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1.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-307540

ABSTRACT

Background: Several repurposed drugs such as hydroxychloroquine (HCQ) have been investigated for treatment of COVID-19, but none was confirmed to be efficacious. While in vitro studies have demonstrated antiviral properties of HCQ, data from clinical trials were conflicting regarding its benefit for COVID-19 treatment. Drugs that limit viral replication may be beneficial in the earlier course of the disease thus slowing progression to severe and critical illness. Design: We conducted a randomized open label Phase II clinical trial from October -December 2020. Methods: Patients diagnosed with COVID-19 using RT-PCR were included in the study if they were 18 years and above and had a diagnosis of COVID-19 made in the last 3 days. Patients were randomized in blocks, to receive either HCQ 400mg twice a day for the first day followed by 200mg twice daily for the next 4 days plus standard of care (SOC) treatment or SOC treatment alone. SARS COV-2 viral load using nasal/orapharyngeal swabs was performed at baseline, day 2, 4, 6, 8 and 10. The primary outcome was median time from randomization to SARS COV-2 viral clearance by day 6. Results: Of the 105 participants enrolled, 55 were assigned to the intervention group (HCQ plus SOC) and 50 to the control group (SOC only). Baseline characteristics were similar across treatment arms. Viral clearance did not differ by treatment arm, 20 and 19 participants respectively had SARS COV-2 viral load clearance by day 6 with no significant difference, median (IQR) number of days to viral load clearance between the two groups was 4(3-4) vs 4(2-4): p=0.457. There were no significant differences in secondary outcomes (symptom resolution and adverse events) between the intervention group and the control group. There were no significant differences in specific adverse events such as elevated alkaline phosphatase, prolonged QTc interval on ECG, among patients in the intervention group as compared to the control group. Conclusion: Our results show that HCQ 400mg twice a day for the first day followed by 200mg twice daily for the next 4 days was safe but not associated with reduction in viral clearance or symptom resolution. Trial registration: NCT04860284

2.
BMC Infect Dis ; 21(1): 1218, 2021 Dec 06.
Article in English | MEDLINE | ID: covidwho-1555215

ABSTRACT

BACKGROUND: Several repurposed drugs such as hydroxychloroquine (HCQ) have been investigated for treatment of COVID-19, but none was confirmed to be efficacious. While in vitro studies have demonstrated antiviral properties of HCQ, data from clinical trials were conflicting regarding its benefit for COVID-19 treatment. Drugs that limit viral replication may be beneficial in the earlier course of the disease thus slowing progression to severe and critical illness. DESIGN: We conducted a randomized open label Phase II clinical trial from October-December 2020. METHODS: Patients diagnosed with COVID-19 using RT-PCR were included in the study if they were 18 years and above and had a diagnosis of COVID-19 made in the last 3 days. Patients were randomized in blocks, to receive either HCQ 400 mg twice a day for the first day followed by 200 mg twice daily for the next 4 days plus standard of care (SOC) treatment or SOC treatment alone. SARS COV-2 viral load (CT values) from RT-PCR testing of samples collected using nasal/orapharyngeal swabs was performed at baseline, day 2, 4, 6, 8 and 10. The primary outcome was median time from randomization to SARS COV-2 viral clearance by day 6. RESULTS: Of the 105 participants enrolled, 55 were assigned to the intervention group (HCQ plus SOC) and 50 to the control group (SOC only). Baseline characteristics were similar across treatment arms. Viral clearance did not differ by treatment arm, 20 and 19 participants respectively had SARS COV-2 viral load clearance by day 6 with no significant difference, median (IQR) number of days to viral load clearance between the two groups was 4(3-4) vs 4(2-4): p = 0.457. There were no significant differences in secondary outcomes (symptom resolution and adverse events) between the intervention group and the control group. There were no significant differences in specific adverse events such as elevated alkaline phosphatase, prolonged QTc interval on ECG, among patients in the intervention group as compared to the control group. CONCLUSION: Our results show that HCQ 400 mg twice a day for the first day followed by 200 mg twice daily for the next 4 days was safe but not associated with reduction in viral clearance or symptom resolution among adults with COVID-19 in Uganda. TRIAL REGISTRATION:  NCT04860284.


