An initial report from the French SOT COVID Registry suggests high mortality due to COVID-19 in recipients of kidney transplants
Authors: Sophie Caillard, Dany Anglicheau, Marie Matignon, Antoine Durrbach, Clarisse Greze, Luc Frimat, Olivier Thaunat, Tristan Legris, Valerie Moal, Pierre Francois Westeel, 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 Westeel, Maïté Jaureguy, Luc Frimat, Didier Ducloux, Jamal Bamoulid, Dominique Bertrand, Michel Tsimaratos, Florentine Garaix-Gilardo, 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 Augusto, Agnès Duveau, Cécile Vigneau, Marie-Christine Morin, 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 Rerolle, Anne-Élisabeth Heng, Cyril Garrouste, Henri Vacher Coponat, Éric Epailly, Olivier Brugiere, Sébastien Dharancy, Éphrem Salame, Faouzi Saliba
Journal: Kidney International (2020)

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 of this registry-based observational study was to explore characteristics and clinical outcomes of recipients of kidney transplants included in the French nationwide Registry of Solid Organ Transplant Recipients with Covid-19. Covid-19 was diagnosed in symptomatic patients who had a positive PCR assay for SARS-CoV-2 or having typical lung lesions on imaging. Clinical and laboratory characteristics, management of immunosuppression, treatment for Covid-19, and clinical outcomes (hospitalization, admission to intensive care unit, mechanical ventilation, or death) were recorded. Risk factors for severe disease or death were determined. Of the 279 patients, 243 were admitted to hospital and 36 were managed at home. The median age of hospitalized patients was 61.6 years; most had comorbidities (hypertension, 90.1%; overweight, 63.8%; diabetes, 41.3%; cardiovascular disease, 36.2%). Fever, cough, dyspnea, and diarrhea were the most common symptoms on admission. Laboratory findings revealed mild inflammation frequently accompanied by lymphopenia. Immunosuppressive drugs were generally withdrawn (calcineurin inhibitors: 28.7%; antimetabolites: 70.8%). Treatment was mainly based on hydroxychloroquine (24.7%), antiviral drugs (7.8%), and tocilizumab (5.3%). Severe Covid-19 occurred in 106 patients (46%). Forty-three hospitalized patients died (30-day mortality 22.8%). Multivariable analysis identified overweight, fever, and dyspnea as independent risk factors for severe disease, whereas age over 60 years, cardiovascular disease, and dyspnea were independently associated with mortality. Thus, Covid-19 in recipients of kidney transplants portends a high mortality rate. Proper management of immunosuppression and tailored treatment of this population remain challenging. 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 of this registry-based observational study was to explore characteristics and clinical outcomes of recipients of kidney transplants included in the French nationwide Registry of Solid Organ Transplant Recipients with Covid-19. Covid-19 was diagnosed in symptomatic patients who had a positive PCR assay for SARS-CoV-2 or having typical lung lesions on imaging. Clinical and laboratory characteristics, management of immunosuppression, treatment for Covid-19, and clinical outcomes (hospitalization, admission to intensive care unit, mechanical ventilation, or death) were recorded. Risk factors for severe disease or death were determined. Of the 279 patients, 243 were admitted to hospital and 36 were managed at home. The median age of hospitalized patients was 61.6 years; most had comorbidities (hypertension, 90.1%; overweight, 63.8%; diabetes, 41.3%; cardiovascular disease, 36.2%). Fever, cough, dyspnea, and diarrhea were the most common symptoms on admission. Laboratory findings revealed mild inflammation frequently accompanied by lymphopenia. Immunosuppressive