34290

You might also like

Download as pdf or txt
Download as pdf or txt
You are on page 1of 31

Hepatic and gastrointestinal

involvement in coronavirus disease


2019 (COVID-19): What do we know till
now? Sherief Musa
Visit to download the full and correct content document:
https://ebookmass.com/product/hepatic-and-gastrointestinal-involvement-in-coronavir
us-disease-2019-covid-19-what-do-we-know-till-now-sherief-musa/
More products digital (pdf, epub, mobi) instant
download maybe you interests ...

Coronavirus Disease 2019 (COVID-19) Pandemic and


Pregnancy Pradip Dashraath

https://ebookmass.com/product/coronavirus-
disease-2019-covid-19-pandemic-and-pregnancy-pradip-dashraath/

Coronavirus Disease 2019 (Covid-19): A Clinical Guide


1st Edition Ali Gholamrezanezhad

https://ebookmass.com/product/coronavirus-
disease-2019-covid-19-a-clinical-guide-1st-edition-ali-
gholamrezanezhad/

Coronavirus Disease 2019: Coronaviruses and Blood


Safety Le Chang

https://ebookmass.com/product/coronavirus-
disease-2019-coronaviruses-and-blood-safety-le-chang/

Severe acute respiratory syndrome coronavirus 2 (SARS-


CoV-2) and coronavirus disease-2019 (COVID-19): The
epidemic and the challenges Chih-Cheng Lai

https://ebookmass.com/product/severe-acute-respiratory-syndrome-
coronavirus-2-sars-cov-2-and-coronavirus-
disease-2019-covid-19-the-epidemic-and-the-challenges-chih-cheng-
Severe Acute Respiratory Syndrome (SARS) and
Coronavirus disease-2019 (COVID-19): From Causes to
Preventions in Hong Kong Siukan Law

https://ebookmass.com/product/severe-acute-respiratory-syndrome-
sars-and-coronavirus-disease-2019-covid-19-from-causes-to-
preventions-in-hong-kong-siukan-law/

Psychiatric Emergencies (What Do I Do Now Emergency


Medicine) Eileen Baker

https://ebookmass.com/product/psychiatric-emergencies-what-do-i-
do-now-emergency-medicine-eileen-baker/

Neuropathic Pain (WHAT DO I DO NOW PAIN MEDICINE)


Nadine Attal

https://ebookmass.com/product/neuropathic-pain-what-do-i-do-now-
pain-medicine-nadine-attal/

Headache and Facial Pain (What Do I Do Now), 2nd


Edition Lawrence Newman

https://ebookmass.com/product/headache-and-facial-pain-what-do-i-
do-now-2nd-edition-lawrence-newman/

Emergency Neurology (What Do I Do Now?) 2nd Edition


Sara C. Lahue

https://ebookmass.com/product/emergency-neurology-what-do-i-do-
now-2nd-edition-sara-c-lahue/
Arab Journal of Gastroenterology xxx (xxxx) xxx

Contents lists available at ScienceDirect

Arab Journal of Gastroenterology


journal homepage: www.elsevier.com/locate/ajg

Review article

Hepatic and gastrointestinal involvement in coronavirus disease 2019


(COVID-19): What do we know till now?
Sherief Musa
Endemic Hepatogastroenterology Department, Faculty of Medicine, Cairo University, Cairo, Egypt

a r t i c l e i n f o a b s t r a c t

Article history: Since December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative
Available online xxxx pathogen of coronavirus disease 2019 (COVID-19), has posed a serious threat to global health and is cur-
rently causing a major pandemic. While patients typically present with fever and a respiratory illness,
Keywords: mounting evidence indicates that patients might also report extra-pulmonary manifestations, including
SARS-Cov-2 those affecting the liver and gastrointestinal tract. This involvement may have important implications to
COVID-19 the disease management, transmission, and prognosis, especially in patients with pre-existing hepatic or
Liver
digestive co-morbidities.
Gastrointestinal tract
Endoscopy
In this review, the characteristics and possible explanations of hepatic and gastrointestinal involve-
ment caused by SARS-CoV-2 infection are summarized, adding to our knowledge of the spectrum of
COVID-19. In addition, preventive measures implemented in endoscopy departments to prevent further
dissemination of SARS-CoV-2 infection are proposed.
Ó 2020 Pan-Arab Association of Gastroenterology. Published by Elsevier B.V. All rights reserved.

The end of 2019 was marked by emergence of an outbreak COVID-19 and the liver
caused by a novel coronavirus, severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2), initially reported in Wuhan, China [1]. Liver involvement has been reported in patients infected with
More than 200 000 laboratory confirmed cases and nearly 10 000 SARS-CoV [6] and MERS-CoV [7]. Likewise, published case studies
deaths in over 100 countries have been reported to date [2], lead- reporting clinical features of patients with COVID-19 have shown
ing the World Health Organization in March 11, 2020 to character- that they may develop different degrees of liver dysfunction (sum-
ize the infection, subsequently named coronavirus disease 2019 marized in Table 1). In these studies, the incidence of liver injury
(COVID-19), as a pandemic [3]. The spectrum of symptomatic ranged from 14.8% to 78%, mainly presenting with abnormal levels
COVID-19 ranges from mild respiratory tract infection to severe of alanine aminotransferase (ALT) and aspartate aminotransferase
pneumonia that may progress to acute respiratory distress syn- (AST) accompanied by slightly elevated bilirubin levels [8–19]. A
drome or multi-organ dysfunction [4]. It is well established that deeper look at available data shows higher rates of abnormal levels
fever along with respiratory symptoms such as cough and dysp- in severe COVID-19, as high as 78% in one study [18].
noea represent the common symptoms of COVID-19 similar to Currently, the underlying mechanisms for hepatic injury in
the diseases caused by the other two highly pathogenic coron- patients with COVID-19 are still unclear. Liver damage might be
aviruses: severe acute respiratory syndrome (SARS) in 2003 and directly caused by virus-induced cytopathic effects. SARS-CoV-2
Middle East respiratory syndrome (MERS) in 2012 [5]. There is binds to the angiotensin-converting enzyme 2 (ACE2) receptor to
uncertainty about extra-pulmonary manifestations of COVID-19, enter its target cells [20]. Data from two independent cohorts
including those affecting the liver and gastrointestinal tract. This revealed significant enrichment of ACE2 expression in cholangio-
review aims to provide insight into characteristics, possible mech- cytes (59.7% of cells) compared to hepatocytes (2.6% of cells) sug-
anisms and implications of hepatic and gastrointestinal involve- gesting that SARS-CoV-2 might directly bind to ACE2-positive
ment caused by SARS-CoV-2 infection, adding to our knowledge cholangiocytes to dysregulate liver function [21]. Although ACE2
of the spectrum of COVID-19. is highly expressed in bile duct cells, recent works suggest that
gamma-glutamyl transferase (GGT) was elevated in 54% of
COVID-19 patients, whereas only 1.8% of patients (1/56) had ele-
vated alkaline phosphatase level [22]. Elsewhere, pathological

E-mail address: sheriefmusa@cu.edu.eg

https://doi.org/10.1016/j.ajg.2020.03.002
1687-1979/Ó 2020 Pan-Arab Association of Gastroenterology. Published by Elsevier B.V. All rights reserved.

Please cite this article as: S. Musa, Hepatic and gastrointestinal involvement in coronavirus disease 2019 (COVID-19): What do we know till now?, Arab
Journal of Gastroenterology, https://doi.org/10.1016/j.ajg.2020.03.002
2 S. Musa / Arab Journal of Gastroenterology xxx (xxxx) xxx

Table 1
Characteristics of liver biochemical profile in published COVID-19 case studies.

