Ineffectiveness of international travel restrictions to contain spread of the SARS-CoV-2 Omicron BA.1 variant: a continent-wide laboratory-based observational study from Africa (preprint)

Background: In mid-November 2021, the SARS-CoV-2 Omicron BA.1 variant was detected in Southern Africa, prompting international travel restrictions of unclear effectiveness that exacted a substantial economic toll. Methods: Amidst the BA.1 wave, we tested 13,294 COVID-19 patients in 24 African countries between mid-2021 to early 2022 for BA.1 and Delta variants using real-time reverse transcription-PCR tests. The diagnostic precision of the assays was evaluated by high-throughput sequencing in four countries. The observed BA.1 spread was compared to mobility-based mathematical simulations. Findings: By November-December 2021, BA.1 had replaced the Delta variant in all African sub-regions following a South-North gradient, with a median Rt of 2.4 up to 30 days before BA.1 became predominant. PCR-based South-North spread was in agreement with phylogeographic reconstructions relying on 939 SARS-CoV-2 genomes from GISAID. PCR-based reconstructions of country-level BA.1 predominance correlated significantly in time with the emergence of BA.1 genomic sequences on GISAID (p=0.0035, cor=0.70). First BA.1 detections in affluent settings beyond Africa were predicted adequately in time by mobility-based mathematical simulations (p<0.0001). BA.1-infected inbound travelers departing from five continents were identified in five Western countries and one Northern African country by late November/early December 2021, highlighting fast global BA.1 spread aided by international travel. Interpretation: Unilateral travel bans were poorly effective because by the time they came into effect, BA.1 was already widespread in Africa and beyond. PCR-based variant typing combined with mobility-based mathematical modelling can inform rapidly and cost-efficiently on Rt, spread to inform non-pharmaceutical interventions.

Impaired performance of SARS-CoV-2 antigen-detecting rapid tests at elevated temperatures (preprint)

Rapid antigen-detecting tests (Ag-RDTs) can complement molecular diagnostics for COVID-19. The recommended temperature for storage of SARS-CoV-2 Ag-RDTs ranges between 5-30°C. In many countries that would benefit from SARS-CoV-2 Ag-RDTs, mean temperatures exceed 30°C. We assessed analytical sensitivity and specificity of eleven commercially available SARS-CoV-2 Ag-RDTs using different storage and operational temperatures, including (i) long-term storage and testing at recommended conditions, (ii) recommended storage conditions followed by 10 minutes exposure to 37°C and testing at 37°C and (iii) 3 weeks storage followed by testing at 37°C. The limits of detection of SARS-CoV-2 Ag-RDTs under recommended conditions ranged from 8.2×10 5 -7.9×10 7 genome copies/ml of infectious SARS-CoV-2 cell culture supernatant. Despite long-term storage at recommended conditions, 10 minutes pre-incubation of Ag-RDTs and testing at 37°C resulted in about ten-fold reduced sensitivity for 46% of SARS-CoV-2 Ag-RDTs, including both Ag-RDTs currently listed for emergency use by the World Health Organization. After 3 weeks of storage at 37°C, 73% of SARS-CoV-2 Ag-RDTs exhibited about ten-fold reduced sensitivity. Specificity of SARS-CoV-2 Ag-RDTs using cell culture-derived human coronaviruses HCoV-229E and HCoV-OC43 was not affected by storage and testing at 37°C. In summary, short- and long-term exposure to elevated temperatures likely impairs sensitivity of several SARS-CoV-2 Ag-RDTs that may translate to false-negative test results at clinically relevant virus concentrations compatible with inter-individual transmission. Ensuring appropriate transport and storage conditions, and development of tests that are more robust across temperature fluctuations will be important for accurate use of SARS-CoV-2 Ag-RDTs in tropical settings.

Diagnostics and spread of SARS-CoV-2 in Western Africa: An observational laboratory-based study from Benin (preprint)

Information on severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spread in Africa is limited by fragile surveillance systems and insufficient diagnostic capacity. We assessed the coronavirus disease-19 (COVID-19)-related diagnostic workload in Benin, Western Africa, characterized SARS-CoV-2 genomes from 12 acute cases of COVID-19, used those together with public data to estimate SARS-CoV-2 transmission dynamics in a Bayesian framework, validated a widely used diagnostic dual target RT-PCR kit donated to African countries, and conducted serological analyses in 68 sera from confirmed COVID-19 cases and from febrile patients sampled before the predicted SARS-CoV-2 introduction. We found a 15-fold increase in the monthly laboratory workload due to COVID-19. Genomic surveillance showed introductions of three distinct SARS-CoV-2 lineages. SARS-CoV-2 genome-based analyses yielded an R0 estimate of 4.4 (95% confidence interval: 2.0-7.7), suggesting intense spread of SARS-CoV-2 in Africa. RT-PCR-based tests were highly sensitive but showed variation of internal controls and between diagnostic targets. Commercially available SARS-CoV-2 ELISAs showed up to 25% false-positive results depending on antigen and antibody types, likely due to unspecific antibody responses elicited by acute malaria according to lack of SARS-CoV-2-specific neutralizing antibody responses and relatively higher parasitemia in those sera. We confirm an overload of the diagnostic capacity in Benin and provide baseline information on the usability of genome-based surveillance in resource-limited settings. Sero-epidemiological studies needed to assess SARS-CoV-2 spread may be put at stake by low specificity of tests in tropical settings globally. The increasing diagnostic challenges demand continuous support of national and supranational African stakeholders. FundingThis work was supported by the Deutsche Gesellschaft fur Internationale Zusammenarbeit (GIZ) GmbH.