Prolonged 59‐day course of COVID‐19: The case of a SARS‐CoV‐2 shedding persistency in a healthcare provider

Abstract For health professionals, repeated SARS‐CoV‐2 RNA detection through PCR combined with properly validated serologic assays for the presence of anti‐IgM and anti‐IgG antibodies should be mandatory.

papules. Her dry cough gradually turned into a wet cough during the second week. She became asymptomatic on April 2, and despite a negative serologic test with colloidal gold particles for detection of anti-SARS-CoV-2 IgM and IgG on March 29, she was allowed to go back to work on April 6th.
In brief, she became asymptomatic during 5 weeks of convalescence. On May 6, she presented with rhinitis, flu symptoms, and great fatigue along with a dry cough, nausea, ageusia, and eruption of erythematosus red papules on the hand. On May 9, she tested positive for SARS-CoV-2 RNA on quantitative PCR for the second time. Of note, other dental residents showed negative PCR results.
On May 12, 59 days after the appearance of the first set of symptoms of COVID-19, once again, she became asymptomatic with a negative PCR. In addition, a serologic ELISA test for IgG antibodies to SARS-COV-2 was positive with an index (signal-to-cutoff ratio) of 5 with a positive SARS-CoV-2 cutoff of 1.1. Of note, on August 31, the serologic ELISA test for IgG antibodies to SARS-COV-2 was negative.

| DISCUSSION
Our case presents useful data on a possible clinical course of this novel illness including viral shedding: incubation period, contagious phase, and stages of a mild COVID-19.
In the absence of nasopharyngeal swab during the first convalescence period, the recurrence of the symptoms along with the second positive (SARS-CoV-2 RNA) PCR after the first convalescence period could convey two hypotheses: either reactivation or persistence of SARS-CoV-2 shedding. To date, only a 33-year-old man from Hong Kong was reported to have the first confirmed case of COVID-19 reinfection. 2 In this very recent case, 24 nucleotides differed between the viruses from the first and second infection episode. These were amino acid differences in nine proteins, including a 58 amino acid truncation of ORF8 protein that was present only in the virus from the first infection. The latter findings suggest that acquired immunity after natural infection may be short lived. In our presented case, re-infection hypothesis seemed unlikely according to the following. The reported COVID-19 infection rate in our region was low with no new COVID-19-positive patients during the previous 8 days before her relapse.
Furthermore, according to the Guangdong COVID-19 surveillance system on epidemiology and characteristics of re-positive cases between 23 January and 26 February 2020, 3 the percentage of SARS-CoV-2 re-positive cases was around 14%. All re-positive cases in the Guangdong study developed only mild or moderate symptoms on initial diagnosis, with the median age being significantly lower than that of the general COVID-19 cases. Furthermore, according to the WHO public health surveillance guidance for COVID-19, 4 a robust neutralizing antibody response and potential virus genome degradation are detected in almost all re-positive cases, suggesting a substantially lower transmission risk, especially through respiratory routes. In our case report, although the symptoms were mild, the neutralizing antibody response was weak.
Our case presents the first reported COVID-19 healthcare provider with prolonged viral shedding due to either disease reactivation or persistence 5 in Europe. To date, this is one of the longest reported prolonged viral shedding, that is, a 59day course of the disease. Consistent with our case report, six cases of healthcare professionals in Brazil who recovered but again presented symptoms consistent with COVID-19, with new positive RT-PCR test results were also recently reported. 6

| CONCLUSION
Clinicians should be alerted on the rationale for a close monitoring of viral load and acquired immunity and a longer than recommended 15 days of isolation strategy in such subgroup of COVID-19 patients.