Detecting the Coronavirus (COVID-19)
Pravin Pokhrel, Changpeng Hu, and Hanbin Mao*
Department of Chemistry and Biochemistry, Kent State University, Kent, OH, USA (44240)
Keywords: Diagnosis, Detection Kits, RT-PCR, Immunoassay, False Negative, False Positive, Sensitivity, Specificity, Pointof-care testing (POCT)
ABSTRACT: The COVID-19 pandemic has created huge damage to society and brought panics around the world. Such panics can
be ascribed to the seemingly deceptive features of the COVID-19: compared to other deadly viral outspreads, it has medium transmission and mortality rates. As a result, the severity of the causative coronavirus, SARS-CoV-2, was deeply underestimated by the
society at the beginning of the COVID-19 outbreak. Based on this, in this review, we define the viruses with features similar to those
of SARS-CoV-2 as the Panic Zone viruses. To contain those viruses, accurate and fast diagnosis followed by effective isolation and
treatment of patients are pivotal at the early stage of virus breakouts. This is especially true when there is no cure or vaccine available
for a transmissible disease, which is the case for current COVID-19 pandemic. As of June 2020, more than one hundred kits for the
COVID-19 diagnosis on the market are surveyed in this review. It is of critical importance to rationally use these kits for the efficient
management and control of the Panic Zone viruses. Therefore, we discuss guidelines to select diagnostic kits at different outbreak
stages of the Panic Zone viruses, SARS-CoV-2 in particular. While it is of utmost importance to use nucleic-acid based detection kits
with low false negativity (high sensitivity) at the early stage of an outbreak, the low false positivity (high specificity) gains its importance at later stages of the outbreak. When the society is set to reopen from the lock-down stage of the COVID-19 pandemic, it
becomes critical to have immunoassay based kits with high specificity to identify people who can safely return to the society after
their recovery of SARS-CoV-2 infections. Finally, since a massive attack from a viral pandemic requires a massive defense from the
whole society, we urge both government and private sectors to research and develop affordable and reliable point-of-care testing
(POCT) kits, which can be used massively by the general public (and therefore called as massive POCT) to contain Panic Zone
viruses in future.
1. Background
Since the beginning of the 21st century, our world has been
facing unprecedented crises of deadly viruses like Zika, Ebola,
SARS, MERS, and so forth. The epidemics of these viral diseases were sparked either by the evolution of pre-existing viruses or by the emergence of new viral species. Such diseases
have already caused colossal damage to the society. Loss of
lives struck the most, but the consequences aftermath was
equally dreadful: the psychological wellbeing of survivors and
socio-economic fallout were rather distressing. Now, in December 2019, the world was hit by another virus known as SARSCoV-2 (the disease associated with this virus is called COVID19).
[Figure 1]
1.1. The Panic Zone viruses
Compared to other viruses, SARS-CoV-2 has a medium reproduction rate (R0=2.25*) and a medium mortality rate of
5.7%*1 (as of June 7, 2020, *subject to change). Such mediocre
characteristics give a rather deceiving impression of this virus.
When the virus first started in China, it did not draw immediate
attention to the public due to its seemingly “benign” appearance. Indeed, compared to the Death Zone viruses which include Ebola and smallpox (see definition in Figure 1), this disease was considered merely as another type of influenza even
among health professionals. However, the virus soon revealed
its damaging nature. Staying untreated, the disease spread out
quickly to overwhelm the health systems in a society. This
eventually caused panics in the general public. People rushed to
see doctors even if they developed very mild or even unrelated
symptoms, which overran hospitals. This is because in modern
society, the production system of healthcare supplies is profit
driven2. Decisions regarding the management of disease can no
longer be made based solely on scientific grounds. Unless a disease poses a specific risk to a wide population, its mere presence
in a localized area or population may not be significant from a
business perspective. As a result, necessary resources such as
PPE (Personal Protective Equipment) are in short supply to
fight pandemic diseases promptly. Due to these reasons, the diseases in the Panic Zone (see Figure 1 for definition) often wreck
huge collateral damages due to its paralyzing role for the whole
society.
In the Panic Zone, SARS was most recently contained by
means of massive syndromic surveillance, prompt isolation of
patients, and strict quarantine of all contacts. By interrupting all
human-to-human transmissions, SARS was effectively eradicated in 20033. Although there are striking similarities between
SARS and COVID-19, the differences in the virus characteristics will ultimately determine whether the same measures for
SARS will also be successful for the current COVID-19 outbreak. COVID-19 differs from the SARS in terms of infectious
period, transmissibility, clinical severity, and extent of the community spread3. Although COVID-19 has lower transmissibility
than SARS4, many more COVID-19 patients have mild symptoms that contribute to the rapid spread of the virus as these patients are often missed and not isolated.
1.2. The early detections
It is generally true that for a rapidly transmitting disease with
no cure or vaccine available, the most effective way to curb its
spread is the early detection to isolate patients5,6. The first step
to achieve this is to identify those patients using detection kits.
Never before is a virus detection system so critical to contain a
viral outbreak as dangerous as COVID-19. As shown in Figure
2, for the five countries with similar age distribution and hospital resources, the more extensive the early tests on the COVID19, the lower the overall mortality rates in a country. Indeed,
Korea and Germany conducted a substantial number of the tests
right at the beginning of the COVID-19 outbreak. Correspondingly, their death rates are among the lowest so far (Figure 2,
inset). This confirmed the importance of the early testing to curb
the spreading of the COVID-19.
[Figure 2]
In this review, we first describe the COVID-19 outbreak
briefly. Given the importance of the diagnosis for this deadly
pandemic disease, we then survey the detection kits used for the
COVID-19. After summarizing the challenges facing current
commercial kits, we discuss emerging techniques to address
these issues. Next, we propose and discuss guidelines to use
various kits during different stages of the COVID-19 outbreak.
Finally, we wrap up by proposing the research and development
of affordable point-of-care testing (POCT) kits that can be used
massively (massive POCT) to battle these viral pandemics in
the future.
2. The COVID-19 outbreak
2.1. COVID-19 Timeline
In December 2019, a cluster of pneumonia cases were reported in Wuhan, China7. The causative virus of that disease
was determined as SARS-CoV-2 (later this disease was called
as COVID-19, Corona Virus Disease 2019, by the WHO) since
the virus shared ~80% genome from the SARS-CoronaVirus8.
On January 11, 2020, the first death caused by this virus was
reported in China. This disease was highly contagious and
therefore was declared by the WHO as a Public Health Emergency of International Concern (PHEIC) within a month after
the first case. On March 11, WHO declared COVID-19 a pandemic disease as it started to spread across the globe.
