An initial report from the French SOT COVID Registry suggests high mortality due to COVID-19 in recipients of kidney transplants

• DOI: 10.1016/j.kint.2020.08.005
• Publication Date: 2020-08-24T15:21:41Z
• Authors: Sophie Caillard; Dany Anglicheau; Marie Matignon; Antoine Durrbach; Clarisse Greze; Luc Frimat; Olivier Thaunat; Tristan Legris; Valerie Moal; Pierre Francois W...; Nassim Kamar; Philippe Gatault; Renaud Snanoudj; Antoine Sicard; Dominique Bertrand; Charlotte Colosio; Lionel Couzi; Jonathan M. Chemouny; Christophe Masset; Gilles Blancho; Jamal Bamoulid; Agnes Duveau; Nicolas Bouvier; Nathalie Chavarot; Philippe Grimbert; Bruno Moulin; Yannick Le Meur; Marc Hazzan; Sophie Caillard; Bruno Moulin; Samira Fafi-Kremer; Marc Hazzan; Dany Anglicheau; Alexandre Hertig; Jérôme Tourret; Benoit Barrou; Emmanuel Morelon; Olivier Thaunat; Lionel Couzi; Pierre Merville; Valérie Moal; Tristan Legris; Pierre-François W...; Maïté Jaureguy; Luc Frimat; Didier Ducloux; Jamal Bamoulid; Dominique Bertrand; Michel Tsimaratos; Florentine Garaix...; Jérôme Dumortier; Sacha Mussot; Antoine Roux; Laurent Sebbag; Yannick Le Meur; Gilles Blancho; Christophe Masset; Nassim Kamar; Hélène Francois; Eric Rondeau; Nicolas Bouvier; Christiane Mousson; Matthias Buchler; Philippe Gatault; Jean-François Aug...; Agnès Duveau; Cécile Vigneau; Marie-Christine M...; Jonathan Chemouny; Leonard Golbin; Philippe Grimbert; Marie Matignon; Antoine Durrbach; Clarisse Greze; Renaud Snanoudj; Charlotte Colosio; Betoul Schvartz; Paolo Malvezzi; Christophe Mariat; Antoine Thierry; Moglie Le Quintrec; Antoine Sicard; Jean Philippe Rer...; Anne-Élisabeth Heng; Cyril Garrouste; Henri Vacher Coponat; Éric Epailly; Olivier Brugiere; Sébastien Dharancy; Éphrem Salame; Faouzi Saliba
• Keywords: Hydroxychloroquine; Immunosuppression; Tocilizumab; Lymphocytopenia

Notwithstanding the ongoing coronavirus disease-2019 (Covid-19) pandemic, information on its clinical presentation and prognosis in recipients of a kidney transplant remain scanty. The aim this registry-based observational study was to explore characteristics outcomes transplants included French nationwide Registry Solid Organ Transplant Recipients with Covid-19. Covid-19 diagnosed symptomatic patients who had positive PCR assay for SARS-CoV-2 or having typical lung lesions imaging. Clinical laboratory characteristics, management immunosuppression, treatment Covid-19, (hospitalization, admission intensive care unit, mechanical ventilation, death) were recorded. Risk factors severe disease death determined. Of 279 patients, 243 admitted hospital 36 managed at home. median age hospitalized 61.6 years; most comorbidities (hypertension, 90.1%; overweight, 63.8%; diabetes, 41.3%; cardiovascular disease, 36.2%). Fever, cough, dyspnea, diarrhea common symptoms admission. Laboratory findings revealed mild inflammation frequently accompanied by lymphopenia. Immunosuppressive drugs generally withdrawn (calcineurin inhibitors: 28.7%; antimetabolites: 70.8%). Treatment mainly based hydroxychloroquine (24.7%), antiviral (7.8%), tocilizumab (5.3%). Severe occurred 106 (46%). Forty-three died (30-day mortality 22.8%). Multivariable analysis identified fever, dyspnea as independent risk whereas over 