Humoral Immune Response to SARS-CoV-2 in Iceland

Abstract

Background: Little is known about the nature and durability of the humoral immune response to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Methods: We measured antibodies in serum samples from 30,576 persons in Iceland, using six assays (including two pan-immunoglobulin [pan-Ig] assays), and we determined that the appropriate measure of seropositivity was a positive result with both pan-Ig assays. We tested 2102 samples collected from 1237 persons up to 4 months after diagnosis by a quantitative polymerase-chain-reaction (qPCR) assay. We measured antibodies in 4222 quarantined persons who had been exposed to SARS-CoV-2 and in 23,452 persons not known to have been exposed.

Results: Of the 1797 persons who had recovered from SARS-CoV-2 infection, 1107 of the 1215 who were tested (91.1%) were seropositive; antiviral antibody titers assayed by two pan-Ig assays increased during 2 months after diagnosis by qPCR and remained on a plateau for the remainder of the study. Of quarantined persons, 2.3% were seropositive; of those with unknown exposure, 0.3% were positive. We estimate that 0.9% of Icelanders were infected with SARS-CoV-2 and that the infection was fatal in 0.3%. We also estimate that 56% of all SARS-CoV-2 infections in Iceland had been diagnosed with qPCR, 14% had occurred in quarantined persons who had not been tested with qPCR (or who had not received a positive result, if tested), and 30% had occurred in persons outside quarantine and not tested with qPCR.

Conclusions: Our results indicate that antiviral antibodies against SARS-CoV-2 did not decline within 4 months after diagnosis. We estimate that the risk of death from infection was 0.3% and that 44% of persons infected with SARS-CoV-2 in Iceland were not diagnosed by qPCR.

Figure 1. Schematic Overview of the Eight Sample Groups Used in the Study.

The eight sample groups are shown in the upper boxes, and the arrows within the upper boxes indicate the main utility of each sample collection. The two lower boxes describe the six assays that were used; the arrows outside the boxes show which assays were used for the two collection types (not positive by quantitative polymerase-chain-reaction assay [non–qPCR-positive] and qPCR-positive). For the Health Care group, samples were obtained during a visit to the health care system. For the Quarantine group, all samples were obtained on completion of quarantine. The two groups of samples from persons who tested qPCR-positive were obtained at different times during the course of the disease: the Hospitalized group consists of samples obtained during hospitalization, and the Recovered group consists of samples obtained after recovery. ECLIA denotes electrochemiluminescence immunoassay, and ELISA enzyme-linked immunosorbent assay.

Figure 2. Antibody Prevalence and Titers among qPCR-Positive Cases as a Function of Time since Diagnosis by qPCR.

Shown are the percentages of samples positive for both pan-Ig antibody assays and the antibody titers. Red denotes the count or percentage of samples among persons during their hospitalization (249 samples from 48 persons), and blue denotes the count or percentage of samples among persons after they were declared recovered (1853 samples from 1215 persons). Vertical bars denote 95% confidence intervals. The dashed lines indicated the thresholds for a test to be declared positive. OD denotes optical density, and RBD receptor binding domain.