2.2. Clinical characteristics of COVID-19
Based on current epidemiological researches, the clinical
characteristics for COVID-19 appeared in 1-14 days after the
infection and most patients developed symptoms within 3-7
days9. The common symptoms include fever, coughing, and
body weakness. A few patients developed nasal congestion,
running nose, pharyngalgia, myodynia, and diarrhea. In severe
cases, by the end of the first week, the disease can develop into
dyspnea and/or hypoxia. In deadly cases, the disease can
quickly progress to acute respiratory distress syndrome, septic
shock, coagulation disorders, and multiple organ failure9. It is
noteworthy that patients with high viral loads may have low or
insignificant fever during the infection. Some children and neonates did not have typical symptoms, but they presented with
gastrointestinal symptoms such as vomiting and diarrhea or presented with depression or shortness of breath10. The elderly and
patients with chronic underlying diseases had poor prognosis11.
2.3. Epidemiology of COVID-19
People are generally susceptible to the SARS-CoV-2 infection at all ages. The infection is transmitted by droplet (direct
inhalation of droplets from the sneeze, cough, or talking of an
infected person) or contact (contacting the virus deposited on
the object surface, which then enters the body via the mouth,
nose, eyes, or other mucous membrane12). Study showed a
higher viral load in the nasal cavity than the throat, suggesting
the nasal sampling is a more effective approach to detect the
virus. There was no difference in the viral load between symptomatic and asymptomatic patients13, the latter of which can
also transmit the disease14. Guan et al. reported that some patients were tested positive for SARS-CoV-2 in stool and urine
samples also9.
3. Diagnosis of the COVID-19
As discussed in the Background, in the absence of effective
therapeutic drugs or vaccines for COVID-19, it is essential to
detect the disease at an early stage and immediately isolate infected patients. Currently, there are three methods in clinical
practice to diagnose COVID-19, which are summarized below.
3.1. Chest CT Imaging
Studies showed that chest CT images contained characteristic
features for COVID-19 patients. The hallmarks of these CT images include ground glass opacities, crazy-paving pattern, consolidative opacities, septal thickening, and the reverse-halo
sign15–18. These features demonstrate a highly organized pattern
of pneumonia16. Unlike these features, nodules, cystic changes,
bronchiectasis, pleural diffusion, and lymphadenopathy are less
common18.
Despite such features, the Centers for Disease Control (CDC)
in the US does not currently recommend CT to diagnose
COVID-19. Laboratory testing of the virus remains the reference standard, even if the CT findings are suggestive of SARSCoV-2 infections19. This is because features of the chest imaging from COVID-19 patients may overlap with other infections
caused by influenza, H1N1, or SARS-CoV20,21.
However, studies on the sensitivity of CT imaging over RTPCR (Reverse Transcription - Polymerase Chain Reaction,
which is considered as the reference standard for laboratory
testing of SARS-CoV-2, see section 3.2 below) showed that CT
imaging is more sensitive and rather reliable in detecting SARSCoV-2 infections during certain stage of the COVID-19. Fang
et al. studied 51 patients with COVID-19 symptoms based on
their clinical manifestations and epidemiological histories22.
They found that the chest CT scan was more sensitive (98%)
than the RT-PCR method (71%). This study was limited by the
number of subjects involved. However, another study involving
more than 1000 patients reached similar conclusions23. Among
1014 patients, 59% were RT-PCR positive, from which 97%
showed positive CT features. In addition, 75% of RT-PCR negative patients showed positive CT features. To further validate
this, Ai et al. studied multiple RT-PCR testing and serial CT
imaging in a selected group. They found 60 - 93% people who
were RT-PCR negative showed initial positive CT images consistent with SARS-CoV-2 infections. From the patients in the
recovery stage, 42% showed improvement in CT features before their RT-PCR results turned negative.
According to these diagnostic studies, RT-PCR assays were
not as sensitive and reliable as CT images in certain stages of
the COVID-19. The false negative results from RT-PCR assays
can be detrimental to the control of the COVID-19, especially
at the beginning of the outbreak. The caveat for the CT scans is
that at an early stage of infection, the lungs of a patient may not
develop damaging features that can be picked up by CT scans,
increasing its false negative rate. In addition, the COVID-19 CT
features share similarities with other viral pneumonia, resulting
in false positive detections. Nevertheless, given the rapid
spreading of the COVID-19, the priority is to identify any suspicious case for patient isolation and proper treatment. In the
context of emergency disease control, some false-positive cases
(i.e. compromised specificity) may be acceptable. It is the false
negative cases, due to the poor sensitivity of testing methods,
that present a threat to public health at the beginning of an outbreak. In some cases, chest CT imaging showed positive SARSCoV-2 infection while RT-PCR testing was negative22. These
findings suggest that a combination of clinical symptoms, epidemiologic history, and CT imaging of a patient may be instrumental to identify SARS-CoV-2 infections at the time when
chemical detection kits are in short supply.
3.2. Nucleic acid based methods
After identification of the SARS-CoV-2 as the causative virus for this pandemic, the SARS-CoV-2 genome was quickly
sequenced24, from which unique sequences have been identified
for COVID-19 diagnosis. Reverse transcriptase-polymerase
chain reaction (RT-PCR) is a nucleic acid amplification assay
that has long been used routinely for the detection of RNA viruses in clinical settings25. In RT-PCR, reverse transcriptase is
first used to convert RNA to its complementary DNA, which is
amplified by PCR (polymerase chain reaction). There are variants of RT-PCR methods that share the same mechanism while
differing in the detection strategy. For example, real time RTPCR reads fluorescent signals during PCR amplification26 to
quantify the target, whereas nested RT-PCR uses two sets of
primers to avoid non-specific PCR amplifications27.
The SARS-CoV-2 genes targeted for detection so far include
the RdRP gene, Nucleocapsid (N) gene, E gene, Spike protein
(S gene), and ORF1ab gene. Chu et al. used two different onestep real-time RT-PCR approaches to detect ORF1ab and N
genes of the viral genome28. This assay showed a high dynamic
range of 0.0002-20 TCID50 (50% tissue culture infective dose)
per reaction and the detection limit below 10 RNA copies per
reaction. Later, WHO developed a technical guidance including
the protocols from different countries to aid COVID-19 diagnosis29. According to this compilation, in the US, CDC developed
a real time RT-PCR diagnostic kit with detection limits as low
as 4-10 RNA copies per µl. Scientists from Germany used the
E gene for the first-line screening and the RdRP gene for confirmatory testing29. This method further increased sensitivity to
detect as low as 5.6 RNA copies per reaction for the E gene and
3.8 RNA copies per reaction for the RdRP gene. In Hongkong,
the N gene was used as the first-line screening while the ORF1b
as the confirmatory testing29. In France, two RdRP genes were
used for initial screening followed by the confirmatory E gene
testing29. In Japan, nested RT-PCR was used,29 which significantly reduced non-specific target amplification, leading to decreased false-positive results (i.e. increased specificity). In general, the sensitivity of these assays ranges from 3.8 to 10 RNA
copies per reaction, with high specificities.
