Hyperimmune anti-COVID-19 Intravenous Immunoglobulin (C-IVIG) is an unexplored therapy amidst the rapidly evolving spectrum of medical therapies for COVID-19 and is expected to counter the three most life-threatening consequences of COVID-19 including lung injury by the virus, cytokine storm and sepsis. A single center, phase I/II, randomized controlled, single-blinded trial was conducted at Dow University of Health Sciences, Karachi, Pakistan. Participants were COVID-19 infected individuals, classified as either severely or critically ill with Acute Respiratory Distress Syndrome (ARDS). Participants were randomized through parallel-group design with sequential assignment in a 4:1 allocation to either intervention group with four C-IVIG dosage arms (0.15, 0.20, 0.25, 0.30 g/kg), or control group receiving standard of care only (n = 10). Primary outcomes were 28-day mortality, patient's clinical status on ordinal scale and Horowitz index (HI), and were analysed in all randomized participants that completed the follow-up period (intention-to-treat population). The trial was registered at clinicaltrials.gov (NCT04521309). Fifty participants were enrolled in the study from June 19, 2020 to February 3, 2021 with a mean age of 56.54±13.2 years of which 22 patients (44%) had severe and 28 patients (56%) had critical COVID-19. Mortality occurred in ten of 40 participants (25%) in intervention group compared to six of ten (60%) in control group, with relative risk reduction in intervention arm I (RR, 0.333; 95% CI, 0.087–1.272), arm II (RR, 0.5; 95% CI, 0.171–1.463), arm III (RR, 0.167; 95% CI, 0.024–1.145), and arm IV (RR, 0.667; 95% CI, 0.268–1.660). In intervention group, median HI significantly improved to 359 mmHg [interquartile range (IQR) 127–400, P = 0.009)] by outcome day, while the clinical status of intervention group also improved as compared to control group, with around 15 patients (37.5%) being discharged by 7th day with complete recovery. Additionally, resolution of chest X-rays and restoration of biomarkers to normal levels were also seen in intervention groups. No drug-related adverse events were reported during the study. Administration of C-IVIG in severe and critical COVID-19 patients was safe, increased the chance of survival and reduced the risk of disease progression. Higher Education Commission (HEC), Pakistan (Ref no. 20-RRG-134/RGM/R&D/HEC/2020).

Background: This study assesses the feasibility of producing hyperimmune anti-COVID-19 intravenously administrable immunoglobulin (C-IVIG) from pooled convalescent plasma (PCP) to provide a safe an...

Objectives: The aim of this trial is to investigate the safety and clinical efficacy of passive immunization therapy through Hyperimmune anti-COVID-19 Intravenous Immunoglobulin (C-IVIG: 5% liquid formulation), on severe and critically ill patients with COVID-19. Trial design: This is a phase I/II single centre, randomised controlled, single-blinded, superiority trial, through parallel-group design with sequential assignment. Participants will be randomised either to receive both C-IVIG and standard care or only standard care (4:1). Participants: The study is mono-centric with the participants including COVID19 infected individuals (positive SARS-CoV-2 PCR on nasopharyngeal and/or oropharyngeal swabs) admitted in institute affiliated with Dow University Hospital, Dow University of Health Sciences, Karachi, Pakistan. Consenting patients above 18 years that are classified by the treating physician as severely ill i.e. showing symptoms of COVID-19 pneumonia; dyspnea, respiratory rate ≥30/min, blood oxygen saturation ≤93%, PaO₂/FiO₂ 50% on CXR; or critically ill i.e. respiratory failure, septic shock, and multiple organ dysfunction or failure. Patients with reported IgA deficiency, autoimmune disorder, thromboembolic disorder, and allergic reaction to immunoglobulin treatment were excluded from study. Similarly, pregnant females, patients requiring two or more inotropic agents to maintain blood pressure and patients with acute or chronic kidney injury/failure, were also excluded from the study. Intervention and comparator: The study consists of four interventions and one comparator arm. All participants receive standard hospital care which includes airway support, anti-viral medication, antibiotics, fluid resuscitation, hemodynamic support, steroids, painkillers, and anti-pyretics. Randomised test patients will receive single dose of C-IVIG in following four dosage groups: Group 1: 0.15g/Kg with standard hospital care Group 2: 0.2g/Kg with standard hospital care Group 3: 0.25g/Kg with standard hospital care Group 4: 0.3g/Kg with standard hospital care Group 5 (comparator) will receive standard hospital care only Main outcomes: The primary outcomes are assessment and follow-up of participants to observe 28-day mortality and, • the level and duration of assisted ventilation during hospital stay, • number of days to step down (shifting from ICU to isolation ward), • number of days to hospital discharge, • adverse events (Kidney failure, hypersensitivity with cutaneous or hemodynamic manifestations, aseptic meningitis, hemolytic anemia, leuko-neutropenia, transfusion related acute lung injury (TRALI)) during hospital stay, • change in C-Reactive Protein (CRP) levels, • change in neutrophil lymphocyte ratio to monitor inflammation. Randomisation: Consenting participants who fulfill the criteria are allocated to either intervention or comparator arm with a ratio of 4:1, using sequentially numbered opaque sealed envelope simple randomization method. The participant allocated for intervention will be sequentially assigned dosage group 1-4 in ascending order. Participants will not be recruited in the next dosage group before a set number of participants in one group (10) are achieved. Blinding (masking): Single blinded study, with participants blinded to allocation. Numbers to be randomised (sample size): Total 50 patients are randomised. The intervention arms consist of 40 participants divided in four groups of 10 participants while the comparator group consists of 10 patients. Trial Status: Current version of the protocol is “Version 2” dated 29^th September, 2020. Participants are being recruited. Recruitment started on June, 2020 and is estimated to primarily end on January, 2021. Trial registration: This trial was registered at ClinicalTrials.gov, NCT04521309 on 20 August 2020 and is retrospectively registered. Full protocol: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1).

