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Covid-19: Hong Kong scientists report first confirmed case of reinfection

BMJ 2020; 370 doi: (Published 26 August 2020) Cite this as: BMJ 2020;370:m3340

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Rapid Response:

COVID-19: Regarding Case of Re-infection

Dear Editor,

This is indeed a very interesting case of re-infection with COVID-19 confirmed by both serological and genetic testing. 8 new cases of re-infection have been reported worldwide since the publication of this case [1]. In fact we are about to submit a case report from the UK. Earlier animal experiments have shown that re-infection with the same COVID-19 strain did not lead to clinical symptoms and signs of COVID-19 which is reassuring suggesting adequate immunity post initial exposure [2].

However this case has highlighted a number of issues. This of course has been confirmed to be a re-infection with a genetically different strain of virus. This could pose worry as it would mean immunity is either short lived or there is no cross immunity, and there is a real threat of mutated strains. Hence the wider efficacy of any future vaccines may be questionable. The question remains as to who is vulnerable for re-infection. Do the same risk factors matter as for initial infection or are there other factors to consider e.g. initial severity of infection, immunocompromised state, age, acquired humoral immunity (antibody titre) or T-cell immunity? Interestingly the second infection in this case was mild and asymptomatic even though there was no demonstrable antibody level, which may be explained by acquired T-cell immunity.

Reports suggest that viral shedding usually lasts for up to 3 weeks from the onset of symptoms, but can continue up to 5-6 weeks after [3][4][5]. It may be related to the age, severity of infection and immunocompetent status of the patient [5][6].

Duggan et al describe a case, where the patient was retested seven days after discharge from prolonged intensive care unit (ICU) care for 47 days. However this case had new respiratory symptoms and radiographic changes and needed oxygen therapy. This may also have been a case of prolonged viral shedding as, it has previously been shown that viral shedding may last as long as two months post symptoms onset [5,6].This case needed a higher threshold of number of PCR cycles to detect the virus suggesting insensitivity of testing at the time of discharge [7].

Persistently positive tests in COVID-19 have been well demonstrated previously. Is it intermittent viral shedding, viral distribution or false negativity due to poor sensitivity of the tests that needs to be investigated? [8],[9],[10],[11]. A recent report by Zhang et al showed that 14.5% (38/262) of patients in a retesting cohort with COVID-19 infections were retested positive within fourteen days of discharge form the hospital after they had two negative RT-PCR tests. Interestingly they found retest positive (RP) patients had milder disease at diagnosis and became RT-PCR negative earlier than non-retest positive (NRP) patients. This suggests that more severely ill patients may develop stronger immunity. However the assays for detection of RNA at the time of discharge were questionable since a few patients tested positive by more sensitive assays later. Those who had true reinfection were shown to have milder disease; further suggesting that immunity from previous exposure may be protective. They did not, however, perform genetic assay of the viruses to see if new mutations were present [12].

The sensitivity of the RT-PCR tests is variable ranging from 60-80%, hence there is a potential for missing a large number of early asymptomatic cases or those cases where the patient may have recovered but has detectable RNA present [13],[14], leading to an automatic assumption of re-infection if patients are screened again for a different reason. The RT-PCR tests are also not specific and may detect other corona viruses of no significance. Similarly another report demonstrated incomplete virus on cell cultures in samples from patients who tested positive post-recovery from COVID-19, again mitigating chances of re-infection [15].

The question of immunity is still unanswered, particularly relating to how long the antibody levels last far and how long antibodies confer protection if any. Recent reports suggest antibody levels decline within months making us vulnerable to re-infection [16][17]. However, the role of T-cell immunity still needs to be elucidated, with some evidence suggesting T-cell immunity lasts many months [18]. Until we gather more scientific evidence about long lasting immunity, the threat of re-infection albeit small will continue to haunt us.

The implications of this case and ours are clear: re-infection can occur. Those who have had COVID-19 must adhere to the same principals of hygiene and social distancing as others and will also need to be vaccinated when available. Caution is needed in immunocompromised patients as they may not clear the virus and may be prone to re-infection.