In the public health emergency, highly sensitive methods are
desirable. Although studies have shown that RT-PCR may be
less sensitive than CT imaging at certain stages of the COVID19, its specificity makes it superior to other methods to detect
SARS-CoV-2. It is of critical importance to rationally choose
specific diagnostic methods to battle viral outbreaks. Any negligence or compromise in the diagnosis may lead to devastating
consequences. Wang et al. suggested combining RT-PCR with
other methods as well as epidemiological history of patients to
diagnose SARS-CoV-2 infection more credibly30. Indeed, the
Chinese authority has adopted this approach to diagnose
COVID-19 in Wuhan by combining RT-PCR with CT scans23.
Studies also showed that the sensitivity of RT-PCR varies with
the specimen types. To et al. revealed that the saliva samples
were more promising to be used in RT-PCR31 while Yam et al.
concluded that testing more than one specimen could significantly maximize the sensitivity of the RT-PCR testing32. These
findings suggest it is rather important to apply nucleic acid
based kits with optimized conditions to maximize their diagnosis potency. In particular, the finding of effective SARS-CoV-2
detection in the non-invasive saliva33 provides a convenient way
to develop affordable point-of-care testing kits that can be massively used by the general public (see Sections 4 and 5 below).
Table 1 lists the nucleic acid based kits used for the diagnosis
of COVID-19. The sensitivity of those kits ranges from 1001000 copies/mL.
3.3. Immunoassays
Immunoassay is another established diagnostic method. This
method detects viral protein antigens or serum antibodies in patients who have been exposed to the SARS-CoV-2. These antibody tests are important in detecting prior infections.
In the SARS-CoV-2 infection, studies have shown that the
seroconversion in the patient-generally starts after a week of the
first symptom34. In a study of post symptomatic patients,
Amanat et al. detected high IgA and IgM immune responses35.
Using recombinant viral proteins, this immunoassay could detect antibodies as early as 3 days after the development of the
first symptom. Liu et al. reported that the accuracy of the ELISA
for IgG and IgM antibodies was more than 80%36. The efficacy
of the immunoassay also depends on the specificity of the antigens used to capture the antibodies from the patients. Between
the spike (S) proteins and nucleocapsid (N) proteins, the sensitivity of the S proteins is higher for the antibody capture.
Among various spike proteins, the S1 protein has shown more
capabilities to bind to SARS-CoV-2 antibodies37. In a comparative study, both ELISA and colloidal gold immunochromatographic kits showed equal sensitivity with 100% specificity for
the SARS-CoV-2 detection38.
Several immunoassay kits are already on market for emergency detection of COVID-19 specific antibodies (see Table 2).
However, the major problem of this method is that it only works
for post-symptomatic patients who must have an immune response to the SARS-CoV-2. At this stage, some patients may
already be critically ill. Other drawbacks of immunoassay include changes in viral load over the course of infection39, potential cross reactivity (less specific)40, and low sensitivity with
respect to nucleic-acid based methods. Nevertheless, immunoassays are faster41 and cheaper than the RT-PCR methods. They
can be used for rapid screening of previous SARS-CoV-2 infections. This is particularly useful in the reopening stage of the
society at which people recovered from previous COVID-19 infections and therefore, immune to the virus, can safely re-engage to the society. The method also has a unique advantage of
identifying individuals who have strong immune responses
against the virus and therefore, can serve as potential donors for
therapeutic and research purposes.
4. Ideal characteristics of diagnostic methods
Diagnostic testing has become indispensable for diagnosis,
prognoses, and monitoring the progress of different diseases.
Efficient diagnostic testing is an important intervention for pandemic management and control. WHO has developed the
ASSURED criteria as a benchmark to decide if a test efficiently
addresses the needs for disease control: Affordable, Sensitive,
Specific, User-friendly, Rapid and robust, Equipment-free and
Deliverable to end-users42. It is ideal to have all the criteria fulfilled in a single test. In practice, however, testing methods can
rarely fit all the ASSURED criteria. In pandemics for example,
rapid and sensitive methods are dearly needed at the beginning
of an outbreak. But many kits available require qualified laboratories and personnel for testing. In such a case, accommodation of the ASSURED principles must be taken to facilitate the
testing.
In a pandemic, it is always important to understand the nature
of the pathogen before developing efficient diagnostic tests.
Translating the tests into the point-of-care (POC)43 mode can
help decision-making and improve the efficiency of the treatment. POC provides rapid and actionable information for patient management and care at the time when it is most needed.
Many affordable POC testing kits such as lateral flow immunoassays44 are also appropriate for resource-limited settings in
middle- or low-income countries where laboratory infrastructure is weak. One example for affordable POC testing is the
Rapid HIV test45 in which HIV infection can be quickly determined at home using paper strips on specimens such as blood
samples. Due to the requirements of easy usage and cheap price,
they often use colloidal gold based immunoassay mechanisms.
Such POC testing kits perhaps represent the best solution to
fight fast transmitting pandemics.
5. Emerging techniques to detect SARS-CoV-2
Given a variety of problems associated with current clinical
diagnosis for the SARS-Cov-2 (Section 3), here, we discuss
some promising techniques that may address these issues.
5.1 Isothermal amplification for nucleic acid targets
Although RT-PCR is a widely used method in the confirmatory screening of COVID-19 infections (see Section 3.2), it is
time consuming and requires sophisticated laboratory facility
and trained personal to operate46. To simplify the testing procedures, isothermal nucleic acid amplifications have been developed. These methods do not require any thermal cycler to perform the amplification and therefore, can be carried out in a
simple water bath at a constant temperature of 40-65 ᵒC47. One
promising isothermal nucleic acid amplification approach is
Reverse Transcription Loop Mediated Isothermal Amplification (RT-LAMP). In this method, the RNA genome of SARSCoV-2 is first reverse transcribed to cDNA, which is then amplified using four to six target-specific primers. Prior to the
LAMP amplification, a dumbbell shaped single-stranded DNA
(ssDNA) is formed through the annealing and the strand displacing cycle on both ends of the target sequence with the help
of the primers and a strand-displacing polymerase. The looped
ssDNA on each end then serves as a seed for the LAMP amplification cycle48–51. As a result, the target sequence is amplified
exponentially, which is detected by turbidimetry52 or fluorescence53/colorimetry48.
As an example, the RNA extraction and LAMP amplification
have been performed in the same tube51,54. This method has the
LOD ranging from 80 to 500 SARS-Cov-2 RNA copies per milliliter, which is comparable to the RT-PCR assay. To improve
the LOD, El-Tholoth et al. developed a two-stage closed tube
test (named Penn-RAMP) by combining LAMP with Recombinase Polymerase Amplification55. In the Penn-RAMP, each
amplification was performed at a separate compartment in a single tube followed by mixing. The method demonstrated 10
times higher sensitivity than LAMP or RT-PCR alone. In other
developments, Zhang group56 and Chiu group57 integrated the
LAMP with the CRISPR-based SHERLOCK (see Table 1)58
and CRISPR-Cas12 based methods, respectively, to detect the
SARS-Cov-2 RNA with a detection limit as low as 10 copies/µl
on a point-of-care testing (POCT) format. Some commercial
COVID-19 diagnostic kits based on isothermal RT-LAMP assays are already on the market (see Table 1). Abbott ID NowTM
COVID-19 is such an example. This method only requires 5
minutes to give positive results. Recently however, issues on
the false negativity have been raised for the Abbott ID NowTM
because of its relatively high LOD 59. This may be attributed to
the compromised performance of the RdRP target60,61 used in
this assay, which is found to be mutating and evolving62.
