Systematic Review With Meta-analysis

SARS-CoV-2 Stool Testing and the Potential for Faecal-oral Transmission

Amarylle S. van Doorn; Berrie Meijer; Chris M. A. Frampton; Murray L. Barclay; Nanne K. H. de Boer

Disclosures

Aliment Pharmacol Ther. 2020;52(8):1276-1288. 

In This Article

Results

Search Strategy

The search strategy resulted in 300 articles suitable for title and abstract screening. After the exclusion of articles which met the exclusion criteria, we included a total of 95 articles for final analysis. Figure 1 shows details of the selection procedure.

Figure 1.

Flowchart of included articles

The majority of the included studies were performed in China (74 (77%)), other studies were conducted in Korea (6), Singapore (2), the United States of America (5), Italy (4), France (1), Germany (1), Thailand (1) and Austria (1). All included studies had a case report/case series design. In most study populations, the subpopulation on which stool and/or anal testing were conducted was considerably lower. In total, stool samples or anal swabs (from now on collectively named as GI specimens) from 2175 patients were tested for SARS-CoV-2 RNA. Four studies were included for qualitative analysis, but due to the lack of necessary (follow-up) information, these studies were excluded before final quantitative analysis.[17–20] Therefore, 2149 patients were included for final analysis.

In 23 studies, only children were included, of which four studies did not specify the age of included children. In 43 studies, only adults were included, whereas 12 studies included both children and adults. In the remaining 17 studies, the range of age was not reported. Detailed study characteristics are depicted in Table 1 and Table 2, with subdivision by study population size (Table 1: n < 10 and Table 2: n ≥ 10).

Test Characteristics

Seventeen (18%) studies tested SARS-CoV-2 presence in anal swabs and 81 (85%) in stool samples. In three studies, both specimens were tested. In all studies but one, real-time reverse transcription polymerase chain reaction (RT-PCR) was used to detect SARS-CoV-2. One study performed inoculation of stool suspension into Vero cells followed by virus detection through electron microscopy.[21]

Outcomes

In 91/95 (96%) of the included studies, SARS-CoV-2 RNA was identified in GI specimens from at least one of the included patients (Table 1 and Table 2). In total, 934 patients had one or more positive GI specimens (43%). A meta-analysis performed on studies with at least 10 patients showed a pooled positive proportion of 51.8% (95%CI 43.8 - 59.7%; Figure 2; Supplementary Table 1). It has to be mentioned that there is a significant amount of heterogeneity among the included studies, with an I2 of 91.9%. SARS-CoV-2 RNA was detected in GI specimens up to a maximum of 70 days after the onset of symptoms and 26 days after discharge from hospital.[22,23] In total, 42 studies reported the maximum days of GI specimen positivity after symptom onset or first positive test in any specimens, with a mean of 25.0 (range 3–70) days after symptom onset.

Figure 2.

Meta-analysis of included articles. The proportion positive shows the number of tests positive for SARS-CoV-2 divided by the total number of tests. Bars show 95% CI indeed. Data are further specified in Supplementary Table 1

In 22 patients (1%), infection with COVID-19 would not have been diagnosed without GI specimens testing, meaning these patients had negative results in every other specimen type tested and would not have been confirmed as carriers of the virus otherwise.[19,24–28]

Out of 54 studies with serial SARS-CoV-2 RNA test results for both respiratory and GI specimens, 49 (91%) studies reported persistently positive tests for SARS-CoV-2 RNA in GI specimens after respiratory specimens had become negative. Almost two thirds of the patients (282/443 (64%)) who had a positive GI specimen test had persistent positive GI specimen tests despite negative respiratory tests. The mean duration of positive GI testing after negative respiratory testing was 12.5 days. The maximum duration of positive GI testing after negative respiratory testing was 33 days.[13] Interestingly, several studies reported patients with ongoing positive GI specimen tests after hospital discharge.

Detectability of SARS-CoV-2 RNA depends on the type of specimen tested during different stages of the disease (eg respiratory or faecal sample). In most studies in which serial measurements took place, it was reported that viral RNA was more likely to be detected in respiratory tract samples during an early stage of the disease, whereas GI specimens were more likely to be positive later on during the disease.[12–14,22,29–37]

Twelve studies discussed the association between positive GI specimens and GI symptoms.[13,14,19,38–46] In all studies, the majority of patients with GI symptoms tested positive in GI specimens, but the association was not statistically significant in most studies. In the study by Han et al, it was observed that patients with GI symptoms were significantly more likely to test positive for SARS-CoV-2 in a stool test (P = 0.033).[44] Furthermore, Cheung et al found that the proportion of positive stool tests and the stool viral load was higher in patients with diarrhoea than without (P = 0.019 and 0.06 respectively).[46]

In addition to the clinical symptoms and the positive GI specimens testing, two studies detected SARS-CoV-2 RNA in endoscopic specimens of the oesophagus, stomach, duodenum and rectum in 1/1 and 2/6 patients.[41,45] Viability of SARS-CoV-2 was investigated and detected in five studies, in which six patients (6/17 (35%)) had live active virus in their GI specimens using Vero cell testing.[19,21,47–49]

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