Chicago serum prevalence studies show that COVID-19 cases are 16 times higher than currently predicted

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pathogen-induced cases of globally reported coronavirus disease 2019 (COVID-19) are significantly less common than in reality. Evidence is accumulating. A surprising new case study in Chicago, led by a team of researchers at Northwestern University in Illinois, USA, suggests that the incidence of SARS-CoV-2 infection is 16 times higher than previously thought. This is determined not by the number of RT-PCR positives reported there, but by the serum prevalence (antibody presence blood test) (via a swab sample test of symptomatological patients).

This study emphasizes the importance of using a convenient and sensitive self-collecting sampling method that can provide a quantitative assessment of community antibody titers, even at low titers.

Serological testing of antibodies is important in many respects in the current COVID-19 pandemic. It may not only help assess the magnitude of population exposure to pathogens, but may also make it possible to measure immunity levels by understanding the prevalence and titers of antibodies in the community. .. However, the test method and the viral antigen from which the antibody is produced may differ, and their use will result in different estimates of seropositive.

Chicago-April 4, 2020: A Chicago theater building passed by a man wearing a mask during a coronavirus pandemic. Image Credit: iwonder TV / Shutterstock.

The team reported the findings on a preprint server medRxiv* November 2020.

Dry blood spot serology

Currently, most antibody tests are based on blood or serum tests. However, this depends on the availability of healthcare centers and the skilled workers who manage them. Therefore, such studies may be biased from the beginning. Another option is to use point-of-care assays based on lateral flow devices, which are not as sensitive or specific as laboratory assays.

A current screening (SCAN) study of coronavirus antibodies in the neighborhood evaluated serum prevalence as measured from dry blood spots (DBS) from finger stings. This method has previously been validated with qualitative measurements of anti-RBD IgG using ELISA.

COVID-19 Collection card dry blood spot for IgG / IgM antibody screening. Image Credit: Marc Bruxelle / Shutterstock

Researchers used a dry blood spot (DBS) assay to quantitatively measure the presence of anti-spiked receptor-binding domain (RBD) antibodies against SARS-CoV-2 in more than 1,500 individuals. Participants were enrolled through online advertising (813) or medical school (730 staff, faculty, and non-treatment staff).

The latter group included both mandatory workers (people working outside the home) and non-essential workers (people working at home) during the first blockade in early 2020. Bloodstains were in card form and could be mailed or mailed. I dropped in at the test center directly.

20% serum positive

Researchers found that about one-fifth of the samples tested showed anti-RBD IgG antibodies. Serum positivity was approximately 23% between the ages of 18-29 and 40-49, and approximately 18-19% between the ages of 30-39 and 50-59. However, it was the lowest among those over 60 years old, about 13%.

The rate of detection was similar between samples mailed or returned directly. Serum prevalence was similar between mandatory and non-essential workers, and between men and women.

Testing began from late June 2020 to the first week of September 2020, after home orders were partially relaxed. The importance of comparable seropositive estimates between mandatory and non-essential workers was a study when some shelter-in-place orders had already been relaxed.

Quantitative measurement of IgG directed at the receptor binding domain of SARSCoV-2 spike glycoprotein. Samples were taken through a nearby coronavirus antibody screening (SCAN) between June 24, 2020 and September 6, 2020 (n = 1545). A) Overlapping IgG range in community-infected SCAN serum-positive samples (light purple) and unhospitalized COVID-19 + serum-positive samples (dark purple, far right). B) 19.8% of SCAN samples (306 of 1545) were serum positive, with a median IgG concentration of 0.62 µg / ml SCAN in the serum positive group. The median concentration of the seronegative SCAN group was 0.11 µg / ml. For comparison, the range of IgG detected in 96 unhospitalized COVID-19 and 22 ICU-hospitalized patients who tested positive for SARS-CoV-2 virus nucleic acids is shown. The median IgG concentration was 5.2 µg / ml in the non-hospitalized COVID-19 + group and 98.5 µg / ml in the ICU-hospitalized COVID-19 + group. The serum positive threshold for SARS-CoV-2 RBD IgG ELISA is indicated by the red line at 0.39 µg / ml. 244 serum-negative samples with IgG concentrations <0.001 were plotted at 0.001. Comparison of serum positive groups * Wilcoxon-Mann-Whitney test p <0.0001. Both seronegative groups are significantly different from all seropositive groups.

Equivalent IgG titers in mild and asymptomatic cases

The researchers also observed similar IgG titers among those who were seropositive in the study and those who were identified by self-detection but were not hospitalized. This may indicate that the degree of immune stimulation and response was similar between these groups.

However, the median potency of patients admitted to the intensive care unit was 12-fold higher than in the latter group (98.5 μg / ml vs. 5.2 μg / ml).

Meanwhile, only 19 participants (1.2%) reported that they tested positive for COVID-19 prior to this date. Of these, 18 were also anti-RBD IgG positive.

Anti-RBD antibody that is more useful than anti-nucleocapsid antibody

Researchers cross-checked 28 samples from patients who recovered after symptomatological COVID-19, all from symptomatic individuals who tested positive for the virus but did not get such results. Compared with 92 samples of. They found that both groups showed low levels of agreement between antibodies to these two antigens, nucleocapsid (N) and RBD.

About one-fifth of the 28 symptomatological COVID-19 positives were only anti-RBD IgG without anti-N antibodies. Conversely, about 75% were positive for both antibodies. Only one participant was negative for both antibodies.

Of the 92 SCAN samples, over 70% were anti-RBD IgG, 45/65 were anti-RBD IgG only, 20/65 samples contained both antibodies, and none were both negative. did. What that means is that antibodies that target RBD are probably more useful in detecting serum prevalence.

Most of the participants who received the first seropositive test continued to show median detectable IgG levels from day 0 to 73-166 days, or about 4 months. In one case, anti-RBD IgG titers were stable for 3 months and then surged. The patient had a history of suggestive symptoms two days ago, but had a negative PCR test. However, the test was done 25 days after the earliest symptoms, which may have resulted in negative results.Or Viral load You may never have exceeded the detection limit of your test. However, researchers attribute this result to the possibility of re-exposure to the virus.

What is the impact?

Researchers have detected a high prevalence of anti-RBD antibodies, but it is not clear whether they are protective or neutralizing. Further research is needed to determine whether seropositives are less susceptible to infection than seronegatives.

Approximately 75% of the community showed persistent seropositive and at least one showed evidence of re-exposure. Regarding the longitudinal pattern of anti-RBD IgG, the researchers said: “We assume that this pattern reflects re-exposure to SARS-CoV-2. Whether this pattern generally predicts that re-exposure can occur, or is available to vaccines. Even after it becomes possible, future researchers will need to investigate.

The study concludes that: “These data underscore the importance of quantitative and self-collected serum prevalence in monitoring the COVID-19 pandemic response. The SCAN platform provides easy home monitoring and laboratory accuracy. It depends on the combination and is arranged to help address this and other knowledge gaps. “

*Important Notices

medRxiv Publish preliminary scientific reports that should not be considered definitive as they are not peer-reviewed, guide clinical practice / health-related behaviors, and should not be treated as established information.