Rolling circle amplification (RCA)63 is another isothermal
amplification method that gives sensitive detection of nucleic
acids. In this method, a segment of the target genome is circularized and amplified by a highly processive strand-displacing
DNA polymerase. Wang et al. used this method to develop a
highly sensitive and efficient assay for SARS-CoV64. Compared to the LAMP assay, the RCA method is simpler since it
requires fewer steps and it can be performed at room temperature. The method offers high sensitivity comparable to RTPCR65 since it amplifies the target sequence by ~10,000 folds.
In addition, it presents high specificity as the RCA is initiated
only after the formation of a circular template upon which a
specific primer is hybridized65. Therefore, RCA reduces falsepositive results often encountered in PCR-based assays. A major difficulty in this method is that it requires a circular template
whose preparation is dependent on the length of a linear template and the ligation efficiency of the circularization. Inappropriate design of complementary sequences therefore results in
the failure of amplifications.
5.2 Lateral flow based detection on nucleic acids and proteins
The nucleic acid-based isothermal amplifications discussed
above partially overcome the limitations of conventional RTPCR assays as they do not require sophisticated laboratory facilities while their turnaround time is short. However, these
methods still require trained staff to operate various sample collection and processing steps. To address these problems, paperbased lateral flow assays (LFAs) have gained interest because
of their low cost, easy manufacturing, and full compatibility
with POCT, which allows them to be conveniently performed
by anyone at home.
In LFAs, both nucleic acid detection methods and immunoassays can be utilized. The device is often made of papers with
immobilized capture probes. Upon binding with nucleic acid
targets, the probes give a visible signal66–68. Such methods still
require initial nucleic acid extraction and amplification steps,
the latter of which can be accomplished by the PCR or isothermal amplifications as discussed above. On the POCT platform,
all those steps are integrated in a single device. Reboud et. al.68
developed a paper-plastic lateral flow method to detect nucleic
acids of malaria. They used a foldable paper in which extraction
of malaria genome and LAMP amplification of target sequences
were performed at separate locations. The LAMP amplified
DNA was carried by capillary flow to the detection zone, giving
a visible color change68. Similarly, Byers et al developed a 2D
paper network to perform immunoassay for the detection of nucleic acids of SARS-CoV-2 with the POCT format69.
Although nucleic acid-based lateral flow assays are sensitive,
lateral flow immunoassays have gained interest in the massive
surveillance of COVID-19 pandemic because of their simplicity
and cheap cost. Currently, IgM/IgG rapid test kits are available
for qualitative antibody test of COVID-19. Many such commercial devices have already been developed (See Table 2). One
problem associated with the immunoassay based lateral flow
assay is the weak signal, which results in reduced sensitivity66.
Various signal enhancement strategies therefore have been proposed. A promising signal amplification strategy in lateral flow
assays is the use of colloidal gold nanoparticles conjugated with
the probes. Upon binding with the target, the gold nanoparticles
linked to the capture probe aggregate to change the color, enhancing the signal70. Other signal amplification strategies include solvent evaporation for analyte preconcentrations, nanoparticle catalyzed nanoparticle labeled assays, and ion concentration polarization methods71.
Due to the low-cost requirement of the POCT, detection in
the LFA is usually achieved by visual inspection. To improve
detection sensitivity, cameras in smartphones have been used72.
These cameras are sensitive to subtle color changes and hence
provide more effective color detection than traditional RGB
sensors or the naked eye73. For improved read-out of the results
and data processing, machine learning algorithm could also be
used74. Smartphones can also be coupled with external adapters
to integrate external biosensor platforms for more versatile POC
testing75.
5.3 Other emerging methods
As discussed in section 4, diagnostic tests developed so far
rarely meet all the ASSURED criteria. The most important features for the SARS-CoV-2 detection are sensitivity, specificity,
and efficiency (throughput and cost-effectiveness). In addition
to the approaches discussed in the sections 5.1 and 5.2, other
emerging methods have been developed to improve these features. To improve the sensitivity, methods with single-molecule detection capability can be used76–78. As an example, the
single molecule enzyme linked immunosorbent assay (ELISA)
has been developed to offer detection limit of subfemtomolar
protein concentrations79. In this method, each microscopic bead
decorated with specific antibodies is loaded into individual
femtoliter wells. Sensing was accomplished by the ELISA on
each bead, whereas the excellent concentration detection limit
was achieved by a large array of such beads. To be applied in
clinical setting, however, this method requires special equipment, increasing its cost.
To increase the specificity, Proximity Ligation Assay (PLA)
has been developed. the method utilizes two or more DNAtagged aptamers or antibodies for bindings of multiple targets80.
The DNA tags on the probes are amplified only when the two
different targets are in close proximity. The multiple targets ensure the specificity of the target detection. However, this
method requires intact SARS-CoV-2 virus particles from which
two different targets are present for positive detections. This demands stringent sample processing steps.
To increase the throughput, fast sequencing such as next generation sequencing81 and DNA microarray82 can be used. In the
case of COVID-19, evidences have suggested that the SARSCoV-2 is rapidly evolving while infecting people. Therefore, it
is critical to rapidly identify the genome of the causative
agent83. The DNA microarray has been used in high-throughput
identification of mutations in SARS-CoV-284. However, for
these methods, the time limiting step becomes the sample collection, which must be performed one-at-a-time. In addition,
these methods involve rather advanced equipment with high
cost, therefore, they may not be appropriate for the economic
and rapid screening in the COVID-19 pandemic.
6. Rationales in choosing diagnostic methods in the COVID19 outbreak
As stated in the introduction, diagnosis becomes one of the
most important approaches to curb a viral outbreak such as
COVID-19, which does not have a cure or vaccine. As shown
in Figure 3, intervention such as identification of patients for
isolation at the early stage before the inflection point of the viral
spreading will significantly slow down the transmission of the
virus. It will not only delay the time at which the peak occurs,
but also reduces the magnitude of the peak population. While
decreased peak magnitude directly reduces the burden on hospitals, the delay of the peak occurrence gives more time for the
public to prepare well for the peak-time challenge. Both are expected to decrease the mortality rate. Such an early intervention
heavily relies on the quality and quantity of the detection kits
for specific viruses. Since the start of the COVID-19 outbreak,
many diagnostic kits have been developed in different countries
(see Tables 1-3). With the increase in the number of diagnostic
tests, it is difficult for policymakers, laboratories, and other endusers to make rational decisions on the selection and use of
these tests. As a result, tests have been used unnecessarily and
incorrectly, with results misinterpreted. Here, based on the epidemiology of the COVID-19 and the available diagnostic kits
on the market, we suggest some guidelines to rationally select
kits for efficient disease control and suppression. In particular,
we will discuss the relative importance of sensitivity and specificity85,86 of different assays in the fight against the COVID-19
pandemic.
