Patients characteristics

The characteristics of consecutive 179 hospitalized COVID-19 patients were showed in Table 1. The comparison between serious and non-serious infection group was showed in Supplementary Table 1. Forty-three (24%) and 136 (76%) patients were diagnosed as serious and non-serious infection, respectively. The median duration of disease was 18days (range 2102) days, and duration of SARS-CoV-2 infection>18days and18days was defined as long-term (n=90) and short-term infection (n=89), respectively (Supplementary Table 2). The median time from transplantation to COVID-19 infection occurrence was 149days (range 63038) days. A total of 116 (64.8%) patients received immunosuppressants, including cyclosporin (n=85), tacrolimus (n=8), ruxolitinib (n=8), or glucocorticoids (n=32) when COVID-19 occurrence. Seventeen patients received more than 1 type of immunosuppressants. A total of 144 (80.4%) patients received anti-viral treatment (140 for Paxlovid and 4 for Azvudine). Forty serious infection cases (93.0%) received anti-viral treatment (39 for Paxlovid and 1 for Azifudine), 85 long-term infection cases (94.4%) received anti-viral treatment (83 for Paxlovid and 2 for Azifudine). Sixty-two patients received newly added drugs corticosteroid treatment, that is, 23 (53.5%) and 39 (28.7%) patients were in the serious and non-serious infection group, 9 (10.1%) and 53 (58.9%) patients were in the short- and long-term infection group, respectively.

A total of 26, 33, and 11 patients showed PGF, leukopenia and thrombocytopenia, respectively, after COVID 19 infection. The 150-day cumulative incidence of leukopenia, thrombocytopenia, and PGF was 18.4% (95% confidence interval [CI] 12.724.1%), 6.1% (95% CI 2.619.6%), and 14.5% (95% CI 9.319.7%) respectively, after COVID-19.

The 150-day cumulative incidence of PGF after COVID-19 was 11.8% (95% CI 6.417.2%) versus 23.3% (95% CI 10.536.1%) (P=0.071) between non-serious and serious infection group, which was 9.0% (95% CI 3.015.0%) versus 20.0% (95% CI 11.728.3%) (P=0.045) between short- and long-term infection group (Fig.1A).

The 150-day cumulative incidence of PGF and leukopenia after COVID-19 between short and long-term infection group. (A) PGF; (B) leukopenia. PGF poor graft function.

The 150-day cumulative incidence of leukopenia after COVID-19 was 19.9% (95% CI 13.226.6%) versus 14.0% (95% CI 3.524.5%) (P=0.325) between non-serious and serious infection group, which was 12.4% (95% CI 5.519.3%) versus 24.4% (95% CI 15.533.3%) (P=0.049) between short- and long-term infection group (Fig.1B).

The 150-day cumulative incidence of thrombocytopenia after COVID-19 was 5.1% (95% CI 1.48.8%) versus 9.3% (95% CI 0.518.1%) (P=0.331) between non-serious and serious infection group, which was 5.6% (95% CI 0.810.4%) versus 6.7% (95% CI 1.511.9%) between short- and long-term infection group (P=0.779).

The median duration of leukopenia, thrombocytopenia, and PGF was 14days (range 4118) days, 10days (range 878) days, and 17days (range 978) days, respectively. Until the last follow up, leukopenia, thrombocytopenia and PGF were still persistence 22 patients.

In multivariable analysis, after adjusted by other factors, the duration of COVID-19 was associated with PGF (hazard ratio [HR], 2.31; 95% CI 1.045.11; P=0.039) and leukopenia (HR 2.29; 95% CI 1.045.07; P=0.04) (Table 2). The other risk factors for PGF and leukopenia were showed in Supplementary Table 4.

A total of 5 patients showed aGVHD after COVID 19 infection, and the cumulative incidence of total aGVHD was 2.8% (95% CI 0.45.2%) after COVID-19. The cumulative incidence of aGVHD after COVID-19 was 3.7% (95% CI 0.56.9%) versus 0% (P=0.204), respectively, between non-serious and serious infection group, which was 3.4% (95% CI 0.47.2%) versus 2.2% (95% CI 0.95.3%) (P=0.651), respectively, between short- and long-term infection group. No risk factors were associated with aGVHD in multivariable analysis.

A total of 4, 4 and 3 patients showed mild, moderate, and severe cGVHD after COVID 19 infection, and the cumulative incidence of cGVHD was 6.70% after COVID-19. The 150-day cumulative incidence of cGVHD after COVID-19 was 7.4% (95% CI 2.911.8%) versus 4.7% (95% CI 1.711.1%), respectively, between non-serious and serious infection group (P=0.544). The 150-day cumulative incidence of cGVHD after COVID-19 was 6.7% (95% CI 1.511.9%) versus 5.6% (95% CI 0.810.4%), respectively, between short- and long-term infection group (P=0.741). No risk factors were associated with cGVHD in multivariable analysis.

