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Topics in Antiviral Medicine ; 30(1 SUPPL):101, 2022.
Article in English | EMBASE | ID: covidwho-1880973


Background: The emergence of new SARS-CoV-2 variants raises concerns whether preexisting artificial (vaccine-induced) and natural immunity from prior COVID-19 prevents re-infections. Here, we investigated the differences in primary humoral immune response following SARS-CoV-2 variants of concern (VOCs) infection and aimed to identify the key mutations involved in these differences. Methods: Patients with primary PCR-proven SARS-CoV-2 infection with no history of previous COVID-19 vaccination were included between October 2020 and May 2021 at Amsterdam UMC and via the Dutch SARS-CoV-2 sequence surveillance program. Serum was collected 4-8 weeks after symptom onset and tested for IgG binding and pseudovirus neutralization of the wild-type (WT, Wuhan/D614G), Alpha, Beta and Delta variants. Results: We included 51 COVID-19 patients, who were infected with the WT (n=20), Alpha (n=10), Beta (n=9) or Delta variant (n=12). Generally, the highest neutralization titers were against the autologous virus. After stratifying for hospitalization status, non-hospitalized patients infected with the WT (ID50 817) or Alpha (ID50 2524) variant showed the strongest geometric mean autologous neutralization, followed by the Delta variant (ID50 704) infected participants. By contrast, only one participant infected with the Beta variant showed strong autologous neutralization (median ID50 171). The VOCs also differed in their ability to induce cross-neutralizing responses, with WT-infected patients showing the broadest immune response, followed by Alpha, Delta and Beta infected participants. Additionally, participants infected with the WT, Alpha or Delta variant showed the lowest cross-neutralization against the Beta variant, with a median 5.0-fold (2 to 16-fold), 7.7-fold (2 to 32-fold), and 5.3-fold (1 to 19-fold) reduction compared to the autologous neutralization, respectively. We identified the E484K mutation as the key mutation responsible for this low cross-neutralization. Conclusion: We demonstrated that even small differences in the S protein influences the polyclonal antibody response following infection. The low level of (cross-)neutralization induced by the Beta variant may implicate a higher re-infection risk, but further research of the memory B cell compartment and clinical studies are needed. The broadest cross-neutralizing response observed for WT-infected patients suggests that artificial immunity induced by the current approved COVID-19 vaccines already protects against many re-infections.

Microbiol Spectr ; 9(3): e0088421, 2021 12 22.
Article in English | MEDLINE | ID: covidwho-1532978


This study evaluates the performance of the PanBio COVID-19 antigen (Ag) test as part of a hospital infection control policy. Hospital staff was encouraged to get tested for COVID-19 when presenting with SARS-CoV-2-related symptoms. In a period of approximately 5 months, a steady decline in the performance of the Ag test was noted, epidemiologically coinciding with the rise of the SARS-CoV-2 B.1.1.7 (alpha) variant of concern (VOC) in the Netherlands. This led to the hypothesis that the diagnostic performance of the PanBio COVID-19 Ag test was influenced by the infecting viral variant. The results show a significantly lower sensitivity of the PanBio COVID-19 Ag test in persons infected with the B.1.1.7 (alpha) variant of SARS-CoV-2 in comparison with that in persons infected with non-B.1.1.7 variants, also after adjustment for viral load. IMPORTANCE Antigen tests for COVID-19 are widely used for rapid identification of COVID-19 cases, for example, for access to schools, festivals, and travel. There are several FDA- and CE-cleared tests on the market. Their performance has been evaluated mainly on the basis of infections by the classical variant of the causing virus, SARS-CoV-2. This paper provides evidence that the performance of one of the most widely used antigen tests detects significantly fewer cases of COVID-19 by the alpha variant than by the classical variants of SARS-CoV-2. This means that the role of antigen tests needs to be reevaluated in regions where other variants of SARS-CoV-2 predominate.

Antigens, Viral/immunology , COVID-19 Serological Testing/methods , COVID-19/diagnosis , COVID-19/immunology , SARS-CoV-2/classification , Antibodies, Viral/analysis , Diagnostic Tests, Routine , Humans , Netherlands , SARS-CoV-2/isolation & purification , Sensitivity and Specificity , Viral Load
O'Toole, A.; Hill, V.; Pybus, O. G.; Watts, A.; Bogoch, II, Khan, K.; Messina, J. P.; consortium, Covid- Genomics UK, Network for Genomic Surveillance in South, Africa, Brazil, U. K. Cadde Genomic Network, Tegally, H.; Lessells, R. R.; Giandhari, J.; Pillay, S.; Tumedi, K. A.; Nyepetsi, G.; Kebabonye, M.; Matsheka, M.; Mine, M.; Tokajian, S.; Hassan, H.; Salloum, T.; Merhi, G.; Koweyes, J.; Geoghegan, J. L.; de Ligt, J.; Ren, X.; Storey, M.; Freed, N. E.; Pattabiraman, C.; Prasad, P.; Desai, A. S.; Vasanthapuram, R.; Schulz, T. F.; Steinbruck, L.; Stadler, T.; Swiss Viollier Sequencing, Consortium, Parisi, A.; Bianco, A.; Garcia de Viedma, D.; Buenestado-Serrano, S.; Borges, V.; Isidro, J.; Duarte, S.; Gomes, J. P.; Zuckerman, N. S.; Mandelboim, M.; Mor, O.; Seemann, T.; Arnott, A.; Draper, J.; Gall, M.; Rawlinson, W.; Deveson, I.; Schlebusch, S.; McMahon, J.; Leong, L.; Lim, C. K.; Chironna, M.; Loconsole, D.; Bal, A.; Josset, L.; Holmes, E.; St George, K.; Lasek-Nesselquist, E.; Sikkema, R. S.; Oude Munnink, B.; Koopmans, M.; Brytting, M.; Sudha Rani, V.; Pavani, S.; Smura, T.; Heim, A.; Kurkela, S.; Umair, M.; Salman, M.; Bartolini, B.; Rueca, M.; Drosten, C.; Wolff, T.; Silander, O.; Eggink, D.; Reusken, C.; Vennema, H.; Park, A.; Carrington, C.; Sahadeo, N.; Carr, M.; Gonzalez, G.; Diego, Search Alliance San, National Virus Reference, Laboratory, Seq, Covid Spain, Danish Covid-19 Genome, Consortium, Communicable Diseases Genomic, Network, Dutch National, Sars-CoV-surveillance program, Division of Emerging Infectious, Diseases, de Oliveira, T.; Faria, N.; Rambaut, A.; Kraemer, M. U. G..
Wellcome Open Research ; 6:121, 2021.
Article in English | MEDLINE | ID: covidwho-1259748


Late in 2020, two genetically-distinct clusters of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with mutations of biological concern were reported, one in the United Kingdom and one in South Africa. Using a combination of data from routine surveillance, genomic sequencing and international travel we track the international dispersal of lineages B.1.1.7 and B.1.351 (variant 501Y-V2). We account for potential biases in genomic surveillance efforts by including passenger volumes from location of where the lineage was first reported, London and South Africa respectively. Using the software tool grinch (global report investigating novel coronavirus haplotypes), we track the international spread of lineages of concern with automated daily reports, Further, we have built a custom tracking website ( which hosts this daily report and will continue to include novel SARS-CoV-2 lineages of concern as they are detected.