Asymptomatic carrier state, acute

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Facts and myths Chih-Cheng Lai
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Journal of Microbiology, Immunology and Infection xxx (xxxx) xxx

Available online at www.sciencedirect.com

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Review Article

Asymptomatic carrier state, acute

respiratory disease, and pneumonia due to
severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2): Facts and myths
Chih-Cheng Lai a, Yen Hung Liu b, Cheng-Yi Wang b,
Ya-Hui Wang c, Shun-Chung Hsueh d, Muh-Yen Yen e,f,
Wen-Chien Ko g, Po-Ren Hsueh h,i,*

a
Department of Internal Medicine, Kaohsiung Veterans General Hospital, Tainan Branch, Tainan,
Taiwan
b
Department of Internal Medicine, Cardinal Tien Hospital and School of Medicine, College of Medicine,
Fu Jen Catholic University, New Taipei City, Taiwan
c
Medical Research Center, Cardinal Tien Hospital and School of Medicine, College of Medicine, Fu Jen
Catholic University, New Taipei City, Taiwan
d
Department of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
e
Section of Infectious Diseases, Taipei City Hospital, Taipei, Taiwan
f
Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
g
Department of Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan
h
Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University
College of Medicine, Taipei, Taiwan
i
Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University
College of Medicine, Taipei, Taiwan

Received 25 February 2020; accepted 25 February 2020

Available online - - -

KEYWORDS Abstract Since the emergence of coronavirus disease 2019 (COVID-19) (formerly known as
Coronavirus; the 2019 novel coronavirus [2019-nCoV]) in Wuhan, China in December 2019, which is caused
2019-nCoV; by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), more than 75,000 cases have
SARS-CoV-2; been reported in 32 countries/regions, resulting in more than 2000 deaths worldwide. Despite
COVID-19; the fact that most COVID-19 cases and mortalities were reported in China, the WHO has
Asymptomatic declared this outbreak as the sixth public health emergency of international concern. The
carrier; COVID-19 can present as an asymptomatic carrier state, acute respiratory disease, and pneu-
monia. Adults represent the population with the highest infection rate; however, neonates,

* Corresponding author. Departments of Laboratory Medicine and Internal Medicine, National Taiwan University Hospital, Number 7,
Chung-Shan South Road, Taipei, 100, Taiwan.
E-mail address: hsporen@ntu.edu.tw (P.-R. Hsueh).

https://doi.org/10.1016/j.jmii.2020.02.012
1684-1182/Copyright ª 2020, Taiwan Society of Microbiology. Published by Elsevier Taiwan LLC. This is an open access article under the CC
BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Please cite this article as: Lai C-C et al., Asymptomatic carrier state, acute respiratory disease, and pneumonia due to severe acute
respiratory syndrome coronavirus 2 (SARS-CoV-2): Facts and myths, Journal of Microbiology, Immunology and Infection, https://doi.org/
10.1016/j.jmii.2020.02.012
 + MODEL
2 C.-C. Lai et al.

children, and elderly patients can also be infected by SARS-CoV-2. In addition, nosocomial
Acute respiratory
infection of hospitalized patients and healthcare workers, and viral transmission from asymp-
disease;
tomatic carriers are possible. The most common finding on chest imaging among patients with
Wuhan pneumonia
pneumonia was ground-glass opacity with bilateral involvement. Severe cases are more likely
to be older patients with underlying comorbidities compared to mild cases. Indeed, age and
disease severity may be correlated with the outcomes of COVID-19. To date, effective treat-
ment is lacking; however, clinical trials investigating the efficacy of several agents, including
remdesivir and chloroquine, are underway in China. Currently, effective infection control
intervention is the only way to prevent the spread of SARS-CoV-2.
Copyright ª 2020, Taiwan Society of Microbiology. Published by Elsevier Taiwan LLC. This is an
open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-
nc-nd/4.0/).

Introduction gastrointestinal, or respiratory symptoms, and no signifi-

In December 2019, an outbreak of pneumonia due to un-
known cause occurred in Wuhan, China and rapidly spread
throughout the country within 1 month. The pathogen of
this disease was confirmed as a novel coronavirus by mo-
lecular methods and was initially named as 2019 novel
coronavirus (2019-nCoV); however, the World Health Or-
ganization (WHO) announced a new name on February 11,
2020 for the epidemic disease: Corona Virus Disease
(COVID-19). To date, COVID-19 has affected people in more
than 28 countries/regions, including Taiwan, and has
become a global threat.1e4 In addition, the Coronavirus
Study Group of the International Committee on Taxonomy
of Viruses has renamed the virus, which was provisionally
named 2019-nCoV, as severe acute respiratory syndrome
coronavirus-2 (SARS-CoV-2) based on phylogeny, taxonomy,
and established practice.5 Prior to this, on January 30,
2020, the WHO declared the COVID-19 outbreak as the sixth
public health emergency of international concern; there-
fore, this outbreak constitutes a public health risk through
the international spread of disease and requires a coordi-
nated international response. Increased dissemination of
information through use of the internet is associated with
increased transmission of information from all geographical
regions and across disciplines regarding recognition of
SARS-CoV-2 and COVID-196; nevertheless, important factors
associated with COVID-19, specifically age and sex distri-
bution, incubation period, clinical features, and optimal
treatment, remain uncertain. Therefore, herein, we per-
formed a literature review, focusing on the epidemiological
characteristics and clinical manifestations of COVID-19,
including asymptomatic carrier state, acute respiratory
disease (ARD), and pneumonia.
Severity of COVID-19
COVID-19 was defined as the respiratory disease caused by
SARS-CoV-2 that emerged in China in 2019 (https://www.
who.int/westernpacific/emergencies/covid-19). The
clinical manifestations of COVID-19 are protean, which
include asymptomatic carrier, ARD, and pneumonia of
varying degrees of severity. First, asymptomatic cases were
diagnosed based on positive viral nucleic acid test results,
but without any COVID-19 symptoms, such as fever,
cant abnormalities on chest radiograph7,8 However, the
transmission of COVID-19 through asymptomatic carriers via
person-to-person contact was observed in many re-
ports.4,7,9,10 Second, patients with ARD defined as
laboratory-confirmed COVID-19 cases had respiratory
symptoms; however, chest computed tomography (CT) did
not reveal signs of pneumonia.11 Third, patients with
pneumonia defined as COVID-19 cases had both respiratory
symptoms and pneumonia on chest radiograph. This cate-
gory includes severe pneumonia e either respiratory rate
30/minute, SpO2  93%, or PaO2/FiO2  300 mmHg, and a
critical condition, characterized by respiratory failure
requiring mechanical ventilation, shock, or other organ
failure requiring ICU management.8
Epidemiology
As of February 21, 2020, data from the WHO revealed
altogether 76,769 cases of COVID-19.1 Thirty-two countries
or regions have reported confirmed cases, including main-
land China, Japan, Singapore, Hong Kong Special Adminis-
trative Region (SAR), Thailand, South Korea, Taiwan,
Australia, Malaysia, Germany, Vietnam, the United States,
Macao SAR, the United Arab Emirates, Canada, France, the
Philippines, the United Kingdom, Italy, India, Russia,
Finland, Sweden, Sri Lanka, Cambodia, Nepal, Spain,
Belgium, Iran, Egypt, Israel, and Lebanon. In addition, 643
cases were found in international conveyance e Diamond
Princess. China has the largest number of patients with
COVID-19 (n Z 75,543), followed by South Korea (n Z 204),
Japan (n Z 93), and Singapore (n Z 85). To date, the re-
ported number of deaths is 2247 and only 11 occurred
outside of mainland China, including two each in Hong Kong
Special administrative regions (SAR), Iran, and Diamond
Princess, and one each in Taiwan, South Korea, Japan,
Philippines, and France. However, asymptomatic patients
or patients with mild COVID-19 symptoms may not seek
health care, nor receive diagnosis, which leads to under-
estimation of the burden of COVID-19.
Age and sex
Initially, most reported COVID-19 cases in Wuhan were
adult patients; however, all of these cases had pneumo-
nia.12e14 Their median or mean ages were 55.5, 49.0, and