drugs were generally withdrawn (calcineurin inhibitors: 28.7%; antimetabolites: 70.8%). Treatment was mainly based on hydroxychloroquine (24.7%), antiviral drugs (7.8%), and tocilizumab (5.3%). Severe Covid-19 occurred in 106 patients (46%). Forty-three hospitalized patients died (30-day mortality 22.8%). Multivariable analysis identified overweight, fever, and dyspnea as independent risk factors for severe disease, whereas age over 60 years, cardiovascular disease, and dyspnea were independently associated with mortality. Thus, Covid-19 in recipients of kidney transplants portends a high mortality rate. Proper management of immunosuppression and tailored treatment of this population remain challenging. Editor's NoteThis is one of several articles we think you will find of interest that are part of our special issue of Kidney International addressing the challenges of dialysis and transplantation during the COVID-19 pandemic. Please also find additional material in our commentaries and letters to the editor sections. We hope these insights will help you in the daily care of your own patients. This is one of several articles we think you will find of interest that are part of our special issue of Kidney International addressing the challenges of dialysis and transplantation during the COVID-19 pandemic. Please also find additional material in our commentaries and letters to the editor sections. We hope these insights will help you in the daily care of your own patients. Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created an ongoing global pandemic of major concern. Frail patients with comorbidities are at high risk of developing severe disease, as shown by initial reports from China1Guan W.J. Ni Z.Y. Hu Y. et al.Clinical characteristics of coronavirus disease 2019 in China.N Engl J Med. 2020; 382: 1708-1720Crossref PubMed Scopus (20519) Google Scholar,2Zhou F. Yu T. Du R. et al.Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study.Lancet. 2020; 395: 1054-1062Abstract Full Text Full Text PDF PubMed Scopus (18962) Google Scholar and other countries.3Goyal P. Choi J.J. Pihneiro L.C. et al.Clinical characteristics of COVID-19 in New York City.N Engl J Med. 2020; 382: 2372-2374Crossref PubMed Scopus (1602) Google Scholar,4Grasselli G. Zangrillo A. Zanella A. et al.Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy Region.Italy. JAMA. 2020; 323: 1574-1581Crossref PubMed Scopus (3886) Google Scholar Although preexisting kidney disease is a predisposing factor for COVID-19 morbidity and mortality,5Arentz M. Yim E. Klaff L. et al.Characteristics and outcomes of 21 critically ill patients with COVID-19 in Washington state.JAMA. 2020; 323: 1612-1614Crossref PubMed Scopus (1635) Google Scholar information on its clinical presentation and prognosis in kidney transplant (KT) recipients under immunosuppressive therapy remains scant. Published data are limited to case reports6Guillen E. Pineiro G.J. Revuelta I. et al.Case report of COVID-19 in a kidney transplant recipient: Does immunosuppression alter the clinical presentation?.Am J Transplant. 2020; 20: 1875-1878Crossref PubMed Scopus (221) Google Scholar, 7Zhu L. Xu X. Ma K. et al.Successful recovery of COVID-19 pneumonia in a renal transplant recipient with long-term immunosuppression.Am J Transplant. 2020; 20: 1859-1863Crossref PubMed Scopus (268) Google Scholar, 8Zhong Z. Zhang Q. Xia H. et al.Clinical characteristics and immunosuppressants management of coronavirus disease 2019 in solid organ transplant recipients.Am J Transplant. 2020; 20: 1916-1921Crossref PubMed Scopus (91) Google Scholar, 9Gandolfini I. Delsante M. Fiaccadori E. et al.COVID-19 in kidney transplant recipients.Am J Transplant. 