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

Abstract

Prior to the emergence of antigenically distinct SARS-CoV-2 variants, reinfections were reported infrequently - presumably due to the generation of durable and protective immune responses. However, case reports also suggested that rare, repeated infections may occur as soon as 48 days following initial disease onset. 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 - confirmed by whole virus genome sequencing - 7 months after primary infection. To elucidate the immunological mechanisms responsible for SARS-CoV-2 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. The patients immune system was further compromised by intervening treatment for acute rejection of the renal allograft prior to reinfection. Importantly, we also identified the development of neutralizing antibodies and the formation of 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 in this patient. In summary, our study suggests that a low neutralizing antibody presence alone is not sufficient to confer resistance against reinfection. Thus, patients with solid organ transplantation, or patients who are otherwise immunosuppressed, who recover from infection with SARS-CoV-2 may not develop sufficient protective immunity and are at risk of reinfection.

Severe Acute Respiratory Syndrome Coronavirus 2 Reinfection Cases Corroborated by Sequencing

“…In total, 35 articles describing the clinical courses of 60 unique individuals were identified that met the criteria. 7 – 14 , 18 – 43 An additional 114 articles were identified following abstract screening, but were not included in the analysis because they did not have sufficient sequencing results to conclude that the cases were reinfections. In total, 60 cases of verified reinfection were identified in this search.…”

SARS-CoV-2 Reinfection Is a New Challenge for the Effectiveness of Global Vaccination Campaign: A Systematic Review of Cases Reported in Literature

“…Then, we extracted the relevant data and organized them in tables. The original papers that were peer-reviewed and published in English and fulfilled the eligibility criteria were included in the final report, together with two works not reviewed at the time of preparation of this report [30,31].…”

Evaluation of accuracy, exclusivity, limit-of-detection and ease-of-use of LumiraDx™: An antigen-detecting point-of-care device for SARS-CoV-2

“…This could explain variable performance between two geographically distinct sites (in the Pacific North West of the USA in the study by Drain et al [ 15 ] and Germany). However, this appears very unlikely given the multiple antibodies used in the test that target the nucleocapsid, which is a rather conserved target even in recent strain variants [ 30 ]. While a hook or prozone effect could be considered, it appears unlikely in light of the sample type and has not been shown in prior experiments by the manufacturer [ 12 ].…”