42 Matching Annotations
  1. Oct 2020
    1. For every one confirmed case, Redfield said, the CDC estimates that 10 more people have been infected.

      Take away: While this estimate may be the most accurate at the time there are several reasons (addressed below) why any estimate provided at this time may be imprecise. As more data is accrued, including information on the immunological dynamics of the SARS-CoV2 antibodies, we should expect to see a more accurate estimate.

      The claim: For every one confirmed case the CDC estimates that another 10 more people have been infected.

      The evidence: This estimate was revealed in a press briefing with CDC Director Robert Redfield on June, 25, 2020. It is important to emphasize that this is an estimate extrapolated from the collective data of numerous seroprevalence surveys (antibody tests) performed in different locations across the U.S. While it is most definitely true that the reported case numbers are lower than the actual, given the prevalence of asymptomatic individuals that do not visit medical centers to be tested, the actual figure may be lower or higher than the estimate presented here due to a variety of factors including:

      1) Areas surveyed: Indeed, it is known that the number of cases vary disproportionately across different areas of the U.S. According to the CDC, three types of seroprevalence surveys are commonly performed: large-scale geographic, community-level, and special populations. It is important to note that each survey may or may not be completely representative of the specific area yet alone the U.S. as a whole.

      2)Type of antibody testing: The FDA reported on the performance of numerous EUA authorized serology tests. The conclusion is that each test has varying levels of accuracy and confidence intervals. As the estimate provided by Redfield was most likely obtained from data derived from the specific test used at each individual surveillance site, the figure may be further skewed by the accuracy of each test.

      3)Origin of blood samples: The type of individuals from which the blood samples tested originated may have a significant effect on the Redfield’s estimate. For example, if certain surveillance sites are exclusively testing samples from sick patients, the estimate may be an overestimate as a population presenting COVID symptoms is more likely to test positive than a healthy-looking population. Therefore, a detailed characterization of the individuals from which the blood was obtained would be needed in order to uphold accuracy.

      4)Time of tests: As the advent of antibodies can occur a week or longer post-infection, individuals who have recently been infected may not have detectable levels of antibodies and may come up as false negatives. It is also possible for an individual to simply not produce enough antibodies to be detectable by a given serology test. Furthermore, a recent paper published in medrxiv suggests that certain antibodies have reduced titers within 50 days of symptom onset.

      Take away: While this estimate may be the most accurate at the time there are several reasons (addressed below) why any estimate provided at this time may be imprecise. As more data is accrued, including information on the immunological dynamics of the SARS-CoV2 antibodies, we should expect to see a more accurate estimate.

      The claim: For every one confirmed case the CDC estimates that another 10 more people have been infected.

      The evidence: This estimate was revealed in a press briefing with CDC Director Robert Redfield on June, 25, 2020. It is important to emphasize that this is an estimate extrapolated from the collective data of numerous seroprevalence surveys (antibody tests) performed in different locations across the U.S. While it is most definitely true that the reported case numbers are lower than the actual, given the prevalence of asymptomatic individuals that do not visit medical centers to be tested, the actual figure may be lower or higher than the estimate presented here due to a variety of factors including:

      1) Areas surveyed: Indeed, it is known that the number of cases vary disproportionately across different areas of the U.S. According to the CDC, three types of seroprevalence surveys are commonly performed: large-scale geographic, community-level, and special populations (1). It is important to note that each survey may or may not be completely representative of the specific area yet alone the U.S. as a whole.

      2)Type of antibody testing: The FDA reported on the performance of numerous EUA authorized serology tests (2). The conclusion is that each test has varying levels of accuracy and confidence intervals. As the estimate provided by Redfield was most likely obtained from data derived from the specific test used at each individual surveillance site, the figure may be further skewed by the accuracy of each test.

      3)Origin of blood samples: The type of individuals from which the blood samples tested originated may have a significant effect on the Redfield’s estimate. For example, if certain surveillance sites are exclusively testing samples from sick patients, the estimate may be an overestimate as a population presenting COVID symptoms is more likely to test positive than a healthy-looking population. Therefore, a detailed characterization of the individuals from which the blood was obtained would be needed in order to uphold accuracy.

      4)Time of tests: As the advent of antibodies can occur a week or longer post-infection, individuals who have recently been infected may not have detectable levels of antibodies and may come up as false negatives. It is also possible for an individual to simply not produce enough antibodies to be detectable by a given serology test. Furthermore, a recent paper published in medrxiv suggests that certain antibodies have reduced titers within 50 days of symptom onset (3).

      To conclude, while this estimate may be the most accurate at the time given the available data, many factors can affect the figure and, in some instances, more information is needed as it is unclear exactly how this number was obtained from the information provided in the press briefing.

      Sources: 1) https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/about-serology-surveillance.html

      2) https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/eua-authorized-serology-test-performance

      3) https://www.medrxiv.org/content/10.1101/2020.07.09.20148429v1

    1. Not so novel coronavirus?

      Take away: More research is needed before the conclusion can be reached that T-cells from common cold coronaviruses are protective against SARS-CoV-2.