2020; 20: 1941-1943Crossref PubMed Scopus (161) Google Scholar and small single-center case series.10Alberici F. Delbarba E. Manenti C. et al.A single center observational study of the clinical characteristics and short-term outcome of 20 kidney transplant patients admitted for SARS-CoV2 pneumonia Kidney.Int. 2020; 97: 1083-1088Scopus (286) Google Scholar, 11The Columbia University Transplant ProgramEarly description of coronavirus 2019 disease in kidney transplant recipients in New York.J Am Soc Nephrol. 2020; 31: 1150-1156Crossref PubMed Scopus (191) Google Scholar, 12Fernandez Ruiz M. Andres A. Lopez-Medrano F. San Juan R. COVID-19 in solid organ transplant recipients: a single-center case series from Spain.Am J Transplant. 2020; 20: 1849-1858Crossref PubMed Scopus (341) Google Scholar, 13Akalin E. Azzi Y. Bartash R. et al.COVID-19 and kidney transplantation.N Engl J Med. 2020; 382: 2475-2477Crossref PubMed Scopus (632) Google Scholar, 14Pereira M.R. Mohan S. Cohen D.J. et al.COVID-19 in solid transplant organ recipients: initial report of the US epicenter.Am J Transplant. 2020; 20: 1800-1808Crossref PubMed Scopus (631) Google Scholar, 15Banerjee D. Popoola J. Shah S. et al.COVID-19 infection in kidney transplant recipients.Kidney Int. 2020; 97: 1076-1082Abstract Full Text Full Text PDF PubMed Scopus (295) Google Scholar, 16Yi S.G. Rogers A.W. Saharia A. et al.Early experience with COVID-19 and solid organ transplantation at a US high-volume transplant center.Transplantation. 2020; 104: 2208-2214Crossref PubMed Scopus (92) Google Scholar, 17Nair V. Jandovitz N. Hirsch J.S. et al.COVID-19 in kidney transplant recipients.Am J Transplant. 2020; 20: 1819-1825Crossref PubMed Scopus (193) Google Scholar, 18Zhu L. Gong N. Liu B. et al.Coronavirus disease 2019 pneumonia in immunosuppressed renal transplant recipients: a summary of 10 confirmed cases in Wuhan, China.Eur Urol. 2020; 77: 748-754Abstract Full Text Full Text PDF PubMed Scopus (158) Google Scholar, 19Chen T.Y. Farghaly S. Cham S. et al.COVID-19 pneumonia in kidney transplant recipients: focus on immunosuppression management.Transpl Infect Dis. 2020; 23: e13378Google Scholar, 20Hoek R.A.S. Manintveld O.C. Betjes M.G.H. et al.COVID-19 in solid organ transplant recipients: a single-center experience.Transpl Int. 2020; 33: 1099-1105Crossref PubMed Scopus (65) Google Scholar, 21Husain S.A. Dube G. Morris H. et al.Early outcomes of outpatient management of kidney transplant recipients with coronavirus disease 2019.Clin J Am Soc Nephrol. 2020; 15: 1174-1178Crossref PubMed Scopus (78) Google Scholar On March 1, 2020, a French nationwide registry of patients with COVID-19 and a history of solid organ transplantation was established under the auspices of the French-Speaking Society of Transplantation. As of April 21, 2020, a total of 598 patients were included in the registry—of whom 426 were KT recipients, 61 heart transplant recipients, 72 liver transplant recipients, and 39 lung transplant recipients. Here, we describe the disease presentation, immunosuppression management, clinical outcomes, and independent prognostic variables in a large sample of 279 KT recipients with COVID-19. Of the 279 KT recipients included in the registry, COVID-19 was diagnosed by reverse transcriptase–polymerase chain reaction in 93% of cases. The diagnosis in the remaining 7% of the study participants was based on clinical presentation and pulmonary computed tomography findings (7%). A total of 243 patients were admitted to the hospital, and 36 were managed at home following assessment by a transplant physician (Table 1). In brief, the latter group consisted of younger patients with a lower frequency of dyspnea, fever, and gastrointestinal manifestations. One patient received home treatment with hydroxychloroquine. Antimetabolites and mammalian target of rapamycin (mTOR) inhibitors were stopped in 13 patients (36%). The general characteristics of hospitalized patients are summarized in Table 1. The median age was 61.6 years (interquartile range: 50.8−69.0 years; range: 19−93 years), and two-thirds were men. Most of them were overweight (63.8%), and the most common comorbidities were hypertension (90.1%), cardiovascular disease (36.2%), diabetes (41.3%), and a history of respiratory disease (14.8%). SARS-CoV-2 infection was identified after a median of 74.1 months (interquartile range: 27.6−138.7 months; range: 1−1943 months) from KT. The median delay between the onset of symptoms and hospital admission was 5 days (interquartile range: 3−8 days, range: 0−34 days). The most frequent symptom on admission was fever (80%), followed by cough (63.6%), diarrhea (43.5%), dyspnea (40.3%), and anosmia (14.1%). Median levels of C-reactive protein and procalcitonin were 62 mg/L and 0.20 ng/mL, respectively (Table 2). The median lymphocyte count was 0.66 × 109/L, whereas thrombocytopenia was identified in 54 (29%) patients. Lung infiltrates on chest computed tomography images were detected in 87% of cases.Table 1Baseline characteristics of kidney transplant recipients with COVID-19 managed at home versus in-hospitalVariableHome managementIn-hospital managementPn(n = 36)(n = 243)Baseline characteristics 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 (0.0)4 (1.6) Time from Tx to COVID-19 [IQR], mo58.9 [25.0–118.9]74.1 [27.6–138.7]0.626279 Time from Tx to 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 immunosuppression 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 (2.8)15 (6.2)0.703279Clinical presentation 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, coronavirus disease 2019; mTOR, mammalian target of rapamycin; RAS, renin–angiotensin system; Ref, reference; Tx, transplantation.Data are expressed as median [interquartile range] or count (%), as appropriate, unless otherwise indicated. Open table in a new tab Table 2Laboratory data, management of immunosuppression, treatment modalities, and outcomes of kidney transplant recipients hospitalized with COVID-19VariableValuenLaboratory data 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 count, ×109/l178 [145–238]188 Thrombocytopenia <150 × 109/l54 (29)188 SaO296 (91–98)176 Creatinine, μmol/l176 [131–244]200Immunusuppression management CNI withdrawal58 (28.7)202 Antimetabolite withdrawal136 (70.8)192 mTOR inhibitor withdrawal18 (62.1)29 Belatacept withdrawal7 (46.7)15COVID-19 treatment 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 (2.5)243 Hydroxychloroquine60 (24.7)243 Tocilizumab13 (5.3)243Outcome Bacterial coinfection57 (23.5)243 Viral coinfection5 (2.1)243 Fungal coinfection6 (2.5)243 Oxygen therapy152 (72.4)210 Mechanical ventilation72 (29.6)243 Vasopressor support27 (11.1)243 Acute kidney injury106 (43.6)243 Renal replacement therapy27 (11.1)243CNI, calcineurin inhibitors; COVID-19, coronavirus disease 2019; CRP, C-reactive protein; mTOR, mammalian target of rapamycin; SaO2, arterial oxygen saturation.Data are expressed as median [interquartile range] or count (%), as appropriate, unless otherwise indicated. Laboratory tests were performed on admission. Open table in a new tab BMI, body mass index; CNI, calcineurin inhibitor; COVID-19, coronavirus disease 2019; mTOR, mammalian target of rapamycin; RAS, renin–angiotensin system; Ref, reference; Tx, transplantation. Data are expressed as median [interquartile range] or count (%), as appropriate, unless otherwise indicated. CNI, calcineurin inhibitors; COVID-19, coronavirus disease 2019; CRP, C-reactive protein; mTOR, mammalian target of rapamycin; SaO2, arterial oxygen saturation. Data are expressed as median [interquartile range] or count (%), as appropriate, unless otherwise indicated. Laboratory tests were performed on