Study 1 |
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Study 2 |
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|
Matching variables used for all comparisons |
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Age |
|
As 5-year bins between 16 and 111 years |
Sex |
|
Male or female |
Vaccination status |
|
Not vaccinated; received a single-dose vaccine (i) <14 days before COVID-19 diagnosis; ii) 14-90 days before or (iii) >90 days before COVID-19 diagnosis; received the 1st dose of a two-dose vaccine (i) <14 days before; (ii) 14-90 days before or (iii) >90 days before COVID-19 diagnosis; received the 2nd dose of a two-dose vaccine (i) <14 days before; (ii) 14-90 days before or (iii) >90 days before COVID-19 diagnosis |
Calendar period |
|
Up to January 9 2020 (including) – still no vaccination, Alpha strain(s) prevailing; January 10 – July 15 2021 – Alpha strain(s) prevailing, mass vaccination in progress; after July 15 2021 – Delta strain starts to prevail, mass vaccination in progress. |
Comorbidities |
|
Charlson comorbidity index (CCI) subseted at 4 levels: 0, 1-2, 3-4 and ≥5, and also individual comorbidities: atrial fibrillation/undulation, autoimmune disease, malignant disease (cancer), congestive heart failure, chronic obstructive pulmonary disease, history of ischemic heart disease or a cerebrovascular disease, renal disease (in addition to codes in CCI: chronic kidney disease, N18; and dependence on renal dialysis, Z99.2), diabetes without complications, diabetes with complications and dementia (same ICD-10 codes as for the calculation of CCI). |
Pharmacological treatments |
|
Inhibitors of the renin-angiotensine-aldosterone system (RAAS) (includes any of the following: angiotensine converting enzyme inhibitors, angiotensine receptor antagonists and mineralocorticoid receptor antagonists); diuretics (any). |
Matching variables additionally used in the comparison between patients burdened with psychiatric difficulties that may require antidepressant/anxyolytic treatment. In Study 1 this refers to Cohorts A and B (Cohort C by definition is free of such conditions). In Study 2, it refers to both cohorts. |
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Mood disorders |
|
Mood (affective) disorders (F30-F39) |
Nonpsychotic mood disorders |
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Anxiety, dissociative, stress-related, somatoform and other nonpsychotic mood disorders (F40-F48) |
Substance use |
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Mental and behavioral disorders due to psychoactive substance use (F10-F19) |
Non-mood psychotic disorders |
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Schizophrenia, schizotypal, delusional and other non-mood psychotic disorders (F20-F29) |
Cumulatively: F50-F59, F60-F69, F70-F79, F80-F89, F90-F98, F04-F09 |
|
Behavioral syndromes associated with physiological disturbances and physical factors; Disorders of adult personality and behavior; Intellectual disabilities; Pervasive and specific developmental disorders; Behavioral and emotional disorders with onset in childhood and adolescence; mental disorders due to know physiological condition (F04,05,06, 07, 09) |
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|
Study 1 |
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Study 2 |
||||||
|
|
Cohort A |
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Cohort B |
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Cohort C |
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Fluvoxamine |
|
Paroxetine |
N |
|
1016 |
|
95984 |
|
275804 |
|
994 |
|
1796 |
Age (years)1 [meanSD (range)] |
|
5518 (16-99) |
|
5817 (16-105) |
|
4316 (16-96) |
|
5517(16-98) |
|
5816(16-95) |
Male |
|
441 (43.4) |
|
33604 (35.0) |
|
144548 (52.4) |
|
431 (43.4) |
|
564 (31.4) |
Vaccination status |
|
|
|
|
|
|
|