[Figure 3]
Among all current methods, nucleic acid based kits are considered the most reliable because of their excellent sensitivity
and specificity. This is not surprising since these methods target
unique sequences in the viral genome for identification. Due to
these advantages, it becomes a detection of choice at the beginning of a viral outbreak (Figure 4). At this stage, it is critical to
identify and isolate all possible patients before the virus enters
an exponential growth stage (around the inflection point, see
Figure 3). Therefore, it is important to reduce the false negative
results of the diagnosis. To achieve this, high sensitivity is a
necessity. The PCR amplification used in various RT-PCR kits
can detect as low as 100 copies/mL reaction (see Table 1),
which is equivalent to 0.167 attoMolar (for a reaction volume
of 100 microliters). It is noteworthy that high sensitivity is often
accompanied with increased false positive results87,88. But at the
beginning of a viral outbreak, some false positive level may be
tolerated. Since there are not so many infected patients at the
initial stage of the outbreak, the chance of cross contamination
from COVID-19 patients to these false positive cases is small,
even if they are isolated together (but well protected by PPE) in
spacious locations such as convention centers. When the viral
outbreak becomes stronger, false positive cases should be reduced (i.e. specificity increased) as much as possible due to the
increasing cross contamination concerns.
[Figure 4]
Due to the extensive amplifications, isothermal amplification-based methods89 (see Table 1) usually have superior sensitivities albeit with increased false positive levels87,88 (see section 5.1). Therefore, at the beginning of an outbreak, isothermal
amplification may be used first. However, this method usually
involves many testing steps, therefore, it is more complex to
run. Due to the same reason, its development and approval also
take time, which makes the technique slow to be adopted at the
beginning of an outbreak. With easy performance and fast approval, PCR-based kits still remain the gold standard at the beginning of a viral outbreak.
Another means to reduce the false negativity in nucleic acid
based testing is to perform CT scans. As discussed in Section
3.1, it can be more sensitive to diagnose COVID-19 using CT
scans at certain stages of the disease. The caveat for the CT scan
is its relatively low specificity (i.e. high false positive results),
which may be tolerated at the initial stage of an outbreak. However, positive CT scans only diagnose patients at the later stage
of their SARS-CoV-2 infections, which limits its use for early
stage screening. The method is still valuable to quickly screen
serious cases from mild ones. Due to limited testing kits and
over-burdened clinical resources, many patients with mild
symptoms have been self-isolated first. When their conditions
deteriorate, it becomes important to streamline life-threatening
cases as soon as these patients are sent to the hospital. Due to
the fast performance and interpretation of CT scans within tens
of minutes as demonstrated in China hospitals for example,
these patients can be quickly identified, followed by appropriate
treatment to save lives.
Immunoassays work well only after the human body develops antibodies against the viruses. Therefore, these kits are not
appropriate to detect infection cases at the early stage of an infection at which patients may be asymptomatic. Given that
asymptomatic patients also transmit COVID-1914, it is not recommended to use immunoassays at the beginning of the pandemic. In the current COVID-19 breakout, we have often seen
that during the exponential increase stage of the disease (around
the inflection point, see Figure 3), there have been insufficient
number of nucleic acid-based kits to test all suspicious cases.
Current strategy to solve this issue is rather passive. These precious testing kits are reserved only for more serious cases. For
the patients with light symptoms, they were sent home for selfisolation. The immunoassay can be used to test those patients
after their symptoms lasted about one week. Since these immunoassays are cheaper, faster, and easier to perform44 with respect to nucleic acid based methods, they can be quickly and
massively conducted by staff at drive-thru stations for example.
This is particularly important during the society reopening stage
of the COVID-19 pandemic in which the recurrence of the disease must be avoided while the lifestyle is set to be normal again
(Figure 4).
In this stage where the society is set to reopen, it is important
to ensure that there is no recurrence of the COVID-19 breakout.
To this end, one of the most important approaches is to identify
people who have been previously infected with the COVID-19,
and therefore immune to the SARS-Cov-2 virus. Since these
people are clear of viral load, only immunoassay based
detection can be used for this purpose. It is a fatal mistake for
the whole society if false positive cases are high in such screening. In such cases, people who have not been exposed to the
virus and therefore, vulnerable to the COVID-19, are wrongly
identified as immune to the disease. This misidentification will
expose them to the SARS-Cov-2 infection, which increases the
chance for the recurrence of the COVID-19 in a recovering society.
In the future, affordable POC testing (POCT) kits as discussed in section 4 may present a viable direction to address the
bottleneck diagnosis problem caused by shortage of testing kits.
These kits can be performed at home for self-isolated people
with mild symptoms. If they are tested positively by the POCT
kits, their conditions will be closely monitored for further medical treatments or other interventions. The inherent properties of
these POCT kits (cheap, fast, and easy-to-use) afford their massive usage by the general public to fight with pandemic. We
therefore name such an approach a massive POCT strategy.
Given there is no such massive POCT product on the market for
the COVID-19 diagnosis yet, research and development on the
affordable POCT kits are dearly needed at this stage for virus
detections.
7. Conclusions and Perspectives
In summary, like other viruses in the Panic Zone, the SARSCoV-2 has caused unexpected damage to society. During the
outbreak of the COVID-19, most studies have focused on the
potential causes and epidemiology of the virus while the information on the epidemic prevention is obscure. From the data we
have collected so far, it is imperative to carry out the diagnosis
to isolate and treat patients at the early breakout stage of the
viruses in the Panic Zone. This is especially important for the
virus without a cure or vaccine. The burden of accurate and
rapid diagnosis falls on the detection kits used for the SARSCoV-2 detection, which include nucleic acid based methods and
immunoassays. Given the epidemiology of the COVID-19 and
the features of available detection kits, it is crucial to reduce
false negative results (i.e. increased sensitivity) at the expense
of some false positive level (i.e. reduced specificity) during the
early stage of the outbreak. It becomes important to reduce the
false positivity in later stages of the outbreak, especially when
the society is poised to reopen from the lock-down stage. Although nucleic acid based detection kits, RT-PCR in particular,
offer best solutions so far to these requirements because of their
high sensitivity and specificity, immunoassays can well supplement the detection armory due to their cheaper price, simpler
operation, and faster detection time. The use of immunoassays
is especially useful at the later stages of the virus outbreak when
people who have been recovered from the COVID-19 are identified for their reengagement to the society. We believe a massive attack from a Panic Zone viral outbreak requires a massive
defense from the whole society. The best approach to deal with
this massive attack is the development of cheap, fast, and easyto-use point-of-care testing (POCT) kits that can be used in a
massive fashion by the general public. In the future, intensive
research and development on the so-called massive POCT kits
for Panic Zone viruses therefore should be encouraged both by
the government and private sectors.