admission. On admission, calcineurin inhibitors (CNIs), antimetabolites, and steroids were being taken by 83.1%, 79.8%, and 72.8% of patients, respectively. Of note, 29 (12%) and 15 (6.2%) patients were on mammalian target of rapamycin inhibitors and belatacept, respectively. During hospitalization (Table 2), antimetabolites, CNIs, and mammalian target of rapamycin inhibitors were withdrawn in 70.8% (136 of 192), 28.7% (58 of 202), and 62.1% (18 of 29) of patients, respectively. Moreover, belatacept administration was postponed in 7 of the 15 participants taking this drug. Of note, changes in immunosuppressive drugs other than those withdrawn were not recorded. Most patients received nasal oxygen therapy (72.4%) and antibiotics other than azithromycin (63%). Hydroxychloroquine and azithromycin were given to 60 (24.7%) and 71 (29.2%) patients, respectively (Table 2). CNIs were stopped in 7 of the 11 patients treated with lopinavir/ritonavir. Tocilizumab was administered to 13 (5.3%) cases. Bacterial coinfections were identified in 57 (23.5%) participants. Mechanical ventilation was required for approximately 30% of cases. Acute kidney injury occurred in 43.6% of patients, with renal replacement therapy being necessary in 11.1% of cases. A total of 88 patients (36%) required intensive care unit (ICU) care either on admission (n = 25) or during hospitalization (n = 63). In the latter subgroup, the median interval between hospitalization and transfer to the ICU was 4 days (range: 1−25 days). The 30-day mortality rate of hospitalized patients was 22.8% (Figure 1). Nine patients lost their graft during hospitalization, 4 of whom died. The composite endpoint of severe COVID-19 within 30 days of hospital admission was reached by 46% of the study patients (Figure 2a).Figure 2Probability of reaching the composite endpoint of severe disease. (a) The 30-day severe disease–free survival in the entire study cohort was 54.2% (48%–61.4%). Kaplan–Meier plots stratified according to (b) age (<60 years vs. >60 years), (c) diabetes (yes vs. no), (d) body mass index (BMI; <25 kg/m2 vs. >25 kg/m2), (e) fever on admission (yes vs. no), (f) dyspnea on admission (yes vs. no), (g) arterial oxygen saturation (SaO2) on admission (>95% vs. <95%), (h) C-reactive protein (CRP) level on admission (<60 mg/l vs. >60 mg/l), and (i) procalcitonin level on admission (<0.2 ng/ml vs. >0.2 ng/ml). PCT, procalcitonin.View Large Image Figure ViewerDownload Hi-res image Download (PPT) Table 3 compares the general characteristics of hospitalized patients who developed severe COVID-19 (n = 109) versus those who did not (n = 137). Patients aged >60 years who were overweight or had diabetes were significantly overrepresented in the former group. Fever and dyspnea on admission—but not cough—were associated with severe disease. However, the time elapsed between symptom onset and hospitalization was similar in the 2 groups (5 days). C-reactive protein levels >60 mg/L, procalcitonin concentrations >0.2 g/L, and a partial pressure of oxygen <95% on admission were significantly associated with severe COVID-19. No similar associations were observed with lymphocyte count, platelet count, or creatinine levels. Treatment modalities and management of immunosuppression (Table 4) were slightly different in the 2 study groups in relation to disease presentation and the clinical evolution over time. These differences were especially evident with respect to CNI withdrawal (52% and 11% in patients with severe and nonsevere disease, respectively, P < 0.001). Kaplan–Meier plots of severe COVID-19–free survival according to different risk factors are provided in Figure 2b–i. Multivariable analysis identified overweight, fever, and dyspnea as independent risk factors for severe disease (Figure 3a).Table 3Baseline