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Coronavirus disease 2019 (COVID-19) is a newly emerging human infectious disease caused by acute respiratory syndrome coronavirus 2 (SARS-CoV-2, previously called 2019-nCoV) [1,2]. Based on the rapid increase in the rate of human infections, the World Health Organization (WHO) has classified theCOVID-19 outbreak as a pandemic [3-5]. Because no specific drugs are yet available [6], early diagnosis and management are crucial for containing the outbreak. Furthermore, the duration of immunization after clinical recovery is still unknown and this could be of particular concern regarding the future management and spread of infection.

Several case series have been published to date documented cases which turned polymerase chain reaction (PCR) negative in nasopharyngeal swab at discharge with resolution of symptoms and subsequently returned PCR positive in follow-up swab tests [7-12]. Usually, the patients had mild to moderate symptoms and the time of recurrence of positive tests ranging from few days to several weeks after discharge. Several hypothesis have been postulated to explain these findings: false negative PCR at the time of discharge due to improper sampling, transport or processing or laboratory errors or low viral load; all these conditions possibly related to false negative results. On the contrary, persistent positive tests could be attributed to false positive results due to contamination in sampling or in the laboratory, residual viral RNA or cross reaction with other viruses. As a consequence, as in all these case series viral culture and genetic analysis were not performed, these recurrences could be re-infections, viral relapses or laboratory errors. However, such uncertain results have significant implications regarding the variable presence of viral infection, the risk of re-infection and the need of quarantine for prolonged periods to prevent the spread of infection.

It has been recently documented from Hong Kong [13] a case of COVID-19 re-infection by a phylogenetically distinct strain; this finding leaded to several assumptions on long-term immunity, sampling technique standardization, viral mutation and efficacy of herd immunity. As a consequence, SARS-CoV-2 may continue to circulate among the global population despite herd immunity due to natural infection or vaccination. In particular, this case has a time gap of over 4 months, a laboratory proven different genotype resembling the European virus and the patient was also returning from Europe; all these considerations make it more likely that it is a re-infection rather than a recurrence.

CDC suggests that antibody response to COVID-19 lasts for 2-3 months; nevertheless, there is variability in duration among different individuals. Further, the antibody response to COVID-19 infection may be influenced by the immunological status of the single individual and by the use of immune-modulatory therapy. These observations make the risk of re-infection plausible, especially after exposure to a different strain of the virus. As a consequence, the concept of generating herd immunity seems practically difficult to achieve [14]. Thus, in the actual absence of global vaccination coverage, there is little we can do to prevent the spread of COVID-19, except for the use of personal protective equipment, physical distancing and lockdown strategies that have been shown to be useful in delaying and preventing precipitous rise of cases [15].

Prolonged shedding of SARS-CoV-2 is an intriguing issue on the long-term management of COVID-19 infected subjects. Several reports assessed that a significant amount of COVID-19 infected individuals remained positive for a very long time [16-19]. In particular, in the Italian population, older age has been associated with an augmented risk of prolonged viral shedding [17], whilst in Chinese studies male gender and advanced disease (patients underwent to mechanical ventilation) were also correlated [18,19]. The real infectivity and the risk of SARS-CoV-2 transmission of these individuals is still unclear, but their management during follow-up certainly needs special attention.

Recent reports of positive PCR tests after a variable period of negativity suggest that at least a proportion of recovered patients may still be virus carriers. These observations may have significant implications in daily life; in particular, criteria for hospital discharge, discontinuation of quarantine period and return to work are difficult to generalize to the entire population and, when possible, should be tailored on the single individual. In Italy, a circular of the Ministry of Health [20] established that an asymptomatic patient with COVID-19 infection may exit from the quarantine after 21 days from the diagnosis, even if nasopharyngeal swab persists positive, as it is believed that these subjects are non-infectious. Recently, we demonstrated that the median time for viral clearance in a cohort of Italian healthcare workers was over 30 days [21]. These findings should be considered when re-admitting at work these subjects and are in partial contradiction with the above mentioned circular. Given the lack of clear data on the non-infectious of subjects with prolonged viral shedding, is it ethically correct to return to the community 21 days after positivity if the healthcare worker, though asymptomatic, is still positive? Probably, in absence of clear evidences of non-infectious, the best and more cautious option would be to differentiate the criteria for quarantine exit and return to work according to the risk of possible contagiousness. In particular, those individuals who works closely with several people, as healthcare workers, should probably return to work only when there is absolute certainty that the nasopharyngeal swab for SARS-CoV-2 infection will be negative.

