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As shown in Table 1, a total of 27 adult patients, with a median 44.0 (30.0–47.0) days between symptom onset and last positive test of SARS-CoV-2 RNA before CP therapy, were included. Their median age was 64.0 (57.0–72.0) years and 15 (55.5%) patients were male.
Characteristic Total
n = 27EN group
n = 15LN group
n = 12P value Age, median (IQR)—y 64.0 (57.0–72.0) 63.0 (57.0–72.0) 65.0 (56.2–78.0) 0.581 Male sex—no. (%) 15 (55.5) 6 (40) 9 (75) 0.121 Coexisting chronic disease—no. (%) Hypertension 12 (44.4) 6 (40) 6 (50) 0.707 Coronary artery disease 2 (7.4) 1 (6.6) 1 (8.3) 1.000 Diabetes 2 (7.4) 1 (6.6) 1 (8.3) 1.000 Malignant tumor 3 (11.1) 2 (13.3) 1 (8.3) 1.000 Neurological disorders 6 (22.2) 3 (20) 3 (25) 1.000 Chronic kidney disease 1 (3.7) 0 1 (8.3) HIV/AIDS 2 (7.4) 0 2 (16.6) Chronic liver disease 2 (7.4) 0 1 (8.3) Laboratory tests before transfusion White-cell count, median (IQR)—(× 10−9/L) 5.37 (4.81–7.99) 6.49 (4.81–7.99) 4.16(3.31–7.47) 0.075 Neutrophil count, median (IQR)—(× 10−9/L) 3.57 (2.58–5.58) 4.25 (2.94–5.70) 2.83(1.91–4.26) 0.083 Lymphocyte count, median (IQR)—(× 10−9/L) 1.24 (0.62–1.85) 1.44 (0.46–1.85) 1.07 (0.64–1.33) 0.614 Platelet count, median (IQR)—(× 10−9/L) 175 (137–194) 185 (163–219) 148 (78–183) 0.054 Hematocrit, median (IQR)—(%) 33.4 (28.4–38.4) 33.4 (26.4–40.1) 34.1 (28.7–38.3) 0.943 Serum creatinine, median (IQR)—(μmol/L) 69.1 (57.4–75.0) 66.0 (56.0–75.0) 70.5 (59.0–112.0) 0.683 Total bilirubin, median (IQR)—(μmol/L) 11.4 (8.6–18.0) 11.9 (9.4–18.0) 10.8(8.1–20.0) 0.648 Alanine aminotransferase, median (IQR)— (U/L) 17.0 (10.0-28.0) 24.0 (13.0–33.0) 13.0 (8.5–26.0) 0.103 Aspartate aminotransferase, median (IQR)—(U/L) 26.0 (20.0–42.0.0) 27.0 (21.0–60.0) 24.5 (15.5–34.5) 0.516 High-sensitivity C-reactive protein, median (IQR)—(mg/L) 3.1 (0.8–37.8) 3.1 (0.8–38.1) 3.9 (0.7–42.8) 0.733 Table 1. Demographic and clinical characteristics of patient before CP therapy.
We conducted a subgroup analysis between patients of EN group and LN group. Demographic data was shown as Table 1, median age, percentage of male patients, coexisting chronic diseases of patients in both groups were not significantly different (Table 1). Each patient of both groups underwent laboratory tests before CP therapy including white cell count, neutrophil count, lymphocyte count, platelet count, hematocrit, serum creatinine test, serum total bilirubin, serum alanine aminotransferase, serum aspartate aminotransferase, and hsCRP test, and the results were shown as Table 1.
As shown in Table 2, patients in both groups have a longer median interval between symptom onset and date of CP transfusion as compared to former reports [40.0 (26.0-47.0) days in EN group and 45.5 (41.2-57.0) days in LN group]. The median body temperature and oxygen therapy before CP transfusion were not significant different. The median fraction of inspiration O2 (FiO2), peripheral oxygen saturation and anti-viral therapies of both groups before CP therapy are shown in Table 2. Before transfusion, eight patients in EN group and seven in LN group received broad-spectrum antibiotic therapy, three patients in EN group and two in LN group received corticoid therapy after admission. Four patients in EN group and two in LN group received infusion of immunoglobulin after admission. As shown in Tables 1, 2, demographics and baseline characteristics of patients in EN group and LN group were not significant different before CP therapy.
