There has been increasing evidences express that SARS-CoV-2 RNA could be detected not only in respiratory tract but also in gastrointestinal tract [7, 13]. In this study, 1008 hospitalized severe COVID-19 patients were detected positive SARS-CoV-2 RNA in 12 types of specimens collected from respiratory tract, gastrointestinal tract, urinary system, blood, eyes, the nervous system and sweat. The nasopharyngeal swab specimens showed the highest positive rates (71.06%), followed by BALF (66.67%), oropharyngeal swab (30.77%), sputum (28.53%), blood (12.5%), stool (12.21%) and anal swab (11.22%). We also found the SARS-CoV-2 in urine (16.30%). These features of our results of the viral positive rate among various tissues were very different from a previous study[14]. In this study, the highest SARS-CoV-2 RNA positive rate was 71.06% in nasopharyngeal swab, followed by 66.67% in BALF, 30.77% in oropharynx swab, 28.53% in sputum, 16.30% in urine, 12.50% in blood, 12.21% in stool, 11.22% in anal swab, and 2.99% in corneal secretion. These results showed that the specimen should firstly collect nasopharyngeal swabs, followed by oropharyngeal swabs, and collect sputum, stool, anal swabs or blood. The specimen of BALF could be collected for patients with bronchial intubation in inpatient. The specimen of corneal secretion maybe collected if there were eye symptoms for the patients with suspected COVID-19.
The SARS-CoV-2 RNA was found turning back to positive in some patients after discharge for one month or longer time. It is urgent to know whether the recovery positive viral RNA is caused by second infection or resulted from uncured patient itself. Therefore, our data bring to the focus of discussion whether it is appropriate to perform viral RNA detection only in two consecutive respiratory specimens (at least 1 day of time interval of sampling) for patients who have reached the standards of quarantine time (14 days) after clinical cured and discharge after treatment [9]. In this study, the SARS-CoV-2 RNA was found in respiratory tract, gastrointestinal tract, urinary system, blood and eyes, which means this virus may appear almost everywhere in human body. So we selected seven types of specimens of nasopharynx swab, oropharynx swab, sputum, stool, anal swab, urine and blood to detect SARS-CoV-2 RNA simultaneously for 20 patients who were clinically cured but still in quarantine time based on the findings of organ infection with SARS-CoV-2 and the convenience of sample collection.
Among 20 discharged patients, 5 of them expressed both ORF1ab gene and N gene RNA positive, in which 2 cases showed positive in sputum, 1 case showed positive in nasopharynx swab, 1 case showed positive in anal swab, and 1 case in 3 specimens (nasopharynx swab, oropharynx swab and sputum) showed positive simultaneously. These 5 cases were diagnosed as carriers of SARS-CoV-2. This result showed that the SARS-CoV-2 recovery positive might indicate that patient had not been fully cured when discharged at that time, though it met the criteria of discharge. The results didn’t seem to support the possibility of reinfection of the virus. As a result, the current discharge criteria could be improved according to the clinical findings and the sole detection of SARS-CoV-2 RNA in respiratory tract specimen seemed inadequate. It is necessary to collect multiple types of specimens to detect the viral RNA before the discharge of the patients, though they may meet the criteria of clinical cure. Once the patient is detected positive for SARS-CoV-2 RNA in the quarantine time, another 14 days’ isolation will be recommended until viral RNA become negative in all of 7 types of the specimens.
The 7 types of specimens that we used in this study may be a good choice, but if the patients have other concurrent diseases, it may also enlarge the scope of additional enrolled specimens to study. Moreover, a larger sample needs to be enrolled to exclude the possibility of peritoneal fluid and CSF containing the SARS-CoV-2 RNA in our cohort. In addition to the 5 cases, another 1 case (P8 at table 2) was only detected ORF1ab gene RNA from nasopharynx swab and N gene RNA from oropharyngeal swab in the quarantine time, this patient did not meet the criteria of viral carrier. This may suggest that SARS-CoV-2 virus is dead and is being cleared by the patients. It is known that false negative of RNA detection in respiratory tract specimens is unavoidable in the severe patients[15]. Therefore, multiple types of specimen should be analyzed simultaneously to exclude the possibility of the discharge patients as the source of infection again.