Table 5 Estimating the predictive ability of various analytes in identifying severe COVID-19 patients in a patient population with either moderate or severe disease using the area under a receiver operating characteristic curve (AUC) method.

From: Multivariate indicators of disease severity in COVID-19

Variable	Area	p-value	Asymptotic 95% confidence interval
Variable	Area	p-value	Lower bound	Upper bound
Combined profiles
Discriminant scores	1.000	1.08 × 10⁻⁴	1.000	1.000
BLR probabilities	0.993	1.35 × 10⁻⁴	0.970	1.000
AUC (analytes elevated in severe COVID-19)
Neutrophils	0.900	1.95 × 10⁻³	0.766	1.000
CD27⁺ Ki67⁺ CD8⁺ CD45RA⁺ effector memory	0.871	4.01 × 10⁻³	0.735	1.000
PD1⁺ CD4⁺ transitional memory	0.857	5.67 × 10⁻³	0.717	0.997
CD38⁺ CD4⁺ transitional memory	0.836	9.31 × 10⁻³	0.661	1.000
Ki67⁺ CD8⁺ MAIT	0.836	9.31 × 10⁻³	0.683	0.988
PD1⁺ NK cells	0.829	1.09 × 10⁻²	0.666	0.991
Ki67⁺ CD8⁺ memory	0.821	1.28 × 10⁻²	0.628	1.000
PD1⁺ CD4⁺ memory	0.814	1.49 × 10⁻²	0.652	0.976
PD1⁺ CD8⁺ central memory	0.814	1.49 × 10⁻²	0.649	0.980
CD27⁻ Ki67⁺ CD8⁺ CD45RA⁺ effector memory	0.811	1.61 × 10⁻²	0.646	0.975
Ki67⁺ CD8⁺ CD45RA⁺ effector memory	0.807	1.74 × 10⁻²	0.641	0.973
PD1⁺ CD8⁺ MAIT	0.807	1.74 × 10⁻²	0.613	1.000
Ki67⁺ CD4⁺ central memory	0.796	2.17 × 10⁻²	0.582	1.000
Ki67⁺ CD8⁺ central memory	0.796	2.17 × 10⁻²	0.605	0.988
PD1⁺ CD8⁺ transitional memory	0.793	2.33 × 10⁻²	0.609	0.977
PD1⁺ CD8⁺ memory	0.793	2.33 × 10⁻²	0.603	0.983
CD38⁺ CD4⁺ central memory	0.793	2.33 × 10⁻²	0.619	0.966
PD1⁺ CD8⁺ CD45RA⁺ effector memory	0.779	3.09 × 10⁻²	0.568	0.989
Ki67⁺ CD8⁺ effector memory	0.775	3.32 × 10⁻²	0.595	0.955
PD1⁺ CD4⁺ central memory	0.771	3.55 × 10⁻²	0.592	0.950
Ki67⁺ CD4⁺ memory	0.768	3.80 × 10⁻²	0.551	0.985
CD27⁺ CD38⁺ CD8⁺ CD45RA⁺ effector memory	0.764	4.06 × 10⁻²	0.571	0.957
CD27⁻ PD1⁺ CD8⁺ CD45RA⁺ effector memory	0.757	4.64 × 10⁻²	0.528	0.986
PD1⁺ CD8⁺ effector memory	0.754	4.95 × 10⁻²	0.563	0.944
CD69⁺ CD4⁺ transitional memory	0.746	5.63 × 10⁻²	0.553	0.940
Ki67⁺ NK cells	0.743	5.99 × 10⁻²	0.562	0.924
Ki67⁺ CD8⁺ transitional memory	0.743	5.99 × 10⁻²	0.532	0.954
CD38⁺ CD4⁺ memory	0.736	6.79 × 10⁻²	0.540	0.931
