Modified ARCHITECT® serologic assays enable plasma-level performance from dried blood spot samples.

Dried blood spots (DBSs) provide an alternative sample input for serologic testing. We evaluated DBSs for the ARCHITECT® hepatitis B surface antigen (HBsAg) NEXT, hepatitis B e-antigen (HBeAg), anti-hepatitis B core antigen (anti-HBc II), HIV antigen/antibody (Ag/Ab) Combo and AdviseDx SARS-CoV-2 IgG II assays. Assay performance with DBSs was assessed with or without assay modification and compared with on-market assay with plasma samples. DBS stability was also determined. HBsAg NEXT and HIV Ag/Ab Combo assays using DBSs showed sensitivity and specificity comparable to that of on-market assays. Modified HBeAg, anti-HBc II and SARS-CoV-2 IgG II DBS assays achieved performance comparable to on-market assays. Use of DBSs as input for high-throughput serologic assays is expected to have significant implications for improving population surveillance and increasing access to diagnostic testing.

Assessing the impacts of COVID-19 vaccination programme's timing and speed on health benefits, cost-effectiveness, and relative affordability in 27 African countries.

BACKGROUND: The COVID-19 vaccine supply shortage in 2021 constrained roll-out efforts in Africa while populations experienced waves of epidemics. As supply improves, a key question is whether vaccination remains an impactful and cost-effective strategy given changes in the timing of implementation. METHODS: We assessed the impact of vaccination programme timing using an epidemiological and economic model. We fitted an age-specific dynamic transmission model to reported COVID-19 deaths in 27 African countries to approximate existing immunity resulting from infection before substantial vaccine roll-out. We then projected health outcomes (from symptomatic cases to overall disability-adjusted life years (DALYs) averted) for different programme start dates (01 January to 01 December 2021, n = 12) and roll-out rates (slow, medium, fast; 275, 826, and 2066 doses/million population-day, respectively) for viral vector and mRNA vaccines by the end of 2022. Roll-out rates used were derived from observed uptake trajectories in this region. Vaccination programmes were assumed to prioritise those above 60 years before other adults. We collected data on vaccine delivery costs, calculated incremental cost-effectiveness ratios (ICERs) compared to no vaccine use, and compared these ICERs to GDP per capita. We additionally calculated a relative affordability measure of vaccination programmes to assess potential nonmarginal budget impacts. RESULTS: Vaccination programmes with early start dates yielded the most health benefits and lowest ICERs compared to those with late starts. While producing the most health benefits, fast vaccine roll-out did not always result in the lowest ICERs. The highest marginal effectiveness within vaccination programmes was found among older adults. High country income groups, high proportions of populations over 60 years or non-susceptible at the start of vaccination programmes are associated with low ICERs relative to GDP per capita. Most vaccination programmes with small ICERs relative to GDP per capita were also relatively affordable. CONCLUSION: Although ICERs increased significantly as vaccination programmes were delayed, programmes starting late in 2021 may still generate low ICERs and manageable affordability measures. Looking forward, lower vaccine purchasing costs and vaccines with improved efficacies can help increase the economic value of COVID-19 vaccination programmes.

Diagnostic performance of molecular and serological tests of SARS-CoV-2 on well-characterised specimens from COVID-19 individuals: The EDCTP "PERFECT-study" protocol (RIA2020EF-3000).

