The longest persistence of viable SARS-CoV-2 with recurrence of viremia and relapsing symptomatic COVID-19 in an immunocompromised patient – a case study

Abstract

BackgroundImmunocompromised patients show prolonged shedding of SARS-CoV-2 in nasopharyngeal swabs. We report a case of a prolonged persistence of viable SARS-CoV-2 associated with clinical relapses of COVID-19 in a lymphoma patient.MethodsNasopharyngeal swabs and blood samples were tested for SARS-CoV-2 by Real time-PCR (RT-PCR). On five positive nasopharyngeal swabs, we performed viral culture and next generation sequencing. We analysed the patients’ adaptive and innate immunity to characterize T and NK cell subsets.FindingsSARS-CoV-2 RT-PCR on nasopharyngeal swabs samples remained positive with cycle threshold mean values of 22 ± 1·3 for over 8 months. All five performed viral cultures were positive and genomic analysis confirmed a persistent infection with the same strain. Viremia resulted positive in three out of four COVID-19 clinical relapses and cleared each time after remdesivir treatment. T and NK cells dynamic was different in aviremic and viremic samples and no SARS-CoV-2 specific antibodies were detected throughout the disease course.InterpretationIn our patient, SARS-CoV-2 persisted with proven infectivity for over eight months. Viremia was associated with COVID-19 relapses and remdesivir treatment was effective in viremia clearance and symptoms remission, although it was unable to clear the virus from the upper respiratory airways. During the viremic phase, we observed a low frequency of terminal effector CD8+ T lymphocytes in peripheral blood that are probably recruited in inflammatory tissue for viral eradication. In addition we found a high level of NK cells repertoire perturbation with a relevant involvement during SARS-CoV-2 viremia.FundingNone.

Insertions in SARS-CoV-2 genome caused by template switch and duplications give rise to new variants that merit monitoring

“…Compared to the receptor binding domain, the NTD initially attracted much less attention. Subsequently, however, multiple substitutions associated with variants of concern and observed in immunocompromised individuals with extended COVID-19 disease were identified in the NTD 2,35,36 . To evaluate potential functional effects of the inserts in the NTD, we mapped them onto the protein structure.…”

Investigating the presence of SARS-CoV-2 on the Surfaces, Fomites, and in Indoor Air of a referral COVID-19 Hospital in a Middle Eastern Area

“…Besides, SARS-Co-V-2 was not detected in the air of patients' rooms in a study by Sean Wei Xiang Ong (Ong et al 2020).3.2 Results of surfaces and fomites sampling Many studies on the airborne transmission of the SARS-CoV-2 have used the RT-PCR test for diagnosis. Nevertheless, the RT-PCR test detects only SARS-CoV-2 RNA, not the viable or infectious form of virus (Sepulcri et al 2021). Therefore, this technique cannot express the infectious ability of the virus (Ram et al 2021).…”

A Possible Role of Remdesivir and Plasma Therapy in the Selective Sweep and Emergence of New SARS-CoV-2 Variants

“…Until autumn 2020, SARS-CoV-2 genetic diversity was most often deemed to be low, as reported in the study of 27,977 SARS-CoV-2 genomes from 84 countries [ 37 ] or in analyses suggesting that the diversity in the surface glycoproteins of influenza A viruses was 437-fold greater than that measured in the SARS-CoV-2 spike [ 38 ]. Thereby, the rapid emergence of several SARS-CoV-2 strains with increased number of mutations, particularly in the spike-encoding gene, that has been reported in some recent observations [ 13 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ] ( Table 1 ) questions whether an event (e.g., genetic or ecologic) has occurred that may have modified the virus replication process or the host-dependent virus selection to promote and spread variant viruses that are more transmissible than the previously-circulating strains and capable of escaping immune responses in some cases [ 30 , 32 , 39 ]. It raises fears of an over-amplification of the pandemic worldwide.…”

“…A second hypothesis to explain the emergence and selection of new SARS-CoV-2 variants, the interventionist therapy hypothesis, is linked to the selective pressure of treatments. In order to treat severe COVID-19, some patients received immunoglobulin-based immunotherapy with hyper-immune sera from convalescent COVID-19 patients [ 13 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 61 ] ( Table 1 ). However, a study reported that, of the sera from 26 patients who recovered from COVID-19 and exhibited high titers of anti-SARS-CoV-2 immunoglobulins, only three effectively blocked the binding of the SARS-CoV-2 spike protein to ACE2 [ 62 ].…”

“…These findings could possibly explain why such variants harboring Delta69/70 deletion and N501Y substitution emerged in countries such as the UK where remdesivir is routinely used for the treatment of hospitalized SARS-CoV-2 patients with chronic infection. Seven other studies reported cases of 50–75-year-old immunocompromised patients with hematological malignancies or severe hypogammaglobulinemia who experienced viral shedding between 41 and 268 days and received one to four cures of remdesivir and/or one or five administrations of convalescent plasma [ 21 , 22 , 23 , 24 , 25 , 26 , 27 ]. Four patients eventually died at days 74–271 after SARS-CoV-2 diagnosis.…”