6 Matching Annotations
  1. Last 7 days
    1. He added that while it would not be possible to check every test to see whether there was active virus, the likelihood of false positive results could be reduced if scientists could work out where the cut-off point should be.

      Take Away: This is an incorrect usage of the term "false positive." A positive PCR test result from a recovered infection is a valid and true positive.

      Claim: PCR tests for SARS-CoV-2 give false positive results when there is no active virus.

      Evidence: The diagnostic PCR tests currently in widespread use are designed to detect the presence of the SARS-CoV-2 viral RNA in a clinical sample. The RNA is only a part of the complete virus and is not infectious on its own. Research has shown that viral RNA can be detected in some samples up to 12 weeks after onset of symptoms (1). In other words, this is like testing if an oven is warmer than the room temperature - it could be hot even after it has been turned off.

      By definition, in the context of SARS-CoV-2 PCR tests, a "false positive" means that a test result is deemed positive when in reality there was no viral RNA in the sample. If a person is recovering from an infection, gets tested, and then is given a positive test result, that is a true positive regardless of whether they are infectious or not.

      Sources: 1) https://www.cdc.gov/coronavirus/2019-ncov/hcp/duration-isolation.html

  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].

    1. Your Coronavirus Test Is Positive. Maybe It Shouldn’t Be.

      Take Away: Diagnostic tests are most useful when they are both sensitive and rapid. The sensitivity of SARS-CoV-2 PCR tests is not the issue, but rather the time it takes to get a result. Additionally, the "90%" statistic is likely misleading due to the data source and not generalisable to all testing results.

      The Claim: The usual PCR diagnostic tests may be too sensitive and too slow, with up to 90% of positive cases due to trace amounts of virus.

      The Evidence: Polymerase Chain Reaction (PCR)-based tests, which are currently in the most widespread use for detection of SARS-CoV-2 RNA, involves a molecular process that amplifies target DNA sequences in repeated temperature-dependent cycles. The amount of target DNA is measured after each cycle and the number of the cycle when the target can be reliably detected is often referred to as the cycle threshold (Ct). The Ct value is proportional to the amount of starting DNA in the sample and can be used to estimate the viral load of a patient. In some ways this is like a teacher making photocopies of a chapter from a textbook until they have enough for all their students.

      However, Ct values are relative measurements and need to be directly compared to controls for every sample - a Ct value taken alone can be meaningless. For instance, consider an infected patient who is tested twice: the first time they are gently swabbed and the sample is relatively dilute, the second time they are vigorously swabbed and the sample is relatively concentrated. The resulting Ct values could be drastically different. Therefore, Ct values need to be considered carefully in the proper context for making medical or policy decisions. The FDA also recommends that a PCR result alone should not be used to determine infection status.

      Positive results are indicative of the presence of SARS-CoV-2 RNA; clinical correlation with patient history and other diagnostic information is necessary to determine patient infection status. (1)

      Current PCR test results are generally given as a binary positive/negative based on a cutoff value for Ct. The cutoff needs to be determined based on the performance of each individually developed SARS-CoV-2 test, of which there are currently over 160 that have been granted emergency use authorization by the FDA (2). Based on unpublished data from the CDC, setting a stringent Ct cutoff of 30 could return negative results in patients who are both infected and potentially infectious (3 Fig 5). Furthermore, a 30 cycle cutoff would return invalid results for samples which are too diluted. Based on the same CDC data, up to 30% of potentially infectious patients would get invalid results and need to be re-swabbed, thereby extending the time between getting infected and getting a positive result.

      The period of time when RNA from SARS-CoV-2 can be detected (and a positive PCR test result returned) may extend up to 12 weeks after recovery, with Ct values trending higher over time (3,4). According to The New York Times article, they looked at Ct values from people who tested positive in Massachusetts in July and found 85-90% of results had Ct values greater than 30. The epidemiology of COVID-19 is highly time and region dependent. Massachusetts had a peak in COVID-19 hospitalizations on April 21 (5), which is 9-12 weeks prior to the testing data analyzed by The NY Times. Therefore, the detection of a large proportion of people with lingering viral RNA is not surprising. These results are likely not universal and can not be applied to other regions, especially where community spread is still significant.

      Sources:

      (1) https://www.fda.gov/media/135900/download

      (2) https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/vitro-diagnostics-euas

      (3) https://www.cdc.gov/coronavirus/2019-ncov/hcp/duration-isolation.html

      (4) Li N, Wang X, Lv T. Prolonged SARS-CoV-2 RNA Shedding: Not a Rare Phenomenon. J Med Virol 2020 Apr 29. doi: 10.1002/jmv.25952.

      (5) https://www.bostonherald.com/2020/05/22/massachusetts-finally-seeing-downward-coronavirus-trends/

  3. Aug 2020
    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. Asymptomatic spread of coronavirus is ‘very rare,’ WHO says

      Take away: Dr. Van Kerkhove appeared to refer to only “asymptomatic” individuals and not “presymptomatic” individuals in her statement. Clarification from the WHO, and public availability of the data leading to the claim, is needed for proper interpretation. At the current time, existing published data indicates that a significant amount of SARS-CoV-2 infections are due to individuals who did not have symptoms when they spread the virus.

      The claim: According to the WHO, asymptomatic spread of coronavirus is ‘very rare’.

      The evidence: This statement is attributed to WHO official Dr. Maria Van Kerkhove during a recent news conference. It deserves greater clarification from the WHO, but Dr. Van Kerkhove appears to make the distinction between “asymptomatic” and “pre-symptomatic” individuals during her comments. This distinction is essential for proper interpretation of her statement. “Asymptomatic” refers to persons who test positive, but who never display symptoms throughout the course of their SARS-CoV-2 infection. In contrast, “presymptomatic” individuals are those with confirmed infection, who do not currently display symptoms, but later go on to develop COVID-19 related symptoms (fever, cough, loss of taste/smell, etc).

      Importantly, the distinction between asymptomatic and presymptomatic can only be made retrospectively. From a clinical standpoint, if someone currently has no symptoms, but tests positive, there is no way of knowing at that time if they are “asymptomatic” or “presymptomatic”. Preliminary data estimates that around 20% of SARS-CoV-2 infections are truly “asymptomatic”.

      If “asymptomatic” individuals were rarely involved in transmission of the virus, this would be an important finding, but from a practical standpoint if “presymptomatic” individuals still spread the virus (as the data indicates), then the rationale for preventative measures still stands. Early studies [1] [2] have estimated that up to 40-60% of virus spread occurs when people don’t have symptoms. Preventative measures such as social distancing and universal mask wearing have been implemented to prevent the spread of virus from individuals not currently demonstrating symptoms.

  4. Jul 2020
    1. The vaccine uses messenger RNA (mRNA), which are cells used to build proteins -- in this case, the proteins that are needed to build the coronavirus' spike protein, which the virus uses to attach itself to and infect human cells. Once the immune system learns to recognize this target -- thanks to the vaccine -- it can mount a response faster than if it encountered the virus for the first time due to an infection.

      This explanation is garbled and misstated. Genetic material is stored in DNA in the nucleus of the cell. Messenger RNA (mRNA) molecules carry the information stored within the DNA to the rest of the cell. Both DNA and RNA are a type of molecule called a "nucleic acid." Once outside the nucleus, the information in the messenger RNA can then be read, or "translated," to create proteins, such as the spike protein used by SARS-CoV-2. These proteins in turn carry out a wide variety of tasks that allow cells to function. This process is known as the "Central Dogma of Molecular Biology".