AUTHOR INFORMATION
Corresponding Author
*Hanbin Mao, PhD
Department of Chemistry and Biochemistry, Kent State University, OH, USA
hmao@kent.edu; (+1) 330-672 9380
850 University Esplanade, Kent, OH, 44242-0001, P.O. Box 5190
ORCID: 0000-0002-6720-9429
15.
Author Contributions
16.
The manuscript was written through contributions of all authors.
All authors have given approval to the final version of the manuscript.
17.
Funding Sources
HM thanks NIH (R01 CA236350) and NSF (CBET-1904921) for
financial support.
18.
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FIGURE 1. Viruses with high transmission rates (R0) are less fatal. R0 is the reproduction rate of a virus, which measures its transmissibility77.
Solid curve represents an inverse fitting between the mortality rate and the R0, which has been proposed as the trade-off principle between
the virulence and transmissibility of virus91. The inverse function fits well except for the two viruses in the Death Zone (blue), which is
defined to have a rather high mortality rate. The Panic Zone contains viruses with medium levels of transmission and mortality rates. The
data used here are taken from references92–100.
11
FIGURE 2. Critical importance of the early detection in the COVID-19 outbreak. COVID-19 daily tests are shown for 5 countries with
similar medical resources and age distributions. Inset shows the mortality rates (percentage of the death cases among all confirmed COVID19 cases) as of 06/07/2020 vs the number of the early detections per thousand population performed during 03/04/2020 - 03/26/2020. The
early detection data for each country101 are taken from different periods (marked by stretches) to reflect the timing of the outbreak in Asia,
Europe, and North America (~2 weeks apart). The inset data are linearly fit (r=-0.94), which indicates a negative correlation between the
early detection and the mortality rate.
12
FIGURE 3. Intervention of the COVID-19 outbreak. The intervention at an early stage (before the inflection point, which is the point where
the half width of a Gaussian peak is equivalent to the sigma of the Gaussian) of a viral breakout is the key to slow down the transmission of
the virus. It not only decreases the peak value of newly confirmed daily cases, but also saves the time to increase the hospital capacity, each
of which reduces the overall mortality rate.
13
FIGURE 4. Schematic diagram of the relative usage of nucleic acid vs antibody detection methods (left y axis) and the relative importance
of sensitivity vs specificity (right y axis) in the detection of SARS-CoV-2 virus during the COVID-19 pandemic. At the initial breakout
stage, nucleic acid-based detection methods are important because of their high sensitivity with low false negativity. It allows quick isolation
of infected individuals for timely treatment and disease containment. At the healing stage when a society is set to reopen, antibody detection
methods are important to identify individuals immune to the disease due to previous COVID-19 infections. Highly specific immunoassays
with low false positivity are desirable to correctly identify these individuals who are safe to return to the society. Interestingly, the same
pattern can be used to describe individual cases of COVID-19 infections.
14
Table 1: Kits based on nucleic acid detection
Authorization
Manufacturer
Mechanism
Target
LOD
Time
-
1drop Inc
RT-PCR
RdRP, E
8 cp/rxn
~2 h
05/11/2020*
1drop Inc.
RT-PCR
E, RdRp
200 cp/mL
-
3B BlackBio Biotech India Ltd
RT-PCR
RdRP, E, N
-
-
3D Medicines
A*Star Tan Tock Seng Hospital of Singapore
RT-PCR
-
-
-
RT-PCR
-
-
-
3/27/2020*
Abbott Diagnostics Scarborough, Inc.
RT-LAMP
RdRP
5-13
min
3/18/2020*
Abbott Molecular
RT-PCR
RdRP, N
Abbott Molecular Inc.
RT-PCR
RdRp, N
125
GE/mL
100-200
cp/mL
100 cp/mL
ƛ
03/2020
#
€
05/11/2020*
04/22/2020*
02/2020
#
05/13/2020*
**
-
Altona Diagnostics GmbH
RT-PCR
N, S
0.1
PFU/mL
Anatolia Geneworks
RT-PCR
-
-
-
Applied DNA Sciences, Inc.
RT-PCR
RNaseP
5 cp/rxn
-
ARUP Laboratories
RT-PCR
-
-
Assurance Scientific Laboratories
RT-PCR
37 cp/rxn
-
-
Atila BioSystems, Inc
RT-PCR
N1, N2,
RNaseP
N, ORF1ab
4 cp/µL
-
AUSDiagnostics
RT-PCR
-
-
-
Avellino Lab USA, Inc.
RT-PCR
RNase P (RP)
55 cp/µL
4/8/2020*
Becton, Dickinson & Company
RT-PCR
N, RP
40 GE/mL
1-2
days
-
4/2/2020*
Becton, Dickinson and Company
RT-PCR
N (N1, N2)
40 GE/mL
90 min
05/15/2020*
4/10/2020*
03/2020#
3/25/2020*
3/26/2020*,
3/2/2020#,
1/2020$
05/21/2020*
3/23/2020*
05/01/2020*
05/06/2020*
05/01/2020*
**
2/4/2020*
3/20/2020*
03/2020
4/3/2020*
03/2020#
05/22/2020*
4/8/2020*
****
3/19/2020*
-
Beijing Applied
RT-PCR
ORF1ab, N, E
1000
cp/mL
BGI Genomics Co. Ltd.
RT-PCR
ORF1ab
100 cp/mL
-
BGI Wuhan Biotech Co., Ltd
RT-PCR
ORF1ab
100 cp/mL
90 min
BioCore Co., Ltd.
RT-PCR
N, RdRp
500 cp/mL
-
BioFire Defense, LLC
RT-PCR
ORF1ab, ORF8
330 cp/mL
50 min
BioFire Diagnostics, LLC
Multiplex RT-PCR
-
-
-
N, RdRp, E
300
GE/mL
-
BioMérieux SA
RT-PCR
Bioneer
RT-PCR
-
-
-
Bio-Rad Laboratories, Inc
Endpoint RT-PCR
N1, N2
625 cp/mL
-
BioReference Laboratories
RT-PCR
-
-
-
Centers for Disease Control and Prevention's (CDC)
RT-PCR
N1, N2. RP
4-10 cp/µL
-
Cepheid
RT-PCR
N2, E
250 cp/mL
45 min
CerTest BioTec
RT-PCR
-
-
-
Co-Diagnostics, Inc
RT-PCR
RdRP
600 cp/spl
-
Credo Diagnostics Biomedical
RT-PCR
-
-
-
Daan Gene Co., Ltd., Sun Yat-sen University
RT-PCR
ORF1ab, N
500 cp/mL
110
min
Dba SpectronRx
RT-PCR
N, E
5 cp/rxn
-
DiaCarta, Inc
RT-PCR
E, N, ORF1ab
100 cp/mL
-
Diagnostic Solutions Laboratory
RT-PCR
-
-
-
DiaSorin Molecular LLC
RT-PCR
ORF1ab, S
500 cp/mL
1-1.5 h
Diatherix Eurofins
RT-PCR
-
-
-
15
N1, N2,
RNaseP
5 cp/mL
-
RT-PCR
ORF1ab, N, E
300 cp/mL
-
Sequencing
-
-
-
GeneMatric, Inc.