References

1. Tang JW, Tambyah PA, Hui DSC (2020) Emergence of a novel coronavirus causing respiratory illness from Wuhan, China. J Infect 80: 350-371. [Crossref]
2. Zhu N, Zhang D, Wang W, Li X, Yang B, et al. (2020) A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med 382: 727-733. [Crossref]
3. Chan JFW, Yuan S, Kok KH, To KKW, Chu H, et al. (2020) A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet 395: 514-523.
4. Rothe C, Schunk M, Sothmann P, Bretzel G, Froeschl G, et al. (2020) Transmission of SARS-CoV-2 infection from an asymptomatic contact in Germany. N Engl J Med 382: 970-971. [Crossref]
5. Holshue ML, DeBolt C, Lindquist S, Lofy KH, Wiesman J, et al. (2020) First case of 2019 novel coronavirus in the United States. N Engl J Med 382: 929-936. [Crossref]
6. Sanders JM (2020) Pharmacologic treatments for Coronavirus Disease 2019 (COVID-19): a review. JAMA 323: 1824-1836. [Crossref]
7. Bongiovanni M, Basile F (2020) Re-infection by COVID-19: a real threat for the future management of pandemia? Infect Dis 52: 581-582. [Crossref]
8. Yuan J, Kou S, Liang Y, Zeng J, Pan Y, et al. (2020) PCR assays turned positive in 25 discharged COVID-19 patients. Clin Infect Dis 8: ciaa398. [Crossref]
9. Wu J, Liu X, Liu J, Liao H, Long S, et al. (2020) Coronavirus Disease 2019 test results after clinical recovery and hospital discharge among patients in China. JAMA Netw Open 3: e209759. [Crossref]
10. Ye G, Pan Z, Pan Y, Deng Q, Chen L, et al. (2020) Clinical characteristics of severe acute respiratory syndrome coronavirus 2 reactivation. J Infect 80: e14-e17. [Crossref]
11. Bongiovanni M, Vignati M, Giuliani G, Manes G, Arienti S, et al. (2020) The dilemma of COVID-19 recurrence after clinical recovery. J Infect 81: 979-980. [Crossref]
12. Batisse D, Benech N, Botelho-Nevers E, Bouiller K, Collarino R, et al. (2020) Clinical recurrences of COVID-19 symptoms after recovery: viral relapse, reinfection or inflammatory rebound? J Infect 81: 816-846. [Crossref]
13. To KK, Hung IF, Ip JD, Chu AW, Chan WM, et al. (2020) COVID-19 re-infection by a phylogenetically distinct SARS-coronavirus-2 strain confirmed by whole genome sequencing. Clin Infect Dis 25: ciaa1275. [Crossref]
14. Ramachandran R (2020) COVID-19 a very visible pandemic. Lancet 396: e13-e14. [Crossref]
15. Giesecke J (2020) The invisible pandemic. Lancet 395: e98. [Crossref]
16. Walsh KA, Jordan K, Clyne B, Rohde D, Drummond L, et al. (2020) SARS-CoV-2 detection, viral load and infectivity over the course of an infection. J Infect 81: 357-371. [Crossref]
17. Bongiovanni M, Bini F, Giuliani G, Gianturco L (2020) Insight into the reason of prolonged viral RNA shedding in patients with COVID-19 infection. J Infect (in press). [Crossref]
18. Shi D, Wu W, Wang Q, Xu K, Xie J, et al. (2020) Clinical characteristics and factors associated with long-term viral excretion in patients with severe acute respiratory syndrome coronavirus 2 infection: a single center 28-day study. J Infect Dis 222: 910-918. [Crossref]
19. Fang Z, Zhang Y, Hang C, Ai J, Li S, et al. (2020) Comparison of viral shedding time of SARS-CoV-2 of different samples in ICU and non-ICU patients. J Infect 81: 147-148. [Crossref]
20. Https://www.trovanorme.salute.gov.it/norme/renderNormsanPdf?anno=2020&codLeg=76613&parte=1%20&serie=null
21. Bongiovanni M, Marra AM, De Lauretis A, Bini F, Di Carlo D, et al. (2020) Natural history of SARS-CoV-2 infection in healthcare workers in Northern Italy. J Hosp Infect Dec 106: 709-712. [Crossref]