SARS-CoV-2 serologic
analyses
A total of eight conscripts were SARS CoV-2 serology positive during the
six-week observation period, one female and seven males. Seven
conscripts (0. 6 %) were SARS-CoV-2 serology positive at the day of
enrollment (Table 1), including the three conscripts with PCR-positive
results for SARS-CoV-2 described above. One conscript with negative
PCR-tests and a negative SARS-CoV-2 serology at enrollment developed
positive and rising titers at week three and six.
None of these eight conscripts had fever or reported respiratory
symptoms at the enrollment day, nor did they report any respiratory
symptoms during the service period. One of the eight reported mild
respiratory symptoms during the two weeks prior to enrollment. However,
based on the clinical interview, six of the eight conscripts with
positive serology had been ill with symptom onset three to seven weeks
before enrollment (Table 1).
Antibody titers increased up to almost five-fold in all but one of the
seropositive conscripts during the six weeks observation period (Table 1
and Figure 2).
SARS-CoV-2 antibody rapid-test
Of the 1170 conscripts, seven were both rapid-test
IgG-positive and serology-positive (Table 1), while none of them were
rapid-test-negative and serology-positive. Based on the serological test
at Oslo University Hospital as the gold standard, the sensitivity of the
rapid- test was calculated to 100 %.Two conscripts of the 1170 tested
both IgG and IgM positive on the rapid-test, 25 tested IgM positive and
29 tested IgG positive. Hence, a total of 56 conscripts tested either
IgG, IgM or IgG and IgM positive on the rapid-test. Forty-nine of these
56 conscripts were serology-negative, whereas 1114 were both serology
and rapid-test negative. A total of 1163 were consequently
serology-negative, and the specificity of the rapid-test was calculated
to be
96%.
In this cohort, with a seroprevalence of SARS-CoV-2 of 0. 6
%, the positive predictive value of the rapid-test was calculated to be
13 %.
Discussion
In this study of 1170 healthy conscripts, the sero-prevalence of
SARS-CoV-2 was 0. 6 %, and 0. 2 % had a positive PCR for SARS-CoV-2 at
the day of enrollment to military service. Eighteen conscripts reported
mild respiratory symptoms during the 14 days prior to enrollment (all
were PCR negative, one had positive serology), whereas 17 conscripts
reported respiratory symptoms and nine had fever at the day of
enrollment (all were PCR and serology negative). These low numbers may
partly be due to the high awareness of infection control rules in the
Norwegian population during the study period which was 3-4 weeks after
the pandemic peaked in Norway in ultimo March/primo April 2020.
SARS-CoV-2 PCR specimen detection
Two conscripts had a positive PCR test at enrollment, and one had a
positive PCR after six weeks. Whether this represents ongoing or
previous sub-clinical infection is up to debate. The PCR assay detects
the presence of viral RNA. Whether positive SARS-CoV-2 PCR represent
viable and contagious virus or only viral remnants might vary depending
on patients and stages of disease. A study found that the infectivity
peaked three days after symptom onset, and it was not possible to
culture virus from samples obtained more than eight days after symptom
onset 7.
Seroprevalence and
serodynamics
Eight of the 1170 conscripts (0. 7 %) were seropositive for SARS CoV-2
IgG during the observation period. As antibodies against SARS-CoV-2 can
be detected in the middle and later stages of the COVID-19 illness8, testing may help confirm COVID-19 diagnoses in
individuals who have not previously been referred to PCR testing.
Systematic antibody testing may also shed light on the actual prevalence
of COVID-19 in the general population, and thus their immunisation
status, which is key to the overall pandemic response in most countries.
Recent studies have revealed prevalence numbers in the range of 1-5% in
European countries 9. Our results indicate that the
prevalence of Covid-19 among young asymptomatic adults in Norway is less
than 1 %, which coheres with recent mathematical estimates from the
Norwegian Institute of Public Health 10.
Six of eight seropositive conscripts, among them two with a positive
PCR-test, had a history of symptoms compatible with COVID-19, with
symptom onset between three and seven weeks before enrollment. Titer
levels increased up to nearly five-fold over the six weeks observation
period. No new symptoms were reported during this period. Most people
infected with SARS- CoV-2 display an antibody response between 10 and 14
days after infection, however, the antibody response may depend on
disease severity 11. In some mild cases, detection of
antibodies is only possible a long time after symptoms, and in a few
cases, antibodies are not detected at all, at least during the time
scale of the reported studies 12. The duration of
antibody response is still unknown, but it is known that antibodies to
other coronaviruses wane over time (range: 12 – 52 weeks from the onset
of symptoms) 12. A study found that SARS-CoV-2 IgM and
IgG antibody levels may remain over the course of seven weeks after
onset of symptoms 13.
The symptoms and disease reported by the six seropositive conscripts
were mild. COVID-19 is considered a generally mild disease in
adolescents 2,3,14. One of the questions that need
further study is to what extent young COVID-19-patients actually present
with no symptoms at all, which may increase the risk of spreading the
virus to others. Our study confirms that symptoms are generally mild
among young adults, but hardly supports the idea of frequent occurrence
of asymptomatic spreaders, at least not in Norway 1.
SARS-CoV-2 antibody rapid-test
The sensitivity and specificity of the
rapid-test used in this study were 100 % and 96 %, respectively. The
relatively large proportion of false positive rapid-tests is probably
partly due to the fact that the instructions given from the manufacturer
recommended that “The intensity of the color in the test line regions
may vary depending on the concentration of SARS-CoV-2 antibodies present
in the specimen. Therefore, any shade of color in the test line region
should be considered positive” 15. This may have
resulted in negative tests being interpreted as positive based on nearly
invisible lines in the test field, and illustrates that adequate
instruction and training of health personnel is crucial when introducing
and using new rapid-tests.
The Acro rapid-test has recently been
evaluated by the Norwegian Organization for Quality Improvement of
Laboratory Examinations 16, and was rated
“acceptable”, with a sensitivity of 0.88 and a specificity of 0.99.
Value of testing and self-reported data
In our study, asymptomatic testing did not identify any individuals
suspected of active transmission, as both conscripts with a positive PCR
at enrollment had been symptom-free for more than 20 days when tested.
Seven of eight conscripts with a positive serology during the study
period had been symptom-free for at least 14 days before enrollment.
Testing of symptomatic conscripts, on the other hand, is widely
recommended 17 and used as both as a diagnostic tool
and a screening method to detect cases of COVID-19 in outbreak areas.
The incidence numbers in Norway have been < 5 % throughout
the pandemic. Symptomatic testing in this cohort did not confirm
SARS-CoV-2 in any of the 26 conscripts who reported having mild
respiratory symptoms or had fever at enrollment.
Only one of the eight people with positive serology reported respiratory
symptoms during the 14 days before enrollment. Given the reported time
of symptom onset among the conscripts with positive serology, five of
these would probably have been contagious if they had been enrolled a
month earlier and three might have presented symptoms of COVID-19.
Self-reported data and questionnaires therefore may have potential to be
effective tools in detecting COVID-19, especially in combination with
symptom-based testing. Asymptomatic testing does not seem justified
given the low prevalence and corresponding low predictive value of tests
in this cohort of young healthy conscripts.
Conclusion
The prevalence of SARS-CoV-2 in young adults in Norway is less than 1
%. Self-reported symptoms and questionnaires may prove useful in
detecting COVID-19, especially in combination with symptom-based
testing. Asymptomatic testing seems of no value in times of low COVID-19
prevalence. SARS-CoV-2 antibody titer levels increased substantially
over time in young adults with relatively mild symptoms.
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