Risk of Underlying Diseases and Effectiveness of Drugs on COVID-19 Inpatients Assessed Using Medical Claims in Japan: Retrospective Observational Study

Figures & data

Figure 1 Number of new hospitalizations in MIA data and number of drugs used against COVID-19.

Notes: Blue bars show the numbers of newly COVID-19 hospitalizations in MIA data by their hospitalized week measured by the left scale. Yellow, orange, red, green, and pink lines, respectively, represent the number of inpatients who had been administered remdesivir, dexamethasone, tocilizumab, baricitinib and casirivimab/imdevimab or sotrovimab by their hospitalized week, as shown on the right scale. A single patient could have been administered several of the considered drugs.

Figure 2 Number of underlying diseases of SARS-CoV-2 infected inpatients, by MIA data.

Notes: Blue, orange, gray, and yellow lines, respectively, represent the numbers of underlying diseases in which inpatients with cancer, hypertension, diabetes mellitus, and heart failure by their hospitalized week. One patient could have multiple considered underlying diseases.

Table 1 Estimation Results of Logistic Regression for Death with the Administered Drug and Proportion of Mutated Strains

	All Ages		65 Years Old or Older		Younger Than 65 Years Old
	Estimated Coefficient	p	Estimated Coefficient	p	Estimated Coefficient	p
All inpatients
Age	1.09	0.00	1.08	0.00	1.09	0.00
Gender	0.56	0.00	0.56	0.00	0.53	0.01
Cancer	2.05	0.00	1.74	0.00	6.18	0.00
Hypertension	0.67	0.00	0.70	0.00	0.40	0.01
DM	1.12	0.18	1.01	0.93	2.10	0.00
Heart failure	1.67	0.00	1.57	0.00	4.64	0.00
Completed two-dose vaccination 14 days prior	1.00	1.00	0.99	0.43	1.02	0.21
Proportion of Alpha variant strain (%)	1.00	0.09	1.00	0.22	1.00	0.37
Proportion of Delta variant strain (%)	1.00	0.54	1.01	0.50	1.00	0.58
Proportion of Omicron variant strain (%)	1.00	0.39	1.01	0.54	0.99	0.23
Remdesivir	1.44	0.00	1.47	0.00	1.11	0.74
Casirivimab/imdevimab or sotrovimab	0.27	0.00	0.25	0.00	0.52	0.52
Dexamethasone	1.85	0.00	1.91	0.00	1.44	0.11
Baricitinib	1.62	0.00	1.79	0.00	1.00	0.99
Tocilizumab	2.73	0.00	2.66	0.00	3.05	0.00
Constant	0.00	0.00	0.00	0.00	0.00	0.00
Number of samples	18,566		7224		11,332
Adjusted coefficient of determination (R^2)	0.24		0.11		0.18
Inpatients receiving oxygen therapy
Age	1.09	0.00	1.09	0.00	1.05	0.02
Gender	0.71	0.00	0.68	0.00	1.01	0.98
Cancer	2.81	0.00	2.20	0.00	20.05	0.00
Hypertension	0.77	0.02	0.79	0.05	0.50	0.22
DM	0.86	0.16	0.85	0.16	0.95	0.90
Heart failure	1.44	0.01	1.40	0.02	3.10	0.11
Completed two-dose vaccination 14 days prior	1.01	0.11	1.00	0.86	1.00	0.89
Proportion of Alpha variant strain (%)	1.00	0.22	1.00	0.18	1.00	0.57
Proportion of Delta variant strain (%)	0.99	0.01	1.00	0.99	0.99	0.27
Proportion of Omicron variant strain (%)	0.99	0.04	1.00	0.95	0.99	0.57
Remdesivir	1.25	0.06	1.22	0.10	1.38	0.46
Casirivimab/imdevimab or sotrovimab	0.43	0.06	0.37	0.04	2.12	0.53
Dexamethasone	1.27	0.02	1.32	0.01	0.95	0.89
Baricitinib	1.37	0.06	1.43	0.04	0.93	0.89
Tocilizumab	2.41	0.00	2.46	0.00	2.17	0.16
Constant	0.00	0.00	0.00	0.00	0.00	0.00
Number of samples	6403		3612		2791
Adjusted coefficient of determination (R^2)	0.20		0.09		0.20
Inpatients receiving respiratory ventilation
Age	1.07	0.00	1.08	0.00	1.05	0.01
Gender	0.90	0.53	0.95	0.79	0.60	0.22
Cancer	0.86	0.66	0.69	0.32	4.37	0.14
Hypertension	0.57	0.01	0.59	0.02	0.40	0.06
DM	0.82	0.23	0.67	0.05	1.43	0.28
Heart failure	1.25	0.48	0.99	0.97	7.44	0.02
Completed two-dose vaccination 14 days prior	1.00	0.68	0.93	0.10	1.03	0.20
Proportion of Alpha variant strain (%)	1.01	0.00	1.01	0.08	1.01	0.03
Proportion of Delta variant strain (%)	1.01	0.20	1.07	0.09	1.00	0.54
Proportion of Omicron variant strain (%)	1.01	0.13	1.08	0.08	0.99	0.70
Remdesivir	1.00	0.98	1.06	0.81	0.71	0.45
Casirivimab/imdevimab or sotrovimab	0.09	0.03	0.09	0.03	NA	NA
Dexamethasone	0.83	0.25	0.76	0.15	1.05	0.89
Baricitinib	0.91	0.70	1.20	0.58	0.51	0.11
Tocilizumab	1.28	0.29	1.47	0.18	0.74	0.51
Constant	0.01	0.00	0.00	0.00	0.01	0.00
Number of samples	923		571		352
Adjusted coefficient of determination (R^2)	0.12		0.08		0.09