BACKGROUND: The SARS-CoV-2 pandemic is a global threat affecting 210 countries, with 2,177,469 confirmed cases and 6.67% case fatality rate as of April 16, 2020. In Africa, 17,243 cases have been confirmed, but many remain undiagnosed due to limited laboratory-capacity, suboptimal performance of used molecular-assays (~30% false negative, Yu et al. and Zhao et al., 2020) and limited WHO-recommended rapid-tests. OBJECTIVES: We aim to implement measures to minimize risks for COVID-19 in Cameroon, putting together multidisciplinary highly-experienced virologists, immunologists, bioinformaticians and clinicians, to achieve the following objectives: (a) to integrate/improve available-infrastructure, methodologies, and expertise on COVID-19. For this purpose, we will create a platform enabling researchers/clinicians to better integrate and translate evidence into the COVID-19 clinical-practice; (b) to enhance capacities in Cameroon for screening/detecting individuals with high-risks of COVID-19, by setting-up effective core-facilities on-site; (c) to validate point-of-care SARS-CoV-2 molecular assays allowing same-day result delivery, thus permitting timely diagnosis, treatment, and retention in care of COVID-19 patients; (d) to implement SARS-CoV-2 diagnosis with innovative/highly sensitive ddPCR-based assays and viral genetic characterization; (e) to validate serological assays to identify COVID-19-exposed persons and follow-up of convalescents. METHODS: This is a prospective, observational study conducted among COVID-19 suspects/contacts during 24 months in Cameroon. Following consecutive sampling of 1,536 individuals, oro/nasopharyngeal swabs and sera will be collected. Well characterised biorepositories will be established locally; molecular testing will be performed on conventional real-time qPCR, point-of-care GeneXpert, antigen-tests and digital droplet PCR (ddPCR); SARS-CoV2 amplicons will be sequenced; serological testing will be performed using ELISA, and antibody-based kits. Sensitivity, specificity, positive- and negative-predictive values will be evaluated. EXPECTED OUTCOMES: These efforts will contribute in creating the technical and clinical environment to facilitate earlier detection of Sars-CoV-2 in Africa in general and in Cameroon in particular. Specifically, the goals will be: (a) to implement technology transfer for capacity-building on conventional and point-of-care molecular assays, achieving a desirable performance for clinical diagnosis of SARS-CoV2; (b) to integrate/improve the available infrastructure, methodologies, and expertise on Sars-CoV2 detection; (c) to improve the turn-around-time for diagnosing COVID-19 infection with obvious advantage for patients/clinical management thanks to low-cost assays, thus permitting timely treatment and retention in care; (d) to assess the epidemiology of COVID-19 and circulating-variants in Cameroon as compared to strains found in other countries.

Associations between COVID-19 testing status, non-communicable diseases and HIV status among residents of sub-Saharan Africa during the first wave of the pandemic.

BACKGROUND: This study determined if non-communicable disease status, HIV status, COVID-19 status and co-habiting were associated with COVID-19 test status in sub-Saharan Africa. METHODS: Data of 5945 respondents age 18-years-old and above from 31 countries in sub-Saharan Africa collected through an online survey conducted between June and December 2020, were extracted. The dependent variable was COVID-19 status (testing positive for COVID-19 and having symptoms of COVID-19 but not getting tested). The independent variables were non-communicable disease status (hypertension, diabetes, cancer, heart conditions, respiratory conditions, depression), HIV positive status, COVID-19 status (knowing a close friend who tested positive for COVID-19 and someone who died from COVID-19) and co-habiting (yes/no). Two binary logistic regression models developed to determine associations between the dependent and independent variables were adjusted for age, sex, employment, sub region and educational status. RESULTS: Having a close friend who tested positive for COVID-19 (AOR:6.747), knowing someone who died from COVID-19 infection (AOR:1.732), and living with other people (AOR:1.512) were significantly associated with higher odds of testing positive for COVID-19 infection, while living with HIV was associated with significantly lower odds of testing positive for COVID-19 infection (AOR:0.284). Also, respondents with respiratory conditions (AOR:2.487), self-reported depression (AOR:1.901), those who had a close friend who tested positive for COVID-19 infection (AOR:2.562) and who knew someone who died from COVID-19 infection (AOR:1.811) had significantly higher odds of having symptoms of COVID-19 infection but not getting tested. CONCLUSION: Non-communicable diseases seem not to increase the risk for COVID-19 positive test while cohabiting seems to reduce this risk. The likelihood that those who know someone who tested positive to or who died from COVID-19 not getting tested when symptomatic suggests there is poor contact tracing in the region. People with respiratory conditions and depression need support to get tested for COVID-19.

High concordance in SARSCoV-2 detection between automated (Abbott m2000) and manual (DaAn gene) RT-PCR systems: The EDCTP PERFECT-Study in Cameroon.

Molecular diagnosis of COVID-19 is critical to the control of the pandemic, which is a major threat to global health. Several molecular tests have been validated by WHO, but would require operational evaluation in the field to ensure their interoperability in diagnosis. In order to ensure field interoperability in molecular assays for detection of SARS-CoV-2 RNA, we evaluated the diagnostic concordance of SARS-CoV-2 between an automated (Abbott) and a manual (DaAn gene) realtime PCR (rRT-PCR), two commonly used assays in Africa. A comparative study was conducted on 287 nasopharyngeal specimens at the Chantal BIYA International Reference Centre (CIRCB) in Yaounde- Cameroon. Samples were tested in parallel with Abbott and DaAn gene rRT-PCR, and performance characteristics were evaluated by Cohen's coefficient and Spearman's correlation. A total of 273 participants [median age (IQR) 36 (26-46) years] and 14 EQA specimens were included in the study. Positivity was on 30.0% (86/287) Abbott and 37.6% (108/287) DaAn gene. Overall agreement was 82.6% (237/287), with k=0.82 (95%CI: 0.777-0.863), indicating an excellent diagnostic agreement. The positive and negative agreement was 66.67% (72/108) and 92.18 % (165/179) respectively. Regarding Viral Load (VL), positive agreement was 100% for samples with high VLs (CT<20). Among positive SARS-CoV- 2 cases, the mean difference in Cycle Threshold (CT) for the manual and Cycle Number (CN) for the automated was 6.75±0.3. The excellent agreement (>80%) between the Abbott and DaAn gene rRTPCR platforms supports interoperability between the two assays. Discordance occurs at low-VL, thus underscoring these tools as efficient weapons in limiting SARS-CoV-2 community transmission.

