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 Digestive and Liver Disease 52 (2020) 1403–1406

Contents lists available at ScienceDirect

Digestive and Liver Disease

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

Correspondence

Hospitalized coronavirus disease-2019 (COVID-19) patients Table 1

Baseline characteristics.
with gastrointestinal symptoms have improved survival to
discharge
Variables Number Percent
Dear Editor Survived to Discharge Yes 497 [67.7]
No 237 [32.3]
The coronavirus disease-2019 (COVID-19) has become a global Sex Women 355 [48.4]
Men 379 [51.6]
pandemic affecting over 192 countries [1]. It is caused by the
Any GI Symptoms on Admission Yes 231 [31.5]
severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), No 503 [68.5]
which enters cells via interactions with angiotensin converting en- Nausea Yes 109 [14.9]
zyme II (ACE2) receptors that line the respiratory tract, esophagus, No 625 [85.1]
Vomiting Yes 62 [8.45]
ileum and colon, thereby providing a potential means for fecal-oral
No 672 [91.6]
transmission [2]. Concurrent gastrointestinal (GI) complaints have Abdominal Pain Yes 68 [9.26]
been reported in up to 61% of COVID-19 patients [3], and early re- No 666 [90.7]
ports from Asian populations suggested that hospitalized COVID- Diarrhea Yes 149 [20.3]
19 patients with concurrent GI symptoms require more antibiotics No 585 [79.7]
Hematemesis Yes 4 [0.545]
and have worse coagulopathy compared to those without GI symp-
No 730 [99.5]
toms [4]. Hematochezia Yes 12 [1.63]
We undertook a mortality analysis of COVID-19 patients hos- No 722 [98.4]
pitalized at our New York City (NYC) hospital at the height of Underlying Hypertension Yes 494 [67.3]
No 240 [32.7]
the pandemic to determine whether or not the presence of gas-
Underlying Chronic Renal Insufficiency Yes 174 [23.7]
trointestinal symptoms was associated with patient survival to dis- No 560 [76.3]
charge. Our primary endpoint was survival to discharge with and Underlying History of Coronary Artery Disease Yes 281 [38.3]
without the presence of GI symptoms upon admission, which in- No 452 [61.7]
cluded nausea, vomiting, hematemesis, abdominal pain, diarrhea, Underlying History of Diabetes Mellitus Yes 319 [43.5]
No 415 [56.5]
and hematochezia.
Underlying Chronic Lung Disease Yes 138 [18.8]
We performed a retrospective review of the electronic health No 596 [81.2]
records (EHR) of all adults aged 18 years and above who have Underlying Autoimmune Disease Yes 74 [10.1]
tested positive on nasal swabs for SARS-CoV-2 polymerase chain No 660 [89.9]
Underlying Chronic Liver Disease Yes 26 [3.54]
reaction (PCR) and required hospital admission. We identi-
No 708 [96.5]
fied patients with assistance from our institutional information Active Neoplastic Disease Yes 27 [3.7]
technology (IT) department and utilization of the international No 703 [96.3]
classification of diseases code 10th Revision (ICD-10) U07.1. Data
abstraction from the EHR was uniform for all patients. We col-
lected demographic data, vital status, and clinical history, among
other variables, listed in Table 1. Our study period was from without GI symptoms after adjusting for significant variables iden-
our institution’s first positive SARS-CoV-2 PCR test on 10 March tified with univariable analysis. A two-tailed p-value <0.05 was
2020 through 13 April 2020, with follow-up to 30 April 2020. We considered statistically significant.
obtained approval from our hospital’s Institutional Review Board To corroborate our findings, we also used predictive analysis,
(IRB-1591128–1). We excluded patients ≤ 17 years of age, those which is a technique that allows direct estimation of relevant prob-
still hospitalized at time of analysis, those who tested positive for abilities, in this case survival to discharge. This technique provided
COVID-19 but who did not require hospitalization, and persons direct probabilities of survival to discharge based upon the demo-
under investigation for COVID-19 who tested negative despite graphic and clinical variables of interest. The predictive models are
having typical COVID-19 symptoms. presented in plots that depict the probability of surviving at each
We used Chi-square tests to compare the survival percentages age level therefore there are no confidence bounds or p-value in-
between those with and without GI symptoms. T-tests were used volved. The models were then expanded to incorporate those with
to examine continuous variables and their relationship to survival. and without GI complaints on admission. Since predictive analy-
We utilized multivariable Cox proportional hazard regressions to sis gives direct probabilities, there are no confidence bounds or p-
calculate hazard ratios (HR) for mortality for patients with and values involved. All analyses were carried out in R version 3.6.3

https://doi.org/10.1016/j.dld.2020.08.043
1590-8658/© 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
1404 Correspondence / Digestive and Liver Disease 52 (2020) 1403–1406

Table 2
Predictors of in-hospital mortality.