Subject(s)
COVID-19 , Hydroxychloroquine , Adult , COVID-19/drug therapy , Humans , Hydroxychloroquine/adverse effects , SARS-CoV-2 , Treatment Outcome , Uganda
3.
Trials ; 22(1): 831, 2021 Nov 23.
Article in English | MEDLINE | ID: covidwho-1529943

ABSTRACT

BACKGROUND: Remdesivir is a novel broad-spectrum antiviral therapeutic with activity against several viruses that cause emerging infectious diseases. The purpose of this study is to explore how commonly utilized antiretroviral therapy (tenofovir disoproxil fumarate/lamivudine [TDF/3TC] and atazanavir/ritonavir [ATV/r]) influence plasma and intracellular concentrations of remdesivir. METHODS: This is an open-label, randomized, fixed sequence single intravenous dosing study to assess pharmacokinetic interactions between remdesivir and TDF/3TC (Study A, crossover design) or TDF/3TC plus ATV/r (Study B). Healthy volunteers satisfying study entry criteria will be enrolled in the study and randomized to either Study A; N=16 (Sequence 1 or Sequence 2) or Study B; N=8. Participants will receive standard adult doses of antiretroviral therapy for 7 days and a single 200mg remdesivir infusion administered over 60 min. Pharmacokinetic blood sampling will be performed relative to the start of remdesivir infusion; predose (before the start of remdesivir infusion) and 30 min after the start of remdesivir infusion. Additional blood samples will be taken at 2, 4, 6, 12, and 24 h after the end of remdesivir infusion. DISCUSSION: This study will characterize the pharmacokinetics of remdesivir from a typical African population in whom clinical use is anticipated. Furthermore, this study will deliver pharmacokinetic datasets for remdesivir drug concentrations and demographic characteristics which could support pharmacometric approaches for simulation of remdesivir treatment regimens in patients concurrently using tenofovir/lamivudine and/or atazanavir/ritonavir. TRIAL REGISTRATION: ClinicalTrials.gov NCT04385719 . Registered 13 May 2020.


Subject(s)
Anti-HIV Agents , Lamivudine , Adenosine Monophosphate/analogs & derivatives , Adult , Alanine/analogs & derivatives , Atazanavir Sulfate , Healthy Volunteers , Humans , Oligopeptides , Pyridines , Ritonavir , Tenofovir , Uganda
4.
Open Forum Infect Dis ; 8(11): ofab530, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1528173

ABSTRACT

BACKGROUND: We evaluated clinical outcomes of patients hospitalized with coronavirus disease 2019 (COVID-19) in the second wave of the pandemic in a national COVID-19 treatment unit (CTU) in Uganda. METHODS: We conducted a retrospective cohort study of COVID-19 patients hospitalized at the Mulago National Referral Hospital CTU between May 1 and July 11, 2021. We performed Kaplan-Meier analysis to evaluate all-cause in-hospital mortality. RESULTS: Of the 477 participants, 247 (52%) were female, 15 (3%) had received at least 1 dose of the COVID-19 vaccine, and 223 (46%) had at least 1 comorbidity. The median age was 52 (interquartile range, 41-65) years. More than 80% of the patients presented with severe (19%, n=91) or critical (66%, n=315) COVID-19 illness. Overall, 174 (37%) patients died. Predictors of all-cause in-hospital mortality were as follows; age ≥50 years (adjusted odds ratio [aOR], 1.9; 95% confidence interval [CI], 1.2-3.2; P=.011), oxygen saturation at admission of ≥92% (aOR, 0.97; 95% CI, 0.91-0.95; P<.001), and admission pulse rate of ≥100 beats per minute (aOR, 1.01; 95% CI, 1.00-1.02; P=.042). The risk of death was 1.4-fold higher in female participants compared with their male counterparts (hazards ratio, 1.4; 95% CI, 1.0-2.0; P=.025). CONCLUSIONS: In this cohort, where the majority of the patients presented with severe or critical illness, more than one third of the patients hospitalized with COVID-19 at a national CTU died of the illness.

