SARS-CoV-2 variants-associated outbreaks of COVID-19 in a tertiary institution, North-Central Nigeria: Implications for epidemic control.

The COVID-19 global pandemic is being driven by evolving SARS-CoV-2 variants with consequential implications on virus transmissibility, host immunity, and disease severity. Continuous molecular and genomic surveillance of the SARS-CoV-2 variants is therefore necessary for public health interventions toward the management of the pandemic. This study is a retrospective analysis of COVID-19 cases reported in a Nigerian tertiary institution from July to December 2021. In total, 705 suspected COVID-19 cases that comprised 547 students and 158 non-students were investigated by real time PCR (RT-PCR); of which 372 (~52.8%) tested positive for COVID-19. Using a set of selection criteria, 74 (~19.9%) COVID-19 positive samples were selected for next generation sequencing. Data showed that there were two outbreaks of COVID-19 within the university community over the study period, during which more females (56.8%) tested positive than males (47.8%) (p<0.05). Clinical data together with phylogenetic analysis suggested community transmission of SARS-CoV-2 through mostly asymptomatic and/or pre-symptomatic individuals. Confirmed COVID-19 cases were mostly mild, however, SARS-CoV-2 delta (77%) and omicron (4.1%) variants were implicated as major drivers of respective waves of infections during the study period. This study highlights the importance of integrated surveillance of communicable disease during outbreaks.

Comparison of one single-antigen assay and three multi-antigen SARS-CoV-2 IgG assays in Nigeria.

Objectives: Determining an accurate estimate of SARS-CoV-2 seroprevalence has been challenging in African countries where malaria and other pathogens are endemic. We compared the performance of one single-antigen assay and three multi-antigen SARS-CoV-2 IgG assays in a Nigerian population endemic for malaria. Methods: De-identified plasma specimens from SARS-CoV-2 RT-PCR positive, dried blood spot (DBS) SARS-CoV-2 RT-PCR positive, and pre-pandemic negatives were used to evaluate the performance of the four SARS-CoV-2 assays (Tetracore, SARS2MBA, RightSign, xMAP). Results: Results showed higher sensitivity with the multi-antigen (81% (Tetracore), 96% (SARS2MBA), 85% (xMAP)) versus the single-antigen (RightSign (64%)) SARS-CoV-2 assay. The overall specificities were 98% (Tetracore), 100% (SARS2MBA and RightSign), and 99% (xMAP). When stratified based on <15 days to ≥15 days post-RT-PCR confirmation, the sensitivities increased from 75% to 88.2% for Tetracore; from 93% to 100% for the SARS2MBA; from 58% to 73% for RightSign; and from 83% to 88% for xMAP. With DBS, there was no positive increase after 15-28 days for the three assays (Tetracore, SARS2MBA, and xMAP). Conclusion: Multi-antigen assays performed well in Nigeria, even with samples with known malaria reactivity, and might provide more accurate measures of COVID-19 seroprevalence and vaccine efficacy.

Contribution of PEPFAR-Supported HIV and TB Molecular Diagnostic Networks to COVID-19 Testing Preparedness in 16 Countries.

The US President's Emergency Plan for AIDS Relief (PEPFAR) supports molecular HIV and tuberculosis diagnostic networks and information management systems in low- and middle-income countries. We describe how national programs leveraged these PEPFAR-supported laboratory resources for SARS-CoV-2 testing during the COVID-19 pandemic. We sent a spreadsheet template consisting of 46 indicators for assessing the use of PEPFAR-supported diagnostic networks for COVID-19 pandemic response activities during April 1, 2020, to March 31, 2021, to 27 PEPFAR-supported countries or regions. A total of 109 PEPFAR-supported centralized HIV viral load and early infant diagnosis laboratories and 138 decentralized HIV and TB sites reported performing SARS-CoV-2 testing in 16 countries. Together, these sites contributed to >3.4 million SARS-CoV-2 tests during the 1-year period. Our findings illustrate that PEPFAR-supported diagnostic networks provided a wide range of resources to respond to emergency COVID-19 diagnostic testing in 16 low- and middle-income countries.

Effect of Nigeria Presidential Task Force on COVID-19 Pandemic, Nigeria.