Please cite this article as: Lai C-C et al., Asymptomatic carrier state, acute respiratory disease, and pneumonia due to severe acute
respiratory syndrome coronavirus 2 (SARS-CoV-2): Facts and myths, Journal of Microbiology, Immunology and Infection, https://doi.org/
10.1016/j.jmii.2020.02.012
 + MODEL
Coronavirus 2 (SARS-CoV-2): facts and myths
56 years in three separate studies.12e14 A similar finding
was observed in two recent non-peer-reviewed studies: one
study with 1099 patients from 552 hospitals in 31 provinces
in China, in which the median age was 47.0 years, and
55.1% of the patients were between the ages of 15e49
years; and a second study that included 4021 confirmed
cases in 30 provinces of China, in which the mean age was
49 years and 50.7% of patients were between the ages of
20e50 years.11,15 Both these studies included ARD and
pneumonia cases.11,15 Similarly, the Novel Coronavirus
Pneumonia Emergency Response Epidemiology Team in
China reported that 66.7% (n Z 29,798) of 44,672 cases of
COVID-19 of varying degrees of severity were between 20
and 60 years of age.8 In Korea, Ryu et al. found that the
initial 15 cases were aged between 25 and 62 years.16
Regarding elderly patients infected with SARS-CoV-2, one
study showed that 14.6% (6 in 41) of patients were aged 65
years,13 while another study showed that 15.2% (15 in 99)
patients were aged 70 years, among pneumonia cases.12
In addition, two non-peer-reviewed studies showed only
153 (15.1%) patients were elderly patients aged 65
years,11 and 407 (10.1%) patients were aged >70 years.15
According to the recent China CDC report,8 12.0%
(n Z 5326) of patients were aged 70 years. Regarding
children with COVID-19, nine (0.9%) patients aged 0e14
years were found in only one study,11 while 14 (0.35%) pa-
tients were aged 10 years in another study.15 The largest
study in China showed that 0.9% (n Z 416) of patients were
aged <10 years.8 Further, Wei et al. reported that nine
infants under 1 year of age were infected with SARS-CoV-2
in China.8 Regarding patient sex ratio, male sex comprised
more than half of the cases in most COVID-19 studies11e14
and the proportion of males ranged from 51.4% to
73.2%.8,11e14,16
Initially, approximately half of the cases had Huanan
seafood market exposure and animal-to-human trans-
mission was suspected.12,13 However, fewer cases had
exposure to this seafood market and an increasing number
of cases demonstrated human-to-human transmission.11,17
Fortunately, no evidence was found for intrauterine infec-
tion caused by vertical transmission in women who con-
tracted COVID-19 pneumonia in late pregnancy.18 In
addition to family cluster infections due to human-to-
human transmission,19 nosocomial spread of SARS-CoV-2 is
a serious concern. Indeed, one study in a Zhongnan hospital
of the Wuhan University showed 29.0% (n Z 40) were
medical staff and 12.3% (n Z 17) contracted COVID-19
during hospitalization.14 Two other studies showed that
2.1% (n Z 23) and 3.8% (n Z 1716) of patients were health
workers.8,11
Risk factors
Although the risk factors of COVID-19 remain unclear, many
studies reported that a significant proportion of patients
had underlying conditions.8,11e14 For patients with SARS-
CoV pneumonia, Chen et al. showed that 50.5% (n Z 51)
of patients had chronic medical illness, namely cardiovas-
cular and cerebrovascular diseases (40.4%).12 Among 1099
patients with SARS-CoV-2 ARD, Guan et al. showed that
23.2% (n Z 255) of patients had at least one coexisting
Please cite this article as: Lai C-C et al., Asymptomatic carrier state, acute respiratory disease, and pneumonia due to severe acute
respiratory syndrome coronavirus 2 (SARS-CoV-2): Facts and myths, Journal of Microbiology, Immunology and Infection, https://doi.org/
10.1016/j.jmii.2020.02.012
3
disorder, and hypertension was the most common under-
lying disease (14.9%), followed by diabetes mellitus
(7.4%).11 Another large study on COVID-19 cases of varying
degrees of severity also showed that hypertension was the
most common underlying disease (n Z 2,683, 12.8%), fol-
lowed by diabetes mellitus (n Z 1,102, 5.3%), and cardio-
vascular disease (n Z 873, 4.2%).8 Moreover, patients with
severe COVID-19 were more likely to have comorbidities
than those with non-severe diseases (37.6% vs. 20.5%,
p < 0.001).11 A similar trend was observed in another study
of 138 hospitalized patients with SARS-CoV-2 pneumonia, in
which 46.4% (n Z 64) of patients had comorbidities and the
intensive care unit (ICU) patients were more likely to have
underlying diseases compared to non-ICU patients (72.2%
vs. 37.3%, p < 0.001).14
In summary, these studies disclosed several significant
findings. First, although most patients with COVID-19 were
middle-aged adults, elderly patients and children also
contracted COVID-19. Second, there is a higher prevalence
of men with COVID-19 than that of women; however,
further studies are warranted to confirm this finding. Third,
health care workers and hospitalized patients could be
infected by SARS-CoV-2 in the hospital setting. Finally, at
least 20% of COVID-19 cases had underlying diseases, and
more severe cases were more likely to have comorbidities
than non-severe cases.
Incubation period
It is essential to know the incubation period, the time
elapsing between the moment of exposure to an infectious
agent and the appearance of signs and symptoms of the
disease, for infection control and guidance for the duration
of isolation. Initially, Li et al. used the data on exposure
among 10 confirmed cases in Wuhan to estimate the mean
incubation period, which was 5.2 days (95% confidence in-
terval [CI], 4.1e7.0); the 95th percentile of the distribution
was 12.5 days (95% CI, 9.2e18).20 One estimation based on
125 patients with clearly defined exposure periods in China
indicated that the median incubation period was 4.75
(interquartile range: 3.0e7.2) days.15 Using the travel his-
tory and symptom onset of 88 confirmed cases that were
detected outside of Wuhan in the early outbreak phase,
Backer et al. estimated that the mean incubation period
was 6.4 days (95% credible interval: 5.6e7.7), ranging from
2.1 to 11.1 days (2.5th to 97.5th percentile).21 However,
Guan et al., using a large sample for estimation, suggested
that the median incubation period was only 3.0 days, but
could be as long as 24 days.11 Overall, these estimates will
be refined as more data become available. Detailed
epidemiological information based on a larger sample of
patients infected with COVID-19 is needed to determine the
infectious period of SARS-CoV-2, as well as to determine
whether transmission can occur from asymptomatic in-
dividuals during the incubation period.
Clinical manifestations
Previous reports revealed that there are asymptomatic
patients infected with SARS-CoV-2.7,8,22 These patients can
spread the virus and may represent a population that can
 + MODEL
4 C.-C. Lai et al.

