ABSTRACT
The levels of immune response to SARS-CoV-2 infection or vaccination are poorly understood in African populations and is complicated by cross-reactivity to endemic pathogens as well as differences in host responsiveness. To begin to determine the best approach to minimize false positive antibody levels to SARS-CoV-2 in an African population, we evaluated three commercial assays, namely Bio-Rad Platelia SARS-CoV-2 Total Antibody (Platelia), Quanterix Simoa Semi-Quantitative SARS-CoV-2 IgG Antibody Test (anti-Spike), and the GenScript cPass™ SARS-CoV-2 Neutralization Antibody Detection Kit (cPass) using samples collected in Mali in West Africa prior to the emergence of SARS-CoV-2. A total of one hundred samples were assayed. The samples were categorized in two groups based on the presence or absence of clinical malaria. Overall, thirteen out of one hundred (13/100) samples were false positives with the Bio-Rad Platelia assay and one of the same one hundred (1/100) was a false positive with the anti-Spike IgG Quanterix assay. None of the samples tested with the GenScript cPass assay were positive. False positives were more common in the clinical malaria group, 10/50 (20%) vs. the non-malaria group 3/50 (6%); p = 0.0374 using the Bio-Rad Platelia assay. Association between false positive results and parasitemia by Bio-Rad remained evident, after adjusting for age and sex in multivariate analyses. In summary, the impact of clinical malaria on assay performance appears to depend on the assay and/or antigen being used. A careful evaluation of any given assay in the local context is a prerequisite for reliable serological assessment of anti-SARS-CoV-2 humoral immunity.
Subject(s)
COVID-19 , SARS-CoV-2 , Humans , COVID-19/diagnosis , Antibodies, Viral , Biological Assay , Black People , Sensitivity and SpecificityABSTRACT
Background: Emergence of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants may contribute to prolonging the pandemic and increasing morbidity, and mortality related to coronavirus disease 2019 (COVID-19). We describe the dynamics of circulating SARS-CoV-2 variants identified during the different COVID-19 waves that occurred in Mali between April 2021 and October 2021. Methods: We sequenced respiratory SARS-CoV-2 complete spike (S) gene from positive samples. Generated sequences were aligned by Variant Reporter v3.0 using Wuhan-1 strain as a reference. Mutations were noted using the GISAID and Nextclade platforms. Results: Of 16,797 nasopharyngeal swab samples tested, 6.0 % (1008/16,797) were RT-qPCR positive for SARS-CoV-2. Of these, 16.07% (162/1008) had a Ct value ≤ 28 and were amplified and sequenced. We recovered complete S-gene sequence from 80 of 162 [49.8%] samples. We identified seven distinct variants including Delta [62.5%], Alpha [1.2%], Beta [1.2%], Eta [30.0%], 20B [2.5%], 19B and 20A [1.2% each]. Conclusion and perspectives: Our results show the presence of several SARS-CoV-2 variants during COVID-19 waves in Mali between April and October 2021. The continued emergence of new variants highlights the need to strengthen local real-time sequencing capacity, and genomic surveillance for better and coordinated national responses to SARS-CoV-2.
ABSTRACT
The currently devastating pandemic of severe acute respiratory syndrome known as coronavirus disease 2019 or COVID-19 is caused by the coronavirus SARS-CoV-2. Both the virus and the disease have been extensively studied worldwide. A trimeric spike (S) protein expressed on the virus outer bilayer leaflet has been identified as a ligand that allows the virus to penetrate human host cells and cause infection. Its receptor-binding domain (RBD) interacts with the angiotensin-converting enzyme 2 (ACE2), the host-cell viral receptor, and is, therefore, the subject of intense research for the development of virus control means, particularly vaccines. In this work, we search for smaller fragments of the S protein able to elicit virus-neutralizing antibodies, suitable for production by peptide synthesis technology. Based on the analysis of available data, we selected a 72 aa long receptor binding motif (RBM436-507) of RBD. We used ELISA to study the antibody response to each of the three antigens (S protein, its RBD domain and the RBM436-507 synthetic peptide) in humans exposed to the infection and in immunized mice. The seroreactivity analysis showed that anti-RBM antibodies are produced in COVID-19 patients and immunized mice and may exert neutralizing function, although with a frequency lower than anti-S and -RBD. These results provide a basis for further studies towards the development of vaccines or treatments focused on specific regions of the S virus protein, which can benefit from the absence of folding problems, conformational constraints and other advantages of the peptide synthesis production.
Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Antibodies, Viral , Humans , Mice , Peptides , Spike Glycoprotein, CoronavirusABSTRACT
The currently devastating pandemic of severe acute respiratory syndrome known as coronavirus disease 2019 or COVID-19 is caused by the coronavirus SARS-CoV-2. Both the virus and the disease have been extensively studied worldwide. A trimeric spike (S) protein expressed on the virus outer bilayer leaflet has been identified as a ligand that allows the virus to penetrate human host cells and cause infection. Its receptor-binding domain (RBD) interacts with the angiotensin-converting enzyme 2 (ACE2), the host-cell viral receptor, and is, therefore, the subject of intense research for the development of virus control means, particularly vaccines. In this work, we search for smaller fragments of the S protein able to elicit virus-neutralizing antibodies, suitable for production by peptide synthesis technology. Based on the analysis of available data, we selected a 72 aa long receptor binding motif (RBM436-507) of RBD. We used ELISA to study the antibody response to each of the three antigens (S protein, its RBD domain and the RBM436-507 synthetic peptide) in humans exposed to the infection and in immunized mice. The seroreactivity analysis showed that anti-RBM antibodies are produced in COVID-19 patients and immunized mice and may exert neutralizing function, although with a frequency lower than anti-S and -RBD. These results provide a basis for further studies towards the development of vaccines or treatments focused on specific regions of the S virus protein, which can benefit from the absence of folding problems, conformational constraints and other advantages of the peptide synthesis production.
ABSTRACT
Despite the global interest and the unprecedented number of scientific studies triggered by the COVID-19 pandemic, few data are available from developing and low-income countries. In these regions, communities live under the threat of various transmissible diseases aside from COVID-19, including malaria. This study aims to determine the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroreactivity of antibodies from COVID-19 and pre-COVID-19 samples of individuals in Mali (West Africa). Blood samples from COVID-19 patients (n = 266) at Bamako Dermatology Hospital (HDB) and pre-COVID-19 donors (n = 283) from a previous malaria survey conducted in Dangassa village were tested by ELISA to assess IgG antibodies specific to the full-length spike (S) protein, the receptor-binding domain (RBD), and the receptor-binding motif (RBM436-507). Study participants were categorized by age, gender, treatment duration for COVID-19, and comorbidities. In addition, the cross-seroreactivity of samples from pre-COVID-19, malaria-positive patients against the three antigens was assessed. Recognition of the SARS-CoV-2 proteins by sera from COVID-19 patients was 80.5% for S, 71.1% for RBD, and 31.9% for RBM (p < 0.001). While antibody responses to S and RBD tended to be age-dependent, responses to RBM were not. Responses were not gender-dependent for any of the antigens. Higher antibody levels to S, RBD, and RBM at hospital entry were associated with shorter treatment durations, particularly for RBD (p < 0.01). In contrast, higher body weights negatively influenced the anti-S antibody response, and asthma and diabetes weakened the anti-RBM antibody responses. Although lower, a significant cross-reactive antibody response to S (21.9%), RBD (6.7%), and RBM (8.8%) was detected in the pre-COVID-19 and malaria samples. Cross-reactive antibody responses to RBM were mostly associated (p < 0.01) with the absence of current Plasmodium falciparum infection, warranting further study.
Subject(s)
COVID-19 , Malaria , Antibodies, Viral , Humans , Malaria/epidemiology , Mali , Pandemics , SARS-CoV-2ABSTRACT
Mali, like the rest of the world, has seen a rapid spread of COVID-19 since the first report of imported cases. Despite being a low-income country, Mali has leveraged scientific research resources via coordinated approaches to enable public health emergency planning and response to the COVID-19 pandemic. Mali's approach includes the harmonization of research activities; leveraging of research laboratory capacity of the University Clinical Research Center, Mali International Center for Excellence and three other in-country laboratories for community COVID-19 testing; strengthening relationships amongst local and international stakeholders; and collaboration with the Ministry of Health to integrate scientific evidence into public policy and emergency management of COVID-19 through a platform of consultation and open communication. The country has implemented national coordination of its COVID-19 response by establishing a COVID-19 Scientific Advisory Committee and a COVID-19 Technical Coordination Committee, both within the Ministry of Health and working collaboratively with other stakeholders. Members of Mali's COVID-19 Scientific Advisory Committee also serve as leaders of its principal academic and government clinical and public health research entities. This centralised approach has enabled the prioritisation of COVID-19 control activities, informed allocation of resources, evidence-based public health practices and timely decision-making in the pandemic setting. Though challenges remain, lessons learned from Mali's harnessing of clinical research capacity to guide and support its COVID-19 response can be applied to future global health research challenges and illustrate the power of building public health-responsive research capacity in resource-limited settings through international collaboration.