of 25
Index Cases First Identified by Nasal-Swab Ra
pid COVID-19 Tests
Had More Transmission to
Household Contacts Than
Cases Identified by Other Test Types
Jenny Ji
1†
, Alexander Viloria Winnett BS
1,2†
, Natasha Shelby PhD
1
, Jessica A. Reyes MPH
1
, Noah W. Schlenker BS
1
, Hannah Davich
MPH
1
, Saharai Caldera BS
1
, Colten Tognazzini BSN
3
, Ying-Ying Goh MD MPH
3
, Matt Feaster PhD MPH
3
, Rustem F. Ismagilov PhD
1*
1.
California Institute of Technology, Pasadena, CA, USA
2.
University of California Los Angeles – Ca
lifornia Institute of Technology Medical Scientist Training Program, Los Angeles,
CA USA
3.
Pasadena Public Health Department, Pasadena, CA, USA
† These authors contributed equally to this report.
*Correspondence to: Rustem F. Ismagilov, 1200 E.
California Blvd., Pasadena, CA 91125, 626-395-8130,
rustem.admin@caltech.edu
ABSTRACT
Importance:
At-home rapid COVID-19 tests utilize nasal-swab specimens and require high viral loads to reliably give
positive results. Longitudinal studies from the onset of infection
have found infectious virus can present in oral specimens
days before nasal. Detection and initiation of infection-control practices may ther
efore be delayed when nasal-swab rapid
tests are used, resulting in greater e
xposure and transmission to contacts.
Objective:
We assessed whether index cases first
identified by rapid nasal-swab COVID-19 tests had more tran
smission to household contacts than index cases who used
other test types (tests with higher analytical sensitivity but longer turnaround times, and/or that utilize non-nasal specimen
types).
Design:
In this observational cohort study, members of hou
seholds with a recent COVID-19 case were screened for
infection at least daily by RT-qPCR on one or more self-co
llected upper-respiratory specimen types. Participants reported
demographic/medical information (inc
luding COVID-19 testing), symptom and
exposure information, and household
infection-control practices. A two-level random intercept m
odel was used to assess the associ
ation between the infection
outcome of household contacts and each covariable (household si
ze, race/ethnicity, age, vaccination status, viral variant,
infection-control practices, and whether a rapid nasal-swab
test was used to initially id
entify the household index case).
Setting:
Southern California, September 2020—J
une 2021 and November 2021—March 2022.
Participants:
Cohort of
370 individuals from 85 households.
Main Outcome(s) and Measure(s):
Transmission was quantified by adjusted
secondary attack rates (aSAR) and adjusted odds ratios (aOR).
Results:
An aSAR of 53.6% (95% CI 38.8
–68.3%) was
observed among households where the index case first tested positive by a rapid nasal-swab COVID-19 test, which was
significantly higher than the aSAR for households where the
index case utilized another test type (27.2% 95% CI 19.5
35.0%,
P
=0.003 pairwise comparisons of predictive margins). We observed an aOR of 4.90 (95% CI 1.65
–14.56) for
transmission to household contacts when a nasal-swab rapid test
was used to identify the inde
x case, compared to other test
types.
Conclusions and Relevance:
Use of nasal-swab rapid COVID-19 tests for initial detection of infection and initiation
of infection control may not limit transmission as well as other test types.
Keywords:
Household, Transmission, Rapid, Nasal, Antigen, Swabs,
Omicron, Secondary Attack Rate, Delta, Southern
California variant, association
Key Points:
1. Question:
Does identification of index cases by rapid nasal-swab t
ests limit household transmission of SARS-CoV-2 as
well as other test types?
2. Finding:
Significantly higher adjusted secondary attack rates and ad
justed odds ratios for transmission were observed in
households where the index case used a nasal rapid COVID-19
test for initial detection ve
rsus other test types.
3. Meaning:
The use of
nasal-swab rapid COVID-19 tests for initial detection
of infection and initiation of infection control
may not limit transmission as well as other test types.
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NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.
Introduction
The majority of SARS-CoV-2 transmissi
on events occur among household contacts.
1,2
Numerous studies have characterized
household transmission of SARS-CoV-2
3-8
and identified factors that modulate the risk of transmission within households,
such as larger household size being associated with higher risk.
9-12
Similarly, disparities by race and ethnicity have been
observed, while controlling for socioeconomic differences.
