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
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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
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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.
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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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discovered. But even the victims of that malady find atmospheric and other
conditions friendly to a prolongation of life in the salubrious air and sunshine of
the South African tablelands.

On the whole, there can be no question as to the general good effect upon
health of the South African climate. Europeans and Americans living therein
pursue their athletic sports with all the zest experienced in their native climates,
and the descendants of the original Dutch and Huguenot settlers—now in the
sixth and seventh generations—have lost nothing of the stature nor of the
physical energy that characterized their forefathers.

South Africa used to be the habitat of an unusually rich fauna. The lion, leopard,
elephant, giraffe, rhinoceros, hippopotamus, antelope in thirty-one species,
zebra, quagga, buffalo and various other wild creatures—some of them savage,
and all of them beautiful after their kind—abounded. But of late years all this has
been changed. Since firearms have been greatly improved and cheapened and
the country has been opened to the Nimrods of the world and the [269]swarming
natives have procured guns and learned to use them, the wild animals have
been thinned out. There are now but two regions in South Africa where big
game can be killed in any great numbers—the Portuguese territory from the
Zambesi to Delagoa Bay, and the adjoining eastern frontier of the Transvaal.

Snakes of various kinds and sizes, from the poisonous black mamba to the
python that grows to over twenty feet in length, used to infest many parts of the
country, but they have almost disappeared from the temperate regions inhabited
by the whites.

The farmers’ worst enemies are not now the great beasts and reptiles of former
years, but the baboons, which gather in the more rocky districts and kill the
lambs, and two species of insects—the white ants and the locusts—which
sometimes ravage the eastern coast.

Beyond that of most countries in the world of equal extent the flora of South
Africa is rich in both genera and species. The neighborhood of Cape Town and
the warm, sub-tropical regions of eastern Cape Colony and Natal are specially
affluent in beautiful flowers. In the Karoo district, and northeastward over the
plateau into Bechuanaland and the Transvaal, vegetation presents [270]but little
variety of aspect, owing in part to the general sameness of geological formations
and in part to the prevailing dryness of the surface.
In general, South Africa is comparatively bare of forests—a fact for which
denudation by man cannot account, for it is yet a country new to civilization.
Some primitive forests are to be found on the south coast of Cape Colony and in
Natal. These have been put under the care of a Forest Department of the
government. In the great Knysna forest wild elephants still roam at large. The
trees, however, even in the preserved forests, are small, few of them being more
than fifty or sixty feet in height. The yellowwood grows the tallest, but the less
lofty sneezewood is the most useful to man. Up the hillsides north of Graham’s
Town and King William’s Town are immense tracts of scrub from four to eight
feet high, with occasional patches of prickly pear—a formidable invader from
America, through which both men and cattle make their passage at the cost of
much effort and many irritating wounds from the sharp spines. A large part of
this region, being suitable for little else, has been utilized for ostrich farming.

In the Karoo district and northward through [271]Cape Colony, western

Bechuanaland and the German possessions in Namaqualand and Damaraland
—a desert region—there are few trees except small and thorny mimosas.
Farther east, where there is a greater rainfall, the trees are more numerous and
less thorny. The plain around Kimberley, once well wooded, has been stripped of
its trees to furnish props for the diamond mines and fuel.

The lack of forests is one of the principal drawbacks to the development of

South Africa. Timber is everywhere costly; the rainfall is less than it would be if
the country were well wooded; and when rains do come the moisture is more
rapidly dissipated by absorption, evaporation and sudden freshets because of
the absence of shade. Of late energetic measures have been taken to supply
nature’s lack by artificial forestry. On the great veldt plateau in the vicinity of
Kimberley and of Pretoria and in other localities the people have planted the
Australian gum tree, the eucalyptus and several varieties of European trees,
including the oak, which, besides being useful, is very beautiful. If the practice
be continued the country will reap an incalculable benefit, not only in
appearance, but also in climatic conditions. [272]