A total of 34 and 7 patients showed CMV DNAemia and CMV disease (CMV pneumonia: 5, CMV gastrointestinal disease: 1, CMV encephalitis+retinitis: 1) after COVID 19 infection. The 150-day cumulative incidence of CMV DNAemia after COVID-19 was 19.9% (95% CI 13.226.6%) versus 11.6% (95% CI 1.921.3%) (P=0.204), respectively, between non-serious and serious infection group, which was 14.6% (95% CI 7.222.0%) versus 23.3% (95% CI 14.532.1%) (P=0.118), respectively, between short- and long-term infection group. The 150-day cumulative incidence of CMV disease after COVID-19 was 0.7% (95% CI 0.72.1%) versus 14.0% (95% CI 3.524.5%) (P<0.0001, Fig.2A), respectively, between non-serious and serious infection group, which was 0% versus 7.8% (95% CI 2.213.4%) (P=0.007, Fig.2B), respectively, between short- and long-term infection group. Particularly, the 150-day cumulative incidence of CMV pneumonia after COVID-19 was 0% versus 11.6% (95% CI 1.921.4%) (P<0.0001, Fig.2C), respectively, between non-serious and serious infection group, which was 0% versus 5.6% (95% CI 0.810.4%) (P=0.0245, Fig.2D), respectively, between short- and long-term infection group. In multivariable analysis, after adjusted by other factors, the severity of COVID-19 was associated with CMV disease (HR, 20.15; 95% CI 2.43167.36, P=0.005) (Table 2).

The association between COVID-19 and CMV disease. The 150-day cumulative incidence of CMV disease after COVID-19 between (A) non-serious and serious infection group; (B) short and long-term infection group. The 150-day cumulative incidence of CMV pneumonia after COVID-19 between (C) non-serious and serious infection group; (D) short and long-term infection group. CMV cytomegalovirus.

A total of 11 and 3 patients showed Epstein-Barr virus (EBV) DNAemia and EBV associated posttransplant lymphoproliferative disorders (PTLD) after COVID-19. The 150-day cumulative incidence of EBV DNAemia after COVID-19 was 7.4% (95% CI 3.011.8%) versus 0.00% (P=0.068), respectively, between non-serious and serious infection group. The 150-day cumulative incidence of EBV DNAemia after COVID-19 was 5.6% (95% CI 0.810.4%) versus 5.6% (95% CI 0.810.4%) (P=0.968), respectively, between short- and long-term infection group. All the 3 PTLD patients were in the non-serious group. No risk factors were associated with EBV DNAemia and PTLD in multivariable analysis.

A total of 27 patients died after COVID-19, and the caused were summarized in Table 3. The most common cause was infection besides of COVID-19 (n=9, 33.3%), followed by relapse (n=7, 25.9%) and COVID-19 (n=4, 14.8%).

The 150-day cumulative incidence of non-relapse mortality (NRM) after COVID-19 infection was 11.2% (95% CI 6.615.8%), which was 2.2% (95% CI 0.34.7%) and 39.5% (95% CI 24.654.4%) between non-serious and serious infection group (P<0.0001, Fig.3A), and was 2.2% (95% CI 0.95.3%) and 20.0% (95% CI 11.728.3%) (P=0.002, Fig.3B) between short- and long-term infection group.

The association between COVID-19 and survival. The 150-day cumulative incidence of NRM after COVID-19 between (A) non-serious and serious infection group; (B) short and long-term infection group. The 150-day probability of OS after COVID-19 infection between (C) non-serious and serious infection group; (D) short and long-term infection group. NRM non-relapse mortality, OS overall survival.

The 150-day probability of overall survival (OS) after COVID-19 infection was 84.9% (95% CI 79.690.2%), which was 94.9% (95% CI 91.298.6%) and 53.5% (95% CI 38.168.5%) between non-serious and serious infection group (P<0.0001, Fig.3C), and was 93.3% (95% CI 88.198.5%) and 76.7% (95% CI 67.985.5%) (P=0.002, Fig.3D) between short- and long-term infection group.

In multivariable analysis, after adjusted by other factors, the severity of COVID-19 was associated with NRM (HR, 17.26; 95% CI 4.8761.21, P<0.0001). The severity of COVID-19 were associated with OS (HR, 14.00; 95% CI 5.8733.42, P<0.0001) (Table 2), The other risk factors for NRM and OS were showed in Supplementary Table 4.

A total of 179 patients without COVID-19 infection were enrolled as controlled and the characteristics between patients with and without COVID-19 were showed in Supplementary Table 5. The 150-day probability of NRM and OS were 11.2% (95% CI 6.615.8%) versus 3.9% (95% CI 1.16.7%) with P=0.009 and 84.9% (95% CI 79.690.2%) versus 93.9% (95% CI: 88.7%99.1%) with P=0.006, respectively, for patients in the group with and without COVID-19 infection (Fig.4A,B). The probability of NRM and OS for patients without COVID-19 infections were superior to those in serious infection group or long-term infection group (Fig.4C,D).

Clinical outcomes of patients with and without COVID 19 infection. (A) The 150-day cumulative incidence of NRM in the group with and without COVID-19 infection; (B) The 150-day cumulative incidence of OS in the group with and without COVID-19 infection; (C) The 150-day cumulative incidence of NRM in the group without COVID-19 infection, serious infection and long-term infection; (D) The 150-day cumulative incidence of OS in the group without COVID-19 infection, serious infection and long-term infection, NRM non-relapse mortality, OS overall survival.

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