High-resolution African HLA resource uncoversHLA-DRB1expression effects underlying vaccine response (preprint)

How human genetic variation contributes to vaccine immunogenicity and effectiveness is unclear, particularly in infants from Africa. We undertook genome-wide association analyses of eight vaccine antibody responses in 2,499 infants from three African countries and identified significant associations across the human leukocyte antigen (HLA) locus for five antigens spanning pertussis, diphtheria and hepatitis B vaccines. Using high-resolution HLA typing in 1,706 individuals from 11 African populations we constructed a continental imputation resource to fine-map signals of association across the class II HLA observing genetic variation explaining up to 10% of the observed variance in antibody responses. Using follicular helper T-cell assays, in silico binding, and immune cell eQTL datasets we find evidence of HLA-DRB1 expression correlating with serological response and inferred protection from pertussis following vaccination. This work improves our understanding of molecular mechanisms underlying HLA associations that should support vaccine design and development across Africa with wider global relevance. Teaser High-resolution typing of HLA diversity provides mechanistic insights into differential potency and inferred effectiveness of vaccines across Africa.

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance. (preprint)

Investment in Africa over the past year with regards to SARS-CoV-2 genotyping has led to a massive increase in the number of sequences, exceeding 100,000 genomes generated to track the pandemic on the continent. Our results show an increase in the number of African countries able to sequence within their own borders, coupled with a decrease in sequencing turnaround time. Findings from this genomic surveillance underscores the heterogeneous nature of the pandemic but we observe repeated dissemination of SARS-CoV-2 variants within the continent. Sustained investment for genomic surveillance in Africa is needed as the virus continues to evolve, particularly in the low vaccination landscape. These investments are very crucial for preparedness and response for future pathogen outbreaks.

A year of genomic surveillance reveals how the SARS-CoV-2 pandemic unfolded in Africa (preprint)

The progression of the SARS-CoV-2 pandemic in Africa has so far been heterogeneous and the full impact is not yet well understood. Here, we describe the genomic epidemiology using a dataset of 8746 genomes from 33 African countries and two overseas territories. We show that the epidemics in most countries were initiated by importations, predominantly from Europe, which diminished following the early introduction of international travel restrictions. As the pandemic progressed, ongoing transmission in many countries and increasing mobility led to the emergence and spread within the continent of many variants of concern and interest, such as B.1.351, B.1.525, A.23.1 and C.1.1. Although distorted by low sampling numbers and blind-spots, the findings highlight that Africa must not be left behind in the global pandemic response, otherwise it could become a breeding ground for new variants.

Differential Performance of CoronaCHEK SARS-CoV-2 Lateral Flow Antibody Assay by Geographic Origin of Samples (preprint)

Background: We assessed the performance of CoronaCHEK lateral flow assay on samples from Uganda and Baltimore to determine the impact of geographic origin on assay performance. Methods: Serum samples from SARS-CoV-2 PCR+ individuals (Uganda: 78 samples from 78 individuals and Baltimore: 266 samples from 38 individuals) and from pre-pandemic individuals (Uganda 1077 and Baltimore 532) were evaluated. Prevalence ratios (PR) were calculated to identify factors associated with a false-positive test. Results: After first positive PCR in Ugandan samples the sensitivity was: 45% (95% CI 24,68) at 0-7 days; 79% (95%CI 64,91) 8-14 days; and 76% (95%CI 50,93) >15 days. In samples from Baltimore, sensitivity was: 39% (95% CI 30, 49) 0-7 days; 86% (95% CI 79,92) 8-14 days; and 100% (95% CI 89,100) 15 days post positive PCR. The specificity of 96.5% (95% CI 97.5,95.2) in Ugandan samples was significantly lower than samples from Baltimore 99.3% (95% CI 98.1,99.8), p<0.01. In Ugandan samples, individuals with a false positive result were more likely to be male (PR 2.04, 95% CI 1.03,3.69) or individuals who had a fever more than a month prior to sample acquisition (PR 2.87, 95% CI 1.12,7.35). Conclusions: Sensitivity of the CoronaCHEK was similar in samples from Uganda and Baltimore. The specificity was significantly lower in Ugandan samples than in Baltimore samples. False positive results in Ugandan samples appear to correlate with a recent history of a febrile illness, potentially indicative of a cross-reactive immune response in individuals from East Africa.

A SARS-CoV-2 lineage A variant (A.23.1) with altered spike has emerged and is dominating the current Uganda epidemic (preprint)

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was first detected in March 2020 in Uganda. Recently the epidemic showed a shift of SARS-CoV-2 variant distribution and we report here newly emerging A sub-lineages, A.23 and A.23.1, encoding replacements in the spike protein, nsp6, ORF8 and ORF9, with A.23.1 the major virus lineage now observed in Kampala. Although the clinical impact of the A.23.1 variant is not yet clear it is essential to continue careful monitoring of this variant, as well as rapid assessment of the consequences of the spike protein changes for vaccine efficacy.

