To date, no vaccine or specific antiviral treatment is yet available for COVID-19. The most effective control measures for the disease mainly depend on early diagnosis, strict patient quarantine, and close contact monitoring[1]. Thus, reliable and accurate diagnostic methods play a critical role in global disease control and prevention. Reverse transcription-polymerase chain reaction (RT-PCR) assays are widely used for the laboratory diagnosis of virus-borne diseases. As a molecular Nucleic Acid Test (NAT), RT-PCR has been approved by the FDA for diagnostic use, such as SARS-CoV-2, with higher sensitivities and specificities compared to other biochemical and immunological based assays. According to the SARS-CoV-2 technical guidance implemented by the Chinese National Health Committee, the open reading frame 1ab and nucleocapsid protein encoding genes are selected as targets for RT-PCR assay[2,3]. A positive result is reported if either of these genes is detected with a cycle threshold (Ct) value of less than 37.0. Negative results from nasal/pharyngeal swabs tested for SARS-CoV-2 are an important criterion for the assessment of medical care and discharge of hospitalized patients. However, from January 2020 to June 2020, we noted 22 atypical cases out of 314 cases in our clinical practice; these atypical cases showed positive NAT results in their fecal samples.