Patients with Patients with abnormal biochemical liver profile Patients with pre-existing
COVID-19 liver co-morbidities
Guan et al. [8] 1099 Abnormal ALT, 158/741 (21.3%): 23 (2.1%)
- 198% in non-severe COVID-19
- 281% in severe COVID-19
Abnormal AST, 168/757 (22.2%):
- 182% in non-severe COVID-19
- 394% in severe COVID-19
Abnormal total bilirubin 76/722 (10.5%)
- 9.9% in non-severe COVID-19
- 13.3% in severe COVID-19
Cai et al. [9] 298 44 (14.8%) 8 (2.7%)
9.6% in non-severe COVID-19
36.2% in severe COVID-19
Fan et al. [10] 148 75 (50.7%)- Abnormal ALT (18.2%)- Abnormal AST 6 (8%)
(21.6%)- Abnormal total bilirubin (6.1%)
Wang et al [11] 138 Mild elevation of ALT and AST 4 (29%)
Chen et al [12] 99 43 (43%) NA
- Abnormal ALT 28%
- Abnormal AST 35%
- Abnormal total bilirubin 18%
- Abnormal albumin 98%
Lu et al. [13] 85 33 (38.8%) 6 (7%)
Shi et al. [14] 81 43 (53%) 7 (9%)
Xu et al. [15] 62 10 (16%) 7 (11%)
Yang et al. [16] 52 15 (29%) NA
Huang et al. [17] 41 15(31%) 1(2%)
Zhang et al. [18] 82, deaths 64 (78%) 2(2.4%)
- Abnormal ALT 30.6%
- Abnormal AST 61.1%
- Abnormal total bilirubin 30.6%
Huang et al. [19] 36, non-survivors - Abnormal ALT 13% NA
- Abnormal AST 58%
- Abnormal total bilirubin 12.9%

Abbreviations: SARS-Cov-2, severe acute respiratory syndrome coronavirus 2; ALT, alanine transaminase; AST, aspartate aminotransferase.

analysis of hepatic tissue from a patient who died from COVID-19 received remdesivir at the time of clinical worsening, reported ele-
did not find viral inclusions in the liver [23]. vated liver enzymes [32].
In addition, immune-mediated inflammation might contribute
to liver injury in patients with COVID-19 who are critically ill COVID-19 and pre-existing liver disease
[22]. Previous studies have shown that inflammatory cytokine
storm is associated with adverse outcomes of SARS-CoV [24] or Given the high burden of chronic liver disease worldwide, inter-
MERS-CoV infection [25]. Inflammatory cytokine storm is an over- actions between pre-existing liver disease and COVID-19 need to
active inflammatory response, which leads to persistent activation be further investigated. Preliminary data indicate 2–11% of
of lymphocytes and macrophages that secrete huge amount of patients with COVID-19 had liver comorbidities [22]. However,
inflammatory cytokines [26]. Lymphocytes are important for the exact cause of pre-existing liver conditions has not been out-
inhibiting overactive innate immune responses during viral infec- lined in the published case studies (Table 1).
tion [27]. Thus, the typical lymphopenia during SARS-CoV-2 infec- In a study of 1099 patients with laboratory confirmed COVID-
tion may result in increases in interleukin-6 (IL-6), IL-10, IL-2 and 19, 23 (2.1%) patients had hepatitis B infection. Severe cases were
IFN-c levels and aggravated inflammatory responses, leading not more likely to have hepatitis B infection (2.4% vs 0.6%) than non-
only to pulmonary injury, but also the injury of non-pulmonary severe cases [8]. SARS patients with HBV/HCV infection were more
organs including the liver [28]. A study of the risk factors involved prone to develop severe hepatitis, probably due to enhanced viral
with hepatic injury in patients with COVID-19, found that lym- replication during SARS-CoV infection [33]. Individuals at high risk
phopenia and CRP level were independently associated with liver for severe COVID-19 are typically of older age and/or present with
injury, suggesting that inflammatory cytokine storm might be the comorbid conditions such as diabetes, cardiovascular disease, and
major mechanism [29]. hypertension, a similar profile to those at increased risk for nonal-
Another possible contributing factor may be the high levels of coholic fatty liver disease, making them more susceptible to liver
positive end expiratory pressure that can cause hepatic congestion injury. In patients with COVID-19 with autoimmune hepatitis,
by increasing right atrial pressure and impeding venous return. the effects of administration of glucocorticoids on disease progno-
However, published data suggest that admitted patients with sis is unclear. Given the expression of the ACE2 receptor in cholan-
COVID-19 have liver abnormalities without mechanical ventila- giocytes, whether infection with SARS-CoV-2 aggravates
tion. Furthermore, the distribution of aminotransferase levels cholestasis in patients with primary biliary cholangitis, needs to
among patients with COVID-19 does not support hypoxic hepatitis be studied [22].
being common [30]. Importantly, drug-induced liver injury during Moreover, patients with liver cirrhosis might be more suscepti-
COVID-19 treatment should be carefully investigated. It might be ble to infections because of their systemic immunocompromised
caused by antiviral medications (lopinavir/ritonavir), antipyretics status [34], thus, preventing infection with SARS-CoV-2 is of
(acetaminophen), antibiotics (macrolides, quinolones) or steroids utmost importance. In a study of 111 patients with decompensated
[31]. In a paper describing the first 12 patients with COVID-19 in cirrhosis in Wuhan, none of the participants had clinical symptoms
the United States (U.S.), the three hospitalized patients, who suggestive of SARS-CoV-2 infection, when certain precautionary

Please cite this article as: S. Musa, Hepatic and gastrointestinal involvement in coronavirus disease 2019 (COVID-19): What do we know till now?, Arab
Journal of Gastroenterology, https://doi.org/10.1016/j.ajg.2020.03.002
S. Musa / Arab Journal of Gastroenterology xxx (xxxx) xxx 3

approach was maintained, in contrast to an incidence of 17% of digestive tract flora mutually affect the respiratory tract through
COVID-19 among a comparative group of 101 decompensated cir- immune regulation, the so-called ‘‘gut-lung axis” [46].
rhotics at other hospitals where these measures had not been Autopsy studies are needed to understand the digestive system
implemented [35]. Finally, liver transplantation might involve a involvement of COVID-19; however, to date, there has been only
risk of transmission of viral infection from donor to recipient, as one autopsy report for an 85-year-old man with COVID-19, which
shown in the previous SARS outbreak [36]. Michaels and colleagues showed segmental dilatation and stenosis in the small intestine
recently described possible risks associated with transplant in [47]. Whether this finding is secondary to COVID-19 is unknown
COVID-19 positive recipients [37]. In Italy, where the COVID-19 [48].
outbreak is rapidly spreading, the Italian Transplant Authority rec- All these findings and hypotheses could have a clear impact
ommended nasopharyngeal swab or bronchoalveolar lavage to regarding transmission precautions, especially in hospitalized
identify COVID-19 before donation, with consequent exclusion of patients. Considering the evidence of faecal excretion for both
positive donors [38]. SARS-CoV and MERS-CoV [49], it is possible that the digestive sys-
tem may serve as an alternative route of SARS-CoV-2 infection. It
has been reported that the stool from confirmed cases tested pos-
COVID-19 and the gastrointestinal tract itive by RT-PCR for SARS-CoV-2 [39]. In terms of the fact that most
of the patients in the initial outbreak reported a link to a wild ani-
Since SARS-CoV-2 RNA was first detected in a stool specimen of mal market, this observation raises questions about whether this
the first reported COVID-19 patient in the U.S., much attention has virus was transmitted via contaminated food at the small intestine
been paid to gastrointestinal tract infection by SARS-CoV-2 [39]. [45]. Another issue of potential significance, is the extended dura-
Gastrointestinal involvement is well known in coronavirus infec- tion of viral shedding in faeces. In one study, it was observed that
tions of animals and humans [40]. Previous studies have revealed for over half of patients, faecal samples remained positive for SARS-
that 10.6% of patients with SARS and up to 30% of patients with CoV-2 RNA for a mean of 11.2 days after viral clearance in respira-
MERS had diarrhea [41]. tory tract samples [50]. According to current guidance, the decision
Similarly, data from early reports of the current pandemic sug- to discharge hospitalized COVID-19 patients is based on negative
gest that concurrent gastrointestinal symptoms are not uncommon results of RT-PCR testing for SARS-CoV-2 from at least two sequen-
in patients with COVID-19 [42]. In one of these studies, nausea or tial respiratory tract specimens collected 24 h apart [51]. There-
vomiting, or both, and diarrhoea were reported in 55 (56%) and 42 fore, routine stool sample testing with RT-PCR could be added and
(38%) patients [8]. In another cross-sectional study, enrolling 204 transmission-based precautions should be continued if faecal sam-
patients with confirmed COVID-19 from 3 hospitals in Hubei pro- ples test positive [50].
vince, 99 patients (48.5%) presented with digestive symptoms as
the chief complaint, including 7 cases in which there were no res-
COVID-19 and pre-existing digestive diseases
piratory symptoms [40]. This should alert gastroenterologists to
raise their index of suspicion when at-risk patients present with
In general, presence of co-morbidities is associated with poorer
digestive symptoms rather than waiting for respiratory symptoms
outcomes in patients with COVID-19. This may have implications
to emerge. This may help with earlier identification of COVID-19
for the management of patients with pre-existing digestive dis-
with earlier treatment and isolation [42].
eases [52]. Patients with cancer are more susceptible to infection,
A recent study by Wei et al. attempted to delineate differences
however, whether patients with gastrointestinal cancers are more
between COVID-19 patients with diarrhoea (26/84) and those
likely to be infected with SARS-CoV-2 than healthy individuals
without. Despite finding no difference in most of the laboratory
remains unknown [48]. In a nationwide analysis from China, 18
and radiologic findings, they noticed that COVID-19 patients with
(1%) of 1590 COVID-19 cases had a history of cancer. Among these
diarrhoea suffered headache, myalgia or fatigue, cough, sputum
18 cases, three had a history of colorectal cancer. Patients with
production, nausea, vomiting more frequently than those patients
COVID-19 and cancer had a higher risk of severe events [53]. Like-
without diarrhoea, but seldomly suffered abdominal pain, abdom-
wise, patients with inflammatory bowel disease (IBD) using biolog-
inal distension and tenesmus [43].
ics and immunosuppressive agents are at increased risk for more
Patients without digestive symptoms were more likely to be
frequent and severe infections and could be more susceptible to
cured and discharged than patients with digestive symptoms
SARS-CoV-2 infection [48]. Fortunately, with early precautions
(60% vs. 34.3%). This could be due to either viral replication in
for COVID-19 prevention and control, not a single patient of the
the gastrointestinal tract causing more severe disease or that
318 patients (204 with ulcerative colitis and 114 with Crohn’s dis-
patients who do not initially have typical respiratory symptoms
ease) in the IBD registry in Wuhan, has been reported to be
present with later stages of disease [42].
infected with SARS-CoV-2 [54]. These precautions included recom-
There are many hypotheses why COVID-19 appears to cause
mendations on the use of immunosuppressive agents and biolog-
digestive symptoms, but, the exact molecular mechanism needs to
ics, diet, and intentional postponement of elective surgery and
be further investigated. Firstly, interaction between SARS-CoV-2
endoscopy, as well as personal protection provisions [55]. In regard
and ACE2 might result in diarrhoea. A recent bioinformatics analysis
to recurrent Clostridioides difficile infection, experts in faecal
revealed that ACE2 was not only highly expressed in alveolar type II
microbiota transplantation believe that screening of stool donors
(AT2) cells in the lung, but also in the glandular cells of gastric and
is needed, as the risk of transmitting SARS-CoV-2 might be higher
duodenal epithelia [44]. Similar findings were found in the study
than that in other tissue transplants [56].
by Liang et al. [45], ACE2 was highly expressed in proximal and distal
enterocytes, directly exposed to food and foreign pathogens. The
ACE2-expressing enterocytes are invaded by SARS-CoV-2, leading COVID-19 in the endoscopy unit
to malabsorption, unbalanced intestinal secretion and activated
enteric nervous system, resulting in diarrhoea finally [44]. Secondly, Worldwide, as millions of people are instructed to stay home to
SARS-CoV-2 indirectly damages the digestive system through a minimize SARS-CoV-2 transmission, health-care workers are at
chain of inflammatory responses [42]. Another possible factor caus- high risk from COVID-19. Figures from China’s National Health
ing diarrhoea in COVID-19 patients might be antibiotic associated Commission show that more than 3300 health-care workers have
diarrhea [43]. Finally, changes in the composition and function of been infected as of early March [57]. Despite being not directly