Nigeria had a confirmed case of COVID-19 on February 28, 2020. On March 17, 2020, the Nigerian Government inaugurated the Presidential Task Force (PTF) on COVID-19 to coordinate the country's multisectoral intergovernmental response. The PTF developed the National COVID-19 Multisectoral Pandemic Response Plan as the blueprint for implementing the response plans. The PTF provided funding, coordination, and governance for the public health response and executed resource mobilization and social welfare support, establishing the framework for containment measures and economic reopening. Despite the challenges of a weak healthcare infrastructure, staff shortages, logistic issues, commodity shortages, currency devaluation, and varying state government cooperation, high-level multisectoral PTF coordination contributed to minimizing the effects of the pandemic through early implementation of mitigation efforts, supported by a strong collaborative partnership with bilateral, multilateral, and private-sector organizations. We describe the lessons learned from the PTF COVID-19 for future multisectoral public health response.

Epidemiology, diagnostics and factors associated with mortality during a cholera epidemic in Nigeria, October 2020-October 2021: a retrospective analysis of national surveillance data.

OBJECTIVES: Nigeria reported an upsurge in cholera cases in October 2020, which then transitioned into a large, disseminated epidemic for most of 2021. This study aimed to describe the epidemiology, diagnostic performance of rapid diagnostic test (RDT) kits and the factors associated with mortality during the epidemic. DESIGN: A retrospective analysis of national surveillance data. SETTING: 33 of 37 states (including the Federal Capital Territory) in Nigeria. PARTICIPANTS: Persons who met cholera case definition (a person of any age with acute watery diarrhoea, with or without vomiting) between October 2020 and October 2021 within the Nigeria Centre for Disease Control surveillance data. OUTCOME MEASURES: Attack rate (AR; per 100 000 persons), case fatality rate (CFR; %) and accuracy of RDT performance compared with culture using area under the receiver operating characteristic curve (AUROC). Additionally, individual factors associated with cholera deaths and hospitalisation were presented as adjusted OR with 95% CIs. RESULTS: Overall, 93 598 cholera cases and 3298 deaths (CFR: 3.5%) were reported across 33 of 37 states in Nigeria within the study period. The proportions of cholera cases were higher in men aged 5-14 years and women aged 25-44 years. The overall AR was 46.5 per 100 000 persons. The North-West region recorded the highest AR with 102 per 100 000. Older age, male gender, residency in the North-Central region and severe dehydration significantly increased the odds of cholera deaths. The cholera RDT had excellent diagnostic accuracy (AUROC=0.91; 95% CI 0.87 to 0.96). CONCLUSIONS: Cholera remains a serious public health threat in Nigeria with a high mortality rate. Thus, we recommend making RDT kits more widely accessible for improved surveillance and prompt case management across the country.

Analysis of sociodemographic and clinical factors associated with Lassa fever disease and mortality in Nigeria.

Over past decades, there has been increasing geographical spread of Lassa fever (LF) cases across Nigeria and other countries in West Africa. This increase has been associated with significant morbidity and mortality despite increasing focus on the disease by both local and international scientists. Many of these studies on LF have been limited to few specialised centres in the country. This study was done to identify sociodemographic and clinical predictors of LF disease and related deaths across Nigeria. We analysed retrospective surveillance data on suspected LF cases collected during January-June 2018 and 2019. Multivariable logistic regression analyses were used to identify the factors independently associated with laboratory-confirmed LF diagnosis, and with LF-related deaths. There were confirmed 815 of 1991 suspected LF cases with complete records during this period. Of these, 724/815 confirmed cases had known clinical outcomes, of whom 100 died. LF confirmation was associated with presentation of gastrointestinal tract (aOR 3.47, 95% CI: 2.79-4.32), ear, nose and throat (aOR 2.73, 95% CI: 1.80-4.15), general systemic (aOR 2.12, 95% CI: 1.65-2.70) and chest/respiratory (aOR 1.71, 95% CI: 1.28-2.29) symptoms. Other factors were being male (aOR 1.32, 95% CI: 1.06-1.63), doing business/trading (aOR 2.16, 95% CI: 1.47-3.16) and farming (aOR 1.73, 95% CI: 1.12-2.68). Factors associated with LF mortality were a one-year increase in age (aOR 1.03, 95% CI: 1.01-1.04), bleeding (aOR 2.07, 95% CI: 1.07-4.00), and central nervous manifestations (aOR 5.02, 95% CI: 3.12-10.16). Diverse factors were associated with both LF disease and related death. A closer look at patterns of clinical variables would be helpful to support early detection and management of cases. The findings would also be useful for planning preparedness and response interventions against LF in the country and region.

Seroprevalence of SARS-CoV-2 in four states of Nigeria in October 2020: A population-based household survey.