be easily neglected in epidemic prevention. Therefore, it is common underlying disease, followed by diabetes mellitus.
important to identify asymptomatic patients with COVID- Approximately two-thirds of patients had cough, but only
19. Since these patients are asymptomatic, careful moni- 44.7% patients had fever. In addition, sputum production
toring of the natural course of the disease and contact was observed in one-third of patients and sore throat was
history may only identify them. Based on the current data, found in 14.0% of patients. Only fewer than 5% of patients
we do not know whether these patients are only asymp- had gastrointestinal symptoms, such as diarrhea, nausea,
tomatic initially after contracting the disease or if they are and vomiting. Meanwhile, 32.4% of patients required oxy-
asymptomatic throughout the course of the disease. gen therapy, but none required mechanical ventilation.
Among a pooled analysis of 970 patients with ARD (Table Only one patient with ARD died and the mortality rate was
1) based on two studies with detail clinical characteris- 0.1%.
tics,11,23 males comprised more than half of the patients Among a pooled analysis of 468 patients with pneumonia
and the mean age was 45 years. Hypertension was the most (Table 2) based on five studies with detailed description of
clinical features of the disease,11e14,23 male sex comprised
60.3% of patients and the mean age was 53 years. Approx-
imately one-fifth of patients reported smoking history.
Table 1 Demographic data, underlying medical condi- Hypertension was the most common underlying disease
tions, clinical manifestations, and laboratory findings of (20.5%), followed by diabetes mellitus (14.4%). Addition-
patients with acute respiratory disease caused by SARS-CoV- ally, 76.3% of patients had fever and 70.5% of patients
2. presented cough. Furthermore, dyspnea and sputum pro-
Liu et al.23 Guan et al.11 duction were observed in approximately one-third of pa-
(n Z 44) (n Z 926) tients. Moreover, 8% and 6% of patients had nausea/
Sex vomiting or diarrhea, respectively. In all, 70.9% of patients
Male 21 (47.7) 540 (58.3) required oxygen therapy, and 28.8% required mechanical
Female 23 (52.3) 386 (41.7) ventilation. Moreover, 5.1% and 3.1% of patients required
Age, year 39.8 (17.1) 45.3 (17.3) renal replacement therapy and extracorporeal membrane
Smoking 2 (4.5) 120 (13.0) oxygenation, respectively. The overall mortality was 8.2%
Comorbidities (n Z 37); however, 313 (66.9%) patients remained
Hypertension 6 (13.6) 123 (13.3) hospitalized.
Diabetes mellitus 2 (4.5) 53 (5.7) Furthermore, patients with pneumonia were older, with
COPD 2 (4.5) 6 (0.6) a higher prevalence of smoking history, more underlying
Chronic liver disease NA 22 (2.4) diseases, and were more likely to have fever, myalgia/fa-
Chronic kidney disease NA 5 (0.5) tigue, dyspnea, headache, and nausea/vomiting compared
Malignancy NA 7 (0.8) to patients with ARD (all p < 0.05) (Table 3). In addition,
Presentation pneumonia cases presented a higher white blood cell count
Fever 43 (97.7) 391 (42.2) and neutrophil count, but had a reduced leukocyte count
Cough 25 (56.8) 622 (67.2) compared to ARD cases. Serum procalcitonin levels of
Myalgia/fatigue 23 (52.3) 133 (14.4) 0.5 ng/mL were found in 6.1% (6/99),12 7.7% (3/39),13 to
Headache 18 (40.9) 124 (13.4) 13.7% (16/117),11 among SARS-CoV-2 pneumonia patients
Sputum production 16 (36.4) 306 (33.0) reported from three studies.11e13 Moreover, patients with
Sore throat 6 (13.6) 130 (14.0) pneumonia were more likely to require oxygenation ther-
Chills 6 (13.6) 99 (10.7) apy, mechanical ventilator, renal replacement, and extra-
Diarrhea 5 (11.4) 31 (3.3) corporeal membrane oxygenation, and received more
Dyspnea 4 (9.1) 139 (15.0) antibiotics and antiviral therapy than patients with ARD.
Nausea or vomiting 3 (6.8) 43 (4.6) Finally, pneumonia was associated with a higher mortality
White blood cell, 109/L 4.2 (1.4) 4.9 (1.6) rate than ARD (p < 0.0001).
Neutrophil 2.6 (1.1) NA
Lymphocyte 1.1 (0.4) 1.1 (0.5)
Treatment
Image
Oxygen therapy 10 (22.7) 304 (32.8)
Ventilator 0 (0.0) 0 (0.0) Based on the findings of 1099 ARD cases of COVID, only
Renal replacement therapy 0 (0.0) 0 (0.0) 14.7% (n Z 162) of patients had an abnormal chest radio-
ECMO 0 (0.0) 0 (0.0) graph.11 In contrast, 840 (76.4%) patients had abnormal and
Antibiotic therapy 12 (27.3) 493 (53.2) diverse chest CT images, in which ground-glass opacity
Antiviral therapy 23 (52.3) 313 (33.8) (GGO) was the most common abnormality (n Z 550, 65.5%),
Outcome followed by local patchy shadowing (n Z 409, 48.7%), and
Discharged 3 (6.8) 50 (5.4) interstitial abnormalities (n Z 143, 17.0%). In addition, 505
Remained hospitalized 41 (93.2) 875 (94.5) (50.1%) had bilateral involvement.11 The predominance of
Died 0 (0.0) 1 (0.1) GGO and bilateral involvement in chest CT is consistent
with previous studies.24e26 In contrast, other types of ab-
Data are n (%), n/N (%), and mean (SD).
normalities, such as cavitation, pleural effusion, and
COPD, chronic obstructive pulmonary disease; ECMO, extra-
lymphadenopathy, were not found.24,27 As the disease
corporeal membrane oxygenation; NA, not available.
progressed, follow-up CT showed enlargement and

