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International Health 2022; 14: 18–52
https://doi.org/10.1093/inthealth/ihab005 Advance Access publication 23 February 2021
Humoral immunological kinetics of severe acute respiratory syndrome
coronavirus 2 infection and diagnostic performance of serological
assays for coronavirus disease 2019: an analysis of global reports
Anthony Uchenna Emeribe a, Idris Nasir Abdullahi b,∗, Halima Ali Shuwac, Leonard Uzairued, Sanusi Musab,
Abubakar Umar Ankab, Hafeez Aderinsayo Adekolae, Zakariyya Muhammad Bellof, Lawal Dahiru Rogog,
Dorcas Aliyua, Shamsuddeen Harunab, Yahaya Usmanb, Habiba Yahaya Muhammadg,
Abubakar Muhammad Gwarzoh, Justin Onyebuchi Nwofei, Hassan Musa Chiwarj, Chukwudi Crescent Okwumek,
Olawale Sunday Animasaunl, Samuel Ayobami Fasogbonm, Lawal Olayemin, Christopher Ogara,
Chinenye Helen Emeribeo, Peter Elisha Ghambap, Luqman O. Awoniyiq and Bolanle O. P. Musar
aDepartment of Medical Laboratory Science, Faculty of Allied Medical Sciences, University of Calabar, P.M.B 1115, Calabar, Cross River
State, Nigeria; bDepartment of Medical Laboratory Science, Faculty of Allied Health Sciences, College of Medical Sciences, Ahmadu Bello
University, Zaria, Nigeria; cUniversity Health Services, College of Health and Medical Sciences, Federal University, Dutse, Nigeria;
dDepartment of Microbiology, Federal University of Agriculture Abeokuta, Nigeria; eDepartment of Microbiology, Olabisi Onabanjo
University, Ago-Iwoye, Nigeria; fDepartment of Medical Laboratory Science, Faculty of Allied Health Sciences, College of Medical
Sciences, Ahmadu Bello University, Zaria, Nigeria; gDepartment of Medical Laboratory Science, Faculty of Allied Health Sciences, Bayero
University, Kano Nigeria; hDepartment of Medical Microbiology and Parasitology, Federal University, Dutse, Nigeria; iDepartment of
Medical Laboratory Science, University of Nigeria, Enugu, Nigeria; jDepartment of Medical Laboratory Science, University of Maiduguri
Maiduguri, Nigeria; kDepartment of Medical Laboratory Services, University of Nigeria Teaching Hospital, Enugu, Nigeria; lNigeria Field
Epidemiology and Laboratory Training Programme, African Field Epidemiology Network, Abuja, Nigeria; mPublic Health In-vitro
Diagnostic Control Laboratory, Medical Laboratory Science Council of Nigeria, Lagos, Nigeria; nSchool of Medicine, Faculty of Health
Sciences, National University of Samoa, Apia, Samoa; oDepartment of Family Medicine, University of Calabar Teaching Hospital, PMB
1278 Calabar, Cross River, Nigeria; pWHO National Polio Reference Laboratory, University of Maiduguri Teaching Hospital, Maiduguri,
Nigeria; qInstitute of Biomedicine, and MediCity Research Laboratories, University of Turku, 20014 Turku, Finland; rImmunology Unit,
Department of Medicine, Ahmadu Bello University, Zaria, Nigeria
∗Corresponding author: Tel: +2348030522324; E-mail: eedris888@yahoo.com; inabdullahi@abu.edu.ng
Received 8 August 2020; revised 23 November 2020; editorial decision 20 January 2021; accepted 25 January 2021
As the coronavirus disease 2019 (COVID-19) pandemic continues to rise and second waves are reported in some
countries, serological test kits and strips are being considered to scale up an adequate laboratory response. This
study provides an update on the kinetics of humoral immune response to severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2) infection and performance characteristics of serological protocols (lateral flow assay
[LFA], chemiluminescence immunoassay [CLIA] and ELISA) used for evaluations of recent and past SARS-CoV-
2 infection. A thorough and comprehensive review of suitable and eligible full-text articles was performed on
PubMed, Scopus, Web of Science, Wordometer and medRxiv from 10 January to 16 July 2020. These articles
were searched using the Medical Subject Headings terms ‘COVID-19’, ‘Serological assay’, ‘Laboratory Diagnosis’,
‘Performance characteristics’, ‘POCT’, ‘LFA’, ‘CLIA’, ‘ELISA’ and ‘SARS-CoV-2’. Data from original research articles
on SARS-CoV-2 antibody detection ≥second day postinfection were included in this study. In total, there were
7938 published articles on humoral immune response and laboratory diagnosis of COVID-19. Of these, 74 were
included in this study. The detection, peak and decline period of blood anti-SARS-CoV-2 IgM, IgG and total an-
tibodies for point-of-care testing (POCT), ELISA and CLIA vary widely. The most promising of these assays for
POCT detected anti-SARS-CoV-2 at day 3 postinfection and peaked on the 15th day; ELISA products detected
anti-SARS-CoV-2 IgM and IgG at days 2 and 6 then peaked on the eighth day; and the most promising CLIA
product detected anti-SARS-CoV-2 at day 1 and peaked on the 30th day. The most promising LFA, ELISA and
CLIA that had the best performance characteristics were those targeting total SARS-CoV-2 antibodies followed
© The Author(s) 2021. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. This is an Open Access
article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/
4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
For commercial re-use, please contact journals.permissions@oup.com
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by those targeting anti-SARS-CoV-2 IgG then IgM. Essentially, the CLIA-based SARS-CoV-2 tests had the best
performance characteristics, followed by ELISA then POCT. Given the varied performance characteristics of all
the serological assays, there is a need to continuously improve their detection thresholds, as well as to mon-
itor and re-evaluate their performances to assure their significance and applicability for COVID-19 clinical and
epidemiological purposes.
Keywords: COVID-19 serology, diagnostics, laboratory tests, SARS-CoV-2.
Introduction
The coronavirus disease 2019 (COVID-19) pandemic has caused
an unprecedented global health emergency and economic un-
certainty. As the incidence of COVID-19 continues to rise, many
countries have sought to develop or procure serological test kits
and strips with the plan of scaling up laboratory investigations
into the COVID-19 pandemic.
Severe acute respiratory syndromecoronavirus 2 (SARS-CoV-2)
is the etiological agent of COVID-19. It is one of the three highly
pathogenic members of the family of coronaviridae.1 Infection
with SARS-CoV-2 has been associated with a range of hallmarks
that progress from mild to severe clinical presentations before
terminating in death in less than 10% of cases.2
TheWHO has recommended RT-PCR as the gold standard pro-
tocol for screening individuals with typical symptoms who are
suspected of having COVID-19. Although appropriate use of RT-
PCR provides very accurate results, test reagents and consum-
ables are mostly in short supply. Besides, this protocol is labo-
rious, expensive to operate, requiring technical expertise and it
has a long test turnaround time. Also, one of the major techni-
cal drawbacks in using RT-PCR is the significant number of cases
of false-negative results, despite patients having clinical features
and radiologic findings that are highly suspicious of SARS-CoV-2
infection. The false-negative results could be due to wrong sam-
pling, where SARS-CoV-2 might have been present in the lower
respiratory tract rather than upper respiratory tract samples of-
ten collected for laboratory diagnosis. This poses a challenge in
the proper evaluation of some SARS-CoV-2-infected people.3
It has been observed that the transmission dynamics of
COVID-19 have made it an arduous task and challenge in
the control of the pandemic, despite WHO-proposed measures
having already been introduced.4 Consequently, the COVID-19
pandemic has seriously challenged the operation of the en-
tire healthcare system, including hospitals, laboratory diagnosis,
the management of patients and every other aspect of human
endeavor.5,6
In the quest to augment several lapses in the use of RT-
PCR testing for COVID-19, serological assays that detect and /or
measure antibodies (immunoglobulins) against SARS-CoV-2 have
been developed and evaluated for performance by many institu-
tions and private biotechnology firms. Global efforts to scale up
the testing and diagnosis of COVID-19 has led to the commercial
production of serological kits and devices. Someof these products
have gained executive approval in some countries. For instance,
the US Food and Drug Administration (FDA) gave expedient ap-
proval for some COVID-19 serological kits based on their accuracy
and reliability.7
Instances have arisen where massive production and the use
of finger-prick assays and in vitro testing have been encouraged
in the UK and the USA to scale up COVID-19 surveillance through
rapid testing and measurement of either antigens or antibodies
to SARS-CoV-2. These rapid testing protocols adopted in these
countries are point-of-care testing (POCT), which are designed as
lateral flowdevices (colloid gold-based immunochromatographic
cassettes or test strips) with a diverse range of performance char-
acteristics. These devices require a small sample volume (in mi-
croliters), are conducted within a short period (a few seconds to
minutes), and are easier to performas their use requires less tech-
nical expertise and equipment compared with protocols that de-
tect nucleic acid.8
The transmission dynamics of the COVID-19 pandemic make
it very challenging to control despite measures put in place
in various countries of Africa and elsewhere outside the con-
tinent. Adequate laboratory diagnosis of COVID-19 plays a
highly significant role in the control and prevention of the pan-
demic. However, some of the emerging challenges of testing for
SARS-CoV-2 generally include sourcing personal protective equip-
ment, low human capacity, scaling up testing, overwhelming
contact tracing and inadequate hospital capacity to accom-
modate COVID-19 patients, resulting in increased morbidity
and mortality. Hence, improved testing capacity, adequate
provision of human and material resources, combined with
innovative ways of scaling up contact tracing and improved
testing capacity, are essential in the control of the COVID-19
pandemic.
This study sought to provide an update on the kinetics of
humoral immune response to SARS-CoV-2 infection and perfor-
mance characteristics of serological protocols (lateral flow assay
[LFA], chemiluminescence immunoassay [CLIA] and ELISA) used
for evaluations of recent and past SARS-CoV-2 infection. Data
from original research articles on SARS-CoV-2 antibody detection
≥second day postinfection were included in this study. Further-
more, this study examined whether these tests could be possible
solutions that can ameliorate the constraints of underdiagnosis
in resource-limited settings.
This review is conducted under the following sections:
1. Virology and structural organization of SARS CoV-2 useful in
molecular and serological diagnosis.
2. Humoral immune response to SARS CoV-2.
3. COVID-19 serological assays.
4. Challenges of SARS-CoV-2 serological testing.
5. Accuracy and applicability of COVID-19 serological assays.
6. Performance characteristics of COVID-19 serological assays.
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A. U. Emeribe et al.
Article selection criteria
Search strategy
A thorough and comprehensive review of suitable and eligible
full-text articles was performed on PubMed, Scopus, Web of Sci-
ence,Wordometer andmedRxiv from10 January to 16 July 2020.
These articles were searched using the MeSH terms ‘COVID-19’,
‘Serological assay’, ‘Laboratory Diagnosis’, ‘Performance charac-
teristics’, ‘POCT’, ‘CLIA’, ‘ELISA’ and ‘SARS-CoV-2’.
Article evaluation and data extraction
Eight authors independently evaluated and scrutinized titles and
abstracts to prospective studies to check for potentially eligible
articles and to acquire full texts from credible databases. Articles
that were unavailable, incomplete or contained duplicate data
were excluded. Furthermore, data from review articles were not
considered for computing the antibody kinetics and performance
characteristics of the serological assays.
Data were extracted from all eligible studies using the follow-
ing criteria: (1) author, title, published date, the countries where
studies were conducted, study design, sampling technique, par-
ticipant inclusion criteria, number of participants enrolled and
number of participantswith known and available results; (2)main
data, consisting of the results of serologic tests and RT-PCR for
COVID-19 (sensitivity, specificity, positive predictive value [PPV]
and negative predictive value [NPV]), number of days after the
onset of symptoms, days of detection, peak and decline of anti-
bodies; and (3) the test protocol used for serology and SARS-CoV-
2 RNA detection.
Search outcome
In total, there were 7938 published articles on humoral immune
response and laboratory diagnosis of COVID-19. Of these, 74were
included in this study based on selection criteria.
Main findings
Structural organization of SARS-COV-2 useful in
serological diagnosis
SARS-CoV-2 is a single-stranded RNA virus with positive polar-
ity.9,10
The SARS-CoV-2 genome consists of 14 open reading frames
(ORFs) that code for 27 viral proteins, where the longest ORF
coding for the 15 non-structural proteins plays an important
role in viral propagation and immune evasion; the ORF codings
for structural and accessory proteins are located on the 5´ end
and 3´ end, respectively.11 The first ORF code encompasses
two-thirds of the viral genome and translates the polyproteins
pp1a and pp1ab, which are implicated in the encoding of the
16 non-structural proteins. However, the remaining ORFs code
for the viral structural and accessory proteins. The structural
protein nucleocapsid (N) proteins, spike (S) glycoprotein, matrix
(M) protein and small envelope (E) complete the remaining one
third of the viral genome.12 These proteins and RNA-dependent
RNA polymerase have been substantially harnessed for primers
and antigens in the molecular and serological assays used for
COVID-19, respectively.13
Humoral immune response to SARS-COV-2 infection
There is ongoing research into better understanding the viral
genome assembly, replication and mutation of SARS-CoV-2.
These viral attributes drastically influence the diagnostic perfor-
mance of both molecular and serological assays as well as the
transmissibility of SARS-CoV-2 and its immune responses.14
Prior to SARS-CoV-2 infection, an unexposed individual was
expected to have a negative test for either anti-SARS-CoV-2 IgM
or IgG (Figure 1). However, following exposure to the infection,
SARS-CoV-2 now induces a humoral immune response, which
commences with the development of IgM, indicating an acute
or ongoing infection from the third day of the first week of
infection, as reflected by a positive outcome in either the IgM or
IgM/IgG serological test.15 The level of IgM in an individual with
the activated humoral immune response against SARS-CoV-2
continues to rise until it peaks during the third week following
infection.15 By the end of the third week, IgM levels decrease with
a concomitant elevation in the level of IgG from the third to the
seventh week post symptom onset (PSO), which is revealed by
a positive outcome in either the IgG or IgM/IgG serological test
(Figure 2).15
The median period for the development of all the classes of
immunoglobulins following the activation of humoral immune
response is 13 d.16 Individually, IgM, IgG and total immunoglob-
ulins have an average duration of 11, 12 and 14 d, respectively.16
These immunoglobulins can be measured and monitored by a
diverse range of antibody-based serological testing techniques,
which include rapid diagnostic assay (e.g. lateral flow immunoas-
say [LFIA] with colloidal gold], CLIA, ELISA and neutralization
assay with various diagnostic performance ratings (e.g. sensi-
tivity, specificity, accuracy, PPV and NPV), sampling methods
(e.g. finger prick, venipuncture), turnaround time and setting.16
Previous studies have demonstrated the diagnostic roles of these
antibody-based serological testing techniques based on their
performance. Zhao et al.17 demonstrated that within the first 7 d
PSO of COVID-19 infection, the sensitivity of total antibody, IgM
and IgG were 38.3%, 28.7% and 19.1%, respectively, which was
lower compared with the RNA-based test of 66.7% sensitivity. As
the duration of PSO increased, the sensitivity of the RNA-based
test decreased by 21.2%, while those of the total antibody, IgM
and IgG increased by 61.7%, 65.6% and 60.78%, respectively,
within the 15th to 39th day PSO. When the RNA- and antibody-
based tests were combined, sensitivity significantly improved to
78.7%, 97.0% and 100% within 1–7, 8–14 and 15–39 d PSO, re-
spectively. The implication of this study indicates the unreliability
and unsuitability of serology within the window period of infec-
tion, but also reveals an impressive sensitivity for total antibody-
based assay in detection of SARS-CoV-2 as the PSO period
progresses.
The study further revealed that the percentage of patients
with undetectable RNA but with detectable immunoglobulin
increased from 28.7% within the first 3 d to 100% within 15–
39 d of PSO. This is where the total Ab (which is better than
testing IgM and IgG individually) comes in, to rule out people
with undetectable RNA.17 The same study recommended the
combination of both RNA- and antibody-based tests to scale
up the sensitivity of RNA during the course of the infection. This
combined approach was observed to attain timely diagnosis of
SARS-CoV-2 infection, prevent multiple sampling several days
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Figure 1. Kinetics of antibody response in SARS-CoV-2 infection. The entry of the SARS-CoV-2 virus into the host cell through interaction and binding
between the host’s angiotensin-converting enzyme 2 (ACE2) proteins (receptor) and the viral spike (S) protein (ligand) (1). Following replication and
release from the host cells (2), antigen-presenting cells (APCs) like macrophages and dendritic cells engulf some of the viruses, digest and present the
digested antigen fragments on their class II MHCmolecules to the helper T (Th) cells (3). Th cells, in turn, activate B cells (4), activated B cells proliferate
and differentiate into memory B cells or plasma cells with high affinity to the SARS-CoV-2 antigens (5). Plasma cells release SARS-CoV-2-specific
antibodies (IgM, IgG or IgA) that bind and neutralize the viruses, thus preventing the viral entry into the host cell (6).
for infection status confirmation, and enhance the ability to
prioritize relevant treatments and isolation management.18–20
The changes of the antibody response against SARS-CoV-2
are presently under study, as antibodies may be regarded as
potent diagnostic tools to complement RT-PCR-based findings.
The SARS-CoV-triggered humoral S- and N-specific IgM response
reached a climax within 4 wk and was no more detectable at
3 mo PSO; the switch to IgG often occurred about day 14 and
IgG were demonstrated up to 36 mo.21,22
In another study, the authors demonstrated that in 34 SARS-
CoV-2 laboratories established, the cases studied were positive
for IgM and IgG at week 3 PSO.15 Therefore, in the majority
of those patients, the acute phase of infection persisted for
>30 d. In an inverse relation, as IgM levels decrease, IgG levels
rise gradually from the third to the seventh week, signifying the
activation of the humoral immune response against the virus.15
Thus, the humoral response activated by SARS-CoV-2 may be
similar to that elicited by SARS-CoV.15,16
In an immunodynamics study reported by Zhao et al.,17 it was
observed that the antibody profile in COVID-19 patients showed
that seroconversion sequentially appeared for total antibodies,
IgM and IgG with a median time of 11, 12 and 14 d, respectively.
Full concentrations of SARS-CoV-2 antibodies were detected by
double recombinant antigen sandwich immunoassay, which
utilized the receptor-binding domain (RBD) of S1 protein and
the horse raddish peroxidase-conjugated antigen; IgM μ-chain
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Figure 2. Timeline of IgM, IgG and total antibody kinetics during SARS-CoV-2 infection. The level of IgM in an individual with the activated humoral
immune response against SARS-CoV-2 continues to rise until it peaks at the third week following infection. By the end of the third week, IgM levels
decrease with a concomitant elevation in the level of IgG from the third to the seventh week postonset symptom (POS). For the total antibody, it
peaks at the middle of the second week and reaches a plateau in the middle of the third week. The blood concentration persists for several weeks
and months postinfection (image made with Biorender.com).
capture immunoassay was used for anti-SARS-CoV-2 IgM de-
tection. On the other hand, an indirect ELISA kit based on
recombinant NP antigen was used for anti-SARS-CoV-2 IgG de-
tection.17 The seroconversion rates recorded were 93.1%, 82.7%
and 64.7% for total antibodies, IgM and IgG, respectively, and no
significant difference was observed between severely and mildly
affected COVID-19 patients.
The sensitivity of serum anti-SARS-CoV-2 detection was
lower than the RT-PCR RNA assay within 7 d from the onset of
illness (38.3% vs 66.7% for serological vs RT-PCR). However, the
sensitivity increased steadily from the eighth to the 39th day
PSO and overtook that of the RT-PCR test.17 More significantly,
detectable and measurable levels of total anti-SARS-CoV-2 in
the sera were found in COVID-19 patients with undetectable
SARS-CoV-2 RNA in their respiratory tract samples.17 These re-
sults highlighted the importance of combining molecular and
serological tests for the correct diagnosis of COVID-19 patients
at different stages of the disease. In agreement with these
reports, Jin et al. recorded the specificity of serum anti-SARS-
CoV IgM and IgG as 90% compared with that of the RT-PCR
test.23
In a study by Guo et al., which was carried out on two cohorts
of SARS-CoV-2-infected patients, the early antibody response to
NP protein was evaluated. Of 208 patients, 90.4% and 93.3%
harbored plasma IgM and IgA, respectively. Also, 77.9% of
plasma samples were IgG positive, and the median time for both
IgM and IgA detection was on day 5 PSO (IQR 3–6) and day 14
PSO (IQR 10–18) for IgG.24 The authors observed that swift and
unanticipated IgA seroconversion might be an upshot of the
cytokine storm promoting the germline transcription of α and μ
genes of the heavy chain constant.
Furthermore, it has been reported and established that T-
cell-independent antibody responses can cause excitation of a
specialized B cell subset to produce both IgA and IgM throughout
the infection of some pathogens.25 Although T-cell-independent
antibody response against viruses is still controversial, some
viruses can act in vivo as T-cell-independent antigens and there-
fore cause eliciting protective isotype-switched antibodies in the
non-appearance of conventional T-cell help. Inactivated virus
or virus-like particles can also elicit IgM response, but factors
induced when an active virus infection is ongoing seem very
important and are required before there can be induction of the
isotype switch and then IgG or IgA responses.26
In another study of 214 COVID-19 patients, 68.2% and 70.1%
were positive for rN-specific IgM and IgG, respectively; and 77.1%
and 74.3% were positive for rS-specific IgM and IgG, respec-
tively.27 These findings indicated that the detection of rS-specific
IgM was more sensitive compared with that of rN-specific IgM,
whichmay be because of the lower immunogenicity of the N pro-
tein compared with that of the S protein. A bioinformatics study
reported a lower number of B cell epitopes in the NP protein of
SARS-CoV-2 than in the S protein, especially as the positive rates
of IgM and IgG were low during the early stages of the disease
(0–10 days post-disease onset (DPO)). On the other hand, IgM
and/or IgG specific for rN and rS reached a climax at 11–15 DPO.27
The sensitivity of the tests and the epitope on which the test
is based are significant factors for the well-organized detec-
tion of specific SARS-CoV-2 antibodies and timing of the humoral
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response. Consequently, several tests are rapidly being developed
in many laboratories. For example, Li et al. developed a point-of-
care LFIA test based on the RBD antigen of the SARS-CoV-2 S1
protein that can help in the concomitant detection of IgM and
IgG in human blood within 15 min, with higher sensitivity than
the individual IgG and IgM tests; however, the detection limit of
the test was not determined.19 Also, Amanat et al. developed
sensitive and specific ELISA assays based on the recombinant full-
length S protein and RBD epitope, permitting the screening and
detection of seroconversion upon SARS-CoV-2 infection 3 d PSO.28
Of note, no cross-reactivity from other human coronaviruses was
noted, in agreement with another study highlighting that S1 is
a specific antigen for SARS-CoV-2 diagnosis, as cross-reactive
antibodies against the S protein of Middle East respiratory
syndrome-related coronavirus (MERS-CoV) were not detected in
a COVID-19 patient.29 Additionally, strong IgA and IgM responses
were discovered and the IgG3 response was stronger than that
of IgG1.28 The sensitivity of the test may create challenges for
the early detection of IgM. Several patients were more positive
for IgG than IgM during the time of hospital stay and 5 d later;
likewise, they had an earlier IgG than IgM seroconversion.30
Furthermore, SARS-CoV-2-specific antibodies were detected
in the sera of six infants born to mothers with COVID-19. Five of
the six infants and their mothers had elevated levels of IgG and
two of them also had elevated levels of anti-SARS-CoV-2 IgM.
