Extracorporeal Photopheresis as a Possible Therapeutic Approach for Adults with Severe and Critical COVID-19 Non-Responsive to Standard Treatment: A Pilot Investigational Study
Abstract
:1. Introduction
2. Methods
2.1. Study Design
2.2. Patient Enrollment
2.3. Data Collection
2.4. Diagnostic and Therapeutic Strategies, Follow-Up
2.5. Protocol of Extracorporeal Photopheresis
2.6. Outcomes and Statistical Analysis
3. Results
3.1. Demographic Characteristics of Patients
3.2. Clinical Characteristics of Patients
3.3. Laboratory Characteristics of Patients
3.4. Immune Biomarker Profiling of Patients
3.5. Outcome Characteristics of Patients
3.6. ECP MNC Apoptosis Assessment
4. Discussion
4.1. Main Study Findings
4.2. Previous Literature Findings
4.3. Limitations
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
ANA | anti-nuclear antibody |
ANCA | anti-neutrophil cytoplasmic antibody |
ARDS | acute respiratory distress syndrome |
C | complement |
CD | cluster of differentiation |
COVID-19 | coronavirus disease 2019 |
CT | computed tomography |
ECP | extracorporeal photopheresis |
ENA | extractable nuclear antigen |
EOT | end of treatment |
FACS | fluorescence-activated cell sorting |
FiO2 | fraction of inspired oxygen |
ICU | intensive care unit |
IFN | interferon |
Ig | immunoglobulin |
IL | interleukin |
LDH | lactate dehydrogenase |
LOS | length of stay |
NK | natural killer |
MNC | mononuclear cell collection |
PaO2 | partial arterial oxygen tension |
RNA | ribonucleic acid |
RT-PCR | real-time polymerase chain reaction |
SARS-CoV-2 | severe acute respiratory syndrome coronavirus 2 |
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Patient Identification | Pt. 1. | Pt. 2. | Pt. 3. | Pt. 4. | Pt. 5. | Pt. 6. | Pt. 7. | Total |
---|---|---|---|---|---|---|---|---|
Age (years) | 55 | 65 | 32 | 54 | 51 | 41 | 72 | 54 ± 14 (32–72) |
Gender (n, %) | M | M | M | M | M | F | F | M: 5/7 (71.4) F: 2/7 (28.6) |
Comorbidities (n, %) | AC | HT OB | CCD CHD CRD CVD HT | CPD HEM TOB | CPD HT OB | AID CHD CPD CVD HT TOB | AID CHD CRD CVD HEM HT | AC: 1/7 (14.3) AID: 2/7 (28.6) CCD: 1/7 (14.3) CHD: 3/7 (42.9) CPD: 3/7 (42.9) CRD: 2/7 (28.6) CVD: 3/7 (42.9) HEM: 2/7 (28.6) HT: 5/7 (71.4) OB: 2/7 (28.6) TOB: 2/7 (28.6) |
