Les virus émérgents en République Démocratique du Congo : caractérisation de la réponse immunitaire humorale contre Ebola virus et le SARS-CoV-2

The frequency of Ebola virus outbreaks has been increasing since 2017, resulting in an increase in the number of known survivors treated with specific molecules and others not identified by response teams in an emergency setting of new viruses such as SARS-CoV-2.We have shown that people discharged after two RT-PCR tests could be Ebola patients who presented with a pauci-symptomatic form and who presented after the viraemic phase. We have also shown that the production of anti-Ebola antibodies in people treated with anti-Ebola molecules appears to be delayed and that antibody levels drop very rapidly over time. Contrary to official reports on the number of confirmed COVID-19 cases in the Democratic Republic of the Congo, we have reported a very wide spread of SARS-CoV-2 in Kinshasa following the first wave of the pandemic.This work, conducted in the context of emerging disease studies, demonstrates on the one hand the importance of serology for understanding the evolution of newly identified or previously known emerging diseases and, on the other, the importance to contibue with studies in survivors of Ebola virus disease to prevent relapse, which could be possible factors for disease emergenceLa fréquence des épidémies de la maladie à virus Ebola est de plus en plus élevée depuis 2017 avec comme conséquence l’augmentation du nombre des survivants connus et traités par des molécules spécifiques et d’autres non identifiés par des équipes de riposte dans un contexte d’émergence de nouveaux virus tel que le SARS-CoV-2.Nous avons démontré que des personnes déchargées après deux tests RT-PCR pourraient être des patients Ebola ayant présenté une forme pauci-symptomatique et qui se sont présentés après la phase virémique. Nous avons aussi démontré que la production des anticorps anti-Ebola chez des personnes traitées avec des molécules anti-Ebola semble être tardive et les taux d’anticorps déclinent très rapidement au fil du temps. Contrairement aux rapports officiels sur le nombre de cas confirmés de COVID-19 en RDC, nous avons rapporté une diffusion très grande du SARS-CoV-2 à Kinshasa après la première vague de la pandémie.Ces travaux réalisés dans le cadre des études sur les émergences montrent d’une part l’importance de la sérologie dans la compréhension de l’évolution des maladies nouvellement émergentes identifiées ou anciennement connues et d’autre part, l’importance de continuer des études chez des survivants de la maladie à virus Ebola pour prévenir des cas de relapse qui peuvent être des facteurs d’émergence potentiels

Evaluation of a surrogate virus neutralization test for high-throughput serosurveillance of SARS-CoV-2

High-throughput serological tests that can detect neutralizing antibodies against SARS-CoV-2 are desirable for serosurveillance and vaccine efficacy evaluation. Although the conventional neutralization test (cVNT) remains the gold standard to confirm the presence of neutralizing antibodies in sera, the test is too labour-intensive for massive screening programs and less reproducible as live virus and cell culture is involved. Here, we performed an independent evaluation of a commercially available surrogate virus neutralization test (sVNT, GenScript cPass™) that can be done without biosafety level 3 containment in less than 2 hours. When using the cVNT and a Luminex multiplex immunoassay (MIA) as reference, the sVNT obtained a sensitivity of 94% (CI 90-96%) on a panel of 317 immune sera that were obtained from hospitalized and mild COVID-19 cases from Belgium and a sensitivity of 89% (CI 81-93%) on a panel of 184 healthcare workers from the Democratic Republic of Congo. We also found strong antibody titer correlations (r(s)>0.8) among the different techniques used. In conclusion, our evaluation suggests that the sVNT could be a powerful tool to monitor/detect neutralising antibodies in cohort and population studies. The technique could be especially useful for vaccine evaluation studies in sub-Saharan Africa where the basic infrastructure to perform cVNTs is lacking

A Multidisciplinary Investigation of the First Chikungunya Virus Outbreak in Matadi in the Democratic Republic of the Congo

Early March 2019, health authorities of Matadi in the Democratic Republic of the Congo alerted a sudden increase in acute fever/arthralgia cases, prompting an outbreak investigation. We collected surveillance data, clinical data, and laboratory specimens from clinical suspects (for CHIKV-PCR/ELISA, malaria RDT), semi-structured interviews with patients/caregivers about perceptions and health seeking behavior, and mosquito sampling (adult/larvae) for CHIKV-PCR and estimation of infestation levels. The investigations confirmed a large CHIKV outbreak that lasted February–June 2019. The total caseload remained unknown due to a lack of systematic surveillance, but one of the two health zones of Matadi notified 2686 suspects. Of the clinical suspects we investigated (n = 220), 83.2% were CHIKV-PCR or IgM positive (acute infection). One patient had an isolated IgG-positive result (while PCR/IgM negative), suggestive of past infection. In total, 15% had acute CHIKV and malaria. Most adult mosquitoes and larvae (>95%) were Aedes albopictus. High infestation levels were noted. CHIKV was detected in 6/11 adult mosquito pools, and in 2/15 of the larvae pools. This latter and the fact that 2/6 of the CHIKV-positive adult pools contained only males suggests transovarial transmission. Interviews revealed that healthcare seeking shifted quickly toward the informal sector and self-medication. Caregivers reported difficulties to differentiate CHIKV, malaria, and other infectious diseases resulting in polypharmacy and high out-of-pocket expenditure. We confirmed a first major CHIKV outbreak in Matadi, with main vector Aedes albopictus. The health sector was ill-prepared for the information, surveillance, and treatment needs for such an explosive outbreak in a CHIKV-naïve population. Better surveillance systems (national level/sentinel sites) and point-of-care diagnostics for arboviruses are needed

Ebola Virus Transmission Initiated by Relapse of Systemic Ebola Virus Disease

During the 2018-2020 Ebola virus disease (EVD) outbreak in North Kivu province in the Democratic Republic of Congo, EVD was diagnosed in a patient who had received the recombinant vesicular stomatitis virus-based vaccine expressing a ZEBOV glycoprotein (rVSV-ZEBOV) (Merck). His treatment included an Ebola virus (EBOV)-specific monoclonal antibody (mAb114), and he recovered within 14 days. However, 6 months later, he presented again with severe EVD-like illness and EBOV viremia, and he died. We initiated epidemiologic and genomic investigations that showed that the patient had had a relapse of acute EVD that led to a transmission chain resulting in 91 cases across six health zones over 4 months. (Funded by the Bill and Melinda Gates Foundation and others.)