Three of the six infants who had elevated levels of IgG also had
normal levels of IgM. However, two of their mothers displayed
elevated levels of IgM. How the newborns that developed IgM
require additional investigation. Undeniably, due to its large
magnitude, IgM is not typically transferred through the placenta;
however, it is affected by some pathology that compromises its
configuration. The newborn might be in contact with the virus if
the latter crosses the placenta, although no virus was detected
from RT-PCR analysis.31
Currently, several studies are investigating the connection
between antigen-specific antibodies and the clinical characteris-
tics of COVID-19 patients, but interestingly, among people with
comorbidities, lesser anti-RBD IgG, but not anti-NP IgM or IgG,
have been reported, although the difference was not significant
when compared with people without comorbidities.
COVID-19 serological assays
The recent pandemic outbreak of the SARS-CoV-2 virus and its
rapid spread poses an urgent need for both diagnostic and ther-
apeutic interventions to manage the infection and the outcome
of the disease. The diminishment or absence of IgG and per-
sistence of IgM are considered biomarkers for recent infection.
As the epidemic progresses more individuals could get infected.
The measurement of these antibodies is a good differential
that helps to distinguish between recent and older infections.17
The detection of IgM (from days 1 to 7) in the absence of IgG
represent an acute/recent infection, whereas the simultaneous
detection of IgM and IgG could represent acute reinfection.18
On the other hand, the detection of IgG in the absence of IgM
denotes a past infection.18
The increasing number of confirmed COVID-19 cases has
resulted in an unprecedented rise in demand for antibody-based
tests from researchers and healthcare policymakers. Recently, a
list of >200 serological products was released by the Foundation
for Innovative New Diagnostics (FIND); these products, which are
predominately from China, are currently either available for use
or are in industrial development and evaluation. However, only
12 have received emergency use authorization from the FDA.
Serological products from a host of other countries, including
South Korea, Germany, the USA and the UK, were also present
on the FIND list.
Some commercially available serology-based tests have been
considered to be inadequate for COVID-19 diagnosis if used
alone, due to their low degrees of sensitivity and specificity. For
instance, anti-SARS-CoV-2 IgG takes a relatively long period (not
yet reported) for quantification.18 More details regarding the lim-
itations of COVD-19 serological assay follow later in this article.
Cases of poor performance characteristics of some serological
kits/devices underscore the need for re-evaluation and validation
before being made available to end-users. This is to prevent
clinicians and healthcare professionals from using these sero-
logical kits/strips off the shelf for clinical purposes. Furthermore,
despite kits’ satisfactory diagnostic performance, it is important
to include internal quality control and external quality assurance
measures in all tests run on human samples to ensure accuracy,
precision and reproducibility of test results.
Challenges of SARS-CoV-2 serological testing
Serological tests rely on the detection of specific anti-viral anti-
bodies (IgM, IgA, IgG or total antibody) in patient sera, plasma
or whole blood.32 Determining the optimal antigenic epitopes
to maximize sensitivity, but minimize cross-reactivity, particu-
larly against other human coronaviruses, has meant that the
development of high-quality serological testing has been slower
than molecular-based diagnostics.17,32 Initial candidate epi-
topes have largely focused on the immunogenic viral structural
proteins which include nucleocapsid (N) and spike (S) protein,
particularly the S1 subunit and the RBD.32 To date, a range of
serological tests for COVID-19 have been developed, each with
particular test characteristics. Broadly, these serological tests
can be divided into tests that (1) can be performed at the point of
care; (2) can be performed in routine diagnostic laboratories; and
(3) can only be performed in specialized reference laboratories.
Initial studies have reported that most patients with COVID-
19 seroconvert by day 10–14 (approximately 80%), with almost
100% seroconversion by day 20.6,7 However, comparisons across
published studies are challenging due to (1) different antigens
used in assays; (2) differences in the complexity of patient pop-
ulations; and (3) variations in the RT-PCR assays used as the gold
standard for determining the sensitivity of serological assays.
Further, it is not clear whether the type and number of antibodies
correlate with the severity of COVID-19, or more importantly,
with immune protection from reinfection.
At present, the most widely available (and most publicized)
serological tests are POCT, which involves the detection of anti-
SARS-CoV-2 antibodies through binding to immobilized antigen,
generally bound to colloidal gold on a test strip. The relatively
cheap and simple nature of lateral flow assays means that pro-
duction is suited to scaling up for increased testing capacity. How-
ever, there are limited published data on the performance char-
acteristics of serological POCT, and high-quality data are urgently
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 https://academ
ic.oup.com
/inthealth/article/14/1/18/6147255 by Turun Yliopisto user on 09 M
ay 2022
A. U. Emeribe et al.
Ta
bl
e
1.
Di
ag
no
st
ic
pe
rf
or
m
an
ce
of
po
in
t-
of
-c
ar
e
te
st
se
ro
lo
gi
ca
lp
ro
to
co
lf
ro
m
pu
bl
is
he
d
da
ta
Ci
ta
tio
n
Pr
od
uc
tn
am
e/
so
ur
ce
Ty
pe
Sa
m
pl
e
si
ze
Se
ns
iti
vi
ty
(%
)
Sp
ec
ifi
ci
ty
(%
)
PP
V
(%
)
N
PV
(%
)
Li
m
ita
tio
n
of
st
ud
y
Ge
ur
ts
va
nK
es
se
l
et
al
.b
43
Ra
pi
d
SA
RS
-C
oV
-2
an
tib
od
y
(I
gM
/I
gG
)t
es
tf
ro
m
In
Te
c
(T
es
to
f
lo
tS
20
20
02
15
05
)
To
ta
l
93
96
.5
5
(2
8/
29
)
73
.4
4
(4
7/
64
)
62
.2
2
(2
8/
45
)
97
.9
2
(4
7/
48
)
a.
N
o
ad
di
tio
na
lv
al
id
at
io
n
in
pa
rt
ic
ip
an
ts
w
ith
m
ild
sy
m
pt
om
s;
th
is
is
re
qu
ire
d
to
ru
le
ou
ta
ny
po
ss
ib
le
un
de
re
va
lu
at
ed
pa
tie
nt
Ig
G
93
96
.5
5
(2
8/
29
)
76
.5
6
(4
9/
64
)
65
.1
2
(2
8/
43
)
98
.0
(4
9/
50
)
b.
Th
er
e
is
a
ris
k
of
in
te
rp
re
tin
g
a
po
si
tiv
e
ou
tc
om
e
as
a
m
ea
su
re
of
pr
ot
ec
tio
n
ag
ai
ns
tt
he
vi
ru
s
Ig
M
93
89
.6
6
(2
6/
29
)
73
.4
4
(4
7/
64
)
60
.4
7
(2
6/
43
)
94
.0
(4
7/
50
)
c.
Se
ns
iti
vi
ty
in
th
e
ea
rly
ph
as
e
of
in
fe
ct
io
n
w
as
po
or
qS
AR
S-
Co
V-
2
Ig
G/
Ig
M
ca
ss
et
te
ra
pi
d
te
st
(G
IC
A)
fro
m
Ce
lle
x
In
c.
(t
es
tl
ot
02
00
31
1W
I5
51
3C
-3
)
To
ta
l
93
87
.7
6
(4
3/
49
)
84
.0
9
(3
7/
44
)
86
.0
(4
3/
50
)
86
.0
5
(3
7/
43
)
d.
Re
la
tiv
el
y
sm
al
ls
iz
e
us
ed
fo
rd
et
er
m
in
in
g
ki
t
sp
ec
ifi
ci
ty
fo
ro
rie
nt
ge
ne
RD
T
Ig
G
93
83
.6
7
(4
1/
49
)
84
.0
9
(3
7/
44
)
85
.4
2
(4
1/
48
)
82
.2
2
(3
7/
45
)
Ig
M
93
87
.7
6
(4
3/
49
)
81
.8
2
(3
6/
44
)
84
.3
1
(4
3/
51
)
85
.7
1
(3
6/
42
)
CO
VI
D-
19
Ig
G/
Ig
M
ra
pi
d
te
st
ca
ss
et
te
(w
ho
le
bl
oo
d/
se
ru
m
/p
la
sm
a)
fro
m
or
ie
nt
ge
ne
/H
ea
lg
en
(t
es
tl
ot
20
03
26
0)
To
ta
l
90
91
.3
6
(7
4/
81
)
10
0.
0
(9
/9
)
10
0
(7
4/
74
)
56
.2
5
(9
/1
6)
Ig
G
90
91
.3
6
(7
4/
81
)
10
0.
0
(9
/9
)
10
0
(7
4/
74
)
56
.2
5
(9
/1
6)
Ig
M
90
88
.8
9
(7
2/
81
)
10
0.
0
(9
/9
)
10
0.
0
(7
2/
72
)
50
.0
(9
/1
8)
Li
et
al
.a
19
Go
at
an
ti-
hu
m
an
Ig
G
an
d
Ig
M
an
tib
od
ie
s,
ra
bb
it
Ig
G
an
d
go
at
an
ti-
ra
bb
it
Ig
G
an
tib
od
ie
s
w
er
e
ob
ta
in
ed
fro
m
Si
gm
a-
Al
dr
ic
h
To
ta
l
52
5
88
.6
6
(3
52
/3
97
)
90
.6
3
(1
16
/1
28
)
96
.7
(3
52
/3
64
)
72
.0
5
(1
16
/1
61
)
a.
In
ab
ili
ty
to
co
nfi
rm
th
e
pr
es
en
ce
of
th
e
SA
RS
-C
oV
-2
Ig
G
52
5
70
.5
3
(2
80
/3
97
)
98
.4
4
(1
26
/1
28
)
99
.2
9
(2
80
/2
82
)
53
.0
9
(1
26
/2
43
)
b.
Cr
os
s-
re
ac
tiv
ity
st
ud
ie
s
w
ith
ot
he
r
co
ro
na
vi
ru
se
s
an
d
flu
vi
ru
se
s
w
er
e
no
t
pe
rf
or
m
ed
Ig
M
52
5
82
.6
2
(3
28
/3
97
)
91
.4
1
(1
17
/1
28
)
96
.7
6
(3
28
/3
39
)
62
.9
0
(1
17
/1
86
)
c.
Th
e
le
ve
lo
fc
ha
ng
es
in
im
m
un
og
lo
bu
lin
s
w
as
no
tc
om
pa
re
d
w
ith
th
e
va
rio
us
st
ag
es
of
SA
RS
-C
oV
-2
in
fe
ct
io
n
24
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ow
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ic.oup.com
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ay 2022
International Health
Ta
bl
e
1.
Co
nt
in
ue
d
Ci
ta
tio
n
Pr
od
uc
tn
am
e/
so
ur
ce
Ty
pe
Sa
m
pl
e
si
ze
Se
ns
iti
vi
ty
(%
)
Sp
ec
ifi
ci
ty
(%
)
PP
V
(%
)
N
PV
(%
)
Li
m
ita
tio
n
of
st
ud
y
Ca
ss
an
iti
et
al
.a
44
Vi
va
Di
ag
TM
CO
VI
D-
19
Ig
M
/I
gG
ra
pi
d
te
st
To
ta
l
50
18
.4
2
(7
/3
8)
91
.6
7
(1
1/
12
)
87
.5
(7
/8
)
26
.1
9
(1
1/
42
)
a.
Sm
al
ls
am
pl
e
si
ze
Ig
G
50
13
.1
6
(5
/3
8)
10
0
(1
2/
12
)
10
0
(5
/5
)
26
.6
7
(1
2/
45
)
b.
Po
or
se
ns
iti
vi
ty
Ig
M
50
15
.7
9
(6
/3
8)
91
.6
7
(1
1/
12
)
85
.7
1
(6
/7
)
25
.5
8
(1
1/
43
)
c.
H
ig
h
fa
ls
e-
ne
ga
tiv
e
va
lu
e,
w
hi
ch
ca
n
le
ad
to
m
is
di
ag
no
si
s
Po
rt
e
et
al
.a
45
Fl
uo
re
sc
en
ce
im
m
un
oc
hr
om
at
og
ra
ph
ic
SA
RS
-C
oV
-2
an
tig
en
te
st
(B
io
ea
sy
Bi
ot
ec
hn
ol
og
y
Co
.,
Sh
en
zh
en
,C
hi
na
)
To
ta
l
12
7
93
.9
(7
7/
82
)
10
0
(4
5/
45
)
10
0
(7
7/
77
)
90
.0
(4
5/
50
)
a.
U
se
of
sa
m
pl
es
no
ts
pe
ci
fic
al
ly
pe
rm
itt
ed
by
th
e
m
an
uf
ac
tu
re
ro
ft
he
ki
t
Ig
G
12
7
N
Aa
N
Aa
N
Aa
N
Aa
b.
Re
tr
os
pe
ct
iv
e
us
e
of
cl
in
ic
al
da
ta
Ig
M
12
7
N
Aa
N
Aa
N
Aa
N
Aa
Pa
n
et
al
.a
46
Co
llo
id
al
go
ld
-b
as
ed
im
m
un
oc
hr
om
at
og
ra
ph
ic
st
rip
(Z
hu
ha
iL
iv
zo
n
Di
ag
no
si
tic
In
c.
)
To
ta
l
10
8
68
.6
(5
9/
86
)
63
.6
4
(1
4/
22
)
88
.0
6
(5
9/
67
)
34
.1
5
(1
4/
41
)
a.
In
te
ns
ity
of
co
lo
rb
an
ds
fo
rm
ed
do
no
tc
or
re
la
te
w
ith
th
e
ab
un
da
nc
e
of
im
m
un
og
lo
bu
lin
Ig
G
10
8
54
.6
5
(4
7/
86
)
59
.0
9
(1
3/
22
)
83
.9
3
(4
7/
56
)
25
.0
(1
3/
52
)
b.
Ve
ry
lo
w
pr
ob
ab
ili
ty
of
ha
vi
ng
ne
ga
tiv
e
ou
tc
om
es
w
ith
ou
tt
he
in
fe
ct
io
n
Ig
M
10
8
55
.8
1
(4
8/
86
)
36
.3
6
(8
/2
2)
77
.4
2
(4
8/
62
)
17
.3
9
(8
/4
6)
La
ss
au
ni
er`
e
et
al
.a
35
20
19
-n
CO
V
Ig
G/
Ig
M
ra
pi
d
te
st
(D
yn
am
ik
er
Bi
ot
ec
hn
ol
og
y,
Ti
an
jin
,
Ch
in
a
Ca
t#
DN
K-
14
19
–1
)
To
ta
l
62
90
(2
7/
30
)
10
0
(3
2/
32
)
10
0
(2
7/
27
)
89 (3
2/
35
)
a.
Sm
al
ls
am
pl
e
si
ze
Ig
G
62
N
Ab
N
Ab
N
Ab
N
Ab
b.
Al
lk
its
w
er
e
no
tt
es
te
d
un
ifo
rm
ly
w
ith
th
e
sa
m
e
nu
m
be
ro
fc
on
tr
ol
se
ra
Ig
M
62
N
Ab
N
Ab
N
Ab
N
Ab
c.
Ac
ro
Bi
ot
ec
h
an
d
Al
lte
st
Bi
ot
ec
h
ha
d
co
m
pa
ra
tiv
el
y
po
or
te
st
pe
rf
or
m
an
ce
s,
w
hi
ch
le
d
to
th
e
su
sp
en
si
on
of
fu
rt
he
rt
es
tin
g
O
nS
ite
TM
CO
VI
D-
19
Ig
G/
Ig
M
ra
pi
d
te
st
(C
TK
Bi
ot
ec
h,
Po
w
ay
,C
A,
U
SA
;c
at
.#
R0
18
0C
)
To
ta
l
62
90
(2
7/
30
)
10
0
(3
2/
32
)
10
0
(2
7/
27
)
89 (3
2/
35
)
c.
Ac
ro
Bi
ot
ec
h
te
st
ha
d
a
cr
os
s-
re
ac
tio
n
w
ith
a
co
nt
ro
ls
er
um
of
a
pa
tie
nt
in
fe
ct
ed
w
ith
hu
m
an
co
ro
na
vi
ru
s
H
KU
1
25
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ow
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ic.oup.com
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ay 2022
A. U. Emeribe et al.
Ta
bl
e
1.
Co
nt
in
ue
d
Ci
ta
tio
n
Pr
od
uc
tn
am
e/
so
ur
ce
Ty
pe
Sa
m
pl
e
si
ze
Se
ns
iti
vi
ty
(%
)
Sp
ec
ifi
ci
ty
(%
)
PP
V
(%
)
N
PV
(%
)
Li
m
ita
tio
n
of
st
ud
y
Ig
G
62
N
Ab
N
Ab
N
Ab
N
Ab
d.
Th
e
in
di
ca
tio
ns
of
th
e
pr
es
en
ce
of
SA
RS
-C
oV
-2
ha
s
no
co
rr
el
at
io
n
w
ith
im
m
un
ity
ag
ai
ns
tS
AR
S-
Co
V-
2
in
fe
ct
io
n
Ig
M
62
N
Ab
N
Ab
N
Ab
N
Ab
e.
Sa
m
pl
e
si
ze
us
ed
w
as
sm
al
l
An
ti-
SA
RS
-C
oV
-2
ra
pi
d
te
st
(A
ut
oB
io
Di
ag
no
st
ic
s,
Zh
en
gz
ho
u,
Ch
in
a;
ca
t.
#
RT
A0
20
4)
To
ta
l
62
93
(2
8/
30
)
10
0
(3
2/
32
)
10
0
(2
8/
28
)
94
.1
(3
2/
34
)
Ig
G
62
N
Ab
N
Ab
N
Ab
N
Ab
Ig
M
62
N
Ab
N
Ab
N
Ab
N
Ab
Co
ro
na
vi
ru
s
di
se
as
es
20
19
(C
O
VI
D-
19
)I
gM
/I
gG
an
tib
od
y
te
st
(A
rt
ro
n
La
bo
ra
to
rie
s,
Bu
rn
ab
y,
Ca
na
da
;c
at
.#
A0
3–
51
-3
22
)
To
ta
l
47
83
(2
5/
30
)
10
0
(1
7/
17
)
10
0
(2
5/
25
)
74
(1
7/
22
)
Ig
G
47
N
Ab
N
Ab
N
Ab
N
Ab
Ig
M
47
N
Ab
N
Ab
N
Ab
N
Ab
20
19
-n
Co
V
Ig
G/
Ig
M
ra
pi
d
te
st
ca
ss
et
te
(A
cr
o
Bi
ot
ec
h,
Ra
nc
ho
Cu
ca
m
on
ga
,C
A,
U
SA
;c
at
.#
IN
CP
-4
02
)
To
ta
l
20
80
(4
/5
)
80
(1
2/
15
)
57
.1
(4
/7
)
92
.3
(1
2/
13
)
Ig
G
20
N
Ab
N
Ab
N
Ab
N
Ab
Ig
M
20
N
Ab
N
Ab
N
Ab
N
Ab
20
19
-n
Co
V
Ig
G/
Ig
M
ra
pi
d
te
st
ca
ss
et
te
(H
an
gz
ho
u
Al
lte
st
Bi
ot
ec
h,
H
an
gz
ho
u,
Ch
in
a;
ca
t.
#
IN
CP
-4
02
)
To
ta
l
16
10
0
(1
/1
)
86
.7
(1
3/
15
)
33
.3
(1
/3
)
N
Ab
Ig
G
16
N
Ab
N
Ab
N
Ab
N
Ab
Ig
M
16
N
Ab
N
Ab
N
Ab
N
Ab
H
of
fm
an
et
al
.a
20
CO
VI
D-
19
Ig
G/
Ig
M
ra
pi
d
te
st
ca
ss
et
te
(Z
he
jia
ng
O
rie
nt
Ge
ne
Bi
ot
ec
h
Co
Lt
d,
H
uz
ho
u,
Zh
ej
ia
ng
,
Ch
in
a;
pr
od
uc
t/
m
od
el
:
GC
CO
V-
40
2a
,L
ot
:2
00
32
42
)
To
ta
l
15
3
93
.1
(2
7/
29
)
10
0
(1
24
/1
24
)
10
0
(2
7/
27
)
98
.4
(1
24
/1
26
)
a.
In
ad
eq
ua
te
co
m
pa
ris
on
w
ith
cl
in
ic
al
sy
m
pt
om
s
of
po
si
tiv
e
ca
se
s
26
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ow
nloaded from
 https://academ
ic.oup.com
/inthealth/article/14/1/18/6147255 by Turun Yliopisto user on 09 M
ay 2022
International Health
Ta
bl
e
1.
Co
nt
in
ue
d
Ci
ta
tio
n
Pr
od
uc
tn
am
e/
so
ur
ce
Ty
pe
Sa
m
pl
e
si
ze
Se
ns
iti
vi
ty
(%
)
Sp
ec
ifi
ci
ty
(%
)
PP
V
(%
)
N
PV
(%
)
Li
m
ita
tio
n
of
st
ud
y
Ig
G
15
3
68
.9
7
(2
0/
29
)
10
0
(1
24
/1
24
)
10
0
(2
0/
20
)
93
.2
3
(1
24
/1
33
)
Ig
M
15
3
93
.1
(2
7/
29
)
99
.1
9
(1
23
/1
24
)
96
.4
3
(2
7/
28
)
98
.4
(1
23
/1
25
)
Pa
lle
te
ta
l.a
47
CO
VI
D-
19
Ig
G/
Ig
M
ra
pi
d
te
st
ca
ss
et
te
s
(O
rie
nt
Ge
ne
)
To
ta
l
20
0
82
.6
7
(1
24
/1
50
)
96
.0
(4
8/
50
)
98
.4
8
(1
30
/1
32
)
70
.5
9
(4
8/
68
)
a
Po
or
pe
rf
or
m
an
ce
in
pa
tie
nt
s
w
ith
≤1
4
d
PO
S
Ig
G
20
0
82
.6
7
(1
24
/1
50
)
96
.0
(4
8/
50
)
98
.4
1
(1
24
/1
26
)
64
.8
6
(4
8/
74
)
Ig
M
20
0
83
.3
3
(1
25
/1
50
)
10
0
(5
0/
50
)
10
0
(1
25
/1
25
)
66
.6
7
(5
0/
75
)
Sp
ic
uz
za
et
al
.a
48
20
19
-n
Co
V
Ig
G/
Ig
M
an
tib
od
y
ra
pi
d
te
st
ki
t(
Be
iji
ng
Di
ag
re
at
Bi
ot
ec
hn
ol
og
ie
s
Co
.,
Lt
d)
To
ta
l
37
82
.6
1
(1
9/
23
)
92
.8
6
(1
3/
14
)
95
.0
(1
9/
20
)
76
.4
7
(1
3/
17
)
a.