Please cite this article as: S. Musa, Hepatic and gastrointestinal involvement in coronavirus disease 2019 (COVID-19): What do we know till now?, Arab
Journal of Gastroenterology, https://doi.org/10.1016/j.ajg.2020.03.002
4 S. Musa / Arab Journal of Gastroenterology xxx (xxxx) xxx

Fig. 1. Suggested workflow in GI endoscopy units during SARS-CoV-2 outbreak.

involved in management of COVID-19 patients, personnel working COVID-19, the following steps should be implimented in endo-
in endoscopy units are still at increased risk from inhalation of air- scopy units:
borne droplets, conjunctival contact, and touch contamination
[58]. Human-to-human transmission occurs primarily via infected 1. Reduction of non-essential exposure to SARS-CoV-2: It is rec-
droplets [59]. Airway suctioning, and other cough-inducing proce- ommended to limit endoscopy during the current outbreak to
dures pose an increased risk of transmission of SARS-CoV-2 [58]. It emergency procedures to treat patients with conditions such
must be noted that the risk of exposure is not limited to upper as acute gastrointestinal bleeding, foreign bodies in the gas-
endoscopy considering the potential transmission through faecal trointestinal tract and acute cholangitis secondary to biliary
shedding [60]. obstruction [62].
All endoscopy facilities should develop standard operating mea- 2. Risk assessment and stratification of patients prior to any
sures for COVID-19 prevention and control in conjunction with endoscopic procedure: A high index of suspicion to diagnose
infection control team members, and share these widely among SARS-CoV-2 infection, is crucial for prevention of transmission.
staff members [61]. Based on prior experience from SARS and our Screening of patients for COVID-19 should be based on case def-
current understanding of epidemiological characteristics of initions established by WHO and local health authorities [63].

Please cite this article as: S. Musa, Hepatic and gastrointestinal involvement in coronavirus disease 2019 (COVID-19): What do we know till now?, Arab
Journal of Gastroenterology, https://doi.org/10.1016/j.ajg.2020.03.002
S. Musa / Arab Journal of Gastroenterology xxx (xxxx) xxx 5