5.
BMJ Open Respir Res ; 8(1)2021 08.
Article in English | MEDLINE | ID: covidwho-1350030

ABSTRACT

RATIONALE: Convalescent plasma (CCP) has been studied as a potential therapy for COVID-19, but data on its efficacy in Africa are limited. OBJECTIVE: In this trial we set out to determine the efficacy of CCP for treatment of COVID-19 in Uganda. MEASUREMENTS: Patients with a positive SARS-CoV-2 reverse transcriptase (RT)-PCR test irrespective of disease severity were hospitalised and randomised to receive either COVID-19 CCP plus standard of care (SOC) or SOC alone. The primary outcome was time to viral clearance, defined as having two consecutive RT-PCR-negative tests by day 28. Secondary outcomes included time to symptom resolution, clinical status on the modified WHO Ordinal Clinical Scale (≥1-point increase), progression to severe/critical condition (defined as oxygen saturation <93% or needing oxygen), mortality and safety. MAIN RESULTS: A total of 136 patients were randomised, 69 to CCP+SOC and 67 to SOC only. The median age was 50 years (IQR: 38.5-62.0), 71.3% were male and the median duration of symptom was 7 days (IQR=4-8). Time to viral clearance was not different between the CCP+SOC and SOC arms (median of 6 days (IQR=4-11) vs 4 (IQR=4-6), p=0.196). There were no statistically significant differences in secondary outcomes in CCP+SOC versus SOC: time to symptom resolution (median=7 (IQR=5-7) vs 7 (IQR=5-10) days, p=0.450), disease progression (9 (22.0%) vs 7 (24.0%) patients, p=0.830) and mortality (10 (14.5%) vs 8 (11.9%) deaths, p=0.476). CONCLUSION: In this African trial, CCP therapy did not result in beneficial virological or clinical improvements. Further trials are needed to determine subgroups of patients who may benefit from CCP in Africa.Trial registration number NCT04542941.


Subject(s)
COVID-19/therapy , Pandemics , Adult , COVID-19/epidemiology , Female , Follow-Up Studies , Humans , Immunization, Passive , Male , Middle Aged , Retrospective Studies , SARS-CoV-2 , Treatment Outcome , Uganda/epidemiology
7.
PLoS One ; 16(6): e0252306, 2021.
Article in English | MEDLINE | ID: covidwho-1278173

ABSTRACT

INTRODUCTION: Evidence that supports the use of COVID-19 convalescent plasma (CCP) for treatment of COVID-19 is increasingly emerging. However, very few African countries have undertaken the collection and processing of CCP. The aim of this study was to assess the feasibility of collecting and processing of CCP, in preparation for a randomized clinical trial of CCP for treatment of COVID-19 in Uganda. METHODS: In a cross-sectional study, persons with documented evidence of recovery from COVID-19 in Uganda were contacted and screened for blood donation via telephone calls. Those found eligible were asked to come to the blood donation centre for further screening and consent. Whole blood collection was undertaken from which plasma was processed. Plasma was tested for transfusion transmissible infections (TTIs) and anti-SARS CoV-2 antibody titers. SARS-CoV-2 testing was also done on nasopharyngeal swabs from the donors. RESULTS: 192 participants were contacted of whom 179 (93.2%) were eligible to donate. Of the 179 eligible, 23 (12.8%) were not willing to donate and reasons given included: having no time 7(30.4%), fear of being retained at the COVID-19 treatment center 10 (43.5%), fear of stigma in the community 1 (4.3%), phobia for donating blood 1 (4.3%), religious issues 1 (4.4%), lack of interest 2 (8.7%) and transport challenges 1 (4.3%). The median age was 30 years and females accounted for 3.7% of the donors. A total of 30 (18.5%) donors tested positive for different TTIs. Antibody titer testing demonstrated titers of more than 1:320 for all the 72 samples tested. Age greater than 46 years and female gender were associated with higher titers though not statistically significant. CONCLUSION: CCP collection and processing is possible in Uganda. However, concerns about stigma and lack of time, interest or transport need to be addressed in order to maximize donations.


