key: cord-0699625-q4j1ne8j
authors: Kaiyasah, Hadiel; Fardan, Hana; Bashir, Oghowan; Hussein, Mawada; Alsubbah, Hamzeh; Dabal, Laila Al
title: Hepatic and Gastrointestinal manifestations in COVID-19 Patients and Its Relation to Disease Severity, single-center experience
date: 2022-04-02
journal: IJID Regions
DOI: 10.1016/j.ijregi.2022.03.025
sha: d48af22cc8e9aaf6e646c6662536cc18f29b6e6e
doc_id: 699625
cord_uid: q4j1ne8j

Background and Aim The outbreak of coronavirus disease (COVID-19) attributed to severe acute respiratory syndrome (SARS-CoV-2) virus emerged by late 2019. While the infection is commonly perceived as a respiratory disease, gastrointestinal complaints have been described in a significant number of patients since the beginning of the pandemic. In our research, we studied the prevalence of hepatic and gastrointestinal manifestations among infected patients in terms of symptoms and biochemical findings and its relation with COVID-19 disease severity and outcomes. Methods We retrospectively analyzed patients admitted to a tertiary medical center in Dubai, UAE, from March until June 2020, with COVID-19 infection. Patients were stratified into two main groups based on presence or absence of hepatic and gastrointestinal manifestations. Results Among 521 eligible patients, 119 patients (22.8%) had gastrointestinal (GI) manifestations and majority of patients were middle-age males (90%). The most common symptom was diarrhea followed by vomiting and abdominal pain and most commonly observed biochemical abnormality was raised alanine transferase. There was no difference in COVID-19 pneumonia severity score or overall mortality rates between two groups. However, patients with COVID-19 pneumonia even without any hepatic or GI manifestation had longer hospital stay (p<0.05) and other infection related complications. Conclusion Our paper adds to the literature information on the protean extra pulmonary manifestations of SARS-Cov 2 with a focus on hepatic and GI system. In our study, the presence of hepatic and GI manifestations in COVID-19 infected patients at the time of admission was not associated neither with increased pneumonia severity nor with overall mortality.

In our paper, we looked into the prevalence of hepatic and GI manifestations in terms of 89 symptoms and biochemical findings and its relation with COVID-19 disease severity and 90 outcomes among admitted patients to our hospital over four months' study period. 91 92 93 94 95

This is an analytical cross-sectional study conducted on 521 patients with infection who were admitted to Rashid Hospital, Dubai from the period of March until June 99 2020. Demographic data, clinical presentation and laboratory data were extracted from the 100 hospital electronic medical records (EPIC system) after obtaining ethical approval from the 101 Dubai Health Authority Ethical Review Board. Inclusion criteria were all adult patients above 102 the age of 18 years admitted with confirmed with SAR-S viral PCR test confirmed cases from 103

March until June 2020. Pregnant women, patients known to have inflammatory bowel disease or 104 chronic liver diseases were excluded from the study population. Patients were divided into two 105 main groups based on the presence or absence of gastrointestinal symptoms upon initial 106 assessment and admission to the hospital. 107

Statistical analysis was performed using IBM SPSS software version 26 (SPSS Inc., 109 Armonk, NY, USA). Descriptive summary statistics are presented as means and SD for 110 continuous variables and frequencies with percentages for categorical variables. Categorical period, which matched other regional and global reports over the same period. In addition, 189 mortality rates corresponded to the age distribution of ICU cases with 35 mortality cases (67.3%) 190 among 45-65 years' age group, 13 cases (25.5%) in patients below the age of 45 years, and 4 191 cases (7.7%) in above 65 years old group. As observed in other studies, age on its own 192 contributed to higher rates of ICU admission and subsequent mortality with p values below 0. 05. 193 Patients older than 65 had the seven times the odds for ICU admissions and six times the odds 194 for mortality . 195 There was no statistically significant association between the presence of GI 196 manifestation and ICU admission among our study patients with similar distribution between the 197 two groups (17.6% in patients with GI manifestation and 16.4% in patients without GI 198 manifestation) 199 200 The presence of other medical co-morbidities, mainly diabetes mellitus and hypertension 201 were associated with longer time for viral clearance (p<0.005) and it was not observed to be 202 statistically significant in those with GI manifestations of COVID-19 infection (p>0.05). 203