Sm
al
ls
am
pl
e
si
ze
Ig
G
37
N
Ab
N
Ab
N
Ab
N
Ab
b.
N
ot
re
lia
bl
e
fo
rp
at
ie
nt
s
w
ith
sy
m
pt
om
s
w
ith
in
th
e
ea
rly
da
ys
of
in
fe
ct
io
n
Ig
M
37
N
Ab
N
Ab
N
Ab
N
Ab
W
u
et
al
.a
49
AL
LT
ES
T
20
19
-n
Co
V
Ig
G/
Ig
M
ra
pi
d
te
st
(H
an
gz
ho
u
AL
LT
ES
T
Bi
ot
ec
h
Co
.,
Lt
d.
[C
hi
na
])
To
ta
l
12
2
10
0
(2
2/
22
)
98
(9
8/
10
0)
91
.6
7
(2
2/
24
)
10
0
(9
8/
98
)
a.
Si
ng
le
-c
en
te
rs
tu
dy
Ig
G
12
2
10
0
(2
2/
22
)
98
(9
8/
10
0)
91
.6
7
(2
2/
24
)
10
0
(9
8/
98
)
b.
In
ad
eq
ua
te
nu
m
be
ro
fc
as
es
,w
hi
ch
co
ul
d
no
tr
ev
ea
lt
he
st
at
is
tic
al
di
ffe
re
nc
e
in
th
e
pe
rf
or
m
an
ce
ch
ar
ac
te
ris
tic
s
fo
rt
he
va
rio
us
PO
CT
Ig
M
12
2
90
.9
1
(2
0/
22
)
96
(9
6/
10
0)
83
.3
3
(2
0/
24
)
97
.9
6
(9
6/
98
)
c.
La
bo
ra
to
ry
in
ve
st
ig
at
io
n
fo
rc
ro
ss
-r
ea
ct
iv
ity
st
ud
ie
s
w
er
e
in
ad
eq
ua
te
Dy
na
m
ik
er
20
19
-n
Co
V
Ig
G/
Ig
M
ra
pi
d
te
st
(D
yn
am
ik
er
Bi
ot
ec
hn
ol
og
y
[T
ia
nj
in
]C
o.
,
Lt
d.
[C
hi
na
])
To
ta
l
46
2
89
.5
1
(1
45
/1
62
)
96
.3
3
(2
89
/3
00
)
92
.9
5
(1
45
/1
56
)
94
.4
4
(2
89
/3
06
)
d.
Po
ss
ib
le
m
is
cl
as
si
fic
at
io
n
of
CO
VI
D-
19
pn
eu
m
on
ia
pa
tie
nt
w
ith
pa
tie
nt
s
ha
vi
ng
su
bc
lin
ic
al
pu
lm
on
ar
y
in
fil
tr
at
io
n
Ig
G
46
2
89
.5
1
(1
45
/1
62
)
96
.3
3
(2
89
/3
00
)
92
.9
5
(1
45
/1
56
)
94
.4
4
(2
89
/3
06
)
Ig
M
46
2
87
.6
5
(1
42
/1
62
)
95
.3
3
(2
86
/3
00
)
91
.0
3
(1
42
/1
56
)
93
.4
6
(2
86
/3
06
)
W
on
df
o
SA
RS
-C
oV
-2
an
tib
od
y
te
st
(G
ua
ng
zh
ou
W
on
df
o
Bi
ot
ec
h
Co
.,
Lt
d
[C
hi
na
])
To
ta
l
59
6
86
.4
3
(3
12
/3
61
)
82
.1
1
(2
34
/2
85
)
99
.6
8
(3
12
/3
13
)
82
.6
9
(2
34
/2
83
)
Ig
G
59
6
N
Ab
N
Ab
N
Ab
N
Ab
Ig
M
59
6
N
Ab
N
Ab
N
Ab
N
Ab
27
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ow
nloaded from
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ic.oup.com
/inthealth/article/14/1/18/6147255 by Turun Yliopisto user on 09 M
ay 2022
A. U. Emeribe et al.
Ta
bl
e
1.
Co
nt
in
ue
d
Ci
ta
tio
n
Pr
od
uc
tn
am
e/
so
ur
ce
Ty
pe
Sa
m
pl
e
si
ze
Se
ns
iti
vi
ty
(%
)
Sp
ec
ifi
ci
ty
(%
)
PP
V
(%
)
N
PV
(%
)
Li
m
ita
tio
n
of
st
ud
y
Gr
ee
n
et
al
.a
50
CO
VI
D-
19
Ig
M
-I
gG
Ra
pi
d
Te
st
(B
io
M
ed
om
ic
s,
BD
,U
SA
)
To
ta
l
52
5
88
.6
6
(3
52
/3
97
)
90
.6
3
(1
16
/1
28
)
96
.7
(3
52
/3
64
)
72
.0
5
(1
16
/1
61
)a
.N
o
de
ta
il
on
th
e
di
ag
no
st
ic
pe
rf
or
m
an
ce
of
bo
th
Ig
G
an
d
Ig
M
fo
rm
os
tP
O
C
di
ag
no
st
ic
de
vi
ce
s
th
at
w
er
e
ev
al
ua
te
d
Ig
G
52
5
N
Ab
N
Ab
N
Ab
N
Ab
Ig
M
52
5
N
Ab
N
Ab
N
Ab
N
Ab
Xp
er
tS
AR
S-
Co
V-
2
(C
ep
he
id
[U
SA
/w
or
ld
w
id
e
di
st
rib
ut
io
n]
)
To
ta
l
65
10
0
(3
0/
30
)
10
0
(3
5/
35
)
10
0
(3
0/
30
)
10
0
(3
5/
35
)
Ig
G
65
N
Ab
N
Ab
N
Ab
N
Ab
Ig
M
65
N
Ab
N
Ab
N
Ab
N
Ab
Vi
ta
PC
R
CO
VI
D-
19
as
sa
y
(C
re
do
[S
in
ga
po
re
])
To
ta
l
18
0
10
0
(1
20
/1
20
)
10
0
(6
0/
60
)
10
0
(1
20
/1
20
)
10
0
(6
0/
60
)
Ig
G
18
0
N
Ab
N
Ab
N
Ab
N
Ab
Ig
M
18
0
N
Ab
N
Ab
N
Ab
N
Ab
Ac
cu
la
SA
RS
-C
oV
-2
(M
es
a
Bi
ot
ec
h
[U
SA
])
To
ta
l
80
10
0
(5
0/
50
)
10
0
(3
0/
30
)
10
0
(5
0/
50
)
10
0
(3
0/
30
)
Ig
G
80
N
Ab
N
Ab
N
Ab
N
Ab
Ig
M
80
N
Ab
N
Ab
N
Ab
N
Ab
ID
N
O
W
CO
VI
D-
19
(A
bb
ot
t
Di
ag
no
st
ic
s
[w
or
ld
w
id
e]
)
To
ta
l
60
10
0
(3
0/
30
)
10
0
(3
0/
30
)
10
0
(3
0/
30
)
10
0
(3
0/
30
)
Ig
G
60
N
Ab
N
Ab
N
Ab
N
Ab
Ig
M
30
N
Ab
N
Ab
N
Ab
N
Ab
GT
-1
00
SA
RS
-C
oV
-2
Ig
G/
Ig
M
ki
t
(G
ol
ds
ite
Di
ag
no
st
ic
s
In
c.
[C
hi
na
])
To
ta
l
70
10
0
(2
0/
20
)
98
(4
9/
50
)
90
.9
(2
0/
22
)
10
0
(4
9/
49
)
Ig
G
70
10
0
(2
0/
20
)
98
(4
9/
50
)
90
.9
(2
0/
22
)
10
0
(4
9/
49
)
Ig
M
70
85
(1
7/
20
)
96
(4
8/
50
)
89
.4
7
(1
7/
19
)
94
.1
2
(4
8/
51
)
M
lc
oc
ho
va
et
al
.a
51
SA
M
BA
II
SA
RS
-C
oV
-2
po
in
to
f
ca
re
te
st
in
g
To
ta
l
45
79
.1
7
(1
9/
24
)
10
0
(2
1/
21
)
10
0
(1
9/
19
)
80
.7
7
(2
1/
26
)
a.
Sm
al
ls
am
pl
e
si
ze
Ig
G
45
50
.0
(1
2/
24
)
10
0
(2
1/
21
)
10
0
(1
2/
12
)
63
.6
2
(2
1/
33
)
b.
Re
co
m
m
en
da
tio
n
of
co
m
bi
ne
d
ra
pi
d
te
st
in
g
pr
ot
oc
ol
w
ith
PC
R
in
or
de
rt
o
en
su
re
:
Ig
M
45
87
.5
(2
1/
24
)
10
0
(2
1/
21
)
10
0
(2
1/
21
)
87
.5
(2
1/
24
)
i.
Ex
pa
ns
iv
e
te
st
in
g
in
ar
ea
s
w
he
re
di
ag
no
st
ic
ce
nt
er
s
ar
e
sp
ar
se
,a
nd
tr
an
sm
is
si
on
is
ra
pi
d
CO
VI
DI
X
20
19
SA
RS
-C
oV
-2
Ig
G/
Ig
M
te
st
(C
O
VI
DI
X
H
ea
lth
ca
re
,C
am
br
id
ge
,U
K)
To
ta
l
45
95
.8
3
(2
3/
24
)
85
.7
1
(1
8/
21
)
88
.4
6
(2
3/
26
)
94
.7
4
(1
8/
19
)
ii.
Th
at
re
pe
at
ed
sa
m
pl
in
g
is
av
oi
de
d,
w
hi
ch
ca
n
ge
ne
ra
te
ae
ro
so
ls
an
d
en
co
ur
ag
e
tr
an
sm
is
si
on
Ig
G
45
10
0
(2
4/
24
)
80
.9
5
(1
7/
21
)
85
.7
1
(2
4/
28
)
10
0
(1
7/
17
)
iii
.T
ha
tp
at
ie
nt
s
ar
e
sa
fe
ly
an
d
qu
ic
kl
y
re
cr
ui
te
d
fo
r
tr
ea
tm
en
t
28
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ow
nloaded from
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ic.oup.com
/inthealth/article/14/1/18/6147255 by Turun Yliopisto user on 09 M
ay 2022
International Health
Ta
bl
e
1.
Co
nt
in
ue
d
Ci
ta
tio
n
Pr
od
uc
tn
am
e/
so
ur
ce
Ty
pe
Sa
m
pl
e
si
ze
Se
ns
iti
vi
ty
(%
)
Sp
ec
ifi
ci
ty
(%
)
PP
V
(%
)
N
PV
(%
)
Li
m
ita
tio
n
of
st
ud
y
Ig
M
45
95
.8
3
(2
3/
24
)
90
.4
8
(1
9/
21
)
92
.0
(2
3/
25
)
95
.0
(1
9/
20
)
Va
n
El
sl
an
de
et
al
.a
52
Cl
un
ge
ne
CO
VI
D-
19
Ig
G/
Ig
M
ra
pi
d
te
st
To
ta
l
25
6
35
.9
5
(5
5/
15
3)
99
.0
3
(1
02
/1
03
)
98
.2
1
(5
5/
56
)
51
.0
(1
02
/2
00
)
a.
Co
nt
ro
ls
am
pl
es
w
er
e
lim
ite
d
in
nu
m
be
rf
ro
m
pa
tie
nt
s
w
ith
fre
qu
en
tr
es
pi
ra
to
ry
di
so
rd
er
s
Ig
G
25
6
62
.0
9
(9
5/
15
3)
98
.0
6
(1
01
/1
03
)
97
.9
4
(9
5/
97
)
63
.5
2
(1
01
/1
59
)
b.
An
tib
od
y
re
sp
on
se
st
ud
ie
s
in
as
ym
pt
om
at
ic
or
m
ild
in
di
vi
du
al
s
w
er
e
no
tp
er
fo
rm
ed
Ig
M
25
6
39
.2
2
(6
0/
15
3)
91
.2
6
(9
4/
10
3)
86
.9
6
(6
0/
69
)
50
.2
7
(9
4/
18
7)
c.
Pa
rt
ic
ip
an
ts
w
er
e
no
tt
es
te
d
da
ily
to
ac
cu
ra
te
ly
de
te
rm
in
e
th
e
tr
ue
pe
rio
d
of
se
ro
co
nv
er
si
on
O
rie
nt
Ge
ne
CO
VI
D-
19
Ig
G/
Ig
M
ra
pi
d
te
st
To
ta
l
25
6
64
.0
5
(9
8/
15
3)
97
.0
9
(1
00
/1
03
)
97
.0
3
(9
8/
10
1)
64
.5
2
(1
00
/1
55
)
Ig
G
25
6
67
.9
7
(1
04
/1
53
)
93
.2
(9
6/
10
3)
93
.6
9
(1
04
/1
11
)
66
.2
1
(9
6/
14
5)
Ig
M
25
6
72
.5
5
(1
11
/1
53
)
95
.1
5
(9
8/
10
3)
95
.6
9
(1
11
/1
16
)
70
.0
(9
8/
14
0)
Vi
va
Di
ag
CO
VI
D-
19
Ig
G/
Ig
M
ra
pi
d
te
st
To
ta
l
25
6
62
.7
5
(9
6/
15
3)
10
0
(1
03
/1
03
)
10
0
(9
6/
96
)
64
.3
8
(1
03
/1
60
)
Ig
G
25
6
62
.7
5
(9
6/
15
3)
99
.0
3
(1
02
/1
03
)
98
.9
7
(9
6/
97
)
64
.1
5
(1
02
/1
59
)
Ig
M
25
6
65
.3
6
(1
00
/1
53
)
10
0
(1
03
/1
03
)
10
0
(1
00
/1
00
)
66
.0
3
(1
03
/1
56
)
St
ro
ng
St
re
p
CO
VI
D-
19
Ig
G/
Ig
M
ra
pi
d
te
st
To
ta
l
25
6
30
.0
7
(4
6/
15
3)
10
0
(1
03
/1
03
)
10
0
(4
6/
46
)
49
.0
5
(1
03
/2
10
)
Ig
G
25
6
64
.7
1
(9
9/
15
3)
99
.0
3
(1
02
/1
03
)
99
.0
(9
9/
10
0)
65
.3
8
(1
02
/1
56
)
Ig
M
25
6
32
.0
3
(4
9/
15
3)
99
.0
3
(1
02
/1
03
)
98
.0
(4
9/
50
)
49
.5
1
(1
02
/2
06
)
Dy
na
m
m
ik
er
CO
VI
D-
19
Ig
G/
Ig
M
ra
pi
d
te
st
To
ta
l
25
6
61
.4
4
(9
4/
15
3)
99
.0
3
(1
02
/1
03
)
98
.9
4
(9
4/
95
)
63
.3
5
(1
02
/1
61
)
Ig
G
25
6
61
.4
4
(9
4/
15
3)
99
.0
3
(1
02
/1
03
)
98
.9
4
(9
4/
95
)
63
.3
5
(1
02
/1
61
)
Ig
M
25
6
69
.2
8
(1
06
/1
53
)
95
.1
5
(9
8/
10
3)
95
.5
(1
06
/1
11
)
67
.5
9
(9
8/
14
5)
M
ul
ti-
G
CO
VI
D-
19
Ig
G/
Ig
M
ra
pi
d
te
st
To
ta
l
25
6
37
.2
5
(5
7/
15
3)
10
0
(1
03
/1
03
)
10
0
(5
7/
57
)
51
.7
6
(1
03
/1
99
)
Ig
G
25
6
64
.7
1
(9
9/
15
3)
97
.0
9
(1
00
/1
03
)
97
.0
6
(9
9/
10
2)
64
.9
4
(1
00
/1
54
)
Ig
M
25
6
43
.7
9
(6
7/
15
3)
91
.2
6
(9
4/
10
3)
88
.1
6
(6
7/
76
)
52
.2
2
(9
4/
18
0)
Pr
im
a
CO
VI
D-
19
Ig
G/
Ig
M
ra
pi
d
te
st
To
ta
l
25
6
48
.3
7
(7
4/
15
3)
98
.0
6
(1
01
/1
03
)
97
.3
7
(7
4/
76
)
56
.1
1
(1
01
/1
80
)
Ig
G
25
6
71
.2
4
(1
09
/1
53
)
90
.2
9
(9
3/
10
3)
91
.6
(1
09
/1
19
)
67
.8
8
(9
3/
13
7)
Ig
M
25
6
56
.2
1
(8
6/
15
3)
93
.2
(9
6/
10
3)
68
.2
5
(8
6/
12
0)
71
.6
7
(8
6/
12
0)
29
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ow
nloaded from
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ic.oup.com
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ay 2022
A. U. Emeribe et al.
Ta
bl
e
1.
Co
nt
in
ue
d
Ci
ta
tio
n
Pr
od
uc
tn
am
e/
so
ur
ce
Ty
pe
Sa
m
pl
e
si
ze
Se
ns
iti
vi
ty
(%
)
Sp
ec
ifi
ci
ty
(%
)
PP
V
(%
)
N
PV
(%
)
Li
m
ita
tio
n
of
st
ud
y
Jä
äs
ke
lä
in
en
et
al
.b
53
20
19
-n
Co
V
Ig
G/
Ig
M
ra
pi
d
te
st
ca
ss
et
te
(A
cr
o
Bi
ot
ec
h,
Ca
lif
or
ni
a,
U
SA
)
To
ta
l
12
3
56
.1
(2
3/
41
)
74
.3
9
(6
1/
82
)
52
.2
7
(2
3/
44
)
77
.2
2
(6
1/
79
)
a.
Lo
w
PP
Vs
fo
rA
cr
o
Bi
ot
ec
h
Ig
G/
Ig
M
ra
pi
d
te
st
du
e
to
lo
w
SA
RS
-C
oV
-2
se
ro
pr
ev
al
en
ce
Ig
G
12
3
56
.1
(2
3/
41
)
74
.3
9
(6
1/
82
)
52
.2
7
(2
3/
44
)
77
.2
2
(6
1/
79
)
Ig
M
12
3
46
.3
4
(1
9/
41
)
69
.5
1
(5
7/
82
)
43
.1
8
(1
9/
44
)
72
.1
5
(5
7/
79
)
SA
RS
-C
oV
-2
Ig
G/
Ig
M
ra
pi
d
te
st
(X
ia
m
en
Bi
ot
im
e,
Fu
jia
n,
Ch
in
a)
To
ta
l
11
2
81
.2
5
(2
6/
32
)
97
.5
(7
8/
80
)
92
.8
6
(2
6/
28
)
92
.8
6
(7
8/
84
)
Ig
G
11
2
71
.8
8
(2
3/
32
)
97
.5
(7
8/
80
)
92
(2
3/
25
)
89
.6
6
(7
8/
87
)
Ig
M
11
2
81
.2
5
(2
6/
32
)
88
.7
5
(7
1/
80
)
81
.2
5
(2
6/
35
)
92
.2
1
(7
1/
77
)
Ko
hm
er
et
al
.c
54
Fa
sS
te
p
(C
O
VI
D-
19
Ig
G/
Ig
M
)
ra
pi
d
te
st
ca
ss
et
te
s
(C
O
V-
W
32
M
,A
ss
ur
e
Te
ch
(H
an
gz
ho
u)
Co
.,
Lt
d,
Ch
in
a)
To
ta
l
29
93
.7
5
(1
5/
16
)
10
0.
0
(1
3/
13
)
10
0.
0
(1
5/
15
)
92
.8
6
(1
3/
14
)
a.
Sm
al
ls
am
pl
e
si
ze
Ig
G
29
93
.7
5
(1
5/
16
)
10
0.
0
(1
3/
13
)
10
0.
0
(1
5/
15
)
92
.8
6
(1
3/
14
)
Ig
M
29
62
.5
(1
0/
16
)
10
0.
0
(1
3/
13
)
10
0.
0
(1
0/
10
)
68
.4
2
(1
3/
19
)
M
on
te
si
no
s
et
al
.a
5
20
19
-n
-C
oV
Ig
G/
Ig
M
ra
pi
d
te
st
ca
ss
et
te
(L
ab
O
n
Ti
m
e)
(L
ab
O
n
Ti
m
e,
Bi
o
M
ar
ke
tin
g
Di
ag
no
st
ic
s,
or
Ak
iv
a,
Is
ra
el
)
To
ta
l
20
0
71
.8
8
(9
2/
12
8)
10
0.
0
(7
2/
72
)
10
0.
0
(9
2/
92
)
66
.6
7
(7
2/
10
8)
a.
Th
e
re
fe
re
nc
e
st
an
da
rd
us
ed
fo
rt
he
co
m
pa
ra
tiv
e
st
ud
y
of
th
e
se
ro
lo
gi
ca
lk
its
Ig
G
20
0
67
.1
9
(8
6/
12
8)
10
0.
0
(7
2/
72
)
10
0.
0
(8
6/
86
)
63
.1
6
(7
2/
11
4)
b.
Po
or
di
ag
no
st
ic
pe
rf
or
m
an
ce
ba
se
d
on
th
e
se
ns
iti
vi
ty
of
Ig
M
an
d
Ig
G
fo
rL
ab
O
n
an
d
Q
ui
ck
ze
n,
re
sp
ec
tiv
el
y
Ig
M
20
0
48
.4
4
(6
2/
12
8)
10
0.
0
(7
2/
72
)
10
0.
0
(6
2/
62
)
52
.1
7
(7
2/
13
8)
N
ov
el
co
ro
na
vi
ru
s
(2
01
9-
n-
Co
V)
an
tib
od
y
Ig
G/
Ig
M
as
sa
y
(c
ol
lo
id
al
go
ld
)(
Av
io
q,
Bi
ot
ec
h,
Sh
an
do
ng
,C
hi
na
)
To
ta
l
20
0
68
.7
5
(8
8/
12
8)
95
.8
3
(6
9/
72
)
96
.7
(8
8/
91
)
63
.3
(6
9/
10
9)
Ig
G
20
0
68
.7
5
(8
8/
12
8)
95
.8
3
(6
9/
72
)
96
.7
(8
8/
91
)
63
.3
(6
9/
10
9)
Ig
M
20
0
68
.7
5
(8
8/
12
8)
95
.8
3
(6
9/
72
)
96
.7
(8
8/
91
)
63
.3
(6
9/
10
9)
Q
ui
ck
Ze
n
CO
VI
D-
19
Ig
M
/I
gG
ki
t
(Q
ui
ck
Ze
n)
(Z
en
Te
ch
,A
ng
le
ur
,
Be
lg
iu
m
)
To
ta
l
20
0
71
.0
9
(9
1/
12
8)
10
0.