Epidemiological, virological and clinical features of SARS-CoV-2 among individuals during the first wave in Cameroon: Baseline analysis for the EDCTP PERFECT-Study RIA2020EF-3000.

In Cameroon, COVID-19 infection spread rapidly and nationwide, with up to 721 deaths reported. To the best of our knowledge, no study reported the on-theground data using a large patients' dataset to give a comprehensive knowledge on COVID-19 pandemic in Cameroon. The objective of this study was to shade lights on the epidemiological, virological and clinical features of COVID-19 in the Cameroonian context. An observational study was conducted among symptomatic and asymptomatic individuals tested for SARS-CoV-2 by PCR on nasopharyngeal samples from April 22nd, 2020 to January 5th, 2021. Out of 14119 individuals (59.8% male), overall SARS-CoV-2 positivity was 12.7% (from 7.9% in <10 years to 17.3% in >60 years, p<0.001). The positivity rate of symptomatic individuals was 36.1% versus 9.8% among asymptomatic ones, p<0.001. Age group ≤10 [aOR (95%CI): 0.515 (0.338-0.784), p=0.002] and being symptomatic [aOR (95% CI): 5.108 (4.521-5.771), p<0.001] were predictors of SARS-CoV-2 positivity. Regarding PCR Cycle Threshold (CT), 53.8% of positive individuals had a CT <30. According to age, compared to older individuals, those aged 21-40 years showed a higher proportion with high viraemia (CT<20; 21.3% versus 12.5% respectively, p=0.003). Similarly, symptomatic individuals showed a higher proportion with high viraemia (22.4%), when compared to asymptomatic (13.9%); p<0.001. During this first wave of the pandemic, overall SARS-CoV-2 positivity remained high (>10%) and was associated with the presence of symptoms and older age. Most of the infection is among young and asymptomatic individuals, suggesting the "track-and-test" strategy should target these potential transmitters.

Factors Associated With Experiences of Fear, Anxiety, Depression, and Changes in Sleep Pattern During the COVID-19 Pandemic Among Adults in Nigeria: A Cross-Sectional Study.

Background: Multiple facets of the pandemic can be a source of fear, depression, anxiety and can cause changes in sleep patterns. The aim of this study was to identify health profiles and the COVID-19 pandemic related factors associated with fear, depression, anxiety and changes in sleep pattern in adults in Nigeria. Methods: The data for this analysis was extracted from a cross-sectional online survey that collected information about mental health and well-ness from a convenience sample of adults 18 years and above resident in Nigeria from July to December 2020. Study participants were asked to complete an anonymous, closed-ended online questionnaire that solicited information on sociodemographic profile, health profiles (high, moderate and low COVID-19 infection risk profile) including HIV status, COVID-19 status, and self-reported experiences of fear, anxiety, depression and changes in sleep patterns. Results: In total, 4,439 participants with mean age of 38.3 (±11.6) years responded to the survey. Factors associated with higher odds of having COVID-19 related fear were health risk (p < 0.05); living with HIV (AOR: 3.88; 95% CI: 3.22-4.69); having COVID-19 symptoms but not tested (AOR: 1.61; 95% CI: 1.30-1.99); having a friend who tested positive to COVID-19 (AOR: 1.28; 95% CI: 1.07-1.53) and knowing someone who died from COVID-19 (AOR: 1.43; 95% CI: 1.24-1.65). The odds of feeling anxious was significantly higher for those with moderate or low health risk profile (p < 0.05); living with HIV (AOR: 1.64; 95% CI: 1.32-2.04); had a friend who tested positive for COVID-19 (AOR: 1.35; 95% CI: 1.08-1.68) or knew someone who died from COVID-19 (AOR: 1.53; 95% CI: 1.28-1.84). The odds of feeling depressed was significantly higher for those with health risk profile (p < 0.05); living with HIV (AOR: 2.49; 95% CI: 1.89-3.28); and respondents who had COVID-19 symptoms but had not taken a test (AOR: 1.41; 95% CI: 1.02-1.94). Factors associated with higher odds of having sleep pattern changes were having moderate and low health risk profiles (p < 0.05). Conclusion: The study findings suggest that the pandemic may cause fear, anxiety, depression and changes in sleep patterns differently for people with different health profile, HIV status and COVID-19 status.