Note: Yellow denotes significance.

Abbreviation: DM, diabetes mellitus.

Table 2 Estimation Results of Logistic Regression for Death with Proportion of the Mutated Strains and with and without Administered Drugs

	All Ages		65 Years Old or Older		Younger Than 65 Years Old
	Estimated Coefficient	p	Estimated Coefficient	p	Estimated Coefficient	p
All inpatients
Age	1.09	0.00	1.08	0.00	1.10	0.00
Gender	0.51	0.00	0.52	0.00	0.52	0.01
Cancer	2.01	0.00	1.69	0.00	5.96	0.00
Hypertension	0.67	0.00	0.71	0.00	0.40	0.01
DM	1.23	0.01	1.10	0.31	2.28	0.00
Heart failure	1.63	0.00	1.55	0.00	4.32	0.00
Completed two-dose vaccination 14 days prior	1.00	0.18	0.98	0.34	1.01	0.39
Proportion of Alpha variant strain (%)	1.01	0.00	1.01	0.00	1.01	0.18
Proportion of Delta variant strain (%)	1.00	0.39	1.02	0.39	1.00	0.93
Proportion of Omicron variant strain (%)	1.00	0.64	1.01	0.42	0.99	0.38
Constant	0.00	0.00	0.00	0.00	0.00	0.00
Number of samples	18,566		7224		11,332
Adjusted coefficient of determination (R^2)	0.21		0.07		0.17
Inpatients receiving oxygen therapy
Age	1.09	0.00	1.08	0.00	1.06	0.01
Gender	0.68	0.00	0.66	0.00	1.01	0.99
Cancer	2.76	0.00	2.14	0.00	20.72	0.00
Hypertension	0.77	0.02	0.80	0.05	0.50	0.22
DM	0.89	0.29	0.89	0.29	1.00	1.00
Heart failure	1.38	0.03	1.35	0.04	2.65	0.17
Completed two-dose vaccination 14 days prior	1.01	0.21	1.00	0.86	1.00	0.89
Proportion of Alpha variant strain (%)	1.00	0.05	1.00	0.04	1.00	0.53
Proportion of Delta variant strain (%)	0.99	0.03	1.00	0.98	0.99	0.26
Proportion of Omicron variant strain (%)	0.99	0.09	1.00	0.94	0.99	0.62
Constant	0.00	0.00	0.00	0.00	0.00	0.00
Number of samples	6403		3612		2791
Adjusted coefficient of determination (R^2)	0.19		0.07		0.20
Inpatients receiving respiratory ventilation
Age	1.07	0.00	1.07	0.00	1.05	0.01
Gender	0.89	0.51	0.96	0.85	0.59	0.21
Cancer	0.83	0.60	0.67	0.28	4.18	0.15
Hypertension	0.57	0.01	0.59	0.02	0.41	0.07
DM	0.84	0.30	0.70	0.08	1.37	0.33
Heart failure	1.14	0.67	0.88	0.70	7.59	0.02
Completed two-dose vaccination 14 days prior	1.00	0.72	0.94	0.13	1.03	0.12
Proportion of Alpha variant strain (%)	1.01	0.01	1.01	0.10	1.01	0.05
Proportion of Delta variant strain (%)	1.01	0.22	1.07	0.11	1.00	0.99
Proportion of Omicron variant strain (%)	1.01	0.15	1.07	0.10	0.99	0.48
Constant	0.01	0.00	0.00	0.00	0.01	0.00
Number of samples	923		571		352
Adjusted coefficient of determination (R^2)	0.11		0.07		0.08

Note: Yellow denotes significance.

Abbreviation: DM, diabetes mellitus.