60 years, independently associated mortality. Thus, portends high rate. Proper immunosuppression tailored population challenging. Editor's NoteThis is one several articles we think you will find interest that are part our special issue Kidney International addressing challenges dialysis transplantation during COVID-19 pandemic. Please also additional material commentaries letters editor sections. We hope these insights help daily your own patients. This Coronavirus 2019 (COVID-19) caused acute respiratory syndrome 2 (SARS-CoV-2) has created an global pandemic major concern. Frail developing shown initial reports from China1Guan W.J. Ni Z.Y. Hu Y. et al.Clinical China.N Engl J Med. 2020; 382: 1708-1720Crossref PubMed Scopus (20519) Google Scholar,2Zhou F. Yu T. Du R. course adult inpatients Wuhan, China: A retrospective cohort study.Lancet. 395: 1054-1062Abstract Full Text PDF (18962) Scholar other countries.3Goyal P. Choi J.J. Pihneiro L.C. New York City.N 2372-2374Crossref (1602) Scholar,4Grasselli G. Zangrillo A. Zanella al.Baseline 1591 infected ICUs Lombardy Region.Italy. JAMA. 323: 1574-1581Crossref (3886) Although preexisting predisposing factor morbidity mortality,5Arentz M. Yim E. Klaff L. al.Characteristics 21 critically ill Washington state.JAMA. 1612-1614Crossref (1635) (KT) under immunosuppressive therapy remains scant. Published data limited case reports6Guillen Pineiro G.J. 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Saharia al.Early experience high-volume center.Transplantation. 104: 2208-2214Crossref (92) 17Nair V. Jandovitz N. Hirsch J.S. 1819-1825Crossref (193) 18Zhu Gong Liu B. al.Coronavirus immunosuppressed summary 10 confirmed cases China.Eur Urol. 77: 748-754Abstract (158) 19Chen T.Y. Farghaly Cham focus management.Transpl Infect Dis. 23: e13378Google 20Hoek R.A.S. Manintveld O.C. Betjes M.G.H. experience.Transpl 33: 1099-1105Crossref (65) 21Husain S.A. Dube Morris outpatient 2019.Clin 15: 1174-1178Crossref (78) On March 1, 2020, registry history established auspices French-Speaking Society Transplantation. As April 21, total 598 registry—of whom 426 KT recipients, 61 heart 72 liver 39 recipients. Here, describe presentation, management, outcomes, prognostic variables large sample COVID-19. registry, reverse transcriptase–polymerase chain reaction 93% cases. diagnosis remaining 7% participants pulmonary computed tomography (7%). hospital, home following assessment physician (Table 1). In brief, latter group consisted younger lower frequency gastrointestinal manifestations. One patient received hydroxychloroquine. Antimetabolites mammalian target rapamycin (mTOR) inhibitors stopped 13 (36%). general summarized Table 1. years (interquartile range: 50.8−69.0 19−93 years), two-thirds men. Most them overweight (63.8%), hypertension (90.1%), (36.2%), diabetes (41.3%), (14.8%). after 74.1 months 27.6−138.7 months; 1−1943 months) KT. delay between onset 5 days 3−8 days, 0−34 days). frequent symptom fever (80%), followed cough (63.6%), (43.5%), (40.3%), anosmia (14.1%). Median levels C-reactive protein procalcitonin 62 mg/L 0.20 ng/mL, respectively 2). lymphocyte count 0.66 × 109/L, thrombocytopenia 54 (29%) Lung infiltrates chest images detected 87% cases.Table 1Baseline