Persistence of SARS-CoV-2 antibodies in kidney transplant recipients

Abstract

To the Editor: Data on the long- and middle-term dynamics of antibody response to SARS-CoV-2 after COVID-19 in the immunocompromised population remain scanty while reports on a decrease in antibody titers in immunocompetent patients are controversial.1Yang OO Ibarrondo FJ. Loss of anti-SARS-CoV-2 antibodies in mild Covid-19. Reply.N Engl J Med. 2020; 383: 1697-1698PubMed Google Scholar,2Baumgarth N Nikolich-Žugich J Lee FE-H Bhattacharya D. Antibody responses to SARS-CoV-2: let’s stick to known knowns.J Immunol. 2020; 205: 2342-2350Crossref PubMed Scopus (55) Google Scholar We have previously described the serological response against SARS-CoV-2 in 35 kidney transplant recipients (KTR) hospitalized for COVID-19 until 2 months after symptoms onset.3Benotmane I Gautier-Vargas G Wendling M-J et al.In-depth virological assessment of kidney transplant recipients with COVID-19.Am J Transplant. 2020; 20: 3162-3172Abstract Full Text Full Text PDF PubMed Scopus (57) Google Scholar Here, antibody levels were prospectively measured in the same cohort for up to 6 months after symptom onset. Titers of IgM and IgG binding antibodies against SARS-CoV-2 recombinant nucleocapsid and spike antigens were quantified using a commercially available ELISA (DIA.PRO Diagnostic BioProbes Srl, Sesto San Giovanni, Italy).3Benotmane I Gautier-Vargas G Wendling M-J et al.In-depth virological assessment of kidney transplant recipients with COVID-19.Am J Transplant. 2020; 20: 3162-3172Abstract Full Text Full Text PDF PubMed Scopus (57) Google Scholar Samples with a signal to cutoff ratio (S/CO) ≥1.1 were considered positive, ≥0.9 and <1.1 equivocal, and <0.9 negative. The study protocol was reviewed and approved by the local Institutional Review Board (approval number: DC-2013–1990). All surviving patients (n = 29) described in our previous study3Benotmane I Gautier-Vargas G Wendling M-J et al.In-depth virological assessment of kidney transplant recipients with COVID-19.Am J Transplant. 2020; 20: 3162-3172Abstract Full Text Full Text PDF PubMed Scopus (57) Google Scholar (86% men; median age: 60.3 years; interquartile range [IQR]: 52.3–66.8 years; median body mass index: 28 kg/m2 [IQR: 24–33 kg/m2]) were included in this follow-up. Eight patients had severe COVID-19 (oxygen requirement >6 L/min; need for intensive care unit admission; and/or death), whereas the remaining 21 had a non-severe disease. Overall, 194 samples were analyzed (median number of sera per patient: 7; IQR: 5.5–8). All sera tested as of day 13 (D13) were positive. IgM and IgG were detectable after a median of D17 and reached a peak at D37 (IQR: 23–48) and D38 (IQR: 30–50), respectively (Figure 1A,B). IgG peak levels were positively associated with viral load peaks in nasopharyngeal swabs (Spearman’s ρ = 0.36, p = .05) and inversely correlated with the duration of positive RNA testing for SARS-CoV-2 (ρ = –0.46, p = .001). The median percentage decline for IgM and IgG was 83% (IQR: 70–91%) and 68% (IQR: 32%–83%), respectively. Between D145 and D190, the vast majority of patients (n = 21, 72.4%) remained seropositive, two had equivocal IgG results in the absence of IgM, and only six (20.7%) were found to be seronegative. Patients treated with calcineurin inhibitors and steroids showed a more pronounced IgG reduction (Table 1), which was inversely correlated with the IgG peak (ρ = –0.46, p = .001). IgG peak levels and kinetics did not differ significantly according to COVID-19 severity (Table 1).TABLE 1Anti-SARS-CoV-2 IgG peak levels and anti-SARS-CoV-2 IgG decrease rates according to demographic and clinical characteristics of hospitalized kidney transplant recipients with COVID-19 (n = 29)NIgG peak levelpIgG decrease ratepDisease severityaOxygen requirement >6 L/min; need for intensive care unit admission; and/or death.Non-severe patient2110.0 [5.7–11.2].6668% [34–84].56Severe patient810.0 [7.4–10.5]59% [28–77]Age, years<60148.4 [6.0–10.9].6371% [61–84].09≥601510.3 [9.3–11.2]45% [18–80]SexFemale48.7 [6.3–10.3].4584% [69–86].27Male2510.3 [6.9–11.2]63% [32–78]Body mass index, kg/m2<301610.0 [7.3–11.3].6164% [33–80].79≥301310.3 [5.5–10.8]69% [32–83]Cardiovascular comorbidityNo1810.3 [5.5–11.5].9871% [31–80].91Yes1110 [9.1–10.8]61% [36–84]Respiratory diseaseNo229.9 [6.1–10.7].2373% [61–84].01Yes711.1 [8.8–11.8]23% [9–23]DiabetesNo1810 [7.4–12].8264% [32–82].43Yes1110.3 [5–11]73% [38–88]HBPNo710 [7.1–11.1].8568% [42–88].63Yes2210.1 [5.9–12.1]66% [31–80]Immunosuppressive induction therapyAnti-thymocyte globulin149.1 [6–12].665% [32–85].75Anti-CD251210.6 [8.5–11.4]79% [35–79]No induction310 [8.7–10.6]51% [40–73]Immunosuppressive maintenance therapyCNINo49.7 [8–10.3].6637% [17–54].05Yes2510.3 [6.9–11.2]73% [34–84]MMF/MPANo410.1 [9.4–10.4]169% [55–79].68Yes2510 [5.7–11.2]68% [31–83]mTORiNo2410 [5.7–11.3].7568% [32–83].84Yes510 [10–10.8]63% [51–75]SteroidsNo1410.6 [9.1–12.1].2248% [24–74].06Yes159.4 [5.6–12]73% [62–88]Clinical symptomsDyspneaNo1211.4 [6.6–11.4].4869% [32–82]1Yes1710 [7.4–10.8]64% [35–82]CoughNo86.6 [5–9.3].0869% [34–83].72Yes2110.3 [9.4–11.2]64% [31–82]DiarrheaNo59.4 [7.4–9.7].2261% [38–74].43Yes2410.3 [6.6–11.3]71% [32–85]IgG peak is presented as the signal to cutoff ratio (S/CO) and is expressed as median (interquartile range). IgG decrease is summarized as the median percentage decline (interquartile range).Abbreviations: CNI, calcineurin inhibitors; HBP, high blood pressure; MMF, mycophenolate mofetil; MPA, mycophenolic acid, mTORi, mammalian target of rapamycin inhibitors.a Oxygen requirement >6 L/min; need for intensive care unit admission; and/or death. Open table in a new tab IgG peak is presented as the signal to cutoff ratio (S/CO) and is expressed as median (interquartile range). IgG decrease is summarized as the median percentage decline (interquartile range). Abbreviations: CNI, calcineurin inhibitors; HBP, high blood pressure; MMF, mycophenolate mofetil; MPA, mycophenolic acid, mTORi, mammalian target of rapamycin inhibitors. To our knowledge, this is the first study to describe the 6-month evolution of SARS-CoV-2 antibodies in an immunocompromised population. While 20.7% of the study patients became seronegative, 72.4% were found to display anti-SARS-CoV-2 antibodies up to 6 months after COVID-19. Despite a prolonged period of viral shedding in KTR,4Caillard S, Benotmane I, Vargas GG, Perrin P, Fafi-Kremer S. SARS-CoV-2 viral dynamics in immunocompromised patients. Am J Transplant. 2020. https://doi.org/10.1111/ajt.16353.Google Scholar the antibody kinetics were close to those observed in immunocompetent subjects—with an antibody peak titer reached at approximately D40. An initial decline in antibody titers does not necessarily imply their disappearance. Accordingly, low antibody levels may persist for several years, as it was previously observed for SARS-CoV.2Baumgarth N Nikolich-Žugich J Lee FE-H Bhattacharya D. Antibody responses to SARS-CoV-2: let’s stick to known knowns.J Immunol. 2020; 205: 2342-2350Crossref PubMed Scopus (55) Google Scholar Moreover, disappearance of binding antibodies is not invariably correlated with neutralizing antibodies, B-cell memory, and T-cell response.2Baumgarth N Nikolich-Žugich J Lee FE-H Bhattacharya D. Antibody responses to SARS-CoV-2: let’s stick to known knowns.J Immunol. 2020; 205: 2342-2350Crossref PubMed Scopus (55) Google Scholar A recent study reported a reduction of antibody titers in two KTR without a corresponding decline in T-cell response 2 months after COVID-19,5Candon S, Guerrot D, Drouot L, et al. T cell and antibody responses to SARS-CoV-2: experience from a French transplantation and hemodialysis center during the COVID-19 pandemic. Am J Transplant. 2020;https://doi.org/10.1111/ajt.16348.Google Scholar but these results require confirmation by following a larger cohort for a longer period of time. In conclusion, our findings indicate that SARS-CoV-2 antibodies are present in the majority of KTR at 6 months after COVID-19. The presence of antibodies against SARS-CoV-2 in KTR should be viewed as encouraging with respect to the possibility of eliciting of an immune response to vaccination in this clinical population. However, the question as to whether the 20% of patients who lost their antibodies may be at risk of being re-infected remains unanswered. This study was supported by the Strasbourg University Hospital (COVID-HUS study-HUS No. 7760). The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation.

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