Clinical and CT imaging features of SARS-CoV-2 patients presented with diarrhea.

Dear Editor,

Graham et al. and colleagues have written to this journal reporting the clinical features and outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients in United Kingdom nursing homes. The results demonstrated that over half of the infected patients were asymptomatic or only had atypical symptom such as diarrhea and anorexia, indicating the possible viral transmission potential of these patients.

Here, we reported the clinical and compute tomography (CT) imaging features of SARS-CoV-2 patients presented with diarrhea at admission, to familiarize clinicians with clinical features of patients with this atypical symptom. Epidemiological, clinical, laboratory, CT characteristics, and outcomes events were obtained through detailed medical chart review between January 1st to February 10th, 2020 at the Renmin Hospital of Wuhan University. All patients were first screened by chest CT scan to identify pneumonia, and then confirmed as SARS-CoV-2 pneumonia by test of reverse transcription-polymerase chain reaction (RT-PCR) for SARS-CoV-2 RNA from paired nasopharyngeal swabs. Case definitions of confirmed patients were in accordance with the National guideline of China. Clinical data were double entered by two medical residents (PL and JH). CT data were reviewed and characterized following a standardized protocol, which has been previously described by us in details.

A total of 120 patients with confirmed disease were identified in this study, in which seven patients (6%) presented with diarrhea at admission. The distribution of clinical characteristics of study participants stratified by diarrhea was demonstrated in Table 1 . Patients with diarrhea were more likely to be older (59.7 vs. 44.5 years old, P = 0.012), had severe disease (71% vs. 22%, P = 0.011), and more likely to die after admission (43% vs. 7%, P = 0.017) than those without diarrhea. Hypertension (16%) and cardiovascular disease (8%) were the most common comorbidities among patients, however, there was no differences between these two groups of patients in distribution. Fever (68%), cough (63%), and myalgia (48%) were the most common symptoms for all patients. Headache (71% vs. 20%), sneeze (71% vs. 11%), and sputum production (57% vs. 7%) were mostly observed in patients presented with diarrhea, whereas the other symptoms did not show significant differences in distribution between two groups. For laboratory test, we found that deceased lymphocyte count (1.1 vs. 2.5, 109/L, P = 0.042) and elevated LDH level (413.3 vs. 221.9, U/L, P < 0.001) were more prevalent in diarrhea group. Regarding the CT features, the most frequent changes in CT scan were ground glass opacities (GGOs) (89%), linear densities (63%), and nodules (54%). More than half of all patients presented with bilateral lung abnormities. Patients with diarrhea were more likely to have air bronchogram (P = 0.003), diffuse disease extent (P = 0.029), and reticulation lung appearance (P = 0.021) compared to those without.

Table 1

Clinical features of patients with SARS-CoV-2 pneumonia by diarrhea at admission.