The assessment must include history of fever, respiratory symp- [12] Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of
99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive
toms, or diarrhea, history of contact with a suspected or con-
study. Lancet 2020;395:507–13.
firmed case of COVID-19 and any recent travel to a high-risk [13] Lu Li, Shuang Li, Manman Xu, et al. Risk factors related to hepatic injury in
area [61]. patients with corona virus disease 2019. medRxiv preprint doi: https://doi.org/
3. Negative-pressure room: Whenever possible, endoscopy 10.1101/2020.02.28.20028514.
[14] Shi Heshui, Han Xiaoyu, Jiang Nanchuan, Cao Yukun, Alwalid Osamah, Gu Jin,
should be performed in an isolated room with negative pres- Fan Yanqing, Zheng Chuansheng. Radiological findings from 81 patients with
sure. If not available, endoscopy should be performed in a ded- COVID-19 pneumonia in Wuhan, China: a descriptive study. Lancet Infect Dis
icated room with adequate ventilation [64]. 2020. https://doi.org/10.1016/S1473-3099(20)30086-4.
[15] Xu X-W, Wu X-X, Jiang X-G, et al. Clinical findings in a group of patients
4. Staff protection: The minimal composition of personal protec- infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan,
tive equipment (PPE) for personnel in endoscopy units should China: retrospective case series. BMJ 2020; published online Feb 19.
include gloves, hairnet, protective eyewear (goggles or face DOI:10.1136/bmj.m606.
[16] Yang X, Yu Y, Xu J, et al. Clinical course and outcomes of critically ill patients
shield), waterproof gowns, and respiratory protective with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered,
equipment, modified on the basis of risk stratification [61]. retrospective, observational study. Lancet Respir Med 2020. https://doi.org/
The surgical facial mask is effective in blocking splashes and 10.1016/S2213-2600(20)30079-5.
[17] Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019
large-particle droplets, whereas, filtering facepiece (FFP) respi- novel coronavirus in Wuhan, China. Lancet 2020;395:497–506.
rator class 2 or 3 (FFP2/FFP3) achieves efficient filtration of air- [18] Zhang B, Zhou X, Qiu Y et al. Clinical characteristics of 82 death cases with
borne particles (up to 0.3 mm) [65]. In addition to PPE, health COVID-19[J]. medRxiv 2020.02.26.20028191; in press. https://doi.org/
10.1101/2020.02.26.20028191.
care workers must be educated the principles of contact and
[19] Huang Y, Zhou H, Yang R et al. Clinical characteristics of 36 non-survivors with
airborne precautions for both suspect and probable COVID-19 COVID-19 in Wuhan, China. medRxiv 2020.02.27.20029009; in press.
patients [64]. https://doi.org/10.1101/2020.02.27.20029009.
5. Reprocessing of endoscopes and endoscopic accessories: [20] Hoffmann M, Kleine-Weber H, Krüger N, et al. The novel coronavirus 2019
(2019-nCoV) uses the SARS-1 coronavirus receptor ACE2 and the cellular
Enveloped viruses such as SARS-CoV-2 can be inactivated by protease TMPRSS2 for entry into target cells. bioRxiv 2020.01.31.929042; in
disinfectants having virucidal activity [67]. Whereas high- press. https://doi.org/10.1101/2020.01.31.929042.
level disinfection is recommended for endoscopes, and other [21] Chai X, Hu L, Zhang Y, et al. Specific ACE2 expression in cholangiocytes may
cause liver damage after 2019-nCoV infection. bioRxiv 2020; published online
‘‘semi-critical’’ instruments, sterilization is recommended for Feb 4. https://doi.org/10.1101/2020.02.03.931766.
‘‘critical’’ instruments, including biopsy forceps, polypectomy [22] Zhang Chao, Shi Lei, Wang Fu-Sheng. Liver injury in COVID-19: management
snares and papillotomes. Disposable accessories are an alterna- and challenges. Lancet Gastroenterol Hepatol 2020. https://doi.org/10.1016/
S2468-1253(20)30057-1.
tive to sterilization of reusable devices [68]. [23] Zhe Xu, Lei Shi, Yijin Wang, et al. Pathological findings of COVID-19 associated
6. Decontamination of endoscopy rooms: This process should with acute respiratory distress syndrome. Lancet Respir Med 2020. https://doi.
include cleaning all surfaces in the procedure room to remove org/10.1016/S2213-2600(20)30076-X.
[24] Chien JY, Hsueh PR, Cheng WC, et al. Temporal changes in cytokine/chemokine
all soil and biofilm, followed by proper disinfection [61]. profiles and pulmonary involvement in severe acute respiratory syndrome.
Chlorine-containing detergents are recommended for floor Respirology 2006;11:715–22. https://doi.org/10.1111/j.1440-
cleaning every day [67]. 1843.2006.00942.x.
[25] Chu H, Zhou J, Wong BH, et al. Middle east respiratory syndrome coronavirus
efficiently infects human primary T lymphocytes and activates the extrinsic
To prevent SARS-CoV-2 transmission in endoscopy units during and intrinsic apoptosis pathways. J Infect Dis 2016;213:904–14. https://doi.
the current outbreak, a workflow is proposed (Fig. 1) in accordance org/10.1093/infdis/jiv380.
with recommendations of endoscopy societies [61–66]. [26] Tisoncik JR, Korth MJ, Simmons CP, et al. Into the eye of the cytokine storm.
Microbiol Mol Biol Rev 2012;76:16–32. https://doi.org/10.1128/MMBR.05015-
11.
[27] Kim KD, Zhao J, Auh S, et al. Adaptive immune cells temper initial innate
References responses. Nat Med 2007;13:1248–52. https://doi.org/10.1038/nm1633.
[28] Liu J, Li S, Liu J, et al. Longitudinal characteristics of lymphocyte responses and
[1] Del Rio C, Malani PN. 2019 novel coronavirus-important information for cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients.
clinicians. JAMA 2020. medRxiv, 2020. doi: https://doi.org/10.1101/2020.02.16.20023671.
[2] WHO. Coronavirus disease 2019 (COVID-19) Situation Report – 60. 20 March [29] Lu L, Shuang L, Manman X, et al. Risk factors related to hepatic injury in
2020, https://www.who.int/docs/default-source/coronaviruse/situation- patients with corona virus disease 2019. medRxiv preprint doi: https://doi.org/
reports/20200320-sitrep-60-covid-19.pdf?sfvrsn=8894045a_2 10.1101/2020.02.28.20028514.
[3] WHO Director-General’s opening remarks at the media briefing on COVID-19 - [30] Bangash MN, Patel J, Parekh D. COVID-19 and the liver: little cause for concern
11 March 2020. https://www.who.int/dg/speeches/detail/who-director- Lancet Gastroenterol Hepatol 2020 Published Online March 20, 2020.
general-s-opening-remarks-at-the-media-briefing-oncovid-19—11-march- https://doi.org/10.1016/ S2468-1253(20)30084-4.
2020 [31] Fan Z, Chen L, Li J, et al. Clinical Features of COVID-19-Related Liver Damage.
[4] Wu Z, McGoogan JM. Characteristics of and important lessons from the bioRxiv, 2020. doi: https://doi.org/10.1101/2020.02.26.20026971
Coronavirus Disease 2019 (COVID-19) outbreak in China: summary of a Report [32] The COVID-19 Investigation Team. First 12 patients with coronavirus disease
of 72314 cases from the Chinese Center for Disease Control and Prevention. 2019 (COVID-19) in the United States. medRxiv preprint doi: https://doi.org/
JAMA 2020. 10.1101/2020.03.09.20032896.
[5] Su S, Wong G, Shi W, et al. Epidemiology, genetic recombination, and [33] Huang Y, Gao Z. Study of the relationship SARS and hepatitis virus B. Chin J
pathogenesis of coronaviruses. Trends Microbiol 2016;24(6):490–502. Clini Hepatol 2003;06:342–3.
[6] Chau TN, Lee KC, Yao H, et al. SARS-associated viral hepatitis caused by a novel [34] Strnad P, Tacke F, Koch A, et al. Liver—guardian, modifier and target of sepsis.
coronavirus: report of three cases. Hepatology 2004;39(2):302–10. https://doi. Nat Rev Gastroenterol Hepatol 2017;14:55–66.
org/10.1002/hep.20111. [35] Xiao Yong, Pan Hong, She Qian, Wang Fen, Chen Mingkai. Prevention of SARS-
[7] Alsaad KO, Hajeer AH, Al Balwi M, et al. Histopathology of Middle East CoV-2 infection in patients with decompensated cirrhosis. Lancet
respiratory syndrome coronovirus (MERS-CoV) infection—clinicopathological Gastroenterol Hepatol 2020. https://doi.org/10.1016/S2468-1253(20)30080-7.
and ultrastructural study. Histopathology 2018;72:516–24. [36] Kumar D, Tellier R, Draker R, et al. Severe acute respiratory syndrome (SARS) in
[8] Guan W, Ni Z, Hu Y, et al. Clinical characteristics of novel coronavirus infection a liver transplant recipient and guidelines for donor SARS screening. Am J
in China. NEJM 2019. https://doi.org/10.1056/NEJMoa2002032. Transplant 2003;3:977–81.
[9] Cai Q, Huang D, Ou P et al. COVID-19 in a Designated Infectious Diseases [37] Michaels MG, La Hoz RM, Danziger IL, et al. Coronavirus Disease 2019:
Hospital Outside Hubei Province, China [J]. medRxiv 2020.02.17.20024018; in Implications of Emerging Infections for Transplantation. Am J Transplant
press. https://doi.org/10.1101/2020.02.17.20024018. February 2020:ajt.15832. doi:10.1111/ajt.15832.
[10] Fan Z, Chen L, Li Jun et al. Clinical Features of COVID-19-Related Liver Damage. [38] Andrea G, Daniele D, Barbara A, et al. Coronavirus disease 2019 and
medRxiv 2020.02.26.20026971; in press. Available from: https://doi.org/ transplantation: a view from the inside. Am J Transplant 2020 Mar 17.
10.1101/2020.02.26.20026971. https://doi.org/10.1111/ajt.15853.
[11] Wang D, Hu B, Hu C, et al. Clinical characteristics of 138 hospitalised patients [39] Holshue Michelle L, DeBolt Chas, Lindquist Scott, Lofy Kathy H, Wiesman John,
with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA Bruce Hollianne, Spitters Christopher, Ericson Keith, Wilkerson Sara, Tural
2020; published online Feb 7. DOI:10.1001/jama.2020.1585. Ahmet, Diaz George, Cohn Amanda, Fox LeAnne, Patel Anita, Gerber Susan I,

Please cite this article as: S. Musa, Hepatic and gastrointestinal involvement in coronavirus disease 2019 (COVID-19): What do we know till now?, Arab
Journal of Gastroenterology, https://doi.org/10.1016/j.ajg.2020.03.002
6 S. Musa / Arab Journal of Gastroenterology xxx (xxxx) xxx

