key: cord-1033373-9e4txeck
authors: Fu, Wei; Chen, Qian; Wang, Tao
title: Letter to the Editor: Three cases of re‐detectable positive SARS‐CoV‐2 RNA in recovered COVID‐19 patients with antibodies
date: 2020-05-05
journal: J Med Virol
DOI: 10.1002/jmv.25968
sha: 1667f6ad933323b00371b1640d9118262647345b
doc_id: 1033373
cord_uid: 9e4txeck

The number of hospitalized cases has declined significantly in Wuhan. However, there have been reports that several cases of re‐detectable positive SARS‐CoV‐2 RNA in recovered COVID‐19 patients, the potential reasons of re‐detectable positive patients remained elusive. Here, we report three confirmed cases of COVID‐19 whose IgM was negative and IgG was positive before the first discharge, while nasopharyngeal swab test of SARS‐CoV‐2 RNA turned positive again during hotel isolation. In addition, all three cases presented negative results for IgM antibodies and positive results for IgG antibodies during re‐admission period. These cases suggested that the reasons for re‐detectable positive patients with profile of antibodies may be related to several factors. It is necessary to quarantine COVID‐19 patients for 14 days after discharge, and the role of antibodies in anti‐SARS‐CoV‐2 warrants further investigation. This article is protected by copyright. All rights reserved.

Three re-admission patients with COVID-19 admitted to Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from Feb 12 to Mar 1, 2020. One of them was male and two were female. The ages of the patients was 36, 74 and 34 years old, respectively. These three patients were admitted to Tongji Hospital from Feb 12 to Mar 1, 2020 . Epidemiological data showed that all three patients had a long history of residence in Wuhan. Case 2 had a medical history of hypertension.The first onset date of these three patients was Jan 19 -Feb 8, 2020. All three patients presented with a fever, and two of them had a cough. Patients' body temperatures fluctuated within the range of 37.1-38.6 °C. The respiratory rate of three patients were 19, 20 and 17 per minute, respectively. The length of the first hospitalization of these three patients was 10 d, 16 d, and 10 d, respectively. Diagnosis of patients were confirmed by a positive SARS-CoV-2 RNA test [4] . All three patients had a chest CT scan and showed multiple patchy groundglass shadows in lungs. The re-admission of the three patients was from Mar 10 to Mar 20, 2020 due to positivity for the SARS-CoV-2 RNA test. During there re-admission period, the patient's temperature was normal and there was no special symptom. The respiratory rate of three patients were 20, 18 and 18 per minute, respectively. The time from the first discharge to the second admission was 7 d, 12 d, and 9 d, respectively. The length of the second hospitalization of Case 1 was more than 17 d while Case 2 was 16 d and Case 3 was 11 d.

The SARS-CoV-2 RNA test of all three patients was positive before being admitted to hospital. The results of SARS-CoV-2 RNA test during the two periods of hospitalization were shown in Table 1 . During the first hospitalization, physical examination revealed normal vital signs of three patients with oxygen saturation of 99%, 99%, 98%, respectively, while the patients were breathing ambient air. Some relevant auxiliary examinations such as blood routine, urine routine, stool routine, coagulation function, liver and renal function, electrolytes, inflammation indicators were completed and the results were normal. IgM test for respiratory syncytial virus, adenovirus, influenza A and Immunomodulators include Thymosin, Tocilizumab, Human immunoglobulin, and Human blood albumin. After the treatment, the symptoms of all three patients were alleviated, and they maintained normal body temperature. The dynamics of chest HRCT revealed gradual absorption of lung lesions, as shown in Figure 1 . Nasopharyngeal swab tests of SARS-CoV-2 RNA were performed repeatedly for surveillance, the results were negative for at least 2 consecutive times (sampling interval≥1d), which meets the discharge standards. All patients were isolated in hotel for two weeks after discharge. All three patients were observed in isolation hotel after the first discharge, and continuously treated with Traditional Chinese Medicine. Although no special discomfort was found, all patient's nasopharyngeal swab test of SARS-CoV-2 RNA were positive during the isolation. All three patients had no fever, only one patient has developed the symptom of cough.

After re-admission, CT examination showed that the lesions of all three patients were further absorbed compared with first hospitalization period, see First of all, these patients were isolated in a single room after being discharged, they were not exposed to new sources of infection. It is not proved that the patients had contagious virus by detection of specific gene fragments. The detoxification procedure does occur which will cause re-detectable positive SARS-CoV-2 RNA in recovered COVID-19 Accepted Article patients [6] . Furthermore, viral RNA detection is almost the only way to confirm the infection of SARS-CoV-2 in practice. However, various factors could lead to reduced sensitivity by RNA detection, such as sample type, specimen collection and transport, RNA extraction, detection reagents, and viral load, which proposes serious challenge to disease control [7] . Therefore, even if the RNA test is negative, it cannot be used as a basis for exclusion of COVID-19, and it needs to be comprehensively judged in combination with actual conditions. Lastly, with the continued passage of SARS-CoV-2, it may show a tendency of weakened toxicity and enter into a symbiosis between human and virus [8] . As a result, the recovered COVID-19 patients may become silent carriers.

Recent studies indicated that the concentration of antibodies in the plasma were independently associated with disease severity in COVID-19 patients [9,10]. However, these patients re-detectable positive for SARS-CoV-2 RNA displayed high levels of IgG and negative IgM in the plasma during two hospitalization periods. Future studies are needed to investigate humoral immune reaction to the SARS-CoV-2 virus.

This study was supported by grants from the general program of Health Commission of Hubei Province (WJ2019M137) and HUST COVID-19 Rapid Response Call (2020kfyXGYJ015).

This study was approved by the Ethics Committee of Tongji Hospital (TJ-IRB20200353). Patient identities were protected via anonymization, and the requirement for informed consent was waived due to the observational nature of the study.

We declare no competing interests. Table   Table 1 . Results of SARS-CoV-2 RNA and Antibody tests of re-admission patients 

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