Characteristics	All	Diarrhea	No Diarrhea	Pa,b
	(N = 120)	(n = 7)	(n = 113)
Demographics
Survival status (alive,%)	109 (91%)	4 (57%)	105 (93%)	0.017
Severity (Severe,%)	30 (25%)	5 (71%)	25 (22%)	0.011
Age, mean (SD), years	45.4 (15.6)	59.7 (16.9)	44.5 (15.1)	0.012
Sex (male,%)	43 (36%)	2 (29%)	41 (36%)	1.0
Huanan seafood market exposure	3 (3%)	1 (14%)	2 (2%)	0.17
Current smoking (yes,%)	6 (5%)	0	6 (5%)	1.0
Comorbidity
Any comorbidity	32 (27%)	3 (43%)	29 (26%)	0.38
Number, mean (SD)	0.4 (0.8)	0.7 (0.9)	0.4 (0.8)	0.35
Diabetes	7 (6%)	1 (14%)	6 (5%)	0.35
Hypertension	19 (16%)	2 (29%)	17 (15%)	0.31
Cardiovascular disease	9 (8%)	1 (14%)	8 (7%)	0.43
COPD	4 (3%)	1 (14%)	3 (3%)	0.22
Malignancy	7 (6%)	0	7 (6%)	1.0
Chronic liver disease	1 (1%)	0	1 (1%)	1.0
Other disease	5 (4%)	0	5 (4%)	1.0
Laboratory findings
WBC, mean (SD), 109/L	5.0 (2.2)	4.7 (1.8)	5.0 (2.3)	0.68
Neu, mean (SD), 109/L	2.0 (1.7)	3.1 (2.2)	1.9 (1.7)	0.075
Lym, mean (SD), 109/L	2.4 (1.8)	1.1 (0.95)	2.5 (1.8)	0.042
LDH, mean (SD), U/L	235.6 (109.6)	413.3 (132.4)	221.9 (93.1)	< 0.001
Symptoms
Any symptom (yes,%)	104 (87%)	7 (100%)	97 (86%)	0.59
Fever (yes,%)	81 (68%)	7 (100%)	74 (66%)	0.095
Cough (yes,%)	75 (63%)	6 (86%)	69 (61%)	0.25
Dyspnea (yes,%)	38 (32%)	5 (71%)	33 (29%)	0.032
Myalgia or fatigue (yes,%)	57 (48%)	6 (86%)	51 (45%)	0.052
Headache (yes,%)	28 (23%)	5 (71%)	23 (20%)	0.008
Sneeze (yes,%)	17 (14%)	5 (71%)	12 (11%)	< 0.001
Sputum production (yes,%)	12 (10%)	4 (57%)	8 (7%)	0.002
Pharyngalgia (yes,%)	16 (16%)	0	16 (14%)	0.59
CT findings
Bilateral	68 (57%)	7 (100%)	61 (54%)	0.019
GGO	107 (89%)	7 (100%)	100 (89%)	1.0
Nodules	65 (54%)	3 (43%)	62 (55%)	0.70
Linear densities	75 (63%)	6 (86%)	69 (61%)	0.25
Crazy paving	30 (25%)	3 (43%)	27 (24%)	0.37
Bronchiectasis	14 (12%)	1 (14%)	13 (12%)	0.59
Effusion	9 (8%)	2 (29%)	7 (6%)	0.087
Lymphadenopathy	5 (4%)	1 (14%)	4 (4%)	0.26
Air bronchograms	24 (20%)	5 (71%)	19 (17%)	0.003
Tree-in-bud sign	9 (8%)	2 (29%)	7 (6%)	0.087
White Lung	20 (17%)	3 (43%)	17 (15%)	0.090
Consolidation	66 (55%)	6 (86%)	60 (53%)	0.13
Reticulation	22 (18%)	4 (57%)	18 (16%)	0.021

Abbreviation: SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; n, number of cases; SD, standard deviation; COPD: chronic obstructive pulmonary disease; WBC, white blood cell; Neu, neutrophil; Lym, lymphocyte; LDH, lactate dehydrogenase.

For categorical variables, P values were derived from χ2 test, Fisher's exact test. For continuous variables, P values were derived from t-test or Analysis of Variance (ANOVA).

P values for the comparison between patients with diarrhea and those without.

The association between selected variables and the severity of disease were further examined by multivariate logistic regression models in Table 2 . Significant associations were observed for those with older age (OR: 9.2, 95%CI: 2.8–30.2), pre-existing comorbidities (OR: 8.2, 95%CI: 2.3–28.9), elevated LDH level (OR: 6.2, 95%CI: 2.1–18.1), symptoms of dyspnea (OR: 29.6, 95%CI: 6.9–127.9), headache (OR: 5.0, 95%CI: 1.1–22.9), and those with air bronchogram (OR: 7.5, 95%CI: 0.85–67.3) in CT scans. Moreover, predictors for severe disease of SARS-CoV-2 pneumonia were more prevalent (All P values < 0.05) in patients presenting with diarrhea, patients with diarrhea were more likely to be older (57% vs. 16%), have elevated LDH level (86% vs. 20%,), have symptoms of dyspnea and headache (P < 0.05), and more CT presentation of air bronchogram.

