Reemergent Cases of COVID-19 - Xinfadi Wholesales Market, Beijing Municipality, China, June 11, 2020.
01 Jul 2020-Vol. 2, Iss: 27, pp 502-504
TL;DR: The genome sequences of these Xinfadi strains provide strong evidence that the reemergent of COVID-19 cases in Beijing may be caused by an imported source of infections, suggesting that it is not continuous transmission of the local CO VID-19 virus strain.
Abstract: No new local coronavirus disease 2019 (COVID19) cases were reported in Beijing for over 56 days before the reemergent COVID-19 cases that were reported on June 11, 2020, and more than 200 confirmed cases have been reported as of June 20 in Beijing. All confirmed COVID-19 cases were associated with Xinfadi Wholesale Market. Here, we reported the phylogenetic characteristics of the COVID-19 viruses (also known as severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, and human coronavirus 2019, HCoV-19) sequenced from the clinical specimens of 2 human cases and 1 environmental sample. We conducted whole-genome sequencing of COVID-19 viruses using the Illumina NextSeq 550 platform. A total of 3 whole genomes of COVID-19 virus were submitted to GISAID website and these sequences were named as nCoV Beijing IVDC-001 (EPI_ ISL_469254, from the first confirmed case in a 53-year-old male), -002 (EPI_ ISL_469255, from another confirmed case in a 25-year-old male), -003 (EPI_ ISL_469256, from environmental sample), respectively. These genomes (Beijing Xinfadi strains) showed 99.96%–99.97% nucleic acid identity to the reference strain hCoV-19/Wuhan/IVDC-HB-01/2019| EPI_ISL_402119|2019-12-30 that was isolated from Wuhan on January 7, 2020 (1). A total of 7 nucleotide variations were identified among the 3 whole genomes of Xinfadi strains, including C241T, C3037T, C14408T, A23403G, G28881A, G28882A, and G28883C, which were consistent with the characteristics of Branch 1 of the L-lineage from Europe (Figure 1) and different from the previous pandemic COVID-19 virus in Wuhan (Dec-2019) and Beijing (Feb-2020), which belong to the S-lineage (2). Additional genetic variations were also identified among these Xinfadi strains including the C6026T mutation in all 3 genomes of the virus, C12085T and A29694C in nCoV Beijing IVDC-001 and A11910G, A29694C, and G29868A in nCoV Beijing IVDC-003. Among them, C6026T (P1291S), C14408T (P4715L), A23403G (D614G), and the GGG mutated to AAC at position 28881–28883 (R203K, R203R, G204R), caused amino acid substitutions that were located on ORF 1ab (6026, 14408), S protein (23403), and N protein (28881–28883), respectively. Some amino acid mutations (ORF1ab: P1291S, P4715L; S: D614G; N: R203K, G204R) in the COVID-19 virus may change its biological characteristics significantly. For example, the D614G mutation of the COVID-19 S protein caused by A23403G may increase the ability of the virus to infect cells (3). The genome sequences of these Xinfadi strains provide strong evidence that the reemergent of COVID-19 cases in Beijing may be caused by an imported source of infections, suggesting that it is not continuous transmission of the local COVID-19 virus strain. It is worth noting that these Xinfadi strains have high homology with several genomes from the recently imported COVID-19 cases in northeastern China (Shulan strain, Heilongjiang strains) (4–5) that also belong to Branch 1 of L-lineage from Europe (Figure 1). Furthermore, the whole genome sequence analysis of the COVID-19 virus further confirmed that the source of the virus in this outbreak did not spread from natural animal hosts or intermediate animal hosts to humans. COVID-19 cases are associated with the Xinfadi Wholesale Market, the virus could be transmitted from person to person via the respiratory tract or direct contact of the contaminated environment at market. The source of the virus needed to be further determined based on epidemiological, serological, and etiological monitoring. Fundings: This work was supported by the National Key Research and Development Program of China (2016YFD0500301, 2020YFC0840900). doi: 10.46234/ccdcw2020.132 Corresponding authors: Wenjie Tan, tanwj@ivdc.chinacdc.cn; Huang Chun, huangch@bjcdc.org; Wenbo Xu, xuwb@ivdc.chinacdc.cn; Guizhen Wu, wugz@ivdc.chinacdc.cn. China CDC Weekly
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References
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TL;DR: The phylogenetic analysis suggests that bats might be the original host of this virus, an animal sold at the seafood market in Wuhan might represent an intermediate host facilitating the emergence of the virus in humans.
9,474 citations
TL;DR: The results suggest that the development of new variations in functional sites in the receptor-binding domain (RBD) of the spike seen in SARS-CoV-2 and viruses from pangolin SARSr-CoVs are likely caused by natural selection besides recombination.
Abstract: The SARS-CoV-2 epidemic started in late December 2019 in Wuhan, China, and has since impacted a large portion of China and raised major global concern. Herein, we investigated the extent of molecular divergence between SARS-CoV-2 and other related coronaviruses. Although we found only 4% variability in genomic nucleotides between SARS-CoV-2 and a bat SARS-related coronavirus (SARSr-CoV; RaTG13), the difference at neutral sites was 17%, suggesting the divergence between the two viruses is much larger than previously estimated. Our results suggest that the development of new variations in functional sites in the receptor-binding domain (RBD) of the spike seen in SARS-CoV-2 and viruses from pangolin SARSr-CoVs are likely caused by natural selection besides recombination. Population genetic analyses of 103 SARS-CoV-2 genomes indicated that these viruses had two major lineages (designated L and S), that are well defined by two different SNPs that show nearly complete linkage across the viral strains sequenced to date. We found that L lineage was more prevalent than the S lineage within the limited patient samples we examined. The implication of these evolutionary changes on disease etiology remains unclear. These findings strongly underscores the urgent need for further comprehensive studies that combine viral genomic data, with epidemiological studies of coronavirus disease 2019 (COVID-19).