COVID-19 vaccination status: | ||||||||
- Primary series (n, %) | N | 2 × AZ | 2 × Sp | 2 × Pf | 2 × Pf | 2 × Pf | 2 × Pf | Y: 6/7 (85.7) |
- Booster vaccination (n, %) | n.a. | 1 × Pf | N | N | N | N | 1 × Pf | Y: 2/6 (33.3) |
- Time since last vaccine (months) | n.a. | 1 | 8 | 7 | 6 | 6 | 2 | 6 ± 5 (1–8) |
Symptom duration before COVID-19 diagnosis (days) | 7 | 6 | 1 | 1 | 2 | 2 | 4 | 2 ± 4 (1–7) |
Therapies against COVID-19 (n, %): | ||||||||
- Remdesivir | Y | Y | Y | Y | Y | Y | Y | Y: 7/7 (100) |
- Dexamethasone | Y | Y | Y | Y | Y | Y | Y | Y: 7/7 (100) |
- Tocilizumab | Y | Y | Y | N | N | Y | N | Y: 4/7 (57.1) |
- Baricitinib | Y | Y | N | N | Y | N | Y | Y: 4/7 (57.1) |
- Ruxolitinib | N | N | N | Y | N | N | N | Y: 1/7 (14.3) |
- Reconvalescent plasmatherapy | Y | N | Y | Y | Y | Y | Y | Y: 6/7 (85.7) |
Clinical outcomes (n, %): | ||||||||
- All-cause death | N | N | N | N | N | Y | Y | Y: 2/7 (28.6) |
- Invasive mechanical ventilation | Y | N | Y | N | N | N * | N * | Y: 2/7 (28.6) |
- ICU admission | Y | N | Y | N | Y | N * | Y * | Y: 4/7 (57.1) |
Virological outcomes (n, %): | ||||||||
- Respiratory SARS-CoV-2 RT-PCR positivity | N | Y | N | N | Y | Y * | Y * | Y: 4/7 (57.1) |
- Blood SARS-CoV-2 RT-PCR positivity | N | N | N | N | N | N * | N * | Y: 0 (0) |
Radiological outcomes (n, %) | ||||||||
- Radiological progression on chest CT scan | N | N | N | N | N | Y * | Y * | Y: 2/7 (28.6) |
- Radiological regression on chest CT scan | N | Y | N | Y | Y | N | N | Y: 3/7 (42.9) |
- Fixed infiltration on chest CT scan | Y | N | Y | N | N | N | N | Y: 2/7 (28.6) |
Hospital ward length of stay (days) ** | 86 | 45 | 0 | 30 | 51 | 24 | 0 | 45 ± 42 (24–86) |
Intensive care unitlength of stay (days) | 69 | 0 | 91 | 0 | 48 | 0 | 22 | 59 ± 45 (22–91) |
Time to death from hospital admission (days) | n.a. | n.a. | n.a. | n.a. | n.a. | 24 | 22 | 23 ± n.a. (22–24) |
Patient Identification | Pt. 1. | Pt. 2. | Pt. 3. | Pt. 4. | Pt. 5. | Pt. 6. | Pt. 7. | Total | p Value ** | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Time of Assessment | Baseline | Inclusion | Baseline | Inclusion | Baseline | Inclusion | Baseline | Inclusion | Baseline | Inclusion | Baseline | Inclusion | Baseline | Inclusion | Baseline | Inclusion | |