Kim Lindsay, Tong Suxiang, Lu Xiaoyan, Lindstrom Steve, Pallansch Mark A, [55] Chinese Society of IBD. Managing IBD patients during the outbreak of COVID-
Weldon William C, Biggs Holly M, Uyeki Timothy M, Pillai Satish K. First case of 19. Chin J Dig 2020;40:E001.
2019 novel coronavirus in the United States. N Engl J Med 2020;382 [56] Ianiro G, Mullish BH, Kelly CR, et al. Screening of faecal microbiota transplant
(10):929–36. https://doi.org/10.1056/NEJMoa2001191. donors during the COVID-19 outbreak: suggestions for urgent updates from an
[40] Leung WK, To KF, Chan PK, et al. Enteric involvement of severe acute international expert panel. Lancet Gastroenterol Hepatol 2020. March 16,
respiratory syndrome associated coronavirus infection. Gastroenterology 2020. https://doi.org/10.1016/S2468 1253(20)30082-0.
2003;125:1011–7. [57] COVID-19: protecting health-care workers. Lancet 395 (10228) P922, MARCH
[41] Chan JF-W, Yuan S, Kok K-H, et al. A familial cluster of pneumonia associated 21, 2020. DOI: https://doi.org/10.1016/S0140-6736 (20)30644-9.
with the 2019 novel coronavirus indicating person-to-person transmission: a [58] Tang JW, Li Y, Eames I, et al. Factors involved in the aerosol transmission of
study of a family cluster. Lancet 2020;395:514–23. infection and control of ventilation in healthcare premises. J Hosp Infect
[42] Pan L, Mu M, Ren HG et al., Clinical characteristics of COVID-19 patients with 2006;64:100–14.
digestive symptoms in Hubei, China: a descriptive, cross-sectional, [59] Wang C, Horby PW, Hayden FG, et al. A novel coronavirus outbreak of global
multicenter study, The American Journal of Gastroenterology. Published health concern. Lancet 2020;395:470–3.
online March 18, 2020 [60] Gu Jinyang, Han Bing, Wang Jian. COVID-19: Gastrointestinal manifestations
[43] Wei XS, Wang X, Niu YR, et al. Clinical characteristics of SARS-CoV-2 infected and potential fecal-oral transmission. Gastroenterology 2020. https://doi.org/
pneumonia with diarrhea. The Lancet Respiratory Medicine-Manuscript Draft. 10.1053/j.gastro.2020.02.054.
[44] Zhang H, Kang ZJ, Gong HY, et al. The digestive system is a potential route of [61] Repici A, Maselli R, Colombo M, et al. Coronavirus (COVID-19) outbreak: what
2019-nCov infection: a bioinformatics analysis based on single-cell the department of endoscopy should know. Gastrointest Endosc 2020. https://
transcriptomes. Preprint. Posted online January 30, 2020. bioRxiv 927806. doi.org/10.1016/j.gie.2020.03.019.
doi: 10.1101/2020.01.30.927806. [62] Endoscopy activity and COVID-19: BSG and JAG guidance – update 20.03.20
[45] Liang W, Feng Z, Rao S, et al. Diarrhoea may be underestimated: a missing link https://www.bsg.org.uk/covid-19-advice/endoscopy-activity-and-covid-19-
in 2019 novel coronavirus. Gut 2020:1–3. https://doi.org/10.1136/gutjnl- bsg-and-jag-guidance/. Accessed 20/3/2020
2020-320832. [63] Zhang Y, Zhang X, Liu L, et al. Suggestions of Infection Prevention and Control
[46] Budden KF, Gellatly SL, Wood DL, et al. Emerging pathogenic links between in Digestive Endoscopy During Current 2019-nCoV Pneumonia Outbreak in
microbiota and the gut-lung axis. Nat Rev Microbiol. 2017;15:55–63. Wuhan, Hubei Province, China. http://www.worldendo.org/wp-content/
[47] Liu Q, Wang R, Qu G, et al. Macroscopic autopsy findings in a patient with uploads/2020/02/Suggestions-of-Infection-Prevention-and-Control-in-
COVID-19. J Forensic Med 2020;36:1–3 (in Chinese). Digestive-Endoscopy-During-Current-2019-nCoV-Pneumonia-Outbreak-in-
[48] Mao R, Liang J, Shen J, et al. Implications of COVID-19 for patients with pre- Wuhan-Hubei-Province-China.pdf
existing digestive diseases Published: March 11, 2020. DOI: https://doi.org/ [64] ESGE and ESGENA Position Statement on gastrointestinal endoscopy and the
10.1016/S2468-1253 (20)30076-5. COVID-19 pandemic. Update 1 (18.03.2020). https://www.esge.com/esge-and-
[49] Yeo C, Kaushal S, Yeo D. Enteric involvement of coronaviruses: is faecal–oral esgena-position-statement-on-gastrointestinal-endoscopy-and-the-covid-19-
transmission of SARS-CoV-2 possible? Lancet Gastroenterol Hepatol 2020; pandemic/
published online Feb 19. https://doi.org/10.1016/ S2468-1253(20)30048-0. [65] European Centre for Disease Prevention and Control (ECDC). Personal
[50] Wu Y, Guo C, Tang L, et al. Prolonged presence of SARS-CoV-2 viral RNA in protective equipment (PPE) needs in healthcare settings for the care of
faecal samples. Lancet Gastroenterol Hepatol 2020. https://doi.org/10.1016/ patients with suspected or confirmed novel coronavirus (2019-nCoV) 2020.
S2468-1253(20)30083-2. Stockholm: ECDC; 2020. https://www.ecdc.europa.eu/sites/
[51] Xiao F, Tang M, Zheng X, Liu Y, Li X, Shan H. Evidence for gastrointestinal default/files/documents/novel-coronavirus-personal-protective-equipment-
infection of SARS-CoV-2. Gastroenterology 2020. https://doi.org/10.1053/ needs-healthcare-settings.pdf
j.gastro.2020.02.055. [66] Tse F, Borgaonkar M, Leontiadis G. COVID-19: Advice from the Canadian
[52] Yang J, Zheng Y, Gou X, et al. Prevalence of comorbidities in the novel Wuhan Association of Gastroenterology for Endoscopy Facilities, as of March 16, 2020.
coronavirus (COVID-19) infection: a systematic review and meta-analysis. Int J https://www.cag-acg.org/images/publications/CAG-Statement-COVID-&-
Infect Dis 2020. https://doi.org/10.1016/j.ijid.2020.03.017. Endoscopy.pdf
[53] Liang W, Guan W, Chen R, et al. Cancer patients in SARS-CoV-2 infection: a [67] Geller C, Varbanov M, Duval RE. Human coronaviruses: insights into
nationwide analysis in China. Lancet Oncol 2020 Mar;21(3):335–7. https://doi. environmental resistance and its influence on the development of new
org/10.1016/S1470-2045(20)30096-6. antiseptic strategies. Viruses 2012;4(11):3044–68.
[54] An P, Ji M, Ren H, et al. Protection of 318 inflammatory bowel disease patients [68] ASGE Quality Assurance in Endoscopy Committee, Calderwood AH, Day LW,
from the outbreak and rapid spread of COVID-19 infection in Wuhan, China. Muthusamy VR, et al. ASGE guideline for infection control during GI
Available at SSRN: https://ssrn.com/abstract=3543590 endoscopy. Gastrointest Endosc 2018 May;87(5):1167–79.

Please cite this article as: S. Musa, Hepatic and gastrointestinal involvement in coronavirus disease 2019 (COVID-19): What do we know till now?, Arab
Journal of Gastroenterology, https://doi.org/10.1016/j.ajg.2020.03.002
Another random document with
no related content on Scribd:
“You want to know how old Henry C. Terry is,” promptly said Reese.
Then plainly puzzled, he shook his head and went on to a question as to
what was the floor covering. The next question was: “Where did I do my
first newspaper work?”
He gave correctly the answer. The last slip Reese took in his hand, but
did not open it. He handed it back and directed the writer to hold it. Then
Reese said:
“Emma Drew was your mother’s maiden name.”
The answer to the first five questions had been given in a room adjoining
the court, but for the last Reese walked into the courtroom and gave his
answer in the presence of the judge and jury.
Judge Rosalsky wrote several questions, as follows:
“What was the ruling in the Shelly case?”
“How much money have I in the bank?” and
“What is the name of my favorite school-teacher?”
The demonstrator not only told what the questions were, but gave the
correct replies. Reese is seventy-four years old.
“I don’t know myself how I do it,” he said. “The answers just sort of
flash on my brain as a picture, just as ordinary objects are seen through the
eye.”

Kaiser’s Big Cannon Can’t Make Raindrops.