versus in-hospitalVariableHome managementIn-hospital managementPn(n = 36)(n 243)Baseline Age, yr55.6 [48.0–61.1]61.6 [50.8–69.0]0.002279 Male20 (55.6)162 (66.7)0.263279 BMI, kg/m225.0 [23.4–28.9]26.1 [23.0–30.7]0.608270 BMI >25 kg/m218 (51.4)150 (63.8)0.221270 Blood group0.691275A18 (50.0)105 (43.9)AB1 (2.8)12 (5.0)B6 (16.7)29 (12.1)O11 (30.6)93 (38.9) Transplanted organ0.525279Kidney35 (97.2)233 (95.9)Kidney–heart0 (0.0)4 (1.6)Kidney–liver1 (2.8)2 (0.8)Kidney–pancreas0 (1.6) Time Tx [IQR], mo58.9 [25.0–118.9]74.1 [27.6–138.7]0.626279 COVID, stratified, mo no. (%):0.827279<63 (8.3)20 (8.2)6–111 (2.8)15 (6.2)12–5914 (38.9)73 (30.0)60–1199 (25.0)60 (24.7)≥1209 (25.0)75 (30.9) Hypertension24 (82.8)201 (90.1)0.213252 RAS blockers15 (55.6)97 (44.5)0.377245 Cardiovascular disease6 (20.0)81 (36.2)0.122254 Respiratory disease5 (16.7)33 (14.8)0.786253 Diabetes12 (40.0)92 (41.3)1.000253 Cancer4 (13.3)35 (15.5)1.000256 Smoking3 (13.0)30 (15.5)1.000217Baseline CNIs28 (77.8)202 (83.1)0.581279 Mycophenolate acid29 (80.6)183 (75.3)0.632279 Azathioprine1 (2.8)11 (4.5)1.000279 mTOR inhibitors5 (13.9)29 (11.9)0.784279 Steroids25 (69.4)177 (72.8)0.822279 Belatacept1 (6.2)0.703279Clinical Cough20 (55.6)145 (63.6)0.459264 Rhinitis6 (16.7)20 (9.3)0.231251 Dyspnea2 (5.6)98 (40.3)<0.001279 Anosmia10 (29.4)29 (14.1)0.046240 Fever15 (41.7)180 (80.0)<0.001261 Headache11 (30.6)39 (17.5)0.106259 Diarrhea9 (25.0)97 (43.5)0.056259BMI, body mass index; CNI, calcineurin inhibitor; COVID-19, 2019; mTOR, rapamycin; RAS, renin–angiotensin system; Ref, reference; Tx, transplantation.Data expressed [interquartile range] (%), appropriate, unless otherwise indicated. Open table new tab 2Laboratory data, modalities, COVID-19VariableValuenLaboratory CRP, mg/l62 [27–114]186 Procalcitonin, ng/ml0.20 [0.14–0.48]90 Lymphocyte count, ×109/l0.66 [0.40–0.96]184 Platelet ×109/l178 [145–238]188 Thrombocytopenia <150 109/l54 (29)188 SaO296 (91–98)176 Creatinine, μmol/l176 [131–244]200Immunusuppression CNI withdrawal58 (28.7)202 Antimetabolite withdrawal136 (70.8)192 inhibitor withdrawal18 (62.1)29 Belatacept withdrawal7 (46.7)15COVID-19 modalities Azithromycin71 (29.2)243 Other antibiotics153 (63.0)243 Antifungal drugs6 (2.5)243 Remdesivir2 (0.8)243 Lopinavir/ritonavir11 (4.5)243 Oseltamivir6 Hydroxychloroquine60 (24.7)243 Tocilizumab13 (5.3)243Outcome Bacterial coinfection57 (23.5)243 Viral coinfection5 (2.1)243 Fungal coinfection6 Oxygen therapy152 (72.4)210 Mechanical ventilation72 (29.6)243 Vasopressor support27 (11.1)243 Acute injury106 (43.6)243 Renal replacement therapy27 (11.1)243CNI, inhibitors; protein; SaO2, arterial oxygen saturation.Data tests performed transplantation. Data saturation. admission, (CNIs), antimetabolites, steroids being taken 83.1%, 79.8%, 72.8% respectively. note, 29 (12%) 15 (6.2%) belatacept, During hospitalization 2), CNIs, 70.8% (136 192), 28.7% (58 202), 62.1% (18 29) Moreover, belatacept administration postponed 7 taking drug. changes than those not nasal (72.4%) antibiotics azithromycin (63%). Hydroxychloroquine given (24.7%) 71 (29.2%) CNIs 11 treated lopinavir/ritonavir. Tocilizumab administered (5.3%) coinfections 57 (23.5%) participants. ventilation required approximately 30% injury 43.6% necessary 11.1% 88 (36%) unit (ICU) either (n 25) 63). subgroup, interval transfer ICU 4 (range: 1−25 30-day rate 22.8% (Figure Nine lost their graft hospitalization, died. composite endpoint within 30 reached 46% 2a).Figure 2Probability reaching disease. (a) disease–free survival entire 54.2% (48%–61.4%). Kaplan–Meier plots stratified according (b) (<60 vs. >60 (c) (yes no), (d) index (BMI; <25 kg/m2 kg/m2), (e) (f) (g) saturation (SaO2) (>95% <95%), (h) (CRP) level mg/l mg/l), (i) (<0.2 ng/ml >0.2 ng/ml). PCT, procalcitonin.View Large Image Figure ViewerDownload Hi-res image Download (PPT) 3 compares developed 109) did 137). Patients aged significantly overrepresented former group. Fever admission—but cough—were However, time elapsed similar groups (5 mg/L, concentrations g/L, partial pressure <95% No associations observed platelet creatinine levels. 4) slightly different relation evolution time. These differences especially evident respect withdrawal (52% 11% nonsevere respectively, P < 0.001). COVID-19–free provided 2b–i. 3a).Table 3Baseline COVID-19CharacteristicsNonsevereSevereHR [95% CI]Pn(n =137)(n 106)Baseline yr59.5 [48.7–67.8]63.5 [54.7–69.6]1.02 [1.00–1.04]0.013243 Age yr67 (48.9)67 (63.2)1.63 [1.10–2.43]0.015243 Male90 (65.7)72 (67.9)1.07 [0.71–1.61]0.740243 > 25 kg/m278 (57.8)72 (72.0)1.80 [1.16–2.79]0.008235 group239A65 (48.5)40 (38.1)RefRefAB6 (4.48)6 (5.71)1.52 [0.64–3.59]0.340B16 (11.9)13 (12.4)1.27 [0.68–2.38]0.449O47 (35.1)46 (43.8)1.32 [0.86–2.02]0.198 organ243Kidney129 (94.2)104 (98.1)RefRef Kidney–heart2 (1.46)2 (1.89)1.36 [0.34–5.51]0.668Kidney–liver2 (1.46)0 (0.00)0.00 [–]0.997Kidney–pancreas4 (2.92)0 [–]0.996 mo73.4 [30.9–151]77.8 [25.4–131]1.00 [1.00–1.00]0.660243 1 yr19 (13.9)16 (15.1)0.97 [0.57–1.65]0.912243 Hypertension112 (89.6)89 (90.8)1.14 [0.57–2.25]0.717223 blockers58 (47.2)39 (41.1)0.83 [0.55–1.25]0.377218 disease41 (32.5)40 (40.8)1.32 [0.88–1.98]0.176224 disease19 (15.2)14 (14.3)0.96 [0.54–1.69]0.885223 Diabetes42 (33.6)50 (51.0)1.73 [1.16–2.57]0.007223 Cancer17 (13.4)18 (18.2)1.33 [0.80–2.21]0.276226 Smoking16 (14.8)14 (16.3)0.99 [0.56–1.76]0.977194 CNIs115 (83.9)87 (82.1)0.96 [0.58–1.58]0.868243 acid102 (74.5)81 (76.4)1.08 [0.69–1.69]0.743243 Azathioprine5 (3.65)6 (5.66)1.32 [0.58–3.01]0.509243 inhibitors15 (10.9)14 (13.2)1.08 [0.62–1.90]0.785243 Steroids96 (70.1)81 (76.4)1.24 [0.79–1.94]0.347243 Belatacept8 (5.84)7 (6.60)1.08 [0.50–2.33]0.844243On Cough81 (62.3)64 (65.3)1.20 [0.79–1.82]0.390228 Rhinitis12 (9.76)8 (8.70)0.82 [0.40–1.69]0.592215 Dyspnea42 (30.7)56 (52.8)2.28 [1.55–3.34]<0.001243 Anosmia19 (16.1)10 (11.4)0.71 [0.37–1.38]0.315206 Fever98 (75.4)82 (86.3)1.77 [0.99–3.19]0.055225 Headache25 (19.5)14 (14.7)0.75 [0.43–1.32]0.322223 Diarrhea59 (46.1)38 (40.0)0.86 [0.57–1.30]0.486223 d5.00 [3.00–9.00]5.00 [3.00–7.00]1.00 [0.96–1.04]0.873219 mg/l51 (46.4)49 (64.5)2.07 [1.29–3.31]0.003186 Procalcitonin 0.2 ng/ml21 (37.5)23 (67.6)3.19 [1.55–6.57]0.00290 ×109/l0.70 [0.40–0.95]0.60 [0.40–0.96]1.10 [0.74–1.64]0.627184 [146–229]178 [145–247]1.00 [1.00–1.00]0.742188 150 109/l31 (28.7)23 (28.7)0.98 [0.60–1.58]0.923188 SaO2 95%26 (26.8)40 (50.6)2.47 [1.59–3.84]<0.001176 μmol/l173 [126–230]182 [132–251]1.00 [1.00–1.00]0.378200BMI, HR, hazard ratio; 4Treatment presence