0
(7
2/
72
)
10
0.
0
(9
1/
91
)
66
.0
6
(7
2/
10
9)
Ig
G
20
0
49
.2
2
(6
3/
12
8)
10
0.
0
(7
2/
72
)
10
0.
0
(6
3/
63
)
52
.5
5
(7
2/
13
7)
Ig
M
20
0
68
.7
5
(8
8/
12
8)
10
0.
0
(7
2/
72
)
10
0.
0
(8
8/
88
)
64
.2
9
(7
2/
11
2)
30
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ow
nloaded from
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ic.oup.com
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ay 2022
International Health
Ta
bl
e
1.
Co
nt
in
ue
d
Ci
ta
tio
n
Pr
od
uc
tn
am
e/
so
ur
ce
Ty
pe
Sa
m
pl
e
si
ze
Se
ns
iti
vi
ty
(%
)
Sp
ec
ifi
ci
ty
(%
)
PP
V
(%
)
N
PV
(%
)
Li
m
ita
tio
n
of
st
ud
y
Ad
am
s
et
al
.a
56
RD
T
1
To
ta
l
93
54
.5
5
(1
8/
33
)
10
0.
0
(6
0/
60
)
10
0.
0
(1
8/
18
)
80
.0
(6
0/
75
)
a.
Pr
es
en
ce
of
fa
ls
e-
po
si
tiv
es
du
e
to
cr
os
s-
re
ac
tiv
ity
of
no
n-
sp
ec
ifi
c
im
m
un
og
lo
bu
lin
s,
w
hi
ch
re
fle
ct
s
pa
st
ex
po
su
re
to
ot
he
rs
ea
so
na
lv
ira
li
nf
ec
tio
ns
of
th
e
co
ro
na
vi
ru
s
gr
ou
p
Ig
G
93
N
Ab
N
Ab
N
Ab
N
Ab
b.
Sm
al
ls
am
pl
e
si
ze
,w
hi
ch
di
d
no
te
nc
ou
ra
ge
st
ro
ng
co
nfi
de
nc
e
in
te
rv
al
s
ar
ou
nd
th
e
di
ag
no
st
ic
pe
rf
or
m
an
ce
of
th
e
LF
IA
ki
ts
Ig
M
93
N
Ab
N
Ab
N
Ab
N
Ab
c.
Th
e
ki
ts
co
ul
d
no
td
is
tin
gu
is
h
th
e
im
m
un
og
lo
bu
lin
s
RD
T
2
To
ta
l
12
9
60
.5
3
(2
3/
38
)
98
.9
(9
0/
91
)
95
.8
3
(2
3/
24
)
85
.7
1
(9
0/
10
5)
Ig
G
12
9
N
Ab
N
Ab
N
Ab
N
Ab
Ig
M
12
9
N
Ab
N
Ab
N
Ab
N
Ab
RD
T
3
To
ta
l
93
63
.6
4
(2
1/
33
)
96
.6
7
(5
8/
60
)
91
.3
(2
1/
23
)
82
.8
6
(5
8/
70
)
Ig
G
93
N
Ab
N
Ab
N
Ab
N
Ab
Ig
M
93
N
Ab
N
Ab
N
Ab
N
Ab
RD
T
4
To
ta
l
98
65
.7
9
(2
5/
38
)
98
.3
3
(5
9/
60
)
96
.1
5
(2
5/
26
)
81
.9
4
(5
9/
72
)
Ig
G
98
N
Ab
N
Ab
N
Ab
N
Ab
Ig
M
98
N
Ab
N
Ab
N
Ab
N
Ab
RD
T
5
To
ta
l
91
61
.2
9
(1
9/
31
)
96
.6
7
(5
8/
60
)
90
.4
8
(1
9/
21
)
82
.8
6
(5
8/
70
)
Ig
G
91
N
Ab
N
Ab
N
Ab
N
Ab
Ig
M
91
N
Ab
N
Ab
N
Ab
N
Ab
RD
T
6
To
ta
l
91
64
.5
2
(2
0/
31
)
98
.3
3
(5
9/
60
)
95
.2
4
(2
0/
21
)
84
.2
9
(5
9/
70
)
Ig
G
91
N
Ab
N
Ab
N
Ab
N
Ab
Ig
M
91
N
Ab
N
Ab
N
Ab
N
Ab
RD
T
7
To
ta
l
93
69
.7
0
(2
3/
33
)
95
.0
(5
7/
60
)
88
.4
6
(2
3/
26
)
85
.0
7
(5
7/
67
)
Ig
G
93
N
Ab
N
Ab
N
Ab
N
Ab
Ig
M
93
N
Ab
N
Ab
N
Ab
N
Ab
RD
T
8
To
ta
l
92
56
.2
5
(1
8/
32
)
10
0.
0
(6
0/
60
)
10
0.
0
(1
8/
18
)
81
.0
8
(6
0/
74
)
Ig
G
92
N
Ab
N
Ab
N
Ab
N
Ab
Ig
M
92
N
Ab
N
Ab
N
Ab
N
Ab
RD
T
9
To
ta
l
18
2
55
.0
(2
2/
40
)
97
.1
8
(1
38
/1
42
)
84
.6
2
(2
2/
26
)
88
.4
6
(1
38
/1
56
)
Ig
G
18
2
N
Ab
N
Ab
N
Ab
N
Ab
Ig
M
18
2
N
Ab
N
Ab
N
Ab
N
Ab
N
uc
ce
te
lli
et
al
.a
57
SA
RS
-C
oV
-2
im
m
un
oc
hr
o-
m
at
og
ra
ph
ic
CA
RD
1
To
ta
l
83
83
.7
2
(3
6/
43
)
10
0.
0
(4
0/
40
)
10
0.
0
(3
6/
36
)
85
.1
1
(4
0/
47
)
a.
Be
ca
us
e
th
e
pe
rf
or
m
an
ce
of
th
es
e
ki
ts
is
ba
se
d
on
th
e
PC
R-
re
fe
re
nc
e
st
an
da
rd
,t
he
de
te
rm
in
at
io
n
of
th
e
ac
tu
al
pr
ev
al
en
ce
of
th
e
vi
ra
li
nf
ec
tio
n
is
lim
ite
d
an
d
ca
nn
ot
re
ve
al
th
e
ac
tu
al
st
at
us
of
pa
rt
ic
ip
an
ts
w
ith
vi
ra
ll
oa
d
va
lu
es
th
at
ar
e
be
lo
w
th
e
PC
R
de
te
ct
io
n
lim
it
31
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ow
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ic.oup.com
/inthealth/article/14/1/18/6147255 by Turun Yliopisto user on 09 M
ay 2022
A. U. Emeribe et al.
Ta
bl
e
1.
Co
nt
in
ue
d
Ci
ta
tio
n
Pr
od
uc
tn
am
e/
so
ur
ce
Ty
pe
Sa
m
pl
e
si
ze
Se
ns
iti
vi
ty
(%
)
Sp
ec
ifi
ci
ty
(%
)
PP
V
(%
)
N
PV
(%
)
Li
m
ita
tio
n
of
st
ud
y
Ig
G
83
83
.7
2
(3
6/
43
)
10
0.
0
(4
0/
40
)
10
0.
0
(3
6/
36
)
85
.1
1
(4
0/
47
)
Ig
M
83
60
.4
7(
26
/4
3)
10
0.
0
(4
0/
40
)
10
0.
0
(2
6/
26
)
70
.1
8
(4
0/
57
)
SA
RS
-C
oV
-2
im
m
un
oc
hr
om
at
og
ra
ph
ic
CA
RD
2
To
ta
l
83
90
.7
0
(3
9/
43
)
10
0.
0
(4
0/
40
)
10
0
(3
9/
39
)
90
.9
1
(4
0/
44
)
Ig
G
83
90
.7
0
(3
9/
43
)
10
0.
0
(4
0/
40
)
10
0
(3
9/
39
)
90
.9
1
(4
0/
44
)
Ig
M
83
88
.3
7
(3
8/
43
)
10
0.
0
(4
0/
40
)
10
0.
0
(3
8/
38
)
88
.8
9
(4
0/
45
)
SA
RS
-C
oV
-2
im
m
un
ofl
uo
re
sc
en
ce
CA
RD
3
To
ta
l
83
93
.0
2
(4
0/
43
)
10
0.
0
(4
0/
40
)
10
0.
0
(4
0/
40
)
93
.0
2
(4
0/
43
)
Ig
G
83
93
.0
2
(4
0/
43
)
10
0.
0
(4
0/
40
)
10
0.
0
(4
0/
40
)
93
.0
2
(4
0/
43
)
Ig
M
83
83
.7
2
(3
6/
43
)
10
0.
0
(4
0/
40
)
10
0.
0
(3
6/
36
)
85
.1
1
(4
0/
47
)
Pé
re
z-
Ga
rc
ía
et
al
.a
58
Al
lT
es
tC
O
V-
19
Ig
G/
Ig
M
ki
t(
Al
lT
es
t
Bi
ot
ec
h,
H
an
gz
ho
u,
Ch
in
a)
To
ta
l
19
0
64
.4
4
(5
8/
90
)
10
0.
0
(1
00
/1
00
)
10
0.
0
(5
8/
58
)
75
.7
6
(1
00
/1
32
)a
.S
tu
dy
lo
ca
tio
n
w
as
re
st
ric
te
d
to
a
he
al
th
ca
re
ce
nt
er
,w
hi
ch
pr
od
uc
ed
da
ta
th
at
ne
ed
s
to
be
re
in
fo
rc
ed
us
in
g
a
m
ul
tic
en
te
rs
tu
dy
Ig
G
19
0
60
.0
(5
4/
90
)
10
0.
0
(1
00
/1
00
)
10
0.
0
(5
4/
54
)
73
.5
3
(1
00
/1
36
)b
.N
o
co
ns
id
er
at
io
n
of
th
e
st
ud
y
pa
rt
ic
ip
an
ts
w
ith
a
ra
ng
e
of
cl
in
ic
al
m
an
ife
st
at
io
ns
so
as
to
ge
ne
ra
te
no
n-
bi
as
ed
da
ta
Ig
M
19
0
27
.7
8
(2
5/
90
)
10
0.
0
(1
00
/1
00
)
10
0.
0
(2
5/
25
)
60
.6
1
(1
00
/1
65
)c
.V
al
id
at
io
n
of
ju
st
a
ki
t
d.
Po
or
di
ag
no
st
ic
pe
rf
or
m
an
ce
fo
rI
gM
ba
se
d
on
se
ns
iti
vi
ty
Ab
br
ev
ia
tio
ns
:C
EF
A,
cy
cl
ic
en
ha
nc
ed
flu
or
es
ce
nc
e
as
sa
y;
CL
IA
,c
he
m
ilu
m
in
es
ce
nc
e
im
m
un
oa
ss
ay
;L
FI
A,
la
te
ra
lfl
ow
im
m
un
oa
ss
ay
;M
N
T,
m
ic
ro
ne
ut
ra
liz
at
io
n
te
st
;N
Aa
,n
ot
ap
pl
ic
ab
le
;N
Ab
,n
ot
av
ai
la
bl
e;
N
PV
,n
eg
at
iv
e
pr
ed
ic
tiv
e
va
lu
e;
PO
CT
,p
oi
nt
of
ca
re
te
st
;P
O
S,
po
st
on
se
t
of
sy
m
pt
om
s;
PP
V,
po
si
tiv
e
pr
ed
ic
tiv
e
va
lu
e;
PR
N
T,
pl
aq
ue
re
du
ct
io
n
ne
ut
ra
liz
at
io
n
te
st
.
a
di
ag
no
st
ic
pe
rf
or
m
an
ce
pe
rf
or
m
ed
w
ith
re
fe
re
nc
e
to
RT
-P
CR
.
b
di
ag
no
st
ic
pe
rf
or
m
an
ce
pe
rf
or
m
ed
w
ith
re
fe
re
nc
e
to
a
m
ic
ro
ne
ut
ra
liz
at
io
n
te
st
(M
N
T)
.
c
Di
ag
no
st
ic
pe
rf
or
m
an
ce
pe
rf
or
m
ed
w
ith
re
fe
re
nc
e
to
pl
aq
ue
-r
ed
uc
tio
n
ne
ut
ra
liz
at
io
n
te
st
(P
RN
T)
.
N
ot
e:
1.
Al
lc
om
pu
te
d
va
lu
es
w
er
e
PS
O
.
2.
Al
lp
ro
du
ct
s
w
ith
≥9
5%
ea
ch
fo
r
se
ns
iti
vi
ty
,s
pe
ci
fic
ity
,P
PV
an
d
N
PV
m
ay
be
us
ed
fo
r
ep
id
em
io
lo
gi
ca
lp
ur
po
se
s.
Fu
rt
he
rm
or
e,
pe
rf
or
m
an
ce
ch
ar
ac
te
ris
tic
s
≥9
5%
va
lu
es
re
po
rt
ed
fro
m
ac
ut
e
CO
VI
D-
19
sa
m
pl
es
co
ul
d
be
co
ns
id
er
ed
fo
rc
lin
ic
al
us
e
(in
co
nj
un
ct
io
n
w
ith
cl
in
ic
al
pr
es
en
ta
tio
ns
of
pa
tie
nt
s)
.
32
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ow
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ic.oup.com
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ay 2022
International Health
Ta
bl
e
2.
Di
ag
no
st
ic
pe
rf
or
m
an
ce
of
EL
IS
A
an
d
EL
FA
pr
ot
oc
ol
fro
m
pu
bl
is
he
d
da
ta
Ci
ta
tio
n
Pr
od
uc
tn
am
e/
so
ur
ce
Ty
pe
Sa
m
pl
e
si
ze
Se
ns
iti
vi
ty
(%
)
Sp
ec
ifi
ci
ty
(%
)
PP
V
(%
)
N
PV
(%
)
Li
m
ita
tio
n
of
st
ud
y
Va
n
El
sl
an
de
et
al
.a
52
Eu
ro
im
m
un
To
ta
l
25
6
N
Ab
N
Ab
N
Ab
N
Ab
a.
Sa
m
pl
es
us
ed
to
de
te
rm
in
e
bo
th
sp
ec
ifi
ci
ty
an
d
se
ns
iti
vi
ty
w
er
e
ch
al
le
ng
in
g
Ig
G
25
6
55
.5
6
(8
5/
15
3)
96
.1
2
(9
9/
10
3)
95
.5
1
(8
5/
89
)
56
.2
8
(9
9/
16
7)
b.
Di
ag
no
st
ic
pe
rf
or
m
an
ce
da
ta
bo
th
fo
r
to
ta
la
nt
ib
od
y
an
d
Ig
M
w
er
e
no
t
m
ad
e
av
ai
la
bl
e
Ig
M
25
6
N
Ab
N
Ab
N
Ab
N
Ab
Zh
ao
et
al
.a
17
CO
VI
D-
19
EL
IS
A
ki
t(
Be
iji
ng
W
an
ta
iB
io
lo
gi
ca
lP
ha
rm
ac
y
En
te
rp
ris
e
Co
.L
td
)
To
ta
l
38
6
93
.0
6
(1
61
/1
73
)
99
.0
6
(2
11
/2
13
)
98
.7
7
(1
61
/1
63
)
94
.6
2
(2
11
/2
23
)
a.
Sa
m
pl
in
g
w
as
fo
ru
pp
er
re
sp
ira
to
ry
tr
ac
ti
ns
te
ad
of
lo
w
er
re
sp
ira
to
ry
tr
ac
t
w
ith
hi
gh
er
se
ns
iti
vi
ty
fo
rR
N
A
te
st
s
Ig
G
38
6
64
.7
4
(1
12
/1
73
)
98
.9
8
(1
95
/1
97
)
98
.2
5
(1
12
/1
14
)
76
.1
7
(1
95
/2
56
)
b.
N
o
ev
al
ua
tio
n
of
th
e
pe
rs
is
te
nc
e
of
an
tib
od
ie
s
as
sa
m
pl
in
g
w
as
pe
rf
or
m
ed
du
rin
g
th
e
ac
ut
e
ph
as
e
of
th
e
pa
rt
ic
ip
an
ts
Ig
M
37
0
82
.6
6
(1
43
/1
73
)
98
.5
9
(2
10
/2
13
)
97
.9
5
(1
43
/1
46
)
87
.5
(2
10
/2
40
)
c.
Cr
os
s-
re
ac
tiv
ity
st
ud
ie
s
w
er
e
no
t
pe
rf
or
m
ed
fo
rt
he
se
ro
lo
gi
ca
lk
its
Xi
an
g
et
al
.a
59
Sa
nd
w
ic
h
EL
IS
A
ki
t(
Li
vz
on
In
c,
Zh
uh
ai
,C
hi
na
,l
ot
nu
m
be
rs
20
20
03
08
[I
gM
]
an
d
20
20
03
08
[I
gG
])
To
ta
l
12
6
83
.3
3
(5
5/
66
)
10
0
(6
0/
60
)
10
0
(5
5/
55
)
84
.5
1
(6
0/
71
)
a.
Sm
al
ls
am
pl
e
si
ze
s
w
er
e
us
ed
to
de
te
rm
in
e
th
e
se
ro
po
si
tiv
e
ra
te
of
Ig
G
Ig
G
12
6
83
.3
3
(5
5/
66
)
95
.0
(5
7/
60
)
94
.8
3
(5
5/
58
)
83
.8
2
(5
7/
68
)
b.
U
nr
el
ia
bl
e
fo
rt
es
tin
g
w
ith
in
th
e
w
in
do
w
pe
rio
d
of
in
fe
ct
io
n
du
e
to
m
is
di
ag
no
si
s;
re
te
st
in
g
w
as
re
co
m
m
en
de
d
fo
rt
ho
se
w
ith
ea
rly
se
ro
ne
ga
tiv
e
im
m
un
og
lo
bu
lin
s
Ig
M
12
6
77
.2
7
(5
1/
66
)
10
0
(6
0/
60
)
10
0
(5
1/
51
)
80
.0
(6
0/
75
)
33
D
ow
nloaded from
 https://academ
ic.oup.com
/inthealth/article/14/1/18/6147255 by Turun Yliopisto user on 09 M
ay 2022
A. U. Emeribe et al.
Ta
bl
e
2.
Co
nt
in
ue
d
Ci
ta
tio
n
Pr
od
uc
tn
am
e/
so
ur
ce
Ty
pe
Sa
m
pl
e
si
ze
Se
ns
iti
vi
ty
(%
)
Sp
ec
ifi
ci
ty
(%
)
PP
V
(%
)
N
PV
(%
)
Li
m
ita
tio
n
of
st
ud
y
Jä
äs
ke
lä
in
en
et
al
.b
53
An
ti-
SA
RS
-C
oV
-2
Ig
A
an
d
Ig
G
EI
A
(E
ur
oi
m
m
un
,L
u¨
be
ck
,
Ge
rm
an
y)
To
ta
l
12
3
87
.8
(3
6/
41
)
86
.5
9
(7
1/
82
)
76
.6
(3
6/
47
)
93
.4
2
(7
1/
76
)
a.
N
o
ex
te
ns
iv
e
in
ve
st
ig
at
io
n
on
pr
oz
on
e
ph
en
om
en
on
ca
pa
bl
e
of
ca
us
in
g
fa
ls
e-
ne
ga
tiv
e
re
su
lts
Ig
G
12
3
70
.7
3
(2
9/
41
)
86
.5
9
(7
1/
82
)
72
.5
(2
9/
40
)
85
.5
4
(7
1/
83
)
b.
Ig
A
de
te
ct
io
n
is
no
tu
se
fu
lf
or
sc
re
en
in
g
pu
rp
os
es
bu
tc
an
on
ly
be
ap
pl
ie
d
fo
rf
ol
lo
w
-u
p
in
ve
st
ig
at
io
ns
in
pa
tie
nt
s
w
ith
pr
ov
en
CO
VI
D-
19
in
fe
ct
io
ns
Ig
A
12
3
87
.8
(3
6/
41
)
68
.2
9
(5
6/
82
)
58
.0
6
(3
6/
62
)
91
.8
(5
6/
61
)
Jä
äs
ke
lä
in
en
et
al
.a
60
An
ti-
SA
RS
-C
oV
-2
Ig
A
an
d
Ig
G
EI
A
(E
ur
oi
m
m
un
,L
u¨
be
ck
,
Ge
rm
an
y)
To
ta
l
40
92
.8
6
(1
3/
14
)
92
.3
1
(2
4/
26
)
86
.6
7
(1
3/
15
)
96
.0
(2
4/
25
)
a.
Sm
al
ls
am
pl
e
si
ze
Ig
G
40
92
.8
6
(1
3/
14
)
92
.3
1
(2
4/
26
)
86
.6
7
(1
3/
15
)
96
.0
(2
4/
25
)
Ig
A
40
78
.5
7
(1
1/
14
)
73
.0
8
(1
9/
26
)
61
.1
1
(1
1/
18
)
86
.3
6
(1
9/
22
)
Ge
ur
ts
va
n
Ke
ss
el
et
al
.c
43
W
an
ta
iS
AR
S-
Co
V-
2
to
ta
lI
g
an
d
Ig
M
EL
IS
A
(B
ei
jin
g
W
an
ta
iB
io
lo
gi
ca
lP
ha
rm
ac
y
En
te
rp
ris
e
Co
.,
Lt
d)
To
ta
l
22
6
98
.6
8
(7
5/
76
)
99
.3
3
(1
49
/1
50
)
98
.6
8
(7
5/
76
)
99
.3
3
(1
49
/1
50
)
a.
N
ot
en
tir
el
y
ad
eq
ua
te
fo
rp
op
ul
at
io
n
sc
re
en
in
g
du
rin
g
an
ea
rly
ph
as
e
of
th
e
pa
nd
em
ic
Ig
G
22
6
N
Ab
N
Ab
N
Ab
N
Ab
Ig
M
22
6
89
.4
7
(6
8/
76
)
98
.6
7
(1
48
/1
50
)
97
.1
4
(6
8/
70
)
94
.8
7
(1
48
/1
56
)
An
ti-
SA
RS
-C
oV
-2
Ig
G
an
d
Ig
A
EL
IS
A
as
sa
y
(E
U
RO
IM
M
U
N
M
ed
iz
in
is
ch
e
La
bo
rd
ia
gn
os
tik
a
AG
)
To
ta
l
23
7
97
.3
7
(7
4/
76
)
99
.3
8
(1
60
/1
61
)
98
.6
7
(7
4/
75
)
98
.7
7
(1
60
/1
62
)
Ig
G
23
7
81
.5
8
(6
2/
76
)
99
.3
8
(1
60
/1
61
)
98
.4
1
(6
2/
63
)
91
.9
5
(1
60
/1
74
)
Ig
A
23
7
97
.3
7
(7
4/
76
)
93
.7
9
(1
51
/1
61
)
88
.1
0
(7
4/
84
)
98
.6
9
(1
51
/1
53
)
34
D
ow
nloaded from
 https://academ
ic.oup.com
/inthealth/article/14/1/18/6147255 by Turun Yliopisto user on 09 M
ay 2022
International Health
Ta
bl
e
2.