Table 2

Final multivariate analysis of the association for selected characteristics with the severity of SARS-CoV-2 pneumonia.

Characteristics	Common	Severe	OR (95%CI)a	Pa	Diarrhea	No diarrhea	Pb
	(n = 90)	(n = 30)
Baselinec
Age (< 60 years as ref.)	6 (7%)	16 (53%)	9.2 (2.8–30.2)	< 0.001	4 (57%)	18 (16%)	0.021
LDH (< 250 U/L as ref.)	11 (12%)	18 (60%)	6.2 (2.1–18.1)	0.001	6 (86%)	23 (20%)	0.001
Comorbidityd
Any comorbidities (no as ref.)	10 (11%)	22 (73%)	8.2 (2.3–28.9)	0.001	3 (43%)	29 (26%)	0.38
Symptoms and signse
Dyspnea (no as ref.)	11 (12%)	27 (90%)	29.6 (6.9–127.9)	< 0.001	5 (71%)	33 (29%)	0.032
Headache (no as ref.)	10 (11%)	18 (60%)	5.0 (1.1–22.9)	0.037	5 (71%)	23 (20%)	0.008
CT findingsf
Air bronchogram (no as ref.)	5 (6%)	19 (63%)	7.5 (0.85–67.3)	0.071	5 (71%)	19 (17%)	0.003
Total severe score (mean, SD)	2.0 (1.5)	11.6 (6.2)	1.9 (1.3–2.9)	< 0.001	11.7 (6.1)	4.0 (5.0)	< 0.001

Abbreviation: SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; n, number of cases; LDH, lactate dehydrogenase.

Derived from multivariate analysis of logistic regression models.

P values were derived from χ2 test, P values for the comparison between patients with diarrhea and those without.

Retained in this model were age and LDH.

Retained in this model were age, any comorbidities, and LDH.

Retained in this model were age, LDH, dyspnea, and headache.

Retained in this model were age, LDH, air bronchogram, and total severe score.

In the current study, we systematically characterized the clinical features for SARS-CoV-2 pneumonia patients presented with diarrhea at admission. Consistent with the previous findings, , the main symptoms at presentation in this study were fever, cough, and myalgia, whereas the reported frequency of diarrhea among confirmed cases varied from 2% to 33%. The identified risk factors for severe disease in our study included the older age, an elevated LDH level, pre-existing medical comorbidity, the presentation of dyspnea and headache, and CT presentation of air bronchogram. These findings were consistent with the previous report. Although diarrhea was not statistically significantly associated with the risk of severe disease, Ji et al. found diarrhea (OR: 1.80, 95%CI: 1.06–3.03) was associated with elevated risk of severity after reviewing the published studies of SARS-CoV-2. Meanwhile, our findings were similar to the Jin et al. in that the survival status (43% vs. 7%, P = 0.017) and severity (71% vs. 22%, P = 0.011) of diarrhea group did show differences compared with non-diarrhea group. Moreover, the predictors identified in this study were found to be more prevalent in patients with diarrhea. Therefore, the consistent findings suggested SARS-CoV-2 pneumonia patients presented with diarrhea at admission had worse outcomes compared with those non-diarrhea patients.

In conclusion, we found SARS-CoV-2 pneumonia patients presented with diarrhea at admission were characterized by high prevalence of features for severe disease (older age, elevated LDH level, and comorbidities) and they recovered slowly. These findings should catch the clinicians’ attention. Increased clinical vigilance is warranted for SARS-CoV-2 pneumonia patients with diarrhea at admission.

Declaration of Competing Interest

The authors have nothing to declare.