11,13
Age of both the index case (first person in the household to
become infected) and at-risk household
contacts (who either remain uninfected
or become infected secondary cases) has
also been implicated in SARS-C
oV-2 household-transmission patterns.
6,14-16
Furthermore, although vaccination does not
fully prevent breakthrough infections,
17
vaccination has been shown to be protec
tive and decrease the risk of infection
8,18-
22
. Specific infection-control practices, such as wearing a
mask around infected contacts, physical distancing, and
quarantining sick individuals have also shown protective effects.
14,18,23-25
Lastly, SARS-CoV-2 variants such as Delta and
Omicron have been shown in large studies to have greater transmissibility
compared with ancestral variants.
8,18,19,26-33
Early identification of an infectious individual is a critical step to reduce subsequent transmission, including within
households. Because transmission of SARS-CoV-2 occurs dur
ing both the asymptomatic
and symptomatic periods of
infection,
34-37
diagnostic testing to quickly prompt
infection control practices has been
effective to limit additional exposures
and transmission.
38
Conversely, infectious individuals that go unidentified or delay identification allow for greater exposure
to contacts and thereby more transmission.
12,39,40
Delayed detection can occur due to test turnaround times or when
a test yields a false-negative result. Rapid tests (e.g.,
antigen and some molecular tests) offer
fast turnaround times, but require higher le
vels of virus to reliably result positive;
e.g., ~100,000 times more virus is need
ed to yield a positive result by the Lumi
raDx SARS-CoV-2 Ag Test than the
PerkinElmer New Coronavirus Nucleic Acid Detection Kit
41,42
. Additionally, SARS-CoV-2 can infect different upper-
respiratory compartments, so numerous sp
ecimen types are used to detect infec
tion (e.g., anterior-nares nasal swab, mid-
turbinate nasal swab, nasopharyngeal swab, oropharyngeal
swab, tonsillar swab, buccal swab, lingual swab, gingival
crevicular fluid, saliva). The rise and fall of viral loads in each specimen type throughout infection affects whether SARS-
CoV-2 is detectable in that specimen type at the time of tes
ting. A diagnostic test successfully detects infection when the
viral load in the tested specimen type is above
the limit of detection (LOD) of the test.
In our recent analysis
43
of viral loads from three specimen types (anterior-nares swab, oropharyngeal swab, and saliva)
prospectively collected daily before or at the incidence of in
fection with the Omicron variant, we observed that longitudinal
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viral-load timecourses in different specimen types from th
e same person often exhibit
extreme differences and do not
correlate. Further, most people in that study
43
and our prior study of ancestral variants
44
had delayed accumulation of virus
in nasal swabs compared with oral sp
ecimens. A delayed rise in nasal-swab viral loads has been observed in many studies,
45-
48
including among participants in a SARS-CoV-2 human
challenge study who received intra-nasal inoculation.
49
We
50
and
others
43,46,48,51,52
found that this delayed rise in nasal
viral loads, in combination with th
e high levels of virus required for
detection by tests with low analytical sensitivity, leads to dela
yed detection of infected and infectious individuals by nasal-
swab rapid antigen tests. Non-nasal upper respiratory specimen types and/or tests with hi
gh-analytical-sensitivity could
detect these individuals earlier in the infection.
43
In this study, we aimed to investigate whether test analyti
cal sensitivity and differences in viral-load patterns among differe
nt
specimen types may have implications for household transmission
. We specifically tested whether the type of test (rapid
nasal-swab vs all other COVID-19 tests) used to first iden
tify household index cases was correlated with higher rates of
transmission to household contacts. Data were collected from a 2-year COVID-19 household transmission study in Southern
California. We applied a two-level random intercept m
odel, clustering by household
and controlling for potential
confounders
53
to assess the relationship between the use of a nasal-swa
b rapid COVID-19 tests to first identify the household
index case, and subsequent transm
ission to household contacts (
Fig 1
).
Methods
Participant Enrollment and Metadata
We conducted a case-ascertained COVID-19 household transmission observational cohor
t study in Southern California in
two phases: between September 2020 and June 2021,
44,54
prior to the predominance of the Delta variant
55
, and between
November 2021 and March 2022,
43
during the emergence and subsequent
predominance of the Omicron variant
55
(
Table
S1A
). The study was approved by the California Institute of Techno
logy IRB (protocol #20-1026). Participants aged 8 years
and older provided written informed consent, and all minor
s additionally provided verbal assent accompanied by written
parental permission.