Co
nt
in
ue
d
Ci
ta
tio
n
Pr
od
uc
tn
am
e/
so
ur
ce
Ty
pe
Sa
m
pl
e
si
ze
Se
ns
iti
vi
ty
(%
)
Sp
ec
ifi
ci
ty
(%
)
PP
V
(%
)
N
PV
(%
)
Li
m
ita
tio
n
of
st
ud
y
M
ül
le
re
ta
l.d
61
EU
RO
IM
M
U
N
an
ti-
SA
RS
-C
oV
-2
Ig
A
an
d
Ig
G
EL
IS
A
te
st
To
ta
l
42
46
.1
5
(1
2/
26
)
10
0.
0
(1
6/
16
)
10
0.
0
(1
2/
12
)
53
.3
3
(1
6/
30
)
a.
Di
ag
no
st
ic
pe
rf
or
m
an
ce
ba
se
d
on
se
ns
iti
vi
ty
w
as
ve
ry
po
or
Ig
G
42
46
.1
5
(1
2/
26
)
10
0.
0
(1
6/
16
)
10
0.
0
(1
2/
12
)
53
.3
3
(1
6/
30
)
Ig
A
42
46
.1
5
(1
2/
26
)
10
0.
0
(1
6/
16
)
10
0.
0
(1
2/
12
)
53
.3
3
(1
6/
30
)
Ko
hm
er
et
al
.c
54
Eu
ro
im
m
un
SA
RS
-C
oV
-2
Ig
G
EL
IS
A
(E
ur
oi
m
m
un
,L
üb
ec
k,
Ge
rm
an
y)
To
ta
l
40
93
.7
5
(1
5/
16
)
95
.6
5
(2
2/
23
)
93
.7
5
(1
5/
16
)
95
.6
5
(2
2/
23
)
a.
Sm
al
ls
am
pl
e
si
ze
Ig
G
40
93
.7
5
(1
5/
16
)
95
.6
5
(2
2/
23
)
93
.7
5
(1
5/
16
)
95
.6
5
(2
2/
23
)
Ig
A
40
58
.8
2
(1
0/
17
)
95
.6
5
(2
2/
23
)
90
.9
1
(1
0/
11
)
75
.8
6
(2
2/
29
)
Vi
rc
el
lC
O
VI
D-
19
EL
IS
A
Ig
G
(V
irc
el
lS
pa
in
S.
L.
U
.,
Gr
an
ad
a,
Sp
ai
n)
To
ta
l
38
10
0.
0
(1
6/
16
)
95
.2
4
(2
0/
21
)
94
.1
2
(1
6/
17
)
10
0.
0
(2
0/
20
)
Ig
G
38
10
0.
0
(1
6/
16
)
95
.2
4
(2
0/
21
)
94
.1
2
(1
6/
17
)
10
0.
0
(2
0/
20
)
Ig
A
38
70
.5
9
(1
2/
17
)
95
.2
4
(2
0/
21
)
92
.3
1
(1
2/
13
)
80
.0
(2
0/
25
)
Ko
hm
er
et
al
.c
62
An
ti-
SA
RS
-C
oV
-2
EL
IS
A
Ig
G
(S
1
pr
ot
ei
n-
ba
se
d)
(E
ur
oi
m
m
un
,L
üb
ec
k,
Ge
rm
an
y)
To
ta
l
65
N
Ab
N
Ab
N
Ab
N
Ab
a.
Bo
th
EL
IS
A
as
sa
ys
co
ul
d
no
td
et
ec
t
im
m
un
og
lo
bu
lin
s
in
sa
m
pl
es
of
pa
rt
ic
ip
an
ts
w
ith
m
ild
fo
rm
of
CO
VI
D-
19
Ig
G
65
71
.1
1
(3
2/
45
)
10
0.
0
(2
0/
20
)
10
0.
0
(3
2/
32
)
60
.6
1
(2
0/
33
)
b.
Th
e
st
ud
y
on
th
e
pr
ot
ec
tiv
e
m
ec
ha
ni
sm
an
d
th
e
du
ra
tio
n
of
im
m
un
e
re
sp
on
se
,w
hi
ch
w
as
no
t
pe
rf
or
m
ed
in
de
ta
il,
w
as
fu
rt
he
r
pr
op
os
ed
Ig
A
65
N
Ab
N
Ab
N
Ab
N
Ab
Vi
ro
te
ch
SA
RS
-C
oV
-2
Ig
G
EL
IS
A
(N
pr
ot
ei
n-
ba
se
d)
(V
iro
te
ch
Di
ag
no
st
ic
s
Gm
bH
Ri
is
se
is
he
im
,G
er
m
an
y)
To
ta
l
80
N
Ab
N
Ab
N
Ab
N
Ab
35
D
ow
nloaded from
 https://academ
ic.oup.com
/inthealth/article/14/1/18/6147255 by Turun Yliopisto user on 09 M
ay 2022
A. U. Emeribe et al.
Ta
bl
e
2.
Co
nt
in
ue
d
Ci
ta
tio
n
Pr
od
uc
tn
am
e/
so
ur
ce
Ty
pe
Sa
m
pl
e
si
ze
Se
ns
iti
vi
ty
(%
)
Sp
ec
ifi
ci
ty
(%
)
PP
V
(%
)
N
PV
(%
)
Li
m
ita
tio
n
of
st
ud
y
Ig
G
80
66
.6
7
(3
0/
45
)
10
0.
0
(3
5/
35
)
10
0.
0
(3
0/
30
)
70
.0
(3
5/
50
)
Ig
A
80
N
Ab
N
Ab
N
Ab
N
Ab
W
ol
ff
et
al
.a
63
Eu
ro
im
m
un
an
ti-
SA
RS
Co
V-
2
EL
IS
A
Ig
G
an
d
Ig
A
as
sa
ys
(E
ur
oi
m
m
un
,L
ue
be
ck
,
Ge
rm
an
y)
To
ta
l
20
7
82
.8
8
(9
2/
11
1)
95
.8
3
(9
2/
96
)
95
.8
3
(9
2/
96
)
82
.8
8
(9
2/
11
1)
a.
Pr
ol
on
ge
d
av
er
ag
e
sa
m
pl
in
g
co
lle
ct
io
n
pe
rio
d
w
as
12
d,
w
hi
ch
co
ul
d
in
flu
en
ce
th
e
di
ag
no
st
ic
pe
rf
or
m
an
ce
of
as
sa
ys
Ig
G
20
7
75
.6
8
(8
4/
11
1)
95
.8
3
(9
2/
96
)
95
.4
5
(8
4/
88
)
77
.3
1
(9
2/
11
9)
b.
Ba
se
d
on
th
e
us
e
of
qR
T-
PC
R
as
re
fe
re
nc
e
pr
ot
oc
ol
fo
rt
he
st
ud
y,
th
er
e
is
a
po
ss
ib
ili
ty
of
m
is
si
ng
po
si
tiv
e
ca
se
s
w
ho
se
re
sp
ira
to
ry
vi
ra
ll
oa
d
is
lo
w
er
th
an
th
e
de
te
ct
io
n
lim
it
fo
rP
CR
Ig
A
20
7
82
.8
8
(9
2/
11
1)
95
.8
3
(9
2/
96
)
95
.8
3
(9
2/
96
)
82
.8
8
(9
2/
11
1)
VI
DA
S
an
ti-
SA
RS
Co
V-
2
(E
LF
A)
(B
io
M
ér
ie
ux
,M
ar
cy
-l’
Et
oi
le
,
Fr
an
ce
)
To
ta
l
20
7
72
.9
7
(8
1/
11
1)
10
0.
0
(9
6/
96
)
10
0.
0
(8
1/
81
)
76
.1
9
(9
6/
12
6)
Ig
G
20
7
72
.9
7
(8
1/
11
1)
10
0.
0
(9
6/
96
)
10
0.
0
(8
1/
81
)
76
.1
9
(9
6/
12
6)
Ig
M
20
7
64
.8
6
(7
2/
11
1)
10
0.
0
(9
6/
96
)
10
0.
0
(7
2/
72
)
71
.1
1
(9
6/
13
5)
Fr
an
ce
sc
a
et
al
.e
64
An
ti-
SA
RS
-C
oV
-2
Ig
G,
Ig
M
an
d
Ig
A
EL
IS
A
te
st
s
(E
N
ZY
-W
EL
L
SA
RS
-C
oV
-2
EL
IS
A,
DI
ES
SE
Di
ag
no
st
ic
a
Se
ne
se
S.
p.
a.
)
To
ta
l
46
8
93
.9
1
(1
08
/1
15
)
98
.0
2
(3
46
/3
53
)
93
.9
1
(1
08
/1
15
)
98
.0
2
(3
46
/3
53
)
a.
Al
la
ss
ay
s
in
di
ca
te
d
m
od
er
at
e
cr
os
s-
re
ac
tiv
ity
w
ith
sa
m
pl
es
fro
m
pa
rt
ic
ip
an
ts
fo
ro
th
er
co
m
m
un
ic
ab
le
an
d
no
n-
co
m
m
un
ic
ab
le
di
so
rd
er
s
Ig
G
46
8
92
.1
7
(1
06
/1
15
)
91
.7
8
(3
24
/3
53
)
78
.5
2
(1
06
/1
35
)
97
.3
0
(3
24
/3
33
)
Ig
M
46
8
87
.8
3
(1
01
/1
15
)
88
.1
0
(3
11
/3
53
)
70
.6
3
(1
01
/1
43
)
95
.6
9
(3
11
/3
25
)
Ig
A
46
8
93
.9
1
(1
08
/1
15
)
98
.0
2
(3
46
/3
53
)
93
.9
1
(1
08
/1
15
)
98
.0
2
(3
46
/3
53
)
36
D
ow
nloaded from
 https://academ
ic.oup.com
/inthealth/article/14/1/18/6147255 by Turun Yliopisto user on 09 M
ay 2022
International Health
Ta
bl
e
2.
Co
nt
in
ue
d
Ci
ta
tio
n
Pr
od
uc
tn
am
e/
so
ur
ce
Ty
pe
Sa
m
pl
e
si
ze
Se
ns
iti
vi
ty
(%
)
Sp
ec
ifi
ci
ty
(%
)
PP
V
(%
)
N
PV
(%
)
Li
m
ita
tio
n
of
st
ud
y
M
on
te
si
no
s
et
al
.a
55
Eu
ro
im
m
un
an
ti-
SA
RS
-C
oV
-2
EL
IS
A
Ig
G
an
d
Ig
A
as
sa
ys
(E
ur
oi
m
m
un
,L
ue
be
ck
,
Ge
rm
an
y)
To
ta
l
20
0
84
.3
8
(1
08
/1
28
)
87
.5
(6
3/
72
)
92
.3
1
(1
08
/1
17
)
75
.9
(6
3/
83
)
a.
Th
e
re
tr
os
pe
ct
iv
e
na
tu
re
of
th
e
st
ud
y,
w
hi
ch
in
vo
lv
ed
no
fre
sh
sa
m
pl
es
,
co
ul
d
ad
ve
rs
el
y
af
fe
ct
th
e
ac
cu
ra
cy
of
re
su
lts
Ig
G
20
0
61
.7
2
(7
9/
12
8)
98
.6
1
(7
1/
72
)
98
.7
5
(7
9/
80
)
59
.1
7
(7
1/
12
0)
Ig
A
20
0
83
.5
9
(1
07
/1
28
)
86
.1
1
(6
2/
72
)
91
.4
5
(1
07
/1
17
)
74
.7
(6
2/
83
)
Ad
am
s
et
al
.a
56
In
-h
ou
se
EL
IS
A
re
co
m
bi
na
nt
SA
RS
-C
oV
-2
tr
im
er
ic
sp
ik
e
pr
ot
ei
n
To
ta
l
90
N
Ab
N
Ab
N
Ab
N
Ab
a.
N
o
de
ta
ile
d
da
ta
to
in
ve
st
ig
at
e
im
m
un
og
lo
bu
lin
-p
os
iti
vi
ty
as
a
co
rr
el
at
e
of
pr
ot
ec
tiv
e
im
m
un
ity
.
Ig
G
90
85
.0
(3
4/
40
)
10
0.
0
(5
0/
50
)
10
0.
0
(3
4/
34
)
89
.2
9
(5
0/
56
)
b.
N
o
fu
rt
he
rs
tu
di
es
to
co
nfi
rm
th
e
la
ck
of
ev
id
en
ce
to
es
ta
bl
is
h
th
e
re
la
tio
ns
hi
p
be
tw
ee
n
se
ve
rit
y
of
th
e
di
so
rd
er
an
d
an
tib
od
y
tit
er
s
Ig
M
90
N
Ab
N
Ab
N
Ab
N
Ab
Be
av
is
et
al
.a
65
EU
RO
IM
M
U
N
an
ti-
SA
RS
-C
oV
-2
as
sa
y
To
ta
l
16
8
N
Ab
N
Ab
N
Ab
N
Ab
a.
Sm
al
ls
am
pl
e
si
ze
Ig
G
16
8
67
.0
7
(5
5/
82
)
97
.6
7
(8
4/
86
)
96
.4
9
(5
5/
57
)
75
.6
8
(8
4/
11
1)
b.
Pr
ol
on
ge
d
av
er
ag
e
sa
m
pl
in
g
co
lle
ct
io
n
pe
rio
d,
w
hi
ch
co
ul
d
af
fe
ct
th
e
di
ag
no
st
ic
pe
rf
or
m
an
ce
of
th
e
ki
t
Ig
A
16
8
82
.9
3
(6
8/
82
)
88
.3
7
(7
6/
86
)
87
.1
8
(6
8/
78
)
84
.4
4
(7
6/
90
)
Ab
br
ev
ia
tio
ns
:E
LF
A,
en
zy
m
e
lin
ke
d
flu
or
es
ce
nc
e
as
sa
y;
IF
A,
im
m
un
ofl
uo
re
sc
en
ce
as
sa
y;
IF
T,
im
m
un
ofl
uo
re
sc
en
ce
te
st
;M
N
T,
m
ic
ro
ne
ut
ra
liz
at
io
n
as
sa
y;
N
Ab
,n
ot
av
ai
la
bl
e;
N
PV
,
ne
ga
tiv
e
pr
ed
ic
tiv
e
va
lu
e;
N
T,
ne
ut
ra
liz
at
io
n
te
st
;P
O
S,
po
st
on
se
to
fs
ym
pt
om
s;
PP
V,
po
si
tiv
e
pr
ed
ic
tiv
e
va
lu
e;
PR
N
T,
pl
aq
ue
-r
ed
uc
tio
n
ne
ut
ra
liz
at
io
n
as
sa
y.
a
Di
ag
no
st
ic
pe
rf
or
m
an
ce
pe
rf
or
m
ed
w
ith
re
fe
re
nc
e
to
RT
-P
CR
.
b
Di
ag
no
st
ic
pe
rf
or
m
an
ce
pe
rf
or
m
ed
w
ith
re
fe
re
nc
e
to
m
ic
ro
ne
ut
ra
liz
at
io
n
te
st
(M
N
T)
.
c
Di
ag
no
st
ic
pe
rf
or
m
an
ce
pe
rf
or
m
ed
w
ith
re
fe
re
nc
e
to
pl
aq
ue
-r
ed
uc
tio
n
ne
ut
ra
liz
at
io
n
te
st
(P
RN
T)
.
d
Di
ag
no
st
ic
pe
rf
or
m
an
ce
pe
rf
or
m
ed
w
ith
re
fe
re
nc
e
to
N
T
an
d
IF
T.
e
Di
ag
no
st
ic
pe
rf
or
m
an
ce
pe
rf
or
m
ed
w
ith
re
fe
re
nc
e
to
IF
A.
N
ot
e:
1.
Al
lc
om
pu
te
d
va
lu
es
w
er
e
PO
S.
2.
Al
lp
ro
du
ct
s
w
ith
≥9
5%
ea
ch
fo
r
se
ns
iti
vi
ty
,s
pe
ci
fic
ity
,P
PV
an
d
N
PV
m
ay
be
us
ed
fo
r
ep
id
em
io
lo
gi
ca
lp
ur
po
se
s.
Fu
rt
he
rm
or
e,
pe
rf
or
m
an
ce
ch
ar
ac
te
ris
tic
s
≥9
5%
va
lu
es
re
po
rt
ed
fro
m
ac
ut
e
CO
VI
D-
19
sa
m
pl
es
co
ul
d
be
co
ns
id
er
ed
fo
rc
lin
ic
al
us
e
(in
co
nj
un
ct
io
n
w
ith
cl
in
ic
al
pr
es
en
ta
tio
ns
of
pa
tie
nt
s)
.
37
D
ow
nloaded from
 https://academ
ic.oup.com
/inthealth/article/14/1/18/6147255 by Turun Yliopisto user on 09 M
ay 2022
A. U. Emeribe et al.
Ta
bl
e
3.
Di
ag
no
st
ic
pe
rf
or
m
an
ce
of
ch
em
ilu
m
in
es
ce
nc
e
im
m
un
oa
ss
ay
(C
LI
A)
,e
le
ct
ro
-c
he
m
ilu
m
in
es
ce
nc
e
(E
CL
IA
)a
nd
ch
em
ilu
m
in
es
ce
nt
m
ic
ro
pa
rt
ic
le
im
m
un
oa
ss
ay
(C
M
IA
)
pr
ot
oc
ol
fro
m
pu
bl
is
he
d
da
ta
Ci
ta
tio
n
Pr
od
uc
tn
am
e/
so
ur
ce
Ty
pe
Sa
m
pl
e
Si
ze
Se
ns
iti
vi
ty
(%
)
Sp
ec
ifi
ci
ty
(%
)
PP
V
(%
)
N
PV
(%
)
Li
m
ita
tio
n
of
st
ud
y
Ji
n
et
al
.a
23
CL
IA
te
st
ki
tS
he
nz
he
n
YH
LO
Bi
ot
ec
h
Co
.,
Lt
d
(C
hi
na
)
To
ta
l
76
88
.3
7
(3
8/
43
)
10
0
(3
3/
33
)
10
0
(3
8/
38
)
86
.8
4
(3
3/
38
)
a.
Sa
m
pl
e
si
ze
us
ed
w
as
sm
al
la
s
ju
st
43
la
b-
co
nfi
rm
ed
CO
VI
D-
19
pa
rt
ic
ip
an
ts
an
d
33
ap
pa
re
nt
ly
he
al
th
y
pa
rt
ic
ip
an
ts
Ig
G
76
88
.3
7
(3
8/
43
)
90
.9
1
(3
0/
33
)
92
.6
8
(3
8/
41
)
85
.7
1
(3
0/
35
)
b.
Th
e
pe
rio
d
to
vi
ra
lm
ol
ec
ul
ar
de
te
ct
io
n
an
d
to
se
ro
lo
gi
ca
li
nv
es
tig
at
io
n
w
as
no
tc
on
st
an
t
an
d
w
as
ba
se
d
on
cl
in
ic
al
ju
dg
m
en
t
Ig
M
76
48
.8
4
(2
1/
43
)
10
0
(3
3/
33
)
10
0
(3
8/
38
)
86
.8
4
(3
3/
38
)
c.
Th
e
va
lu
e
of
se
ro
lo
gi
ca
li
nv
es
tig
at
io
n
in
pa
rt
ic
ip
an
ts
w
ith
se
ve
re
ca
se
s
re
qu
ire
s
as
se
ss
m
en
ta
s
th
os
e
en
ro
lle
d
in
to
th
e
st
ud
y
ha
d
m
ild
to
m
od
er
at
e
CO
VI
D-
19
ca
se
s
d.
Th
e
av
er
ag
e
pe
rio
d
fro
m
cl
in
ic
al
ha
llm
ar
k
on
se
tt
o
se
ro
lo
gi
ca
li
nv
es
tig
at
io
n
w
as
lo
ng
du
e
to
th
e
la
te
av
ai
la
bi
lit
y
of
te
st
in
g
ki
ts
e.
Th
er
e
w
as
sc
ar
se
fo
llo
w
-u
p
da
ta
on
pa
rt
ic
ip
an
ts
w
ho
w
er
e
di
sc
ha
rg
ed
Ge
ur
ts
va
n
Ke
ss
el
et
al
.c
43
Di
aS
or
in
Li
ai
so
n
XL
To
ta
l
12
2
73
.5
8
(3
9/
53
)
98
.5
5
(6
8/
69
)
97
.5
(3
9/
40
)
82
.9
3
(6
8/
82
)
a.
La
ck
of
se
ns
iti
vi
ty
at
th
e
ea
rly
ph
as
e
of
sy
m
pt
om
on
se
t
M
ül
le
r
et
al
.d
61
LI
AI
SO
N
SA
RS
-C
oV
-2
S1
/S
2
Ig
G
CL
IA
te
st
(D
ia
So
rin
S1
/S
2
Ig
G)
To
ta
l
42
N
Ab
N
Ab
N
Ab
N
Ab
a.
Sm
al
ls
iz
e
us
ed
fo
rt
he
st
ud
y
Ig
G
42
61
.5
4
(1
6/
26
)
68
.7
5
(1
1/
16
)
76
.1
9
(1
6/
21
)
52
.3
8
(1
1/
21
)
b.
Al
lt
es
tk
its
m
is
se
d
a
gr
ea
tp
ro
po
rt
io
n
of
ne
ut
ra
liz
in
g
an
tib
od
y
Ig
M
42
N
Ab
N
Ab
N
Ab
N
Ab
SA
RS
-C
oV
-2
Ig
G
CM
IA
fro
m
Ab
bo
tt
de
te
ct
in
g
An
ti-
nu
cl
eo
ca
ps
id
Ig
G
an
tib
od
ie
s
(A
bb
ot
tN
Ig
G)
To
ta
l
42
N
Ab
N
Ab
N
Ab
N
Ab
38
D
ow
nloaded from
 https://academ
ic.oup.com
/inthealth/article/14/1/18/6147255 by Turun Yliopisto user on 09 M
ay 2022
International Health
Ta
bl
e
3.