So many days during the last two months have been rainy or cloudy that
a great many people are led to believe that so much wet weather is owing to
the war in Europe. “Our heavy rainfall is probably caused by so much firing
over there,” is a remark frequently heard. Indeed, as long as man can
remember, it has been a theory accepted by many that constant or heavy
explosions in the air will produce rainfall. Tests of this kind have been made
in various parts of the country—more often in the west and southwest—and
sometimes with evident success, yet skeptics were quick to say: “Shucks, it
was time they had a shower, anyway.”
Now let us see how the ancients looked at this question. Almost since
the beginning of history there has been a theory—a silly one, says one
scientist—that battles caused rain. Battles, not explosives, observe, for in
the early centuries, A. D., there were no gunpowder or similar explosives.
“Banish the thought,” says Forecaster Pennywitt, of the United States
Weather Bureau, in discussing the question of explosives and rainfall.
“There never was a more absurd idea. Not in all the history of the world is it
recorded that human endeavor wrung rain from the skies, either
intentionally or unknowingly. Rain falls by the will of nature only, and the
influence of man over nature, in so far as producing rain is concerned, does
not exist.
“None of men’s activities on earth has the slightest effect on the rainfall.
If nature decrees it shall rain, then rain it will; no other power or force can
bring precipitation.
“Almost since the beginning of history there has been a silly theory that
battles caused rain. This was the case even before gunpowder came into
use. The Greek writer, Plutarch, as far back as the year 150 A. D., held the
belief that the glitter and clash of the sabers of the ancient Greek and
Roman warriors on the field of honor produced rain. He believed it because
it generally rained after every battle. As a matter of fact, it had to rain after
every battle, because they fought only on clear days in those times; and,
besides, it always rains once every three days in the year, according to
average.
“After gunpowder became an instrument of destruction, rains during
time of war were blamed on it. Even the United States government has
shared this belief that powder will produce rain, and it wasted thousands of
dollars trying to make it rain in Texas. Similar experiments were made in
Europe several years ago, and in France one scientist thought that by
employing the explosive he could transform hail into more harmless rain.
“Strange as it may seem to a good many people, there has been less than
a normal rainfall in western Pennsylvania and other eastern districts during
the last six months.”

Bees Settle in a Mail Box.


The wanderlust of summer got into the blood of a swarm of bees
belonging to Leo Nickoli, 448 Bellaire Avenue, Kansas City, Mo. They
circled in the air and flew away. Mr. Nickoli followed.
The awning in front of the drug store of the Klee Drug Company first
attracted the bees. But finding no place to alight there, the bees transferred
their attentions to a mail box near by. In a moment the box was the center of
the swarm, who were preparing to settle down among the letters.
Mr. Nickoli, however, had different plans. With a hive baited with honey
comb, he began coaxing the bees into a new home. A crowd of two hundred
persons watched his operation, which lasted several hours.

Aged Preacher Finds His Long Lost Sister.


An only sister, whom he had not seen nor heard from for more than
forty-five years, and whom he believed to be dead, has been found by
Reverend W. H. H. Ruble, of Harrison, Ark., and immediately after the
locating of the long-lost sister, he has received news that sight has been
restored to the woman who has been blind for many years, as a result of
cataract.
Reverend Ruble’s sister is Mrs. E. J. Willis, of Knoxville, Tenn. She is
ninety-two years of age, and was last seen by her brother more than forty-
five years ago in Cleveland, a small town of Tennessee. As many people do,
the brother and sister kept in touch for a time, but gradually ceased writing,
until each had changed address and the old addresses were forgotten.
Receiving no word for years, each believed the other to be dead, until
last January, when the annual conference of the M. E. Church was held in
Harrison, Ark. At that time Reverend Ruble met Reverend Murphy, a
delegate, who told him of the whereabouts of Chaplain J. A. Ruble, of the
Old Settlers’ Home in Johnson City, to whom Reverend Ruble wrote,
believing that the chaplain might be his nephew. The belief was true, and
the letter from Harrison was forwarded to Mrs. Willis, who was overjoyed
when she wrote again to her brother, the first time in nearly half a century.

Arizona Girl Carries Mail on Horse.


Miss Matilda Sorey, of Higley, Ariz., may not be the only girl in the
United States who carries mail on a R. F. D. route, but she is probably the
only one who does so on horseback. When a new route was established out
of Higley, Miss Sorey, who is just twenty-one years old, was appointed
carrier. Her friends supposed she would use a horse and buggy, but, instead,
she covers the route six days a week on her handsome gray saddle horse.
She carries the mail in a sack swung over the pommel of her cowboy
saddle.

Didn’t Even Have a Barrel.


A short time ago C. J. Debes, who lives on a farm a few miles south of
Hagerman, N. M., arose early, as was his custom, and, after lighting his
gasoline stove and placing his kettle on, sauntered out through the
delightful morning air to feed his stock, without changing his night robe for
the more substantial clothing of the day.
Debes being a bachelor, and there being no near neighbors, everything
went well with him until he started to return to his house and found it
almost consumed by fire. His predicament seemed precarious, when the
neighbors, seeing the flames, rushed to the scene. Debes, however, took
refuge in the barn until a friendly neighbor brought in some heavier
raiment. The gasoline stove had exploded and enveloped the entire building
in flames, making quick work of its destruction.

No Government Reward for Passenger Pigeon.


Recent widespread newspaper accounts to the effect that the United
States Department of Agriculture is offering ten thousand dollars reward to
the person finding a passenger or “wood”-pigeon nest containing two eggs,
resulted in hundreds of letters being sent to the department.
The report is not based upon facts, as the department has offered no such
reward, and there is every reason to believe the passenger pigeon which
formerly roamed the country in flocks of millions is extinct. In 1910 about
one thousand dollars in rewards was offered by Clark University for the
first undisturbed nests of the passenger pigeon to be found in the United
States. This was a great stimulus to action. The hunt for this pigeon was
fruitless. The offer of rewards was renewed for several years, until it was
fully established that the pigeon was extinct.
The passenger pigeon up to 1885 ranged the American continent east of
the Rocky Mountains. The mourning dove has often been mistaken for the
passenger pigeon, which in a general way it resembles. However, this bird
is quite distinct from the passenger pigeon; it is shorter and has different
color markings.
The press reports stated that the now extinct passenger pigeon was
valued because of its usefulness in destroying the gipsy moth and other
moths and pests which are doing millions of dollars of damage. Although
the preservation of this pigeon is much to be desired, it would be of
absolutely no value in eliminating the gipsy moth, as the pigeons are almost
entirely vegetarian in their diet.

Wounded Dog Returns Home.


A dog belonging to Edward Dougherty, of Spring Grove, Pa., was shot
through the head twice with a thirty-eight-caliber revolver by Dougherty.
The dog lay on the same spot for seven days and seven nights, but on the
beginning of the eighth day he came back to his old home, hardly able to
drag himself along. After being fed and given water to drink, the dog
seemed to be all right.
The dog ate eggs from the nests in Dougherty’s henhouse before his
punishment and since his extraordinary experience he has not eaten one
egg. Mr. Dougherty is sure he put two bullets through the dog’s brain.

Muskrat and Trout Battle.


Lew McQuiston, a well-known angler of Bellefonte, Pa., witnessed a
unique battle a few days ago between a muskrat and a two-foot trout.
McQuiston went to Spring Creek shortly before dusk to try and land
some big trout. While whipping the stream, he saw something doing on the
other side of the creek, about sixty feet away from where he was standing.
In the quickly gathering shadows it was hard to tell at first what it was, but
after closer inspection he saw that it was a mammoth trout and a muskrat.
They were engaged in mortal combat, and they slashed around through
the water until it was churned into foam. Then the muskrat managed to get
out on the bank, pulling the trout along with it. But the big trout seemed to
be able to fight on land as well as in the water, flopping around and holding
on to the muskrat’s nose until they finally both fell back into the water.
Then there was another lashing and foaming, and the noise died away. A
few ripples told that the struggle was ended.
McQuiston looked around in the water for evidence of who had won the
battle, but found neither the muskrat or the trout. He does not know whether
it was a fight to the finish or a draw.

Tongue Fenders Demanded.


Tongue fenders for salted-peanut vending machines. That’s the latest
slogan of Montclair, N. Y., which already has put a legal muffler on barking
dogs and crowing roosters. It was proposed by Health Commissioner James
McDonough after he saw a small boy thrust his tongue into a cup container
of a vending machine to get the “crumbs.”

Finds Pennies in Turtle.


Roy Bowsher, of Ashville, Ohio, went fishing last week and caught a
turtle, which he sold to C. R. Cook, proprietor of a saloon. When Cook
opened the turtle, preparatory to serving it on his lunch counter, he found
two hundred and thirty-four pennies in it.