      The claim: A significant part of the population may be immune to SARS-CoV-2 due to cross-reactivity to T-cells from HCo infections (“common cold viruses”).

      The evidence: T- cell cross reactivity between common cold coronaviruses and SARS-CoV-2 occurred in 20-50% of people not exposed to SARS-CoV-2 (1-4). This cross-reactivity from T-cells led to the speculative hypothesis that cross-reactivity explains why children and young adults are not affected as badly as older adults (1). Additional research is needed to conclude that the presence of cross-reactive T-cells leads to less severe COVID-19 disease and does not result in the cytokine storm which is harmful instead of helpful in recovery from COVID-19 (2, 4). Significant cross-reactivity between SARS-CoV-2 and HCo antibodies was not observed with 1064 serum samples when tested with ELISA (5). A small study found some cross-reactivity between SARS-CoV-2 and HCo using rapid immunochromatographic antibody test which tests the ability of antibodies to react with SARS-CoV-2 (6).

      The immune system uses multiple components to rid the body of an infection. Innate immunity includes inflammation, fever, and cells which non-specifically destroy infectious/toxic particles (7). The adaptive immune system includes cells which adapt to the specific pathogen it is attacking (8). The adaptive immune system includes B cells and T cells. B cells produce antibodies. Antibodies bind and neutralize toxins/infectious particles. T cells kill infected human cells which present antigens, infectious particle identifiers, which specific T cells recognize. A summary of the immune system's interaction with SARS-CoV-2 is written (9). Additional discussion can be found (10, 11).

      In conclusion, T-cell cross reactivity was shown to occur (1-4). More research is needed to conclusively determine whether the presence of HCo cross-reactive T-cells leads to prevention or less severe infection by SARS-CoV-2.

      Sources:

      1 https://www.nature.com/articles/s41577-020-0389-z

      2 https://www.cell.com/cell/fulltext/S0092-8674(20)30610-3?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867420306103%3Fshowall%3Dtrue

      3 https://pubmed.ncbi.nlm.nih.gov/32766111/

      4 https://www.nature.com/articles/s41586-020-2550-z

      5 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7417941/

      6 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7381928/

      7 https://www.ncbi.nlm.nih.gov/books/NBK26846/

      8 https://www.ncbi.nlm.nih.gov/books/NBK21070/

      9 https://www.cell.com/trends/pharmacological-sciences/pdf/S0165-6147(20)30130-9.pdf?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0165614720301309%3Fshowall%3Dtrue

      10 https://blogs.sciencemag.org/pipeline/archives/2020/07/07/more-on-t-cells-antibody-levels-and-our-ignorance

      11 https://twitter.com/EricTopol/status/1278400526716211200?s=20

    1. 33 staff members, and 12 patients

      dddddd

    2. auma nurse at the hospital.

      sssss

    3. Hospital policy requires testing all patients for the virus when they are admitted, and daily screening for symptoms thereafter, the

      what

    4. postpone taking the next step in the city’s reopening plan because an increasing share of tests have been coming back positive: 3.5 percent in the week ended Sept. 26, compared with 2.7 percent the week before.

      Broader impact on economy - college campuses, tourism.

    5. lack of regular and convenient testing for staff members without symptoms.

      Why wasn't more testing done?

  2. Sep 2020
    1. If you were infected with the novel coronavirus, a new study suggests that your immunity to the virus could decline within months.

      Take away: Waning antibodies don’t necessarily mean that immunity will also decrease, because other components of the immune system retain “memory” for an infection and can combat invaders even after antibody counts have gone down.

      The claim: “If you were infected with the novel coronavirus, a new study suggests that your immunity to the virus could decline within months.”

      The evidence: This study [1], along with others [2], does indeed show evidence for declining neutralizing antibodies within a few months after infection; however, antibody counts alone are not enough to predict whether a patient will have durable immunity to a virus. Neutralizing antibodies are generated by B cells, a type of immune cell that patrols the body looking for their molecular targets. Some B cells carry “memory,” a quality that allows them to respond quickly when they see a virus or pathogen that they have encountered before, which allows them to pump out large quantities of antibody rapidly to fight the infection [3]. It’s actually normal in many viral infections for antibody levels within the blood to wane over time; the real concern is whether there are enough memory B cells to generate new antibodies at a moment’s notice.

      In addition to B cells, a second type of immune cell known as a “T cell” is critical for predicting durable immunity. Like B cells, some T cells carry “memory” and can patrol the body for years looking for their targets. Some T cells play a role in helping B cells produce antibodies quickly, and other T cells can actually target the infection directly [4]. Studies have now shown that T cell responses can persist after SARS-CoV-2 infection, and some patients even have T cells that can react to SARS-CoV-2 due to “cross-reactivity,” likely from preexisting immunity from common cold viruses that share some characteristics of SARS-CoV-2. While this cross-reactivity does not guarantee immunity, the presence of robust B and T cell responses is important, and could be more predictive than presence of antibodies alone.

