Effect of Gastrointestinal Symptoms in Patients With COVID-19 (2020)

See Covering the Cover synopsis on page 2019. See Covering the Cover synopsis on page 2019. Because of accumulating evidence pointing to continuous person-to-person transmission of coronavirus disease 2019 (COVID-19) in hospital and family settings,1Chan J.F. et al.Lancet. 2020; 395: 514-523Abstract Full Text Full Text PDF PubMed Scopus (6268) Google Scholar,2Phan L.T. et al.N Engl J Med. 2020; 382: 872-874Crossref PubMed Scopus (825) Google Scholar the World Health Organization has recently declared COVID-19 a public health emergency of international concern. Fever and respiratory symptoms tend to be initial and major, whereas gastrointestinal (GI) symptoms were also observed in a significant portion of patients.3Huang C. et al.Lancet. 2020; 395: 497-506Abstract Full Text Full Text PDF PubMed Scopus (33292) Google Scholar Positive findings of reverse transcription polymerase chain reaction further showed that COVID-19 may spread by fecal-oral transmission.4Holshue M.L. et al.N Engl J Med. 2020; 382: 929-936Crossref PubMed Scopus (4317) Google Scholar In addition, recent studies have shown that the receptor of ACE2, which is essential for cells infected by COVID-19, is highly expressed not only in lung AT2 cells but also in absorptive enterocytes in the ileum and colon.5Gui M. et al.Cell Res. 2017; 27: 119-129Crossref PubMed Scopus (440) Google Scholar,6Zhang H. et al.bioRxiv. 2020; (https://doi.org/10.1101/2020.01.30.927806)Google Scholar These results further confirmed that the digestive system may be a potential route for COVID-19 infection. Therefore, a study exploring the correlation between GI symptoms and patients’ symptoms, diagnosis, treatment, and outcomes is of great importance to improve the diagnosis and treatment plan of novel coronavirus–infected pneumonia (NCIP). According to the clinical diagnostic standards in the “Diagnosis and Treatment of NCIP”7National Health Commission of China. The State Council's joint prevention and control mechanism for pneumonia epidemic in response to new coronavirus infection(5th edition). Chinese. http://www.nhc.gov.cn/jkj/s3578/202002/dc7f3a7326e249c0bad0155960094b0b.shtml. Accessed February 21, 2020.Google Scholar issued by the National Health Commission of the People’s Republic of China, suspected infected patients with clinical features of pneumonia could be regarded as clinically confirmed patients. The central hospital of Wuhan is one of the first major hospitals designated by the government to treat patients with NCIP. We enrolled 254 patients clinically confirmed with NCIP from December 20, 2019, through February 9, 2020. Medical staff and nonmedical staff are counted separately. Based on whether they had GI symptoms, patients were divided into GI symptom and non–GI symptom groups. The clinical characteristics, laboratory findings, complications, treatment process, and clinical outcomes were compared between the patients with or without GI symptoms. The epidemiologic, clinical, laboratory, and radiologic characteristics and treatment outcome data were obtained from medical records. All these data were reviewed by a group of experienced doctors. The recorded information includes medical history, symptoms, signs, potential comorbidities, laboratory findings, and treatment measures. Categorical variables are described by frequency and percentages, and continuous variables are described by the mean, median, and interquartile