Please cite this article as: Lai C-C et al., Asymptomatic carrier state, acute respiratory disease, and pneumonia due to severe acute
respiratory syndrome coronavirus 2 (SARS-CoV-2): Facts and myths, Journal of Microbiology, Immunology and Infection, https://doi.org/
10.1016/j.jmii.2020.02.012
 + MODEL
Coronavirus 2 (SARS-CoV-2): facts and myths 5

Table 2 Demographic data, underlying medical conditions, clinical manifestations, and laboratory findings of patients with
pneumonia caused by SARS-CoV-2.
Huang et al.13 Chen et al.12 Wang et al.14 Liu et al.23 Guan et al.11
(n Z 41) (n Z 99) (n Z 138) (n Z 17) (n Z 173)
Sex
Male 30 (73.2) 67 (67.7) 75 (54.3) 10 (58.8) 100 (57.8)
Female 11 (26.8) 32 (32.3) 63 (45.7) 7 (41.2) 73 (42.2)
Age, year 49.3 (13.0) 52.7 (46.7) 55.3 (19.9) 54.3 (29.9) 52.3 (19.2)
Smoking 3 (7.3) NA NA 2 (11.8) 38 (22.0)
Comorbidities
Diabetes mellitus 8 (19.5) NA 14 (10.1) 3 (17.6) 28 (16.2)
Hypertension 6 (14.6) NA 43 (31.2) 6 (35.3) 41 (23.7)
COPD 1 (2.4) 1 (1.0) 4 (2.9) 3 (17.6) 6 (3.5)
Chronic kidney disease NA NA 4 (2.9) NA 3 (1.7)
Chronic liver disease 1 (2.4) NA NA NA 1 (0.6)
Malignancy 1 (2.4) 1 (1.0) 10 (7.2) NA 3 (1.7)
Presentation
Fever 40 (97.6) 82 (82.8) 136 (98.6) 17 (100.0) 82 (47.4)
Cough 31 (75.6) 81 (81.8) 82 (59.4) 14 (82.4) 122 (70.5)
Sore throat NA 5 (5.1) 24 (17.4) 4 (23.5) 23 (13.3)
Dyspnea 22 (53.7) 31 (31.3) 43 (31.2) 6 (35.3) 65 (37.6)
Myalgia/fatigue 18 (43.9) 11 (11.1) 96 (69.6) 12 (70.6) 99 (57.2)
Sputum production 11 (26.8) NA 37 (26.8) 11 (64.7) 61 (35.3)
Headache 3 (7.3) 8 (8.1) 9 (6.5) 3 (17.6) 26 (15.0)
Diarrhea 1 (2.4) 2 (2.0) 14 (10.1) 1 (5.9) 10 (5.8)
Nausea or vomiting NA 1 (1.0) 19 (13.8) 2 (11.8) 12 (6.9)
White blood cell, 109/L 6.9 (4.9) 7.5 (3.6) 4.7 (2.2) 4.6 (1.5) 4.3 (2.5)
Neutrophil 5.7 (4.3) 5.5 (3.7) 3.3 (2.2) 3.3 (2.0) NA
Lymphocyte 0.8 (0.4) 0.9 (0.5) 0.8 (0.4) 0.9 (0.3) 0.8 (0.3)
Treatment
Oxygen therapy 27 (65.9) 75 (75.8) 106 (76.8) 10 (58.8) 114 (65.9)
Ventilator 14 (34.1) 17 (17.2) 32 (23.2) 5 (29.4) 67 (38.7)
Renal replacement therapy 3 (7.3) 9 (9.1) 2 (1.4) NA 9 (5.2)
ECMO 2 (4.9) 3 (3.0) 4 (2.9) NA 5 (2.9)
Antibiotic therapy 41 (100.0) 70 (70.7) NA 14 (82.) 139 (80.3)
Antiviral therapy 39 (95.1) 75 (75.8) 124 (89.9) 11 (64.7) 80 (46.2)
Outcome
Discharged 28 (68.3) 31 (31.3) 47 (34.1) 0 (0.0) 5 (2.9)
Remained hospitalized 7 (17.1) 57 (57.6) 85 (61.6) 10 (58.) 154 (89.0)
Died 6 (14.6) 11 (11.1) 6 (4.3) NA 14 (8.1)
Data are n (%), n/N (%), and mean (SD).
COPD, chronic obstructive pulmonary disease; ECMO, extracorporeal membrane oxygenation; NA, not available.