Subject(s)
Blood Specimen Collection/methods , COVID-19/therapy , SARS-CoV-2/isolation & purification , Adolescent , Adult , Aged , Antibodies, Viral/blood , Blood Donors , COVID-19/virology , Convalescence , Cross-Sectional Studies , Feasibility Studies , Female , Humans , Immunization, Passive/methods , Male , Middle Aged , SARS-CoV-2/immunology , SARS-CoV-2/physiology , Uganda , Young Adult
8.
Ther Adv Infect Dis ; 8: 20499361211024376, 2021.
Article in English | MEDLINE | ID: covidwho-1269865

ABSTRACT

BACKGROUND: Immunization is an important strategy for controlling the COVID-19 pandemic. COVID-19 vaccination was recently launched in Uganda, with prioritization to healthcare workers and high-risk individuals. In this study, we aimed to determine the acceptability of COVID-19 vaccine among persons at high risk of COVID-19 morbidity and mortality in Uganda. METHODS: Between 29 March and 14 April 2021, we conducted a cross-sectional survey consecutively recruiting persons at high risk of severe COVID-19 (diabetes mellitus, HIV and cardiovascular disease) attending Kiruddu National Referral Hospital outpatient clinics. A trained research nurse administered a semi-structured questionnaire assessing demographics, COVID-19 vaccine related attitudes and acceptability. Descriptive statistics, bivariate and multivariable analyses were performed using STATA 16. RESULTS: A total of 317 participants with a mean age 51.5 ± 14.1 years were recruited. Of this, 184 (60.5%) were female. Overall, 216 (70.1%) participants were willing to accept the COVID-19 vaccine. The odds of willingness to accept COVID-19 vaccination were four times greater if a participant was male compared with if a participant was female [adjusted odds ratio (AOR): 4.1, 95% confidence interval (CI): 1.8-9.4, p = 0.00]. Participants who agreed (AOR: 0.04, 95% CI: 0.01-0.38, p = 0.003) or strongly agreed (AOR: 0.04, 95% CI: 0.01-0.59, p = 0.005) that they have some immunity against COVID-19 were also significantly less likely to accept the vaccine. Participants who had a history of vaccination hesitancy for their children were also significantly less likely to accept the COVID-19 vaccine (AOR: 0.1, 95% CI: 0.01-0.58, p = 0.016). CONCLUSION: The willingness to receive a COVID-19 vaccine in this group of high-risk individuals was comparable to the global COVID-19 vaccine acceptance rate. Increased sensitization, myth busting and utilization of opinion leaders to encourage vaccine acceptability is recommended.

9.
Adv Med Educ Pract ; 12: 253-262, 2021.
Article in English | MEDLINE | ID: covidwho-1138630

ABSTRACT

BACKGROUND: The coronavirus-2019 (COVID-19) pandemic continues to impose a significant impact on medical education. We aimed to describe the clinical learning experience of undergraduate medical students undertaking internal medicine clerkship during the COVID-19 pandemic at Makerere University, Uganda. METHODS: A descriptive, cross-sectional study among medical students in clinical years of study pursuing the Bachelor of Medicine and Bachelor of Surgery undergraduate degree program was conducted in November 2020. Only 3rd (junior clerks) and 5th (senior clerks) year medical students whose internal medicine clerkships were interrupted by the COVID-19 pandemic were studied. RESULTS: Data of 188 (95%) eligible clinical year students; junior (101, 54.0%) and senior (86, 46.0%) were analysed. Median age was 24 (range: 22-42) years. Majority (70.1%) were male and Ugandan nationals (94.1%). Sixty-four (30.3%) students reported inadequate personal protective equipment, 152 (81.7%) felt at risk of contracting COVID-19, and 127 (67.9%) said it was difficult to observe COVID-19 standard operating procedures. Twenty-two students (11.9%) were discouraged from pursuing a career in internal medicine. Overall, most students reported good or excellent clinical experience pre-COVID-19 era compared to during the COVID-19 era (4.0 vs 3.5, p<0.0001). Senior clerks significantly believed that the time allocated for the rotation was adequate (p<0.0001) and they were able to complete their study objectives (p<0.001), compared to the junior clerks. Senior clerks believed that learning was difficult when combined with junior clerks (p=0.013). About half of the students (51.4%, n=95) reported clinical teaching should remain as it was in the pre-COVID-19 era. CONCLUSION: The COVID-19 pandemic has had a significantly negative effect on the clinical learning experience of the students. There is need to review the current teaching and learning methods to suit teaching and learning during pandemics of highly infectious diseases to ensure safe and effective learning experience.

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