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Try out PMC Labs and tell us what you think. Learn More. Little is known about the nature and durability of the humoral immune response to infection with severe acute respiratory syndrome coronavirus 2 SARS-CoV We measured antibodies in serum samples from 30, persons in Iceland, using six assays including two pan-immunoglobulin [pan-Ig] assaysand we determined that the appropriate measure of seropositivity was a positive result with both pan-Ig assays.
We tested samples collected from persons up to 4 months after diagnosis by a quantitative polymerase-chain-reaction qPCR assay. We measured antibodies in quarantined persons who had been exposed to SARS-CoV-2 and in 23, persons not known to have been exposed. Of quarantined persons, 2.
We estimate that 0. We estimate that the risk of death from infection was 0. The infection fatality risk of SARS-CoV-2 is difficult to estimate because the total of diagnosed and undiagnosed cases is needed as the denominator. The infection fatality risk was reported as 0.
The aim of this study was to assess SARS-CoV-2 seroprevalence in the population of Iceland and to assess longitudinal changes in antibody levels within the first 4 months after SARS-CoV-2 infection and how the changes correlate with sex, age, existing phenotypes, and Covid symptoms. 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. The study was approved by the National Bioethics Committee of Iceland.
The Health Care sample collection was performed on behalf of Icelandic health authorities in agreement with the Act no. Participants who were part of the other sample collections provided written informed consent. Thresholds for positivity were supplied by the assay manufacturers. We used the two pan-Ig antibody assays to evaluate seroprevalence, requiring positive for both assays for a test result to be considered positive Fig.
S1 in Supplementary Appendix 1. We measured antibodies in two groups of qPCR-positive Icelanders and in six groups who had not been Hot sex in Iceland or who had been tested and had received a negative result Figure 1. We collected samples from a group of hospitalized qPCR-positive persons and invited all qPCR-positive persons who had recovered from infection to donate samples, both shortly after recovery and again approximately 3 months after recovery a total of samples from persons.
We used two groups of samples collected before the pandemic in and in early to evaluate assay specificity and to determine when the pandemic reached Iceland. We collected samples from quarantined persons who had not tested qPCR-positive to evaluate infection during quarantine and the effect of exposure type on the probability of infection. We used three groups of samples collected from persons who had neither tested qPCR-positive nor been quarantined to evaluate seroprevalence outside quarantine and the spread of the virus in Iceland the Health Care, Reykjavik, and Vestmannaeyjar sample groups, totaling 23, persons.
The largest of these six groups, the Health Care group, was enriched for older people. To estimate seroprevalence, we weighted this sample by region, sex, and age in the population see Supplementary Appendix 1.
To estimate the of infected Icelanders, we added together the of qPCR-positive persons, the of quarantined persons times the estimated seroprevalence in this group, and the of persons outside quarantine times the estimated seroprevalence outside quarantine. We estimated the percentage of Icelanders infected by dividing the of infected persons by the of Icelanders. We estimated the infection Hot sex in Iceland risk by dividing the of deaths from Covid by the of infected persons.
We tested for associations of age, sex, preexisting conditions 27 phenotypesand clinical outcome 35 characteristics with antibody titers for each of the six assays in the most recent samples obtained from persons in the Recovered group. We recoded categorical clinical characteristics with their ordinal in the analysis. We used a likelihood ratio method to calculate confidence intervals of fractions with the Clopper—Pearson exact method when the estimated fraction was 0 or 1.
To test for association between each clinical characteristic and antibody levels, we performed multiple regression analyses with the phenotype as a covariate and quantile normalized antibody levels as a response, adjusting for age, age squared, sex, and time since qPCR diagnosis, excluding the age and sex covariates when testing for association with age and sex, respectively.
We quantile-normalized the antibody levels by ranking the levels and transforming them, using the inverse normal transform of the rank divided by one plus the of observations. Effects estimates were reported in terms of standard deviations of antibody levels.
We derived P values and confidence intervals from standard errors estimated by the multiple regression. For effects of the exposure type on the probability of infection among quarantined persons, we used logistic regression to estimate the confidence intervals of odds ratios. We did not adjust confidence intervals for multiple testing. Both assays measuring pan-Ig antibodies had low s of false positives among samples collected in there were 0 and 1 false positives for the two assays among samples, that compared favorably with those obtained with the single IgM anti-N and IgG anti-N assays Table S3.