COVID-19 severity | C | C | C | C | C | C | S | S | C | C | S | C | S | S | C: 4/7 (57.1) S: 3/7 (42.9) | C: 5/7 (71.4) S: 2/7 (28.6) | 1.0 |
Infiltrate extension on chest CT (%) * | 80 | 80 | 50 | 50 | 80 | 80 | 20 | 30 | 80 | 80 | 20 | 80 | 20 | 50 | 50 ± 60 (20–80) | 80 ± 30 (30–80) | 0.37 |
Partial arterial oxygen tension per fraction of inspired oxygen (mmHg/%) * | 95 | 85 | 175 | 80 | 115 | 90 | 300 | 200 | 55 | 90 | 205 | 85 | 300 | 200 | 175 ± 205 (55–300) | 90 ± 115 (80–200) | 0.16 |
ARDS | Y | Y | N | N | Y | Y | N | N | Y | Y | N | N | N | N | Y: 3/7 (42.9) | Y: 3/7 (42.9) | 1.0 |
Cytokine storm | Y | Y | Y | Y | Y | Y | Y | Y | Y | Y | N | Y | Y | Y | Y: 6/7 (85.7) | Y: 7/7 (100%) | 1.0 |
Respiratory SARS-CoV-2 RT-PCR positivity | Y | Y | Y | Y | Y | Y | Y | Y | Y | Y | Y | Y | Y | Y | Y: 7/7 (100%) | Y: 7/7 (100%) | 1.0 |
Blood SARS-CoV-2 RT-PCR positivity | Y | Y | N | Y | Y | Y | N | Y | Y | Y | N | N | N | Y | Y: 3/7 (42.9) | Y: 6/7 (85.7) | 0.31 |
ICU admission | N | Y | N | N | Y | Y | N | N | Y | Y | N | N | N | Y | Y: 2/7 (28.6) | Y: 4/7 (57.1) | 0.59 |
Invasive mechanical ventilation | N | Y | N | N | Y | Y | N | N | Y | Y | N | N | N | N | Y: 2/7 (28.6) | Y: 3/7 (42.9) | 1.0 |
Parameter | Baseline | Inclusion | Post-ECP Follow-Up | p Value * | |||
---|---|---|---|---|---|---|---|
+3 Days | +7 Days | +14 Days | +28 Days | ||||
Blood absolute white blood cell count (×109/L) | 8.1 ± 3.2 (2.1–10.5) | 8.9 ± 7.4 (1.9–21.3) | 14.3 ± 7.4 (3.7–23.5) | 8.1 ± 2.4 (4.5–21.4) | 6.4 ± 6.4 (2.3–19.7) | 8.1 ± 2.5 (3.7–9.2) | 0.97 |
Blood absolute neutrophil granulocyte count (×109/L) | 4.7 ± 2.0 (1.8–9.2) | 6.2 ± 7.9 (1.4–16.9) | 8.2 ± 6.9 (2.5–20.1) | 6.1 ± 4.6 (3.0–17.7) | 3.8 ± 5.1 (1.1–15.5) | 4.4 ± 1.9 (2.1–6.1) | 0.46 |
Blood absolute lymphocyte count (×109/L) | 0.8 ± 1.7 (0.1–4.1) | 1.5 ± 1.3 (0.2–3.3) | 1.3 ± 1.1 (0.4–5.4) | 1.4 ± 1.7 (0.5–3.6) | 1.4 ± 1.2 (0.3–2.6) | 1.8 ± 1.6 (0.4–6.0) | 0.52 |
Blood absolute monocyte count (×109/L) | 0.3 ± 0.2 (0.1–0.8) | 0.3 ± 0.3 (0.2–1.5) | 0.6 ± 0.5 (0.1–1.4) | 0.4 ± 0.3 (0.1–1.7) | 0.5 ± 0.7 (0.3–2.0) | 0.7 ± 0.6 (0.3–0.9) | 0.7 |
Blood hemoglobin (g/L) | 113 ± 18 (96–141) | 136 ± 40 (86–140) | 111 ± 31 (76–142) | 98 ± 19 (82–131) | 96 ± 13 (84–133) | 85 ± 12 (75–139) | 0.07 |
