Seven discharged patients turning positive again for SARS-CoV-2 on quantitative RT-PCR

To the Editor:

Since December 2019,the outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has gradually become a global health concern.¹ As of March 23, 2020, 332,930 people had a confirmed infection and 14,510 people died worldwide.² Up to now, respiratory droplets and close contact were considered as the major transmission route of COVID-19.³ Here, we report the clinical and epidemiological characteristics of 7 discharged patients who turned positive again (named as turn-positive patients) for SARS-CoV-2 on quantitative RT-PCR (qRT-PCR). The detailed timeline is presented in Appendix 1.

On January 17, 2020, patient 1 (male, 67-year-old), who had travelled from Wuhan (Hubei, China) to Guangzhou (Guangdong, China), had a fever (37.8°C) and cough with abnormal chest X-ray images, and his throat swab was positive on qRT-PCR (January 24). Patient 2 (son-in-law of patient 1) had a fever (38.9°C) and chills but no cough with normal X-ray and positive throat swab (January 24). Patient 3 (wife of patient 1) had no fever (37.0°C) but cough, expectoration, normal X-ray, and positive throat swab (January 27). Patient 4 (grandson of patient 1) had no fever (36.3°C) but cough, normal X-ray, and positive throat swab (Jan 27). All patients were successively admitted to our hospital. After treatment for 18 days (patient 1 and 2), 19 days (patient 3), or 12 days (patient 4), they were discharged with no symptoms and normal imaging and qRT-PCR results (discharge criteria).⁴ On February 19, patient 1 was readmitted to our hospital with no symptoms but abnormal computed tomography (CT) images and positive qRT-PCR results. On Feb 22, patient 2, 3, and 4 were readmitted to our hospital with no symptoms, normal (patient 4) or abnormal CT images (patient 2 and 3), positive nasal swab but negative throat or anal swab on qRT-PCR. During the second hospitalization, nonorganic insomnia and increased anxiety was observed in patients 2 and 3. After treatment for 6 days(patient 1), 5 days(patient 2 and 4), or 7 days(patient 3), they were discharged but quarantined in our hospital.

On January 24, patient 5 (female, 38-year-old), who returned to Guangzhou from Wuhan and on January 29, patient 6 (male, 29-year-old), whose father had returned to Guangzhou from Wuhan, presented with fever (37.5°C and 38.2°C, respectively) but no cough and had normal X-ray but positive throat swab. Patient 7 (female, 21-year-old) had a fever (37.3°C), itchy throat but no cough, normal X-ray but positive qRT-PCR results (January 31). Patients 5, 6, and 7 were admitted to our hospital. After treatment for 18 days (patient 5), 17 days (patient 6), or 15 days (patient 7), they met the discharge criteria and were discharged. Patients 5 and 6 moved to a hotel, whereas patient 7 went home. On February 22, patient 5 was readmitted to our hospital with no symptoms and normal X-ray but positive throat swab. On February 26, patient 6 was readmitted to our hospital with no symptoms, normal CT, and negative throat swab but positive anal swab. On February 24, patient 7 was readmitted to our hospital with no symptoms but abnormal CT, positive nasal swab but negative throat or anal swabs. During treatment, negative throat swab but positive anal swab was observed on patient 5 (February 24) and patient 6 (February 27, February 28, March 2, March 3, and March 4). After treatment for 8 days (patient 5), 10 days (patient 6), or 5 days (patient 7), they were discharged but quarantined in our hospital.

These cases highlight important issues that need our immediate attention. First, all 7 turn-positive patients had shorter hospital stays, lower medical costs, and milder symptoms in their second hospital visit than in their first-time hospitalization (Appendix 2). These findings may be attributed to convalescent plasma as a potential therapy for SARS-CoV-2 infection,⁵ which will be beneficial in the fight against COVID-19. Second, positive anal swab but negative throat swab was observed in 2 turn-positive patients (patient 5 and 6), and the diagnostic value of anal swab test in late stage of infection requires further investigation. Meanwhile, fomite transmission and environmental contamination by COVID-19 patients should not be ignored.6, 7, 8 Imaging examination and qRT-PCR results were sometimes inconsistent, and therefore, a combination of these methods should be used for diagnoses.⁸ Four of the turn-positive patients (patient 1-4) were from one family, suggesting that the occurrence of turn-positive patients in family cluster is a non-negligible phenomenon. Furthermore, we should consider the possibility that the turn-positive patients were not completely cured the first time and were discharged based on a false-negative diagnostic test. To avoid false-negative diagnosis of positive patients, diagnostic tests with high specificity and sensitivity are urgently needed. Finally, nonorganic insomnia and increased anxiety was observed in 2 turn-positive patients (patient 2 and 3) indicating that timely mental health care for the SARS-CoV-2 infected patients is urgently needed,⁹ especially turn-positive patients who require rehospitalization and medical observation for 14 days after discharge.¹⁰

As a new infectious disease, the pathogenesis and epidemiological and clinical characteristics of SARS-CoV-2 infection is still not well understood.^{1 , 10} Further studies on turn-positive patients infected with SARS-CoV-2 will deepen our understanding of the whole process of occurrence, development, and transformation ofCOVID-19.

Appendix. SUPPLEMENTARY MATERIALS

Fig 1. Detailed timeline of the seven turn-positive patients infected with severe acute respiratory syndrome corona virus 2 (SARS-C oV-2). Days of first-time (Red rectangle), Days of home quarantine after discharge (Blue rectangle), Days of second hospitalization(Light red rectangle), Days of quarantine at the medical institution after discharge(Light blue rectangle) are shown. PCR, polymerase chain reaction; CT, computed tomography.