      This article, written by a two well-known immunologists and COVID-19 experts at Yale University, provides a nice summary of the data that puts these claims in context [6].

  3. Aug 2020
    1. Mateus, J., Grifoni, A., Tarke, A., Sidney, J., Ramirez, S. I., Dan, J. M., Burger, Z. C., Rawlings, S. A., Smith, D. M., Phillips, E., Mallal, S., Lammers, M., Rubiro, P., Quiambao, L., Sutherland, A., Yu, E. D., Antunes, R. da S., Greenbaum, J., Frazier, A., … Weiskopf, D. (2020). Selective and cross-reactive SARS-CoV-2 T cell epitopes in unexposed humans. Science. https://doi.org/10.1126/science.abd3871

    1. Corbett, K. S., Edwards, D. K., Leist, S. R., Abiona, O. M., Boyoglu-Barnum, S., Gillespie, R. A., Himansu, S., Schäfer, A., Ziwawo, C. T., DiPiazza, A. T., Dinnon, K. H., Elbashir, S. M., Shaw, C. A., Woods, A., Fritch, E. J., Martinez, D. R., Bock, K. W., Minai, M., Nagata, B. M., … Graham, B. S. (2020). SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen preparedness. Nature, 1–8. https://doi.org/10.1038/s41586-020-2622-0

    1. Consiglio, C. R., Cotugno, N., Sardh, F., Pou, C., Amodio, D., Zicari, S., Ruggiero, A., Pascucci, G. R., Rodriguez, L., Santilli, V., Tan, Z., Eriksson, D., Wang, J., Lakshmikanth, T., Marchesi, A., Lakshmikanth, T., Campana, A., Villani, A., Rossi, P., … Brodin, P. (2020). The Immunology of Multisystem Inflammatory Syndrome in Children with COVID-19. MedRxiv, 2020.07.08.20148353. https://doi.org/10.1101/2020.07.08.20148353

    1. Although public health officials have warned that the presence of antibodies does not guarantee immunity from the disease, the common perception that this is the case makes the issue of bogus tests nothing short of a matter of life and death.

      Take away: COVID-19 infections result in antibodies in almost all cases. These antibodies probably give immunity to future infection for at least some time, although how long is still not known.

      The claim: The presence of antibodies to SARS-CoV2 does not guarantee future immunity from future COVID-19 infection.

      The evidence: COVID-19 has not been present in the human population long enough to know how long immunity will last. There is some evidence to suggest that having COVID-19 typically leads to antibodies will provide at least some immunity to future infections. The vast majority (>90%) of serious (1-3) and mild (4,5) COVID-19 infections do result in the production of antibodies and it has been found that neutralizing antibodies provide immunity to reinfection in monkeys (6). We do not know how long immunity lasts. The best evidence is from the related coronavirus infections SARS and MERS. SARS and MERS infections result in antibodies that last for at least 1-3 years (7-9).

      Source:

      1. https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa344/5812996
      2. https://erj.ersjournals.com/content/early/2020/05/13/13993003.00763-2020.abstract
      3. https://www.nature.com/articles/s41591-020-0897-1)
      4. https://www.sciencedirect.com/science/article/pii/S2352396420302905
      5. https://www.medrxiv.org/content/10.1101/2020.07.11.20151324v1
      6. https://www.biorxiv.org/content/10.1101/2020.03.13.990226v2.abstract
      7. https://www.jimmunol.org/content/jimmunol/181/8/5490.full.pdf
      8. https://wwwnc.cdc.gov/eid/article/13/10/07-0576_article,
      9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5512479/
    1. Rodda, L. B., Netland, J., Shehata, L., Pruner, K. B., Morawski, P. M., Thouvenel, C., Takehara, K. K., Eggenberger, J., Hemann, E. A., Waterman, H. R., Fahning, M. L., Chen, Y., Rathe, J., Stokes, C., Wrenn, S., Fiala, B., Carter, L. P., Hamerman, J. A., King, N. P., … Pepper, M. (2020). Functional SARS-CoV-2-specific immune memory persists after mild COVID-19. MedRxiv, 2020.08.11.20171843. https://doi.org/10.1101/2020.08.11.20171843

    1. Bangaru, S., Ozorowski, G., Turner, H. L., Antanasijevic, A., Huang, D., Wang, X., Torres, J. L., Diedrich, J. K., Tian, J.-H., Portnoff, A. D., Patel, N., Massare, M. J., Yates, J. R., Nemazee, D., Paulson, J. C., Glenn, G., Smith, G., & Ward, A. B. (2020). Structural analysis of full-length SARS-CoV-2 spike protein from an advanced vaccine candidate. BioRxiv, 2020.08.06.234674. https://doi.org/10.1101/2020.08.06.234674

  4. Jul 2020
  5. Jun 2020
  6. Mar 2020
  7. Nov 2019
  8. Sep 2019