P-Value (Chi-Squared Probability of Survival

Variables Survived to Discharge? Analysis) (Predictive Analysis)

Yes No

Total 497 237 N/A N/A

Any GI Symptoms Yes 169 62 0.04 0.75
No 328 175 0.65
Underlying Hypertension Yes 317 177 0.004 0.64
No 180 60 0.75
Underlying Chronic Renal Yes 104 70 0.013 0.60
Insufficiency No 393 167 0.72
Underlying History of Coronary Yes 156 125 <0.001 0.55
Artery Disease No 340 112 0.75
Underlying History of Diabetes Yes 198 121 0.005 0.63
Mellitus No 299 116 0.72
Underlying Chronic Lung Disease Yes 87 51 0.23 0.63
No 410 186 0.70

Fig. 1. Adjusted survival analysis by presence of gastrointestinal (GI) symptoms on admission

(R Foundation for Statistical Computing, Vienna, Austria) using the for COVID-19 patients with GI symptoms 0.66 (95% CI, 0.49–0.89;
rstanarm version 2.18.2, and models fit using default priors and p = 0.01). There were no statistically significant differences in mor-
10,0 0 0 iterations per chain, 4 chains per model until convergence tality based on individual GI symptoms, specifically nausea, vomit-
was reached. ing, abdominal pain, or diarrhea. Our predictive models found that
During the study period of 3/10/20 through 4/13/20, over 30 0 0 lack of GI symptoms portended lower survival at all ages within
patients tested positive for SARS-Cov-2 at our institution, of whom our cohort. Our findings are shown in Table 2. In-hospital mortal-
865 were adults who required hospitalization. We excluded 131 ity based upon our multivariable Cox proportions and presence of
patients who remained hospitalized at the end of the study pe- GI symptoms are presented in a Kaplan-Meier graph and predictive
riod, thus leaving 734 patients in our analysis. Our cohort included model in Figs. 1-2.
355 women (48.4%), 372 Blacks (50.7%), 214 whites (29.2%), and The presence of GI symptoms was associated with reduced in-
92 Hispanics (12.5%). The mean age for the cohort was 66.1 years hospital mortality.
± 15.6 (median 68 years, range 18–99 years). Our cohort’s baseline In our cohort. This association may hint at a crucial characteris-
characteristics are summarized in Table 1. tic about SARS-CoV-2 and its route of infectivity. We surmise that
A total of 231 patients (31.5%) were documented to have GI SARS-CoV-2 may be transmitted via fecal-oral route in addition to
symptoms on admission. The presence of GI symptoms was sig- the well-established respiratory droplet route, and this fecal-oral
nificantly associated with survival to discharge (169/231, 73.2%) transmission may lead to a milder form of COVID-19. Researchers
when compared to those without GI symptoms (328/503, 65.2%; have detected live SARS-CoV-2 in saliva via viral culture as well
p = 0.04). This finding persisted after multivariable analyses ac- as in stool samples [5]. Nobel’s group found that gastrointestinal
counting for the presence of underlying coronary artery disease symptoms increased likelihood of positive SARS-CoV-2 testing by
(CAD), diabetes mellitus (DM), hypertension (HTN), and chronic 70% [6]. Wei, et al. found that diarrhea was associated with de-
kidney disease (CKD), with hazard ratio for in-hospital mortality tection of SARS-CoV-2 in stool despite negative nose swab testing
 Correspondence / Digestive and Liver Disease 52 (2020) 1403–1406 1405

Fig. 2. Predictive probability of COVID survival with age & GI symptoms

[7], a finding later corroborated in a pooled meta-analysis from bias our sample because we could not exclude the mortality
Hong Kong [3]. More recently, Lamers, et al. have demonstrated risk of hospitalized patients associated with the aforementioned
that SARS-CoV-2 readily infects human small intestinal organoids variables.
and that the intestinal epithelium supports viral replication [8]. We have a sizable U.S.-based cohort from when NYC was the
These findings suggest that, despite negative respiratory testing, pandemic’s epicenter that nonetheless highlights a potential role
SARS-CoV-2 shedding may still be present via the GI tract and can for the digestive system in COVID-19 transmission and hospitaliza-
potentially act as a nidus for asymptomatic spread and may pro- tion outcomes. We look forward to studies that will further eluci-
vide a milder disease course. date the fecal-oral transmission route of SARS-CoV-2.
Our findings are dissimilar to what Wan, et al. found, specifi-
cally that diarrhea was associated with higher in-hospital mortal- Author Contributions
ity, but their study limited GI symptoms of interest to diarrhea,
and their symptomatic sample size was both smaller–49 patients— Intellectual genesis: BDR, DSJ; Data extraction and cleaning:
and included only 6 deaths [9]. In contrast, our study included BDR, NK, KC, EB, DSJ; Statistical consultation and formal data anal-
both upper and lower GI complaints and our univariable analy- ysis: WMB; Data interpretation: BDR, DSJ; Manuscript writing:
sis revealed a numerical increase in survival to discharge among BDR, WMB, DSJ; Critical manuscript review and editing: BDR, DSJ.
our 149 patients with diarrhea compared to those without (74% vs All authors approved the final draft as submitted.
66% respectively, p = 0.09). Virologic studies have also revealed that
early transmission of COVID-19 in NYC originated in Europe, not in
Financial Support
Asia, which could account for differences in disease severity from
those reported in China [10].
None
Despite our best efforts to incorporate multivariable analysis,
the retrospective design allows for selection bias and potential
Declaration of Competing Interest
confounders. We limited our focus to those requiring hospitaliza-
tion. We did not obtain prognostic index scores such as Acute
None
Physiology and Chronic Health Evaluation II (APACHE II) due to
inconsistent documentation at the onset of the pandemic. We
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