Plasmablasts	0.736	6.79 × 10⁻²	0.486	0.986
CD69⁺ CD4⁺ effector memory	0.725	8.14 × 10⁻²	0.540	0.910
Ki67⁺ CD4⁺ effector memory	0.721	8.63 × 10⁻²	0.514	0.929
CD38⁺ CD8⁺ central memory	0.721	8.63 × 10⁻²	0.512	0.931
CD27⁺ CD69⁺ CD8⁺ CD45RA⁺ effector memory	0.718	9.15 × 10⁻²	0.527	0.909
CD21⁺ CD27⁻ CD38^lo B cells	0.714	9.69 × 10⁻²	0.450	0.978
PD1⁺ CD4⁺ effector memory	0.711	1.03 × 10⁻¹	0.500	0.921
Classical monocytes/monocytes	0.707	1.09 × 10⁻¹	0.517	0.898
CD38⁺ HLA-DR⁺ CD4⁺ central memory	0.704	1.15 × 10⁻¹	0.512	0.895
CD38⁺ CD8⁺ transitional memory	0.700	1.21 × 10⁻¹	0.476	0.924
HLA-DR⁺ CD4⁺ central memory	0.686	1.50 × 10⁻¹	0.491	0.880
Ki67⁺ CD4⁺ transitional memory	0.682	1.58 × 10⁻¹	0.463	0.901
CD38⁺ CD4⁺ effector memory	0.664	2.03 × 10⁻¹	0.439	0.889
CD38⁺ HLA-DR⁺ CD4⁺ transitional memory	0.664	2.03 × 10⁻¹	0.456	0.873
CD4⁺ CD45RA⁺ effector memory	0.661	2.13 × 10⁻¹	0.444	0.878
CD38⁺ CD8⁺ memory	0.650	2.45 × 10⁻¹	0.425	0.875
Immature granulocyte CD16 MFI	0.650	2.45 × 10⁻¹	0.384	0.916
CD27⁻ CD69⁺ CD8⁺ CD45RA⁺ effector memory	0.650	2.45 × 10⁻¹	0.447	0.853
CD38⁺ HLA-DR⁺ CD4⁺ memory	0.643	2.68 × 10⁻¹	0.442	0.844
CD8⁺ transitional memory	0.639	2.81 × 10⁻¹	0.387	0.892
Immature granulocyte CD123⁺	0.636	2.93 × 10⁻¹	0.379	0.893
CD4⁺ effector memory	0.636	2.93 × 10⁻¹	0.432	0.840
HLA-DR⁺ CD4⁺ memory	0.636	2.93 × 10⁻¹	0.429	0.842
HLA-DR⁺ CD4⁺ effector memory	0.636	2.93 × 10⁻¹	0.426	0.846
CD69⁺ CD8⁺ CD45RA⁺ effector memory	0.632	3.06 × 10⁻¹	0.430	0.835
CD27⁺ CD38⁺ HLA-DR⁺ CD8⁺ CD45RA⁺ effector memory	0.618	3.61 × 10⁻¹	0.408	0.828
HLA-DR⁺ NK cells	0.614	3.76 × 10⁻¹	0.384	0.844
CD38⁺ HLA-DR⁺ CD4⁺ effector memory	0.614	3.76 × 10⁻¹	0.381	0.848
CXCR5⁺ CD8⁺ effector memory	0.607	4.07 × 10⁻¹	0.386	0.828
CD69⁺ CD8⁺ MAIT	0.607	4.07 × 10⁻¹	0.380	0.834
CD69⁺ CD4⁺ memory	0.604	4.22 × 10⁻¹	0.396	0.812
Immature granulocyte CD16⁺	0.600	4.39 × 10⁻¹	0.363	0.837
HLA-DR⁺ CD8⁺ central memory	0.600	4.39 × 10⁻¹	0.389	0.811
CD27⁺ NK cells	0.600	4.39 × 10⁻¹	0.368	0.832
CD38⁺ CD8⁺ effector memory	0.593	4.72 × 10⁻¹	0.342	0.844
CD38⁺ CD8⁺ CD45RA⁺ effector memory	0.593	4.72 × 10⁻¹	0.324	0.861
HLA-DR⁺ CD4⁺ transitional memory	0.586	5.07 × 10⁻¹	0.374	0.797