Table 3 Estimation Results of Logistic Regression for Death with Administered Drugs and Periods of Waves When the Mutated Strains Were Dominant

	All Ages		65 Years Old or Older		Younger Than 65 Years Old
	Estimated Coefficient	p	Estimated Coefficient	p	Estimated Coefficient	p
All inpatients
Age	1.09	0.00	1.08	0.00	1.09	0.00
Gender	0.56	0.00	0.57	0.00	0.53	0.01
Cancer	2.05	0.00	1.75	0.00	6.39	0.00
Hypertension	0.67	0.00	0.70	0.00	0.39	0.01
DM	1.12	0.19	1.01	0.92	2.11	0.00
Heart failure	1.67	0.00	1.57	0.00	4.65	0.00
Completed two-dose vaccination 14 days prior	1.00	0.82	1.00	0.93	1.02	0.21
4th wave	1.19	0.08	1.17	0.15	1.53	0.16
5th wave	0.80	0.34	0.80	0.63	0.86	0.73
6th wave	0.70	0.25	0.70	0.49	0.32	0.27
Remdesivir	1.44	0.00	1.46	0.00	1.10	0.76
Casirivimab/imdevimab or sotrovimab	0.27	0.00	0.25	0.00	0.50	0.51
Dexamethasone	1.85	0.00	1.91	0.00	1.40	0.14
Baricitinib	1.66	0.00	1.85	0.00	1.01	0.98
Tocilizumab	2.74	0.00	2.68	0.00	3.04	0.00
Constant	0.00	0.00	0.00	0.00	0.00	0.00
Number of samples	18,566		7224		11,332
Adjusted coefficient of determination (R^2)	0.24		0.11		0.18
Inpatients receiving oxygen therapy
Age	1.09	0.00	1.09	0.00	1.05	0.02
Gender	0.70	0.00	0.68	0.00	1.00	0.99
Cancer	2.83	0.00	2.20	0.00	20.54	0.00
Hypertension	0.77	0.02	0.79	0.05	0.50	0.22
DM	0.86	0.16	0.85	0.16	0.94	0.88
Heart failure	1.43	0.02	1.40	0.03	3.12	0.11
Completed two-dose vaccination 14 days prior	1.01	0.16	1.00	0.78	1.01	0.79
4th wave	1.14	0.30	1.20	0.16	0.79	0.61
5th wave	0.39	0.01	0.61	0.41	0.38	0.21
6th wave	0.39	0.04	0.64	0.51	0.23	0.45
Remdesivir	1.26	0.05	1.23	0.10	1.40	0.44
Casirivimab/imdevimab or sotrovimab	0.44	0.06	0.37	0.04	2.09	0.53
Dexamethasone	1.27	0.02	1.32	0.01	0.94	0.88
Baricitinib	1.39	0.04	1.47	0.03	0.90	0.85
Tocilizumab	2.39	0.00	2.46	0.00	2.10	0.18
Constant	0.00	0.00	0.00	0.00	0.00	0.00
Number of samples	6403		3612		2791
Adjusted coefficient of determination (R^2)	0.20		0.09		0.20
Inpatients receiving respiratory ventilation
Age	1.07	0.00	1.08	0.00	1.05	0.01
Gender	0.90	0.56	0.95	0.79	0.65	0.29
Cancer	0.87	0.69	0.71	0.35	4.14	0.16
Hypertension	0.57	0.01	0.57	0.01	0.43	0.09
DM	0.81	0.20	0.65	0.04	1.40	0.30
Heart failure	1.23	0.51	0.98	0.96	7.49	0.02
Completed two-dose vaccination 14 days prior	1.00	0.58	1.00	0.89	1.01	0.67
4th wave	1.85	0.00	1.80	0.01	2.65	0.05
5th wave	1.80	0.12	1.44	0.70	2.51	0.19
6th wave	2.72	0.09	1.84	0.58	2.58	0.58
Remdesivir	1.00	0.99	1.06	0.81	0.67	0.39
Casirivimab/imdevimab or sotrovimab	0.09	0.03	0.11	0.05	N.A.	N.A.
Dexamethasone	0.84	0.26	0.77	0.18	0.99	0.97
Baricitinib	0.93	0.78	1.31	0.40	0.52	0.12
Tocilizumab	1.28	0.29	1.48	0.17	0.72	0.47
Constant	0.01	0.00	0.00	0.00	0.01	0.00
Number of samples	923		571		352
Adjusted coefficient of determination (R^2)	0.12		0.08		0.09

Notes: Yellow denotes significance. The fourth wave was defined as 1 March through 20 June, 2021, when the Alpha variant strain emerged and became dominant. Similarly, the fifth wave was defined as 21 June through 21 November, 2021, when the Delta variant strain emerged and then became dominant. The sixth wave was defined as 22 November, 2021 to the end of the study period, when the Omicron, BA.1 strain emerged and then became dominant.

Abbreviation: DM, diabetes mellitus.