Blood platelet count (×109/L) | 177 ± 113 (49–368) | 302 ± 208 (43–853) | 230 ± 233 (26–432) | 167 ± 220 (30–498) | 111 ± 126 (43–705) | 156 ± 368 (35–783) | 0.87 |
Serum lactate dehydrogenase (IU/L) | 943 ± 283 (400–1168) | 1096 ± 379 (530–1802) | 807 ± 200 (586–2020) | 693 ± 166 (505–847) | 473 ± 88 (389–626) | 522 ± 214 (274–626) | 0.02 |
Serum glutamic pyruvate transaminase (IU/L) | 34 ± 16 (11–48) | 31 ± 39 (18–76) | 75 ± 41 (19–395) | 85 ± 71 (16–253) | 119 ± 192 (19–338) | 38 ± 56 (16–117) | 0.62 |
Serum creatinine (μmol/L) | 117 ± 134 (64–364) | 127 ± 97 (61–315) | 93 ± 38 (46–371) | 113 ± 178 (33–317) | 98 ± 80 (35–281) | 68 ± 57 (29–120) | 0.1 |
Serum ferritin (μg/L) | 1107 ± 1340 (35–2478) | 1488 ± 1110 (249–6241) | 1185 ± 2122 (284–4034) | 1709 ± 1895 (470–3052) | 822 ± 1247 (444–2439) | 715 ± 505 (324–3753) | 0.74 |
Serum C-reactive protein (mg/L) | 114 ± 142 (33–279) | 39 ± 128 (1–245) | 30 ± 50 (4–94) | 44 ± 59 (2–192) | 43 ± 160 (0–338) | 35 ± 3 (0–46) | 0.28 |
Serum procalcitonin (ng/mL) | 0.1 ± 0.1 (0–0.1) | 0.1 ± 0.1 (0–1.2) | 0 ± 0.1 (0–1.3) | 0.1 ± 0.1 (0–2.1) | 0.2 ± 0.6 (0–0.7) | 0 ± 0 (0–2.4) | 0.92 |
Plasma D-dimer (ng/mL) | 1184 ± 568 (642–2128) | 1254 ± 1601 (659–3581) | 1145 ± 327 (799–1473) | 1411 ± 672 (496–2384) | 1592 ± 1108 (261–13920) | 763 ± 250 (597–965) | 0.21 |
Parameter | Baseline | Inclusion | Post-ECP Follow-Up | p Value * | |||
---|---|---|---|---|---|---|---|
+3 Days | +7 Days | +14 Days | +28 Days | ||||
Serum interferon-α (pg/mL) | 33.6 ± 25.8 (8.0–60.4) | 14.8 ± 11.8 (1.5–34.7) | 9.0 ± 3.3 (1.5–47.3) | 9.0 ± 10.5 (8.0–60.4) | 8.0 ± 0.3 (8.0–9.0) | 8.0 ± 0.1 (8.0–14.8) | 0.14 |
Serum interferon-γ (pg/mL) | 7.7 ± 25.5 (1.3–48.6) | 1.3 ± 34.5 (1.3–37.7) | 10.0 ± 16.0 (1.3–44.7) | 1.3 ± 31.6 (1.3–148.3) | 7.4 ± 20.0 (1.3–44.9) | 6.0 ± 4.9 (1.3–22.1) | 0.33 |
Plasma interleukin-1α (pg/mL) | 40.7 ± 23.6 (4.8–67.4) | 23.3 ± 16.3 (4.8–91.9) | 55.7 ± 45.0 (4.8–68.2) | 34.9 ± 48.0 (4.8–68.2) | 20.4 ± 156.1 (4.8–535.2) | 8.2 ± 55.9 (4.8–60.7) | 0.18 |
Plasma interleukin-1β (pg/mL) | 7.2 ± 9.0 (1.6–11.9) | 1.6 ± 3.8 (1.6–9.2) | 4,2 ± 5,8 (1.6–10.6) | 1.6 ± 4.6 (1.6–40.1) | 1.9 ± 1.6 (1.6–6.2) | 1.6 ± 0.1 (1.6–1.7) | 0.12 |
