Better late than never: eventual seroconversion against SARS-CoV-2 in a kidney transplant recipient after repeated immune challenge and monoclonal antibody therapy.

To the editor:

Kidney transplant recipients are disproportionately affected by coronavirus disease 2019 (COVID-19). In addition to limited therapeutic options, concerns have arisen regarding poor vaccine efficacy in this population.

We report the case of a 64-year-old kidney transplant recipient treated with an association of tacrolimus, mycophenolate mofetil, and steroids who developed a second severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection 1 year after a first COVID-19 episode, and 55 days after receiving his second BNT162b2-mRNA vaccine injection (Pfizer–BioNTech). Three days after the onset of isolated fever, a high viral load of SARS-CoV-2 gamma variant was detected through reverse transcriptase polymerase chain reaction in a nasopharyngeal swab (Table 1 ). Mycophenolate mofetil was interrupted, and i.v. monoclonal antibody (casirivimab, 1200 mg, and imdevimab, 1200 mg; Regeneron) therapy was given. Clinical and virological evolutions were favorable: viral load decreased <1000 copies/ml on day 8 and was eventually negative on day 28 after perfusion (Table 1). Interestingly, an anti-N native antibody seroconversion was observed on day 28 (Table 1). Notably, 3 serologic tests had been performed before the second SARS-CoV-2 infection (including one 43 days after the second vaccine dose injection) and were all negative for both anti-N and anti–receptor-binding domain antibody.

Table 1

Evolution of SARS-CoV-2 viral load and anti–SARS-CoV-2 antibody titers after monoclonal antibody therapy

Variable	Day 0	Day 8	Day 28
Viral load, copies/ml	10,264,225	570	0
Anti-N antibody (index)	0.083	0.221	7.74
Anti-RBD antibody titer, U/ml	0.701	57,753	40,135

RBD, receptor-binding domain; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

Day 0 indicates day of monoclonal antibody perfusion. Positivity thresholds: anti-N antibody, ≥1; anti-RBD antibody, ≥0.8 U/ml (upper detection limit of the assay, 250 U/ml).

Anti–SARS-CoV-2 monoclonal antibodies have shown promising effects in COVID-19, and preliminary results suggest efficacy in preventing severe disease after solid organ transplantation. Our patient eventually mounted a natural immunity against SARS-CoV-2 in a context of repeated previous immune challenges and immunosuppression tapering. The effect of passive immunization on the development of protective immunity remains unknown. Whether monoclonal antibody infusion has promoted the development of natural immunity against SARS-CoV-2 remains to be investigated.