range. Patient characteristics were compared by using t tests for continuous variables and chi-squared or Fisher exact tests for categorical variables. All statistical analyses were performed using SPSS, version 23.0, software (SPSS, Chicago, IL). P ≤ .05 was considered statistically significant. As outlined in Table 1, this study recruited 254 clinically confirmed patients with NCIP (115 males and 139 females; mean age, 50.6 years; range, 15–87 years), including 93 medical staff and 161 nonmedical staff. Among all patients, 211 (83%), 98 (38.6%), and 66 (26%) complained of fever, cough, and GI symptoms, respectively. The most common complication was pneumonia (209; 82.3%), followed by arrhythmia (16; 0.06%) and shock (7; 0.03%). Patients receiving mechanical ventilation, antibiotics, antivirals, immunoglobulins, hormones, and extracorporeal membrane oxygenation (ECMO) treatment accounted for 7.09%, 97.6%, 75.6%, 59.8%, 88.2%, and 0.008% of the total patients, respectively. At of the end of observation, 46 patients were discharged, 16 died, and 192 continued treatment.Table 1Clinical Features, Treatment and Prognosis of Patients Infected With 2019-nCoVTotal (N = 254)Medical staffNonmedical staffTotal (n = 93)GI symptoms (n = 23)Non-GI symptoms (n = 70)P valueTotal (n = 161)GI symptoms (n = 43)Non-GI symptoms (n = 118)P valueGI symptoms, n (%)66 (26.0)2323 (100)0 (0)—4343 (100)0 (0)—Abdominal pain3 (1.2)00 (0)0 (0)—33 (7.0)0 (0)—Vomiting15 (5.9)11 (4.3)0 (0)—1414 (32.6)0 (0)—Diarrhea46 (18.1)1919 (82.6)0 (0)—2727 (62.8)0 (0)—Nausea21 (8.3)55 (21.7)0 (0)—1616 (37.2)0 (0)—Age, y, median (IQR)50 (36–65)36 (31–41)35 (30–40)36 (31–42).61462 (49–69)61 (49–67)62 (49–70).615Sex, n (%).45.033 Male115 (45.3)326 (26)26 (37)8316 (37)67 (57) Female139 (54.7)6117 (74)44 (63)7827 (63)51 (43)Symptom, n (%) Fever213 (83.9)8019 (83)61 (87).72913339 (91)94 (80).157 Sore throat16 (6.3)60 (0)6 (9).33106 (14)4 (3).023 Dry cough98 (38.6)417 (30)34 (49).1525714 (33)43 (36).712 Expectoration107 (42.1)316 (26)25 (36).4547617 (40)59 (50).286 Chest tightness67 (26.4)213 (13)18 (26).261468 (19)38 (32).115 Dyspnea10 (3.9)21 (4)1 (1).43582 (5)6 (5)> .99 Dizziness18 (7.1)104 (17)6 (9).25685 (12)3 (3).032 Headache28 (11.0)173 (13)14 (20).549113 (7)8 (7)> .99 Fatigue133 (52.4)5212 (52)40 (57).8098129 (67)52 (44).012 Myalgia86 (33.9)4110 (44)31 (44)> .994517 (40)28 (24).073Sign, median (IQR) MAP, mm Hg92 (85–96)90 (85–96)88 (83–98)92 (87–96).25293 (85–98)90 (85–98)93 (86–97).075 HR, beats/min85 (79–98)84 (80–100)82 (76–103)87 (80–100).30285 (78–98)86 (78–98)85 (78–98).902Comorbidities, n (%) Hypertension63 (24.8)60 (0)6 (9).335714 (33)43 (36).712 DM26 (10.2)30 (0)3 (4).572234 (9)19 (16).321 CHD17 (6.7)20 (0)2 (3)> .99156 (14)9 (8).231 Malignancy2 (0.8)10 (0)1 (1)> .9910 (0)1 (1)> .99 CKD0 (0)00 (0)0 (0)—00 (0)0 (0)— CVD13 (5.1)10 (0)1 (1)> .99123 (7)9 (8)> .99 CLD3 (1.2)10 (0)1 (1)> .9920 (0)2 (2)> .99 COPD6 (2.4)10 (0)1 (1)> .9952 (5)3 (3).61 HIV infection1 (0.4)00 (0)0 (0)—11 (2)0 (0).267Laboratory findings HB, g/L——112 (109.5–111)120.2 (112.5–127).104—116.7 (106–127)133 (114–141).028 WBC, ×10^9/L——5.5 (2.6–9.2)5.6 (3.2–6.5).962—5.9 (3.5–6.3)5.5 (3.3–6.7).708 Neutrophil, ×10^9/L——5.1 (1.3–7.2)5 (1.5–8).968—5.9 (1.7–9.9)7.6 (2.3–7.7).604 LYM, ×10^9/L——1.1 (0.7–1.2)1 (0.8–1.1).524—1 (0.7–1.1)0.8 (0.7–0.9).108 PLT, ×10^9/L——223 (86–408)184 (88–237).653—192 (111–248)176 (112–186).842 CRP, mg/dL——2.2 (0.7–2.6)3 (1–2.5).491—7.3 (2.9–6.6)3.8 (1.8–5.8).021 ALT, U/L——65.9 (23.3–103.3)75.6 (44.5–114.8).698—64.1 (51.2–64.4)46.6 (31.9–61.2).049 AST, U/L——26.4 (12.7–45.5)40.4 (12.9–65.3).271—47.8 (18.2–50.6)53.8 (35.7–58.5).44 Albumin, g/L——35.2 (34.5–38.1)36.7 (34.7–38.7).327—35.4 (33.9–36.4)35 (32.8–37.8).648 Globulin, g/L——39.7 (37.6–42)38.7 (30.7–43.8).766—26.1 (22.7–29.4)28.9 (25.3–31.6).185 LDH, U/L——156.2 (103–194.8)289 (229–370.3).069—358.9 (256–425)312.5 (251.5–335).322 CK, U/L——29.8 (15.8–35)398.5 (28.1–587.3).143—316.3 (86–276.5)201.3 (77.8–294.5).359 Creatinine, μmol/L——68 (64.2–75.5)67.6 (73.2–79.3).981—56.9 (43.9–72.1)70.1 (43.8–95.9).217 FBG, mmol/L——8 (6.2–8.7)7.7 (6.5–8.1).787—7.3 (6.3–8.2)8.3 (6.3–9.5).106 Na+, mmol/L——142.6 (139.3–145.8)134.2 (131–136.4).05—138.9 (134.8–141.9)139.3 (135–145.4).88 K+, mmol/L——3.9 (3.3–4)4 (3.2–4.5).934—3.3 (3.1–3.5)9.1 (3.2–4).052 PH——7.4 (7.4–7.5)7.5 (7.4–7.5).485—7.4 (7.5–7.5)7.4 (7.4–7.5).9Sao2, mmHg——91 (97–99)92 (91–99).962—93 (92–94)92 (91–97).796 Pao2, mmHg——74 (62–85)109 (52–151).256—84 (65–105)86 (62–113).809 Paco2, mmHg——42 (33–51)35 (31–39).263—35 (31–36)35 (31–35).777Complications, n (%) Pneumonia209 (82.3)7018 (78.3)52 (74.3).78713938 (88.4)101 (85.6).798 Shock7 (2.8)20 (0)2 (2.9)> .9951 (2.3)4 (3.4)> .99 AHF6 (2.4)11 (4.3)0 (0).24750 (0)5 (4.2).326 Arrhythmia16 (6.3)122 (8.7)10 (14.3).72441 (2.3)3 (2.5)> .99 ARDS5 (2)21 (4.3)1 (1.4).43531 (2.3)2 (1.7)> .99Treatment MV18 (7)51 (4.3)4 (5.7)> .99132 (4.7)11 (9.3).516 Antibiotics248 (97.6)9123 (100)68 (97.1)> .9915742 (97.7)115 (97.5)> .99 Antivirals192 (75.6)6316 (69.6)47 (67.1)> .9912931 (72.1)98 (83.1).179 Immunoglobulins152 (59.8)6219 (82.6)43 (61.4).079028 (65.1)62 (52.5).209 Hormones224 (88.2)7720 (86.9)57 (81.4).7514737 (86)110 (93.2).204 ECMO2 (0.8)21 (4.3)1 (1.4).43500 (0)0 (0)—Clinical outcome Discharge from hospital46 (18.1)324 (17.4)28 (40).075144 (9.3)10 (8.5)> .99 Staying in hospital192 (75.6)5918 (78.3)41 (58.6).13413336 (83.7)97 (82.2)> .99 Death16 (6.3)21 (4.3)1 (1.43).435143 (7)11 (9.3).457AHF, acute heart failure; ALT, alanine aminotransferase; ARDS, acute respiratory distress syndrome; AST, aspartate transaminase; CHD, coronary heart disease; CK, creatine kinase; CKD, chronic kidney disease; CLD, chronic liver disease; COPD, chronic obstructive pulmonary disease; CRP, C-reaction protein; CVD, cerebrovascular disease; DM, diabetes mellitus; ECMO, extracorporeal membrane oxygenation; FBG, fasting blood glucose; HB, hemoglobin; HR, heart rate; LDH, lactate dehydrogenase; LYM, lymphocyte count; MAP, mean arterial pressure; MV, mechanical ventilation; nCoV, novel coronavirus; PLT, platelet count; WBC, blood leukocyte count. Open table in a new tab AHF, acute heart failure; ALT, alanine aminotransferase; ARDS, acute respiratory distress syndrome; AST, aspartate transaminase; CHD, coronary heart disease; CK, creatine kinase; CKD, chronic kidney disease; CLD, chronic liver disease; COPD, chronic obstructive pulmonary disease; CRP, C-reaction protein; CVD, cerebrovascular disease; DM, diabetes mellitus; ECMO, extracorporeal membrane oxygenation; FBG, fasting blood glucose; HB, hemoglobin; HR, heart rate; LDH, lactate dehydrogenase; LYM, lymphocyte count; MAP, mean arterial pressure; MV, mechanical ventilation; nCoV, novel coronavirus; PLT, platelet count; WBC, blood leukocyte count. Among nonmedical staff, the proportion of GI symptoms in female patients was significantly higher than in male patients (62.8% vs 37.2%; P = .033). Clinical manifestations such as sore throat (P = .023), dizziness (P = .032), and fatigue (P = .012) were also more frequent in patients with GI symptoms. In addition, hemoglobin level in the GI symptom group was significantly lower than in the non–GI symptom group (116.7 [range, 106–127]g/L vs 133 [114–141]g/L, respectively; P = .028), whereas C-reactive protein (7.3 [range, 2.9–6.6]mg/dL vs 3.8 [range, 1.8–5.8]mg/dL, respectively; P = .021) and alanine aminotransferase (64.1 [51.2-64.4]U/L vs 46.6 [31.9-61.2]U/L, respectively; P = 0.049) levels were significantly higher than in the GI symptoms group. However, GI symptoms among medical staff were not significantly correlated with symptoms and laboratory findings. Finally, the GI symptom group appeared to have a similar rate of complications, treatment, and clinical prognosis as the non–GI symptom group among medical and nonmedical staff. The study suggests that GI symptoms are common clinical symptoms in patients with NCIP. Among nonmedical staff, women are more likely to have GI symptoms, accompanied by higher inflammatory levels and poorer liver function. However, no significant correlation between GI symptoms and clinical features was observed among medical staff. In addition, the clinical outcome and treatment of patients with NCIP were not associated with GI symptoms in either medical or nonmedical staff. A possible explanation for nonmedical staff with GI symptoms being more likely to have more symptoms and poorer liver function is the changes in the intestinal microecology under the dysfunction of the central nervous system. The infection of COVID-19 in intestinal tissues may lead to GI symptoms, such as diarrhea and abdominal pain. Metabolic disorders increase the absorption of harmful metabolites, which will affect the function of the central nervous system through the gut-brain axis and then lead to dizziness and fatigue. Disorders of intestinal metabolism further lead to more harmful metabolites that are harmful to liver tissue. The reason why medical staff are less susceptible to GI symptoms may be that most of the infected medical staff were younger nurses without comorbidities. In addition, there is less delay from the onset of symptoms to hospital admission. Taking these factors into consideration, we can hypothesize that most of the medical staff infected by COVID-19 had mild symptoms on the day of hospital admission. There are also some deficiencies in this study. First, the standard diagnosis of patients with NCIP is based on nucleic acid testing, but most cases in our study are clinically confirmed patients, which will inevitably lead to several patients without NCIP being included. Second, most patients were still hospitalized at the time of submission. Therefore, it is difficult to further assess the correlation between GI symptoms and clinical outcomes. Zili Zhou, MM, (Data curation: Lead; Formal analysis: Lead; Writing – original draft: Lead; Writing – review & editing: Lead); Ning Zhao, MM, (Data curation: Lead; Formal analysis: Lead; Writing – original draft: Equal; Writing – review & editing: Equal); Yan Shu, MB, (Data curation: Lead; Formal analysis: Equal; Writing – original draft: Equal; Writing – review & editing: Equal); Shengbo Han, MM, (Data curation: Equal; Formal analysis: Equal; Writing – original draft: Supporting; Writing – review & editing: Supporting); Bin Chen, MD, (Conceptualization: Lead; Methodology: Equal; Supervision: Equal); Xiaogang Shu, MD, (Conceptualization: Lead; Methodology: Lead; Supervision: Lead)