Plasma interleukin-2 (pg/mL) | 1.0 ± 1.1 (0.6–10.6) | 0.6 ± 0.7 (0.6–2.2) | 0.6 ± 0.8 (0.6–6.9) | 0.6 ± 0.1 (0.6–16.8) | 0.8 ± 1.1 (0.6–4.5) | 0.6 ± 0.3 (0.6–1.7) | 1.0 |
Plasma interleukin-4 (pg/mL) | 2.2 ± 6.3 (0.9–15.2) | 3.2 ± 2.8 (0.6–10.1) | 1.7 ± 4.6 (0.6–6.2) | 1.0 ± 10.5 (0.6–45.2) | 2.6 ± 5.9 (0.6–12.6) | 1.3 ± 2.1 (0.6–8.4) | 0.44 |
Plasma interleukin-5 (pg/mL) | 4.7 ± 21.7 (0.6–44.9) | 2.7 ± 1.4 (0.6–3.0) | 1.2 ± 0.7 (1.0–5.0) | 1.6 ± 129.5 (0.6–494.3) | 3.7 ± 19.0 (1.1–63.9) | 6.3 ± 21.1 (1.0–23.6) | 0.44 |
Plasma interleukin-6 (pg/mL) | 38.0 ± 38.0 (11.5–168.0) | 203.5 ± 1688.0 (8.5–2776.0) | 134.5 ± 398.5 (7.5–904.0) | 84.0 ± 461.5 (20.5–1952.0) | 751.0 ± 1907.0 (12.5–4381.0) | 6.5 ± 24.0 (3.0–634.5) | 0.04 |
Plasma interleukin-8 (pg/mL) | 28.9 ± 12.6 (5.2–94.0) | 14.3 ± 31.9 (11.3–66.6) | 22.6 ± 8.1 (9.7–68.1) | 34.2 ± 25.1 (8.3 ± 107.3) | 30.0 ± 12.5 (7.0–36.3) | 26.5 ± 21.7 (11.9–44.0) | 0.41 |
Plasma interleukin-10 (pg/mL) | 20.9 ± 10.6 (2.6–26.2) | 8.5 ± 18.5 (2.6–39.6) | 35.7 ± 17.5 (2.6 ± 86.3) | 21.9 ± 90.1 (5.0–135.1) | 4.4 ± 160.7 (2.6–634.7) | 18.0 ± 36.3 (2.6–70.3) | 0.64 |
Plasma interleukin-12 (pg/mL) | 4.0 ± 3.5 (3.0–93.8) | 3.0 ± 4.3 (3.0–57.8) | 3.0 ± 0.1 (3.0–71.9) | 3.0 ± 0.9 (3.0–247.8) | 3.0 ± 15.2 (3.0–63.7) | 3.0 ± 0.3 (3.0–32.2) | 0.11 |
Plasma interleukin-13 (pg/mL) | 32.2 ± 62.2 (6.4–274.5) | 20.7 ± 100.2 (6.4–264.1) | 18.5 ± 76.5 (6.4–111.1) | 10.6 ± 109.7 (6.4–408.7) | 30.5 ± 68.8 (6.4 ± 137.2) | 19.7 ± 30.5 (6.4–79.9) | 0.59 |
Plasma interleukin-15 (pg/mL) | 13.8 ± 7.5 (6.9–21.6) | 9.7 ± 8.2 (7.9–26.3) | 13.5 ± 6.9 (6.4–25.6) | 7.6 ± 3.3 (5.3–32.9) | 4.3 ± 1.0 (3.0–5.9) | 7.2 ± 5.9 (4.0 ± 12.9) | 0.68 |
Plasma interleukin-17A (pg/mL) | 6.5 ± 5.9 (1.3–11.1) | 4.1 ± 3.8 (1.3–9.2) | 4.7 ± 2.8 (1.3–7.4) | 1.3 ± 1.4 (1.3–8.3) | 1.3 ± 0.1 (1.3–1.3) | 1.3 ± 0.1 (1.3–1.3) | <0.01 |
Serum IP-10 (pg/mL) | 1732.8 ± 2939.5 (205.0–5024.9) | 120.7 ± 587.7 (101.8–1071.0) | 166.3 ± 357.7 (63.9–583.4) | 216.3 ± 230.3 (79.9–374.1) | 104.9 ± 135.3 (73.6–488.9) | 135.5 ± 193.9 (95.0–310.1) | 0.5 |
Serum MCP-1 (pg/mL) | 972.8 ± 2068.9 (362.9–4650.5) | 761.2 ± 680.3 (255.9–1886.2) | 600.5 ± 204.6 (372.0–1484.6) | 682.2 ± 123.7 (296.5–4010.7) | 526.6 ± 432.9 (337.5–1512.0) | 468.3 ± 18.8 (335.4–1408.2) | 0.5 |
Serum MIP-1α (pg/mL) | 22.7 ± 17.2 (3.0–43.5) | 15.1 ± 6.6 (3.0–47.9) | 15.1 ± 11.8 (3.0–47.9) | 13.1 ± 39.0 (3.0–87.5) | 9.8 ± 31.4 (3.0–87.9) | 11.3 ± 10.6 (3.0–33.8) | 0.4 |
Serum RANTES (pg/mL) | 2416.4 ± 2479.9 (831.1–6169.0) | 4172.3 ± 1419.0 (1125.9–17271.7) | 3523.7 ± 1976.1 (320.7–7093.2) | 2576.8 ± 1186.9 (624.5–3021.3) | 2040.4 ± 589.2 (1068.8–2959.3) | 1834.2 ± 1262.6 (619.7–2887.7) | 0.85 |
Serum TNF-α (pg/mL) | 59.9 ± 44.0 (24.7–155.6) | 38.5 ± 33.3 (18.5–80.2) | 39.6 ± 16.8 (28.8–60.2) | 39.6 ± 152.4 (6.4–244.0) | 32.0 ± 37.3 (13.4–100.3) | 26.3 ± 18.7 (8.0–47.6) | 0.86 |
Serum TNF-β (pg/mL) | 22.0 ± 54.2 (2.2–69.2) | 18.5 ± 35.4 (1.6–71.0) | 10.8 ± 13.0 (1.6–39.7) | 5.3 ± 56.7 (1.6–72.7) | 9.2 ± 15.8 (1.6–25.8) | 4.6 ± 11.6 (1.6–15.3) | 0.33 |
Serum IgG (g/L) | 7.8 ± 3.8 (1.3–15.4) | 8.0 ± 1.9 (4.8–12.0) | 7.7 ± 0.7 (6.7–8.0) | 6.1 ± 1.8 (4.9–11.9) | 7.6 ± 0.1 (7.0–9.5) | 7.6 ± 2.4 (7.2–9.8) | 0.05 |
Serum IgA (g/L) | 1.9 ± 0.9 (0.5–5.1) | 2.1 ± 0.8 (0.3–3.3) | 1.4 ± 1.0 (0.5–2.6) | 2.0 ± 1.8 (0.4–3.0) | 1.9 ± 0.1 (1.9–1.9) | 1.9 ± 0.7 (0.5–2.0) | 0.97 |
Serum IgM (g/L) | 1.3 ± 1.1 (0.1–2.4) | 0.8 ± 0.6 (0–1.9) | 0.8 ± 1.7 (0–3.5) | 1.0 ± 1.2 (0–2.6) | 0.9 ± 0.1 (0–0.9) | 0.9 ± 0.1 (0.1–3.1) | 0.9 |
Serum electrophoresis/immunofixation | Normal/negative | Normal/negative | Normal/negative | Normal/negative | Normal/negative | Normal/negative | n.a. |
Serum C3 (g/L) | 1.3 ± 0.3 (0.6–1.7) | 1.1 ± 0.3 (1.0–1.6) | 1.3 ± 0.8 (0.9–2.0) | 1.7 ± 0.4 (0.9–1.7) | 0.9 ± 0.1 (0.8–1.0) | 1.0 ± 0.1 (0.8–1.8) | 1 |
Serum C4 (g/L) | 0.3 ± 0.1 (0.2–0.5) | 0.3 ± 0.1 (0.1–0.4) | 0.3 ± 0.2 (0–0.4) | 0.3 ± 0.3 (0–0.4) | 0.1 ± 0.1 (0.1–0.2) | 0.2 ± 0.1 (0.1–0.5) | 0.97 |
Serum ENA ELISA | Below c/o | Below c/o | Below c/o | Below c/o | Below c/o | Below c/o | n.a. |
Serum anti-dsDNA (IU/mL) | 4.0 ± 7.5 (1.0–16.0) | 3.0 ± 0.8 (1.0–4.0) | 2.5 ± 3.0 (1.0–10.0) | 4.0 ± 1.0 (3.0–5.0) | 6.5 ± 0.5 (6.0–7.0) | 3.0 ± 4.0 (1.0–7.0) | 0.46 |
Serum ANCA IF | Below c/o | Below c/o | Below c/o | Below c/o | Below c/o | Below c/o | n.a. |
Serum ANA IF | Below c/o | Below c/o | Below c/o | Below c/o | Below c/o | Below c/o | n.a. |
Parameter | Baseline | Inclusion | Post-ECP Follow-Up | p Value * | |||
---|---|---|---|---|---|---|---|
+3 Days | +7 Days | +14 Days | +28 Days | ||||
Regulatory T-cell ratio (%) | 0.1 ± 0.1 (0.1–0.3) | 0.1 ± 0.1 (0–0.3) | 0.4 ± 0.1 (0.4–0.5) | 0.1 ± 0.5 (0.1–1.0) | 0.3 ± 0.1 (0.3–0.3) | 0.2 ± 0.3 (0.1–0.3) | 0.74 |
CD3+ T-cell count (cells/μL) | 656 ± 654 (277–2377) | 367 ± 473 (321–1267) | 469 ± 113 (382–609) | 802 ± 560 (445–1990) | 1987 ± 447 (1536–2430) | 1888 ± 789 (1454–4324) | 0.28 |
CD3+/CD8+ T-cell count (cells/μL) | 215 ± 164 (158–630) | 117 ± 71 (97–318) | 193 ± 47 (119–213) | 194 ± 31 (150–246) | 189 ± 77 (89–244) | 287 ± 125 (112–361) | 0.87 |
CD3+/CD4+ T-cell count (cells/μL) | 406 ± 542 (213–1834) | 203 ± 677 (96–2187) | 481 ± 796 (342–1934) | 711 ± 741 (282–1766) | 1286 ± 889 (397–2175) | 1159 ± 1946 (61–3954) | 0.46 |
CD3-/CD16+/CD56+ NK-cell count (cells/μL) | 90 ± 33 (65–162) | 38 ± 77 (11–245) | 56 ± 48 (26–124) | 42 ± 24 (20–68) | 35 ± 5 (29–39) | 59 ± 25 (33–84) | 0.88 |
CD19+ B-cell count (cells/μL) | 126 ± 69 (59–198) | 44 ± 97 (6.0–191.7) | 136 ± 213 (96–523) | 188 ± 47 (107–202) | 235 ± 111 (43–267) | 212 ± 197 (59–453) | 0.2 |
Double-negative T-cell ratio (%) | 1.0 ± 0.7 (0–3.4) | 1.7 ± 2.1 (0.2–7.5) | 0.8 ± 2.5 (0.6–5.6) | 1.1 ± 0.8 (0.5–2.0) | 1.1 ± 0.7 (0.4–1.9) | 0.4 ± 2.0 (0.2–4.1) | 0.28 |
Double-positive T-cell ratio (%) | 0.1 ± 0.3 (0.01–0.8) | 0.1 ± 0.4 (0.04–1.2) | 0.1 ± 0.1 (0.03–0.2) | 0.1 ± 0.1 (0.01–0.2) | 0.1 ± 0.1 (0.05–0.12) | 0.2 ± 0.1 (0.1–0.2) | 1.0 |
Counts within the CD3+ gate: | |||||||
CD3+/TCRαβ+ T-cell (cells/μL) | 949 ± 221 (687–1546) | 601 ± 631 (212–2368) | 489 ± 83 (435–601) | 906 ± 774 (434–1982) | 567 ± 1128 (164–2421) | 1440 ± 2067 (172–4301) | 1.0 |
CD3+/TCRγδ+ T-cell (cells/μL) | 23.5 ± 19.6 (14.3–53.7) | 43.1 ± 37.3 (7.1–77.3) | 27.6 ± 21.9 (6.7–45.6) | 10.2 ± 2.5 (6.0–11.0) | 14.1 ± 4.3 (9.7–18.4) | 13.1 ± 3.1 (11.0–17.3) | 0.23 |
CD3+/CD25+ T-cell (cells/μL) | 54.3 ± 26.5 (14.2–67.1) | 19.3 ± 9.9 (2.8–26.6) | 63.5 ± 23.4 (42.1–88.9) | 77.9 ± 148.0 (21.9–317.9) | 48.0 ± 33.5 (14.6–81.5) | 60.5 ± 108.6 (12.7–229.8) | 0.14 |
CD3+/HLA-DR+ T-cell (cells/μL) | 146.6 ± 211.5 (23.1–524.8) | 89.6 ± 203.2 (44.7–615.8) | 304.9 ± 297.1 (49.1–682.4) | 56.1 ± 333.8 (45.0–712.6) | 358.9 ± 307.4 (51.2–666.1) | 98.1 ± 375.0 (41.7–1370.8) | 0.56 |
