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Table 2 Comparison of severe coronavirus infection and the symptoms of HLH

From: Could hemophagocytic lymphohistiocytosis be the core issue of severe COVID-19 cases?

  Adult HLH COVID-19
Source Ramos et al. [14] Zhao et al. [19] Apodaca et al. [16] Otrock and Eby [18] Barba et al. [17] Huang et al. [4] Chen et al. [2] Wang et al. [6] Zhou et al. [8] Yang et al. [7] Spiteri et al. [5]
Number of patients (%) 775 (100%) 171 (100%) 64 (100%) 73 (100%) 71 (100%) 41 (100%) 99 (100%) 138 (100%) 191 (100%) 52 critically ill (100%) 31 (100%)
Clinical symptoms belonging to the HLH criteria [22]
Fever 524/546 (96%) 171/171 (100%) 63/64 (94.4%) 70/73 (95.9%) 59/71 (92%) 32/41 (78%) 82/99 (83%) 136/138 (99%) 180/191 (94%) ≥ 37.3 °C 51/52 (98%) 20/31 (64.5%)
Splenomegaly 420/609 (69%) 146/171 (85.4%) 50/64 (78.1%) 44/73 (60.3%) 27/71 (39%) No data No data No data No data No data No data
Hemophagocytosis 257/304 (85%) 152/171 (88.9%) 49/64 (76.6%) 52/68 (76.5%) 57/71 (83%) No data No data No data No data No data No data
Cytopenias (affecting at least two lineages) Yes Yes 63/64 (98.4%) 62/73 (84.9%) Yes No data No data No data No data No data No data
  Anemia (< 9 g/dL) 122/181 (67%) 98/171 (57.3%) 30/64 (46.9%) No data No data No data 50/99 (51%) No data 29/191 (15%) No data No data
  Thrombocytopenia (< 100 × 103/mL) 178/227 (78%) 156/171 (91.2%) 443/64 (67%) No data 32/71 (45%) 2/41 (5%) 12/99 (12%) Platelet count of 112–202 × 103/mL 13/191 (7%) No data No data
  Neutropenia (< 1 × 103/mL) 61/144 (42%) 59/171 (34.5%) 9/64 (14%) No data No data No data No data Neutrophil count of 2.0–7.9 × 103/mL No data No data No data
  Lymphocytopenia No data No data 20/64 (31%) No data No data 26/41 (63%) 35/99 (35%) 97/138 (70%) 77/191 (40.3%) 44/52 (85%) No data
  Leukopenia 198/285 (69%) No data No data No data 7/71 (10%) No data No data No data No data No data No data
Hypertriglyceridemia > 265 mg/dL > 265 mg/dL, 42/100 (42%)
> 150 mg/dL, 139/192 (69%)
62/171 (36.3%) 33/64 (52%) 49/69 (71%) No data No data No data No data No data No data No data
Hyperferritinemia (> 500 ng/mL) > 500 ng/mL, 178/198 (90%)
> 1000 ng/mL, 164/230 (71%)
165/171 (96.5%) > 500 ng/mL, 64/64 (100%)
> 2000 ng/mL, 49/64 (77.2%)
73/73 (100%) No data No data 62/99 (63%) No data 102/128 (80%) had ferritin > 300 ng/mL No data No data
Elevated sCD25 (soluble IL-2 receptor) > 2400 IU/mL, 95/120 (79%) No data Yes 64/64 (100%) (inclusion criteria) 24/31 (77.4%) No data No data No data No data No data No data No data
Low or absent NK cell activity Yes in some patients, but has not yet been standardized No data Yes 64/64 (100%) (inclusion criteria) 4/11 (36.4%) No data No data No data No data No data No data No data
Hypofibrinogenemia (≤ 150 mg/dL)   106/171 (62%) 20/64 (32%) 24/64 (37.5%) No data No data No data No data No data No data No data
Other symptoms of HLH
Hepatomegaly 389/580 (67%) 70/171 (40.9%) 46/64 (71.9%) 13/73 (17.8%) 31/71 (44%) No data No data No data No data No data No data
Pulmonary involvement 61/145 (42%) No data 21/64 (32.8%) No data ARDS in 44/71 (64%) ARDS in 12/41 (29%) ARDS in 17/99 (17%) ARDS in 27/138 (20%) ARDS in 59/191 (31%) ARDS in 35/52 (67%) No data
Peripheral adenopathy 91/277 (33%) No data No data No data No data No data No data No data No data No data No data
Neurological symptoms 41/161 (25%) No data 10/64 (15.6%) No data Confusion or coma in 6/71 (9%) Headache in 3/38 (8%) Confusion in 9/99 (9%)
Headache in 8/99 (8%)
Headache in 9/138 (6.5%) No data Headache in 3/52 (6%) Headache in 6/31 (19%)
Multi-organ failure (MOF)/sepsis ICU admission in ~ 50% of cases No data No data No data MOF in 40/71 (56%) ICU care in 13/38 (32%) ICU care in 23/99 (23%)
Septic shock in 4/99 (4%)
ICU care in 36/138 (26%) Sepsis in 112/191 (59%)
ICU care in 50/191 (26%)
Sepsis in 1/52 (2%) No data
Renal insufficiency/failure 9/56 (16%) No data 25/64 (39/1%) 38/73 (52.1%) No data 3/41 (7%) 3/99 (3%) 5/138 (3.6%) 28/191 (15%) 15/52 (29%) No data
Elevated CRP 80–90% No data No data No data 44/71 (62%) No data 63/73 (86%) No data No data No data No data
Elevated serum transaminases ALT > 40 IU/L, 164/286 (57%)
AST > 100 IU/L, 48/115 (42%)
Yes 47/64 (74%) 61/73 (83.6%) No data AST 15/41 (37%) ALT 28/99 (28%)
AST 35/99 (35%)
No (normal levels) ALT 59/189 (31%) 15/52 (29%) No data
Elevated LDH > 500 IU/L, 190/243 (78%) Yes No data 64/69 (92.8%) No data 29/40 (73%) 75/99 (76%) 55/138 (40%) 123/184 (67%) No data No data
Elevated D-dimers > 54.8 mmol/L 24/49 (49%) Yes No data No data No data No data 36/99 (36%) No (normal levels) 72/172 (42%) No data No data
Elevated serum levels of immunological markers (e.g., IL-2, IL-7, IL-10, G-SCF, IP-10, MCP1, MIP1A, TNF-α) Yes No data No data No data No data Yes No data No data No data No data No data
Increased IL-6 Yes No data No data No data No data No data 51/99 (52%) No data No data No data No data
  1. Abbreviations: ALT alanine aminotransferase, ARDS acute respiratory distress syndrome, AST aspartate aminotransferase, CRP C-reactive protein, G-CSF granulocyte-colony stimulating factor, HLH hemophagocytic lymphohistiocytosis, ICU intensive care unit, IFN-γ interferon-γ, IL interleukin, IP-10 interferon-γ-induced protein 10, LDH lactate dehydrogenase, TNF-α tumor necrosis factor-alpha