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1.
Emerging Microbes & Infections ; : 1-31, 2022.
Article in English | MEDLINE | ID: covidwho-2028961

ABSTRACT

Omicron variant is circulating in the presence of a globally acquired immunity unlike the ancestral SARS-CoV-2 isolate. Herein, we investigated the normalized viral load dynamics and viral culture status in 44 fully vaccinated healthcare workers (HCWs) infected with the Omicron BA.1 variant. Viral load dynamics of 38 unvaccinated HCWs infected with the 20A variant during the first pandemic wave was also studied. We then explored the impact of Omicron infection on pre-existing immunity assessing anti-RBD IgG levels, neutralising antibody titres against 19A, Delta and Omicron isolates, as well as IFN-gamma release following cell stimulation with SARS-CoV-2 peptides. We reported that, throughout the follow-up, Omicron viral load decreased faster than that of 20A. We found that Omicron breakthrough infections led to an overall enhancement of vaccine-induced humoral and cellular immunity as soon as a median [interquartile range] of 8 [7-9] days post symptom onset. Among samples with similar high viral loads, non-culturable samples exhibited higher neutralising antibody titres and anti-RBD IgG levels than culturable samples. Additionally, Omicron infection led to an enhancement of antibodies neutralisation capacity against other SARS-CoV-2 isolates. Taken together, the results suggest that Omicron BA.1 vaccine breakthrough infection is associated with a faster viral clearance than that of the ancestral SARS-CoV-2, in addition this new variant leads to a rapid enhancement of the humoral response against multiple SARS-CoV-2 variants, and of the cellular response.

2.
Peer Community Journal ; 1(e45), 2021.
Article in English | CAB Abstracts | ID: covidwho-1893604

ABSTRACT

France was one of the first countries to be reached by the COVID-19 pandemic. Here, we analyse 196 SARS-Cov-2 genomes collected between Jan 24 and Mar 24 2020, and perform a phylodynamics analysis. In particular, we analyse the doubling time, reproduction number (Rt) and infection duration associated with the epidemic wave that was detected in incidence data starting from Feb 27. Different models suggest a slowing down of the epidemic in Mar, which would be consistent with the implementation of the national lock-down on Mar 17. The inferred distributions for the effective infection duration and Rt are in line with those estimated from contact tracing data. Finally, based on the available sequence data, we estimate that the French epidemic wave originated between mid-Jan and early Feb. Overall, this analysis shows the potential to use sequence genomic data to inform public health decisions in an epidemic crisis context and calls for further analyses with denser sampling.

3.
Embase; 2022.
Preprint in English | EMBASE | ID: ppcovidwho-338202

ABSTRACT

After monoclonal antibody sotrovimab implementation, Rockett et al have warned on March 9th about two resistant mutations in the spike at position 337 and 340 occurring within the first week in four immunocompromised patients infected by a Delta variant and resulting in viable infection up to 25 days. As sotrovimab is currently the only effective treatment against BA.1 lineage of Omicron variant, we investigated the presence of these mutations in our 22,908 Omicron sequences performed from December 2021 to March 2022. Among 25 Omicron sequences with S:337 and S:340 substitutions, 9 were reported in six patients who had available clinical data and a follow up. All were immunicompromised, and presented a rapid selection of these mutations after sotrovimab monotherapy infusion. With these findings, we underscore that although these mutations are rare, they have been exclusively reported in immunocompromised patients treated with sotrovimab. We urge to consider monoclonal antibody as monotherapy in immunocompromised patients as a risk for escape mutants selection.

4.
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-1450989

ABSTRACT

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 (cov-lineages.org/global_report.html) which hosts this daily report and will continue to include novel SARS-CoV-2 lineages of concern as they are detected.

5.
Virologie ; 25(SUPPL 1), 2021.
Article in English | EMBASE | ID: covidwho-1256144

ABSTRACT

While the SARS-CoV-2 genome has remained relatively stable since its emergence, genomic deletions are a frequently described evolutionary pattern of previous coronaviruses with significant impacts on outbreaks. This was the case in with both the SARS and MERS epidemics and has also recently been described with the massive surveillance of the SARS-CoV-2 genome since its emergence. During routine molecular surveillance of SARS-CoV-2 performed at the National Reference Center of Respiratory Viruses (Lyon, France) (n=229 sequences collected Feb-April 2020), two frameshifting deletions were detected in the open reading frame 6, starting at the same position (27267). While a 26-nucleotide deletion variant (D26) was only found in one nasopharyngeal sample in March 2020, the 34-nucleotide deletion variant D34) was found within a single geriatric hospital unit in 5/9 patients and one health care worker in April 2020. Phylogeny analysis strongly suggested a nosocomial transmission between patients for D34, with potential fecal transmission, as D34 was also identified in a stool sample. No difference in disease severity was observed within the patients hospitalized in the geriatric unit and infected with WT (n=4) or D34 (n=5). In vitro characterization of D26 and D34 revealed comparable replication kinetics with the wild-type (WT), but differential host immune responses. While interferon-stimulated genes were similarly upregulated after infection withWTand ORF6 deletion variants, the latter specifically induced overexpression of 9 genes coding for inflammatory cytokines in the NF-kB pathway, including CCL2/MCP1, PTX3, and TNF, for which high plasma levels of these cytokines have been associated with severe Covid-19. Given the heterogeneous clinical manifestations of Covid-19 and the growing global prevelance of certain SARS-CoV-2 variants, our findings emphasize the need to monitor the occurrence of ORF6 deletions and assess their impact on the host immune response.

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