Humoral Immune Response of SARS-CoV-2 in Iceland

Specifications of SARS-CoV-2 antibody

Samples collected in 2017 of both assays measuring pan-Ig antibodies had lower numbers of false positives: 0 and 1 were false positives for two assays out of 472 samples, with results that were single IgM anti-N and IgG Were favorable compared to those obtained. N – N assays (Table S3). Due to the low prevalence of SARS-CoV-2 infection in Iceland, we required positive results from both pan-Ig antibody assays for a sample to be considered seropositive (see Supplementary Methods in Supplementary Appendix 1). None of the samples collected in the early 2020 cohort were seropositive, indicating that the virus did not spread widely in Iceland before February 2020.

SARS-CoV-2 antibody among qPCR-positive individuals

Antibody proliferation and titers among qPCR-positive cases as a time function since diagnosis by qPCR.

Shown are the percentages of samples positive for both PAN-Ig antibody assays and antibody titers. Red indicates the count or percentage of samples among individuals during their hospitalization (249 samples out of 48 individuals), and the number or percentage of samples after blue individuals (1853 samples from 1215 individuals) were recovered. Shows. Vertical bars indicate 95% confidence intervals. Dashed lines indicated the threshold to declare the test positive. OD denotes optical density and RBD receptor binding domain.

The prevalence of SARS-COV-2 antibody as sample collection is measured by two pan-Ig antibody antibodies.

Twenty-five days after diagnosis by QPCR, more than 90% of samples of recovered individuals tested positive with both pan-Ig antibody assays, and the percentage of individuals who tested positive remained stable thereafter (Figure 2 And figs. S2). Coconut juice is given to hospitalized individuals more frequently and as quickly as possible after qPCR diagnosis than non-authorized persons (Figure 2 And figs. S3). Of the 1215 individuals who had recovered (for those who had recently had multiple samples from us), there were 1107 seropositives (91.1%; 95% confidence interval); [CI], 89.4 to 92.6) (Table 1 And table S4). As some diagnoses may have been made based on false positive qPCR results, we determined that 91.1% represents a lower threshold of sensitivity of combined PAN-Ig tests for detection of SARS-CoV-2 antibodies among recovered individuals. is.

Results of repeated PAN-Ig antibody tests among recovered qPCR-diagnosed individuals.

Among the 487 recovered individuals with two or more samples, 19 (4%) had different PAN-Ig antibody test results at different time points (Table 2 And image. S 4). It is notable that of the 22 individuals with the initial sample who tested negative for both pan-Ig antibodies, 19 remained negative on the most recent test date (again, for both antibodies). One person tested positive for both pan-Ig antibodies in the first test and negative for both in the most recent test.

Longitudinal changes in antibody levels among recovered individuals were consistent with cross-sectional results (Fig. S5); Antibody levels were higher in the final sample than in the first sample when antibodies were measured with two PAN-Ig assays, slightly lower than in the first sample when measured with IgG anti-N and IgG anti-S1 assays Is, and is much less. When compared with earlier samples when measured with IgM anti-N and IgA anti-S1 assays.

IgG anti-N, IgM anti-N, IgG anti-S1, and IgA anti-S1 antibody levels were correlated among qPCR-positive individuals (figs. S5 and S6 and Table S5). Antibody levels measured with both pan-Ig antibody assays increased in the first 2 months after qPCR diagnosis and remained on a plateau over the next 2 months of the study. Immediately after diagnosis IgM anti-N antibody levels increased rapidly and then fell rapidly and were usually not detected after 2 months. IgA anti-S1 antibodies decreased 1 month after diagnosis and remained detectable thereafter. IgG anti-N and anti-S1 antibody levels increased during the first 6 weeks after diagnosis and then decreased slightly.

SARS-CoV-2 infection in quarantine

Infection among quarantine individuals according to the type and presence of SARS-CoV-2 infection.

Of the 1797 qPCR-positive Icelanders, 1088 (61%) were in quarantine when SARS-CoV-2 infection was diagnosed by qPCR. We tested antibodies among 4222 quarantine individuals who did not test qPCR-positive (they received a negative result by qPCR or simply were not tested). Of the 4222 quarantine individuals, 97 (2.3%; 95% CI, 1.9 to 2.8) were seropositive (Table 1). People with domestic exposure are 5.2 (95% CI, 3.3 to 8.0) times more likely to be seropositive than those with other types of exposure (Table 3); Similarly, a positive result by qPCR for people at home risk is 5.2 (95% CI, 4.5 to 6.1) more likely than those with other types of risk. When these two sets of results (qPCR positive and seropositive) were combined, we calculated that 26.6% of quarantined individuals with household exposure and 5.0% of quarantined individuals without household exposure were infected. People who had symptoms during quarantine were 3.2 (95% CI, 1.7 to 6.2) times more likely to be seropositive and 18.2 times (95% CI, 14.8 to 22.4) more positive with qPCR than those with symptoms. There is a possibility to test.