Factors Associated With Experiences of Fear, Anxiety, Depression, and Changes in Sleep Pattern During the COVID-19 Pandemic Among Adults in Nigeria: A Cross-Sectional Study

Background Multiple facets of the pandemic can be a source of fear, depression, anxiety and can cause changes in sleep patterns. The aim of this study was to identify health profiles and the COVID-19 pandemic related factors associated with fear, depression, anxiety and changes in sleep pattern in adults in Nigeria. Methods The data for this analysis was extracted from a cross-sectional online survey that collected information about mental health and well-ness from a convenience sample of adults 18 years and above resident in Nigeria from July to December 2020. Study participants were asked to complete an anonymous, closed-ended online questionnaire that solicited information on sociodemographic profile, health profiles (high, moderate and low COVID-19 infection risk profile) including HIV status, COVID-19 status, and self-reported experiences of fear, anxiety, depression and changes in sleep patterns. Results In total, 4,439 participants with mean age of 38.3 (±11.6) years responded to the survey. Factors associated with higher odds of having COVID-19 related fear were health risk (p < 0.05);living with HIV (AOR: 3.88;95% CI: 3.22–4.69);having COVID-19 symptoms but not tested (AOR: 1.61;95% CI: 1.30–1.99);having a friend who tested positive to COVID-19 (AOR: 1.28;95% CI: 1.07–1.53) and knowing someone who died from COVID-19 (AOR: 1.43;95% CI: 1.24–1.65). The odds of feeling anxious was significantly higher for those with moderate or low health risk profile (p < 0.05);living with HIV (AOR: 1.64;95% CI: 1.32–2.04);had a friend who tested positive for COVID-19 (AOR: 1.35;95% CI: 1.08–1.68) or knew someone who died from COVID-19 (AOR: 1.53;95% CI: 1.28–1.84). The odds of feeling depressed was significantly higher for those with health risk profile (p < 0.05);living with HIV (AOR: 2.49;95% CI: 1.89–3.28);and respondents who had COVID-19 symptoms but had not taken a test (AOR: 1.41;95% CI: 1.02–1.94). Factors associated with higher odds of having sleep pattern changes were having moderate and low health risk profiles (p < 0.05). Conclusion The study findings suggest that the pandemic may cause fear, anxiety, depression and changes in sleep patterns differently for people with different health profile, HIV status and COVID-19 status.

Time to Scale-up Research Collaborations to Address the Global Impact of COVID-19 - A Commentary.

OBJECTIVE: In this commentary, we suggest that the unprecedented global impact of the COVID-19 pandemic provides a compelling reason for researchers to stretch beyond usual limits and find new ways to engage in global collaborations. METHODS: We point to data that have emerged on the mental health and economic consequences of the pandemic to illustrate the extent to which these common issues cross national borders. There is high likelihood that these burdens will continue to persist long after the pandemic is declared "over." RESULTS: We urge researchers, particularly those from countries with higher income economies, to share resources to increase international collaborative research efforts. We present a case study of an ongoing project and offer some lessons learned for individual investigators. CONCLUSION: Global problems require global solutions. The COVID-19 pandemic is a global crisis that should prompt researchers to engage in science and research across national borders.

Incidence Rate of COVID-19 Mortality and its Associated Factors During the First and Second Waves in Nigeria: A Retrospective Cohort Study (preprint)

