of these MWRA adopted LARCs or permanent methods. Factors explaining reluctance to adopt any method by MWRA despite specialized counselling were: age >25 years (AOR:1.28, 95% CI:1.08-1.51), no formal education (AOR:1.58, 95% CI:1.36-1.89), having no decision making role at household (AOR:1.60, 95% CI:1.36-1.89), the desire of female or male progeny (AOR:1.86, 95% CI:1.59-2.25) and age of youngest alive ≥3 years (AOR:1.50, 95% CI:1.22-1.84). Factors explaining adoption of short-term methods instead of LARCs or permanent method were: being resident in high under-five mortality clusters (AOR:1.56, 95% CI:1.14-2.14), maternal age > 25 years (AOR:1.88, 95% CI: 1.47-2.40), no decision-making role (AOR:11.19, 95% CI:8.74-14.34), no history of abortions (AOR:2.59, 95% CI:1.79-3.75), no female child (AOR:1.85, 95% CI:1.30-2.65) and ≤ 2 children (AOR:1.74, 95% CI:1.08-2.81). CONCLUSION: Considering the obstacles mothers face when it comes to accessing extended contraception, public health officials can devise effective strategies that empower MWRA to make well-informed and empowered choices regarding their families and reproductive health.

Barriers to childhood vaccination in urban slums of Pakistan.

Background: The urban slums of Pakistan continue to record low childhood vaccination coverage. It is therefore vital to understand the demand-side barriers to childhood vaccination in the slums to determine the required demand-generation interventions. Aims: To document the demand-side barriers related to childhood vaccination in urban slums of Pakistan and recommend appropriate demand-generation interventions. Methods: We investigated the demand-side barriers to childhood vaccination in 4 urban slums of Karachi, Pakistan, and disseminated the findings to the Expanded Program on Immunization and their partners. Using the findings, we made recommendations for collaborations with the various partners and for the design of demand-generation interventions to address the barriers. We then expanded the scope of the original research through a mapping exercise that gathered information on the vaccination-related research and interventions of the partners and used the information gathered to create a portfolio of activities. We present the demand-side barriers from the original research and the portfolio of demand-generation interventions. Results: The original research showed that 412 (49.0%) children aged 12-23 months, from 840 households, were fully vaccinated. Reasons given for not receiving the recommended vaccinations were mainly related to the fear of side effects, social and religious influences, lack of awareness, and misconceptions about vaccine administration. The mapping of activities revealed 47 initiatives that aimed to generate demand for childhood vaccination in the urban slums of Pakistan. Conclusion: Several stakeholders involved in childhood vaccination in the urban slums of Pakistan act independently, operating programmes that are disconnected. There is a need for better coordination and integration of the childhood vaccination interventions by these partners to achieve the goal of universal vaccination coverage.

Hurler Syndrome (Mucopolysaccharidosis Type 1): A Case Report.

Hurler syndrome is a rare autosomal recessive disorder of deficiency in the metabolism of glycosaminoglycans (GAGs), including heparan sulfate and dermatan sulfate, which consequently accumulate in the different organs of the body, resulting from deficiency of an enzyme named Alpha-L-iduronidase. Here, we present an interesting case of a young female patient who presented with a combination of skeletal, oro-facial, ophthalmologic, neurological, and radiological findings of this disease. A diagnosis of Hurler syndrome (Mucopolysaccharidosis Type I) was made late in the disease due to lack of facilities, and the patient was ultimately managed supportively.

Harmonization of maternal balanced energy-protein supplementation studies for individual participant data (IPD) meta-analyses - finding and creating similarities in variables and data collection.

BACKGROUND: Public health and clinical recommendations are established from systematic reviews and retrospective meta-analyses combining effect sizes, traditionally, from aggregate data and more recently, using individual participant data (IPD) of published studies. However, trials often have outcomes and other meta-data that are not defined and collected in a standardized way, making meta-analysis problematic. IPD meta-analysis can only partially fix the limitations of traditional, retrospective, aggregate meta-analysis; prospective meta-analysis further reduces the problems. METHODS: We developed an initiative including seven clinical intervention studies of balanced energy-protein (BEP) supplementation during pregnancy and/or lactation that are being conducted (or recently concluded) in Burkina Faso, Ethiopia, India, Nepal, and Pakistan to test the effect of BEP on infant and maternal outcomes. These studies were commissioned after an expert consultation that designed recommendations for a BEP product for use among pregnant and lactating women in low- and middle-income countries. The initiative goal is to harmonize variables across studies to facilitate IPD meta-analyses on closely aligned data, commonly called prospective meta-analysis. Our objective here is to describe the process of harmonizing variable definitions and prioritizing research questions. A two-day workshop of investigators, content experts, and advisors was held in February 2020 and harmonization activities continued thereafter. Efforts included a range of activities from examining protocols and data collection plans to discussing best practices within field constraints. Prior to harmonization, there were many similar outcomes and variables across studies, such as newborn anthropometry, gestational age, and stillbirth, however, definitions and protocols differed. As well, some measurements were being conducted in several but not all studies, such as food insecurity. Through the harmonization process, we came to consensus on important shared variables, particularly outcomes, added new measurements, and improved protocols across studies. DISCUSSION: We have fostered extensive communication between investigators from different studies, and importantly, created a large set of harmonized variable definitions within a prospective meta-analysis framework. We expect this initiative will improve reporting within each study in addition to providing opportunities for a series of IPD meta-analyses.