The Nick Carter Stories


ISSUED EVERY SATURDAY BEAUTIFUL COLORED COVERS
When it comes to detective stories worth while, the Nick Carter Stories
contain the only ones that should be considered. They are not overdrawn
tales of bloodshed. They rather show the working of one of the finest minds
ever conceived by a writer. The name of Nick Carter is familiar all over the
world, for the stories of his adventures may be read in twenty languages. No
other stories have withstood the severe test of time so well as those
contained in the Nick Carter Stories. It proves conclusively that they are
the best. We give herewith a list of some of the back numbers in print. You
can have your news dealer order them, or they will be sent direct by the
publishers to any address upon receipt of the price in money or postage
stamps.
730—The Torn Card.
731—Under Desperation’s Spur.
732—The Connecting Link.
733—The Abduction Syndicate.
738—A Plot Within a Plot.
739—The Dead Accomplice.
746—The Secret Entrance.
747—The Cavern Mystery.
748—The Disappearing Fortune.
749—A Voice from the Past.
752—The Spider’s Web.
753—The Man With a Crutch.
754—The Rajah’s Regalia.
755—Saved from Death.
756—The Man Inside.
757—Out for Vengeance.
758—The Poisons of Exili.
759—The Antique Vial.
760—The House of Slumber.
761—A Double Identity.
762—“The Mocker’s” Stratagem.
763—The Man that Came Back.
764—The Tracks in the Snow.
765—The Babbington Case.
766—The Masters of Millions.
767—The Blue Stain.
768—The Lost Clew.
770—The Turn of a Card.
771—A Message in the Dust.
772—A Royal Flush.
774—The Great Buddha Beryl.
775—The Vanishing Heiress.
776—The Unfinished Letter.
777—A Difficult Trail.
782—A Woman’s Stratagem.
783—The Cliff Castle Affair.
784—A Prisoner of the Tomb.
785—A Resourceful Foe.
789—The Great Hotel Tragedies.
795—Zanoni, the Transfigured.
796—The Lure of Gold.
797—The Man With a Chest.
798—A Shadowed Life.
799—The Secret Agent.
800—A Plot for a Crown.
801—The Red Button.
802—Up Against It.
803—The Gold Certificate.
804—Jack Wise’s Hurry Call.
805—Nick Carter’s Ocean Chase.
807—Nick Carter’s Advertisement.
808—The Kregoff Necklace.
811—Nick Carter and the Nihilists.
812—Nick Carter and the Convict Gang.
813—Nick Carter and the Guilty Governor.
814—The Triangled Coin.
815—Ninety-nine—and One.
816—Coin Number 77.
NEW SERIES
NICK CARTER STORIES
1—The Man from Nowhere.
2—The Face at the Window.
3—A Fight for a Million.
4—Nick Carter’s Land Office.
5—Nick Carter and the Professor.
6—Nick Carter as a Mill Hand.
7—A Single Clew.
8—The Emerald Snake.
9—The Currie Outfit.
10—Nick Carter and the Kidnaped Heiress.
11—Nick Carter Strikes Oil.
12—Nick Carter’s Hunt for a Treasure.
13—A Mystery of the Highway.
14—The Silent Passenger.
15—Jack Dreen’s Secret.
16—Nick Carter’s Pipe Line Case.
17—Nick Carter and the Gold Thieves.
18—Nick Carter’s Auto Chase.
19—The Corrigan Inheritance.
20—The Keen Eye of Denton.
21—The Spider’s Parlor.
22—Nick Carter’s Quick Guess.
23—Nick Carter and the Murderess.
24—Nick Carter and the Pay Car.
25—The Stolen Antique.
26—The Crook League.
27—An English Cracksman.
28—Nick Carter’s Still Hunt.
29—Nick Carter’s Electric Shock.
30—Nick Carter and the Stolen Duchess.
31—The Purple Spot.
32—The Stolen Groom.
33—The Inverted Cross.
34—Nick Carter and Keno McCall.
35—Nick Carter’s Death Trap.
36—Nick Carter’s Siamese Puzzle.
37—The Man Outside.
38—The Death Chamber.
39—The Wind and the Wire.
40—Nick Carter’s Three Cornered Chase.
41—Dazaar, the Arch-Fiend.
42—The Queen of the Seven.
43—Crossed Wires.
44—A Crimson Clew.
45—The Third Man.
46—The Sign of the Dagger.
47—The Devil Worshipers.
48—The Cross of Daggers.
49—At Risk of Life.
50—The Deeper Game.
51—The Code Message.
52—The Last of the Seven.
53—Ten-Ichi, the Wonderful.
54—The Secret Order of Associated Crooks.
55—The Golden Hair Clew.
56—Back From the Dead.
57—Through Dark Ways.
58—When Aces Were Trumps.
59—The Gambler’s Last Hand.
60—The Murder at Linden Fells.
61—A Game for Millions.
62—Under Cover.
63—The Last Call.
64—Mercedes Danton’s Double.
65—The Millionaire’s Nemesis.
66—A Princess of the Underworld.
67—The Crook’s Blind.
68—The Fatal Hour.
69—Blood Money.
70—A Queen of Her Kind.
71—Isabel Benton’s Trump Card.
72—A Princess of Hades.
73—A Prince of Plotters.
74—The Crook’s Double.
75—For Life and Honor.
76—A Compact With Dazaar.
77—In the Shadow of Dazaar.
78—The Crime of a Money King.
79—Birds of Prey.
80—The Unknown Dead.
81—The Severed Hand.
82—The Terrible Game of Millions.
83—A Dead Man’s Power.
84—The Secrets of an Old House.
85—The Wolf Within.
86—The Yellow Coupon.
87—In the Toils.
88—The Stolen Radium.
89—A Crime in Paradise.
90—Behind Prison Bars.
91—The Blind Man’s Daughter.
92—On the Brink of Ruin.
93—Letter of Fire.
94—The $100,000 Kiss.
95—Outlaws of the Militia.
96—The Opium-Runners.
97—In Record Time.
98—The Wag-Nuk Clew.
99—The Middle Link.
100—The Crystal Maze.
101—A New Serpent in Eden.
102—The Auburn Sensation.
103—A Dying Chance.
104—The Gargoni Girdle.
105—Twice in Jeopardy.
106—The Ghost Launch.
107—Up in the Air.
108—The Girl Prisoner.
109—The Red Plague.
110—The Arson Trust.
111—The King of the Firebugs.
112—“Lifter’s” of the Lofts.
113—French Jimmie and His Forty Thieves.
114—The Death Plot.
115—The Evil Formula.
116—The Blue Button.
117—The Deadly Parallel.
118—The Vivisectionists.
119—The Stolen Brain.
120—An Uncanny Revenge.
121—The Call of Death.
122—The Suicide.
123—Half a Million Ransom.
124—The Girl Kidnapper.
125—The Pirate Yacht.
126—The Crime of the White Hand.
127—Found in the Jungle.
128—Six Men in a Loop.
129—The Jewels of Wat Chang.
130—The Crime in the Tower.
131—The Fatal Message.
132—Broken Bars.
133—Won by Magic.
134—The Secret of Shangore.
135—Straight to the Goal.
136—The Man They Held Back.
137—The Seal of Gijon.
138—The Traitors of the Tropics.
139—The Pressing Peril.
140—The Melting-Pot.
141—The Duplicate Night.
142—The Edge of a Crime.
143—The Sultan’s Pearls.
144—The Clew of the White Collar.
145—An Unsolved Mystery.
146—Paying the Price.
147—On Death’s Trail.
148—The Mark of Cain.
Dated July 17th, 1915.
149—A Network of Crime.
Dated July 24th, 1915.
150—The House of Fear.
Dated July 31st, 1915.
151—The Mystery of the Crossed Needles.
Dated August 7th, 1915.
152—The Forced Crime.
Dated August 14th, 1915.
153—The Doom of Sang Tu.
Dated August 21st, 1915.
154—The Mask of Death.
Dated August 28th, 1915.
155—The Gordon Elopement.
Dated Sept. 4th, 1915.
156—Blood Will Tell.

PRICE, FIVE CENTS PER COPY. If you want any back numbers of our
weeklies and cannot procure them from your news
dealer, they can be obtained direct from this office. Postage stamps taken
the same as money.

STREET & SMITH, Publishers, 79-89 Seventh Ave., NEW YORK CITY
*** END OF THE PROJECT GUTENBERG EBOOK NICK CARTER
STORIES NO. 155, AUGUST 28, 1915: THE GORDON
ELOPEMENT; OR, NICK CARTER'S THREE OF A KIND ***

Updated editions will replace the previous one—the old editions will
be renamed.

Creating the works from print editions not protected by U.S.


copyright law means that no one owns a United States copyright in
these works, so the Foundation (and you!) can copy and distribute it
in the United States without permission and without paying copyright
royalties. Special rules, set forth in the General Terms of Use part of
this license, apply to copying and distributing Project Gutenberg™
electronic works to protect the PROJECT GUTENBERG™ concept
and trademark. Project Gutenberg is a registered trademark, and
may not be used if you charge for an eBook, except by following the
terms of the trademark license, including paying royalties for use of
the Project Gutenberg trademark. If you do not charge anything for
copies of this eBook, complying with the trademark license is very
easy. You may use this eBook for nearly any purpose such as
creation of derivative works, reports, performances and research.
Project Gutenberg eBooks may be modified and printed and given
away—you may do practically ANYTHING in the United States with
eBooks not protected by U.S. copyright law. Redistribution is subject
to the trademark license, especially commercial redistribution.

