The Magnitude and Functionality of SARS-CoV-2 Reactive Cellular and Humoral Immunity in Transplant Population Is Similar to the General Population Despite Immunosuppression

Thieme, Constantin J.; Anft, Moritz; Paniskaki, Krystallenia; Blázquez-Navarro, Arturo; Doevelaar, Adrian; Seibert, Felix S.; Hoelzer, Bodo; Konik, Margarethe; Meister, Toni Luise; Pfaender, Stephanie; Steinmann, Eike; Berger, Marc Moritz; Brenner, Thorsten; Kölsch, Uwe; Dolff, Sebastian; Roch, Toralf; Witzke, Oliver; Schenker, Peter; Viebahn, Richard; Stervbo, Ulrik; Westhoff, Timm H.; Babel, Nina

doi:10.1097/tp.0000000000003755

Cited by 31 publications

(45 citation statements)

References 46 publications

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“…In a larger cohort, we previously reported that SARS‐CoV‐2‐CMI was present by ICS in 57.1% and 57.9% of KT recipients at months 4 and 6 after the diagnosis, respectively 5 . In other study, SARS‐CoV‐2‐specific CD4 + polyfunctional T cell responses were detected in 9 out of 10 patients—most of them KT recipients—during the acute phase of COVID‐19 6 . Hartzell et al reported that stable KT recipients on tacrolimus‐based immunosuppression hospitalized due to COVID‐19 exhibited changes in peripheral blood immune cell phenotypes similar to those observed in the general population 12 …”

Section: Discussionmentioning

confidence: 82%

“…The absence of significant differences in between LT recipients and matched nontransplant patients in the magnitude of SARS‐CoV‐2‐CMI would support this notion. Thieme et al also reported that SARS‐CoV‐2‐specific M‐ and S‐reactive polyfunctional CD8 + T cell counts and neutralizing antibody‐titers did not differ between SOT recipients and nontransplant controls 6 . In a mixed cohort of SOT recipients, Favà et al demonstrated the development of robust serological and functional responses comparable to nontransplant patients during early convalescence 7 .…”

Section: Discussionmentioning

confidence: 99%

“…Only a few studies have analyzed the kinetics of SARS‐CoV‐2‐CMI in solid organ transplant (SOT) recipients following COVID‐19, 4–7,12,13 and none of them were focused on the LT population. By means of an ELISpot assay, Candon et al characterized SARS‐CoV‐2‐specific T cells in a small group of KT recipients at a shorter interval from symptom onset than in our cohort (median of 38.5 days).…”

Section: Discussionmentioning

confidence: 99%

“…The understanding of the magnitude and durability of natural immunity following SARS‐CoV‐2 infection among immunocompromised patients is of paramount relevance to determine the individual susceptibility to reinfection. Previous studies have assessed SARS‐CoV‐2‐specific T cell–mediated immunity (SARS‐CoV‐2‐CMI) in kidney transplant (KT) recipients recovered from COVID‐19, revealing that interferon (IFN)‐γ‐producing CD4 + and CD8 + T cells reactive to the spike (S) glycoprotein and other structural proteins may be detected for at least 6 months 4–7 . Specific data for LT recipients, however, are lacking.…”

Section: Introductionmentioning

confidence: 99%

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T cell–mediated response to SARS-CoV-2 in liver transplant recipients with prior COVID-19

Fernández‐Ruiz

Olea

Almendro-Vázquez

et al. 2021

American Journal of Transplantation

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Whether immunosuppression impairs severe acute respiratory syndrome coronavirus 2‐specific T cell–mediated immunity (SARS‐CoV‐2‐CMI) after liver transplantation (LT) remains unknown. We included 31 LT recipients in whom SARS‐CoV‐2‐CMI was assessed by intracellular cytokine staining (ICS) and interferon (IFN)‐γ FluoroSpot assay after a median of 103 days from COVID‐19 diagnosis. Serum SARS‐CoV‐2 IgG antibodies were measured by ELISA. A control group of nontransplant immunocompetent patients were matched (1:1 ratio) by age and time from diagnosis. Post‐transplant SARS‐CoV‐2‐CMI was detected by ICS in 90.3% (28/31) of recipients, with higher proportions for IFN‐γ‐producing CD4+ than CD8+ responses (93.5% versus 83.9%). Positive spike‐specific and nucleoprotein‐specific responses were found by FluoroSpot in 86.7% (26/30) of recipients each, whereas membrane protein‐specific response was present in 83.3% (25/30). An inverse correlation was observed between the number of spike‐specific IFN‐γ‐producing SFUs and time from diagnosis (Spearman's rho: −0.418; p value = .024). Two recipients (6.5%) failed to mount either T cell–mediated or IgG responses. There were no significant differences between LT recipients and nontransplant patients in the magnitude of responses by FluoroSpot to any of the antigens. Most LT recipients mount detectable—but declining over time—SARS‐CoV‐2‐CMI after a median of 3 months from COVID‐19, with no meaningful differences with immunocompetent patients.

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Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

T cell–mediated response to SARS-CoV-2 in liver transplant recipients with prior COVID-19

Fernández‐Ruiz

Olea

Almendro-Vázquez

et al. 2021

American Journal of Transplantation

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“…Recently, Thieme et al found comparable cellular and humoral immune responses to SARS-CoV-2 infection in SOT recipients on immunosuppressants vs non-immunosuppressed (non-transplant) patients [49]. Over-activation of the complement system and a prolonged inflammatory response due to discordant expression of type I and II cytokines results in a cytokine storm and unfavourable outcomes in SARS-CoV-2 infection [50].…”

Section: Discussionmentioning

confidence: 99%

Impact of COVID-19 on liver transplant recipients–A systematic review and meta-analysis

et al. 2021

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Background: Immunosuppression and comorbidities increase the risk of severe coronavirus disease-2019 in solid organ transplant (SOT) recipients. The outcomes of COVID-19 in liver transplant (LT) recipients remain unclear. We aimed to analyse the outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in LT recipients. Methods: The electronic databases were searched for articles published from 1 December 2019 to 20 May 2021 with MeSH terms COVID-19, SARS-CoV-2, and liver transplantation. Studies reporting outcomes in more than 10 LT recipients were included for analysis. LT vs non-LT patients with COVID-19 infection were compared for all-cause mortality, which was the primary outcome studied. We also evaluated the relation between the timing of COVID-19 infection post-LT (< one year vs > one year) and mortality. Findings: Eighteen articles reporting 1,522 COVID-19 infected LT recipients were included for the systematic review. The mean age (standard deviation [SD]) was 60¢38 (5¢24) years, and 68¢5% were men. The mean time (SD) to COVID-19 infection was 5¢72 (1¢75) years. Based on 17 studies (I 2 = 7¢34) among 1,481 LT recipients, the cumulative incidence of mortality was 17¢4% (95% confidence interval [CI], 15¢4À19¢6). Mortality was comparable between LT (n = 610) and non-LT (n = 239,704) patients, based on four studies (odds ratio [OR], 0¢8 [0¢6À1¢08]; P = 0¢14). Additionally, there was no significant difference in mortality between those infected within one year vs after one year of LT (OR, 1¢5 [0¢63À3¢56]; P = 0¢35). The cumulative incidence of graft dysfunction was 2¢3% (1¢3À4¢1). Nearly 23% (20¢71À25) of the LT patients developed severe COVID-19 infection. Before infection, 71% and 49% of patients were on tacrolimus and mycophenolate mofetil, respectively. Immunosuppression was modified in 55¢9% (38¢1À72¢2) patients after COVID-19 infection. Interpretation: LT and non-LT patients with COVID-19 have a similar risk of adverse outcomes.

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Humoral and cellular immune response in patients of liver cirrhosis and immunocompetent recipient of ChAdOx1nCoV-19 Vaccine (Covishield)

Dandu,

Goel,

Kumar

et al. 2024

Clin Exp Med

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Despite the effectiveness of COVID-19 vaccination in reducing the severity of the disease, the demand for booster is increasing in vulnerable populations like elderly and immunocompromised individuals especially with each new wave of COVID-19 in different countries. There is limited data on the sustained immunity against COVID-19 in patients with liver cirrhosis. The study was aimed to compare the T cell and humoral immune response after 1 year of ChAdOx1nCoV-19 Vaccine in patients with liver cirrhosis and healthy health care workers (HCW). This was a prospective observational study including 36 HCW, 19 liver cirrhosis patients and 10 unvaccinated individuals. Anti-SARS-CoV-2S antibody, neutralizing antibody and memory T cell subsets were evaluated by ELISA and flow cytometry, respectively, in all three groups after 1 year of initial vaccination. Compared to HCW and unvaccinated individuals, liver cirrhosis patients had significantly depleted T cells, although CD4:CD8 + T cell ratio was normal. Both cirrhotic patients and HCW developed memory T cell subset [effector memory RA (P = 0.141, P < 0.001), effector memory (P < 0.001, P < 0.001), central memory (P < 0.001, P < 0.01), stem cell memory (P = 0.009, P = 0.08) and naïve (P < 0.001, P = 0.02)] compared to unvaccinated unexposed individuals of CD4 + T and CD8 + T, respectively. However, among HCW and cirrhotic group no difference was noted on central memory and stem cell memory cells on T cells. Patients with liver cirrhosis developed comparable memory T cells after vaccination which can evoke sustainable immune response on reinfection. Therefore, additional vaccine doses may not be necessary for cirrhosis patients.

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The Magnitude and Functionality of SARS-CoV-2 Reactive Cellular and Humoral Immunity in Transplant Population Is Similar to the General Population Despite Immunosuppression

Abstract: Supplemental Digital Content is available in the text.

Cited by 31 publications

References 46 publications

T cell–mediated response to SARS-CoV-2 in liver transplant recipients with prior COVID-19

T cell–mediated response to SARS-CoV-2 in liver transplant recipients with prior COVID-19

Impact of COVID-19 on liver transplant recipients–A systematic review and meta-analysis

Humoral and cellular immune response in patients of liver cirrhosis and immunocompetent recipient of ChAdOx1nCoV-19 Vaccine (Covishield)

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