Gutka consumption and dietary partialities explaining anemia in women of a coastal slum of Karachi, Pakistan: A mixed-method study.

BACKGROUND: Limited literature is available on the dietary pattern and its consequences on health of women living in coastal slums of Karachi, Pakistan. MATERIAL AND METHODS: The study employed a mixed-method approach where concurrent quantitative and qualitative assessments were carried out. An analytical cross-sectional survey was conducted to collect information on demographic, household, obstetrics characteristics, and dietary pattern of married women of reproductive age (MWRA). Blood samples were collected to identify the hemoglobin level to determine anemia. For the qualitative component, focus group discussions were carried out with women and in-depth interviews with shopkeepers to understand the availability of food items at household level and in local markets respectively. In addition, observational visits were carried out at different points in time to the local market to document the availability of iron-rich foods for the community. RESULTS: The overall prevalence of anemia in sample population was 68.0%. Women with no formal education (AOR: 2.93 95% CI: 1.90-4.52), who consumed gutka (AOR: 2.84 95% CI: 1.81-4.46), did not eat red meat (AOR: 1.68 95% CI: 1.06-2.65), and only had seafood (AOR: 4.56 95% CI: 1.38-15.02) were more likely to be anemic as compared to their counterparts. Qualitative data revealed that any kind of meat and fruits were beyond the reach of community people due to non-affordable cost. A high percentage of women used a locally produced recreational substance known as gutka which gives them a feeling of wellbeing and suppresses hunger. CONCLUSION: In our study population, lack of access to diversity of food items, illiteracy, and use of gutka are the statistically significant factors which are associated with anemia in married women of this coastal slum area. The lack of demand for diversity in food is related to poverty and preference of spending money on gutka.

Safety of glucose-6 phosphate dehydrogenase deficient donors in living right lobe liver donation.

BACKGROUND: The literature lacks data on World Health Organization (WHO) class II and III deficient liver donors who underwent right hepatectomy during living donor liver transplantation (LDLT). METHODS: In this prospective cohort study, we compared the perioperative outcomes of 15 glucose-6 phosphate dehydrogenase (G6PD) deficient living liver donors with a matched cohort of 39 nondeficient living liver donors undergoing right lobe donation. RESULTS: Out of 15 G6PD deficient donors, four (26.67%) donors had class II, and 11 (73.34%) had class III G6PD deficiency. The mean postoperative trough hemoglobin level was significantly lower in the deficient group than the nondeficient group (9.38 ± 1.59 g/dL vs. 10.27 ± .91 g/dL, p = .046). The mean peak indirect bilirubin level was significantly higher in the deficient group than the nondeficient group (2.22 ± 1.38 mg/dL vs. 1.40 ± .89 mg/dL, p = .047), and a similar trend was observed in total serum bilirubin (3.99 ± 2.57 mg/dL vs. 2.99 ± 1.46 mg/dL, p = .038). Biochemical evidence of hemolysis was found only in three (20%) deficient donors, but none of them needed a blood transfusion. No mortality was observed in either group. All other parameters, including demographics, operative parameters, graft characteristics, and hospital stay were comparable between both groups (p > .05). CONCLUSION: G6PD deficiency with WHO class II and above should not be considered a contraindication for right lobe donation.

Nutritional support and prophylaxis of azithromycin for pregnant women to improve birth outcomes in peri-urban slums of Karachi, Pakistan-a protocol of multi-arm assessor-blinded randomized controlled trial (Mumta PW trial).

BACKGROUND: Maternal undernutrition is critical in the etiology of poor perinatal outcomes and accounts for 20% of small-for-gestational-age (SGA) births. High levels of food insecurity, antenatal undernourishment, and childhood undernutrition necessitate the supplementation of fortified balanced energy protein (BEP) during pregnancy in low-income settings especially with scarce literature available in this subject. Hence, this paper extensively covers the protocol of such a trial conducted in an urban slum of Karachi, Pakistan. METHODS: The trial is community-based, open-labelled, four-arm, and randomized controlled that will include parallel group assignments with a 1:1:1:1 allocation ratio in low-income squatter settlements in urban Karachi, Pakistan. All pregnant women (PW), if identified between > 8 and < 19 weeks of gestation based on ultrasound, will be offered routine antenatal care (ANC) counseling and voluntary participation in the trial after written informed consent. A total number of 1836 PW will be enrolled with informed consent and randomly allocated to one of the four arms receiving: (1) ANC counseling only (control group), (2) ANC counseling plus BEP supplement (intervention arm 1), (3) ANC counseling plus BEP supplement plus 2 doses azithromycin (intervention arm 2), or (4) ANC counseling plus BEP supplement plus daily single dose of nicotinamide and choline (intervention arm 3). TRIAL REGISTRATION: ClinicalTrials.gov NCT04012177 . Registered on July 9, 2019.