Upon enrollment, participants complete
d a questionnaire to provide informati
on about demographics (see Supplementary
Information). At the conclusion of their participation, partic
ipants were asked to complete another questionnaire to report
any SARS-CoV-2 test results from outside of the study, update
d infection status of each house
hold member (including those
unenrolled), and infection-control practices performed.
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Laboratory Screening Testing
Specimens (saliva, anterior nares swabs, oropharyngeal swabs,
Fig 1A,B
) from participants underwent laboratory testing
for SARS-CoV-2 infection, as previously described (Supplementary Information).
43,44,54
Participants reported COVID-19-
like symptoms at each specimen collection timepoint. At
least one specimen from most households underwent viral
sequencing as previously described,
43,44
to ascertain the infecting SARS-CoV-2 variant of household members. For one
household enrolled in early December 2022, sequencing was not
performed but Delta variant was inferred based on the
dominating variants circulating at the time
55
and for 5 households enrolled after
mid-January 2022, sequencing was not
performed, but Omicron variant was
inferred based on local predominance.
55
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FIGURE 1 Overview of study design and analysis. (A)
Study design beginning with recording the COVID-19 test type
first used to identify index cases at study
enrollment, enrollment of household contacts for daily, high-analytical-sensitivity
laboratory screening, and analysis of potential factors modulating transmission.
(B)
CONSORT diagram for study
enrollment.
(C)
Timeline of participant enrollment in study Phase I
(September 2020—June 2021) and Phase II (November
2021—March 2022). Date is liste
d as numeric month over year.
(D)
Breakdown of self-reported COVID-19 test types
(specimen type, and rapid or not) utilized to first identify
household index cases. Test type was not reported by 10 of 85
index cases.
1. Individuals were ineligible for enrollment if they resided outside study jurisdiction, lived alone, or were more than 7 days
from
positive result or symptom onset. 2. Participants in Phase I collect
ed either saliva only, or paired saliva and nasal swabs; pa
rticipants
in Phase II collected paired saliva, nasal swabs, and throat swabs.
3. Households were considered not at risk if no member including
the suspected index case had detectable SARS-CoV-2 in any sample tested upon enrollment. 4. Households in which a majority of
unenrolled household members were considered to have insufficient information. 5. Households in which a single household index case
could not be assigned. 6. Information about unenrolled household
members was reported by enrolled
participants. 7. Test type was
defined as ‘Rapid’ if the particip
ant reported receiving results either within an
hour or on the same day as the specimen was c
ollected.
Longer turnaround times were classified as ‘Not Rapid’ tests. 8.
Oral/oropharyngeal specimen type category included participant
s who
self-reported that saliva, bucca
l swabs, or oropharyngeal swabs were collected for testing.
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Statistical Analyses
We utilized the questionnaire data and la
boratory testing data to investigate SA
RS-CoV-2 transmission within households
.
Households were included in this analysis if laboratory testing confirmed at
least one household member was acutely
infected with SARS-CoV-2 and more than a third of reported household members were enrolled in the study. Three
households were excluded because they withdrew before three
days of screening, 22 households were excluded because all
members were negative for SARS-CoV-2 in all tested specime
ns, five households were excluded because of insufficient
information about unenrolled household c
ontacts, and one household was excluded
because of inability to
determine index
case (
Fig 1B
). See Supplemental Information for details.
For each household, an index case was defined as the first member
of the household (enrolled in the study or not) to test
positive for SARS-CoV-2 infection, usually prior to enrollment. In one case where multiple memb
ers had the same first test
date, the member with earlier self-reported onset of symptoms
was considered the household index case. In five cases where
symptom onset of household members was w
ithin 1 day of each other, we defined the index case as the individual with a
known exposure to a non-household contact with laboratory-confirmed SARS-CoV-2 in
fection. In three cases with similar
timing of exposure to infected, non-household contacts, the i
ndex case was defined as the individual whose viral load peaked
first. All other members of the household who tested positive
for SARS-CoV-2 prior to or
during household enrollment in
the study were considered secondary cases. Household member
s who never tested positive for SARS-CoV-2 prior to or
while the household was enrolled in the study were considered
uninfected. 143 of 149 (96%) participants classified as
uninfected were enrolled and screened for at least 5 da
ys; most (53%) were enrolled for at least 9 days.