We also tested individuals from two regions of Iceland affected by the cluster outbreak. In the SARS-CoV-2 cluster in Westfirdir, 1.4% of residents were qPCR positive and 10% of residents were quarantined. We found that none of the 326 individuals outside of quarantine who were not tested by qPCR (or who tested negative) were serosensitive. In a cluster in Westmanzier, 2.3% of residents were quPCR-positive and 13% were quarantined. Of the 447 collected individuals who did not receive qPCR-positive results, 4 were seropositive (0.9%; 95% CI, 0.3 to 2.1). Out of quarantine, 3 out of 663 were seropositive (0.5%; 95% CI, 0.1 to 0.2%) in Vestmannaeyjar.

SARS-CoV-2 Transparency in Iceland

No serum samples were collected from 470 healthy Icelanders between 18 February and 9 March 2020, both tested positive for Pan-Ig antibodies, although the Pan-Ig anti-N assay (0.9%) There were four positives, a suggestion suggesting that the virus did not spread widely in Iceland before 9 March.

Both of the 18,609 individuals tested for SARS-CoV-2 antibodies through exposure to the Icelandic health care system for reasons other than Kovid-19, 39, pan-Ig antibody assays (to weight the sample based on residence Estimated propoprevalence). , Sex, and aged 10 years, 0.3%; 95% CI, 0.2 to 0.4). There were regional differences in the percentage of qPCR-positive individuals across Iceland that were roughly proportional to the percentage of people (Table S6). However, after exclusion of qPCR-positive and quarantined individuals, the percentage of individuals who tested positive for the SARS-CoV-2 antibody was not associated with the percentage of those who tested positive by qPCR. Estimated sarcopralens health care group (0.3%; 95% CI, 0.2 to 0.2) in random sample collection from Reykjavik (0.5%; 95% CI, 0.3 to 0.3) The table was similar to S६).

We calculate that 0.5% of Iceland residents tested positive with qPCR. 2.3% quarantine with stork-cove-2 seroconversion accounted for 0.1% of Icelandic residents in additional individuals. On the basis of this finding and from the health care group to the survey, we estimate that 0.9% (95% CI, 0.8 to 0.9) of Iceland’s population has been infected with SARS-CoV-2. Approximately 56% of all SARS-CoV-2 infections were diagnosed by qPCR, 14% occurred in quarantine without a diagnosis of qPCR, and the remaining 30% infections occurred outside of quarantine and were detected after qPCR.

Kovid-19 deaths in Iceland

In Iceland, Kovid-19 has been responsible for 10 deaths, which corresponds to 3 deaths per 100,000 nationwide. In QPCR-positive cases, 0.6% (95% CI, 0.3 to 1.0) were fatal. Using a 0.9% prevalence of SARS-CoV-2 infection in Iceland, however, we calculate an infection fatal risk of 0.3% (95% CI, 0.2 to 0.6). Stratified by age, the risk of infection was significantly lower in those 70 years or younger (0.1%; 95% CI, 0.0 to 0.3) than those older than 70 years (4.4%; 95% CI, 1.9 to 8.4). . (Table S7).

Age, sex, clinical signs and antibody levels

Current conditions and Kovid-19 severity among recovered individuals with SARS-CoV-2 antibody levels.

SARS-CoV-2 antibody levels were higher in older people and in those hospitalized (Table 4, And table S8 [described in Supplementary Appendix 1 and available in Supplementary Appendix 2]). Pan-Ig anti-S1-RBD and IgA anti-S1 levels were lower in female individuals. Among the preoperative conditions, and after adjusting for several trials, we found that body-mass index, smoking status, and antiinflammatory drug use were associated with SARS-CoV-2 antibody levels. Body-mass index correlated positively with antibody levels; Antibody levels were lower in smokers and antiinflammatory drug users. With regard to clinical characteristics, antibody levels were most commonly associated with hospitalization and clinical severity, followed by clinical symptoms such as fever, maximum temperature reading, cough, and loss of appetite. The severity of these individual symptoms, with the exception of loss of energy, was associated with higher antibody levels.