Viral shedding prolongation in a kidney transplant patient with COVID-19 pneumonia
Man Zhang, Jing Zhang, Shi Huibo, Bin Liu, Zeng Fanjun
Abstract
To the Editor: The coronavirus disease 2019 (COVID-19) pandemic sweeps the globe. The information regarding the kinetic changes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in immunosuppressed patients is unclear. Herein, we present a case of prolonged viral shedding in a transplant patient with COVID-19 pneumonia. A 49-year-old male kidney recipient was admitted to the hospital on February 7, 2020, for fever and fatigue. He was a permanent resident of Wuhan, China, and began having symptoms on January 29 (day 1 of illness). His maintenance immunosuppressive regimen consisted of tacrolimus (TAC, 1 mg twice a day, orally), mycophenolate mofetil (MMF, 0.5 g twice a day, orally), and prednisone (Pred, 5 mg daily, orally) triple combination. On admission, laboratory tests revealed a reduction in lymphocyte count. Chest computed tomography (CT) scan showed bilateral patchy shadows and multifocal ground-glass opacities. A nasopharyngeal swab specimen was obtained and tested positive for the presence of SARS-CoV-2 RNA. Thus, the diagnosis of COVID-19 pneumonia was established. The patient received antiviral treatment with umifenovir (200 mg, 3 times daily, orally). Immunosuppression was discontinued, and systemic methylprednisolone (MP, 40 mg daily, intravenously) was given to reduce the inflammatory infiltration (Figure 1). The patient had a speedy recovery and was discharged on day 35. He experienced 5 continuous negative test results for SARS-CoV-2 RNA in the recovery period, and IgG/IgM antibody tested positive on day 47. Astonishingly, repeated testing of nasal swabs turned positive on day 57 and on day 63, even after the relief in symptoms and improvement in radiological findings. Afterwards, the patient was quarantined for a 14-day observation and 3 consecutive negative tests were shown with no additional treatment. This case highlights the challenge in the fluctuant results of SARS-CoV-2 RNA testing in immunocompromised patients. First, the sensitivity of tests depends on the viral load of respiratory specimen.1Wang W, Xu Y, Gao R, et al. Detection of SARS-CoV-2 in different types of clinical specimens. JAMA. 2020. [Epub ahead of print]. https://doi.org/10.1001/jama.2020.3786Google Scholar There could be false negatives on occasion for throat swabs tests, affected by the sampling site, the experience of the operator, and the actual quantity of virus. A high rate of false-negative results for SARS-CoV-2 detection was reported in non-immunocompromised patients who may become virus carriers.2Li Y, Yao L, Li J, et al. Stability issues of RT-PCR testing of SARS-CoV-2 for hospitalized patients clinically diagnosed with COVID-19. J Med Virol. 2020. [Epub ahead of print]. https://doi.org/10.1002/jmv.25786Google Scholar Accordingly, recovered patients are instructed to continue isolation and observation after discharge. They receive repeated examinations during that period. Second, SARS-CoV-2 RNA “turned positive” revealed prolonged viral shedding rather than “recurrence,” which was also described in recipients with respiratory syncytial virus infection.3de Lima C Mirandolli TB Carneiro LC et al.Prolonged respiratory viral shedding in transplant patients.Transpl Infect Dis. 2014; 16: 165-169Crossref PubMed Scopus (37) Google Scholar The median duration of virus shedding was 20 days in the general population with COVID-19.4Zhou 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; 395: 1054-1062Abstract Full Text Full Text PDF PubMed Scopus (16298) Google Scholar However, the actual shedding time after the illness onset lasted 65 days in this case under the premise of false negatives. Immunosuppression may pose two opposing effects on COVID-19. It reduces the incidence of severe pneumonia by suppression of the cytokine storm; the majority of transplant patients with COVID-19 had full recovery.5Zhu L, Gong N, Liu B, et al. Coronavirus disease 2019 pneumonia in immunosuppressed renal transplant recipients: a summary of 10 confirmed cases in Wuhan, China. Eur Urol. 2020:S0302-2838(20)30214-1. https://doi.org/10.1016/j.eururo.2020.03.039Google Scholar On the other hand, immunosuppression may prolong viral shedding time. Traces of SARS-CoV-2 RNA are not necessarily correlated with transmissibility. Nevertheless, longer observation periods should be considered. Serial IgG/IgM antibody tests might be conductive to ascertaining the situation. Further studies are needed to investigate the proportion of immunocompromised patients with prolonged nucleic acid conversion. The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation.