SARS-CoV-2 Antibody Responses to AZD1222 Vaccination in West Africa (preprint)

There is a paucity of real-world data on vaccine elicited neutralising antibody responses for AZD1222, in African populations following vaccination scale up. Here, we first measured baseline SARS-CoV-2 seroprevalence and levels of protective neutralizing antibodies prior to vaccination rollout using both flow cytometric based analysis of binding antibodies coupled with pseudotyped virus neutralisation assays in two study cohorts from West Africa: Nigerian healthcare workers; (n = 140) and a Ghanaian general community cohort (n = 527). We found that 44% and 28% of pre-vaccination participants showed IgG anti-N positivity, increasing to 59% and 42% respectively with anti-receptor binding dominan (RBD) IgG specific antibodies. The increased prevalence of prior exposure using anti RBD antibodies was corroborated by Pseudotyped virus (PV) neutralizing antibody assays, indicating that overall, 50% of prior infections were missed by N antibody testing. PV titres (serum dilution required to inhibit 50% of infection, ID50) against wild type following 2-dose vaccination regimen were [145 (4.5) to 2579 (4.2) vs 57 (3.0) to 1049 (6.7)] (GMT ± s.d), delta [75 (3.0) to 549 (3.7) vs 37 (2.4) to 453 (7.4)] (GMT ± s.d) and omicron variants [37 (2.4) to 453 (7.4) vs 29 (1.8) to 95 (5.3)] (GMT ± s.d) in the Nigerian (1 month) vs Ghanaian participants (2 months) post vaccination (total n = 94). Previous IgG anti-N was associated with significantly higher neutralizing antibody levels with an observed 3.5-fold [1423 (3.9) vs 4674 (3.4)] (GMT ± s.d) and 2.7-fold [779 (7.1) vs 2128 (4.8) (GMT ± s.d) difference between N positive and negative participants in the Nigerian and Ghanaian cohorts respectively. We also observed serological evidence from N, S and RBD antibodies of breakthrough infection in 8/49 (16%) of Nigerian vaccinees over only 2 months, with neutralisation profiles suggesting delta variant infection consistent with the sampling period when this variant was known to dominate. Importantly, neutralising antibodies waned at 3 months after second dose vs 1 month post second-dose 1695 (4.3)] vs 2579 (4.2) in the Nigerian population who were N negative throughout. IgG anti-N was also observed to wane below cut-off in a total 19/94 (20%) of subjects highlighting the need for a combination of additional markers to characterise previous infection. We conclude that AZD1222 is immunogenic in two independent real world West African cohorts with high background seroprevalence and incidence of breakthrough infection in 2021. Waning titres at 6 months post second dose indicates the need for booster dosing after AZD1222 in the African setting despite hybrid immunity from previous infection.

Tracking genetic diversity of SARS-CoV-2 infections in Ghana after one year of surveillance (preprint)

This study sequenced 1077 SARS-CoV-2 genomes from patient isolates (106 from arriving travellers and 971 from communities) to track the molecular evolution and spatio-temporal dynamics of the SARS-CoV-2 variants in Ghana. The data show that initial local transmission was dominated by B.1.1 lineages, but the second wave in Ghana was overwhelmingly driven by the Alpha variant, which was detected in community cases from January 2021, with Eta also contributing to reported cases. Subsequently, an unheralded variant under monitoring, B.1.1.318, dominated transmission from April to June 2021 before being displaced by Delta (B.1.1.617) and Delta Plus (AY.*) variants, which were introduced into community transmission in May 2021 and have remained dominant to date. Mutational analysis indicated that variants that took hold in Ghana harboured transmission enhancing and immune escape spike substitutions. The apparent rapid viral evolution observed demonstrate the potential for emergence of novel variants with greater mutational fitness.

Transmission of SARS-CoV-2 in Northern Ghana; Insights from Whole Genome Sequencing (preprint)

In regions lacking genomic data, analysis of sequences from the early stages of an outbreak can provide important insights into the diversity of pathogens present. Following the detection of the first imported case of COVID-19 in the Northern sector of Ghana on 13th March 2020, we have now molecularly characterized and phylogenetically analysed sequences including three (3) complete genomes of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) isolated from nine (9) patients observed in Ghana. Eight (8) of these patients reported with a recent history of foreign travel and one (1) with no history of foreign travel. We performed high throughput sequencing for 9 samples following the determination of high concentration of viral RNA. In addition, we estimated the potential impact that long distance transportation of samples to testing centres may have on sequencing outcomes. Here, two samples that were closest in terms of viral RNA concentration but transported from sites which are over 400km apart were assessed. All sequences were compared to previous sequences from Ghana and representative sequences from regions where our patients had previously travelled. Complete genomes were obtained for three (3) sequences and with another near complete genome with a coverage of 95.6%. Sequences with coverage in excess of 80% were found to belong to three lineages namely A, B.1 and B.2. Our sequences clustered in two different clades with the majority falling within a clade composed of sequences from sub-Saharan Africa. Less RNA fragmentation was seen in sample KATH23 which was collected 9km compared with sample TTH6 which was collected and transported over a distance of 400km to the testing site. The clustering of several sequences from sub-Saharan Africa suggests regional circulation of the viruses in the subregion. Importantly, there may be the need to decentralize testing sites and build more capacity across Africa to boost the sequencing output of the subregion.