The observed epidemiology of SARS-CoV-2 in sub-Saharan Africa has varied greatly from that in Europe and the United States, with much lower reported incidence. Population-based studies are needed to estimate true cumulative incidence of SARS-CoV-2 to inform public health interventions. This study estimated SARS-CoV-2 seroprevalence in four selected states in Nigeria in October 2020. We implemented a two-stage cluster sample household survey in four Nigerian states (Enugu, Gombe, Lagos, and Nasarawa) to estimate age-stratified prevalence of SARS-CoV-2 antibodies. All individuals in sampled households were eligible for interview, blood draw, and nasal/oropharyngeal swab collection. We additionally tested participants for current/recent malaria infection. Seroprevalence estimates were calculated accounting for the complex survey design. Across all four states, 10,629 (96·5%) of 11,015 interviewed individuals provided blood samples. The seroprevalence of SARS-CoV-2 antibodies was 25·2% (95% CI 21·8-28·6) in Enugu State, 9·3% (95% CI 7·0-11·5) in Gombe State, 23·3% (95% CI 20·5-26·4) in Lagos State, and 18·0% (95% CI 14·4-21·6) in Nasarawa State. Prevalence of current/recent malaria infection ranged from 2·8% in Lagos to 45·8% in Gombe and was not significantly related to SARS-CoV-2 seroprevalence. The prevalence of active SARS-CoV-2 infection in the four states during the survey period was 0·2% (95% CI 0·1-0·4). Approximately eight months after the first reported COVID-19 case in Nigeria, seroprevalence indicated infection levels 194 times higher than the 24,198 officially reported COVID-19 cases across the four states; however, most of the population remained susceptible to COVID-19 in October 2020.

COVID-19 mortality rate and its associated factors during the first and second waves in Nigeria.

COVID-19 mortality rate has not been formally assessed in Nigeria. Thus, we aimed to address this gap and identify associated mortality risk factors during the first and second waves in Nigeria. This was a retrospective analysis of national surveillance data from all 37 States in Nigeria between February 27, 2020, and April 3, 2021. The outcome variable was mortality amongst persons who tested positive for SARS-CoV-2 by Reverse-Transcriptase Polymerase Chain Reaction. Incidence rates of COVID-19 mortality was calculated by dividing the number of deaths by total person-time (in days) contributed by the entire study population and presented per 100,000 person-days with 95% Confidence Intervals (95% CI). Adjusted negative binomial regression was used to identify factors associated with COVID-19 mortality. Findings are presented as adjusted Incidence Rate Ratios (aIRR) with 95% CI. 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 COVID-19 mortality 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 COVID-19 mortality 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)]. Relative to South-West, residency in the South-South and North-West was associated with an increased risk of COVID-19 mortality in both waves. In conclusion, the rate of COVID-19 mortality in Nigeria was higher in the first wave than in the second wave, suggesting an improvement in public health response and clinical care in the second wave. However, this needs to be interpreted with caution given the inherent limitations of the country's surveillance system during the study.

Epidemiological description of and response to a large yellow fever outbreak in Edo state Nigeria, September 2018 - January 2019.

BACKGROUND: Edo State Surveillance Unit observed the emergence of a disease with "no clear-cut-diagnosis", which affected peri-urban Local Government Areas (LGAs) from September 6 to November 1, 2018. On notification, the Nigeria Centre for Disease Control deployed a Rapid Response Team (RRT) to support outbreak investigation and response activities in the State. This study describes the epidemiology of and response to a large yellow fever (YF) outbreak in Edo State. METHODS: A cross-sectional descriptive outbreak investigation of YF outbreak in Edo State. A suspected case of YF was defined as "Any person residing in Edo State with acute onset of fever and jaundice appearing within 14 days of onset of the first symptoms from September 2018 to January 2019". Our response involved active case search in health facilities and communities, retrospective review of patients' records, rapid risk assessment, entomological survey, rapid YF vaccination coverage assessment, blood sample collection, case management and risk communication. Descriptive data analysis using percentages, proportions, frequencies were made. RESULTS: A total of 209 suspected cases were line-listed. Sixty-seven (67) confirmed in 12 LGAs with 15 deaths [Case fatality rate (CFR 22.4%)]. Among confirmed cases, median age was 24.8, (range 64 (1-64) years; Fifty-one (76.1%) were males; and only 13 (19.4%) had a history of YF vaccination. Vaccination coverage survey involving 241 children revealed low YF vaccine uptake, with 44.6% providing routine immunisation cards for sighting. Risk of YF transmission was 71.4%. Presence of Aedes with high-larval indices (House Index ≥5% and/or Breteau Index ≥20) were established in all the seven locations visited. YF reactive mass vaccination campaign was implemented. CONCLUSION: Edo State is one of the states in Nigeria with the highest burden of yellow fever. More males were affected among the confirmed. Major symptoms include fever, jaundice, weakness, and bleeding. Majority of surveillance performance indicators were above target. There is a high risk of transmission of the disease in the state. Low yellow fever vaccination coverage, and presence of yellow fever vectors (Ae.aegypti, Ae.albopictus and Ae.simpsoni) are responsible for cases in affected communities. Enhanced surveillance, improved laboratory sample management, reactive vaccination campaign, improved yellow fever case management and increased risk communication/awareness are very important mitigation strategies to be sustained in Edo state to prevent further spread and mortality from yellow fever.