The test type of the household index case was interpreted as
a “nasal-swab rapid test” when the household index case self-
reported “shallow nasal swab (anterior nares or mid turbinat
e nasal swab)” as the specimen type and a result turnaround
time of “within an hour” or “same day.” Participants were not
asked to report the specific test name, laboratory platform, or
viral target (e.g., molecular, antigen), du
e to concerns that laypersons would not be
aware of these terms (especially if the
test was run by a clinic rather than direct-to-consumer).
However, rapid tests (both antigen and molecular) have
characteristically low analytical sensitiv
ity because they forego the time-consumi
ng and technically challenging extraction
steps to purify and concentrate viral targ
ets. Because our hypothesis was related to low-analytical-sensitivity rapid tests
performed on specimens from nasal swabs,
we simply distinguish rapid tests from those with longer turnaround times and
presumably higher analytical sensitivity (
Fig 1D
).
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We calculated unadjusted odds ratios (ORs) for
a priori
confounders,
56
infection-control practices, the use of nasal-swab
rapid tests by index cases, and the risk of SARS-CoV-2 transm
ission to household contacts using mixed-effect logistic
regression (
Fig 2
,
Table S2
). We also used a two-level mixed-effects logi
stic regression model with
random intercepts by
household to account for clustering of individuals within househol
ds and including all covariables to estimate adjusted odds
ratios (aOR) (
Fig 2, Table S3
). This type of model
57
was chosen to estimate the effects of predictors at both individual and
household levels. The model adjusted for a sufficient set
of the following potentially confounding variables: household
size,
10-12
age,
6,15,16
race/ethnicity,
11,13
and vaccination status.
18-22
We also accounted for infecting SARS-CoV-2 viral
variant.
18-20,28,32,33
Observations with missing data were omitted from respective analyses.
We used this model to assess the effect of household preventi
on practices and the COVID-19 test type used to first identify
the household index case. An aOR >1.0 was associated with increased likelihood of household transmission, and deemed
statistically significant if its associated
P
-value was
0.05 by Wald and likelihood ratio tests.
Predictive margins based on th
e results of the regression models were used to estimate unadjusted and adjusted secondary
attack rates (SAR and aSAR). Binomial confidence interv
als (CIs) were calculated as recommended by the Clinical
Laboratory Standards Institute EP12-A guidance.
58
Differences among SARs and aSARs were assessed across strata.
59
We separately assessed the conditional direct effects of viral vari
ant and test type used to identify the household index case
by modifying the model with or without each of these covariables (
Fig 3
). Calculations were pe
rformed in STATA/BE 17.0.
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Table 1. Demographics, COVID-19 Vaccination Status, Vi
ral Variant, and Smoking History of the 85-Household
Cohort Used for Analyses.
*Both sex assigned at birth and current gender identity were se
lf-reported by participants. One participant reported male assig
nment
at birth and current gender identity of woman. Reported gender is listed.
**63 individuals currently listed as ‘Unknown’ did not sele
ct a race category but wrote-in “Latino”/”Latina”/”Latinx.”
***Participants reported date and manufacturer of each vaccine do
se received; vaccination status was defined only by doses rece
ived
at least 7 days prior to enrollment in th
e study. Unvaccinated was defined as having
received no COVID-19
vaccine doses. Partia
l
vaccination was defined as receiving one dose of a multiple-dose
series (e.g., Pfizer-BioNTech, Moderna). Complete vaccination
was
defined as receiving all doses of
an initial COVID-19 va
ccine series. Boosted was defined as
the participant
receiving any dose beyond
an initial COVID-19 vaccine series. Vaccination and viral variant distributions varied by Study Phase; demographics by Study Ph
ase
are shown in
Table S1
.
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Results
We analyzed data from 370 individuals
(enrolled and unenrolled participants) of which 85 were defined as household index
cases (
Table 1
). Among index cases, nasal-swab rapid test use more
than tripled from the first to second study phase (
Fig
1D
). Only 3 of 16 index cases first identified by a rapid nasal-swab rapid tests had a prior negative rapid nasal-test within
three days of their positive result, suggesting repeat rapid nasal testing.
60
Across both study phases, we observed an overall,
unadjusted SAR of 34.4% (95% CI 28.9%–40.2%, 98 of
285 household contacts) in this population.
