Longitudinal immune profiling of a SARS-CoV-2 reinfection in a solid organ transplant recipient

Abstract

The underlying immunologic deficiencies enabling SARS-CoV-2 reinfections are currently unknown. Here we describe a renal-transplant recipient who developed recurrent, symptomatic SARS-CoV-2 infection 7 months after primary infection. To elucidate the immunological mechanisms responsible for reinfection, we performed longitudinal profiling of cellular and humoral responses during both primary and recurrent SARS-CoV-2 infection. We found that the patient responded to the primary infection with transient, poor-quality adaptive immune responses that was further compromised by intervening treatment for acute rejection of the renal allograft prior to reinfection. Importantly, we identified the development of neutralizing antibodies and humoral memory responses prior to SARS-CoV-2 reinfection. However, these neutralizing antibodies failed to confer protection against reinfection, suggesting that additional factors are required for efficient prevention of SARS-CoV-2 reinfection. Further, we found no evidence supporting viral evasion of primary adaptive immune responses, suggesting that susceptibility to reinfection may be determined by host factors rather than pathogen adaptation.

The Immunology of SARS-CoV-2 Infection and Vaccines in Solid Organ Transplant Recipients

“…Ten weeks after discharge, the patient received antithymocyte globulin, methylprednisolone, and rituximab because of biopsy-proven acute T cell-and antibody-mediated rejection. Four months later, the patient developed mild COVID-19 illness with a different lineage of SARS-CoV-2 [134].…”

SARS-CoV-2 reinfection in a healthcare worker: First case in Portugal confirmed by viral genome sequencing

“…12 On the other hand, the presence of neutralizing antibodies during primary infection may be insufficient to confer protection against reinfection, as recently illustrated by a case of a solid organ transplant recipient with COVID-19, whose underlying immune deficiencies (ie, low naïve T CD4+ pools) resulted in a poor neutralizing antibody quality insufficient to protect against SARS-CoV-2 reinfection. 2 To date it is not yet clear if SARS-CoV-2 reinfections are isolated events in individuals unable to mount an effective adaptive immune response, and ultimately what is required to develop strong humoral responses, or if they will be seen more frequently in the setting of newly emerging variants with the potential to evade immune response. Importantly, regarding this last point, in the SARS-CoV-2 Immunity and Reinfection Evaluation study, the variant of concern B.1.1.7 (renamed as Alpha variant) circulated during the observation period, causing nearly 50% of all infections, although not seeming to have an influence on the rates of reinfection.…”

“…On one hand, failure to detect antibodies in serum in an individual after natural infection or even vaccination does not mean that they will not rapidly produce antibody upon re-exposure to the same pathogen, which is attributed to memory B cells and long-lived plasma cells, with a more rapid and stronger response and thus mitigating disease severity or preventing reinfection altogether 12 . On the other hand, the presence of neutralizing antibodies during primary infection may be insufficient to confer protection against reinfection, as recently illustrated by a case of a solid organ transplant recipient with COVID-19, whose underlying immune deficiencies (ie, low naïve T CD4+ pools) resulted in a poor neutralizing antibody quality insufficient to protect against SARS-CoV-2 reinfection 2 . To date it is not yet clear if SARS-CoV-2 reinfections are isolated events in individuals unable to mount an effective adaptive immune response, and ultimately what is required to develop strong humoral responses, or if they will be seen more frequently in the setting of newly emerging variants with the potential to evade immune response.…”

“…However, well documented reports of reinfection with SARS-CoV-2 virus remain relatively uncommon. 1,2 Studies have shown that most COVID-19 patients, regardless of the severity of infection, develop long-lasting SARS-CoV-2 specific adaptive immunity for as long as 8 months, 3 and a prospective cohort study of antibody responses following symptomatic SARS-CoV-2 infection in healthcare workers has demonstrated that >95% of them had persistent detectable spike protein antibodies up to 200 days postinfection and at least 95% of individuals were predicted to remain seropositive to Santibody at 465 days in a mathematical model. 4 Reinfection was investigated in a large cohort of antibody-positive individuals who were followed for up to 35 weeks and it was shown to be a rare phenomenon with natural infection eliciting protection with an efficacy of > 90%.…”

“…On August 2020 the first case of re-infection by a phylogenetically distinct variant of SARS-CoV-2 was reported and, since then, an increasing number of cases have been recognized worldwide. However, well documented reports of reinfection with SARS-CoV-2 virus remain relatively uncommon 1,2 …”