CD38⁺ HLA-DR⁺ CD8⁺ central memory	0.586	5.07 × 10⁻¹	0.374	0.798
CD38⁺ CD8⁺ MAIT	0.579	5.43 × 10⁻¹	0.318	0.839
CD38⁺ HLA-DR⁺ T-follicular helper	0.557	6.58 × 10⁻¹	0.333	0.781
CD38⁺ HLA-DR⁺ CD8⁺ transitional memory	0.557	6.58 × 10⁻¹	0.335	0.780
CD27⁺ HLA-DR⁺ CD8⁺ CD45RA⁺ effector memory	0.557	6.58 × 10⁻¹	0.347	0.767
CD27⁻ CD8⁺ CD45RA⁺ effector memory	0.557	6.58 × 10⁻¹	0.334	0.780
HLA-DR⁺ T-follicular helper	0.550	6.99 × 10⁻¹	0.320	0.780
CD161⁺ monocytes	0.550	6.99 × 10⁻¹	0.255	0.845
Ki67⁺ neutrophils	0.543	7.40 × 10⁻¹	0.297	0.789
CD27⁻ CD38⁺ CD8⁺ CD45RA⁺ effector memory	0.543	7.40 × 10⁻¹	0.270	0.815
Plasmacytoid dendritic cell HLA-DR MFI	0.529	8.25 × 10⁻¹	0.291	0.766
HLA-DR⁺ CD8⁺ transitional memory	0.529	8.25 × 10⁻¹	0.318	0.739
HLA-DR⁺ CD8⁺ memory	0.525	8.46 × 10⁻¹	0.315	0.735
CXCR5⁺ CD4⁺ effector memory	0.521	8.68 × 10⁻¹	0.304	0.739
CD69⁺ CD8⁺ memory	0.521	8.68 × 10⁻¹	0.310	0.733
CD27⁻ CD8⁺ T cells	0.514	9.12 × 10⁻¹	0.302	0.727
CD25⁺ NK cells	0.514	9.12 × 10⁻¹	0.255	0.773
Eosinophils CD15 MFI	0.507	9.56 × 10⁻¹	0.263	0.751
HLA-DR⁺ CD8⁺ effector memory	0.507	9.56 × 10⁻¹	0.286	0.728
CD38⁺ HLA-DR⁺ CD8⁺ effector memory	0.507	9.56 × 10⁻¹	0.264	0.751
CD38⁺HLA-DR⁺ NK cells	0.507	9.56 × 10⁻¹	0.239	0.775
CD21⁺CD27⁺CD38^lo B cells	0.504	9.78 × 10⁻¹	0.252	0.756
CD27⁺ CXCR5⁺ CD8⁺ CD45RA⁺ effector memory	0.500	1.00E+00	0.262	0.738
B cells HLA-DR MFI	0.500	1.00E+00	0.256	0.744
AUC (analytes decreased in severe COVID-19)
Monocyte HLA-DR MFI	0.993	1.35 × 10⁻⁴	0.970	1.000
T cells	0.957	3.99 × 10⁻⁴	0.879	1.000
NK cells	0.957	3.99 × 10⁻⁴	0.873	1.000
CD4⁺ T cells	0.936	7.38 × 10⁻⁴	0.844	1.000
Dendritic cells	0.932	8.16 × 10⁻⁴	0.835	1.000
CD56^dim CD16⁺ NK cells	0.929	9.01 × 10⁻⁴	0.825	1.000
B cells	0.907	1.61 × 10⁻³	0.786	1.000
CD25⁺ CD8⁺ MAIT	0.879	3.36 × 10⁻³	0.746	1.000
CD25⁺ CD8⁺ transitional memory	0.857	5.67 × 10⁻³	0.706	1.000
CD25⁺ CD8⁺ CD45RA⁺ effector memory	0.843	7.91 × 10⁻³	0.620	1.000
Innate lymphoid cells	0.829	1.09 × 10⁻²	0.658	0.999
CD8⁺ T cells	0.829	1.09 × 10⁻²	0.673	0.984
CD56^hi CD16⁻ NK cells	0.821	1.28 × 10⁻²	0.666	0.977
NK cell CD16 MFI	0.814	1.49 × 10⁻²	0.645	0.984
CD16⁺ NK cells	0.800	2.01 × 10⁻²	0.602	0.998
Plasmacytoid dendritic cells	0.796	2.17 × 10⁻²	0.631	0.962
CD25⁺ CD27⁺ CD8⁺ CD45RA⁺ effector memory	0.782	2.89 × 10⁻²	0.553	1.000
MAIT	0.771	3.55 × 10⁻²	0.535	1.000
CD25⁺ CD27⁻ CD8⁺ CD45RA⁺ effector memory	0.764	4.06 × 10⁻²	0.545	0.983
Neutrophil CD16 MFI	0.757	4.64 × 10⁻²	0.528	0.986
CD25⁺ CD8⁺ memory	0.736	6.79 × 10⁻²	0.553	0.919
Conventional dendritic cells	0.736	6.79 × 10⁻²	0.537	0.935
CD21⁺ CD27⁺ Ki67⁺ B cells	0.732	7.21 × 10⁻²	0.478	0.986
CD16⁺ monocytes	0.729	7.66 × 10⁻²	0.539	0.919
Non-classical monocytes/monocytes	0.700	1.21 × 10⁻¹	0.465	0.935
CD25⁺ CD8⁺ central memory	0.693	1.35 × 10⁻¹	0.466	0.920
CD4⁺ central memory	0.679	1.67 × 10⁻¹	0.418	0.939
Neutrophils CD15 MFI	0.675	1.75 × 10⁻¹	0.471	0.879
CD8⁺ central memory	0.664	2.03 × 10⁻¹	0.453	0.876
CD21⁻ CD27⁺ CD38^lo B cells	0.661	2.13 × 10⁻¹	0.359	0.963
Intermediate monocytes/monocytes	0.657	2.24 × 10⁻¹	0.452	0.862
CXCR5⁺ CD8⁺ transitional memory	0.657	2.24 × 10⁻¹	0.448	0.866
CD38⁺ NK cells	0.654	2.34 × 10⁻¹	0.406	0.902
CD21⁻CD27⁻CD38^lo B cells	0.643	2.68 × 10⁻¹	0.395	0.891
CD21⁻ CD27⁺ Ki67⁺ B cells	0.643	2.68 × 10⁻¹	0.412	0.874
Monocyte CD16 MFI	0.643	2.68 × 10⁻¹	0.398	0.888
Conventional dendritic cells HLA-DR MFI	0.636	2.93 × 10⁻¹	0.393	0.878
CXCR5⁺ CD4⁺ memory	0.636	2.93 × 10⁻¹	0.425	0.847
Monocyte CD14 MFI	0.636	2.93 × 10⁻¹	0.380	0.891
HLA-DR⁺ neutrophils	0.629	3.19 × 10⁻¹	0.360	0.897
Non-classical monocytes	0.621	3.47 × 10⁻¹	0.371	0.872
Naïve CD8⁺ T cells	0.621	3.47 × 10⁻¹	0.407	0.836
CD38⁺ NK cells	0.621	3.47 × 10⁻¹	0.406	0.837
CD11c⁺ immature granulocyte	0.614	3.76 × 10⁻¹	0.375	0.854
CD38⁺ CD161⁺ NK cells	0.614	3.76 × 10⁻¹	0.362	0.867
Intermediate monocytes	0.614	3.76 × 10⁻¹	0.392	0.837
CXCR5⁺ CD8⁺ CD45RA⁺ effector memory	0.611	3.91 × 10⁻¹	0.404	0.818
CXCR5⁺ CD8⁺ central memory	0.607	4.07 × 10⁻¹	0.402	0.812
CD27⁻ HLA-DR⁺ CD8⁺ CD45RA⁺ effector memory	0.607	4.07 × 10⁻¹	0.385	0.830
Dendritic cell HLA-DR MFI	0.607	4.07 × 10⁻¹	0.340	0.874
CD27⁺ CD8⁺ CD45RA⁺ effector memory	0.604	4.22 × 10⁻¹	0.378	0.829
CXCR5⁺ CD8⁺ memory	0.600	4.39 × 10⁻¹	0.386	0.814
HLA-DR⁺ CD8⁺ CD45RA⁺ effector memory	0.600	4.39 × 10⁻¹	0.383	0.817
CD25⁺ CD8⁺ effector memory	0.600	4.39 × 10⁻¹	0.388	0.812