The largest political division of South Africa is Cape Colony. The area is about
292,000 square miles and the population, white and native, is 2,011,305. The
whites number about 400,000. But little of it is suitable for agriculture, and
considerable portions of it are too arid for stock raising. Including the natives the
population is only about seven to the square mile. On the lowlands skirting the
sea on the south and west are some fruitful regions that give a profitable yield of
grapes and corn. On the tableland of the interior there is a rainfall of only from
five to fifteen inches in the year. As a consequence the surface is dry and
unfriendly to vegetable life. In an area of three hundred miles by one hundred
and fifty there is not a stream having a current throughout the year, nor is there
any moisture at all in the dry season except some shallow pools which are soon
dried up by evaporation. Nevertheless, in this desert, bare of trees and of
herbage, there is abundance of prickly shrubs, which are sufficiently succulent
when they sprout under the summer rains to afford good browsing for goats and
sheep. In the northwestern part of the interior and northward to Kimberley and
Mafeking, the country is better watered than the more westerly regions, and
[273]grazing animals find a generous growth of grass as well as nutritious shrubs.
In the southeastern part the rainfall is still heavier. The foothills of the
Quathlamba Range toward the sea are covered in places with forests, the grass
is more abundant and much of the land can be tilled to profit without artificial
irrigation. In 1899 there were about 3,000 miles of railway and nearly 7,000
miles of telegraph open in the colony. The number of vessels entering the ports
of Cape Colony in 1897 was 1,093, with a total tonnage of 2,694,370 tons; in
addition to this there were 1,278 vessels engaged in the coastwise trade, with a
tonnage of 3,725,831 tons. The foreign commerce of Cape Colony is large,
including, as it does, the bulk of the import and export trade of all South Africa.
The total importation of merchandise for 1897 was $80,127,495, and the
exports, including a large proportion of the gold and diamond products of
Kimberley and the Transvaal, amounted, in 1898, to $123,213,458.

Natal, beyond any other part of South Africa, is favored by natural advantages. It
lies on the seaward slope of the Quathlamba Mountains, and its scenery is
charmingly diversified by some of the lesser peaks and the foothills of that
range. It is well watered by perennial streams [274]fed by the snows and springs
of the mountains. While the higher altitudes to the west are bare, there is
abundance of grass lower down and toward the coast there is plenty of wood.
The climate in general is much warmer than that of Cape Colony; in the low strip
bordering the sea it is almost tropical. This high temperature is not caused so
much by latitude as by the current in the Mozambique Channel, which brings
from the tropical regions of the Indian Ocean a vast stream of warm water, which
acts on the climate of Natal as does the Gulf Stream on that of Georgia and the
Carolinas. Nearly the whole of Natal may be counted temperate; the soil is rich,
the scenery is beautiful, and, with the exception of certain malarious districts at
the north, the climate is healthful. Foreigners from Europe and America may
reasonably hope to enjoy long life and prosperity in it. The principal crop for
export is sugar, but cereals of all kinds, coffee, indigo, arrowroot, ginger,
tobacco, rice, pepper, cotton and tea are grown to profit. The coal fields of the
colony are large, the output in 1897 being 244,000 tons. There are 487 miles of
railway, built and operated by the government. The imports in 1897 amounted to
nearly $30,000,000. Pop. 828,500; whites, 61,000. [275]

The Orange Free State, in its entire area of 48,000 square miles, is on the great
interior plateau at an altitude of from 4,000 to 5,000 feet above the sea level.
The surface is mostly level, but there are occasional hills—some of them rising
to a height of 6,000 feet. The land is, for the most part, bare of trees, but affords
good grazing for two-thirds of the year. The air is remarkably pure and bracing.
There are no blizzards to encounter. There are, however, occasional violent
thunderstorms, which precipitate enormous hailstones—large enough to kill the
smaller animals, and even men. Notwithstanding the generally parched
appearance of the country, the larger streams do not dry up in winter. The
southeastern part of the Free State, particularly the valley of the Caledon River,
is one of the best corn-growing regions in Africa. In the main, however, with the
exception of the river valleys, the land is more suitable for pasture than for
tillage. The grazing farms are large and require the services of but few men; as a
consequence the population increases slowly. The Free State, corresponding in
size to the State of New York, has only about 80,000 white inhabitants and
130,000 natives. The chief industry is agriculture and stock-raising. A railway,
[276]constructed by the Cape Colony government, connects Bloemfontein, the
capital of the Orange Free State, with the ports of Cape Colony and Natal, and
with Pretoria, the capital of the South African Republic.

