Secondary haemophagocytic lymphohistiocytosis in hospitalised COVID-19 patients as indicated by a modified HScore is infrequent and high scores do not associate with increased mortality

Michael R Ardern-Jones, Matt Stammers, Hang TT Phan, Florina Borca, Anastasia Koutalopoulou, Ying Teo, James Batchelor, Trevor Smith and Andrew S Duncombe
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DOI: https://doi.org/10.7861/clinmed.2021-0053
Clin Med September 2021

Article Figures & Data

Figures

  • Fig 1.
    Fig 1.

    sHLH shows a higher %HScore than COVID-19, but %HScore in COVID-19 shows no correlation with mortality. a) %HScore as measured from data points recorded at virus diagnosis timepoints day –1 to 4, versus day –1 to 21. Spearman's correlation coefficient (r) presented. n=567. b) Plot of %HScores from a retrospective cohort of secondary haemophagocytic lymphohistiocytosis (sHLH) versus COVID-19. Dotted line at 56.7% (80% probability of HLH). Error bars represent 10–90% confidence. Mann Whitney test presented.

  • Fig 2.
    Fig 2.

    Age, %HScore and risk of mortality in COVID-19. a) Violin plot of %HScore in those ≤75 versus >75 years (n = 567). Horizontal bars represent median value, interquartile range dotted. Mann Whitney statistic presented. b) Receiver operator characteristics of prediction of mortality by %HScore. c) %HScore in cases who died (black dots) versus survived (grey dots) by age stratification. Error bars represent 25–75% confidence interval.

Tables

  • Table 1.

    HScore and %HScore algorithm

    ParameterHScore points (criteria)%HScore points (criteria) (Minimum variables 3)
    Temperature (°C)0 (<38.4),
    33 (38.4–39.4),
    or 49 (>39.4)    		0 (<38.4),
    33 (38.4–39.4),
    or 49 (>39.4)
    No of cytopenias*0 (one lineage),
    24 (two lineages),
    or 34 (three lineages)    		0 (one lineage),
    24 (two lineages), or 34 (three lineages)
    Ferritin (mg/L)0 (<2,000),
    35 (2,000–6,000),
    or 50 (>6,000)    		0 (<2,000),
    35 (2,000–6,000), or 50 (>6,000)
    Triglyceride (mmol/L)0 (<1.5), 44 (1.5–4),
    or 64 (>4)    		0 (<1.5), 44 (1.5–4),
    or 64 (>4)
    Fibrinogen (g/L)0 (>2.5) or
    30 (≤2.5)    		0 (>2.5) or
    30 (≤2.5)
    AST/ALT (IU/L)0 (<30) or 19 (≥30)0 (<30) or 19 (≥30)
    Haemophagocytosis†0 (no) or 35 (yes)–
    Immunosuppression0 (no) or 18 (yes)–
    Hepatomegaly / splenomegaly0 (none), 23 (either), or 38 (both)–
    ScoreSum of points above (maximum 337)Sum of points above / maximum score (maximum 100%)

    • ↵*Haemoglobin ≤92 g/L and/or WBC ≤5 × 109/L and/or platelets ≤110 × 109/L.

    • ↵†Features on bone marrow aspirate. ALT = alanine aminotransferase; AST = aspartate transaminase; IU = international units.

  • Table 2.

    COVID cohort characteristics and comorbidities

    Age (median years, IQR)71 (54–82)
    Sex: male (%), female (%)58.20, 41.80
    BAME (%)11.46
    BMI (mean, IQR)25.73 (22.49–30.22)
    Comorbidities (%)
    Cardiac disease
    Renal disease
    Respiratory disease
    Gastrointestinal disease
    Diabetes
    Neurological disease
    Cancer history
    71.78
    59.96
    41.09
    38.10
    26.28
    51.15
    28.04

    • BAME = Black, Asian and minority ethnic; BMI = body mass index; IQR = interquartile range.

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Secondary haemophagocytic lymphohistiocytosis in hospitalised COVID-19 patients as indicated by a modified HScore is infrequent and high scores do not associate with increased mortality
Michael R Ardern-Jones, Matt Stammers, Hang TT Phan, Florina Borca, Anastasia Koutalopoulou, Ying Teo, James Batchelor, Trevor Smith, Andrew S Duncombe
Clinical Medicine Sep 2021, 21 (5) e543-e547; DOI: 10.7861/clinmed.2021-0053
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