characteristics of kidney transplant recipients with severe versus nonsevere COVID-19CharacteristicsNonsevereSevereHR [95% CI]Pn(n =137)(n = 106)Baseline Age, yr59.5 [48.7–67.8]63.5 [54.7–69.6]1.02 [1.00–1.04]0.013243 Age >60 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 BMI > 25 kg/m278 (57.8)72 (72.0)1.80 [1.16–2.79]0.008235 Blood 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 Transplanted 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 (0.00)0.00 [–]0.996 Time from Tx to COVID-19, mo73.4 [30.9–151]77.8 [25.4–131]1.00 [1.00–1.00]0.660243 Tx within 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 RAS blockers58 (47.2)39 (41.1)0.83 [0.55–1.25]0.377218 Cardiovascular disease41 (32.5)40 (40.8)1.32 [0.88–1.98]0.176224 Respiratory 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 Mycophenolate 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 mTOR 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 admission 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 Time from symptom onset to admission, d5.00 [3.00–9.00]5.00 [3.00–7.00]1.00 [0.96–1.04]0.873219 C-reactive protein >60 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 Lymphocyte count, ×109/l0.70 [0.40–0.95]0.60 [0.40–0.96]1.10 [0.74–1.64]0.627184 Platelet count, ×109/l178 [146–229]178 [145–247]1.00 [1.00–1.00]0.742188 Thrombocytopenia < 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 Creatinine, μmol/l173 [126–230]182 [132–251]1.00 [1.00–1.00]0.378200BMI, body mass index; CNI, calcineurin inhibitor; COVID-19, coronavirus disease 2019; HR, hazard ratio; mTOR, mammalian target of rapamycin; RAS, renin–angiotensin system; Ref, reference; Tx, transplantation.Data are expressed as median [interquartile range] or count (%), as appropriate, unless otherwise indicated. Open table in a new tab Table 4Treatment modalities and immunosuppression management in kidney transplant recipients hospitalized for COVID-19 according to the presence of severe versus nonsevere diseaseTherapyNonsevereSeverePnn = 137n = 106COVID-19 treatment Azithromycin38 (27.7)33 (31.1)0.790243 Other antibiotics81 (59.1)72 (67.9)0.190243 Antifungal 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 management CNI withdrawal13 (11.3)45 (51.7)<0.001202 Antimetabolite withdrawal73 (68.2)63 (74.1)0.376192 mTOR inhibitor withdrawal8 (53.3)10 (71.4)0.18729 Belatacept withdrawal4 (50.0)3 (42.9)0.54915COVID-19, coronavirus disease 2019; CNI, calcineurin inhibitor; mTOR, mammalian target of rapamycin.Values are n (%), unless otherwise indicated. Open table in a new tab BMI, body mass index; CNI, calcineurin inhibitor; COVID-19, coronavirus disease 2019; HR, hazard ratio; mTOR, mammalian target of rapamycin; RAS, renin–angiotensin system; Ref, reference; Tx, transplantation. Data are expressed as median [interquartile range] or count (%), as appropriate, unless otherwise indicated. COVID-19, coronavirus disease 2019; CNI, calcineurin inhibitor; mTOR, mammalian target of rapamycin. Values are n (%), unless otherwise indicated. Table 5 compares the general characteristics of hospitalized patients who died (n = 43) versus those who did not (n = 200). Patients aged >60 years, who had cardiovascular disease, were receiving immunosuppressive drugs different from CNIs, and who presented with dyspnea or a partial pressure of oxygen <95% on admission, were significantly overrepresented in the former group. Multivariable analysis identified age >60 years, cardiovascular disease, and dyspnea as independent risk factors for death in hospitalized patients (Figure 3b).Table 5Baseline characteristics of kidney transplant recipients with COVID-19 who died versus those who did notCharacteristicsAliveDeadHR [95% CI]Pn(n = 200)(n = 43)Baseline Age, yr59.8 [49.8–67.5]68.9 [61.7–75.1]1.07 [1.04–1.10]<0.001243 Age >60 