consolidation of single GGO, an enlarged fibrous stripe, and
solid nodules. In contrast, a small fibrous stripe, as well as
the resolution of GGO, may be associated with improve-
ment in the patient’s condition.28,29
Treatment
Several reports suggest the following as potential drug
candidates, although the clinical effectiveness of these
drugs have not yet been evidenced for COVID-19: lopinavir/
ritonavir (Kaletra), nucleoside analogs, neuraminidase
inhibitors, remdesivir, umifenovir (arbidol), DNA synthesis
inhibitors (such as tenofovir disoproxil, and lamivudine),
chloroquine, ACE2-based peptides, 3C-like protease
(3CLpro) inhibitors, novel vinylsulfone protease inhibitor,
teicoplanin, and Chinese traditional medicine (such as
ShuFengJieDu or Lianhuaqingwen capsules).30e39 The
effectiveness of remdesivir is more evident in the literature
to date; indeed, it appears to be the most promising drug
for COVID-19. In fact, an in vitro study demonstrated that
the 50% effective concentration (EC50) of remdesivir against
nCoV-2019/BetaCoV/Wuhan/WIV04/2019 in Vero E6 cells
was 0.77 mM, and the 90% effective concentration (EC90)
was 1.76 mM.31 However, only one case in the US showed a
clinical response to remdesivir, although the viral load
appeared to decline at the time of initiating remdesivir
(cycle threshold from 18e20 to 23e24).33 Subsequently,
two large clinical trials, NCT04252664 (https://
clinicaltrials.gov/ct2/show/NCT04252664) for mild/
moderate COVID-19 and NCT04257656 (https://
clinicaltrials.gov/ct2/show/NCT04257656) for severe

Please cite this article as: Lai C-C et al., Asymptomatic carrier state, acute respiratory disease, and pneumonia due to severe acute
respiratory syndrome coronavirus 2 (SARS-CoV-2): Facts and myths, Journal of Microbiology, Immunology and Infection, https://doi.org/
10.1016/j.jmii.2020.02.012
 + MODEL
6 C.-C. Lai et al.

COVID-18, were initiated in China, with an estimated end

Table 3 Comparison among demographic data, underlying
date in early April 2020. In these two trials, the 10-day
medical conditions, clinical manifestations, and laboratory
regimen of remdesivir was 100 mg once daily for 9 days
findings of patients with acute respiratory disease and
after the loading of 200 mg on day 1.34 Chloroquine is
pneumonia caused by SARS-CoV-2.
another promising drug.35,36 An in vitro study on the time-
Acute Pneumonia, p value of-addition assay in Vero E6 cells demonstrated that chlo-
respiratory N Z 468 roquine functioned at both entry and at post-entry stages
disease, of COVID-19, and the EC90 value of chloroquine against the
N Z 970 2019-nCoV was 6.90 mM.31 In addition, passive immunization
Sex 0.3824 therapy and the use of interferon could theoretically be
Male 561 (57.8) 282 (60.3) helpful, but to date there is no evidence to validate this
Female 409 (42.2) 186 (39.7) hypothesis.
Age, years 45.1 (17.3) 53.1 (27.6) <0.0001 Systemic corticosteroid was administered in 18.6%e
Smoking 122 (12.6) 43/231 (18.6) 0.0166 44.9% patients in order to control the inflammatory
Comorbidities response caused by SARS-CoV-2 in 4 initial large stud-
Hypertension 129 (13.3) 96/369 (26.0) <0.0001 ies.11e14 However, corticosteroid therapy could be associ-
Diabetes mellitus 55 (5.7) 53/369 (14.4) <0.0001 ated with delayed MERS-CoV RNA clearance (adjusted
Chronic liver 22/926 (2.4) 2/214 (0.9) 0.2883 hazard ratio, 0.35; 95% CI, 0.17e0.72; p Z 0.005) for crit-
disease ically ill patients with MERS,40 and early corticosteroid
COPD 8 (0.8) 15 (3.2) 0.0007 treatment could be associated with higher subsequent
Chronic kidney 5/926 (0.5) 7/311 (2.3) 0.0143 plasma RNA load of SARS-CoV for adults with SARS.41
disease Moreover, corticosteroid-associated psychosis and dia-
Malignancy 7/926 (0.8) 15/451 (3.3) 0.0004 betes were observed in the treatment of SARS.42,43 Thus,
Presentation clinical use of corticosteroids in the treatment of COVID-19
Fever 434 (44.7) 357 (76.3) <0.0001 was not recommended in the interim, unless indicated for
Cough 647 (66.7) 330 (70.5) 0.1467 another reason.44,45
Sputum 322 (33.2) 120/369 (32.5) 0.8143
production
Myalgia/fatigue 156 (16.1) 236 (50.4) <0.0001 Outcomes
Dyspnea 143 (14.7) 167 (35.7) <0.0001
Headache 142 (14.6) 49 (10.5) 0.0291 According to WHO reports, the overall mortality rate for
Sore throat 136 (14.0) 56/427 (13.1) 0.6506 COVID-19 was 2.9% (2247 in 76,769),1 however, the mor-
Nausea or 46 (4.7) 34/427 (8.0) 0.0170 tality rate varied among studies. Initial studies reported
vomiting that the mortality rate associated with SARS-CoV-2 pneu-
Diarrhea 36 (3.7) 28 (6.0) 0.0503 monia ranged from 11%12 to 15%,13 but later studies
White blood cell, 4.9 (1.6) 5.3 (3.2) 0.0109 revealed that the mortality rate was between 1.4%11 and
109/L 4.3%.14 The differences in the results among different
Neutrophil 2.6 (1.1)/44 4.4 (3.3)/295 <0.0001 studies could be due to the study population, as well as the
Lymphocyte 1.1 (0.5) 0.8 (0.4) <0.0001 differences among the studies in terms of disease severity.
Treatment In addition, these results need further clarification, since a
Oxygen therapy 314 (32.4) 332 (70.9) <0.0001 majority of the reported mortality was all-cause mortality,
Ventilator 0 (0.0) 135 (28.8) <0.0001 not COVID-attributed mortality; also, the outcome mea-
Renal 0 (0.0) 23/451 (5.1) <0.0001 surement was incomplete because many patients remained
replacement hospitalized before publication of the results.
therapy Several prognostic factors of COVID-19 were also re-
ECMO 0 (0.0) 14/451 (3.1) <0.0001 ported in these studies. In one study using the MulBSTA
Antibiotic 505 (52.1) 264/330 (80.0) <0.0001 score system,46 which includes six indices, namely multi-
therapy locular infiltration, lymphopenia, bacterial co-infection,
Antiviral 336 (34.6) 229 (48.9) <0.0001 smoking history, hypertension, and age, revealed that
therapy these indices were poor prognostic factors.12 Another study
Outcome showed similar findings, and specifically the indicators of
Discharged 53 (5.5) 111 (23.7) <0.0001 disease severity, including oxygenation, respiratory rate,
Remained 916 (94.4) 313 (66.5) <0.0001 leukocyte/lymphocyte count, and the chest imaging find-
hospitalized ings, were associated with a poor clinical outcome.11
Died 1 (0.1) 37/451 (8.2) <0.0001 Moreover, a substantially elevated case-fatality rate
included the following patient characteristics: male sex,
Data are n (%), n/N (%), and mean (SD).
COPD, chronic obstructive pulmonary disease; ECMO, extra-
60 years of age, baseline diagnosis of severe pneumonia,
corporeal membrane oxygenation; NA, not available. and delay in diagnosis.15 Similarly, the China CDC reported
Bold indicates p < 0.05. that patients aged 80 years had the highest case fatality
rate, 14.8%, among different age groups, and the case