Characteristic Total
n = 27EN group
n = 15LN group
n = 12P value Interval between symptom onset and transfusion, median (IQR)—d 45.0 (35.0–49.0) 40.0 (26.0–47.0) 45.5 (41.2–57.0) 0.075 Interval between symptom onset and last positive test before CP therapy, median (IQR)—d 44.0 (30.0–47.0) 39.0 (24.0–45.0) 44.5 (38.2–54.7) 0.126 Body temperature, median (IQR)—℃ 36.9 (36.6–37.0) 36.8 (36.5–37.2) 36.9 (36.7–37.0) 0.516 Fever—no. (%) 6 (22.2) 4 (26.6) 2 (16.6) 0.662 Oxygen therapy—no. (%) No oxygen treatment 19 (70.3) 10 (66.6) 9 (75.0) 0.696 Nasal catheter oxygen therapy 3 (11.1) 3 (20) 0 (0) Mechanical ventilation 5 (18.5) 2 (13.3) 3 (25.0) 1.000 Extracorporeal membrane oxygenation 1 (3.7) 1 (6.6) 0 (0) Fraction of inspiration O2 (n = 26), median (IQR)—% 21.0 (21.0–33.0) 21.0 (21.0–33.0) 21.0 (21.0–35.2) 0.809 Respiratory rate > 24 times/min—no. (%) 5 (18.5) 3 (20) 2 (16.6) 1.000 Peripheral oxygen saturation, median (IQR)—% 98.0 (97.0–99.0) 97.0 (97.0–99.0) 97.0 (97.0–98.5) 0.905 Vasopressors—no. (%) 4 (14.8) 1 (6.6) 3 (25.0) 0.294 Anti-virus therapy—no. (%) Ribavirin 4 (14.8) 2 (13.3) 2 (16.6) 1.000 Lopinavir 8 (29.6) 3 (20.0) 5 (41.6) 0.398 Favipiravir 2 (7.4) 2 (13.3) 0 (0) Definite or suspected coinfection—no. (%) 6 (22.2) 3 (20.0) 3 (25.0) 0.433 Broad-spectrum antibiotic therapy—no. (%) 15 (55.5) 8 (53.3) 7 (58.3) 1.000 Corticoid therapy—no. (%) 5 (18.5) 3 (20) 2 (16.6) 1.000 Immunoglobulin therapy—no. (%) 6 (22.2) 4 (26.6) 2 (16.6) 0.662 Table 2. Patients' status and treatments received before CP therapy.
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As shown in Table 3, the median and interquartile ranged total volume of CP transfusion was 400 (200–400) mL in EN group and 400 (400–800) mL in LN group. No adverse reactions related to blood transfusion were found during infusion in both groups. The median interval between transfusion and discharge was 7.0 (4.0–11.0) days in EN group and 24.0 (14.7–28.7) days in LN group. Most patients underwent X-ray or CT scan before and after transfusion (EN group = 8; LN group = 12), and pulmonary imaging improvement was confirmed in 7 patients in EN group and 8 in LN group after CP therapy.
Characteristic Total
n = 27EN group
n = 15LN group
n = 12P value Total volume dose of CP, median (IQR)—mL 400 (200–600) 400 (200–400) 400 (400–800) 0.861 Transfusion-related adverse reactions—no. (%) 0 (0) 0 (0) 0 (0) Interval between first transfusion and discharge, median (IQR)—d 11.0 (6.0–25.0) 7.0 (4.0–11.0) 24.0 (14.7–28.7) Pulmonary imaging improvement 15/20 7/8 8/12 0.603 Length of hospital stay, median (IQR)—d 43.0 (24.0–54.0) 37.0 (19.0–50.0) 52.0 (35.0–63.7) Mortality of 60 days—no. (%) 3 (11.1) 0 (0) 3 (25) Table 3. Patients' status after transfusion and outcome after CP therapy.
The median length of hospitalization in EN group was 37.0 days and 52.0 days in LN group, as shown in Table 3. Due to the definition of EN group and LN group, the median length of hospitalization in LN group was much longer than EN group, thus we didn't make a comparative analysis. Three patients died in LN group within 60 days, two died from refractory hypoxemia and one in LN group died from severe septic shock. No patients died in EN group within 60 days.
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Five patients in our study underwent CT scan before (within 3 days) and reexamination after transfusion (within 5–8 days). For these patients, comparison and analysis of CT images were performed before and after transfusion by using the AI-assisted diagnostic system described above (Fig. 1A, 1B). Three (60%) patients showed as consolidation of CT images before CP therapy (Fig. 1C), five all showed as ground-glass opacity (GGO) (Fig. 1D) before CP therapy, which were similar to the former report about CT findings in COVID-19 patients (Adair and Ledermann 2020). After transfusion, the total consolidation percentage decreased after transfusion in three patients (Fig. 1C), and the total GGO percentage decreased in five all patients' CT images (Fig. 1D).
Figure 1. CT images before and after CP therapy. A Results of AI-assisted diagnostic system in patient 2 before CPT, blue areas represent GGO in CT images, red areas represent consolidation in CT images. B Results of AI-assisted diagnostic system in patient 2 after CPT. C Consolidation of CT in patients 1, 2, and 3 decreased after the transfusion. D GGO of CT in patients 1, 2, 3, 4, and 5 decreased after CP therapy.
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After admission, patients in both groups underwent SARS-CoV-2 tests by using RT-PCR as described above. The variation trend of Ct value in both groups are show as Fig. 2. The median Ct value on admission is 33.0 (28.7–38.2) in EN group and 32.5 (22.1–38.1) in LN group, without significant differences (P = 0.591, Fig. 2). Besides, the median Ct values was not significant between EN group and LN group before transfusion [34.0 (26.4-38.3) vs. 30.9 (26.7-35.7), P = 0.591, Fig. 2]. After transfusion, Ct values of patients in EN group increased and > 43 within 7 days gradually and most of them (n = 13) discharged within 10 days and were unable to detect at 9, 12, and 15 days. Conversely, the median Ct values of patients in LN group remained < 43 at 3, 5, 7, 9, and 12 days after transfusion, 6 patients in LN group still remained < 43 at 15 days after transfusion (Fig. 2).
Figure 2. Variation trend of viral load of patients before and after CP therapy: Ct value of < 43 is defined to be positive, and Ct value of > 47 would be undetectable. *The median Ct value in early negative group (ENG) was significantly greater than late negative group (LNG) on day 3 after the transfusion, P = 0.043. **: The median Ct value in early negative group was significantly greater than late negative group on day 5, P = 0.008. ***: The median Ct value in early negative group was significantly greater than late negative group on day 7, P = 0.003.