Background: COVID-19 mortality rate has not been formally assessed in Nigeria. We therefore aimed to address this gap and identify associated mortality risk factors during the first and second waves in Nigeria.Methods: We conducted a retrospective cohort study using the national surveillance database between February 27, 2020, and April 3, 2021. The outcome was deaths amongst persons with a laboratory diagnosis of COVID-19. Incidence rates of COVID-19 death per 100,000 person-days were estimated. Adjusted negative binomial regression was used to identify factors associated with COVID-19 death, and presented as adjusted Incidence Rate Ratios (aIRR) with 95% confidence intervals (CI). Results: The first wave included 65,790 COVID-19 patients, of whom 994 (1∙51%) died; the second wave included 91,089 patients, of whom 513 (0∙56%) died. The incidence rate of deaths related to COVID-19 was higher in the first wave [54∙25 (95% CI: 50∙98-57∙73)] than in the second wave [19∙19 (17∙60-20∙93)]. Factors independently associated with increased risk of death in both waves were: age ≥45 years, male gender [first wave aIRR 1∙65 (1∙35-2∙02) and second wave 1∙52 (1∙11-2∙06)], being symptomatic [aIRR 3∙17 (2∙59-3∙89) and 3∙04 (2∙20-4∙21)], and being hospitalised [aIRR 4∙19 (3∙26-5∙39) and 7∙84 (4∙90-12∙54)].Interpretation: The incidence rate of COVID-19 death in Nigeria was higher in the first wave, suggesting improved public health response and care during the second wave. Regional mortality differences suggest that policy makers focus on regional equity in access to testing and quality of care to mitigate the impact of another COVID-19 wave in Nigeria.Funding: None to declare. Declaration of Interest: None to declare. Ethical Approval: Ethical approval for the study was given by the Nigeria National Health Research Ethics Committee (NHREC/01/01/2007-22/06/2020).

COVID-19 preparedness: capacity to manufacture vaccines, therapeutics and diagnostics in sub-Saharan Africa.

OBJECTIVE: The COVID-19 pandemic is a biosecurity threat, and many resource-rich countries are stockpiling and/or making plans to secure supplies of vaccine, therapeutics, and diagnostics for their citizens. We review the products that are being investigated for the prevention, diagnosis, and treatment of COVID-19; discuss the challenges that countries in sub-Saharan Africa may face with access to COVID-19 vaccine, therapeutics, and diagnostics due to the limited capacity to manufacture them in Africa; and make recommendations on actions to mitigate these challenges and ensure health security in sub-Saharan Africa during this unprecedented pandemic and future public-health crises. MAIN BODY: Sub-Saharan Africa will not be self-reliant for COVID-19 vaccines when they are developed. It can, however, take advantage of existing initiatives aimed at supporting COVID-19 vaccine access to resource-limited settings such as partnership with AstraZeneca, the Coalition for Epidemic Preparedness and Innovation, the Global Alliance for Vaccine and Immunisation, the Serum Institute of India, and the World Health Organization's COVID-19 Technology Access Pool. Accessing effective COVID-19 therapeutics will also be a major challenge for countries in sub-Saharan Africa, as production of therapeutics is frequently geared towards profitable Western markets and is ill-adapted to sub-Saharan Africa realities. The region can benefit from pooled procurement of COVID-19 therapy by the Africa Centres for Disease Control and Prevention in partnership with the African Union. If the use of convalescent plasma for the treatment of patients who are severely ill is found to be effective, access to the product will be minimally challenging since the region has a pool of recovered patients and human resources that can man supportive laboratories. The region also needs to drive the local development of rapid-test kits and other diagnostics for COVID-19. CONCLUSION: Access to vaccines, therapeutics, and diagnostics for COVID-19 will be a challenge for sub-Saharan Africans. This challenge should be confronted by collaborating with vaccine developers; pooled procurement of COVID-19 therapeutics; and local development of testing and diagnostic materials. The COVID-19 pandemic should be a wake-up call for sub-Saharan Africa to build vaccines, therapeutics, and diagnostics manufacturing capacity as one of the resources needed to address public-health crises.

Considerations for stakeholder engagement and COVID-19 related clinical trials' conduct in sub-Saharan Africa.

The aim of this study is to determine how stakeholder engagement can be adapted for the conduct of COVID-19-related clinical trials in sub-Saharan Africa. Nine essential stakeholder engagement practices were reviewed: formative research; stakeholder engagement plan; communications and issues management plan; protocol development; informed consent process; standard of prevention for vaccine research and standard of care for treatment research; policies on trial-related physical, psychological, financial, and/or social harms; trial accrual, follow-up, exit trial closure and results dissemination; and post-trial access to trial products or procedures. The norms, values, and practices of collectivist societies in Sub-Saharan Africa and the low research literacy pose challenges to the conduct of clinical trials. Civil-society organizations, members of community advisory boards and ethics committees, young persons, COVID-19 survivors, researchers, government, and the private sector are assets for the implementation and translation of COVID-19 related clinical trials. Adapting ethics guidelines to the socio-cultural context of the region can facilitate achieving the aim of stakeholder engagement.