diseaseTherapyNonsevereSeverePnn 137n 106COVID-19 Azithromycin38 (27.7)33 (31.1)0.790243 antibiotics81 (59.1)72 (67.9)0.190243 drugs1 (0.7)5 (4.7)0.060243 Remdesivir0 (0.0)2 (1.9)0.035243 Lopinavir/ritonavir2 (1.5)9 (8.5)0.002243 Oseltamivir3 (2.2)3 (2.8)0.708243 Hydoxychloroquine28 (20.4)32 (30.2)0.168243 Tocilizumab4 (2.9)9 (8.5)0.077243Immunosuppression withdrawal13 (11.3)45 (51.7)<0.001202 withdrawal73 (68.2)63 (74.1)0.376192 withdrawal8 (53.3)10 (71.4)0.18729 withdrawal4 (50.0)3 (42.9)0.54915COVID-19, rapamycin.Values n rapamycin. Values 43) 200). receiving presented 3b).Table 5Baseline notCharacteristicsAliveDeadHR 200)(n 43)Baseline yr59.8 [49.8–67.5]68.9 [61.7–75.1]1.07 [1.04–1.10]<0.001243 yr99 (49.5)35 (81.4)3.98 [1.85–8.59]<0.001243 Male137 (68.5)25 (58.1)0.68 [0.37–1.25]0.215243 kg/m2122 (61.9)28 (73.7)1.65 [0.80–3.39]0.177235 group239A89 (45.2)16 (38.1)Ref.Ref.AB11 (5.58)1 (2.38)0.58 [0.08–4.40]0.601B23 (11.7)6 (14.3)1.36 [0.53–3.48]0.521O74 (37.6)19 (45.2)1.42 [0.73–2.77]0.299 organ243Kidney190 (95.0)43 (100)Ref.Ref.Kidney–heart4 (2.00)0 [0.00]0.997Kidney–liver2 (1.00)0 [0.00]0.998Kidney–pancreas4 [0.00]0.997 mo72.5 [27.7–147]83.7 [25.7–116]1.00 [1.00–1.00]0.933243 yr29 (14.5)6 (14.0)0.95 [0.40–2.26]0.914243 Hypertension165 (89.7)36 (92.3)1.39 [0.43–4.53]0.580223 blockers80 (44.4)17 (44.7)1.07 [0.56–2.03]0.836218 disease59 (31.9)22 (56.4)2.74 [1.45–5.17]0.002224 disease28 (15.2)5 (12.8)0.77 [0.30–1.96]0.577223 Diabetes69 (59.0)2.27 [1.20–4.29]0.012223 Cancer28 (15.0)7 (17.9)1.17 [0.52–2.65]0.708226 Smoking25 (15.5)5 (15.2)0.97 [0.38–2.52]0.953194 CNIs172 (86.0)30 (69.8)0.46 [0.24–0.88]0.019243 acid152 (76.0)31 (72.1)0.83 [0.43–1.62]0.586243 Azathioprine8 (4.00)3 (6.98)1.41 [0.43–4.55]0.569243 inhibitors22 (11.0)7 (16.3)1.38 [0.61–3.10]0.439243 Steroids147 (73.5)30 (69.8)0.81 [0.42–1.56]0.533243 Belatacept12 (6.00)3 (6.98)1.15 [0.36–3.71]0.817243On Cough123 (64.4)22 (59.5)0.81 [0.42–1.56]0.521228 Rhinitis16 (8.89)4 (11.4)1.24 [0.44–3.51]0.687215 Dyspnea74 (37.0)24 (55.8)1.99 [1.09–3.63]0.025243 Anosmia28 (16.0)1 (3.23)0.20 [0.03–1.45]0.110206 Fever151 (79.9)29 (80.6)1.05 [0.46–2.41]0.901225 Headache35 (18.6)4 (11.4)0.59 [0.21–1.68]0.323223 Diarrhea84 (44.7)13 (37.1)0.75 [0.38–1.48]0.401223 d6.00 [3.00–9.00]4.00 [2.75–6.00]0.94 [0.88–1.02]0.138219 CRP mg/l82 (51.9)18 (64.3)1.69 [0.78–3.66]0.185186 ng/ml34 (44.7)10 (71.4)2.79 [0.87–8.89]0.08390 [0.40–0.97]0.60 [0.44–0.96]0.80 [0.38–1.65]0.538184 [144–232]178 [155–257]1.00 [1.00–1.00]0.894188 ×109/L48 (30.8)6 (18.8)0.54 [0.22–1.32]0.176188 <95%47 (32.2)19 (63.3)3.39 [1.61–7.14]0.001176 Creatinine level, [131–249]184 [131–230]1.00 [1.00–1.00]0.864200BMI, CI, confidence interval; IQR, interquartile range; renin-angiotensin saturation; Subgroup analyses conducted tested negative transcriptase-polymerase (7%) yielded results both terms (data shown). follow-up 22 days; 66 still manuscript written. Despite growing literature focusing manifestations certain selected populations merit consideration—including immunocompromised transplantation—remain To address knowledge gap, herein main adverse outcomes—including mortality—of consisting First, demonstrate reported population—with more symptoms. line showing 77%−94% 68%−79% cases, respectively.1Guan 2Zhou inpa