Journal article

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Humoral Immune Response to SARS-CoV-2 in Iceland

Author(s): Gudbjartsson DF, Norddahl GL, Melsted P, et al

NEJM September 1, 2020

Respiratory infections
Epidemiology
General respiratory patient care
Public health

Digest Author(s): Stylianos Loukides, e-Learning Director / 6 September, 2020

Several published studies reported that the antibodies produced by our immune system against the new coronavirus were rapidly declining in either the milder or more severely COVID-19 patients. In addition, cases of asymptomatic individuals were reported who, while in contact with the virus, did not develop any antibodies. The above data raised some significant concerns mainly attributed to the way that we monitor the course of the pandemic.

The current data from a team of researchers in Iceland, published on 1 September in the New England Journal of Medicine, showed that molecular testing is important, but detects the virus only at the time of infection and only in the areas where the diagnostic material is collected. However, it is lacking significance in terms of long-term monitoring of coronavirus spread in the population. On the contrary, the evaluation of antibodies with special and sensitive tests during the pandemic, is the appropriate way to collect population data related to the exposure and spread of SARS-CoV-2, but also to understand the role of antibodies in the protective immunity and for the proper guidance of researchers towards the development of vaccines.

The researchers used six different antibody tests against different coronavirus proteins and measured specific anti-SARS-CoV-2 antibodies in about 30,000 people in Iceland, a country with a very low incidence (about 2,000) and just 10 deaths. Their aim was to assess seroprevalence in the population of Iceland, but also to record changes in antibody levels in the first 4 months after SARS-CoV-2 infection and how these changes are related to sex, age, specific phenotypes (eg body mass index, smoking, taking anti-inflammatory drugs) and symptoms of COVID-19. Interestingly by the middle of June, 15% of the population had already undergone molecular testing. The most reliable antibody tests from the 6 different ones used in the study were 2 that simultaneously measured all classes of immunoglobulins (IgG, IgM and IgA or pan-Ig). 91.2% of people who became ill and recovered (2,000 people) developed antibodies and their antibody titers increased in the first 2 months after infection and then remained stable. Of those in quarantine (approximately 4200 people), the antibody-positive rate was only 2.3%. Of those who were unaware if they were exposed to the virus only 0.3% developed detectable antibodies in their blood. Antibody levels were higher in the elderly and lower in women. People with higher body mass index also had higher levels of antibodies, while smokers and those taking anti-inflammatory drugs had much lower levels. Of those who tested positive for antibodies, only 56% were diagnosed positive by molecular testing, a result that shows that antibody tests recognize a higher proportion of people exposed to the coronavirus and reinforces the use of antibody tests to assess extent and monitoring of the pandemic. In addition, 14% of those who were quarantined and negative for molecular control were found to be antibody positive, and 30% of those who had neither a positive nor a quarantine molecular test. This result indicates that despite extensive molecular testing in Iceland, a significant proportion of coronavirus infections have not been detected. More than 90% of the molecularly confirmed infections that were sequentially measured for their antibody levels remained positive 4 months after the initial diagnosis, without even reducing their antibodies in their blood. These measurements were confirmed by 2 different tests that measure the total of antibodies produced (pan-Ig). Finally, the sampling time for antibody testing is of particular importance. If it occurs immediately after or near SARS-CoV-2 infection, a transient decrease in antibodies may be observed. A later sampling reflect the immune system response more properly.

One important comment:

The measurement of antibodies is important but simultaneously is affected by many parameters which are mainly attributed to the sampling time as well as to some of the demographic characteristics.