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. 2020 Oct 8;93(3):1221–1224. doi: 10.1002/jmv.26568

Surveillance and re‐positive RNA test in patients recovered from COVID‐19

Junjie Hu 1, Shi Li 2, Yan Wu 3, Zhiguo Xiong 1, Yichen Yang 4, Lichong Gong 5, Fei Tian 6,
PMCID: PMC7646640  PMID: 32990948

To the Editor,

Previous studies suggested that several recovered COVID‐19 patients may still be virus carriers after discharge from the hospital. 1 , 2 Few observational follow‐up studies had been reported. We identified a series of redetectable positive subjects from recovered mild patients.

We prospectively collected 144 hospitalized COVID‐19 patients treated at Wuhan Fangcang Hospital from February 2, 2020 to February 24, 2020. According to the guideline published by the National Health Commission of China, 3 discharge criteria were: (i) no fever more than 3 days; (ii) respiratory symptoms improved significantly; (iii) acute exudative lesions diminished by imaging examination; (iv) two consecutive negative detection of SARS‐CoV‐2 by respiratory tract samples with more than 24‐h interval. Every patient discharged was required strict 14 days isolation and RNA retest (Fluorescence quantitative polymerase chain reaction; Applied Biosystems) every 3 weeks. The epidemiological, laboratorical, and imaging data were collected and presented with a median (interquartile range [IQR]) or mean ± standard deviation. The last follow‐up date is July 20, 2020.

Five patients were transferred to a tertiary hospital for further treatment because of severe anemia, acute myocardial infarction, refractory hypoxemia, and gross hematuria. Twenty‐two cases were lost follow‐up or did not underwent RNA retest. The majority of the remaining 117 subjects were female (58.1%), with a median age of 49.00 years (IQR: 42.00–59.00; Table 1). Mean values of blood oxygen saturation upon hospitalization were 96.64 ± 1.46%. Routine laboratory examination showed white blood cells at normal range in 114 (97.4%) patients, lymphocytopenia in 28 (23.9%) patients, eosinophilic granulocytopenia in 49 (41.9%) patients, and elevated C‐reactive protein in 30 (25.6%) patients. Fifty‐eight (49.6%) cases demonstrated bilateral ground‐glass opacities and segmental consolidation in initial computed tomography (CT) images. After admission, 97 (82.9%) patients received antiviral drugs therapy, including oseltamivir (75 mg per 12‐h, orally), and arbidol (200 mg three times daily, orally). Sixty‐four (57.3%) patients were administrated Chinese medicine therapy synchronously. The median duration from admission to discharge was 13.0 (10.8–15.0) days.

Table 1.

