First article going to start off nerdy to make you think harder about what is going on with the virus. It would seem evolution for covid-19 is happening. Houston is the center of this evolution likely do to the International aspect of Houston. They believe Houston has seen two waves with the second wave being a different covid with more transmission and infectivity. There is a positive plug for remesdivir – but once again focus on effectiveness not overall cost effectiveness https://www.medrxiv.org/content/10.1101/2020.09.22.20199125v1.full.pdf
“We sequenced the genomes of 5,085 SARS-CoV-2 strains causing two COVID-19 disease waves in metropolitan Houston, Texas, an ethnically diverse region with seven million residents. The genomes were from viruses recovered in the earliest recognized phase of the pandemic in Houston, and an ongoing massive second wave of infections. The virus was originally introduced into Houston many times independently. Virtually all strains in the second wave have a Gly614 amino acid replacement in the spike protein, a polymorphism that has been linked to increased transmission and infectivity. Patients infected with the Gly614 variant strains had significantly higher virus loads in the nasopharynx on initial diagnosis. We found little evidence of a significant relationship between virus genotypes and altered virulence, stressing the linkage between disease severity, underlying medical conditions, and host genetics. ”
“There is concern about second and subsequent waves of
92 COVID-19 caused by the SARS-CoV-2 coronavirus occurring in
93 communities globally that had an initial disease wave. Metropolitan
94 Houston, Texas, with a population of 7 million, is experiencing a massive
95 second disease wave that began in late May 2020. To understand SARS96 CoV-2 molecular population genomic architecture, evolution, and
97 relationship between virus genotypes and patient features, we sequenced
98 the genomes of 5,085 SARS-CoV-2 strains from these two waves. Our study
99 provides the first molecular characterization of SARS-CoV-2 strains
100 causing two distinct COVID-19 disease waves.”
“patients in the second wave were significantly younger, had fewer comorbidities, were more likely to be Hispanic/Latino (by self-report), and lived in zip codes with lower median incomes”
“We discovered that the first COVID-19 wave was caused by a
441 heterogenous array of virus genotypes assigned to several different clades. The
442 majority of cases in the first wave are related to strains that caused widespread
443 disease in European and Asian countries, as well as other localities. We
444 conclude that the SARS-CoV-2 virus was introduced into Houston many times
445 independently, likely by individuals who had traveled to or from different parts of
446 the world, including other communities in the United States. In support of this
447 conclusion, the first cases in metropolitan Houston were associated with a travel
history to a known COVID-19 region (16). The data are consistent with the fact
449 that Houston is a large international city characterized by a multi-ethnic
450 population and is a prominent transport hub with direct flights to major cities
451 globally.”
“The second wave of COVID-19 cases also is characterized by SARS453 CoV-2 strains with diverse genotypes. Virtually all cases in the second and
454 ongoing disease wave were caused by strains with the Gly614 variant of spike
455 protein (Figure 1B). Our data unambiguously demonstrate that strains with the
456 Gly614 variant increased significantly in frequency in wave 2 relative to wave 1 in
457 the Houston metropolitan region. This shift occurred very rapidly in a matter of
458 just a few months. Amino acid residue Asp614 is located in subdomain 2 (SD-2)
459 of the spike protein and forms a hydrogen bond and electrostatic interaction with
460 two residues in the S2 subunit of a neighboring protomer. Replacement of
461 aspartate with glycine would eliminate both interactions, thereby substantively
462 weakening the contact between the S1 and S2 subunits”
“virus strains with the Gly614 variant
466 may be better able to enter host cells, potentially resulting in enhanced spread.
467 Consistent with this idea, Korber et al. (66) showed that the Gly614 variant grows
468 to higher titer as pseudotyped virions. On initial diagnosis infected individuals had
469 lower RT-PCR cycle thresholds suggesting higher upper respiratory tract viral
470 loads. Our data (Figure 7) are fully consistent with that finding Zhang et al”
“we identified a
496 correlation between Rh factor-positive blood type and increased mortality and
497 length of ICU stay. (Supplemental Table 3). Thus, our data are consistent with
498 studies suggesting that there are host genetic factors that contribute to disease
499 severity and outcome”
“84 SARS-CoV-2 isolates causing disease in patients in the New York
504 City region (11). Those investigators concluded that the vast majority of disease
505 was caused by progeny of strains imported from Europe. Similarly, Bedford et al.
506 (10) reported that much of the COVID-19 disease in the Seattle, Washington
507 area was caused by strains that are progeny of a virus strain recently introduced
508 from China. “
“Icelandic and Brazilian investigators
513 documented that SARS-CoV-2 was imported by individuals traveling to or from
514 many European and other countries”
“hypothesis is that patient genotypes play an important role
529 in determining virus-human interactions and resulting pathology”
“available data
531 suggest that in the aggregate, host genetics does not play an overwhelming role
532 in determining outcome in the great majority of adult patients, once virus infection
533 is established”
“Inasmuch as remdesivir is now
544 being deployed widely to treat COVID-19 patients in Houston and elsewhere, our
545 findings suggest that the majority of SARS-CoV-2 strains currently circulating in
546 our region should be susceptible to this drug”
“although the strain sample size is
628 relatively large compared to other studies, the sample represents only about 10%
629 of all COVID-19 cases in metropolitan Houston documented in the study period”
“Although the full array of factors contributing
646 to the massive second wave in Houston is not known, it is possible that the
647 potential for increased transmissibility of SARS-CoV-2 with the Gly614 may have
648 played a role, as well as changes in behavior associated with the Memorial Day
and July 4th 649 holidays, and relaxation of some of the social constraints imposed
650 during the first wave.”
So one thing glossed over which IF you were not engrossed in all the other issues as the authors may have not been but look at the PCR test results in Fig 7 – IF they continue to test the second wave like the first wave it is very possible to increase the false positives as the demonstrated the amount of cycle threshold is so much less! Not only do you have to adapt to potential treatment but you will likely need to adapt testing if there are changes in the genome of the virus – at least I would think as non-expert but as analytical person who looks at data all the time.
Discussing false positives – we see it does occur – https://www.oregonlive.com/coronavirus/2020/09/oregons-youngest-suspected-coronavirus-victim-26-did-not-have-covid-special-cdc-test-shows.html?outputType=amp&__twitter_impression=true
“A 26-year-old Oregonian initially identified as the state’s youngest COVID-19 fatality tested negative for coronavirus during a specialized screening by the Centers for Disease Control and Prevention, state officials and family members said Tuesday.
Matthew Stephen Irvin died July 10 at his apartment in Yamhill County after a sudden and severe illness. Irvin visited the hospital before his death and tested negative for coronavirus”
“Now, lung samples collected during a private autopsy and sent to the CDC for specialized testing have also come back negative, the state medical examiner’s office confirmed to The Oregonian/OregonLive.
“He did not have COVID,” Irvin’s stepfather, Mike Laheyne, told the newsroom”
US still below 1K – India leads death chart 1141
CA leads at 123
California may lead but its Miami-Dade taking the lead for all US counties at 39. Something is up in Miami-Dade for sure. Likely need to spend time figuring out why things are so out of hand there. They do have days of 0 reporting so likely this is causing some of this fluctuations.
Perhaps the mega jump in confirmation in Harris county is due to my concern above with the new variant causing false positives given threshold set high?
Added S. Korea to Europe watch chart – showing the massive difference which is discussed in WSJ – https://www.wsj.com/articles/lessons-from-south-korea-on-how-to-manage-covid-11601044329?mod=e2tw
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