Without accounting for index case testing, we observed several co
variables associated with SARS-CoV-2 transmission in
households (
Fig 2
). Household size greater than four members was associated with nearly a 5-fold
increase in the odds of
infection (aOR=4.78, 95% CI 1.80–12.70)
. Whether a household contact had received at least one dose of a COVID-19
vaccine was found to reduce the odds of infection by 70% (aOR=0
.30, 95% CI 0.08–1.17). Most infection-control practices
were associated with reduced risk, such
as not sharing a bedroom with (aOR=0.
25, 95% CI 0.10–0.62) and wearing masks
around (aOR=0.33, 95% CI 0.12-0.88) infected individuals.
Our results were also consistent with prev
ious observations that infection with the
Omicron variant is associated with greater
transmission than ancestral variants.
8,18,19,31-33
Increased transmissibility of the Om
icron variant compared to ancestral
variants was observed in our study by both aOR (3.64, 95
% CI 0.88–15.07), as well as aSAR stratified by whether the
index case was infected with the Omicron variant (46.9%, 95%
CI 32.3%-61.6%) or an ancest
ral variant (27.3%, 95% CI
17.7%-36.9%). Increased transmissibility of the Omicron variant was not
observed in the univariable model (
Table S2
),
likely because this model does not correct for a compensating,
protective effect of vaccination, which was more prevalent
among individuals from households infected with the Om
icron variant (76.7%) than ancestral variants (17.5%,
Table S1
).
Identification of index cases by nasal-swab rapid tests was associated with higher transmission to household contacts than
other test types, both when aggregated (
Fig 2C
) and for all other test type subgroups (
Table S3
), and in both univariable
(OR=2.64, 95% CI 1.41–4.95,
P
=0.003,
Table S2
) and multivariable models (a
OR=4.93, 95% CI 1.65–14.69,
P=
0.004,
Fig 2
). The multivariable model suggests that nasal-swab rapid test use by index cases incre
ased the odds of transmission
relative to other test types by almost five-fold (though both sma
ller and larger increases are also compatible with the data).
Index cases who used nasal-swab rapid tests also had a higher
aSAR of 53.5% (95% CI 38.
7%–68.3%) compared to other
test types (27.0%, 95% CI 19.3%–34.8%).
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Because the use of nasal-swab rapid test
use has increased in parallel with SARS-C
oV-2 variants shown to have increased
transmissibility, we examined the relationship of these two c
ovariables on risk of transmission to household contacts. The
use of a nasal-swab rapid test to identify the index case was
associated with a similar incre
ased risk of transmission to
household contacts) as infection with the Omicron variant (
Fig 3
). Introducing adjustment in the model for nasal-swab rapid
test use by the index case decreased the aOR for infection with the Omicron variant from 3.63
(95% CI 0.88-
15.0) to 2.40
(95% CI 0.63–9.22) (
Fig 3A
). The aOR of rapid nasal-swab
test use also decreas
ed from 5.50 (95% CI 1.78–17.04) to 4.90
(95% CI 1.65–14.59) without or with adjust
ment for viral variant, but nasal-swab ra
pid tests remained associated with at
least a 1.5-fold increase in the odds of household contact infection (
Fig 3B
).
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FIGURE 2 Results of Modeled Risk of
Transmission to Household Contacts.
Counts (N) of enrolled individuals who
did not become infected during enrollment (uninfected)
or became infected after the index case (secondary case) are
provided for each covariable included in the multivariable model (
Fig 1C
). The adjusted secondary attack rate (aSAR) and
adjusted odds ratio (aOR) point estimates with 95% confiden
ce intervals from multivariable analysis are listed for each
covariable and visualized to the right. Resu
lts of univariable analysis are provided in
Table S2
. The Wald test
P
-values for
the analyses likelihood ratio test is shown.
Covariates with an aOR 95% CI >1 are s
hown in red, and those <1 are shown in
blue. Reference groups are shown as a grey point.
(A)
Data for the five covariables included in the sufficient set.
(B)
Covariables related to infection-control practices controlling
for the sufficient set. The aOR represents the conditional effec
t
of the covariable in the model.
(C)
Association between COVID-19 test type used to identify the household index case, and
subsequent transmission to household contacts
.
Unenrolled household index cases’ test type was unknown, resulting in a
lower total count for this category.
*Vaccinated is defined as having received at least one dose of
a COVID-19 vaccine at least 7 days prior to enrollment.
**Participants were asked to respond whether or not they performed each action during interactions data coded. Data on infectio
n
control practices was not available for some participants. Observations with missing data were omitted, resulting in a lower to
tal count
for this category of covariables.