Because of the low prevalence of SARS-CoV-2 infection in Iceland, we required positive 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 early group were seropositive, which indicates that the virus had not spread widely in Iceland before February Hospitalized persons seroconverted more frequently and quickly after qPCR diagnosis than did nonhospitalized persons Figure 2 and Fig. Of persons who had recovered on the basis of for the most recently obtained sample from persons for whom we had multiple sampleswere seropositive Since some diagnoses may have been made on the basis of false positive qPCRwe determined that Shown are the percentages of samples positive for both pan-Ig antibody Hot sex in Iceland and the antibody titers.
Red denotes the count or percentage of samples among persons during their hospitalization samples from 48 personsand blue denotes the count or percentage of samples among persons after they were declared recovered samples from persons. The dashed lines indicated the thresholds for a test to be declared positive. OD denotes optical density, and RBD receptor binding domain.
It is notable that of the 22 persons with an early sample that tested Hot sex in Iceland for both pan-Ig antibodies, 19 remained negative at 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.
The longitudinal changes in antibody levels among recovered persons were consistent with the cross-sectional Fig. S5 ; antibody levels were higher in the last sample than in the first sample when the antibodies were measured with the two pan-Ig assays, slightly lower than in the first sample when measured with IgG anti-N and IgG anti-S1 assays, and substantially lower than in the first sample when measured with IgM anti-N and IgA anti-S1 assays. S5 and S6 and Table S5. Antibody levels measured with both pan-Ig antibody assays increased over the first 2 months after qPCR diagnosis and remained at a plateau over the next 2 months of the study.
IgM anti-N antibody levels increased rapidly soon after diagnosis and then fell rapidly and were generally 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. We tested for antibodies among quarantined persons who had not tested qPCR-positive they had received a negative result by qPCR or had simply not been tested. Of those quarantined persons, 97 2.
Those with household exposure were 5. When these two sets of qPCR-positive and seropositive were combined, we calculated that Those who had symptoms during quarantine were 3. We also tested persons in two regions of Iceland affected by cluster outbreaks. We found that none of the persons outside quarantine who had not been tested by qPCR or who tested negative were seropositive. In a cluster in Vestmannaeyjar, 2. Of the quarantined persons who had not received a qPCR-positive result, 4 were seropositive 0. Of the outside quarantine in Vestmannaeyjar, 3 were seropositive 0.
None of the serum samples collected from healthy Icelanders between February 18 and March 9,tested positive for both pan-Ig antibodies, although four were positive for the pan-Ig anti-N assay 0. Of the 18, persons tested for SARS-CoV-2 antibodies through contact with the Icelandic health care system for reasons other than Covid, 39 were positive for both pan-Ig antibody assays estimated seroprevalence by weighting the sample on the basis of residence, sex, and year age category, 0.
There were regional differences in the percentages of qPCR-positive persons across Iceland that were roughly proportional to the percentage of people quarantined Table S6. However, after exclusion of the qPCR-positive and quarantined persons, the percentage of persons who tested positive for SARS-CoV-2 antibodies did not correlate with the percentage of those who tested positive by qPCR.
The estimated seroprevalence in the random sample collection from Reykjavik 0. We calculate that 0. The 2. On the basis of this finding and the seroprevalence from the Health Care group, we estimate that 0. In Iceland, 10 deaths have been attributed to Covid, which corresponds to 3 deaths pernationwide. Among the qPCR-positive cases, 0.
Using the 0. Stratified by age, the infection fatality risk was substantially lower in those 70 years old or younger 0. Of the preexisting conditions, and after adjustment for multiple testing, we found that body-mass index, smoking status, and use of antiinflammatory medication were associated with SARS-CoV-2 antibody levels. Body-mass index correlated positively with antibody levels; smokers and users of antiinflammatory medication had lower antibody levels.
With respect to clinical characteristics, antibody levels were most strongly associated with hospitalization and clinical severity, followed by clinical symptoms such as fever, maximum temperature reading, cough, and loss of appetite. Severity of these individual symptoms, with the exception of loss of energy, was associated with higher antibody levels.
Our estimate of the infection fatality risk is lower than but consistent with estimates described by others. We therefore conclude that, despite extensive screening by qPCR, a substantial fraction of infections were not detected, which indicates that many infected persons did not have substantial symptoms.
The case fatality risk is straightforward to estimate but may differ across countries and over time. An accurate calculation of infection fatality risk requires an accurate estimate of the of infections, both diagnosed and undiagnosed. By April 30, a total of 20, Hot sex in Iceland had been placed in quarantine. Despite substantial qPCR testing of persons in quarantine, 2. Household exposure was more likely to lead to infection than other types of exposure, which suggests that people who share a household with an infected person should not have contact during quarantine and that contacts of household members should be quarantined.Hot sex in Iceland
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