The Ugandan Severe Acute Respiratory Syndrome -Coronavirus 2 (SARS-CoV-2) Model: A Data Driven Approach to Estimate Risk (preprint)

Objectives The first case of Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) was identified on March 21, 2020, in Uganda. The number of cases increased to 8,287 by September 30, 2020. By May throughout June, most of the cases were predominantly imported cases of truck drivers from neighbouring countries. Uganda responded with various restrictions and interventions including lockdown, physical distancing, hand hygiene, and use of face masks in public, to control the growth rate of the outbreak. By end of September 2020, Uganda had transitioned into community transmissions and most of the reported cases were locals contacts and alerts. This study assessed risks associated with SARS-CoV-2 in Uganda, and presents estimates of the reproduction ratio in real time. An optimal control analysis was performed to determine how long the current mitigation measures such as controlling the exposure in communities, rapid detection, confirmation and contact tracing, partial lockdown of the vulnerable groups and control at the porous boarders, could be implemented and at what cost. Methods The daily confirmed cases of SARS-CoV-2 in Uganda were extracted from publicly available sources. Using the data, relative risks for age, gender, and geographical location were determined. Four approaches were used to forecast SARS-CoV-2 in Uganda namely linear exponential, nonlinear exponential, logistic and a deterministic model. The discrete logistic model and the next generation matrix method were used to estimate the effective reproduction number. Results Results: showed that women were at a higher risk of acquiring SARS-CoV-2 than the men, and the population attributable risk of SARS-CoV-2 to women was 42.22%. Most of the women affected by SARS-CoV-2 were likely contacts of cargo truck drivers at the boarders, where high infection rates were reported. Although most deaths in Uganda were in the age group of 60-69, the highest case fatality rate per 1000 was attributable the age group of 80-89, followed by 70-79. Geographically, Amuru had the highest relative risk compared to the national risk to SARS-CoV-2. For the case of mitigation scenarios, washing hands with 70% com pliance and regular hand washing of 6 times a day, was the most effective and sustainable to reduce SARS- CoV-2 exposure. This was followed by public wearing of face masks if at least 60% of the population complied, and physical distancing by 60% of the population. If schools, bars and churches were opened without compliance, i.e., no distancing, no handwashing and no public wearing of face masks, to mitigation measures, the highest incidence was observed, leading to a big replacement number. If mitigation measures are not followed by the population, then there will be high incidences and prevalence of the virus in the population.

Alternate primers for whole-genome SARS-CoV-2 sequencing (preprint)

As the world is struggling to control the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), there is an urgency to develop effective control measures. Essential information is encoded in the virus genome sequence with accurate and complete SARS-CoV-2 sequences essential for tracking the movement and evolution of the virus and for guiding efforts to develop vaccines and antiviral drugs. While there is unprecedented SARS-CoV-2 sequencing efforts globally, approximately 19 to 43% of the genomes generated monthly are gapped, reducing their information content. The current study documents the genome gap frequencies and their positions in the currently available data and provides an alternative primer set and a sequencing scheme to help improve the quality and coverage of the genomes.

Estimating the Effect and Cost-Effectiveness of Facemasks in Reducing the Spread of the Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) in Uganda (preprint)

Evidence that face masks provide effective protection against respiratory infections in the community is scarce. However, face masks are widely used by health workers as part of droplet precautions when caring for patients with respiratory infections. It would therefore be reasonable to suggest that consistent widespread use of face masks in the community could prevent further spread of the Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2). In this study we examine public face mask wearing in Uganda where a proportion wears masks to protect against acquiring, and the other to prevent from transmitting SARS-CoV-2. The objective of this study was to determine what percentage of the population would have to wear face masks to reduce susceptibility to and infectivity of COVID-19 in Uganda, keeping the basic reproduction number below unity and/or flattening the curve. We used an SEIAQRD model for the analysis. Results show that implementation of facemasks has a relatively large impact on the size of the coronavirus epidemic in Uganda. We find that the critical mask adherence is 5 per 100 when 80% wear face masks. A cost-effective analysis shows that utilizing funds to provide 1 public mask to the population has a per capita compounded cost of USD 1.34. If provision of face masks is done simultaneously with supportive care, the per capita compounded cost is USD 1.965, while for the case of only treatment and no provision of face masks costs each Ugandan USD 4.0579. We conclude that since it is hard to achieve a 100% adherence to face masks, government might consider provision of face masks in conjunction with provision of care.

Infodemic: How an Epidemic of Misinformation Could Lead to a High Number of the Novel Corona Virus Disease Cases in Uganda (preprint)

Misinformation during the COVID-19 outbreak has shaped our perception of the disease. Some people thinkthe disease is a bioweapon while others are convinced that it is a hoax. Heightened anxiety often producesfearful rumors, some of which are absurd while others seem plausible and are laced with some truths. But, how does misinformation affect disease spread? In this paper, we construct a mathematical model parameterized by Ugandan data, to study the effect of misinformation on community COVID-19 spread. The analysis shows that misinformation leads to high number of COVID-19 cases in a community, and the effect is highest in the rumour initiators and spreaders. This analysis underscores the importance of addressing misinformation in COVID risk communication.