Background: COVID-19 poses a global health challenge with more than 325 million cumulative cases and above 5 million cumulative deaths reported till January 17, 2022, by the World Health Organization. Several potential treatments to treat COVID-19 are under clinical trials including antivirals, steroids, immunomodulators, non-specific IVIG, monoclonal antibodies, and passive immunization through convalescent plasma. The need to produce anti-COVID-19 IVIG therapy must be continued, alongside the current treatment modalities, considering the virus is still mutating into variants of concern. In this context, as the present study will exploit pooled diversified convalescent plasma collected from recovered COVID-19 patients, the proposed hyperimmune Anti-COVID-19 intravenous immunoglobulin (C-IVIG) therapy would be able to counter new infectious COVID-19 variants by neutralizing the virus particles. After the successful outcome of the phase I/II clinical trial of C-IVIG, the current study aims to further evaluate the safety and efficacy of single low dose C-IVIG in severe COVID-19 patients for its phase II/III clinical trial. Methods: This is a phase II/III, adaptive, multi-center, single-blinded, randomized controlled superiority trial of SARS-CoV-2 specific polyclonal IVIG (C-IVIG). Patients fulfilling the eligibility criteria will be block-randomized using a sealed envelope system to receive either 0.15 g/Kg C-IVIG with standard of care (SOC) or standard of care alone in 2:1 ratio. The patients will be followed-up for 28 days to assess the primary and secondary outcomes. Discussion: This is a phase II/III clinical trial evaluating safety and efficacy of hyperimmune anti-COVID-19 intravenous immunoglobulin (C-IVIG) in severe COVID-19 patients. This study will provide clinical evidence to use C-IVIG as one of the first-line therapeutic options for severe COVID-19 patients. Trial registration: Registered at clinicaltrial.gov with NCT number NCT04891172 on May 18, 2021.

Data on clinical utility of IGRAs in BCG-vaccinated populations is limited. This cross-sectional study evaluated diagnostic performance of ELISPOT and ELISA-based IGRAs and compared them with conventional Tuberculin Skin Test (TST) for detecting Mtb infection in adult Pakistani population. Subjects (n = 325, age 18–64 years) recruited included active TB cases (n = 150), non-TB other pulmonary diseases patients (n = 50) and healthy individuals (n = 125). Two different IGRAs, X-DOT-TB (ELISPOT-based) and QFT-Plus (ELISA-based) were used to screen Mtb infection. Samples from 112/150 (74.7%) active TB patients, 10/50 (20.0%) non-TB other pulmonary diseases cases and 16/125 (12.8%) healthy individuals were X-DOT-TB positive, while 52.7% (29/55) active TB patients, 20.0% (4/20) non-TB other pulmonary diseases cases and 22.6% (12/53) healthy individuals tested by QFT-Plus had positive results. Sensitivity of X-DOT-TB and QFT-Plus was 79.5% (95%CI 77.4–81.5), and 55.7% (95%CI 52.9–58.5), respectively, significantly higher than TST 35.8% (95%CI 34.4–37.1, p < 0.05). Specificity of X-DOT-TB was 85.1% (95%CI 83.2–87.0), that of QFT-Plus was 78.1% (95%CI 75.3–80.9), comparable with TST specificity of 82.2% (95%CI 80.3-84.1, p > 0.05). IGRAs, particularly X-DOT-TB assay found to have greater sensitivity for detecting Mtb infection than TST. Our study suggests that IGRAs can be used as an adjunct diagnostic tool for detection of Mtb infection in BCG-vaccinated populations.

This study examines the language used in advertorials of Covid 19 from an ecolinguistic perspective. Through the ecolinguistic study of advertorials on Covid 19, the elements of fear and xenophobia are dredged up. Regarding Covid 19, little research has been carried out on advertorials. This study applies Halliday's (1970) metafunctions of language proposed in Systemic Functional Linguistics (SFL) on Covid advertorials from the perspective of ecolinguistics. Fifty Covid 19 related advertorials from ten different Pakistani websites were selected. Five advertorials from each website were chosen. Ecolinguistic analysis of Halliday's three metafunctions was adopted as the analytical framework. The findings of the study indicated that the Covid 19 advertorials are exploited to accentuate and propagate xenophobia and fear in the ecosystem through different lexical choices. The findings of this study provide a guideline of didactic inferences for future researchers in the field.