Background On Dec 31, 2019, China reported a cluster of cases of pneumonia in people at Wuhan, Hubei Province. The responsible pathogen is a novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report the relevant features of the first cases in Europe of confirmed infection, named coronavirus disease 2019 (COVID-19), with the first patient diagnosed with the disease on Jan 24, 2020.Methods In this case series, we followed five patients admitted to Bichat-Claude Bernard University Hospital (Paris, France) and Pellegrin University Hospital (Bordeaux, France) and diagnosed with COVID-19 by semi-quantitative RT-PCR on nasopharyngeal swabs. We assessed patterns of clinical disease and viral load from different samples (nasopharyngeal and blood, urine, and stool samples), which were obtained once daily for 3 days from hospital admission, and once every 2 or 3 days until patient discharge. All samples were refrigerated and shipped to laboratories in the ), where RNA extraction, real-time RT-PCR, and virus isolation and titration procedures were done. Findings The patients were three men (aged 31 years, 48 years, and 80 years) and two women (aged 30 years and 46 years), all of Chinese origin, who had travelled to France from China around mid-January, 2020. Three different clinical evolutions are described: (1) two paucisymptomatic women diagnosed within a day of exhibiting symptoms, with high nasopharyngeal titres of SARS-CoV-2 within the first 24 h of the illness onset (5·2 and 7·4 log 10 copies per 1000 cells, respectively) and viral RNA detection in stools; (2) a two-step disease progression in two young men, with a secondary worsening around 10 days after disease onset despite a decreasing viral load in nasopharyngeal samples; and (3) an 80-year-old man with a rapid evolution towards multiple organ failure and a persistent high viral load in lower and upper respiratory tract with systemic virus dissemination and virus detection in plasma. The 80-year-old patient died on day 14 of illness (Feb 14, 2020); all other patients had recovered and been discharged by Feb 19, 2020.Interpretation We illustrated three different clinical and biological types of evolution in five patients infected with SARS-CoV-2 with detailed and comprehensive viral sampling strategy. We believe that these findings will contribute to a better understanding of the natural history of the disease and will contribute to advances in the implementation of more efficient infection control strategies.
ARS-CoV-2 variants have rapidly emerged in humans and supplanted ancestral strains [1][2][3][4][5] . Their proposed increased rates of interindividual transmission conferred a replication advantage at the population level. One of the first identified variants includes the D614G mutation in the gene encoding the spike (S) protein, which enhances viral infectivity and shifts S protein conformation toward an angiotensin-converting enzyme 2 (ACE2)-binding fusion-competent state, without significantly modifying sensitivity to antibody neutralization 1,6-8 . More recently, novel variants have appeared in multiple countries, with combinations of mutations and deletions in the receptor-binding domain (RBD) and N-terminal domain of S protein, as well as in other proteins. The B.1.1.7 variant emerged in the United Kingdom, the B.1.351 variant (also termed 501Y.V2) in South Africa and the P.1 and P.2 lineages in Brazil 2,3,5,9-12 . Although distinct, the variants share common characteristics, including known escape mutations that were previously identified under antibody pressure selection in vitro 2,3,[13][14][15][16][17] . Some of the mutations or deletions were also identified in immunocompromised individuals with prolonged infectious viral shedding and treated with convalescent plasma or S-protein Sensitivity of infectious SARS-CoV-2 B.1.1.7 and B.1.351 variants to neutralizing antibodies
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