Clinical characteristics of 117 patients with COVID‐19

Variables All patients (n = 117) Repositive patients (n = 8) Negative patients (n = 109) P Value
Age (mean ± SD) 49.32 ± 11.93 46.25 ± 17.70 49.55 ± 11.48 .6186
Range 11–72 11–65 16–72
≤50 62 (53.0%) 4 (50.0%) 58 (53.2%)
50–60 32 (27.4%) 3 (37.5%) 29 (26.6%)
60–70 22 (18.8%) 1 (12.5%) 21 (19.3%)
70–80 1 (0.9%) 0 (0.0%) 1 (0.9%)
>80 0 (0.0%) 0 (0.0%) 0 (0.0%)
Gender .1695
Men 49 (41.9%) 1 (12.5%) 48 (44.0%)
Women 68 (58.1%) 7 (87.5%) 61 (56.0%)
Marriage .5874
Married 55 (47.0%) 5 (62.5%) 50 (45.9%)
Unmarried 62 (53.0%) 3 (37.5%) 59 (54.1%)
Occupation .8611
Farmer 0 (0.0%) 0 (0.0%) 0 (0.0%)
In service 68 (58.1%) 4 (50.0%) 64 (58.7%)
Unemployed 10 (8.5%) 1 (12.5%) 9 (8.3%)
Retired 39 (33.3%) 3 (37.5%) 36 (33.0%)
SaO2 on admission (mean ± SD) 96.64 ± 1.46% 97.13 ± 0.99% 96.61 ± 1.49% .2013
Symptoms onset
Fever 75 (64.1%) 6 (75.0%) 69 (63.3%) .7765
Cough 20 (17.1%) 2 (25.0%) 18 (16.5%) .8974
Myalgia 7 (6.0%) 1 (12.5%) 6 (5.5%) .3992
Fatigue 12 (10.3%) 0 (0.0%) 12 (11.0%) 1.0000
Dyspnea 10 (8.5%) 0 (0.0%) 10 (9.2%) 1.0000
Expectoration 0 (0.0%) 0 (0.0%) 0 (0.0%) 1.0000
Headache 2 (1.7%) 0 (0.0%) 2 (1.8%) 1.0000
Chest distress 9 (7.7%) 0 (0.0%) 9 (8.3%) 1.0000
Diarrhea 4 (3.4%) 0 (0.0%) 4 (3.7%) 1.0000
Vomit 1 (0.9%) 1 (12.5%) 0 (0.0%) .0684
Dizziness 1 (0.9%) 1 (12.5%) 0 (0.0%) .0684
Rhinorrhea 1 (0.9%) 0 (0.0%) 1 (0.9%) 1.0000
More than one symptoms 27 (23.1%) 1 (12.5%) 26 (23.9%) .7635
Asymptomatic 8 (6.8%) 0 (0.0%) 8 (7.3%) 1.0000
Combined chronic diseases
Diabetes 6 (5.1%) 1 (12.5%) 5 (4.6%) .3525
Hypertension 15 (12.8%) 1 (12.5%) 14 (12.8%) 1.0000
Coronary heart disease 2 (1.7%) 0 (0.0%) 2 (1.8%) 1.0000
Cerebrovascular diseases 4 (3.4%) 0 (0.0%) 4 (3.7%) 1.0000
COPD 3 (2.6%) 0 (0.0%) 3 (2.8%) 1.0000
Malignant tumor 2 (1.7%) 0 (0.0%) 2 (1.8%) 1.0000
Chronic renal failure 1 (0.9%) 0 (0.0%) 1 (0.9%) 1.0000
Primary liver disease 3 (2.6%) 0 (0.0%) 3 (2.8%) 1.0000
Other comorbidities 14 (12.0%) 1 (12.5%) 13 (11.9%) 1.0000
Imaging manifestations
Ground glass opacity 106 (90.6%) 8 (100.0%) 98 (89.9%) 1.0000
Reticular opacity 17 (14.5%) 1 (12.5%) 16 (14.7%) 1.0000
Local consolidation 39 (33.3%) 2 (25.0%) 37 (33.9%) .8970
Linear opacity 10 (8.5%) 1 (12.5%) 9 (8.3%) .5220
Septal thickening 18 (15.4%) 1 (12.5%) 17 (15.6%) 1.0000
Normal CT scan 3 (2.6%) 0 (0.0%) 3 (2.8%) 1.0000
Unilateral 56 (47.9%) 4 (50.0%) 52 (47.7%) 1.0000
Bilateral 58 (49.6%) 4 (50.0%) 54 (49.5%) 1.0000
Laboratory test on admission
White blood cell count (×109/L) 5.30 (4.20–6.13) 4.81 (4.20–5.55) 5.30 (4.20–6.13) .6835
Neutrophil count (×109/L) 3.30 (2.56–4.43) 2.89 (2.69–3.46) 3.34 (2.56–4.43) .6631
Eosinophilic granulocyte (×109/L) 0.01 (0.00–0.02) 0.04 (0.01–0.10) 0.01 (0.00–0.02) .4693
Lymphocyte count (×109/L) 1.21 (0.98‐1.53) 1.59 (1.25–23.66) 1.19 (0.97–1.50) .3887
Platelet count (×109/L) 171.00 (136.75–196.75) 179.00 (136.75–222.50) 171.00 (138.00–195.00) .8234
C‐reactive protein (mg/L) 12.24 (5.20–39.86) 4.79 (2.45–7.14) 13.29 (5.57–42.80) .0119
Laboratory test after treatment
White blood cell count (×109/L) 4.92 (4.43–5.64) 4.88 (4.72–5.06) 4.94 (4.42–5.70) .1648
Neutrophil count (×109/L) 2.92 (2.47–3.60) 3.24 (2.90–3.32) 2.91 (2.47–3.68) .8477
Eosinophilic granulocyte (×109/L) 0.08 (0.05‐0.11) 0.07 (0.05–0.09) 0.08 (0.05–0.12) .0573
Lymphocyte count (×109/L) 1.65 (1.22–1.90) 1.35 (1.11–1.49) 1.65 (1.22–1.91) .1070
Platelet count (×109/L) 272.00 (228.00–323.00) 261.00 (227.00–267.00) 273.50 (229.50–323.75) .2839
Treatment modalities
Antiviral drugs 97 (56.4%) 4 (50.0%) 62 (56.9%) .9924
Antibacterial drugs 29 (24.8%) 1 (12.5%) 28 (25.7%) .6820
Traditional Chinese medicine 64 (54.7%) 5 (62.5%) 59 (54.1%) .9273
Inhalation of high flow oxygen 14 (12.0%) 2 (25.0%) 12 (11.0%) .2446

Abbreviation: COPD, chronic obstructive pulmonary disease.