Validation of xMAP SARS-CoV-2 Multi-Antigen IgG assay in Nigeria.

OBJECTIVE: There is a need for reliable serological assays to determine accurate estimates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence. Most single target antigen assays have shown some limitations in Africa. To assess the performance of a multi-antigen assay, we evaluated a commercially available SARS-CoV-2 Multi-Antigen IgG assay for human coronavirus disease 2019 (COVID-19) in Nigeria. METHODS: Validation of the xMAP SARS-CoV-2 Multi-Antigen IgG assay was carried out using well-characterized SARS-CoV-2 reverse transcription polymerase chain reactive positive (97) and pre-COVID-19 pandemic (86) plasma panels. Cross-reactivity was assessed using pre-COVID-19 pandemic plasma specimens (213) from the 2018 Nigeria HIV/AIDS Indicator and Impact Survey (NAIIS). RESULTS: The overall sensitivity of the xMAP SARS-CoV-2 Multi-Antigen IgG assay was 75.3% [95% CI: 65.8%- 82.8%] and specificity was 99.0% [95% CI: 96.8%- 99.7%]. The sensitivity estimate increased to 83.3% [95% CI: 70.4%- 91.3%] for specimens >14 days post-confirmation of diagnosis. However, using the NAIIS pre-pandemic specimens, the false positivity rate was 1.4% (3/213). CONCLUSIONS: Our results showed overall lower sensitivity and a comparable specificity with the manufacturer's validation. There appears to be less cross-reactivity with NAIIS pre-pandemic COVID-19 specimens using the xMAP SARS-CoV-2 Multi-Antigen IgG assay. In-country SARS-CoV-2 serology assay validation can help guide the best choice of assays in Africa.

Cross-Reactivity of Two SARS-CoV-2 Serological Assays in a Setting Where Malaria Is Endemic.

Accurate SARS-CoV-2 serological assays are critical for COVID-19 serosurveillance. However, previous studies have indicated possible cross-reactivity of these assays, including in areas where malaria is endemic. We tested 213 well-characterized prepandemic samples from Nigeria using two SARS-CoV-2 serological assays, Abbott Architect IgG and Euroimmun NCP IgG assay, both targeting SARS-CoV-2 nucleocapsid protein. To assess antibody binding strength, an avidity assay was performed on these samples and on plasma from SARS-CoV-2 PCR-positive persons. Thirteen (6.1%) of 212 samples run on the Abbott assay and 38 (17.8%) of 213 run on the Euroimmun assay were positive. Anti-Plasmodium IgG levels were significantly higher among false positives for both Abbott and Euroimmun; no association was found with active Plasmodium falciparum infection. An avidity assay using various concentrations of urea wash in the Euroimmun assay reduced loosely bound IgG: of 37 positive/borderline prepandemic samples, 46%, 86%, 89%, and 97% became negative using 2 M, 4 M, 5 M, and 8 M urea washes, respectively. The wash slightly reduced avidity of antibodies from SARS-CoV-2 patients within 28 days of PCR confirmation; thereafter, avidity increased for all urea concentrations except 8 M. This validation found moderate to substantial cross-reactivity on two SARS-CoV-2 serological assays using samples from a setting where malaria is endemic. A simple urea wash appeared to alleviate issues of cross-reactivity.

Assessing the capacity of symptom scores to predict COVID-19 positivity in Nigeria: a national derivation and validation cohort study.