START: FULL LICENSE


THE FULL PROJECT GUTENBERG LICENSE
PLEASE READ THIS BEFORE YOU DISTRIBUTE OR USE THIS WORK

To protect the Project Gutenberg™ mission of promoting the free


distribution of electronic works, by using or distributing this work (or
any other work associated in any way with the phrase “Project
Gutenberg”), you agree to comply with all the terms of the Full
Project Gutenberg™ License available with this file or online at
www.gutenberg.org/license.

Section 1. General Terms of Use and


Redistributing Project Gutenberg™
electronic works
1.A. By reading or using any part of this Project Gutenberg™
electronic work, you indicate that you have read, understand, agree
to and accept all the terms of this license and intellectual property
(trademark/copyright) agreement. If you do not agree to abide by all
the terms of this agreement, you must cease using and return or
destroy all copies of Project Gutenberg™ electronic works in your
possession. If you paid a fee for obtaining a copy of or access to a
Project Gutenberg™ electronic work and you do not agree to be
bound by the terms of this agreement, you may obtain a refund from
the person or entity to whom you paid the fee as set forth in
paragraph 1.E.8.

1.B. “Project Gutenberg” is a registered trademark. It may only be


used on or associated in any way with an electronic work by people
who agree to be bound by the terms of this agreement. There are a
few things that you can do with most Project Gutenberg™ electronic
works even without complying with the full terms of this agreement.
See paragraph 1.C below. There are a lot of things you can do with
Project Gutenberg™ electronic works if you follow the terms of this
agreement and help preserve free future access to Project
Gutenberg™ electronic works. See paragraph 1.E below.
1.C. The Project Gutenberg Literary Archive Foundation (“the
Foundation” or PGLAF), owns a compilation copyright in the
collection of Project Gutenberg™ electronic works. Nearly all the
individual works in the collection are in the public domain in the
United States. If an individual work is unprotected by copyright law in
the United States and you are located in the United States, we do
not claim a right to prevent you from copying, distributing,
performing, displaying or creating derivative works based on the
work as long as all references to Project Gutenberg are removed. Of
course, we hope that you will support the Project Gutenberg™
mission of promoting free access to electronic works by freely
sharing Project Gutenberg™ works in compliance with the terms of
this agreement for keeping the Project Gutenberg™ name
associated with the work. You can easily comply with the terms of
this agreement by keeping this work in the same format with its
attached full Project Gutenberg™ License when you share it without
charge with others.

1.D. The copyright laws of the place where you are located also
govern what you can do with this work. Copyright laws in most
countries are in a constant state of change. If you are outside the
United States, check the laws of your country in addition to the terms
of this agreement before downloading, copying, displaying,
performing, distributing or creating derivative works based on this
work or any other Project Gutenberg™ work. The Foundation makes
no representations concerning the copyright status of any work in
any country other than the United States.

1.E. Unless you have removed all references to Project Gutenberg:

1.E.1. The following sentence, with active links to, or other


immediate access to, the full Project Gutenberg™ License must
appear prominently whenever any copy of a Project Gutenberg™
work (any work on which the phrase “Project Gutenberg” appears, or
with which the phrase “Project Gutenberg” is associated) is
accessed, displayed, performed, viewed, copied or distributed:
This eBook is for the use of anyone anywhere in the United
States and most other parts of the world at no cost and with
almost no restrictions whatsoever. You may copy it, give it away
or re-use it under the terms of the Project Gutenberg License
included with this eBook or online at www.gutenberg.org. If you
are not located in the United States, you will have to check the
laws of the country where you are located before using this
eBook.

1.E.2. If an individual Project Gutenberg™ electronic work is derived


from texts not protected by U.S. copyright law (does not contain a
notice indicating that it is posted with permission of the copyright
holder), the work can be copied and distributed to anyone in the
United States without paying any fees or charges. If you are
redistributing or providing access to a work with the phrase “Project
Gutenberg” associated with or appearing on the work, you must
comply either with the requirements of paragraphs 1.E.1 through
1.E.7 or obtain permission for the use of the work and the Project
Gutenberg™ trademark as set forth in paragraphs 1.E.8 or 1.E.9.

1.E.3. If an individual Project Gutenberg™ electronic work is posted


with the permission of the copyright holder, your use and distribution
must comply with both paragraphs 1.E.1 through 1.E.7 and any
additional terms imposed by the copyright holder. Additional terms
will be linked to the Project Gutenberg™ License for all works posted
with the permission of the copyright holder found at the beginning of
this work.

1.E.4. Do not unlink or detach or remove the full Project


Gutenberg™ License terms from this work, or any files containing a
part of this work or any other work associated with Project
Gutenberg™.

1.E.5. Do not copy, display, perform, distribute or redistribute this


electronic work, or any part of this electronic work, without
prominently displaying the sentence set forth in paragraph 1.E.1 with
active links or immediate access to the full terms of the Project
Gutenberg™ License.
1.E.6. You may convert to and distribute this work in any binary,
compressed, marked up, nonproprietary or proprietary form,
including any word processing or hypertext form. However, if you
provide access to or distribute copies of a Project Gutenberg™ work
in a format other than “Plain Vanilla ASCII” or other format used in
the official version posted on the official Project Gutenberg™ website
(www.gutenberg.org), you must, at no additional cost, fee or expense
to the user, provide a copy, a means of exporting a copy, or a means
of obtaining a copy upon request, of the work in its original “Plain
Vanilla ASCII” or other form. Any alternate format must include the
full Project Gutenberg™ License as specified in paragraph 1.E.1.

1.E.7. Do not charge a fee for access to, viewing, displaying,


performing, copying or distributing any Project Gutenberg™ works
unless you comply with paragraph 1.E.8 or 1.E.9.

1.E.8. You may charge a reasonable fee for copies of or providing


access to or distributing Project Gutenberg™ electronic works
provided that:

• You pay a royalty fee of 20% of the gross profits you derive from
the use of Project Gutenberg™ works calculated using the
method you already use to calculate your applicable taxes. The
fee is owed to the owner of the Project Gutenberg™ trademark,
but he has agreed to donate royalties under this paragraph to
the Project Gutenberg Literary Archive Foundation. Royalty
payments must be paid within 60 days following each date on
which you prepare (or are legally required to prepare) your
periodic tax returns. Royalty payments should be clearly marked
as such and sent to the Project Gutenberg Literary Archive
Foundation at the address specified in Section 4, “Information
about donations to the Project Gutenberg Literary Archive
Foundation.”

• You provide a full refund of any money paid by a user who


notifies you in writing (or by e-mail) within 30 days of receipt that
s/he does not agree to the terms of the full Project Gutenberg™
License. You must require such a user to return or destroy all
copies of the works possessed in a physical medium and
discontinue all use of and all access to other copies of Project
Gutenberg™ works.

• You provide, in accordance with paragraph 1.F.3, a full refund of


any money paid for a work or a replacement copy, if a defect in
the electronic work is discovered and reported to you within 90
days of receipt of the work.

• You comply with all other terms of this agreement for free
distribution of Project Gutenberg™ works.

1.E.9. If you wish to charge a fee or distribute a Project Gutenberg™


electronic work or group of works on different terms than are set
forth in this agreement, you must obtain permission in writing from
the Project Gutenberg Literary Archive Foundation, the manager of
the Project Gutenberg™ trademark. Contact the Foundation as set
forth in Section 3 below.

1.F.

1.F.1. Project Gutenberg volunteers and employees expend


considerable effort to identify, do copyright research on, transcribe
and proofread works not protected by U.S. copyright law in creating
the Project Gutenberg™ collection. Despite these efforts, Project
Gutenberg™ electronic works, and the medium on which they may
be stored, may contain “Defects,” such as, but not limited to,
incomplete, inaccurate or corrupt data, transcription errors, a
copyright or other intellectual property infringement, a defective or
damaged disk or other medium, a computer virus, or computer
codes that damage or cannot be read by your equipment.

1.F.2. LIMITED WARRANTY, DISCLAIMER OF DAMAGES - Except


for the “Right of Replacement or Refund” described in paragraph
1.F.3, the Project Gutenberg Literary Archive Foundation, the owner
of the Project Gutenberg™ trademark, and any other party
distributing a Project Gutenberg™ electronic work under this
agreement, disclaim all liability to you for damages, costs and

You might also like