1,369 citations
TL;DR: Functional evidence that the D614G mutation in the Spike protein increases transduction of human cells is provided and the G614 variant is more resistant to cleavage in vitro and in human cells, which may suggest a possible mechanism for the increased transduction.
Abstract: Recently, a novel isolate of the SARS-CoV-2 virus carrying a point mutation in the Spike protein (D614G) has emerged and rapidly surpassed others in prevalence, including the original SARS-CoV-2 isolate from Wuhan, China. This Spike variant is a defining feature of the most prevalent clade (A2a) of SARS-CoV-2 genomes worldwide. Using phylogenomic data, several groups have proposed that the D614G variant may confer increased transmissibility leading to positive selection, while others have claimed that currently available evidence does not support positive selection. Furthermore, in the A2a clade, this mutation is in linkage disequilibrium with a ORF1b protein variant (P314L), making it difficult to discern the functional significance of the Spike D614G mutation from population genetics alone. Here, we perform site-directed mutagenesis on a human codon-optimized spike protein to introduce the D614G variant and produce SARS-CoV-2-pseudotyped lentiviral particles (S-Virus) with this variant and with D614 Spike. We show that in multiple cell lines, including human lung epithelial cells, that S-Virus carrying the D614G mutation is up to 8-fold more effective at transducing cells than wild-type S-Virus. This provides functional evidence that the D614G mutation in the Spike protein increases transduction of human cells. Further we show that the G614 variant is more resistant to cleavage in vitro and in human cells, which may suggest a possible mechanism for the increased transduction. Given that several vaccines in development and in clinical trials are based on the initial (D614) Spike sequence, this result has important implications for the efficacy of these vaccines in protecting against this recent and highly-prevalent SARS-CoV-2 isolate.
122 citations
01 Jun 2020
TL;DR: Wang et al. as mentioned in this paper used real-time reverse transcription-polymerase chain reaction (real-time RT-PCR) targeting the ORF 1ab and N genes of COVID-19 virus of the throat swab was positive.
Abstract: As of February 22, a total of 198 confirmed COVID-19 cases were reported in Harbin, Heilongjiang Province, and no new local cases were reported in Harbin over the next 54 days (1). However, on April 9, a newly confirmed COVID-19 case was reported with an unknown source of infection (2). The patient, a 54-year-old male, developed a fever on March 28 with the highest recorded temperature at 37.5 °C. On April 7, the symptoms worsened and included dyspnea, cough, sputum, chest pain, and other symptoms, though he did not experience chest distress, heart palpitations, nausea and vomiting, abdominal pain or diarrhea. He went to the fever clinic of the Harbin Second Hospital and was admitted to the isolation ward with a temperature of 37.2°C. The patient also had a history of diabetes. The results of a routine blood examination were normal (WBC 5.15×109/L; lymphocyte 1.66×109/L, lymphocyte percentage 32.3%; neutrophil percentage 51.9%, c-reactive protein 36.56 mg/L). Chest computed tomography (CT) showed multiple lymph node shadows in the mediastinum and multiple lamellar ground glass density shadows and mesh shadows in both lungs. On April 7, the throat swabs of the patients were tested by Harbin CDC by using realtime reverse transcription-polymerase chain reaction (real-time RT-PCR) targeting the ORF 1ab and N genes of COVID-19 virus, and the results showed that the nucleic acid of COVID-19 virus of the throat swab was positive. On April 8, Harbin CDC tested his pharyngeal swabs, blood, urine and stool samples again. COVID-19 nucleic acids were detected, but the test for serum antibodies for COVID-19 was negative. The National Institute for Viral Disease Control and Prevention (IVDC) of China CDC conducted wholegenome sequencing analysis on a pharyngeal swab sample of the patient, which showed 99.97% nucleic acid similarity to the reference strain EPI_ISL_402119, which was isolated from Wuhan on January 7, 2020. There was a total of eight nucleotide mutations between them. This strain possessed the nucleotide mutations C241T, C1059T, C3037T, C14408T, A23403G, and G25563T, which were consistent with the characteristics of the North American branch of the L lineage from Europe (Figure 1) (3). In addition, sequence alignment also revealed two mutations C26636T and C27213T in the virus genome from this patient. Among them, C1059T, C14408T, A23403G, and G25563T caused amino acid substitutions, which were located on 5’-UTR, ORF1ab, S protein, and ORF3a, respectively. This means that despite amino acid mutations in the virus, its biological characteristics, including its ability to bind to its receptor have not changed significantly. Epidemiological investigations showed that the patient had no travel, residence, or stay history in Wuhan City and surrounding areas or other communities with confirmed COVID-19 case 14 days before the onset of disease (March 14–March 28). There was no contact with people with fever or respiratory symptoms from Wuhan City and surrounding areas nor from communities with confirmed case reports, nor did the patient have a history of overseas travel. However, because this patient did not seek medical treatment and isolation immediately after the onset of fever, he still had normal social activities including holding a dinner party. Due to the prevalence of asymptomatic COVID-19 infection, epidemiological investigation and virus tracking surrounding this case became more challenging. Although the local transmission of the COVID-19 virus in the mainland of China had been interrupted, COVID-19 is still an epidemic in many other countries. Many cases of COVID-19 and asymptomatic infections entering China through airports and land ports have been detected (4). Therefore, it is necessary to strengthen COVID-19 surveillance in respiratory tract and stool China CDC Weekly
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