1. COVID-19 reinfection tracker,
Published, August 28, 2020
2. Bao L, Deng W, Gao H, et al. Lack of reinfection in rhesus macaques infected with SARS-CoV-2. BioRxiv. 2020 Mar 13;990226 [Preprint].
3. Xiao AT, Tong YX, Gao C, et al. Dynamic profile of RT-PCR findings from 301 COVID19 patients in Wuhan, China: a descriptive study. J Clin Virol. 2020 Jun;127:104346.
4. Lan L, Xu D, Ya G, et al. Positive RT-PCR test results in patients recovered from COVID-19. JAMA. 2020 Feb 27;323(15):1502–3
5. Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054–62.
6. Li J, Zhang L, Liu B, Song D Case Report. Viral shedding for 60 days in a woman with novel coronavirus disease (COVID-19). Am J Trop Med Hyg. 2020 Apr 27. https://doi. org/10.4269/ajtmh.20-0275.
7. N.M. Duggan, S.M. Ludy, B.C. Shannon, et al., Is novel coronavirus 2019 reinfection possible? Interpreting dynamic SARSCoV-2 test results through..., American Journal of Emergency Medicine,
8. Li D, Wang D, Dong J, et al. False-Negative Results of Real-Time Reverse-Transcriptase Polymerase Chain Reaction for Severe Acute Respiratory Syndrome Coronavirus.Korean J Radiol 2020;21(4):505-08.
9. Xia J-H, Tong J-P, Liu M-Y, et al. Evaluation of coronavirus in tears and conjunctival secretions of patients with SARS-CoV-2 infection SARS-CoV-2 through conjunctiva. J Med Virol 2020. published online February 26.
10. Wölfel R, Corman VM, Guggemos W, et al.Virological assessment of hospitalized cases of coronavirus disease 2019. medRxiv 2020. published online March 8.
11. Xing Y-H, Ni W, Wu Q, et al. Prolonged presence of SARS-CoV-2 in feces of pediatric patients during the convalescent phase. medRxiv 2020.published online March 13.
12. Jianghong An,Xuejiao Liao,Tongyang Xiao, Shen Qian, Jing Yuan,Haocheng Ye, Furong Qi, Chengguang Shen, Yang Liu, Lifei Wang,Xiaoya,Cheng, Na Li,Qingxian Cai, Fang Wang, Jun Chen, Yingxia Liu, Yunfang Wang, Zhang, Yang Fu, Xiaohua Tan, Lei Liu,Zheng Zhangef. RClinical characteristics of the recovered COVID-19 patients with re-detectable positive RNA test. medRxiv preprint doi:
13. Ai T, et al. Correlation of chest CT. And RT-PCR testing in coronavirus disease 2019 (COVID-19) in China: a report of 1014 cases. Radiology. 2020 [Feb 26:200642.
14. Xie X, Zhong Z, Zhao W, et al. Chest CT for typical 2019-nCoV pneumonia: relationship to negative RT-PCR testing. Radiology. 2020 [Feb 12;200343].
15. “Findings from investigation and analysis of re-positive cases”. Division of Risk assessment and Internationalcooperation.Updated04Sep2020.
16. Long QX, Tang XJ, Shi QL, Li Q, Deng HJ, Yuan J, et al. Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections. Nat Med 2020;26:1200-4 Downloaded from by guest on 31 August 2020 17
17. Robbiani DF, Gaebler C, Muecksch F, Lorenzi JCC, Wang Z, Cho A, et al. Convergent antibody responses to SARS-CoV-2 in convalescent individuals. Nature 2020;10.1038/s41586-020-2456-9
18. Snyder TM, Gittelman RM, Klinger M, May DH, Osborne EJ, Taniguchi R, et al. Magnitude and Dynamics of the T-Cell Response to SARS-CoV-2 Infection at Both Individual and Population Levels. medRxiv 2020;10.1101/2020.07.31.20165647

Competing interests: No competing interests

07 September 2020
Farooq A Wandroo
Honorary Senior Lecturer, University of Birmingham, UK,Consultant Haematologist
Sehar Farooq, Bsc, Year 6 Medical Student, University College London, Medical School, London UK
Sandwell and West Birmibgham Hospitals NHS Trust, Birmingham,UK
Departemnt of Clinical Haematology, Sandwell and West Birmibgham Hospitals NHS Trust, Birmingham,UK