***Analysis by Other Test Type subgroups is shown in
Table S3
.
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FIGURE 3. Effect Size Interactions of COVID-19 Test Type and Viral Variant on Transmission to Household
Contacts. (A)
The adjusted odds ratios (aOR) for infection with the Omicron variant (with ancestral SARS-CoV-2 variants
as reference). Analysis was performed while controlling for the sufficient set of covariables in the model (grey box), as well
as when additionally controlling for whether the index case w
as first identified using a nasal-swab rapid test or other
COVID-19 test type.
(B)
The aOR for the use of nasal-swab rapid tests
to first identify index cases, as opposed to other
COVID-19 test type. Analysis was performed
while controlling for the sufficient set
of covariables in the model (shown in
grey box), and with all covariables in the suffi
cient set except for viral variant. Wald test
P
-values are shown for each
estimate of effect size. All error bars are 95% CI. Vertical dotted black line indicates an aOR of 1.0.
Discussion
Household contacts of index cases who used nasal-swab rapid an
tigen COVID-19 tests for primary infection detection had
an increased risk of becoming infected compared with household contacts of index cases who used other test types. Greater
transmission of SARS-CoV-2 to household contacts by individua
ls first identified by nasal-swab rapid tests is supported
mechanistically by studies of SARS-CoV-2 viral load and nasal sw
ab rapid test performance. First, a gradual rise in viral
loads, as we
43,44,50,61
and others
52,62-64
have observed, often creates a several-day delay between when an individual likely
becomes infectious and when viral loads reach levels detectable by low-analytical-sensitivity, rapid tests. Second, a delay
in the rise of nasal viral loads rela
tive to oral specimen types, as we
43,44,50
and others
45,49
have observed, renders nasal-swab
rapid tests less able to detect individuals during the early phase of the infection.
46,50
During this early period of low nasal
viral loads, we
43,50
and others
46
find that individuals exhibited high, presumably
infectious viral loads in oral specimens.
Relatedly, among data from a SA
RS-CoV-2 human challenge study,
49
we see that the majority of infected participants had
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replication-competent virus present in thro
at swabs at least one day prior to nasal-swabs. Therefore, nasal-swab rapid tests
may only yield positive results after exposur
e and transmission to contacts has occurre
d. These results together suggest that
nasal-swab rapid tests are not as effective at identifying i
ndex cases to limit subsequent transmission as other test types.
Several additional findings from our model
and dataset were consistent with prior studies. Household size was a significant
risk factor for household transmission,
9-12
whereas vaccination
8,18-22
and infection-control practices
14,18,23-25
were protective.
The overall SAR (34.4%) we observed was si
milar to what others have reported.
5,12,18,31,65,66
Relatedly, in one of those
studies
5
, household transmission was monitored by daily high-a
nalytical-sensitivity screening testing and the SAR
calculated using only nasal-swab test data was lower than wh
en both saliva and nasal-swab
test data were used, which
supports that even high-analytical-sensitivity nasal-swab testing may miss some infected individuals, and that the specimen
type used for evaluation can impact estimates of transmission.
We also observed, as other epidemiological studies have,
8,18,19,31-33
that infection with the Omicron variant was associated
with increased transmission compared with ancestral viral variants. However, the use of rapid nasal-swab tests (as opposed
to other test types) to detect index cases had a similar cond
itional direct effect on transm
ission to household contacts as
infection with the Omicron variant. Because the effect size of the Omicron variant association with transmission to
household contacts decreased when controlling for nasal-swab rapid
test use in our study, we speculate that a portion of the
increased transmissibility attributed to the Omicron vari
ant in published epidemiological studies may be partially
attributable to the increased use of rapid nasal-swab tests in
the U.S. that coincided with the predominance of this variant.
10,67
Although our results do not invalidate studies that conclude an
increased transmissibility of the Omicron variant, they
emphasize the potential impact of COVID-19 test type on es
timates of transmissibility from epidemiological data.
Limitations
Our findings are subject to limitations. First, vaccination status, demographic information, and infection-control practices
are self-reported and may be subject to recall bias. Second,
although questionnaires were written in simple terms (e.g.
“shallow nasal swab” and “deep nasal swab”)
, participants could have misinterpreted test type. Third, age, gender, and
infection status of each unenrolled household member was
independently reported by each enrolled household member,
which could lead to inaccurate reporting.
