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?
| Â | 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%) â„â37.3â°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 |
ââAnemia (<â9âg/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 |
ââThrombocytopenia (<â100âĂâ103/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 112â202âĂâ103/mL | 13/191 (7%) | No data | No data |
ââNeutropenia (<â1âĂâ103/mL) | 61/144 (42%) | 59/171 (34.5%) | 9/64 (14%) | No data | No data | No data | No data | Neutrophil count of 2.0â7.9âĂâ103/mL | No data | No data | No data |
ââLymphocytopenia | 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 |
ââLeukopenia | 198/285 (69%) | No data | No data | No data | 7/71 (10%) | No data | No data | No data | No data | No data | No data |
Hypertriglyceridemiaâ>â265âmg/dL | >â265âmg/dL, 42/100 (42%) >â150âmg/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 (>â500âng/mL) | >â500âng/mL, 178/198 (90%) >â1000âng/mL, 164/230 (71%) | 165/171 (96.5%) | >â500âng/mL, 64/64 (100%) >â2000âng/mL, 49/64 (77.2%) | 73/73 (100%) | No data | No data | 62/99 (63%) | No data | 102/128 (80%) had ferritin >â300âng/mL | No data | No data |
Elevated sCD25 (soluble IL-2 receptor) | >â2400âIU/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 (â€â150âmg/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 ~â50% 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 | 80â90% | 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 >â40âIU/L, 164/286 (57%) AST >â100âIU/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 | >â500âIU/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 | >â54.8âmmol/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 |