CXCR5⁺ CD4⁺ central memory	0.596	4.55 × 10⁻¹	0.385	0.808
CD27⁺ CD8⁺ T cells	0.596	4.55 × 10⁻¹	0.389	0.804
CD21⁺ CD27⁻ Ki67⁺ B cells	0.596	4.55 × 10⁻¹	0.360	0.833
CD21⁻ CD27⁻ Ki67⁺ B cells	0.593	4.72 × 10⁻¹	0.338	0.848
Classical monocytes	0.586	5.07 × 10⁻¹	0.348	0.823
CXCR5⁺ CD8⁺ T cells	0.579	5.43 × 10⁻¹	0.336	0.821
CD69⁺ CD8⁺ central memory	0.579	5.43 × 10⁻¹	0.369	0.788
CD27⁻ CD38⁺ HLA-DR⁺ CD8⁺ CD45RA⁺ effector memory	0.571	5.80 × 10⁻¹	0.289	0.854
CD38⁺ HLA-DR⁺ CD8⁺ CD45RA⁺ effector memory	0.564	6.19 × 10⁻¹	0.326	0.802
CXCR5⁺ CD4⁺ transitional memory	0.564	6.19 × 10⁻¹	0.335	0.794
CD27⁻ CXCR5⁺ CD8⁺ CD45RA⁺ effector memory	0.554	6.78 × 10⁻¹	0.315	0.792
CD4⁺ transitional memory	0.550	6.99 × 10⁻¹	0.310	0.790
CD8⁺ CD45RA⁺ effector memory	0.550	6.99 × 10⁻¹	0.338	0.762
CXCR5⁺ CD8⁺ MAIT	0.550	6.99 × 10⁻¹	0.301	0.799
Monocytes	0.543	7.40 × 10⁻¹	0.293	0.793
CD8⁺ effector memory	0.543	7.40 × 10⁻¹	0.316	0.770
CD69⁺ CD8⁺ transitional memory	0.543	7.40 × 10⁻¹	0.331	0.755
CD4⁺ Tregs	0.536	7.82 × 10⁻¹	0.303	0.768
CD38⁺ HLA-DR⁺ CD8⁺ MAIT	0.536	7.82 × 10⁻¹	0.311	0.761
Ki67⁺ immature granulocyte	0.536	7.82 × 10⁻¹	0.266	0.806
Immature granulocyte	0.529	8.25 × 10⁻¹	0.253	0.804
HLA-DR⁺ CD8⁺ MAIT	0.521	8.68 × 10⁻¹	0.285	0.758
Circulating T-follicular helper	0.521	8.68 × 10⁻¹	0.283	0.760
CD69⁺ CD8⁺ effector memory	0.518	8.90 × 10⁻¹	0.307	0.729
CD38⁺ HLA-DR⁺ CD8⁺ memory	0.514	9.12 × 10⁻¹	0.293	0.736
Naïve CD4⁺ T cells	0.514	9.12 × 10⁻¹	0.264	0.764
CD69⁺ CD4⁺ central memory	0.511	9.34 × 10⁻¹	0.293	0.729
Eosinophils	0.504	9.78 × 10⁻¹	0.233	0.774

BLR binary logistic regression probabilities.
Shown p-values are corrected for multiple testing using Holm method. Cell populations are expressed as percentages of their respective parent populations except for where mean fluorescence intensity (MFI) is indicated.

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Table 5 Estimating the predictive ability of various analytes in identifying severe COVID-19 patients in a patient population with either moderate or severe disease using the area under a receiver operating characteristic curve (AUC) method.

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