Innovative, rapid, high-throughput method for drug repurposing in a pandemic—A case study of SARS-CoV-2 and COVID-19

Several efforts to repurpose drugs for COVID-19 treatment have largely either failed to identify a suitable agent or agents identified did not translate to clinical use. Reasons that have been suggested to explain the failures include use of inappropriate doses, that are not clinically achievable, in the screening experiments, and the use of inappropriate pre-clinical laboratory surrogates to predict efficacy. In this study, we used an innovative algorithm, that incorporates dissemination and implementation considerations, to identify potential drugs for COVID-19 using iterative computational and wet laboratory methods. The drugs were screened at doses that are known to be achievable in humans. Furthermore, inhibition of viral induced cytopathic effect (CPE) was used as the laboratory surrogate to predict efficacy. Erythromycin, pyridoxine, folic acid and retapamulin were found to inhibit SARS-CoV-2 induced CPE in Vero cells at concentrations that are clinically achievable. Additional studies may be required to further characterize the inhibitions of CPE and the possible mechanisms.

Trends in pediatric tuberculosis diagnosis utilizing xpert Mycobacterium tuberculosis/Rifampicin in a poor-resource, high-burden region: A retrospective, multicenter study.

Background: The burden of tuberculosis (TB) in Nigeria remains high, and diagnosis in children, a challenge. We aimed to document yield from Xpert Mycobacterium tuberculosis/rifampicin (MTB/RIF) as a mode of diagnosis for children and the variables associated with a positive result. Methods: This was a retrospective review of TB treatment cards of children aged 0-15 years managed from January 2017 to December 2021 across six public tertiary institutions in Nigeria. The data obtained were analyzed using the descriptive and inferential statistics. Statistical significance was set at P < 0.05. Results: Of 1489 children commenced on TB treatment, 1463 (97.9%) had sufficient data for analysis the median age of study participants was 60 months (interquartile range [IQR]: 24, 120), and 814 (55.6%) were males. Xpert MTB/RIF test was performed in 862 (59%) participants and MTB was detected in 171 (19.8%) participants, of which 6.4% (11/171) had RIF resistance reported. The use of Xpert MTB/RIF rose from 56.5% in 2017 to 64% in 2020 but fell to 60.9% in 2021. We found that older age (> 10 years), the presence of pulmonary TB (PTB), and a negative human immunodeficiency virus (HIV) status were associated with positive Xpert MTB/RIF tests (P = 0.002, 0.001, and 0.012, respectively). Conclusion: The utilization of Xpert MTB/RIF in children increased in the years before the COVID-19 pandemic. Factors associated with MTB detection by Xpert MTB/RIF include older age, the presence of PTB, and a negative HIV status. Clinical and radiological evaluation continues to play vital roles in the diagnosis of childhood TB in Nigeria.

Innovative, rapid, high-throughput method for drug repurposing in a pandemic-A case study of SARS-CoV-2 and COVID-19.

Several efforts to repurpose drugs for COVID-19 treatment have largely either failed to identify a suitable agent or agents identified did not translate to clinical use. Reasons that have been suggested to explain the failures include use of inappropriate doses, that are not clinically achievable, in the screening experiments, and the use of inappropriate pre-clinical laboratory surrogates to predict efficacy. In this study, we used an innovative algorithm, that incorporates dissemination and implementation considerations, to identify potential drugs for COVID-19 using iterative computational and wet laboratory methods. The drugs were screened at doses that are known to be achievable in humans. Furthermore, inhibition of viral induced cytopathic effect (CPE) was used as the laboratory surrogate to predict efficacy. Erythromycin, pyridoxine, folic acid and retapamulin were found to inhibit SARS-CoV-2 induced CPE in Vero cells at concentrations that are clinically achievable. Additional studies may be required to further characterize the inhibitions of CPE and the possible mechanisms.

A national survey of hospital readiness during the COVID-19 pandemic in Nigeria.

INTRODUCTION: The COVID-19 pandemic continues to overwhelm health systems across the globe. We aimed to assess the readiness of hospitals in Nigeria to respond to the COVID-19 outbreak. METHOD: Between April and October 2020, hospital representatives completed a modified World Health Organisation (WHO) COVID-19 hospital readiness checklist consisting of 13 components and 124 indicators. Readiness scores were classified as adequate (score ≥80%), moderate (score 50-79.9%) and not ready (score <50%). RESULTS: Among 20 (17 tertiary and three secondary) hospitals from all six geopolitical zones of Nigeria, readiness score ranged from 28.2% to 88.7% (median 68.4%), and only three (15%) hospitals had adequate readiness. There was a median of 15 isolation beds, four ICU beds and four ventilators per hospital, but over 45% of hospitals established isolation facilities and procured ventilators after the onset of COVID-19. Of the 13 readiness components, the lowest readiness scores were reported for surge capacity (61.1%), human resources (59.1%), staff welfare (50%) and availability of critical items (47.7%). CONCLUSION: Most hospitals in Nigeria were not adequately prepared to respond to the COVID-19 outbreak. Current efforts to strengthen hospital preparedness should prioritize challenges related to surge capacity, critical care for COVID-19 patients, and staff welfare and protection.

Profile of children with COVID-19 infection: a cross sectional study from North-East Nigeria.

INTRODUCTION: available evidence suggests that children infected with COVID-19 tend to have a less severe form of the disease. However, most of the studies that have established this largely emanate from outside sub-Saharan Africa. The pandemic nature of the infection makes it instructive to evaluate its pattern among children across different climes, including ours. This study was set out to describe the clinical characteristics of children with COVID-19 in Bauchi State, North-East Nigeria. METHODS: this was a cross sectional study that involved 53 children between the ages of 0 and 18 years, who had RT-PCR confirmed COVID-19 infection between March and June 2020 in Bauchi State, Nigeria. Data on epidemiological and clinical characteristics was analysed using IBM SPSS Statistics V 21.® Relationship between categorical variables was established using the chi square test. The level of statistical significance was set at < 0.05, at a confidence interval (CI) of 95%. RESULTS: the mean age was 12.63 ± 4.31 years with a slight preponderance of males (1.1: 1). Majority were asymptomatic (60.4%), while 32.1% and 7.5% had mild and moderate diseases respectively. The most common symptoms were cough (20.8%), fever (17%), and sneezing (15.1%). Five children (9.4%) complained of loss of taste while anosmia was documented in one child (1.9%). We observed a significant relationship between age category and the presence of symptoms. In fact, children younger than 10 years (pre-adolescents) were five times more likely to be symptomatic when compared to those above this age (p = 0.029, C I 1.08-21.56). CONCLUSION: our findings have shown a mild pattern of disease and good outcome among infected children. However, we must be mindful of the higher vulnerability among younger children, especially those below 10 years.