Tuesday, June 2, 2020

What do Covid-19 tests tell us?

To understand what various tests for Covid-19 mean, you must first accept one important fact: medical tests are not perfect. Even the most accurate tests we have at our disposal may say that someone has a disease when they do not (a “false positive”) or that they do not have the disease when they do (“false negative”). All tests must be interpreted together with the clinical findings and the likelihood of someone having the disease in question.

Let’s look at how Covid-19 is diagnosed. The “gold standard” is detection of the virus’ RNA in specimens from the respiratory tract of a sick person. These tests go by the highfalutin label of “reverse transcriptase-polymerase chain reaction” or RT-PCR, and this describes a technique by which the presence of viral RNA is measured and quantified. This technique can be used on any specimen, but the earliest and still most common specimen has been a swab taken from the very back of the nasal passage. It has also been used on sputum (spit), throat culture, stool samples and even semen.

In most people who develop symptoms of Covid-19, viral RNA becomes detectable in the nasopharyngeal swab as early as day 1 of symptoms and in over 98% within the first week. Detection falls off after week 3, though positive tests have been reported as late as six weeks after symptoms begin. Tests for Covid-19 RNA in the stool and semen have also been found positive long after patients recover. It appears that late tests often do NOT indicate that the person is still contagious, and that they may simply be shedding decayed viral remnants.

The RT-PCR is highly accurate when positive. False negative tests do occur because of technical problems: the specimen may have not been taken properly or not transported properly to the lab, or there may have been a problem with the way the test was conducted.

The other type of test about which you will read is the antibody test. When we are exposed to an infectious agent (or a vaccine), our immune system gears up to fight it off by producing proteins called antibodies that both directly fight the infectious agent and call in various cells to do the same. It takes time for antibodies to be produced, so they are unlikely to be found very early in an illness. In the case of Covid-19, some antibodies have been found as early as 4 days into symptoms, but it is generally in week 2 or 3 that they are reliably found. First to appear are a group called IgM antibodies, that fall off by week 6, while IgG antibodies appear slightly later but persist, for months or years.

Antibodies are commonly measured in blood samples and provide proof of prior exposure to an infectious agent. In many, but not all, cases, presence of antibodies indicates at least some immunity to the agent against which they are targeted. The degree to which the presence of antibodies means immunity to the disease varies a lot. If you have measles antibodies, you are safe, but that is less true for whooping cough or for the coronaviruses that cause the common cold. We simply do not yet know if antibodies against Covid-19 will protect one from re-infection. It is clearly premature to use these tests to offer “immune passports.”

The other major problem with current Covid-19 antibody tests is that many of the tests now available are far from reliable. Many were rushed to market with limited testing and have a high number of both false positives and false negatives. Remember that Covid-19 is one of a group of coronaviruses, many of which cause the common cold, and a poorly designed antibody test may simply be detecting a prior exposure to one of these other viruses.

Bottom line: until we have more consistently reliable antibody tests, and until we know if the presence of antibodies is a reliable way to guarantee immunity to re-infection, I would not be in a hurry to get tested.

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