Reactivation of SARS‐CoV‐2 after recovery

Coronavirus disease 2019 (COVID‐19) has now spread worldwide as a global pandemic. ¹ We report on an 8‐year‐old boy who might be a patient with reactivation of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) in a family cluster.

We retrospectively reviewed medical records including symptoms and signs, laboratory examination, sequential cycle threshold values of real‐time reverse transcription‐polymerase chain reaction (qRT‐PCR) tests for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), radiological findings, and management. The transmission route to SARS‐CoV‐2 was described based on the report by the epidemiological investigation service officer and the history taken from the parents. qRT‐PCR tests for SARS‐CoV‐2 were performed using samples collected serially from the upper airway (nasopharyngeal swab), lower airway (sputum), urine, stool, saliva, and serum. Viral RNA was detected by using Allplex™2019‐nCoV Assay (Seegene Inc., Seoul, Korea) for amplification of the RNA‐dependent RNA polymerase (RdRP), N genes specific for SARS‐CoV‐2, and E genes for all Sarbecovirus, including SARS‐CoV‐2. The cycle threshold (Ct) values from the qRT–PCR were measured; Ct values <35 were reported as positive, and Ct values between 35 and less than 40 were considered indeterminate.

On March 3, 2020, the 8‐year‐old boy presented a 3‐day history of intermittent cough and was diagnosed with COVID‐19 after having been in contact with his father, who was confirmed SARS‐CoV‐2 positive 3 days before. He was previously healthy and had no travel history within two weeks. Once the father had tested positive, the family members had gone into self‐quarantine at home. They had all been tested for COVID‐19 on February 29 and were negative and had continued to self‐isolate. Other family members were also tested but were found to be negative. The child was then hospitalized in a nationally designated negative pressure room together with his mother.

Upon admission, the boy’s initial blood tests were within reference ranges. Chest X‐rays were performed during admission but the radiographs showed no active lesions. However, chest computed tomography (CT) revealed non‐specific ground glass‐opacity nodules in the subpleural area of the left lower lobe, suggesting a viral pneumonia. Supportive care was given to the boy without antiviral medication.

On day 3 of admission, his cough gradually improved and resolved on day 15, following which symptomatic medication was discontinued. The results of the qRT‐PCR tests from both the upper and lower respiratory tracts were positive until day 8 of admission, becoming negative on day 14 and qRT‐PCR was performed after 24 h (Table 1). The patient was discharged on day 17.

Table 1.

The change of cycle threshold values using qRT‐PCR in two respiratory and three non‐respiratory specimens

	4‐Mar	6‐Mar	9‐Mar	12‐Mar	16‐Mar	17‐Mar	2‐Apr	3‐Apr	6‐Apr	8‐Apr	9‐Apr	11‐Apr	12‐Apr
Upper airway
RdRP gene	24.85	26.33	32.66	− †	−	−	31.16	−	31.09	−	−	−	−
E gene	22.70	23.94	30.97	−	−	−	29.21	−	31.11	−	−	−	−
N gene	25.01	28.46	34.95	−	−	−	30.87	−	31.53	39.85	−	−	−
Lower airway
RdRP gene	26.93	26.49	29.14	−	−	−	∙	−	−	−	−	−	−
E gene	25.44	24.21	32.28	−	−	−	∙	−	−	−	−	−	−
N gene	29.45	27.72	33.38	37.17	−	37.88	∙	−	−	−	−	−	−
Urine
RdRP gene	−	−	−	−	−	∙	−	−	−	−	−	−	−
E gene	−	−	−	−	−	∙	−	−	−	−	−	−	−
Serum
RdRP gene	−	−	−	∙ ‡	∙	∙	−	∙	∙	∙	∙	∙	∙
E gene	−	−	−	∙	∙	∙	−	∙	∙	∙	∙	∙	∙
Saliva
RdRP gene	40.00	∙	−	−	−	∙	−	−	−	−	−	−	−
E gene	23.88	∙	34.34	34.03	−	∙	−	−	−	−	−	−	−
Stool
RdRP gene	∙	28.55	∙	∙	31.19	33.42	∙	−	−	−	−	−	−
E gene	∙	23.88	∙	∙	36.26	30.26	∙	−	−	−	−	−	−

Abbreviations: E, E gene for all Sarbecovirus including SARS‐CoV‐2; N, N genes specific for SARS‐CoV‐2; qRT‐PCR, real‐time reverse transcription‐polymerase chain reaction; RdRP, RNA‐dependent RNA polymerase.

^† Undetectable.

^‡ Not tested.

Bold values, SARS‐CoV‐2 qRT‐PCR positive test results.

The patient stayed at home without contact with other people after discharge. However, his cough reoccurred and he developed a poor appetite 4 days after discharge. The qRT‐PCR test for SARS‐CoV‐2 was therefore conducted again the following day and the results were negative. However, the cough continued and deteriorated, and a follow‐up test was therefore performed 14 days after discharge. On April 4, the test for SARS‐CoV‐2 was positive and so the patient was admitted again (Table 1). Laboratory and imaging studies showed no remarkable abnormalities. Even though he had a mild fever of 37.7 °C, the patient's general condition was very good. Another multiplex PCR test was also performed to assess for various respiratory pathogens and was negative. On April 7, 2020, 4 days after re‐admission, his fever subsided and did not increase further above 37.5 °C after 48 h. Until the 7th day, the qRT‐PCR test at upper airway confirmed that it was positive. However, it was confirmed as negative by two tests conducted at 24 h intervals from the 9th day to the 10th day (Table 1). The patient was then subsequently discharged on April 13, the 11th day of hospitalization. Fortunately, his mother had not been infected since he was first diagnosed.

In a recent report on adults with reactivation of COVID‐19, 5 (9%) of all 55 patients who were discharged from hospital presented with SARS‐CoV‐2 reactivation. ² As the prevalence of COVID‐19 in children has been even lower than adults, ³ , ⁴ our study could be provided as a basis for future studies. Even though detection of viral RNA does not necessarily mean that infectious viruses are shedding, further research is needed to understand its significance for transmission‐based precautions.

Disclosure

The authors declare no conflict of interest.

Author contributions

S.Y.Y., Y.L., G.H.L., and D.H.K. were involved in the medical management of the patient, and collected and analyzed the clinical data. S.Y.Y. wrote the manuscript, and D.H.K. reviewed the manuscript. All authors read and approved the final manuscript.

Ethical approval

This study was approved by the Institution Review Board (IRB) of Inha University Hospital (IUH‐IRB‐2020‐04‐002). Written consent was obtained from the parents of the patient for publication.

Supporting information

Fig S1. The change of cycle threshold values using qRT‐PCR in upper and lower respiratory specimens. Positive range, shown in pink color. Abbreviations: E, E gene for all of Sarbecovirus including SARS‐CoV‐2; N, N genes specific for SARS‐CoV‐2; qRT‐PCR, real‐time reverse transcription‐polymerase chain reaction; RdRP, RNA‐dependent RNA polymerase; SARS‐CoV‐2, severe acute respiratory syndrome coronavirus 2; (U), upper airway specimen; (L), lower airway specimen.

Fig S2. Chest computed tomography revealed non‐specific ground glass‐opacity nodule (white arrow) in the subpleural area of the left lower lobe in axial view.