Eight patients (6.8%) showed a re‐positive SARS‐CoV‐2 test after a median 12.5 (11.8–16.3) days since discharge (Figure 1). All of them denied contact with suspected patients or anybody with fever symptoms during follow‐up period. Seven of them were asymptomatic and follow‐up CT showed no obvious change with the previous manifestation. One 57‐year‐old female patient demonstrated mild fatigue and chest distress 28 days after discharge. Unenhanced follow‐up CT showed small areas of ground‐glass opacities in the left lung and small nodules in the right lung. She received additional antiviral treatment and was in stable condition until the last follow‐up. No surrounding persons or family members were infected. For the eight re‐positive patients, we compared the first time positive C t (cycle threshold) value upon hospitalization and second time positive C t value after discharge, the difference was not significant (30.91 ± 2.50 vs. 30.29 ± 1.70, p = .570). Laboratory examination showed that the values of C‐reactive protein in re‐positive patients were lower than the other 109 patients (p = .012).

Figure 1.

Figure 1

Timeplot of eight re‐positive patients from symptoms onset to discharge. During the follow‐up period, one patient demonstrated mild discomfort, the other seven patients were asymptomatic. RT‐PCR, reverse transcription‐polymerase chain reaction

At present, there are relatively few reports about the redetectable SARS‐CoV‐2 among rehabilitation patients. According to a previous report by Lan et al., 1 four recovered medical professionals demonstrated a positive result during repeated reverse transcription‐polymerase chain reaction (RT‐PCR) test. No typical symptoms or changes in CT images were observed. In our study, 6.8% of patients demonstrated re‐positive RT‐PCR test results 10–28 days after discharge. One patient had mild symptoms and new inflammatory exudative lesions by a follow‐up CT examination. However, no further transmission to surrounding persons had been observed. Although the initial C t value was not obviously different from the subsequent C t value among re‐positive patients, whether the virus load during the follow‐up period was lower or not need more prospective clinical research. In addition, false‐negative may be inevitable as different size and depth of taking samples can affect the accuracy of the oropharyngeal swab. In contrast, the positive rate of RT‐PCR tests through alveolar lavage fluid may be higher. However, this method is invasive and cannot be widely performed in clinical practice. In our opinion, both qualities of respiratory samples and the variability of technique sensitivity can be attributed to the influence factors of re‐positivity.

We noted that the values of C‐reactive protein in re‐positive patients were comparatively lower. Due to the limited sample size, if a relatively weaker inflammatory response might give rise to virus residual in the lungs is still unclear. In addition, redetection of viral RNA by PCR does not imply viral reactivation. Most patients will produce antibodies 10 days or later after infection. 4 Due to the gradual presence of antibody immunoglobulin G, 5 most re‐positive patients will not demonstrate a relapse of symptoms. Further virological and immunological studies related to re‐positive patients need to be conducted to explore the SARS‐CoV‐2 infection mechanism.

CONFLICT OF INTERESTS

The authors declare that there are no conflict of interests.

AUTHOR CONTRIBUTIONS

Concept and design were contributed by Junjie Hu, Shi Li, Yan Wu, and Fei Tian. Acquisition, analysis, or interpretation of data were contributed by Junjie Hu, Shi Li, Yan Wu, and Zhiguo Xiong. Drafting of the manuscript was contributed by Fei Tian and Junjie Hu. Statistical analysis was contributed by Fei Tian, Lichong Gong, and Yichen Yang. Administrative, technical, or material support was contributed by Junjie Hu and Fei Tian.

ACKNOWLEDGMENTS

The authors thank all patients included in this study. They appreciate all medical works and coordinators who are fighting COVID‐19 around the world. Their expertise, humanity, and devotion are important and respectable.

REFERENCES

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