The South African Republic, commonly called the Transvaal, is 119,139 square
miles in area. The white population, numbering 345,397, is largely concentrated
in the Witwatersrand mining district. The native inhabitants number 748,759. All
the Transvaal territory belongs to the interior plateau, with the exception of a
strip of lower land on the eastern and northern borders. This lower section is
malarious. It is thought, however, that drainage and cultivation will correct this,
as they have done in other fever districts. Like the Free State, the Transvaal is
principally a grazing country. The few trees that exist in the more sheltered parts
are of little value, except those in the lower valleys. The winters are severely
cold, and the burning sun of summer soon dries up the moisture and bakes the
soil, causing the grass to be stunted and yellow during most of the year. Until
about sixteen years ago there was little in the surface appearance and known
resources of the Transvaal to attract settlers, and nothing to make it a desirable
[277]possession to any other people than its Africander inhabitants. In 1884
discoveries of gold were made, the first of which that excited the world being
some rich auriferous veins on the Sterkfontein farm. In a little time it became
known that probably the richest deposit of gold in the world was in the
Witwatersrand district of the Transvaal. Later, in 1897, diamonds were
discovered in the Transvaal, the first stone having been picked up at Reitfontein,
near the Vaal River, in August of that year. Since then the precious crystals have
been found in the Pretoria district, in Roodeplaats on the Pienaars River, at
Kameelfontein and at Buffelsduff. The output of gold in 1898 was $68,154,000,
and of diamonds $212,812.01. The total output of gold since it was first
discovered amounts to over $300,000,000, with $3,500,000,000 “in sight,” as
valued by experts. The commerce of the South African Republic, while
necessarily great because of the large number of people employed by the
mining industries, cannot be as accurately stated as that of states whose imports
are all received through a given port or ports. Foreign goods reach it through
several ports in Cape Colony, Natal, Portuguese East Africa, and in smaller
quantities from other ports on the coast. [278]The total imports for 1897 are
estimated at $107,575,000.

Griqualand West, a British possession bordering on Cape Colony on the south

and on the Free State on the east, owes its chief importance to the Kimberley
diamond mines, near the western boundary of the Free State and 600 miles
from Cape Town. These mines were opened in 1868 and 1869. It is estimated
that since that time $350,000,000 worth of diamonds in the rough—worth double
that sum after cutting—have been taken out. This enormous production would
have been greatly exceeded had not the owners of the various mines in the
group formed an agreement by which the annual output was limited to a small
excess over the annual demand in the world’s diamond markets. So plentiful is
the supply, and so inexpensive, comparatively, is the cost of mining that other
diamond-producing works have almost entirely withdrawn from the industry
since the South African mines were opened. It has been estimated that ninety-
eight per cent of the diamonds of commerce are now supplied by these mines.

The British protectorate of Bechuanaland, lying to the north of Cape Colony and
Griqualand and to the west of the Transvaal, has an [279]area of about 213,000
square miles, with a population of 200,000—mostly natives. A railway and
telegraph line connect it with Cape Colony on the south and Rhodesia on the
north.
Rhodesia includes the territory formerly known as British South Africa and a
large part of that known as British East Africa. The area is about 750,000 square
miles—equal to about one-fourth of the area of the United States of America,
excluding Alaska. No exact statement of population can be made; estimates
range from 1,000,000 to 2,000,000, of which only about 6,000 are whites. The
entire territory is under the administration of the British South African Company,
organized and incorporated in 1889, subject to the British High Commissioner at
Cape Town. Rhodesia lies chiefly within the tablelands of South Africa and has
large but yet undeveloped resources, including grazing and agricultural lands
and important mining districts. Owing to the newness of the country to civilization
no definite statement can be made relative to its commerce. In all probability
Rhodesia will open a field wherein enterprise along the lines favored by its
natural resources and conditions will be richly rewarded.

The End.

[281]
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Metadata

Title: The Africanders: A

century of Dutch-
English feud in
South Africa
Author: Le Roy Hooker Info
(1840–1906) https://viaf.org/viaf/104480090/
File 2023-09-23
generation 11:48:34 UTC
date:
Language: English
Original 1900
publication
date:
Keywords: Afrikaners,
Transvaal (South
Africa)
History, South
Africa -- Politics and
government