In regards to gastrointestinal (GI) involvement, none of the comorbidities is significantly 205 related to GI, whether adjusted for covariates or not, as indicated by almost all the p-values (> 206 .05). 207

Only procalcitonin and CRP are significantly related to GI (with p-values of the odds < .05). And 208 these odds are coming from significant models (equations of estimation) with p-values < .05. The 209 same can be seen for the adjusted results as well (Table-6) . 210

When it comes to hepatic involvement (HI), it was found that male gender and 212 dyslipidemia are associated with statistically significant risk, with (OR 2.5, P value 0.003) and 213 (OR 0.13, P value 0.001) respectively. The adjusted results are not far from the unadjusted in 214 terms of size and indication for both mentioned variables (Table-7 However, the models from which these 3 adjusted contributions to the odds come from, are 220 statistically significant (models of significance are < .05) and this is because the covariates 221 adjusted for, are making considerable effect on the severity (more than GI, diarrhea or HI) 222 (Table-8 In another large-scale systematic review and meta-analysis papers, data of 78 798 312 COVID-19 positive patients from 158 studies was analyzed in details. The most frequent GI 313 manifestations were diarrhea (16.5%, 95% CI 14.2% to 18.4%), nausea (9.7%, 95% CI 9.0% to 314 13.2%) and elevated hepatic enzymes (5.6%, 95% CI 4.2% to 9.1%). Overall mortality was 315 23.5% (95% CI 21.2% to 26.1%) whereas GI mortality were 3.5% (95% CI 3.1% to 6.2%). On 316 subgroup analysis, there was non-statistically significant associations between GI 317 symptoms/elevated liver enzymes and ICU admissions (OR=1.01, 95% CI 0.55 to 1.83). The GI 318 mortality was 10.8% (95% CI 7.8% to 11.3%) in the USA and 0.9% (95% CI 0.5% to 2.2%) in 319

Of clinical significance is the fact that GI symptoms tend to worsen with diseases progression 321 and this can be explained by several pathophysiological mechanisms 322

Other reported GI symptoms in COVID-19 patients are anosmia and dysgeusia 323 Patients who developed more than 5 times rise in transaminases were managed by 352 adjusting Favipiravir dose (e.g. 50% reduction in the dose) or stopping it if transaminase level 353 was more than 10% upper limit of normal. 354 355 In our study, we found that 22.8% (n=119) of the patients admitted with COVID-19 356 presented with GI manifestations. Diarrhea was the most common GI symptom in 10.9% (n=57), 357 followed by nausea/vomiting, anorexia and abdominal pain. Rarely, COVID-19 patients can 358 present with isolated GI symptoms without respiratory symptoms (Pan et al., 2020) , as reported 359 in our cohort with 1.9% (n=9). Our study shows that the incidence of GI symptoms in COVID-360 19 patients is 22.8%, which is lower than that reported by other studies in the USA and China in 361 the range of 50.5-61. 3% (Han et al., 2020; Pan et al., 2020 The raw data supporting the conclusions of this article will be made available by the authors, 407 without undue reservation. 408

The Dubai Health Authority Ethical Review Board approved this study while utilizing 410 anonymized and de-identified retrospective data collection and waived the requirement for 411 informed consent. 412

Coronavirus Infection 

Diarrhoea may be underestimated: a missing link in 2019 novel coronavirus

Manifestations and prognosis of gastrointestinal and liver involvement in patients with COVID-19: a systematic review and meta-analysis

Gastroenterological and hepatic manifestations of patients with COVID-19, prevalence, mortality by country, and intensive care admission rate: systematic review and meta-analysis

Clinical characteristics of COVID-19 patients with digestive symptoms in Hubei, China: a descriptive, cross-sectional, multicenter study

Prevalence and characteristics of gastrointestinal symptoms in patients with SARS-CoV-2 infection in the United States: a multicenter cohort study

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Amer Harky. COVID-19 and Multiorgan Response

Medicine (Baltimore)

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Review article: gastrointestinal features in COVID-19 and the possibility of faecal transmission

Continuous renal replacement therapy. All the laboratory values are represented as number and percentage

All authors have no conflicts of interest or financial ties to disclose. 414

☒ The authors declare that they have no known competing financial interests or personal 417 relationships that could have appeared to influence the work reported in this paper. 418

The authors did not receive any funding.