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 BMI >25 kg/m2122 (61.9)28 (73.7)1.65 [0.80–3.39]0.177235 Blood 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 Transplanted organ243Kidney190 (95.0)43 (100)Ref.Ref.Kidney–heart4 (2.00)0 (0.00)0.00 [0.00]0.997Kidney–liver2 (1.00)0 (0.00)0.00 [0.00]0.998Kidney–pancreas4 (2.00)0 (0.00)0.00 [0.00]0.997 Time from Tx to COVID-19, mo72.5 [27.7–147]83.7 [25.7–116]1.00 [1.00–1.00]0.933243 Tx within 1 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 RAS blockers80 (44.4)17 (44.7)1.07 [0.56–2.03]0.836218 Cardiovascular disease59 (31.9)22 (56.4)2.74 [1.45–5.17]0.002224 Respiratory disease28 (15.2)5 (12.8)0.77 [0.30–1.96]0.577223 Diabetes69 (37.5)23 (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 Mycophenolate 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 mTOR 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 admission 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 Time from symptom onset to admission, d6.00 [3.00–9.00]4.00 [2.75–6.00]0.94 [0.88–1.02]0.138219 CRP >60 mg/l82 (51.9)18 (64.3)1.69 [0.78–3.66]0.185186 Procalcitonin > 0.2 ng/ml34 (44.7)10 (71.4)2.79 [0.87–8.89]0.08390 Lymphocyte count, ×109/l0.70 [0.40–0.97]0.60 [0.44–0.96]0.80 [0.38–1.65]0.538184 Platelet count, ×109/l178 [144–232]178 [155–257]1.00 [1.00–1.00]0.894188 Thrombocytopenia <150 ×109/L48 (30.8)6 (18.8)0.54 [0.22–1.32]0.176188 SaO2 <95%47 (32.2)19 (63.3)3.39 [1.61–7.14]0.001176 Creatinine level, μmol/l176 [131–249]184 [131–230]1.00 [1.00–1.00]0.864200BMI, body mass index; CI, confidence interval; CNI, calcineurin inhibitor; COVID-19, coronavirus 2019; CRP, C-reactive protein; HR, hazard ratio; IQR, interquartile range; mTOR, mammalian target of rapamycin; RAS, renin-angiotensin system; Ref, reference; SaO2, arterial oxygen saturation; Tx, transplantation.Data are expressed as median [interquartile range] or count (%), as appropriate, unless otherwise indicated. Open table in a new tab BMI, body mass index; CI, confidence interval; CNI, calcineurin inhibitor; COVID-19, coronavirus 2019; CRP, C-reactive protein; HR, hazard ratio; IQR, interquartile range; mTOR, mammalian target of rapamycin; RAS, renin-angiotensin system; Ref, reference; SaO2, arterial oxygen saturation; Tx, transplantation. Data are expressed as median [interquartile range] or count (%), as appropriate, unless otherwise indicated. Subgroup analyses conducted in patients who tested negative on reverse transcriptase-polymerase chain reaction (7%) yielded similar results both in terms of severe disease and mortality (data not shown). The median follow-up time was 22 days; a total of 66 patients were still in the ICU at the time the manuscript was written. Despite the growing literature focusing on the clinical manifestations and prognosis of COVID-19, data on certain selected clinical populations that merit special consideration—including immunocompromised patients with a history of solid organ transplantation—remain scant. To address this knowledge gap, herein we report the general characteristics and the main risk factors for adverse outcomes—including severe disease and mortality—of a large nationwide French cohort consisting of 279 KT recipients with COVID-19. First, we demonstrate that the clinical presentation of COVID-19 in KT recipients is similar to that reported in the general population—with fever and cough being the 2 more common symptoms. These findings are in line with those from initial large reports showing fever in 77%−94% and cough in 68%−79% of cases, respectively.1Guan W.J. Ni Z.Y. Hu Y. et al.Clinical characteristics of coronavirus disease 2019 in China.N Engl J Med. 2020; 382: 1708-1720Crossref PubMed Scopus (20519) Google Scholar, 2Zhou F. Yu T. Du R. et al.Clinical course and risk factors for mortality of adult inpa