key: cord-0887950-um0x0psz authors: Camprubí-Ferrer, Daniel; Gaya, Anna; Marcos, Maria Angeles; Martí-Soler, Helena; Soriano, Alex; Mosquera, Maria del Mar; Oliver, Aina; Santos, Marta; Muñoz, Jose; García-Vidal, Carol title: Persistent replication of SARS-CoV-2 in a severely immunocompromised treated with several courses of remdesivir date: 2020-12-21 journal: Int J Infect Dis DOI: 10.1016/j.ijid.2020.12.050 sha: 0e48b9c2c94ecc369656c05f6dbf64094c7353da doc_id: 887950 cord_uid: um0x0psz Microbiological response of SARS-CoV-2 to remdesivir in immunocompromised patients has not been evaluated. We present the case of a severely immunocompromised patient with persistent replication of SARS-CoV-2, who required different courses of remdesivir. Short courses of remdesivir might be insufficient in immunocompromised patients due to prolonged viral clearance. More than 37 million people worldwide have been infected and one 1 million has died since first cases of COVID-19 were described [1] . However, data about efficacy of different treatment agents against SARS-CoV-2 is still scarce [2] . Remdesivir is the only antiviral agent that has demonstrated efficacy against COVID-19 in terms of shortening length of hospital stay in a randomized placebo-controlled trial [3]. Another randomized clinical trial (RCT) has shown that a 5-day course of remdesivir is as effective as a 10-day regimen in patients with severe COVID-19 not requiring mechanical ventilation [4] . However, there is no evidence whether these results can be applied to special populations such as immunocompromised patients. Here we present the case of a severely immunocompromised patient with persistent replication of SARS-CoV-2 who required different courses of remdesivir. A 37-year-old woman presented to the hospital with fever. During the previous months, the patient had received 3 cycles of R-ESHAP (rituximab, etoposide, cisplatin, cytarabine and methylprednisolone) due to a relapse of a stage IV-A follicular lymphoma. A partial response was observed by PET-CT and a salvage therapy was about to start when the patient was diagnosed with an upper respiratory tract infection by Influenza A virus, requiring treatment with oseltamivir for 10 days two weeks before the present admission. In March 2020, the patient presented to the hospital with a 3-day history of fever, malaise, anosmia and dysgeusia. At admission, oxygen saturation at room air was 98% and physical exam was unremarkable. Blood tests showed thrombocytopenia and Figure 1 shows the evolution of SARS-CoV-2 adjusted viral load in serial nasopharyngeal swabs and the different antiviral treatments received [5] . Adjusted SARS-CoV-2 viral load initially raised up to 1,1x10 7 copies/1000cells. Coinciding with first remdesivir administration, viral load decreased to 3,1copies/1000cells. However, a new peak on the viral load was observed (4,1x10 3 copies/1000cells) 54 days after symptoms initiation. After a second cycle of remdesivir, a reduction and negativization of viral load was finally achieved (63 days after the onset of symptoms). In this case, remdesivir showed an important antiviral effect in an immunocompromised patient, significantly reducing SARS-CoV-2 viral load, which was not observed with the other antiviral treatments. Remarkably, in our case, the antiviral effect of remdesivir was consistent with different clinical aspects like the resolution of fever, improvement of respiratory insufficiency and decreasing of acutephase reactants (Figure 1) . Notably, the patient presented a positive SARS-CoV-2 PCR 60 days after symptoms' initiation. Median time of viral RNA clearance in nasopharyngeal samples is 20 days but it has been detected after more than 5 weeks [6] . Although some authors suggested possible longer duration of positive PCR in immunocompromised patients, RNA dynamics in this population is unknown [7] [8] [9] . In this case, the increase in the viral load 54 days after symptoms' initiation and the clinical worsening suggested persistent replication of SARS-CoV-2 and supports the hypothesis of persistent replication of SARS-CoV-2 in immunocompromised hosts [8, 9] . Finally, although a RCT showed no benefit of 10-day courses of remdesivir compared with 5 days, no specific evaluation of participants with underlying immunosuppression conditions was reported [4] . Consequently, these results may not be extrapolated to special high-risk populations like severe immunocompromised patients in whom persistent viral replication can play an essential role on the pathogenesis of the disease [4, [7] [8] [9] . In our patient, a late peak on SARS-CoV-2 viral load was detected despite an 8-day regimen of remdesivir. This suggests that short courses of remdesivir might be insufficient for treating high-risk populations such as J o u r n a l P r e -p r o o f severely immunocompromised patients, especially those with humoral immune deficiency [8] . The patient signed an informed consent form and the study was approved the Drug Research Ethics Committee of the Hospital Clinic of Barcelona (CEIm), Barcelona, Spain. WHO Coronavirus disease Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19): A Review Remdesivir for 5 or 10 Days in Patients with Severe Covid-19 Clinical and virological data of the first cases of COVID-19 in Europe: a case series Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan , China : a retrospective cohort study COVID-19 in a Patient With Long-Term Use of Glucocorticoids: A Study of a Familial Cluster Persistent COVID-19 in an immunocompromised patient temporarily responsive to two courses of remdesivir therapy Persistence and evolution of SARS-CoV-2 in an Immunocompromised Host The authors of the article declare no conflicts of interest.The authors of the article want to thank Gilead for allowing reporting the case of a participant included in RCT. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.