Please cite this article as: Lai C-C et al., Asymptomatic carrier state, acute respiratory disease, and pneumonia due to severe acute
respiratory syndrome coronavirus 2 (SARS-CoV-2): Facts and myths, Journal of Microbiology, Immunology and Infection, https://doi.org/
10.1016/j.jmii.2020.02.012
 + MODEL
Coronavirus 2 (SARS-CoV-2): facts and myths
fatality rate of patients in which disease severity was
critical was 49.0%.8 Together, these findings suggest that
old age and increased disease severity could predict a poor
outcome.
In this stage of lack of effective drugs, the imple-
mentation of infection control interventions and traffic
control bundle to effectively limit droplet, contact, and
fomite transmission is the only way to slow the spread of
the SARS-CoV-2. These infection control interventions
include early identification of cases and their contacts,
avoiding close contact with people with airway symptoms,
appropriate hand washing, and enhanced standard infec-
tion prevention, and control practices in the healthcare
setting.47,48
Uncertain issues
Although information on COVID-19 has increased rapidly
since the emergence of SARS-CoV-2, many issues remain
unresolved. First, the clinical manifestation of COVID-19
ranges from the asymptomatic carrier state to severe
pneumonia; however, most early reports only showed the
findings of SARS-CoV-2 pneumonia, in which the ratio of
male patients was much larger than that of female pa-
tients, there were no pediatric cases, and the mortality
rate was high.12e14 Subsequent to the publication of the
studies of patients with only ARD or mild pneumonia, we
found the ratio of male-to-female patients decreased,
children or neonates could contract COVID-19, and the
mortality rate declined compared to that of previous re-
ports.8,11 However, whether children were less susceptible
to SARS-CoV-2, or their presentation was mostly asymp-
tomatic or difficult to detect, remains unclear.49 In addi-
tion, most studies, especially those with a large patient
population, were conducted in China, and the study of
asymptomatic carriers was limited. More studies are
needed to clarify the epidemiologic characteristics of
COVID-19 and to identify the risk and prognostic factors of
patients infected with SARS-CoV-2. Second, Zou et al. re-
ported that the viral load detected in asymptomatic pa-
tients was similar to that found in symptomatic patients;
however, the viral loads from patients with severe diseases
were higher than those in patients with mild-to-moderate
presentations. Moreover, higher viral loads were detected
in the nose than in the throat.50 As there is a concern of
virus spread due to severe cough induced by performing a
throat swab, nasal swab may be a relatively safe and sen-
sitive alternative to collect the respiratory specimen of
patients with COVID-19. However, this study involved a
population of only 18 patients, including one asymptomatic
patient.49 In addition, every test has its own limitation and
sensitivity/specificity; however, the studies investigating
the performance of current diagnostic methods of SARS-
CoV-2 among different COVID-19 populations, including
asymptomatic carriers, ARD, and pneumonia, are lacking.
The false positive and negative rates of each diagnostic tool
among patients with COVID-19 presenting varying degrees
of severity of the disease remain unknown. This type of
information is important for screening patients with COVID-
19 and to aid isolation and infection control strategies.
Finally, since SARS-CoV-2 can be detected in the
Please cite this article as: Lai C-C et al., Asymptomatic carrier state, acute respiratory disease, and pneumonia due to severe acute
respiratory syndrome coronavirus 2 (SARS-CoV-2): Facts and myths, Journal of Microbiology, Immunology and Infection, https://doi.org/
10.1016/j.jmii.2020.02.012
7
asymptomatic individual, the prophylactic or pre-emptive
use of effective anti-viral agents to reduce the viral load
and decrease the risk of virus spread from asymptomatic
carriers may help to control the spread of COVID-19.
Conclusions
This review provides updated information about COVID-19.
SARS-CoV-2 can affect patients of all ages. COVID-19 can
present as asymptomatic carriage, ARD, and pneumonia.
Severe cases are more likely to be older and to have
increased underlying comorbidities compared to mild
cases. Age and disease severity can be correlated with the
outcomes of COVID-19. To date, effective treatment for
SARS-CoV-2 is lacking; however, two trials investigating the
clinical efficacy of remdesivir are underway in China.
Currently, effective infection control intervention is the
only way to prevent the spread of SARS-CoV-2.
Declaration of competing interest
The author declares no conflict of interests.
References
1. WHO. https://www.who.int/docs/default-source/
coronaviruse/situation-reports/20200221-sitrep-32-covid-19.
pdf?sfvrsn&equals;4802d089_2. [Accessed on 21 February 2020].
2. Lee PI, Hsueh PR. Emerging threats from zoonotic
coronaviruses-from SARS and MERS to 2019-nCoV. J Microbiol
Immunol Infect 2020 Feb 4;(20):30011e6. https:
//doi.org/10.1016/j.jmii.2020.02.001. pii: S1684-1182.
3. Huang WH, Teng LC, Yeh TK, Chen YJ, Lo WJ, Wu MJ, et al.
2019 novel coronavirus disease (COVID-19) in Taiwan: reports
of two cases from Wuhan, China. J Microbiol Immunol Infect
2020 Feb 19. https://doi.org/10.1016/j.jmii.2020.02.009.
4. Liu YC, Liao CH, Chang CF, Chou CC, Lin YR. A locally trans-
mitted case of SARS-CoV-2 infection in Taiwan. N Engl J Med
2020 Feb 12. https://doi.org/10.1056/NEJMc2001573.
5. Gorbalenya AE, Baker SC, Baric RS, de Groot RJ, Drosten C,
Gulyaeva AA, et al. Severe acute respiratory syndrome-related
coronavirus: the species and its viruses e a statement of the
Coronavirus Study Group. 2020. 2020.02.07.937862.
6. Lai CC, Shih TP, Ko WC, Tang HJ, Hsueh PR. Severe acute
respiratory syndrome coronavirus 2 (SARS-CoV-2) and corona
virus disease-2019 (COVID-19): the epidemic and the chal-
lenges. Int J Antimicrob Agents 2020 Feb 17. https:
//doi.org/10.1016/j.ijantimicag.2020.105924.
7. Bai Y, Yao L, Wei T, Tian F, Jih DY, Chen L, et al. Presumed
asymptomatic carrier transmission of COVID-19. J Am Med
Assoc 2020 Feb 21. https://doi.org/10.1001/jama.2020.2565.
8. The Novel Coronavirus Pneumonia Emergency Response
Epidemiology Team. The epidemiological characteristics of an
outbreak of 2019 novel coronavirus disease (COVID-19) e
China. China CDC Weekly; 2020.
9. Rothe C, Schunk M, Sothmann P, Bretzel G, Froeschl G,
Wallrauch C, et al. Transmission of 2019-nCoV infection from
an asymptomatic contact in Germany. N Engl J Med 2020 Jan
30. https://doi.org/10.1056/NEJMc2001468.
10. Yu P, Zhu J, Zhang Z, Han Y, Huang L. A familial cluster of
infection associated with the 2019 novel coronavirus indicating
potential person-to-person transmission during the incubation
period. J Infect Dis 2020 Feb 18. https://doi.or-
g/10.1093/infdis/jiaa077. pii: jiaa077.
 + MODEL
8 C.-C. Lai et al.
11. Guan WJ, Ni ZY, Hu Y, Laing WH, Ou CQ, He JX, et al. Clinical
characteristics of 2019 novel coronavirus infection in China.
medRxiv 2020 Feb 9. https:
//doi.org/10.1101/2020.02.06.20020974. preprint.
12. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epide-
miological and clinical characteristics of 99 cases of 2019 novel
coronavirus pneumonia in Wuhan, China: a descriptive study.
Lancet 2020;395:507e13. https://doi.org/10.1016/S0140-
6736(20)30211-7.
13. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical
features of patients infected with 2019 novel coronavirus in
Wuhan, China. Lancet 2020;395:497e506. https:
//doi.org/10.1016/S0140-6736(20)30183-5.
14. Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical
characteristics of 138 hospitalized patients with 2019 novel
coronavirus-infected pneumonia in Wuhan, China. J Am Med
Assoc 2020 Feb 7. https://doi.org/10.1001/jama.2020.1585.
15. Yang Y, Lu Q, Liu M, Wang Y, Zhang A, Jalali N, et al. Epide-
miological and clinical features of the 2019 novel coronavirus
outbreak in China. medRxiv 2020 Feb 11. https:
//doi.org/10.1101/2020.02.10.20021675.
16. Ryu S, Chun BC. An interim review of the epidemiological
characteristics of 2019 novel coronavirus. Epidemiol Health
2020;42:e2020006.
17. Nishiura H, Linton NM, Akhmetzhanov AR. Initial cluster of
novel coronavirus (2019-nCoV) infections in Wuhan, China is
consistent with substantial human-to-human transmission. J
Clin Med 2020;9:E488. https://doi.org/10.3390/jcm9020488.
18. Chen H, Guo J, Wang C, Luo F, Yu X, Zhang W, et al. Clinical
characteristics and intrauterine vertical transmission potential
of COVID-19 infection in nine pregnant women: a retrospective
review of medical records. Lancet 2020 Feb 12. https:
//doi.org/10.1016/S0140-6736(20)30360-3.
19. Chan JF, Yuan S, Kok KH, To KK, Chu H, Yang J, et al. A familial
cluster of pneumonia associated with the 2019 novel corona-
virus indicating person-to-person transmission: a study of a
family cluster. Lancet 2020;395:514e23. https:
//doi.org/10.1016/S0140-6736(20)30154-9.
20. Li Q, Guan X, Wu P, Wang X, Zhou L, Tong Y, et al. Early
transmission dynamics in Wuhan, China, of novel coronavirus-
infected pneumonia. N Engl J Med 2020 Jan 29. https:
//doi.org/10.1056/NEJMoa2001316.
21. Backer JA, Klinkenberg D, Wallinga J. Incubation period of 2019
novel coronavirus (2019-nCoV) infections among travellers
from Wuhan, China, 20-28 January 2020. Euro Surveill 2020;
25(5). https://doi.org/10.2807/1560-7917.
22. Chang Xu H, Rebaza A, Sharma L, Dela Cruz CS. Protecting
health-care workers from subclinical coronavirus infection.
Lancet Respir Med 2020 Feb 13. https://doi.org/10.1016/S2213-
2600(20)30066-7. pii: S2213-2600(20)30066-30067.
23. Liu J, Liu Y, Xiang P, Pu L, Xiong H, Li C, et al. Neutrophil-to-
lymphocyte ratio predicts severe illness patients with 2019
novel coronaviruse in the early stage. medRxiv 2020 Feb 12.
https://doi.org/10.1101/2020.02.10.20021584.
24. Chung M, Bernheim A, Mei X, Zhang N, Huang M, Zeng X, et al.
CT imaging features of 2019 novel coronavirus (2019-nCoV).
Radiology 2020 Feb 4:200230. https:
//doi.org/10.1148/radiol.2020200230.
25. Lei J, Li J, Li X, Qi X. CT Imaging of the 2019 novel coronavirus
(2019-nCoV) pneumonia. Radiology 2020 Jan 31:200236. https:
//doi.org/10.1148/radiol.2020200236.
26. Pan Y, Guan H. Imaging changes in patients with 2019-nCov. Eur
Radiol 2020 Feb 6. https://doi.org/10.1007/s00330-020-06713-z.
27. Kanne JP. Chest CT findings in 2019 novel coronavirus (2019-
nCoV) infections from Wuhan, China: key points for the radi-
ologist. Radiology 2020 Feb 4:200241. https:
//doi.org/10.1148/radiol.2020200241.
Please cite this article as: Lai C-C et al., Asymptomatic carrier state, acute respiratory disease, and pneumonia due to severe acute
respiratory syndrome coronavirus 2 (SARS-CoV-2): Facts and myths, Journal of Microbiology, Immunology and Infection, https://doi.org/
10.1016/j.jmii.2020.02.012
28. Pan Y, Guan H, Zhou S, Wang Y, Li Q, Zhu T, et al. Initial CT
findings and temporal changes in patients with the novel
coronavirus pneumonia (2019-nCoV): a study of 63 patients in
Wuhan, China. Eur Radiol 2020 Feb 13. https:
//doi.org/10.1007/s00330-020-06731-x.
29. Duan YN, Qin J. Pre- and posttreatment chest CT findings: 2019
novel coronavirus (2019-nCoV) pneumonia. Radiology 2020 Feb
12:200323. https://doi.org/10.1148/radiol.2020200323.
30. Lu H. Drug treatment options for the 2019-new coronavirus
(2019-nCoV). Biosci Trends 2020 Jan 28. https:
//doi.org/10.5582/bst.2020.01020.
31. Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, et al. Remdesivir
and chloroquine effectively inhibit the recently emerged novel
coronavirus (2019-nCoV) in vitro. Cell Res 2020 Feb 4. https:
//doi.org/10.1038/s41422-020-0282-0.
32. Liu W, Morse JS, Lalonde T, Xu S. Learning from the past: possible
urgent prevention and treatment options for severe acute respi-
ratory infections caused by 2019-nCoV. ChemBioChem 2020 Feb 4.
https://doi.org/10.1038/s41422-020-0282-0.
33. Holshue ML, DeBolt C, Lindquist S, Lofy KH, Wiesman J,
Bruce H, et al. First case of 2019 novel coronavirus in the
United States. N Engl J Med 2020 Jan 31. https:
//doi.org/10.1056/NEJMoa2001191.
34. Ko WC, Rolain JM, Lee NY, Chen PL, Huang CT, Lee PI, et al.
Arguments in favor of remdesivir for treating SARS-CoV-2 in-
fections. Int J Antimicrob Agents 2020 Mar 6. https:
//doi.org/10.1016/j.ijantimicag.2020.105933.
35. Colson P, Rolain JM, Raoult D. Chloroquine for the 2019 novel
coronavirus. Int J Antimicrob Agents 2020 Feb 17. https:
//doi.org/10.1016/j.ijantimicag.2020.105923.
36. Multicenter collaboration group of Department of Science and
Technology of Guangdong Province and Health Commission of
Guangdong Province for chloroquine in the treatment of novel
coronavirus pneumonia. [Expert consensus on chloroquine
phosphate for the treatment of novel coronavirus pneumonia].
Zhonghua Jie He He Hu Xi Za Zhi 2020 Feb 20;43(0):E019.
https://doi.org/10.3760/cma.j.issn.1001-0939.2020.0019.
37. Szu }th E, Batta G, et al.
}cs Z, Kelemen V, Le Thai S, Csávás M, Ro
Structure-activity relationship studies of lipophilic teicoplanin
pseudoaglycon derivatives as new anti-influenza virus agents.
Eur J Med Chem 2018;157:1017e30.
38. Zhou N, Pan T, Zhang J, Li Q, Zhang X, Bai C, et al. Glyco-
peptide antibiotics potently inhibit cathepsin L in the late
endosome/lysosome and block the entry of Ebola virus, middle
east respiratory syndrome coronavirus (MERS-CoV), and severe
acute respiratory syndrome coronavirus (SARS-CoV). J Biol
Chem 2016;291:9218e32.
39. Balzarini J, Keyaerts E, Vijgen L, Egberink H, De Clercq E, Van
Ranst M, et al. Inhibition of feline (FIPV) and human (SARS)
coronavirus by semisynthetic derivatives of glycopeptide an-
tibiotics. Antivir Res 2006;72:20e33.
40. Arabi YM, Mandourah Y, Al-Hameed F, Sindi AA, Almekhlafi GA,
Hussein MA, et al. Corticosteroid therapy for critically ill pa-
tients with middle east respiratory syndrome. Am J Respir Crit
Care Med 2018;197:757e67.
41. Lee N, Allen Chan KC, Hui DS, Ng EK, Wu A, Chiu RW, et al.
Effects of early corticosteroid treatment on plasma SARS-
associated coronavirus RNA concentrations in adult patients.
J Clin Virol 2004;31:304e9.
42. Lee DT, Wing YK, Leung HC, Sung JJ, Ng YK, Yiu GC, et al.
Factors associated with psychosis among patients with severe
acute respiratory syndrome: a case-control study. Clin Infect
Dis 2004;39:1247e9.
43. Xiao JZ, Ma L, Gao J, Yang ZJ, Xing XY, Zhao HC, et al. Gluco-
corticoid-induced diabetes in severe acute respiratory syndrome:
the impact of high dosage and duration of methylprednisolone
therapy. Zhonghua Nei Ke Za Zhi 2004;43:179e82.
 + MODEL
Coronavirus 2 (SARS-CoV-2): facts and myths 9