Co
nt
in
ue
d
Ci
ta
tio
n
Pr
od
uc
tn
am
e/
so
ur
ce
Ty
pe
Sa
m
pl
e
Si
ze
Se
ns
iti
vi
ty
(%
)
Sp
ec
ifi
ci
ty
(%
)
PP
V
(%
)
N
PV
(%
)
Li
m
ita
tio
n
of
st
ud
y
Ig
G
42
61
.5
4
(1
6/
26
)
10
0.
0
(1
6/
16
)
10
0.
0
(1
6/
16
)
61
.5
4
(1
6/
26
)
Ig
M
42
N
Ab
N
Ab
N
Ab
N
Ab
El
ec
sy
s
an
ti-
SA
RS
-C
oV
-2
EC
LI
A
te
st
fro
m
Ro
ch
e
(R
oc
he
N
Ab
)
To
ta
l
42
65
.3
8
(1
7/
26
)
10
0.
0
(1
6/
16
)
10
0.
0
(1
7/
17
)
64
.0
(1
6/
25
)
Ig
G
42
N
Ab
N
Ab
N
Ab
N
Ab
Ig
M
42
N
Ab
N
Ab
N
Ab
N
Ab
Ko
hm
er
et
al
.c
62
SA
RS
-C
oV
-2
Ig
G
CM
IA
(A
bb
ot
tA
rc
hi
te
ct
i2
00
0
[N
pr
ot
ei
n-
ba
se
d]
;
Ab
bo
tt
Gm
bH
,
W
ie
sb
ad
en
,G
er
m
an
y)
To
ta
l
80
N
Ab
N
Ab
N
Ab
N
Ab
a.
Th
es
e
as
sa
ys
,e
sp
ec
ia
lly
th
at
of
el
ec
sy
s
an
ti-
SA
RS
-C
oV
-2
,a
re
un
ab
le
to
di
ffe
re
nt
ia
te
be
tw
ee
n
Ig
A,
Ig
M
an
d
Ig
G
Ig
G
80
77
.7
8
(3
5/
45
)
10
0.
0
(3
5/
35
)
10
0.
0
(3
5/
35
)
77
.7
8
(3
5/
45
)
b.
Ba
se
d
on
th
e
sm
al
ls
am
pl
e
si
ze
na
tu
re
of
th
is
st
ud
y,
it
is
no
tc
on
cl
us
iv
e
as
to
w
hi
ch
an
tib
od
ie
s
ar
e
th
e
m
os
ta
bu
nd
an
ta
nd
to
w
hi
ch
vi
ra
lp
ro
te
in
s
(N
an
d
S)
ar
e
m
os
t
ta
rg
et
ed
ba
se
d
on
th
e
ob
se
rv
ed
di
ss
im
ila
rit
ie
s
in
th
e
tim
e
fra
m
e
an
d
vi
ra
l
pr
ot
ei
n
ta
rg
et
of
th
e
im
m
un
e
re
sp
on
se
ag
ai
ns
tS
AR
S-
Co
V-
2
Ig
M
80
N
Ab
N
Ab
N
Ab
N
Ab
c.
Th
er
e
is
di
sc
re
pa
nc
y
be
tw
ee
n
th
e
di
ag
no
st
ic
pe
rf
or
m
an
ce
va
lu
es
of
th
e
ki
ts
de
te
rm
in
ed
in
th
e
cu
rr
en
ts
tu
dy
an
d
th
os
e
ge
ne
ra
te
d
by
th
e
m
an
uf
ac
tu
re
r’s
m
an
ua
la
nd
th
os
e
di
sc
lo
se
d
by
pr
ev
io
us
lit
er
at
ur
e
El
ec
sy
s
an
ti-
SA
RS
-C
oV
-2
EC
LI
A
te
st
(R
oc
he
co
ba
s
e
41
1
an
al
yz
er
[N
pr
ot
ei
n-
ba
se
d]
;R
oc
he
Di
ag
no
st
ic
s
In
te
rn
at
io
na
lA
G,
Ro
tk
re
uz
,S
w
itz
er
la
nd
)
To
ta
l
79
N
Ab
N
Ab
N
Ab
N
Ab
39
D
ow
nloaded from
 https://academ
ic.oup.com
/inthealth/article/14/1/18/6147255 by Turun Yliopisto user on 09 M
ay 2022
A. U. Emeribe et al.
Ta
bl
e
3.
Co
nt
in
ue
d
Ci
ta
tio
n
Pr
od
uc
tn
am
e/
so
ur
ce
Ty
pe
Sa
m
pl
e
Si
ze
Se
ns
iti
vi
ty
(%
)
Sp
ec
ifi
ci
ty
(%
)
PP
V
(%
)
N
PV
(%
)
Li
m
ita
tio
n
of
st
ud
y
Ig
G
79
75
.5
6
(3
4/
45
)
97
.0
6
(3
3/
34
)
97
.1
4
(3
4/
35
)
75
.0
(3
3/
44
)
Ig
M
79
N
Ab
N
Ab
N
Ab
N
Ab
LI
AI
SO
N
XL
SA
RS
-C
oV
-2
S1
/S
2
Ig
G
CL
IA
te
st
(D
ia
So
rin
S1
an
d
S2
pr
ot
ei
n-
ba
se
d)
(D
ia
So
rin
De
ut
sc
hl
an
d
Gm
bH
,
Di
et
ze
nb
ac
h,
Ge
rm
an
y)
To
ta
l
80
N
Ab
N
Ab
N
Ab
N
Ab
Ig
G
80
75
.5
6
(3
4/
45
)
10
0.
0
(3
5/
35
)
10
0.
0
(3
4/
34
)
76
.0
9
(3
5/
46
)
Ig
M
80
N
Ab
N
Ab
N
Ab
N
Ab
Vi
rc
el
lV
IR
CL
IA
au
to
m
at
io
n
sy
st
em
Ig
G
M
O
N
O
TE
ST
(C
LI
A)
(S
1
an
d
N
pr
ot
ei
n-
ba
se
d)
(V
irc
el
l
Sp
ai
n
S.
L.
U
.,
Gr
an
ad
a,
Sp
ai
n)
To
ta
l
76
N
Ab
N
Ab
N
Ab
N
Ab
Ig
G
76
88
.8
9
(4
0/
45
)
10
0.
0
(3
1/
31
)
10
0.
0
(4
0/
40
)
86
.1
1
(3
1/
36
)
Ig
M
76
N
Ab
N
Ab
N
Ab
N
Ab
Jä
äs
ke
lä
in
en
et
al
.b
53
LI
AI
SO
N
SA
RS
-C
oV
-2
Ig
G
(C
LI
A)
(D
ia
So
rin
,
Sa
lu
gg
ia
,I
ta
ly
)
To
ta
l
11
1
N
Ab
N
Ab
N
Ab
N
Ab
a.
Po
or
di
ag
no
st
ic
pe
rf
or
m
an
ce
ba
se
d
on
se
ns
iti
vi
ty
;l
ia
is
on
ra
pi
d
te
st
ki
tr
ev
ea
le
d
no
ad
eq
ua
cy
fo
rc
lin
ic
al
us
e
Ig
G
11
1
43
.7
5
(1
4/
32
)
94
.9
4
(7
5/
79
)
77
.7
8
(1
4/
18
)
80
.6
5
(7
5/
93
)
Ig
M
11
1
N
Ab
N
Ab
N
Ab
N
Ab
Ar
ch
ite
ct
SA
RS
-C
oV
-2
Ig
G
CM
IA
as
sa
y
(A
bb
ot
t,
Ill
in
oi
s,
U
SA
)
To
ta
l
12
3
N
Ab
N
Ab
N
Ab
N
Ab
Ig
G
12
3
80
.4
9
(3
3/
41
)
95
.1
2
(7
8/
82
)
89
.1
9
(3
3/
37
)
90
.7
(7
8/
86
)
Ig
M
12
3
N
Ab
N
Ab
N
Ab
N
Ab
40
D
ow
nloaded from
 https://academ
ic.oup.com
/inthealth/article/14/1/18/6147255 by Turun Yliopisto user on 09 M
ay 2022
International Health
Ta
bl
e
3.
Co
nt
in
ue
d
Ci
ta
tio
n
Pr
od
uc
tn
am
e/
so
ur
ce
Ty
pe
Sa
m
pl
e
Si
ze
Se
ns
iti
vi
ty
(%
)
Sp
ec
ifi
ci
ty
(%
)
PP
V
(%
)
N
PV
(%
)
Li
m
ita
tio
n
of
st
ud
y
W
ol
ff
et
al
.a
63
El
ec
sy
s
an
ti-
SA
RS
Co
V-
2
Ig
M
/I
gG
as
sa
y
(R
oc
he
Di
ag
no
st
ic
s,
Vi
lv
oo
rd
e,
Be
lg
iu
m
)
To
ta
l
20
7
81
.0
8
(9
0/
11
1)
10
0.
0
(9
6/
96
)
10
0.
0
(9
0/
90
)
82
.0
5
(9
6/
11
7)
a.
Lo
w
de
te
ct
io
n
ra
te
at
ea
rly
st
ag
e
of
CO
VI
D-
19
in
fe
ct
io
n
Ig
G
20
7
N
Ab
N
Ab
N
Ab
N
Ab
Ig
M
20
7
N
Ab
N
Ab
N
Ab
N
Ab
Li
ai
so
n
SA
RS
-C
oV
-2
Ig
G
ki
t
(C
LI
A)
(D
ia
so
rin
,
Sa
lu
gg
ia
,I
ta
ly
)
To
ta
l
20
7
N
Ab
N
Ab
N
Ab
N
Ab
Ig
G
20
7
70
.2
7
(7
8/
11
1)
97
.9
2
(9
4/
96
)
97
.5
(7
8/
80
)
74
.0
2
(9
4/
12
7)
Ig
M
20
7
N
Ab
N
Ab
N
Ab
N
Ab
M
on
te
si
no
s
et
al
.a
55
M
ag
lu
m
i2
01
9-
n-
Co
v
Ig
G
an
d
Ig
M
(C
LI
A)
To
ta
l
19
4
63
.1
1
(7
7/
12
2)
10
0.
0
(7
2/
72
)
10
0.
0
(7
7/
77
)
61
.5
4
(7
2/
11
7)
a.
Th
e
cr
ite
ria
fo
re
va
lu
at
in
g
th
e
pe
rio
d
of
ill
ne
ss
on
se
tw
er
e
re
tr
ie
ve
d
fro
m
m
ed
ic
al
ar
ch
iv
es
an
d
m
ay
in
cl
ud
e
im
pr
ec
is
io
ns
du
e
to
su
bj
ec
tiv
ity
in
th
e
la
ck
of
ob
je
ct
iv
e
de
te
rm
in
at
io
n
of
sy
m
pt
om
s
an
d
pe
rio
ds
Ig
G
19
8
53
.1
7
(6
7/
12
6)
10
0.
0
(7
2/
72
)
10
0.
0
(6
7/
67
)
54
.9
6
(7
2/
13
1)
b.
Lo
w
di
ag
no
st
ic
pe
rf
or
m
an
ce
ba
se
d
on
se
ns
iti
vi
ty
Ig
M
19
8
58
.7
3
(7
4/
12
6)
10
0.
0
(7
2/
72
)
10
0.
0
(7
4/
74
)
58
.0
6
(7
2/
12
4)
In
fa
nt
in
o
et
al
.a
66
SA
RS
-C
oV
-2
an
tib
od
ie
s
Ig
M
an
d
Ig
G
at
cu
ff
-o
ff
va
lu
es
10
.0
AU
/m
L
re
sp
ec
tiv
el
y
fo
rC
LI
A
ki
ts
(S
he
nz
he
n
YH
LO
Bi
ot
ec
h
Co
,L
td
,C
hi
na
)
To
ta
l
10
5
67
.2
1
(4
7/
61
)
10
0.
0
(4
4/
44
)
10
0.
0
(4
7/
47
)
75
.8
6
(4
4/
58
)
a.
Va
ria
tio
n
in
th
e
pe
rio
d
be
tw
ee
n
sa
m
pl
in
g
an
d
sy
m
pt
om
on
se
ts
Ig
G
10
5
67
.2
1
(4
7/
61
)
10
0.
0
(4
4/
44
)
10
0.
0
(4
7/
47
)
75
.8
6
(4
4/
58
)
b.
La
te
-s
ta
ge
en
ro
lm
en
to
fs
tu
dy
pa
rt
ic
ip
an
ts
Ig
M
10
5
73
.7
7
(4
5/
61
)
93
.1
8
(4
1/
44
)
93
.7
5
(4
5/
48
)
71
.9
3
(4
1/
57
)
c.
N
on
e
of
th
e
te
st
gr
ou
p
of
pa
rt
ic
ip
an
ts
pr
ov
id
ed
a
ne
ga
tiv
e
st
at
us
sa
m
pl
e
N
uc
ce
te
lli
et
al
.a
57
CL
IA
To
ta
l
83
95
.3
5
(4
1/
43
)
(1
00
.0
(4
0/
40
)
10
0.
0
(4
1/
41
)
95
.2
4
(4
0/
42
)
a.
N
o
fu
rt
he
rs
tu
dy
on
th
e
re
la
tio
n
be
tw
ee
n
an
tib
od
y
le
ve
ls
an
d
pr
ot
ec
tiv
e
im
m
un
e
re
sp
on
se
41
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ic.oup.com
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ay 2022
A. U. Emeribe et al.
Ta
bl
e
3.
Co
nt
in
ue
d
Ci
ta
tio
n
Pr
od
uc
tn
am
e/
so
ur
ce
Ty
pe
Sa
m
pl
e
Si
ze
Se
ns
iti
vi
ty
(%
)
Sp
ec
ifi
ci
ty
(%
)
PP
V
(%
)
N
PV
(%
)
Li
m
ita
tio
n
of
st
ud
y
Ig
G
83
95
.3
5
(4
1/
43
)
(1
00
.0
(4
0/
40
)
10
0.
0
(4
1/
41
)
95
.2
4
(4
0/
42
)
Ig
M
83
83
.7
2
(3
6/
43
)
95
.0
(3
8/
40
)
94
.7
4
(3
6/
38
)
84
.4
4
(3
8/
45
)
M
a
et
al
.a
67
CL
IA
RB
D-
sp
ec
ifi
c
an
ti-
SA
RS
-C
oV
-2
Ig
A,
Ig
M
an
d
Ig
G
ki
t
To
ta
l
69
9
94
.4
4
(2
04
/2
16
)
90
.4
8
(4
37
/4
83
)
81
.6
(2
04
/2
50
)
97
.3
3
(4
37
/4
49
)
a.
Ir
re
gu
la
ra
nd
pr
ol
on
ge
d
av
er
ag
e
sa
m
pl
in
g
du
ra
tio
n,
w
hi
ch
co
ul
d
in
flu
en
ce
th
e
ac
cu
ra
cy
of
th
e
as
sa
y
Ig
G
69
9
96
.7
6
(2
09
/2
16
)
99
.7
9
(4
82
/4
83
)
99
.5
2
(2
09
/2
10
)
98
.5
7
(4
82
/4
89
)
b.
N
o
ev
al
ua
tio
n
of
th
e
re
la
tio
ns
hi
p
be
tw
ee
n
im
m
un
og
lo
bu
lin
le
ve
ls
an
d
se
ve
rit
y
of
th
e
di
so
rd
er
Ig
M
69
9
96
.7
6
(2
09
/2
16
)
92
.3
4
(4
46
/4
83
)
84
.9
6
(2
09
/2
46
)
98
.4
5
(4
46
/4
53
)
Q
ia
n et
al
.a
68
CL
IA
te
st
ki
tS
he
nz
he
n
YH
LO
Bi
ot
ec
h
Co
.,
Lt
d
(C
hi
na
)
To
ta
l
21
13
N
Ab
N
Ab
N
Ab
N
Ab
a.
In
su
ffi
ci
en
td
at
a
on
se
ns
iti
vi
ty
fo
r
co
nv
al
es
ce
nt
sa
m
pl
es
du
e
to
lim
ite
d
pe
rio
d
af
te
rt
he
de
ve
lo
pm
en
to
fS
AR
S-
Co
V-
2
Ig
M
/I
gG
as
sa
ys
an
d
ac
ce
ss
to
lim
ite
d
pa
rt
ic
ip
an
td
em
og
ra
ph
ic
s
Ig
G
21
13
95
.6
8
(5
31
/5
55
)
98
.0
7
(1
52
8/
15
58
)
94
.6
5
(5
31
/5
61
)
98
.4
5
(1
52
8/
15
52
)
Ig
M
21
13
84
.6
8
(4
70
/5
55
)
98
.1
4
(1
52
9/
15
58
)
94
.1
9
(4
70
/4
99
)
94
.4
4
(1
52
9/
16
14
)
Su
ha
nd
yn
at
a
et
al
.a
69
Di
az
ym
e
DZ
-L
IT
E
20
19
-n
Co
V
Ig
G
(C
LI
A)
As
sa
y
Ki
t(
ca
t.
#
13
02
19
01
5M
)/
Ig
M
(C
LI
A)
as
sa
y
ki
t(
ca
t.
#
13
02
19
01
6M
)
To
ta
l
28
9
10
0.
0
(5
4/
54
)
98
.7
2
(2
32
/2
35
)94
.7
4
(5
4/
57
)
10
0.
0
(2
32
/2
32
)
a.
50
of
th
e
54
SA
RS
-C
oV
-2
-c
on
fir
m
ed
pa
rt
ic
ip
an
ts
w
er
e
ho
sp
ita
liz
ed
an
d
w
er
e
m
or
e
lik
el
y
ha
ve
ac
ut
e
ph
as
e
in
fe
ct
io
n
co
m
pa
re
d
w
ith
ot
he
r
av
er
ag
e
pa
rt
ic
ip
an
ts
th
at
w
er
e
in
fe
ct
ed
w
ith
CO
VI
D-
19
b.
A
pa
rt
ic
ip
an
th
ad
a
m
ed
ic
al
hi
st
or
y
of
co
m
m
on
va
ria
bl
e
Ig
G
im
m
un
od
efi
ci
en
cy
,w
hi
ch
ca
n
ad
ve
rs
el
y
af
fe
ct
th
e
di
ag
no
st
ic
pe
rf
or
m
an
ce
of
th
e
ki
tb
as
ed
on
se
ns
iti
vi
ty
as
th
e
pa
rt
ic
ip
an
tw
as
w
ro
ng
ly
ca
te
go
riz
ed
as
fa
ls
e-
ne
ga
tiv
e
fo
rI
gG
de
sp
ite
th
e
po
si
tiv
e
st
at
us
as
re
ve
al
ed
us
in
g
PC
R
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ay 2022
International Health
Ta
bl
e
3.
Co
nt
in
ue
d
Ci
ta
tio
n
Pr
od
uc
tn
am
e/
so
ur
ce
Ty
pe
Sa
m
pl
e
Si
ze
Se
ns
iti
vi
ty
(%
)
Sp
ec
ifi
ci
ty
(%
)
PP
V
(%
)
N
PV
(%
)
Li
m
ita
tio
n
of
st
ud
y
c.
In
su
ffi
ci
en
ts
er
ol
og
ic
da
ta
on
SA
RS
-C
oV
-2
pa
rt
ic
ip
an
ts
w
ith
le
ss
se
ve
re
sy
m
pt
om
s
w
ho
re
co
ve
re
d
Ig
G
28
9
94
.4
4
(5
1/
54
)
99
.1
4
(2
33
/2
35
)
96
.2
3
(5
1/
53
)
98
.7
3
(2
33
/2
36
)
Ig
M
28
9
88
.8
9
(4
8/
54
)
99
.5
7
(2
34
/2
35
)
97
.9
6
(4
8/
49
)
97
.5
(2
34
/2
40
)
Ab
br
ev
ia
tio
ns
:C
LI
A,
ch
em
ilu
m
in
es
ce
nc
e
im
m
un
oa
ss
ay
;I
FT
,i
m
m
un
ofl
uo
re
sc
en
ce
te
st
;N
Ab
,n
ot
av
ai
la
bl
e;
N
PV
,n
eg
at
iv
e
pr
ed
ic
tiv
e
va
lu
e;
N
T,
ne
ut
ra
liz
at
io
n
te
st
;P
O
S,
po
st
on
se
t
of
sy
m
pt
om
s;
PP
V,
po
si
tiv
e
pr
ed
ic
tiv
e
va
lu
e;
PR
N
T,
pl
aq
ue
-r
ed
uc
tio
n
ne
ut
ra
liz
at
io
n
as
sa
y;
RB
D,
re
ce
pt
or
-b
in
di
ng
do
m
ai
n.
a
di
ag
no
st
ic
pe
rf
or
m
an
ce
pe
rf
or
m
ed
w
ith
re
fe
re
nc
e
to
RT
-P
CR
.
b
di
ag
no
st
ic
pe
rf
or
m
an
ce
do
ne
w
ith
re
fe
re
nc
e
to
m
ic
ro
ne
ut
ra
liz
at
io
n
as
sa
y
(M
N
T)
c
di
ag
no
st
ic
pe
rf
or
m
an
ce
pe
rf
or
m
ed
w
ith
re
fe
re
nc
e
to
PR
N
T.
d
di
ag
no
st
ic
pe
rf
or
m
an
ce
pe
rf
or
m
ed
w
ith
re
fe
re
nc
e
to
N
T
an
d
IF
T.
N
ot
e:
1.
Al
lc
om
pu
te
d
va
lu
es
w
er
e
PO
S.
2.
Al
lp
ro
du
ct
s
w
ith
≥9
5%
ea
ch
fo
r
Se
ns
iti
vi
ty
,S
pe
ci
fic
ity
,P
PV
an
d
N
PV
m
ay
be
us
ed
fo
r
ep
id
em
io
lo
gi
ca
lp
ur
po
se
s.
Fu
rt
he
rm
or
e,
pe
rf
or
m
an
ce
ch
ar
ac
te
ris
tic
s
≥9
5%
va
lu
es
re
po
rt
ed
fro
m
ac
ut
e
CO
VI
D-
19
sa
m
pl
es
co
ul
d
be
co
ns
id
er
ed
fo
rc
lin
ic
al
us
e
(in
co
nj
un
ct
io
n
w
ith
cl
in
ic
al
pr
es
en
ta
tio
ns
of
pa
tie
nt
s)
.
43
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ay 2022
A. U. Emeribe et al.
needed to guide laboratories, public health agencies and govern-
ments in the appropriate and responsible deployment of POCT,
and serological assays more broadly. Currently, the WHO recom-
mends the use of POCT immunodiagnostic assays in research
settings only, and not for clinical decision-making until further
evidence is available.13 Ideally, validation of serological assays,
including POCT, should be performed against a serum panel that
includes samples from (1) patients at acute and convalescent
stages of infection (to assess sensitivity) and (2) patients with
other human coronavirus infections (to assess specificity).
