Severe relapse of SARS-CoV-2 infection in a kidney transplant recipient with negative nasopharyngeal SARS-CoV-2 RT-PCR after rituximab

Abstract

Immunocompromised patients may experience prolonged viral shedding after their initial SARS‐CoV‐2 infection, however, symptomatic relapses after remission currently remain rare. We herein describe a severe COVID‐19 relapse case of a kidney transplant recipient (KTR) following rituximab therapy, 3 months after a moderate COVID‐19 infection, despite viral clearance after recovery of the first episode. During the clinical relapse, the diagnosis was established on a broncho‐alveolar lavage specimen (BAL) by RT‐PCR. The infectivity of the BAL sample was confirmed on a cell culture assay. Whole genome sequencing confirmed the presence of an identical stain (Clade 20A). However, it had an acquired G142D mutation and a larger deletion of 3‐amino‐acids at position 143–145. These mutations located within the N‐terminal domain are suggested to play a role in viral entry. The diagnosis of a COVID‐19 relapse should be considered in the setting of unexplained persistent fever and/or respiratory symptoms in KTRs (especially for those after rituximab therapy), even in patients with previous negative naso‐pharyngeal SARS‐CoV‐2 PCR.

SARS-COV-2 Delta and Omicron community transmission networks

“…The G142D mutation has been associated with increased viral load and immune evasion, exhibiting frequent back mutation as observed here [17]. This same mutation was also associated with symptomatic relapse in a kidney transplant patient who was unable to clear the virus [18]. It may be that the presence of this mutation is associated with immune pressure and possibly escape.…”

Detection of viable SARS-CoV-2 in deep respiratory specimens despite negative nasopharyngeal SARS-CoV-2 RT-PCR: Occult COVID-19 as an unsuspected cause of pulmonary infiltrates in immunocompromised patients

“…Seroconversion rates of 17.5-40% have been reported in the literature [10] , [11] . Similarly, other cases of occult COVID-19 reported in the literature occurred in individuals who received anti-CD20 treatment and were unable to produce neutralising antibodies to SARS-CoV-2 [5] , [12] . Both our cases made a full recovery after administration of antivirals and monoclonal antibodies directed against COVID-19; this was in keeping with emerging data suggesting good clinical outcomes in B-cell-depleted patients treated with anti-spike monoclonal antibodies [13] .…”

“…A COVID-19 relapse was defined as a clinical episode of symptoms consistent with acute COVID-19, accompanied by re-positive/persisting polymerase-chain-reaction (PCR) test for SARS-CoV-2 in respiratory samples, within 90 days of initial infection [4] . Occult COVID-19 was defined as COVID-19 relapse with negative PCR results on NP swab [5] , with positive PCR on deeper respiratory specimens (endotracheal-aspirates [ETA] or bronchoalveolar- lavage [BAL]).…”

“…In particular, patients with secondary hypogammaglobulinemia after receipt of anti-CD20 treatment (eg.rituximab) tend to have more severe COVID-19 manifestations [1] , [2] , [3] . Amongst COVID-19 cases receiving concurrent rituximab, prolonged shedding or relapse has been encountered [4] , [5] . Cases of occult COVID-19, in which SARS-CoV-2 relapse in lung parenchyma is diagnosed despite repeated demonstration of negative PCR from nasopharyngeal (NP) specimens, have been rarely reported in the literature [5] .…”

“…Amongst COVID-19 cases receiving concurrent rituximab, prolonged shedding or relapse has been encountered [4] , [5] . Cases of occult COVID-19, in which SARS-CoV-2 relapse in lung parenchyma is diagnosed despite repeated demonstration of negative PCR from nasopharyngeal (NP) specimens, have been rarely reported in the literature [5] . We describe two patients who received rituximab and presented with ground-glass opacities (GGO) on lung imaging; COVID-19 relapse was originally not suspected due to negative NP swabs and diagnosed only after invasive sampling.…”