The Politics of Covid-19 Vaccine Distribution and Recognition.

With COVAX touted as the only platform that is built on equity and fairness, there is growing discontent and concern that the platform is falling short of its goals as COVID ravages across multiple countries. There are two serious issues that we address here. Firstly, COVID distribution principles and mechanisms need to be rethought in terms of a shift from private to global interests with a focus on prioritizing deliveries. Secondly, with multiple vaccines present, it is vital that countries recognize all of them, once proven safe and effective, to prevent any form of vaccine apartheid and discrimination.

Challenges of continuation of live liver donor programme during COVID-19 pandemic in Pakistan: outcomes and lessons learned.

BACKGROUND: COVID-19 pandemic has globally affected healthcare including the transplantation programmes. MATERIALS AND METHODS: We retrospectively studied the impact of COVID-19 on live liver donor (LLD) programme at liver transplant centre in Gambat, Pakistan. Standard operative procedures (SOPs) including COVID-19 nasopharyngeal swab PCR, CT scans, personal protective equipment use, 6-feet distancing were developed for LLD and transplant team to mitigate COVID-19 exposure. We compared the complications, healthcare utilisation (hospital stay, readmission) and mortality between two LLD cohorts-before and during COVID-19 pandemic from March 2019 to December 2020. RESULTS: During study period 300 LLD surgeries were performed. There was an increase in rate of LLDs from 132 (44%) in pre-COVID to 168 (56%) during COVID-19 era. Average numbers of transplants per month performed during pre-COVID and during COVID-19 era were 10.1 and 14, respectively. No donor has developed COVID-19 infection during hospitalisation. Rate of all LLD complications (32 (21.47%) and 49 (29.16%), p=0.43), uneventful discharges (120/168 (71.4%) and 88/132 (66.6%), p<0.05), mean hospital stay (6±2 days and 5±2 days, p=0.17) and readmission (5 (4%) and 3 (1.8%), p=0.43) were similar during the pre-COVID and COVID-19 era. No donor mortality was observed during study period. CONCLUSION: With the implementation of mindful SOPs, rate of LLD increased without any case of COVID-19 infection. Our SOPs were helpful in continuation of LLD programme in a developing country during COVID-19 pandemic.

Prophylactic potential of honey and Nigella sativa L. against hospital and community-based SARS-CoV-2 spread: a structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: Considering the therapeutic potential of honey and Nigella sativa (HNS) in coronavirus disease 2019 (COVID-19) patients, the objective of the study is defined to evaluate the prophylactic role of HNS. TRIAL DESIGN: The study is a randomized, placebo-controlled, adaptive clinical trial with parallel group design, superiority framework with an allocation ratio of 1:1 among experimental (HNS) and placebo group. An interim analysis will be done when half of the patients have been recruited to evaluate the need to adapt sample size, efficacy, and futility of the trial. PARTICIPANTS: All asymptomatic patients with hospital or community based COVID-19 exposure will be screened if they have had 4 days exposure to a confirmed case. Non-pregnant adults with significant exposure level will be enrolled in the study High-risk exposure (<6 feet distance for >10min without face protection) Moderate exposure (<6 feet distance for >10min with face protection) Subjects with acute or chronic infection, COVID-19 vaccinated, and allergy to HNS will be excluded from the study. Recruitment will be done at Shaikh Zayed Post-Graduate Medical Institute, Ali Clinic and Doctors Lounge in Lahore (Pakistan). INTERVENTION AND COMPARATOR: In this clinical study, patients will receive either raw natural honey (0.5 g) and encapsulated organic Nigella sativa seeds (40 mg) per kg body weight per day or empty capsule with and 30 ml of 5% dextrose water as a placebo for 14 days. Both the natural products will be certified for standardization by Government College University (Botany department). Furthermore, each patient will be given standard care therapy according to version 3.0 of the COVID-19 clinical management guidelines by the Ministry of National Health Services of Pakistan. MAIN OUTCOMES: Primary outcome will be Incidence of COVID-19 cases within 14 days of randomisation. Secondary endpoints include incidence of COVID-19-related symptoms, hospitalizations, and deaths along with the severity of COVID-19-related symptoms till 14th day of randomization. RANDOMISATION: Participants will be randomized into experimental and control groups (1:1 allocation ratio) via the lottery method. There will be stratification based on high risk and moderate risk exposure. BLINDING (MASKING): Quadruple blinding will be ensured for the participants, care providers and outcome accessors. Data analysts will also be blinded to avoid conflict of interest. Site principal investigator will be responsible for ensuring masking. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): 1000 participants will be enrolled in the study with 1:1 allocation. TRIAL STATUS: The final protocol version 1.4 was approved by institutional review board of Shaikh Zayed Post-Graduate Medical Complex on February 15, 2021. The trial recruitment was started on March 05, 2021, with a trial completion date of February 15, 2022. TRIAL REGISTRATION: Clinical trial was registered on February 23, 2021, www.clinicaltrials.gov with registration ID NCT04767087 . FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). With the intention of expediting dissemination of this trial, the conventional formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines.