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. 2021 Sep 20;106(1):e92-e94. doi: 10.1097/TP.0000000000003962

Efficacy of Convalescent Plasma to Treat Mild to Moderate COVID-19 in Kidney Transplant Patients: A Propensity Score Matching Analysis

Marina Pontello Cristelli 1,, Dante Mário Langhi Junior 2,3, Laila Almeida Viana 1, Luis Gustavo Modelli de Andrade 4, Suelen Bianca Stopa Martins 1, Yasmim Cardoso Dreige 1, José Orlando Bordim 3, Helio Tedesco-Silva 1, José Medina-Pestana 1
PMCID: PMC8667676  PMID: 34581314

Abstract

Supplemental Digital Content is available in the text.


Kidney transplant recipients have higher mortality from coronavirus disease 2019 (COVID-19) compared with the general population.1,2 In the absence of effective treatment,3 the early use of convalescent plasma emerged as an alternative therapy with a favorable safety profile.

This observational, prospective, single-center, single-arm cohort study assessed the 30-d COVID-19–associated lethality in kidney transplant recipients treated with convalescent plasma. The protocol was approved by the local ethics committee, and all patients signed an informed consent form. From February 3, 2021, to March 30, 2021, nonvaccinated patients aged over 30 y with up to 10 d of real-time polymerase chain reaction–confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mild to moderate infection based on the WHO severity criteria4 were eligible to receive 1 single-donor ABO-compatible intravenous infusion of 200 mL of convalescent plasma. Immediately before infusion, the patients were tested for prevalence of anti-SARS-CoV-2 nucleocapsid protein (SARS-CoV-2 IgG test ARCHITECT I System, Abbott Laboratories, IL; cut off of 1.68 S/CO). Plasmas with anti-SARS-CoV-2 immunoglobulin G (IgG) ≥840 AU/mL (absorbance units per milliliter; AdviseDx SARS-CoV-2 IgG II ARCHITECT chemiluminescent immunoassay, Abbott Laboratories) or neutralizing activity ≥68% (%; cPass SARS-CoV-2 Neutralization Antibody Detection Kit, GenScript Laboratories) were labeled as “high-titer plasma” following Food and Drug Administration guidance.5

Between January 1, 2021, and March 30, 2021, 456 kidney transplant recipients developed real-time polymerase chain reaction–confirmed SARS-CoV-2 infection (Figure S3, SDC, http://links.lww.com/TP/C294). Of them, 58 (13%) were treated with convalescent plasma, and 116 were selected to construct the matched control group using a 1 to 2 propensity score matching (Supplementary Statistics S1, SDC, http://links.lww.com/TP/C294).

There were no differences in demographic characteristics, including comorbidities and immunosuppression (Table 1). The median time from symptoms onset to diagnosis of SARS-CoV-2 infection was 3 d in both groups, although patients in the control group had a higher proportion of patients with initial WHO severity scores between 4 and 6 (1.7% versus 6.8%; P = 0.033) and who received azithromycin (8.9% versus 22.2%; P = 0.034), respectively (Table 1).

TABLE 1.

Baseline characteristics, clinical presentation, and management of the 174 patients with confirmed SARS-CoV-2 infection

Convalescent plasma(n = 58) Matched control(n = 116) P
Baseline characteristics
 Age, median (IQR) 50 (40–58) 50 (42–61) 0.676
 Male gender, n (%) 39 (67) 78 (67) >0.999
 BMI >30 kg/m2, n (%) 18 (31) 36 (31) >0.999
 Deceased donor transplants, n (%) 28 (51) 56 (50) 0.956
 Prior transplant, n (%) 2 (3.6) 6 (5.4) >0.999
 Months after transplant, median (IQR) 72 (29–139) 73 (31–134) 0.926
 Immunosuppression, n (%) 0.838
  TAC-AZA 18 (31) 40 (35)
  TAC-MPA 19 (33) 38 (33)
  TAC-mTORi 7(12) 11 (9.6)
  Other 14 (24) 27 (22.5)
 Steroids use, n (%) 55 (98) 114 (98) >0.999
 High steroid dose within the previous 3 mo, n (%) 2 (3.9) 1 (0.9) 0.231
 Antithymocyte globulin within the previous 3 mo, n (%) 2 (3.9) 1 (0.9) 0.231
 Use ACE or ARB, n (%) 18 (33) 43 (39) 0.500
 Current of former smoker, n (%) 9 (44) 28 (30) 0.265
 Hypertension, n (%) 42 (72) 91 (78) 0.377
 Diabetes, n (%) 21 (36) 39 (34) 0.735
 Heart disease, n (%) 2 (3.4) 0 (0) 0.110
 CKD-EPI creatinine eGFR at baseline, median (IQR) 52 (37–64) 50 (34–62) 0.725
 Days from symptoms onset to COVID-19 diagnosis, median (IQR) 3 (2–4) 3 (2–5) 0.458
COVID-19 WHO severity score at presentation, n (%) 0.033
 1—Ambulatory, asymptomatic; viral RNA detected 0 1 (0.9)
 2—Ambulatory, symptomatic; independent 46 (79.3) 62 (53.4)
 3—Ambulatory, symptomatic; assistance needed 11 (19) 45 (38.8)
 4—Hospitalized; no oxygen therapy 1 (1.7) 2 (1.7)
 5—Hospitalized; oxygen by mask or nasal prongs 0 4 (3.4)
 6—Hospitalized; oxygen by NIV or high flow 0 2 (1.7)
Pharmacological treatment during COVID-19,a n (%)
 High-dose steroids 21 (37.5) 48 (44.4) 0.393
 Azithromycin 5 (8.9) 24 (22.2) 0.034
 Other antibiotics 20 (35.7) 42 (38.2) 0.756
 Hydroxychloroquine 0 2 (1.7) 0.301
 Ivermectin 0 2 (1.7) 0.301
 Monoclonal antibodies 0 0
 Remdesivir 0 0
Immunosuppression during COVID-19, n (%)
 No changes 38 (65.5) 67 (58) 0.606
 Suspension of MPA/mTORi/AZA 7(12) 14(12)
 Suspension of all drugs except for steroids 13 (22.5) 28 (24)
 Missing information 0 7 (6)
Outcomes
 Need for oxygen therapy 72% 68% 0.684
 Mechanical ventilation 28% 32% 0.684
 Death 22% 24% 0.950

Bold types means P < 0.05. aOne patient might have used >1 pharmacological treatment during COVID-19.

ACE, angiotensin converting enzyme; ARB, angiotensin receptor blocker; AZA, azathioprine; BMI, body mass index; CKD-EPI, chronic kidney disease epidemiology collaboration; COVID-19, coronavirus disease 2019; eGFR, estimated glomerular filtration rate; IQR, inrequartile range; MPA, mycophenolic acid; mTORi, m-TOR inhibitors; NIV, non Invasive ventilation; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; TAC, tacrolimus.

Patients received convalescent plasma with a median time of 6 d (interquartile range [IQR], 4–7) from the first symptom. The median IgG anti-SARS-CoV-2 concentration in the plasma units was 790 AU/mL (IQR, 399–1996 AU/mL), and the median neutralization activity was 61% (IQR, 39%–85%). Only 28 (48%) were labeled as high-titer plasma units. Only 1 patient had generalized pruritus 24 h after the infusion, which was completely resolved with oral antihistamines. After 30 d from the onset of symptoms, there were no differences in the need for supplementary oxygen (Supplementary Table S1, SDC, http://links.lww.com/TP/C294) (72% versus 68%; P = 0.684) or mechanical ventilation (28% versus 32%; P = 0.684). The Cox model showed a hazard ratio for convalescent plasma of 0.94 (95% confidence interval [CI], 0.49-1.82; P = 0.85). All 4 (6.8%) patients with positive IgG anti-SARS-CoV-2 nucleocapsid protein immediately before infusion had a mild disease and were treated as outpatients. Compared with nonsurvivors, a trend toward a higher proportion of survivors receiving higher-titer plasma was observed based on anti-SARS-CoV-2 IgG ≥840 AU/mL (49% versus 38%; odds ratio [OR], 0.653; 95% CI, 0.185-2.306; P = 0.507), neutralizing activity ≥68% (44% versus 15%; OR, 0.227; 95% CI, 0.045-1.145; P = 0.057), or 1 of the 2 criteria (51% versus 38%; OR, 0.598; 95% CI, 0.169-2.110; P = 0.421).

In summary, this prospective propensity matched cohort study showed that the use of convalescent plasma was not associated with a reduction in COVID-19 progression and lethality among kidney transplant recipients. The small sample size, higher severity in the control group, delayed treatment, and use of a low proportion of high-titer convalescent plasma are significant confounders in this analysis. The study underscores the challenges inherent to COVID-19, including poor response to vaccination, and timely early institution of effective (high-titer plasma or monoclonal antibodies) therapy.

ACKNOWLEDGMENTS

This article and the research behind it would not have been possible without the exceptional contributions of our biochemist Elizabeth França Lucena, BA, who conducted all the laboratory analysis, and the biochemist Akemi Kuroda Chiba from the Hematology Department at the Universidade Federal de São Paulo (UNIFESP), who promptly organized the availability of convalescent plasma units for the treatment of patients.

Supplementary Material

tp-106-e92-s001.pdf (134.2KB, pdf)

Footnotes

The authors declare no funding or conflicts of interest.

M.P.C., H.T.-S., D.M.L., J.O.B., and J.M.-P. participated in the conceptualization of the study and in the research design. M.P.C., L.A.V., and S.B.S.M. participated in the investigation and supervision of the project. M.P.C., L.G.M.d.A., and Y.C.D. participated in the data curation and formal analysis. M.P.C., Y.C.D., and H.T.-S. participated in the writing of the article. All authors participated in the reviewing of the final version of the article.

Supplemental digital content (SDC) is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal’s Web site (www.transplantjournal.com).

REFERENCES

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Supplementary Materials

tp-106-e92-s001.pdf (134.2KB, pdf)

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