RT-PCR
RdRp, N
50 cp/rxn
-
Genetic Signatures
RT-PCR
-
-
-
GenMark Diagnostics, Inc.
RT-PCR, electrowetting
and sensing
-
10^5
cp/mL
2h
Genomica/PharmMar Group
RT-PCR
-
-
-
05/15/2020*
Flugent Therapeutics, LLC
RT-PCR
04/17/2020*
Fosun Pharma USA Inc.
Fulgent Genetics/MedScan laboratory
**
05/14/2020*
03/2020
#
3/19/2020*
03/2020
#
4/16/2020*
GenoSensor, LLC
RT-PCR
E, N, ORF1ab
1 cp/µL
-
4/6/2020*
Gnomegen LLC
RT-PCR
N (N1, N2)
8 GE/rxn
-
05/08/2020*
Gnomegen LLC
RT-PCR
N1, N2
10 cp/rxn
-
N1, N2,
RNaseP
4.8 cp/µL
-
06/01/2020*
Gravity Diagnostics, LLC
RT-PCR
05/14/2020*
Holigic, Inc.
Transcription Mediated
Amplification
3/16/2020*
Hologic, Inc.
RT-PCR
-
InBios International, Inc
RT-PCR
E, N, ORF1ab
Integrated DNA technologies/Danaher
RT-PCR
-
0.01
TCID50/mL
10-2
TCID50/m
L
12.5
GE/rxn
-
4/7/2020*
*
4/1/2020*
#,
ORF1ab
-
Ipsum Diagnostics, LLC
RT-PCR
N, RP
8.5 cp/µL
-
€
JN Medsys
RT-PCR
-
-
-
ψ
Kogene Biotech
RT-PCR
-
-
-
KorvaLabs, Inc
RT-PCR
N1, N2, RP
200 cp/rxn
-
LabGenomics Co., Ltd.
4/16/2020*
04/29/2020*
RT-PCR
RdRp, E
20 GE/mL
-
Laboratory Corporation of America
(LabCorp)
RT-PCR
Rnase P (RP),
N
6.25 cp/µL
-
LGC, Biosearch Technologies
RT-PCR
-
-
-
Luminex Corporation
RT-PCR
75 GE/uL
-
3/27/2020*
Luminex Molecular Diagnostics, Inc.
RT-PCR
ORF1ab, N
ORF1ab, N
gene, E
1.5 cp/µL
4h
4/15/2020*
Maccura Biotechnology (USA) LLC
RT-PCR
E, N, ORF1ab
1 cp/µL
2h
3/23/2020*
Mesa Biotech Inc.
RT-PCR and colorimetry
N
100 cp/rxn
30 min
3/30/2020*
NeuMoDx Molecular
RT-PCR
-
-
-
3/30/2020*
3/20/2020*,
2/2020#,
ƛ
3/26/2020
NeuMoDx Molecular, Inc
RT-PCR
Nsp2, N
150 cp/mL
Novacyt/Primerdesign
RT-PCR
-
-
-
OPTI Medical Systems, Inc.
RT-PCR
N1, N2
0.7 cp/µL
-
3/16/2020*
*
4/3/2020*
05/06/2020*
04/18/2020*
02/2020#
3/24/2020*
06/04/2020*
3/20/2020*
***
OSANG Healthcare
RT-PCR
RdRp, N, E
0.5 cp/µL
-
OsangHealthCare
RT-PCR
-
-
-
PerkinElmer, Inc.
RT-PCR
ORF1ab, N
20 cp/mL
-
Phosphorus Diagnostics LLC
RT-qPCR
N1, N2,
RNaseP
5 cp/µL
-
Primerdesign Ltd.
RT-PCR
-
0.33 cp/µL
-
-
-
-
-
500 cp/mL
-
Promedical
Lateral Flow Immunoassay
RT-PCR
3/30/2020*
QIAGEN GmbH
3/17/2020*
Quest Diagnostics Infectious Disease,
Inc.
RT-PCR
N1 and N3
136 cp/mL
-
Quidel Corporation
RT-PCR
pp1ab
0.8 cp/µL
75 min
3/23/2020*,
3/2020#
16
05/18/2020*
03/2020$
04/29/2020*
3/12/2020*
05/04/2020*
4/3/3030*
Quidel Corporation
RT-PCR
Pp1ab
Rendu Biotechnology
RT-LAMP
-
Endpoint RT-PCR
N1
Roche Molecular Systems, Inc.
RT-PCR
E
-
3 hrs
SANSURE Bio-tech Co., Ltd
RT-PCR
ORF1ab, N
200 cp/mL
90 min
Sansure BioTech Inc.
RT-PCR
ORF1ab, N
200 cp/mL
-
ScienCell Research Laboratories
RT-PCR
N (N1, N2)
500 cp/µL
-
ORF1ab,
RdRp, E
0.5 cp/µL
-
1 cp/µL
-
-
-
-
-
RT-PCR
04/27/2020*
SEASUN BIOMATERIALS
RT-PCR
05/21/2020*
Seasun Biomaterials, Inc.
RT-LAMP
02/2020 ,
See Gene
RT-PCR
ORF1ab, N
ORF1ab,
RNaseP
-
Seegene, Inc.
RT-PCR
E, RdRp, N
-
Shanghai Bio Germ
RT-PCR
ORF1ab, N
-
Shanghai GeneoDx Biotech Co., Ltd
RT-PCR
ORF1ab, N
05/06/2020*
2/2020 , ,
# $$ $$$
05/21/2020*
03/2020
#
3/13/2020*
03/2020#
04/20/2020*
03/2020
#
2/29/2020*
-
-
Rheonix, Inc.
SD Biosensor, Inc
04/21/2020*
-
625
GE/mL
04/23/2020*
# $$
1.28x104
Genome
eq/mL
-
Shanghai ZJ Bio-tech Co., Ltd.
RT-PCR
ORF1ab, N, E
4167
cp/mL
1000
cp/mL
500 cp/mL
1000
cp/mL
1-4.5
cp/µL
-
-
90 min
90 min
90 min
Sherlock BioSciences, Inc.
CRISPR
SolGent
RT-PCR
ORF1ab, N,
RNaseP
-
SolGent Co., Ltd.
RT-PCR
N, ORF1
200 cp/mL
-
Systaaq Diagnostic Products
RT-PCR
-
-
-
-
Thermo Fisher Scientific, Inc.