44. Russell CD, Millar JE, Baillie JK. Clinical evidence does not
support corticosteroid treatment for 2019-nCoV lung injury.
Lancet 2020;395:473e5.
45. Li G, Fan Y, Lai Y, Han T, Li Z, Zhou P, et al. Coronavirus in-
fections and immune responses. J Med Virol 2020;92:424e32.
https://doi.org/10.1002/jmv.25685.
46. Guo L, Wei D, Zhang X, Wu Y, Li Q, Zhou M, et al. Clinical
features predicting mortality risk in patients with viral pneu-
monia: the MuLBSTA score. Front Microbiol 2019;10:2752.
https://doi.org/10.3389/fmicb.2019.02752.
47. Patel A, Jernigan DB. 2019-nCoV CDC Response Team. Initial
public health response and interim clinical guidance for the
2019 novel coronavirus outbreak e United States, December
31, 2019-February 4, 2020. MMWR e Morb Mortal Wkly Rep
2020;69:140e6.
48. Yen MY, Schwartz J, Wu JS, Hsueh PR. Controlling Middle
East respiratory syndrome: lessons learned from severe
acute respiratory syndrome. Clin Infect Dis 2015;61:
1761e2.
49. Lee PI, Hu YL, Chen PY, Huang YC, Hsueh PR. Are children less
susceptible to COVID-19? J Microbiol Immunol Infect 2020 Feb
25. https://doi.org/10.1016/j.jmii.2020.02.011.
50. Zou L, Ruan F, Huang M, Liang L, Huang H, Hong Z, et al. SARS-
CoV-2 viral load in upper respiratory specimens of infected
patients. N Engl J Med 2020 Feb 19. https:
//doi.org/10.1056/NEJMc2001737.

Please cite this article as: Lai C-C et al., Asymptomatic carrier state, acute respiratory disease, and pneumonia due to severe acute
respiratory syndrome coronavirus 2 (SARS-CoV-2): Facts and myths, Journal of Microbiology, Immunology and Infection, https://doi.org/
10.1016/j.jmii.2020.02.012
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