Query: D614G COVID-19

title: Isolation and Full Length Genome Characterization of SARS CoV 2 from COVID 19 Cases in Northern Italy
abstract: In December 2019, the novel coronavirus Severe Acquired Respiratory Syndrome SARS CoV 2 emerged in the city of Wuhan in the Hubei province, People's Republic of China, as the etiologic agent of coronavirus disease 2019 (COVID 19) which has hence spread worldwide causing a global pandemic (1 3)

title: Global Spread of SARS CoV 2 Subtype with Spike Protein Mutation D614G is Shaped by Human Genomic Variations that Regulate Expression of TMPRSS2 and MX1 Genes
abstract: COVID 19 pandemic is a major human tragedy. Worldwide, SARS CoV 2 has already infected over 3 million and has killed about 230,000 people. SARS CoV 2 originated in China and, within three months, has evolved to an additional 10 subtypes. One particular subtype with a non silent (Aspartate to Glycine) mutation at 614th position of the Spike protein (D614G) rapidly outcompeted other pre existing subtypes, including the ancestral. We assessed that D614G mutation generates an additional serine protease (Elastase) cleavage site near the S1 S2 junction of the Spike protein. We also identified that a single nucleotide deletion (delC) at a known variant site (rs35074065) in a cis eQTL of TMPRSS2, is extremely rare in East Asians but is common in Europeans and North Americans. The delC allele facilitates entry of the 614G subtype into host cells, thus accelerating the spread of 614G subtype in Europe and North America where the delC allele is common. The delC allele at the cis eQTL locus rs35074065 of TMPRSS2 leads to overexpression of both TMPRSS2 and a nearby gene MX1. The cis eQTL site, rs35074065 overlaps with a transcription factor binding site of an activator (IRF1) and a repressor (IRF2) IRF1 activator can bind to variant delC allele, but IRF2 repressor fails to bind. Thus, in an individual carrying the delC allele, there is only activation, but no repression. On viral entry, IRF1 mediated upregulation of MX1 leads to neutrophil infiltration and processing of 614G mutated Spike protein by neutrophil Elastase. The simultaneous processing of 614G spike protein by TMPRSS2 and Elastase serine proteases facilitates the entry of the 614G subtype into host cells. Thus, SARS CoV 2, particularly the 614G subtype, has spread more easily and with higher frequency to Europe and North America where the delC allele regulating expression of TMPRSS2 and MX1 host proteins is common, but not to East Asia where this allele is rare.

title: Interim Analysis of Pandemic Coronavirus Disease 2019 (COVID 19) and the SARS CoV 2 virus in Latin America and the Caribbean: Morbidity, Mortality and Molecular Testing Trends in the Region
abstract: The relentless advance of the SARS CoV 2 virus pandemic has resulted in a significant burden on countries, regardless of their socio economic conditions. The virus has infected more than 2.5 million people worldwide, causing to date more than 150,000 deaths in over 210 countries.  The aim of this study was to describe the trends in cases, tests and deaths related to novel coronavirus disease (COVID 19) in Latin American and Caribbean (LAC) countries.  Data were retrieved from the WHO Coronavirus Disease (COVID 2019) situation reports and the Center for Systems Science and Engineering (CSSE) databases from Johns Hopkins University. Descriptive statistics including death rates, cumulative mortality and incidence rates, as well as testing rates per population at risk were performed. A comparison analysis among countries with ]50 confirmed cases was performed from February 26th, 2020 to April 8th, 2020.  Brazil had the greatest number of cases and deaths in the region. Panama experienced a rapid increase in the number of confirmed cases with Trinidad and Tobago, Bolivia and Honduras having the highest case fatality rates. Panama and Chile conducted more tests per million inhabitants and more tests per day per million inhabitants, followed by Uruguay and El Salvador. Dominican Republic, Bolivia, Ecuador and Brazil had the highest positive test rates.  The COVID 19 disease pandemic caused by the SARS CoV 2 virus has progressed rapidly in LAC countries. Some countries have been affected more severely than others, with some adopting similar disease control methods to help slow down the spread of the virus. With limited testing and other resources, social distancing is needed to help alleviate the strain on already stretched health systems.

title: Genome Organization of Covid 19 and Emerging Severe Acute Respiratory Syndrome Covid 19 Outbreak: A Pandemic
abstract: DOI: 10.14744/ejmo.2020.96781 EJMO 2020;4(2):107 115

title: Treatment of COVID 19 Patients with Convalescent Plasma in Houston, Texas
abstract: COVID 19 disease, caused by severe acute respiratory syndrome coronavirus 2 (SARS CoV 2) has spread globally, and no proven treatments are available. Convalescent plasma therapy has been used with varying degrees of success to treat severe microbial infections for more than 100 years.  Patients (n=25) with severe and/or life threatening COVID 19 disease were enrolled at the Houston Methodist hospitals from March 28 to April 14, 2020. Patients were transfused with convalescent plasma obtained from donors with confirmed SARS CoV 2 infection and had been symptom free for 14 days. The primary study outcome was safety, and the secondary outcome was clinical status at day 14 post transfusion. Clinical improvement was assessed based on a modified World Health Organization 6 point ordinal scale and laboratory parameters. Viral genome sequencing was performed on donor and recipient strains.  At baseline, all patients were receiving supportive care, including anti inflammatory and anti viral treatments, and all patients were on oxygen support. At day 7 post transfusion with convalescent plasma, nine patients had at least a 1 point improvement in clinical scale, and seven of those were discharged. By day 14 post transfusion, 19 (76% patients had at least a 1 point improvement in clinical status and 11 were discharged. No adverse events as a result of plasma transfusion were observed. The whole genome sequencing data did not identify a strain genotype disease severity correlation.  The data indicate that administration of convalescent plasma is a safe treatment option for those with severe COVID 19 disease. Randomized, controlled trials are needed to determine its efficacy.