Fourth, our potential misclassification of
which household member was the index
case may impact the analysis,
53
although in almost all (79 of 85) househol
ds, the index case was confirmed by timing of
self-reported positive tests. Fifth, in our transmission model,
we did not analyze ordinal le
vels of contact among household
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members (all household members were assumed to have equal co
ntact). Instead, mitigating factors, including infection-
control practices, were assessed for protective effects against
transmission. Sixth, it is possible that high-analytical-
sensitivity tests could have turnaround times which we classify as rapid. However, such misclassification would bias toward
the null. Finally, evidence suggests
52,68
and the CDC
60
recommends repeating rapid antigen tests over several days to
improve clinical sensitivity. Alt
hough some index cases reported a negative test r
esult in the days prior to their first positi
ve
result, most participants in our study did not use repeated rapid testing.
Conclusion
Rapid COVID-19 tests, such as antigen tests, are less expensiv
e, portable, and offer faster results than high-analytical-
sensitivity molecular tests. However, re
sults from this observational study suggest that the use of nasal-swab rapid COVID-
19 tests to first identify infection do not limit household transmi
ssion as well as other test types. The use of tests with low
analytical sensitivity by an infected individual can have two
effects on transmission: (i) a true-positive result can change
behavior to increase infection-control practices in a timely ma
nner, thus reducing transmission, or (ii) a false-negative resul
t
can result in a health certificate effect,
69
where individuals falsely assume they are not infected/infectious and reduce
precautions, thereby increasing transmission. While imperfect testing may be better than no testing, understanding the
optimal use and limitations of rapid tests is important not
only for SARS-CoV-2, but othe
r pathogens for which timely
infection control and/or early treatment is critical.
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DATA SHARING STATEMENT
Raw data is available at CaltechDAT
A: https://doi.org/10.22002/csh5w-rf132.
ACKNOWLEDGEMENTS
We thank the
University of California, Los Angeles, Office of Advanced Research Computing, Statistical Methods and
Data Analytics Group
for recommendations on statistical methodology a
nd implementation, and Dr. Andy Lin for guidance
designing the analysis and feedback on the manuscript. This st
udy is based on research funded in part by the Bill & Melinda
Gates Foundation (INV-023124). The findings
and conclusions contained within
are those of the authors and do not
necessarily reflect positions or policies of
the Bill & Melinda Gates Foundation. This st
udy was also funded in part by grants
from the Ronald and Maxine Linde Center for New Initiatives at
the California Institute of Technology (to RFI), a grant
from the Jacobs Institute for Molecular Engineering for Medicine at the California Institute of Technology (to RFI), a
DGSOM Geffen Fellowship at the University of California,
Los Angeles (to AVW), and the John Stauffer Charitable Trust
SURF Fellowship at the California Institute of Technology (to JJ).
DISCLOSURE
R.F.I. is a cofounder, consultant, and a director and has stock ownership of Talis Biomedic
al Corp. All other co-authors
report no competing interests.
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Supplemental Information for:
Index Cases First Identified by Nasal Swab Rapid COVID-19 Tests
Had More Transmission to Household Contacts Than Cases
Identified by Other Test Types
Jenny Ji
1†
, Alexander Viloria Winnett BS
1,2†
, Natasha Shelby PhD
1
, Jessica A. Reyes MPH
1
, Noah W. Schlenker BS
1
,
Hannah Davich MPH
1
, Saharai Caldera BS
1
, Colten Tognazzini BSN
4
, Ying-Ying Goh MD MPH
4
, Matthew Feaster PhD
MPH
4
, Rustem F. Ismagilov PhD
1*
1.
California Institute of Technology, Pasadena, CA, USA
1.
University of California Los Angeles – Ca
lifornia Institute of Technology Medical Scientist Training Program, Los Angeles,
CA USA
2.
University of California Los Angeles, Department of Biostatistics, Los Angeles, CA, USA
3.
Pasadena Public Health Department, Pasadena, CA, USA
† These authors contributed equally to this report.
*Correspondence to: Rustem F. Ismagilov, 1200 E.
California Blvd., Pasadena, CA 91125, 626-395-8130,
rustem.admin@caltech.edu
Contents
Tables S1-S3
Supplemental Methods
Supplemental References
Detailed Author Contribution Statements
.
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It is made available under a
is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
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The copyright holder for this preprint
this version posted March 10, 2023.
;
https://doi.org/10.1101/2023.03.09.23286855
doi:
medRxiv preprint