Counts within the CD4+ gate: | |||||||
CD4+/CD45RA+ naive T-cell (cells/μL) | 162.3 ± 487.3 (86.2–1548.2) | 105.8 ± 599.3 (11.9–2045.4) | 152.4 ± 110.1 (29.4–249.6) | 335.6 ± 767.6 (102.4–1637.5) | 1056.0 ± 869.6 (186.4–1925.6) | 547.1 ± 1807.0 (16.2–3630.1) | 0.69 |
CD4+/CD45RO+ memory T-cell (cells/μL) | 89.9 ± 53.9 (26.5–112.2) | 113.4 ± 60.8 (52.0–140.0) | 206.1 ± 21.9 (184.2–227.9) | 178.2 ± 121.1 (129.0–371.2) | 229.4 ± 16.4 (213.0–245.9) | 286.7 ± 195.7 (45.3–602.7) | 0.2 |
Counts within the CD8+ gate: | |||||||
CD8+/CD45RA+ naive T-cell (cells/μL) | 167.2 ± 34.3 (147.8–216.4) | 175.0 ± 171.3 (46.6–506.6) | 173.5 ± 186.5 (65.3–438.1) | 102.2 ± 21.1 (65.2–107.6) | 74.0 ± 24.1 (49.9–98.1) | 90.5 ± 29.5 (78.5–136.9) | 0.93 |
CD8+/CD45RO+ memory T-cell (cells/μL) | 42.5 ± 24.8 (12.8–62.4) | 76.2 ± 94.1 (20.9–136.4) | 51.2 ± 2.2 (48.7–53.1) | 90.0 ± 53.3 (41.6–147.7) | 159.5 ± 33.1 (126.4–192.6) | 144.4 ± 127.0 (21.6–275.7) | 0.03 |
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Szabó, B.G.; Reményi, P.; Tasnády, S.; Korózs, D.; Gopcsa, L.; Réti, M.; Várkonyi, A.; Sinkó, J.; Lakatos, B.; Szlávik, J.; et al. Extracorporeal Photopheresis as a Possible Therapeutic Approach for Adults with Severe and Critical COVID-19 Non-Responsive to Standard Treatment: A Pilot Investigational Study. J. Clin. Med. 2023, 12, 5000. https://doi.org/10.3390/jcm12155000
Szabó BG, Reményi P, Tasnády S, Korózs D, Gopcsa L, Réti M, Várkonyi A, Sinkó J, Lakatos B, Szlávik J, et al. Extracorporeal Photopheresis as a Possible Therapeutic Approach for Adults with Severe and Critical COVID-19 Non-Responsive to Standard Treatment: A Pilot Investigational Study. Journal of Clinical Medicine. 2023; 12(15):5000. https://doi.org/10.3390/jcm12155000
Chicago/Turabian StyleSzabó, Bálint Gergely, Péter Reményi, Szabolcs Tasnády, Dorina Korózs, László Gopcsa, Marienn Réti, Andrea Várkonyi, János Sinkó, Botond Lakatos, János Szlávik, and et al. 2023. "Extracorporeal Photopheresis as a Possible Therapeutic Approach for Adults with Severe and Critical COVID-19 Non-Responsive to Standard Treatment: A Pilot Investigational Study" Journal of Clinical Medicine 12, no. 15: 5000. https://doi.org/10.3390/jcm12155000