title: Decoding SARS CoV 2 Transmission and Evolution and Ramifications for COVID 19 Diagnosis, Vaccine, and Medicine
abstract: Tremendous effort has been given to the development of diagnostic tests, preventive vaccines, and therapeutic medicines for coronavirus disease 2019 (COVID 19) caused by severe acute respiratory syndrome coronavirus 2 (SARS CoV 2) Much of this development has been based on the reference genome collected on January 5, 2020. Based on the genotyping of 15 140 genome samples collected up to June 1, 2020, we report that SARS CoV 2 has undergone 8309 single mutations which can be clustered into six subtypes. We introduce mutation ratio and mutation h index to characterize the protein conservativeness and unveil that SARS CoV 2 envelope protein, main protease, and endoribonuclease protein are relatively conservative, while SARS CoV 2 nucleocapsid protein, spike protein, and papain like protease are relatively nonconservative. In particular, we have identified mutations on 40% of nucleotides in the nucleocapsid gene in the population level, signaling potential impacts on the ongoing development of COVID 19 diagnosis, vaccines, and antibody and small molecular drugs.

title: Near Complete Genome Sequence of a 2019 Novel Coronavirus (SARS CoV 2) Strain Causing a COVID 19 Case in Peru
abstract: A near complete genome sequence was obtained for a novel coronavirus (SARS CoV 2) strain obtained from an oropharyngeal swab from a Peruvian patient with coronavirus syndrome (COVID 19) who had contact with an individual who had returned to Peru from travel to Italy.  A near complete genome sequence was obtained for a novel coronavirus (SARS CoV 2) strain obtained from an oropharyngeal swab from a Peruvian patient with coronavirus syndrome (COVID 19) who had contact with an individual who had returned to Peru from travel to Italy.

title: A pneumonia outbreak associated with a new coronavirus of probable bat origin
abstract: Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS related coronaviruses (SARSr CoVs) have been discovered in their natural reservoir host, bats 1 4 Previous studies have shown that some bat SARSr CoVs have the potential to infect humans 5 7 Here we report the identification and characterization of a new coronavirus (2019 nCoV) which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory confirmed infections including 80 deaths by 26 January 2020. Full length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS CoV. Furthermore, we show that 2019 nCoV is 96% identical at the whole genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non structural proteins domains show that this virus belongs to the species of SARSr CoV In addition, 2019 nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019 nCoV uses the same cell entry receptor angiotensin converting enzyme II (ACE2) as SARS CoV. Characterization of full length genome sequences from patients infected with a new coronavirus (2019 nCoV) shows that the sequences are nearly identical and indicates that the virus is related to a bat coronavirus.

title: A new coronavirus associated with human respiratory disease in China
abstract: Emerging infectious diseases, such as severe acute respiratory syndrome (SARS) and Zika virus disease, present a major threat to public health 1 3 Despite intense research efforts, how, when and where new diseases appear are still a source of considerable uncertainty. A severe respiratory disease was recently reported in Wuhan, Hubei province, China. As of 25 January 2020, at least 1,975 cases had been reported since the first patient was hospitalized on 12 December 2019. Epidemiological investigations have suggested that the outbreak was associated with a seafood market in Wuhan. Here we study a single patient who was a worker at the market and who was admitted to the Central Hospital of Wuhan on 26 December 2019 while experiencing a severe respiratory syndrome that included fever, dizziness and a cough. Metagenomic RNA sequencing 4 of a sample of bronchoalveolar lavage fluid from the patient identified a new RNA virus strain from the family Coronaviridae which is designated here 'WH Human 1' coronavirus (and has also been referred to as '2019 nCoV' Phylogenetic analysis of the complete viral genome (29,903 nucleotides) revealed that the virus was most closely related (89.1% nucleotide similarity) to a group of SARS like coronaviruses (genus Betacoronavirus, subgenus Sarbecovirus) that had previously been found in bats in China 5 This outbreak highlights the ongoing ability of viral spill over from animals to cause severe disease in humans. Phylogenetic and metagenomic analyses of the complete viral genome of a new coronavirus from the family Coronaviridae reveal that the virus is closely related to a group of SARS like coronaviruses found in bats in China.

title: Defining the Pandemic at the State Level: Sequence Based Epidemiology of the SARS CoV 2 virus by the Arizona COVID 19 Genomics Union (ACGU)
abstract: In December of 2019, a novel coronavirus, SARS CoV 2, emerged in the city of Wuhan, China causing severe morbidity and mortality. Since then, the virus has swept across the globe causing millions of confirmed infections and hundreds of thousands of deaths. To better understand the nature of the pandemic and the introduction and spread of the virus in Arizona, we sequenced viral genomes from clinical samples tested at the TGen North Clinical Laboratory, provided to us by the Arizona Department of Health Services, and at Arizona State University and the University of Arizona, collected as part of community surveillance projects. Phylogenetic analysis of 79 genomes we generated from across Arizona revealed a minimum of 9 distinct introductions throughout February and March. We show that >80% of our sequences descend from clades that were initially circulating widely in Europe but have since dominated the outbreak in the United States. In addition, we show that the first reported case of community transmission in Arizona descended from the Washington state outbreak that was discovered in late February. Notably, none of the observed transmission clusters are epidemiologically linked to the original travel related cases in the state, suggesting successful early isolation and quarantine. Finally, we use molecular clock analyses to demonstrate a lack of identifiable, widespread cryptic transmission in Arizona prior to the middle of February 2020.