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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.

SUBMITTER: Klein J

PROVIDER: S-EPMC8132249 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThis is a descriptive study to characterize rates of SARS-CoV-2 infection in pediatric solid organ transplant (SOT) recipients during the early days of the pandemic. We hypothesized that asymptomatic infection may represent a large proportion of SARS-CoV-2 infection in ped SOT recipients.MethodsWe queried OTTR for all pediatric SOT recipients followed at our center and reviewed medical records to identify patients tested for SARS-CoV-2 between March 15, 2020 through June 30, 2021. Patients were tested by PCR: prior to planned procedures or because of symptoms; OR: tested by measurement of IgG to spike protein with their routine labs q 2-monthly. A positive PCR was called acute infection. A positive IgG with negative PCR was called convalescence. For immunologic studies, blood was obtained when the PCR or IgG was positive. Statistical comparisons were made between (i) acute infection vs. convalescence; (ii) acute infection vs. SOT recipients without infection (called healthy controls); (iii) LT vs. SB/MVT; (iii) positive vs. negative test result.ResultsOf 257 liver transplant (LT) recipients, 99 were tested: 6 were PCR positive,13 were antibody positive. Of 150 small bowel (SB)/ multi-visceral transplant (MVT) recipients, 55 were tested: 4 were PCR positive, 6 were antibody positive. Of 8 simultaneous liver, kidney transplant recipients, 3 were tested: 1 was PCR positive. Symptoms when present were mostly mild. Patients with a positive test result were younger (6.3 vs. 10.0-years; p=0.017). We observed a rapid decline in viral load within 96-hours without a change in immunosuppression. Antibody lasted >8-months beyond the time it was monitored. Acute infection was associated with increased CD4 and CD8 TEM cell frequency (p=0.04, p=0.03 respectively), decreased IFN-γ production from T-cells (2.8% vs.11.3% p=0.006), and decreased CD8 TEMRA frequency (4.56% vs.11.70% p=0.006).ConclusionEarly in the pandemic, COVID-19 disease was mostly mild in pediatric SOT recipients with no rejection, patient death, or graft loss observed.

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

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