Also, serological tests are relevant to fully characterize the
SARS-CoV-2-specific antibody response. Differences in the profile
of the antibody response across patients might reveal important
aspects of the pathogenesis of COVID-19, explaining the great
differences observed in the general population. Indeed, the cor-
relation with disease severity and clinical characteristics is poorly
understood. Old age and comorbidities seem to increase the risk
for a poor outcome of the disease; however, increasing cases
of young people who experience severe illness, requiring hos-
pitalization for assistance by mechanical ventilation, may pose
questions about the leading factors of disease progression.32
Some challenges are posed by the potential cross-reactivity
with other human coronaviruses, due to their high homology
at the genetic level. The evidence related to this aspect are still
controversial; however, SARS-CoV-specific antibodies are unde-
tectable in the sera of patients 6 y after infection. This observation
excludes the presence of cross-reactivity in the sera of COVID-19
patients and might make researchers confident about the speci-
ficity of these antibodies.32 Moreover, it would be interesting to
understand whether the differences in the progression of the
disease might be related to the level of the immune response.
Accuracy and applications of COVID-19 serological
assays
Although various reports of reputable serology assays are in-
credibly encouraging, product end-users must be pragmatic
regarding their accuracy and applicability for COVID-19 clinical
and epidemiological use. The unsustainability of RT-PCR tests
for the COVID-19 laboratory response in some countries has
necessitated a search for alternative assays with high sensitivity
and specificity with a short turnaround time from preanalytical
(sample collection) to postanalytical phases (availability of
test results),32 thus enabling prompt and large-scale testing
for COVID-19. While none of the antibody-based serological
assays have been approved by the WHO, a number of them
have been approved for clinical and epidemiological use in some
countries.32 Antibody testing might have a useful role in clinically
diagnosing COVID-19 patients with late presentations, prolonged
symptoms and those with negative results from RT-PCR tests.
Furthermore, these tests could be used to monitor the quality
and duration of humoral immune response in COVID-19 patients
and vaccination. Epidemiologically, SARS-CoV-2 antibody tests
can be used for seroprevalence studies in public health research
and to inform decisions about returning to work following
asymptomatic SARS-CoV-2 infection.
This could offer an opportunity for clinical diagnosis and
interruption of transmission through targeted isolation of the
most infectious cases and their close contacts.32 SARS-CoV-2 an-
tibody testing has been shown to have good clinical applications,
given the varied symptoms of COVID-19 and reported cases of
false-negative results of RT-PCR tests when respiratory swabs are
collected ≥5 d PSO as their sensitivity begins to decline.32
Considering this, many researchers are now conducting an
independent performance evaluation of these antibody-based
assays. For instance, a study referred to as the ‘COVID-19 Testing
Project’ was conducted by the University of California, Mas-
sachusetts General Hospital, the Chan Zuckerberg Biohub and
the University of California.33 This study evaluated 10 lateral flow
assays and 2 ELISAs to assess performance characteristics for
anti-SARS-CoV-233 on plasma/serum of 80 symptomatic COVID-
19 patients with RT-PCR positive results, 52 non-SARS-COV-2
patients’ respiratory viral infections (SARS-CoV-2 RT-PCR nega-
tive) and 108 archived sera of blood donors collected in 2018 or
earlier.33
The assessment found that the assays of the products had
varying sensitivities that increased over time, increasing from
about 81% to 100% at ˃20 d PSO.33 Based on this, it was inferred
that anti-SARS-CoV-2 tests were important for longitudinal stud-
ies because a negative result may indicate an actively infected
person who has not developed a detectable level of antibodies
to the virus. Conversely, the proportion of false-positive samples
reported from the non-COVID-19 group ranged from 0% to 16%.
The detection agreement indices of the lateral flow assays and
ELISAs ranged from 75% to 94%.33
In another evaluation study of SARS-CoV-2 antibody-based
tests by the Chinese company Innovita, anti-SARS-CoV-2 anti-
bodies were found in 83% of COVID-19-confirmed patients with
an assay specificity of 96%.34 After FDA authorization, these
tests were anticipated for at-home use.34 Despite the merits of
serological devices, limitations abound due to issues of misdi-
agnosis following indications of significant false-negative and
false-positive results observed during the evaluation of these kits
and devices during quality checks.
These rapid test kits have been observed to be unsuitable
for testing patients with ≤14 d PSO. To augment these lapses,
several studies recommend combining both the serological and
RT-PCR-based protocols to provide a more accurate diagnosis of
COVID-19 instead of only using the molecular testing approach,
which introduces a myriad of strenuous demands on diagnostic
and healthcare delivery establishments and regulatory bodies,
as well as material, financial and human resourcesmeant to sus-
tain testing capacity.17,19,20,35 Also, there are several studies that
have been conducted by diagnostic industries and independent
researchers aiming to evaluate the performance characteristics
of various anti-SARS-CoV-2 test protocols, some of which have
reported promising results.35–42 It is worth noting that the clin-
ical use of SARS-CoV-2 antibody tests should be on products
that evaluated and reported the performance characteristics
(especially sensitivity and specificity) during the acute phase of
COVID-19.
Performance characteristics of COVID-19 serological
assays
The most promising (best) LFA on total SARS-CoV-2 antibody test
had a sensitivity, specificity, PPV and NPV of 100%, 100%, 100%
and100%at days 4, 5, 4 and 5, respectively, while theworst had a
44
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ay 2022
International Health
Ta
bl
e
4.
Di
ag
no
st
ic
m
on
ito
rin
g
of
im
m
un
og
lo
bu
lin
s
by
po
in
t-
of
-c
ar
e
te
st
se
ro
lo
gi
ca
lp
ro
to
co
lf
ro
m
pu
bl
is
he
d
da
ta
Ci
ta
tio
n
Pr
od
uc
tn
am
e/
so
ur
ce
An
tib
od
y
as
se
ss
m
en
t
ty
pe
De
te
ct
io
n
tim
e
ra
ng
e
(d
)
M
ea
n
tim
e
of
de
te
ct
io
n
(d
)
Pe
ak
pe
rio
d
(d
)
Pe
rio
d
of
de
cl
in
e
(d
)
Va
n
El
sl
an
de
et
al
.52
Cl
un
ge
ne
CO
VI
D-
19
Ig
G/
Ig
M
ra
pi
d
te
st
To
ta
l
5–
6
5
17
–1
8
N
Ab
Ig
G
5–
6
7
17
–1
8
N
Ab
Ig
M
5–
6
5
17
–1
8
N
Ab
O
rie
nt
Ge
ne
CO
VI
D-
19
Ig
G/
Ig
M
ra
pi
d
te
st
To
ta
l
5–
6
5
17
–1
8
N
Ab
Ig
G
5–
6
7
17
–1
8
N
Ab
Ig
M
5–
6
5
17
–1
8
N
Ab
Vi
va
Di
ag
CO
VI
D-
19
Ig
G/
Ig
M
ra
pi
d
te
st
To
ta
l
5–
6
5
17
–1
8
N
Ab
Ig
G
5–
6
7
17
–1
8
N
Ab
Ig
M
5–
6
5
17
–1
8
N
Ab
St
ro
ng
St
re
p
CO
VI
D-
19
Ig
G/
Ig
M
ra
pi
d
te
st
To
ta
l
5–
6
5
17
–1
8
N
Ab
Ig
G
5–
6
7
17
–1
8
N
Ab
Ig
M
5–
6
5
17
–1
8
N
Ab
Dy
na
m
m
ik
er
CO
VI
D-
19
Ig
G/
Ig
M
ra
pi
d
te
st
To
ta
l
5–
6
5
17
–1
8
N
Ab
Ig
G
5–
6
7
17
–1
8
N
Ab
Ig
M
5–
6
5
17
–1
8
N
Ab
M
ul
ti-
G
CO
VI
D-
19
Ig
G/
Ig
M
ra
pi
d
te
st
To
ta
l
5–
6
5
17
–1
8
N
Ab
Ig
G
5–
6
7
17
–1
8
N
Ab
Ig
M
5–
6
5
17
–1
8
N
Ab
Pr
im
a
CO
VI
D-
19
Ig
G/
Ig
M
ra
pi
d
te
st
To
ta
l
5–
6
5
17
–1
8
N
Ab
Ig
G
5–
6
7
17
–1
8
N
Ab
Ig
M
5–
6
5
17
–1
8
N
Ab
M
on
te
si
no
s
et
al
.55
20
19
-n
-C
oV
Ig
G/
Ig
M
ra
pi
d
te
st
ca
ss
et
te
(L
ab
oO
n
Ti
m
e)
(L
ab
O
n
Ti
m
e,
Bi
o
M
ar
ke
tin
g
Di
ag
no
st
ic
s,
or
Ak
iv
a,
Is
ra
el
)
To
ta
l
0–
7
4
>
15
>
15
Ig
G
0–
7
6
>
15
>
15
Ig
M
0–
7
4
>
15
>
15
N
ov
el
co
ro
na
vi
ru
s
(2
01
9-
n-
Co
V)
an
tib
od
y
Ig
G/
Ig
M
as
sa
y
(c
ol
lo
id
al
go
ld
)(
Av
io
q,
Bi
o-
Te
ch
,S
ha
nd
on
g,
Ch
in
a)
To
ta
l
0–
7
4
>
15
>
15
Ig
G
0–
7
6
>
15
>
15
Ig
M
0–
7
4
>
15
>
15
Q
ui
ck
Ze
n
CO
VI
D-
19
Ig
M
/I
gG
ki
t(
Ze
nT
ec
h,
An
gl
eu
r,
Be
lg
iu
m
)
To
ta
l
0–
7
4
>
15
>
15
Ig
G
0–
7
7
>
15
>
15
Ig
M
0–
7
4
>
15
>
15
Pé
re
z-
Ga
rc
ía
et
al
.58
Al
lT
es
tC
O
V-
19
Ig
G/
Ig
M
ki
t(
Al
lT
es
tB
io
te
ch
,H
an
gz
ho
u,
Ch
in
a)
To
ta
l
N
Ab
N
Ab
N
Ab
N
Ab
Ig
G
1–
6
3
31
–3
6
>
36
Ig
M
1–
6
3
13
–1
8
25
–3
0
Ab
br
ev
ia
tio
ns
:N
Ab
,n
ot
av
ai
la
bl
e;
PO
S,
po
st
on
se
to
fs
ym
pt
om
s.
N
ot
e:
Al
lc
om
pu
te
d
da
ys
w
er
e
PO
S.
45
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ay 2022
A. U. Emeribe et al.
Ta
bl
e
5.
Di
ag
no
st
ic
m
on
ito
rin
g
of
im
m
un
og
lo
bu
lin
s
by
EL
IS
A
te
st
se
ro
lo
gi
ca
lp
ro
to
co
lf
ro
m
pu
bl
is
he
d
da
ta
Ci
ta
tio
n
Pr
od
uc
tn
am
e/
so
ur
ce
An
tib
od
y
as
se
ss
m
en
tt
yp
e
De
te
ct
io
n
tim
e
ra
ng
e
(d
)
M
ea
n
tim
e
of
de
te
ct
io
n
(d
)
Pe
ak
pe
rio
d
(d
)
Pe
rio
d
of
de
cl
in
e
(d
)
Va
n
El
sl
an
de
et
al
.5
2
Eu
ro
im
m
un
To
ta
l
N
Ab
N
Ab
N
Ab
N
Ab
Ig
G
5–
6
6
17
–1
8
N
Ab
Ig
M
N
Ab
N
Ab
N
Ab
N
Ab
Zh
ao
et
al
.1
7
CO
VI
D-
19
EL
IS
A
ki
t(
Be
iji
ng
W
an
ta
iB
io
lo
gi
ca
lP
ha
rm
ac
y
En
te
rp
ris
e
Co
.L
td
)
To
ta
l
7
4
14
–2
5
>
35
Ig
G
14
14
25
>
35
Ig
M
7
4
14
21
Xi
an
g
et
al
.5
9
Sa
nd
w
ic
h
EL
IS
A
ki
t(
Li
vz
on
In
c.
,Z
hu
ha
i,
Ch
in
a,
lo
tn
um
be
rs
20
20
03
08
[I
gM
]a
nd
20
20
03
08
[I
gG
])
To
ta
l
4
4
24
31
Ig
G
4
4
24
28
Ig
M
4
4
18
28
Pa
do
an
et
al
.7
0
CO
VI
D-
19
Ig
G/
Ig
A
EL
IS
A
ki
t(
Eu
ro
im
m
un
M
ed
iz
in
is
ch
e
La
bo
ra
di
ag
no
st
ik
a,
Lu
eb
ec
k,
Ge
rm
an
y)
To
ta
l
N
Ab
N
Ab
N
Ab
N
Ab
Ig
G
N
Ab
N
Ab
N
Ab
N
Ab
Ig
A
4
4
18
34
Jä
äs
ke
lä
in
en
et
al
.6
0
An
ti-
SA
RS
-C
oV
-2
Ig
A
an
d
Ig
G
EI
A
(E
ur
oi
m
m
un
,L
u¨
be
ck
,
Ge
rm
an
y)
To
ta
l
11
11
N
Ab
N
Ab
Ig
G
12
12
N
Ab
N
Ab
Ig
A
11
11
N
Ab
N
Ab
O
kb
a
et
al
.2
9
An
ti-
SA
RS
-C
oV
-2
Ig
G
an
d
Ig
A
EL
IS
A
(E
U
RO
IM
M
U
N
M
ed
iz
in
is
ch
e
La
bo
rd
ia
gn
os
tik
a
AG
)
To
ta
l
5
5
13
–2
1
>
21
Ig
G
5
5
13
–2
1
>
21
Ig
A
5
5
11
–1
5
20
M
on
te
si
no
s
et
al
.5
5
Eu
ro
im
m
un
an
ti-
SA
RS
-C
oV
-2
EL
IS
A
Ig
G
an
d
Ig
A
as
sa
ys
(E
ur
oi
m
m
un
,L
ue
be
ck
,G
er
m
an
y)
To
ta
l
0–
7
2
>
15
>
15
Ig
G
0–
7
7
>
15
>
15
Ig
A
0–
7
2
>
15
>
15
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ic.oup.com
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ay 2022
International Health
Ta
bl
e
5.
Co
nt
in
ue
d
Ci
ta
tio
n
Pr
od
uc
tn
am
e/
so
ur
ce
An
tib
od
y
as
se
ss
m
en
tt
yp
e
De
te
ct
io
n
tim
e
ra
ng
e
(d
)
M
ea
n
tim
e
of
de
te
ct
io
n
(d
)
Pe
ak
pe
rio
d
(d
)
Pe
rio
d
of
de
cl
in
e
(d
)
Su
n
et
al
.7
1
In
-h
ou
se
EL
IS
A
pr
od
uc
ed
us
in
g
N
pr
ot
ei
n
(r
es
id
ue
1–
41
9)
fro
m
ba
cu
lo
vi
ru
s
in
se
ct
ce
lls
(c
at
.#
40
58
8-
V0
8B
,S
in
o
bi
ol
og
ic
al
,B
ei
jin
g,
Ch
in
a)
an
d
S
pr
ot
ei
n
(r
es
id
ue
16
–6
85
)
fro
m
H
EK
29
3
ce
lls
(c
at
.#
40
59
1-
V0
8H
,S
in
o
bi
ol
og
ic
al
,
Be
iji
ng
,C
hi
na
)
To
ta
l
0–
7
2
8–
15
>
22
Ig
G
0–
7
7
8–
15
>
22
Ig
M
0–
7
2
8–
15
22
Be
av
is
et
al
.6
5
EU
RO
IM
M
U
N
an
ti-
SA
RS
-C
oV
-2
as
sa
y
To
ta
l
N
Ab
N
Ab
N
Ab
N
Ab
Ig
G
0–
2
2
19
–4
9
≥5
0
Ig
A
0–
2
2
19
–4
9
≥5
0
Ab
br
ev
ia
tio
ns
:N
Ab
,n
ot
av
ai
la
bl
e;
PO
S,
po
st
on
se
to
fs
ym
pt
om
s.
N
ot
e:
1.
Al
lc
om
pu
te
d
va
lu
es
w
er
e
PO
S.
47
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ow
nloaded from
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ic.oup.com
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ay 2022
A. U. Emeribe et al.
Ta
bl
e
6.
Di
ag
no
st
ic
m
on
ito
rin
g
of
im
m
un
og
lo
bu
lin
s
by
CL
IA
te
st
se
ro
lo
gi
ca
lp
ro
to
co
lf
ro
m
pu
bl
is
he
d
da
ta
Ci
ta
tio
n
Pr
od
uc
tn
am
e/
so
ur
ce
An
tib
od
y
as
se
ss
m
en
tt
yp
e
De
te
ct
io
n
tim
e
ra
ng
e
(d
)
M
ea
n
tim
e
of
de
te
ct
io
n
(d
)
Pe
ak
pe
rio
d
(d
)
!P
er
io
d
of
de
cl
in
e
(d
)
Lo
ng
et
al
.7
2
M
CL
IA
ki
ts
(B
io
sc
ie
nc
e
Co
.;
ap
pr
ov
ed
by
th
e
Ch
in
a
N
at
io
na
l
M
ed
ic
al
Pr
od
uc
ts
Ad
m
in
is
tr
at
io
n)
To
ta
l
2–
4
2
11
–1
3
>
23
Ig
G
2–
4
4
11
–1
3
>
23
Ig
M
2–
4
2
11
–1
3
>
23
Ji
n
et
al
.2
3
CL
IA
te
st
ki
tS
he
nz
he
n
YH
LO
Bi
ot
ec
h
Co
.,
Lt
d
(C
hi
na
)
To
ta
l
1–
5
1
16
–2
0
>
32
Ig
G
1–
5
5
16
–2
0
>
32
Ig
M
1–
5
1
16
–2
0
21
–2
5
Pa
do
an
et
al
.7
0
CL
IA
as
sa
y
(M
AG
LU
M
I2
00
0
Pl
us
)
To
ta
l
N
Ab
N
Ab
N
Ab
N
Ab
Ig
G
N
Ab
N
Ab
N
Ab
N
Ab
Ig
M
4
4
12
34
Pa
do
an
et
al
.7
3
M
AG
LU
M
I2
00
0
Pl
us
20
19
-n
Co
v
Ig
M
an
d
Ig
G
as
sa
ys
(S
ni
be
,
Sh
en
zh
en
,C
hi
na
)
To
ta
l
<
5
<
5
26
–3
0
>
30
Ig
G
<
5
<
5
26
–3
0
>
30
Ig
M
<
5
<
5
12
–1
3
18
–1
9
W
ol
ff
et
al
.6
3
El
ec
sy
s
an
ti-
SA
RS
Co
V-
2
Ig
M
/I
gG
as
sa
y
(R
oc
he
Di
ag
no
st
ic
s,
Vi
lv
oo
rd
e,
Be
lg
iu
m
)
To
ta
l
4
4
11
>
24
Ig
G
N
Ab
N
Ab
N
Ab
N
Ab
Ig
M
N
Ab
N
Ab
N
Ab
N
Ab
Li
ai
so
n
SA
RS
-C
oV
-2
Ig
G
ki
t(
CL
IA
)(
Di
as
or
in
,S
al
ug
gi
a,
It
al
y)
To
ta
l
N
Ab
N
Ab
N
Ab
N
Ab
Ig
G
4
4
11
–1
3
>
24
Ig
M
N
Ab
N
Ab
N
Ab
N
Ab
H
ou
et
al
.7
4
An
ti-
SA
RS
-C
oV
-2
CL
IA
-Y
H
LO
ki
t
To
ta
l
Ig
G
3
3
48
>
48
Ig
M
3
3
30
48
M
on
te
si
no
s
et
al
.5
5
M
ag
lu
m
i2
01
9-
n-
Co
v
Ig
G
an
d
Ig
M
(C
LI
A)
To
ta
l
0–
7
4
>
15
>
15
Ig
G
0–
7
7
>
15
>
15
Ig
M
0–
7
4
>
15
>
15
M
a
et
al
.6
7
CL
IA
RB
D-
sp
ec
ifi
c
an
ti-
SA
RS
-C
oV
-2
Ig
A,
Ig
M
,a
nd
Ig
G
ki
t
To
ta
l
N
Ab
N
Ab
N
Ab
N
Ab
Ig
G
4–
10
10
16
–4
1
>
41
Ig
M
4–
10
7
11
–3
0
31
–4
1
Ig
A
4–
10
7
11
–2
0
21
–2
5
48
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ow
nloaded from
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ic.oup.com
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ay 2022
International Health
Ta
bl
e
6.
Co
nt
in
ue
d.
Ci
ta
tio
n
Pr
od
uc
tn
am
e/
so
ur
ce
An
tib
od
y
as
se
ss
m
en
tt
yp
e
De
te
ct
io
n
tim
e
ra
ng
e
(d
)
M
ea
n
tim
e
of
de
te
ct
io
n
(d
)
Pe
ak
pe
rio
d
(d
)
!P
er
io
d
of
de
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A. U. Emeribe et al.
sensitivity, specificity, PPV and NPV of 35.95%, 63.6%, 33.3% and
26.2% at days 1, 3, 1 and 2, respectively. The most promising LFA
with the best anti-SARS-CoV-2 IgM test had a sensitivity, speci-
ficity, PPV and NPV of 95.8%, 100%, 100% and 98.4% at days 5,
6, 6 and 5, respectively, while the least had a sensitivity, speci-
ficity, PPV and NPV of 15.7%, 36.4%, 43.2% and 17.4% at days 1,
3, 1 and 3, respectively. The most promising (best) LFA on anti-
SARS-CoV-2 IgG test had a sensitivity, specificity, PPV and NPV of
100%, 100%, 100% and 100% at days 8, 9, 8 and 10, respec-
tively, while the least had a sensitivity, specificity, PPV and NPV of
13.2%, 59.9%, 65.1%and25.0%at days 1, 2, 3 and2, respectively
(Table 1).
Themost promising (best) ELISA on total SARS-CoV-2 antibody
test had a sensitivity, specificity, PPV and NPV of 93.9%, 100%,
100%and 100%at days 3, 5, 4 and 3, respectively, while the least
had a sensitivity, specificity, PPV and NPV of 46.1%, 86.6%, 76.6%
and 55.3% at days 1, 3, 2 and 1, respectively. Themost promising
ELISA with best anti-SARS-CoV-2 IgM test had a sensitivity, speci-
ficity, PPV and NPV of 89.5%, 100%, 100% and 95.7% at days 4,
6, 4 and 5, respectively, while the least had a sensitivity, speci-
ficity, PPV and NPV of 64.9%, 88.1%, 70.6% and 80.0% at days 1,
3, 2 and 3, respectively. The most promising (best) ELISA on anti-
SARS-CoV-2 IgG test had a sensitivity, specificity, PPV and NPV of
100%, 100%, 100%and 100%at days 8, 10, 8 and 9, respectively,
while the least had a sensitivity, specificity, PPV andNPV of 46.1%,
86.6%, 72.5% and 56.2% at days 5, 7, 6 and 7, respectively. The
most promising (best) ELISA on anti-SARS-CoV-2 IgA test had a
sensitivity, specificity, PPV and NPV of 97.4%, 100%, 100% and
98.0% at days 4, 5, 6 and 5, respectively, while the least had a
sensitivity, specificity, PPV and NPV of 46.1%, 68.3%, 58.1% and
53.3% at days 14, 13, 14 and 13, respectively (Table 2).