OBJECTIVES: This study aimed to develop and validate a symptom prediction tool for COVID-19 test positivity in Nigeria. DESIGN: Predictive modelling study. SETTING: All Nigeria States and the Federal Capital Territory. PARTICIPANTS: A cohort of 43 221 individuals within the national COVID-19 surveillance dataset from 27 February to 27 August 2020. Complete dataset was randomly split into two equal halves: derivation and validation datasets. Using the derivation dataset (n=21 477), backward multivariable logistic regression approach was used to identify symptoms positively associated with COVID-19 positivity (by real-time PCR) in children (≤17 years), adults (18-64 years) and elderly (≥65 years) patients separately. OUTCOME MEASURES: Weighted statistical and clinical scores based on beta regression coefficients and clinicians' judgements, respectively. Using the validation dataset (n=21 744), area under the receiver operating characteristic curve (AUROC) values were used to assess the predictive capacity of individual symptoms, unweighted score and the two weighted scores. RESULTS: Overall, 27.6% of children (4415/15 988), 34.6% of adults (9154/26 441) and 40.0% of elderly (317/792) that had been tested were positive for COVID-19. Best individual symptom predictor of COVID-19 positivity was loss of smell in children (AUROC 0.56, 95% CI 0.55 to 0.56), either fever or cough in adults (AUROC 0.57, 95% CI 0.56 to 0.58) and difficulty in breathing in the elderly (AUROC 0.53, 95% CI 0.48 to 0.58) patients. In children, adults and the elderly patients, all scoring approaches showed similar predictive performance. CONCLUSIONS: The predictive capacity of various symptom scores for COVID-19 positivity was poor overall. However, the findings could serve as an advocacy tool for more investments in resources for capacity strengthening of molecular testing for COVID-19 in Nigeria.

Comparative performance of SARS-CoV-2 real-time PCR diagnostic assays on samples from Lagos, Nigeria.

A key element in containing the spread of the SARS-CoV-2 infection is quality diagnostics which is affected by several factors. We now report the comparative performance of five real-time diagnostic assays. Nasopharyngeal swab samples were obtained from persons seeking a diagnosis for SARS-CoV-2 infection in Lagos, Nigeria. The comparison was performed on the same negative, low, and high-positive sample set, with viral RNA extracted using the Qiagen Viral RNA Kit. All five assays are one-step reverse transcriptase real-time PCR assays. Testing was done according to each assay's manufacturer instructions for use using real-time PCR platforms. 63 samples were tested using the five qPCR assays, comprising of 15 negative samples, 15 positive samples (Ct = 16-30; one Ct = 35), and 33 samples with Tib MolBiol E-gene Ct value ranging from 36-41. All assays detected all high positive samples correctly. Three assays correctly identified all negative samples while two assays each failed to correctly identify one different negative sample. The consistent detection of positive samples at different Ct/Cq values gives an indication of when to repeat testing and/or establish more stringent in-house cut-off value. The varied performance of different diagnostic assays, mostly with emergency use approvals, for a novel virus is expected. Comparative assays' performance reported may guide laboratories to determine both their repeat testing Ct/Cq range and/or cut-off value.

Patient characteristics associated with COVID-19 positivity and fatality in Nigeria: retrospective cohort study.

OBJECTIVE: Despite the increasing disease burden, there is a dearth of context-specific evidence on the risk factors for COVID-19 positivity and subsequent death in Nigeria. Thus, the study objective was to identify context-specific factors associated with testing positive for COVID-19 and fatality in Nigeria. DESIGN: Retrospective cohort study. SETTING: COVID-19 surveillance and laboratory centres in 36 states and the Federal Capital Territory reporting data to the Nigeria Centre for Disease Control. PARTICIPANTS: Individuals who were investigated for SARS-CoV-2 using real-time PCR testing during the study period 27 February-8 June 2020. METHODS: COVID-19 positivity and subsequent mortality. Multivariable logistic regression analyses were performed to identify factors independently associated with both outcome variables, and findings are presented as adjusted ORs (aORs) and 95% CIs. RESULTS: A total of 36 496 patients were tested for COVID-19, with 10 517 confirmed cases. Of 3215 confirmed cases with available clinical outcomes, 295 died. Factors independently associated with COVID-19 positivity were older age (p value for trend<0.0001), male sex (aOR 1.11, 95% CI 1.04 to 1.18) and the following presenting symptoms: cough (aOR 1.23, 95% CI 1.13 to 1.32), fever (aOR 1.45, 95% CI 1.45 to 1.71), loss of smell (aOR 7.78, 95% CI 5.19 to 11.66) and loss of taste (aOR 2.50, 95% CI 1.60 to 3.90). An increased risk of mortality following COVID-19 was observed in those aged ≥51 years, patients in farming occupation (aOR 7.56, 95% CI 1.70 to 33.53) and those presenting with cough (aOR 2.06, 95% CI 1.41 to 3.01), breathing difficulties (aOR 5.68, 95% CI 3.77 to 8.58) and vomiting (aOR 2.54, 95% CI 1.33 to 4.84). CONCLUSION: The significant risk factors associated with COVID-19 positivity and subsequent mortality in the Nigerian population are similar to those reported in studies from other countries and should guide clinical decisions for COVID-19 testing and specialist care referrals.