RT-PCR
S, N
10 GE/rxn
4h
TIB MolBiol Synthesalabor
RT-PCR
E
-
-
Trax Management Services Inc.
RT-PCR
RNaseP
50 cp/mL
-
Ustar
RT-PCR
ORF1ab, N
-
90 min
Vision Medicals
PCR (Clinical Sequencing Assay)
-
-
-
RT-PCR
RP
25 cp/rxn
-
RT-PCR
ORF1ab, N
-
75 min
Wadsworth Center, New York State
Department of Public Health's (CDC)
Wuhan Easydiagnosis
17
Table 2: Kits based on antibodies detection
Authorization
04/26/2020*
Manufacturer
Abbott Laboratories, Inc.
Mechanism
Chemiluminescent microparticle immunoassay
Immunoassay
Target
LOD
Time
IgG
-
-
IgG IgM
-
-
***
Assure Tech
***
Autobio Diagnostics
Immunoassay
-
-
-
Autobio Diagnostics Co. Ltd.
Lateral Flow Immunoassay
IgG IgM
-
50 min
***
Beijing Decombio Biotechnology
Immunoassay
IgG IgM
-
-
***
Beijing Diagreat Biotechnologies
Beijing Kewei Clinical Diagnostic Reagent
Immunoassay
IgG IgM
-
-
Immunoassay
IgG IgM
-
-
04/24/2020*
***
***
Beijing O&D Biotech
Colloidal gold
-
-
-
***
***
Beroni Group
BioMedomics
Immunoassay
Immunoassay
IgG IgM
IgG IgM
-
-
-
BiOSCiENCE
Immunoassay
IgM IgG
-
30 min
***
BTNX
Immunoassay
IgG IgM
-
-
4/1/2020*
Cellex
Immunoassay
IgG IgM
-
-
ChemBio Diagnostic System
Immunoassay
IgG IgM
-
-
Chembio Diagnostic System, Inc
Immunoassay
IgG IgM
-
-
Core Technology
Immunoassay
IgG IgM
-
-
DiaSorin Inc.
Chemiluminescent Immunoassay
IgG
-
-
***
Diazyme Laboratories
Immunoassay
IgG IgM
-
-
***
Eachy Biopharmaceuticals
Immunoassay
IgG IgM
-
-
Eagle Bioscience
Immunoassay
IgG, IgM
-
-
EUROIMMUN US Inc.
ELISA
IgG
-
2.5 h
Guangdong Hecin
Immunoassay
IgM
-
-
***
Guangzhou Wondfo
Immunoassay
-
-
15 min
***
Hangzhou AllTest Biotech
Immunoassay
IgG IgM
-
-
***
Hangzhou Biotest Biotech
Immunoassay
IgG IgM
-
-
Hangzhou Biotest Biotech Co., Ltd.
Lateral Flow Immunoassay
IgG IgM
-
30 min
***
4/14/2020*
***
04/24/2020*
05/04/2020*
-
06/04/2020*
***
Hangzhou Clongene Biotech
Immunoassay
IgG IgM
-
-
***
***
Hangzhou Testsealabs Biotechnology
Healgen Scientific
Immunoassay
Immunoassay
IgG IgM
IgG IgM
-
-
05/29/2020*
Healgen Scientific LLC
Lateral Flow Immunoassay
IgG IgM
-
10 min
-
INNOVITA (Tangshan)
Immunoassay
IgG IgM
-
15 min
***
Jiangsu Macro & Micro-Test Med-Tech
Colloidal gold
IgG IgM
-
-
***
Lifeassay Diagnostics
Immunoassay
IgG IgM
-
-
***
Medical Systems Biotechnology
Immunoassay
IgG IgM
-
-
Mount Sinai Laboratory
Immunoassay
IgG
NA
-
Nanjing Liming Bio-Products
Immunoassay
IgG IgM
-
-
Nanjing Vazyme
Immunoassay
IgM, IgG
-
10 min
***
NanoResearch
Immunoassay
IgG IgM
-
-
***
Nantong Diagnos Biotechnology
Colloidal gold
-
-
-
***
Nirmidas Biotech
Immunoassay
IgG IgM
-
-
Ortho Clinical Diagnostics, Inc
Lateral Flow Immunoassay
IgG IgM
-
10-15
min
PCL
Immunoassay
IgG IgM
-
-
4/15/2020*
***
-
4/14/2020*
***
18
***
PharmaTech
Immunoassay
IgG IgM
-
-
05/08/2020*
Quidel Corporation
Lateral Flow Immunoassay
Nucleocapsid
protein
-
15 min
06/02/2020*
Roche Diagnostics
Immunoassay
IL-6
-
18 min
05/02/2020*
Roche Diagnostics
Immunoassay
-
-
18 min
***
SD Biosensor
Immunoassay
IgG IgM
-
-
***
Shenzhen Landwind Medical
Immunoassay
IgG IgM
-
-
Siemens Healthcare Diagnostics Inc.
Chemiluminescent Immunoassay
Total Antibodies
-
10 min
05/29/2020*
Snibe Diagnostics
Immunoassay
IgG IgM
-
-
***
Telepoint Medical Services
Immunoassay
IgG IgM
-
-
***
Tianjin Beroni Biotechnology
Immunoassay
IgG IgM
-
-
IgG IgM
-
-
-
-
-
-
-
15 min
02/2020
#
06/04/2020*
04/30/2020*
***
Wadsworth Center, New York, State
Department of health
Xiamen innoDx Bio-tech
Chemiluminescence immunoassay
Microsphere Immunoassay
Immunoassay
Zuhai Livzon Diagnostics
Colloidal gold
Vibrant America Clinical Labs
Total Antibodies
IgG IgM
IgG IgM
19
Table 3: Kits based on ‘not identified’ mechanism
Authorization
Manufacturer
Mechanism
Target
LOD
Time
-
Biological Technologies Co., LTD
-
-
-
-
-
(Chongqing) Bio-tech, Co., Ltd
-
-
Health Technology Co., Ltd
-
Bio-tech Co., Ltd
-
Medical Technology Co., Ltd
-
Biotechnologies (Hangzhou) Ltd
-
-
-
-
-
Biomedicine Co., Ltd.
-
-
-
-
*US EUA Authorized, **US EUA Planned, ***US Notified FDA under section IV.D, ****US EUA Submitted, #European Union Conformity Marked, $The National Medical Product Administration Authorized China, $$Korea Ministry of Food and Drug Safety, $$$Philippines Food and Drug Administration, €Singapore Health Sciences Authority, personal authorization for clinical use, ƛEUA India, ψKorea
Centers for Disease Control and the Korea Food and Drug Administration
-Data Not Available
References for kits in table 1-3:
https://www.fda.gov/medical-devices/emergency-situations-medical-device….
http://ph.china-embassy.org/eng/sgdt/t1760281.htm.
https://www.modernhealthcare.com/safety/coronavirus-test-tracker-commer….
https://www.finddx.org/covid-19/pipeline/.
20