The most promising (best) CLIA on total SARS-CoV-2 antibody
test had a sensitivity, specificity, PPV and NPV of 100%, 100%,
100% and 100% at days 2, 3, 2 and 3, respectively, while the
least had a sensitivity, specificity, PPV and NPV of 58.7%, 92.3%,
81.6% and 61.5% at days 1, 2, 1 and 1, respectively. The most
promising (best) CLIA on anti-SARS-CoV-2 IgM test had a sensi-
tivity, specificity, PPV and NPV of 96.8%, 100%, 100% and 98.5%
at days 1, 3, 3 and 2, respectively, while the least had a sensitiv-
ity, specificity, PPV and NPV of 63.1%, 90.5%, 84.9% and 58.1%
at days 12, 10, 9 and 11, respectively. The most promising (test)
CLIA on anti-SARS-CoV-2 IgG test had a sensitivity, specificity, PPV
and NPV of 95.7%, 100%, 100% and 98.7% at days 7, 9, 8 and 7,
respectively, while the least had a sensitivity, specificity, PPV and
NPV of 43.8.1%, 68.7%, 76.1% and 54.9% at days 1, 3, 2 and 1,
respectively (Table 3).
The detection, peak and decline periods of blood anti-SARS-
CoV-2 IgM, IgG and total antibodies for POCT, ELISA and CLIA
vary widely. The most promising of these assays for POCT de-
tected anti-SARS-CoV-2 at day 3 POS in 21.1% (n=19) and
peaked on the 15th day in 93.3% (n=21)58 of COVID-19 pa-
tients; ELISA products detected anti-SARS-CoV-2 IgM and IgG
at days 2 and 6 in 34.1% (n=38)71 and in 46.7% (n=15)52
COVID-19 patients, respectively, and peaked on the eighth day
in 92.1% (n=38)71 of COVID-19 patients. The most promising
CLIA product detected anti-SARS-CoV-2 IgM and IgG at days 1
and 4 in 33.3% (n=6)23 and 60.0% (n=35),63 respectively, and
peaked on the 30th day in 97.8% (n=87)73 of COVID-19 patients
(Tables 4-6).
Conclusions
Given the varied performance characteristics of all the sero-
logical assays, there is a need to continuously improve their
detection thresholds, as well as to monitor and re-evaluate their
performances to ensure their significance and applicability for
COVID-19 clinical and epidemiological purposes. When found
satisfactory, their use will be imperative for scaling up COVID-19
testing in the face of the economic downturn in resource-limited
countries. It is recommended that public institutions, private
firms, researchers and healthcare policymakers consider the
development and evaluation of alternative means of reducing
the current PCR test turnaround time and improving the test
capacity of serological tests to secure improved epidemiological
data for SARS-CoV-2.
Authors’ contributions: INA, LDR and AUE conceptualized and planned
the study. INA, AUE, HAS, LU, SM, AUA, HAA, LDR, DA, SH, YU, HYM, AMG,
JON, HMC, CCO, OSA, LO, CO, CNE, PEG, LOA and BOPM conducted the lit-
erature search and compilation of data. INA, AUE, HAS, LU, SM, AUA, HAA
and LDR performed the data curation and statistical analysis. All the au-
thors participated in writing the draft, revised and final versions of the
manuscript. All the authors read and approved the final version of the
manuscript for intellectual content before submission. INA is responsible
for the overall content as guarantor.
Acknowledgements: The authors greatly appreciate Gabriel Ilerioluwa
Oke for proofreading and copyediting parts of the manuscript.
Funding: None received.
Competing interests: None.
Ethical approval: Not applicable (this is a review article).
Data availability: This study being a review article, the data presented
in the results section and in discussing our main findings are well refer-
enced. However, raw data will be made available on request through the
corresponding author (I.N. Abdullahi).
References
1 Decaro N, Lorusso A. Novel human coronavirus (SARS-CoV-2): A les-
son from animal coronaviruses. Vet Microbiol. 2020;244:108693. doi:
10.1016/j.vetmic.2020.108693.
2 Worldometers.info. Situation Update Worldwide, as of 2 July 2020.
Delaware, USA: Dove, 2020. Available at https://www.worldometers.
info/coronavirus/#countries [accessed 20 July 2020].
3 Padula WV. Why only test symptomatic patients? Consider ran-
dom screening for COVID-19. Appl Health Econ Health Policy.
2020;18(3):333–4.
4 Hellewell J, Abbott S, Gimma A, et al. Feasibility of controlling COVID-
19 outbreaks by isolation of cases and contacts. Lancet Global Health.
2020;8(4):e488–96.
5 Ueda M, Martins R, Hendrie PC, et al. Managing cancer care during
the COVID-19 pandemic: agility and collaboration toward a common
goal. J Natl Compr Canc Netw. 2020;18(4):366–9.
50
D
ow
nloaded from
 https://academ
ic.oup.com
/inthealth/article/14/1/18/6147255 by Turun Yliopisto user on 09 M
ay 2022
International Health
6 Ranney ML, Griffeth V, Jha AK. Critical supply shortages — the need
for ventilators and personal protective equipment during the Covid-
19 pandemic. N Engl J Med. 2020;382(18):e41.
7 Villaraza, Angangco. FDA issuances on evaluation, approval and
use of COVID-19 test kits. Available at https://www.lexology.com/
library/detail.aspx?g=7689832c-83ce-4683-a5ea-4630eee5788f
[accessed 1 June 2020].
8 Rashid ZZ, Othman SN, Samat MNA,, et al.. Diagnostic performance of
COVID-19 serology assays. Malaysian J Pathol. 2020;42(1):13–21.
9 Cui J, Li F, Shi Z-L. Origin and evolution of pathogenic coronaviruses.
Nat Rev Microbiol. 2018;17(3):181–92.
10 Chan JF-W, Kok K-H, Zhu Z, et al. Genomic characterization of the
2019 novel human-pathogenic coronavirus isolated from a patient
with atypical pneumonia after visitingWuhan. EmergMicrobes Infect.
2020;9(1):221–36.
11 Wu A, Peng Y, Huang B, et al. Genome composition and divergence
of the novel coronavirus (2019-nCoV) originating in China. Cell Host
Microbe. 2020;27(3):325–8.
12 Ji W, Wang W, Zhao X, Zai J, Li X. Cross-species transmission of the
newly identified coronavirus 2019-nCoV. J Med Virol. 2020;92(4):433–
40.
13 World Health Organization. 2020 Global Surveillance for human
infection with coronavirus disease (COVID-2019), interim guid-
ance, Geneva. Available at https://www.who.int/publicationsdetail/
global-surveillance-for-humaninfection-with-novel-coronavirus-
(2019-ncov) [accessed 4 April 2020].
14 Happi C, Ihekweazu C, Oluniyi PE,, et al.. SARS-CoV-2 genomes from
Nigeria reveal community transmission, multiple virus lineages
and spike protein mutation associated with higher transmission
and pathogenicity. Virological. 2020. http://virological.org/t/sars-
cov-2-genomes-from-nigeria-reveal-community-transmission-
multiple-virus-lineages-and-spike-protein-mutation-associated-
with-higher-transmission-and-pathogenicity/494. [accessed 2 June
2020].
15 Xiao AT, Gao C, Zhang S. Profile of specific antibodies to SARS-CoV-2:
The first report. J Infect. 2020;81(1):147–78.
16 Morrison A, Li Y, Loshak H. Serological tests for COVID-19. Ottawa:
CADTH; 2020 ( CADTH Horizon Scan; 188:13) .
17 Zhao J, Yuan Q, Wang H, et al. Antibody Responses to SARS-CoV-
2 in Patients With Novel Coronavirus Disease 2019. Clin Infect Dis.
2020;71(16):2027–34. doi: 10.1093/cid/ciaa344.
18 Long QX, Liu BZ, Deng HJ, et al. Antibody responses to SARS-CoV-2 in
patients with COVID-19. Nat Med. 2020;26(6):845–8.
19 Li Z, Yi Y, Luo X, et al. Development and clinical application of a rapid
IgM-IgG combined antibody test for SARS-CoV-2 infection diagnosis.
J Med Virol. 2020;92(9):1518–24.
20 Hoffman T, Nissen K, Krambrich J, et al. Evaluation of a COVID-19 IgM
and IgG rapid test; an efficient tool for assessment of past exposure
to SARS-CoV-2. Infect Ecol Epidemiol. 2020;10(1):1754538.
21 Mo HY, Xu J, Ren XL, et al. Evaluation by indirect immunofluores-
cent assay and enzyme linked immunosorbent assay of the dynamic
changes of serum antibody responses against severe acute respira-
tory syndrome coronavirus. Chin Med J. 2005;118(6):446–50.
22 Cao W-C, Liu W, Zhang P-H, Zhang F, Richardus JH. Disappearance
of antibodies to SARS-associated coronavirus after recovery. N Engl J
Med. 2007;357(11):1162–3.
23 Jin Y, Wang M, Zuo Z, et al. Diagnostic value and dynamic vari-
ance of serum antibody in coronavirus disease 2019. Int J Infect Dis.
2020;94:49–52.
24 Guo L, Ren L, Yang S, et al. Profiling early humoral response to
diagnose novel coronavirus disease (COVID-19). Clin Infect Dis.
2020;71(15):778–85. doi: 10.1093/cid/ciaa310.
25 Cerutti A. The regulation of IgA class switching. Nat Rev Immunol.
2008;8(6):421–34.
26 Szomolanyi-Tsuda E, Welsh RM. T-cell-independent antiviral antibody
responses. Curr Opin Immunol. 1998;10(4):431–5.
27 Liu W, Liu L, Kou G, et al. Evaluation of nucleocapsid and spike
protein-based enzyme-linked immunosorbent assays for detect-
ing antibodies against SARS-CoV-2. J Clin Microbiol. 2020;58(6):
e00461–20.
28 Amanat F, Stadlbauer D, Strohmeier S, et al. A serological as-
say to detect SARS-CoV-2 seroconversion in humans. Nat Med.
2020;26(7):1033–6.
29 Okba NMA, Müller MA, Li W, et al. Severe acute respiratory syndrome
coronavirus 2-specific antibody responses in coronavirus disease pa-
tients. Emerg Infect Dis. 2020;26(7):1478–88.
30 ZhangW, Du R-H, Li B, et al. Molecular and serological investigation of
2019-nCoV infected patients: implication ofmultiple shedding routes.
Emerg Microb Infect. 2020;9:386–9.
31 Zeng H, Xu C, Fan J, et al. Antibodies in Infants Born to
Mothers With COVID-19 Pneumonia. JAMA. 2020;323(18):1848–9.
doi:10.1001/jama.2020.4861.
32 Weinstein MC, Freedberg KA, Hyle EP, Paltiel AD. Waiting for cer-
tainty on Covid-19 antibody tests - at what cost? N Engl J Med.
2020;383(6):e37.
33 Whitman JD, Hiatt J, Mowery CT, et al. Test performance evaluation of
SARS-CoV-2 serological assays. medRxiv. [Preprint]2020 May 17. doi:
10.1101/2020.04.25.20074856.
34 Mandavilli A. Coronavirus Antibody Tests: Can You Trust the Results?
The New York Times, 2020. Retrieved from: https://www.nytimes.
com/2020/04/24/health/coronavirus-antibody-tests.html.
35 Lassaunière R, Frische A, Harboe ZB, et al. Evaluation of nine
commercial SARS-CoV-2 immunoassays. medRxiv. 2020. doi:
https://doi.org/10.1101/2020.04.09.20056325.
36 Nicol T, Lefeuvre C, Serri O, et al. Assessment of SARS-CoV-2 serolog-
ical tests for the diagnosis of COVID-19 through the evaluation of
three immunoassays: Two automated immunoassays (Euroimmun
and Abbott) and one rapid lateral flow immunoassay (NG Biotech).
J Clin Virol. 2020;129:104511.
37 Lin D, Liu L, ZhangM, et al. Evaluations of the serological test in the di-
agnosis of 2019 novel coronavirus (SARS-CoV-2) infections during the
COVID-19 outbreak. Eur J Clin Microbiol Infect Dis. 2020;39(12):2271–
7. doi: 10.1007/s10096-020-03978-6.
38 Chew KL, Tan SS, Saw S, et al. Clinical evaluation of serological IgG
antibody response on the Abbott Architect for established SARS-CoV-
2 infection. Clin Microbiol Infect. 2020;26(9):1256.e9–11.
39 Yang HS, Racine-Brzostek SE, Lee WT, et al. SARS-CoV-2 antibody
characterization in emergency department, hospitalized and conva-
lescent patients by two semi-quantitative immunoassays. Clin Chim
Acta. 2020;509:117–25.
40 Nagura-Ikeda M, Imai K, Tabata S, et al. Clinical Evaluation
of Self-Collected Saliva by Quantitative Reverse Transcription-
PCR (RT-qPCR), Direct RT-qPCR, Reverse Transcription-Loop-
Mediated Isothermal Amplification, and a Rapid Antigen Test
To Diagnose COVID-19. J Clin Microbiol. 2020;58(9):e01438–20.
doi: 10.1128/JCM.01438-20.
41 National SARS-CoV-2 Serology Assay Evaluation Group. Performance
characteristics of five immunoassays for SARS-CoV-2: a head-to-head
51
D
ow
nloaded from
 https://academ
ic.oup.com
/inthealth/article/14/1/18/6147255 by Turun Yliopisto user on 09 M
ay 2022
A. U. Emeribe et al.
benchmark comparison. Lancet Infect Dis. 2020;20(12):1390–1400.
doi: 10.1016/S1473-3099(20)30634-4.
42 Theel ES, Harring J, Hilgart H, Granger D. Performance charac-
teristics of four high-throughput immunoassays for detection of
IgG antibodies against SARS-CoV-2. J Clin Microb. 2020;58:e01243–
20. doi: 10.1128/JCM.01243-20.
43 GeurtsvanKessel CH, OKBA NMA, Igloi Z, et al. Towards the
next phase: evaluation of serological assays for diagnostics
and exposure assessment. medRxiv 2020.04.23.20077156. doi:
https://doi.org/10.1101/2020.04.23.20077156.
44 Cassaniti I, Novazzi F, Giardina F, et al. Members of the San Mat-
teo Pavia COVID-19 Task Force. Performance of VivaDiag COVID-
19 IgM/IgG Rapid Test is inadequate for diagnosis of COVID-19 in
acute patients referring to emergency room department. J Med Vi-
rol. 2020;92(10):1724–7. doi: 10.1002/jmv.25800.
45 Porte L, Legarraga P, Vollrath V, et al. Evaluation of novel antigen-
based rapid detection test for the diagnosis of SARS-CoV-2 in respi-
ratory samples. Int J Infect Dis. 2020;99:328–33.
46 Pan Y, Li X, Yang G, et al. Serological immunochromatographic ap-
proach in diagnosis with SARS-CoV-2 infected COVID-19 patients. J
Infect. 2020;81(1):e28–32. doi: 10.1016/j.jinf.2020.03.051.
47 Pallett S, Denny S, Patel A, et al. Point-of-care serological assays for
SARS-CoV-2 in a UK hospital population: potential for enhanced case.
Research Square Preprint. 2020. doi: 10.21203/rs.3.rs-28006/v1.
48 Spicuzza L,Montineri A, Manuele R, et al. Reliability and usefulness of a
rapid IgM-IgG antibody test for the diagnosis of SARS-CoV-2 infection:
A preliminary report. J Infect. 2020;81:e53–4.
49 Wu J-L, Tseng W-P, Lin C-H, et al. Four point-of-care lateral flow
immunoassays for diagnosis of COVID-19 and for assessing dy-
namics of antibody responses to SARS-CoV-2. J Infect. 2020;81:
435–42.
50 Green K, Graziadio S, Turner P,, et al.. Molecular and antibody
point-of-care tests to support the screening, diagnosis and moni-
toring of COVID-19. The Centre for Evidence-based Medicine. 2020.
https://www.cebm.net/covid-19/molecular-and-antibody-point-of-
care-tests-to-support-the-screening-diagnosis-and-monitoring-of-
covid-19/.
51 Mlcochova P, Collier D, Ritchie AV, et al. Combined point of care
SARS-CoV-2 nucleic acid and antibody testing in suspected moder-
ate to severe COVID-19 disease. Cell Reports Medicine. 2020;1(6):
100099.
52 Van Elslande J, Houben E, Depypere M, et al. Diagnostic performance
of seven rapid IgG/IgM antibody tests and the Euroimmun IgA/IgG
ELISA in COVID-19 patients. Clin Microbiol Infect. 2020;26:1082–7.
53 Jääskeläinen A, Kuivanen S, Kekäläinen E, et al. Performance of six
SARS-CoV-2 immunoassays in comparison with microneutralisation.
J Clin Virol. 2020;129:104512.
54 Kohmer N, Westhaus S, Rühl C, Ciesek S, Rabenau HF. Clinical per-
formance of different SARS-CoV-2 IgG antibody tests. J Med Virol.
2020;92(10):2243–7. doi: 10.1002/jmv.26145.
55 Montesinos I, Gruson D, Kabamba B, et al. Evaluation of two auto-
mated and three rapid lateral flow immunoassays for the detection
of anti-SARS-CoV-2 antibodies. J Clin Virol. 2020;128:104413.
56 Adams ER, Ainsworth M, Anand R, et al. Antibody testing for
COVID-19: a report from the national COVID scientific ad-
visory panel. medRxiv. 2020.04.15.20066407. doi: https://
doi.org/10.1101/2020.04.15.20066407.
57 Nuccetelli M, Pieri M, Grelli S, et al. SARS-CoV-2 infection serol-
ogy: a useful tool to overcome lockdown? Cell Death Discov. 2020;
6:38.
58 Pérez-García F, Pérez-Tanoira R, Romanyk J, Arroyo T, Gómez-Herruz
P, Cuadros-Gonzàlez J. Alltest rapid lateral flow immunoassays
is reliable in diagnosing SARS-CoV-2 infection from 14 days af-
ter symptom onset: A prospective single-center study. J Clin Virol.
2020;129:104473.
59 Xiang F, Wang X, He X, et al. Antibody detection and dynamic char-
acteristics in patients with coronavirus disease 2019. Clini Infect Dis.
2020;71:1930–4.
60 Jääskeläinen AJ, Kekäläinen E, Kallio-Kokko H, et al. Evalua-
tion of commercial and automated SARS-CoV-2 IgG and IgA
ELISAs using coronavirus disease (COVID-19) patient sam-
ples. Eurosurveillance. 2020;25(18):2000603 doi: 10.2807/1560-
7917.ES.2020.25.18.2000603.
61 Müller L, Ostermann PN, Walker A, et al. Sensitivity of
commercial Anti-SARS-CoV-2 serological assays in a high-
prevalence setting. medRxiv. 2020.06.11.20128686. doi: https://
doi.org/10.1101/2020.06.11.20128686.
62 Kohmer N, Westhaus S, Rühl C, Ciesek S, Rabenau HF. Brief clinical
evaluation of six high-throughput SARS-CoV-2 IgG antibody assays. J
Clin Virol. 2020;129:104480.
63 Wolff F, Dahma H, Duterme C, et al. Monitoring antibody response fol-
lowing SARS-CoV-2 infection: Diagnostic efficiency of four automated
immunoassays. Diagn Microbiol Infect Dis. 2020;98:115140.
64 Francesca C, Alessandra B, Daniele L, et al. Evaluation
of ELISA tests for the qualitative determination of IgG,
IgM and IgA to SARSCoV-2. medRxiv preprint. 2020. doi:
https://doi.org/10.1101/2020.05.24.20111682.
65 Beavis KG, Matushek SM, Abeleda PF, et al. Evaluation of the EUROIM-
MUN Anti-SARS-CoV-2 ELISA Assay for detection of IgA and IgG anti-
bodies. J Clin Virol. 2020;129:104468.
66 Infantino M, Grossi V, Lari B, et al. Diagnostic accuracy of an au-
tomated chemiluminescent immunoassay for anti-SARS-CoV-2 IgM
and IgG antibodies: an Italian experience. J Med Virol. 2020;92:
1671–5.
67 Ma H, Zeng W, He H, et al. COVID-19 diagnosis and study of
serum SARS-CoV-2 specific IgA, IgM and IgG 2 by a quanti-
tative and sensitive immunoassay. medRxiv preprint. 2020. doi:
https://doi.org/10.1101/2020.04.17.20064907.
68 Qian C, Zhou M, Cheng F, et al. Development and multicenter
performance evaluation of fully automated SARS-CoV-2 IgM and
IgG immunoassays. Clin Chem Lab Med. 2020;58(9):1601–7. doi:
10.1515/cclm-2020-0548.
69 Suhandynata RT, Hoffman MA, Keiner MJ, McLawhon RW, Reed SL,
Fitzgerald RL. Longitudinal monitoring of SARS-CoV-2 IgM and IgG
seropositivity to detect COVID-19. J App Lab Med. 2020;5:908–20.
70 Padoan A, Sciacovelli L, Basso D, et al. IgA-Ab response to spike gly-
coprotein of SARS-CoV-2 in patients with COVID-19: A longitudinal
study. Clinica Chimica Acta. 2020;507:164–6.
71 Sun B, Feng Y, Mo X, et al. Kinetics of SARS-CoV-2 specific IgM and
IgG responses in COVID-19 patients. Emerg Microb Infect. 2020;9(1):
940–8.
72 Long Q-X, Liu B-Z, Deng H-J, et al. Antibody responses to SARS-CoV-2
in patients with COVID-19. Nat Med. 2020;26(6):845–8.
73 Padoan A, Cosma C, Sciacovelli L, Faggian D, Plebani M. Analytical
performances of a chemiluminescence immunoassay for SARS-CoV-
2 IgM/IgG and antibody kinetics. Clin Chem Lab Med. 2020;58(7):
1081–8.
74 Hou H, Wang T, Zhang B, et al. Detection of IgM and IgG antibod-
ies in patients with coronavirus disease 2019. Clin Transl Immunol.
2020;9(5):e1136.
52
D
ow
nloaded from
 https://academ
ic.oup.com
/inthealth/article/14/1/18/6147255 by Turun Yliopisto user on 09 M
ay 2022