|
|
|
1/1, >90 days |
|
0 (0.0) |
|
1 (<0.1) |
|
1 (<0.1) |
|
0 (0.0) |
|
0 (0.0) |
1/1, <14 days |
|
0 (0.0) |
|
13 (<0.1) |
|
38 (0.1) |
|
0 (0.0) |
|
0 (0.0) |
1/1, 14-90 days |
|
0 (0.0) |
|
8 (<0.1) |
|
43 (0.2) |
|
0 (0.0) |
|
0 (0.0) |
Not vaccinated |
|
958 (94.3) |
|
90719 (94.5) |
|
269392 (97.7) |
|
936 (94.2) |
|
1697 (94.5) |
1/2, >90 days |
|
0 (0.0) |
|
28 (0.0) |
|
16 (0.0) |
|
0 (0.0) |
|
0 (0.0) |
1/2, <14 days |
|
23 (2.3) |
|
1724 (1.8) |
|
2667 (1.0) |
|
23 (2.3) |
|
27 (1.5) |
1/2, 14-90 days |
|
27 (2.7) |
|
2431 (2.5) |
|
2645 (1.0) |
|
27 (2.7) |
|
51 (2.8) |
2/2, >90 days |
|
1 (0.1) |
|
237 (0.2) |
|
201 (0.1) |
|
1 (0.1) |
|
5 (0.3) |
2/2, <14 days |
|
0 (0.0) |
|
298 (0.3) |
|
205 (0.1) |
|
0 (0.0) |
|
4 (0.2) |
2/2, 14-90 days |
|
7 (0.7) |
|
525 (0.5) |
|
596 (0.2) |
|
7 (0.7) |
|
12 (0.7) |
Calendar period |
|
|
|
|
|
|
|
|
|
|
Up to January 9, 2021 |
|
591 (58.2) |
|
55623 (58.0) |
|
163836 (59.4) |
|
574 (57.7) |
|
1061 (59.1) |
January 10 to July 15, 2021 |
|
408 (40.2) |
|
39112 (40.7) |
|
106379 (38.6) |
|
403 (40.5) |
|
716 (39.9) |
After July 15, 2021 |
|
17 (1.7) |
|
1249 (1.3) |
|
5589 (2.0) |
|
17 (1.7) |
|
19 (1.1) |
Weighted CCI |
|
|
|
|
|
|
|
|
|
|
0 |
|
609 (59.9) |
|
55122 (57.4) |
|
230007 (83.4) |
|
598 (60.2) |
|
981 (54.6) |
1-2 |
|
293 (28.8) |
|
31229 (32.5) |
|
40370 (14.6) |
|
285 (28.7) |
|
648 (36.1) |
3-4 |
|
86 (8.5) |
|
7375 (7.7) |
|
4380 (1.6) |
|
85 (8.6) |
|
132 (7.3) |
≥ 5 |
|
28 (2.8) |
|
2258 (2.4) |
|
1047 (0.4) |
|
26 (2.6) |
|
35 (1.9) |
Additional individual conditions |
|
|
|
|
|
|
|
|
|
|
Atrial fibrillation/undulation |
|
61 (6.0) |
|
5850 (6.1) |
|
4017 (1.5) |
|
60 (6.0) |
|
84 (4.7) |
Autoimmune disease |
|
112 (11.0) |
|
13295 (13.9) |
|
14281 (5.2) |
|
110 (11.1) |
|
268 (14.9) |
Cancer |
|
58 (5.7) |
|
7569 (7.9) |
|
7109 (2.6) |
|
55 (5.5) |
|
128 (7.1) |
Congestive heart failure |
|
30 (3.0) |
|
3907 (4.1) |
|
2149 (0.8) |
|
30 (3.0) |
|
66 (3.7) |
COPD |
|
112 (11.0) |
|
12808 (13.3) |
|
17171 (6.2) |
|
109 (11.0) |
|
269 (15.0) |
IHD or CVD |
|
149 (14.7) |
|
12803 (13.3) |
|
8240 (3.0) |
|
146 (14.7) |
|
241 (13.4) |
Renal disease2 |
|
23 (2.3) |
|
2067 (2.2) |
|
1334 (0.5) |
|
23 (2.3) |
|
31 (1.7) |
Diabetes with complications |
|
19 (1.9) |
|
1611 (1.7) |
|
1131 (0.4) |
|
18 (1.8) |
|
34 (1.9) |
Diabetes w/o complications |
|
165 (16.2) |
|
15155 (15.8) |
|
15706 (5.7) |
|
159 (16.0) |
|
315 (17.5) |
Dementia |
|
37 (3.6) |
|
2356 (2.5) |
|
2482 (0.9) |
|
37 (3.7) |
|
56 (3.1) |
Immunocompromised |
|
14 (1.4) |
|
1559 (1.6) |
|
1375 (0.5) |
|
14 (1.4) |
|
23 (1.3) |
Using RAAS inhibitors |
|
293 (28.8) |
|
30443 (31.7) |
|
30386 (11.0) |
|
284 (28.6) |
|
644 (35.9) |
Using diuretics |
|
125 (12.3) |
|
14193 (14.8) |
|
9719 (3.5) |
|
121 (12.2) |
|
281 (15.6) |
F10-F19 |
|
28 (2.8) |
|
2650 (2.8) |
|
--- |
|
27 (2.7) |
|
44 (2.4) |
F20-F29 |
|
119 (11.7) |
|
5306 (5.5) |
|
--- |
|
117 (11.8) |
|
112 (6.2) |
F30-F39 |
|
446 (43.9) |
|
20856 (21.7) |
|
--- |
|
434 (43.7) |
|
971 (54.1) |
F40-F48 |
|
692 (68.1) |
|
71242 (74.2) |
|
--- |
|
676 (68.0) |
|
1199 (66.8) |
Any of F04-F09, F50-F59, F60-F69, F70-F79, F80-F89, F90-F98 |
|
229 (22.5) |
|
19431 (20.2) |
|
--- |
|
218 (21.9) |
|
307 (17.1) |
Outcomes |
|
|
|
|
|
|
|
|
|
|
COVID-related hospitalization |
|
34 (3.35) |
|
3128 (3.25) |
|
2590 (0.94) |
|
32 (3.22) |
|
65 (3.62) |
All-cause 30-day hospitalization |
|
127 (12.5) |
|
11266 (11.7) |
|
14297 (5.18) |
|
125 (12.6) |
|
206 (11.5) |
COVID-related mortality (composite) |
|
38 (3.74) |
|
4261 (4.44) |
|
2898 (1.05) |
|
37 (3.72) |
|
80 (4.44) |
1 For clarity, age is summarized. In the matching process, it was binned (see Table 2).
CCI – Charlson comorbidity index; COPD – chronic obstructive pulmonary disease; CVD – cerebrovascular disease; IHD – ischemic heart disease; RAAS – renin angiotensin aldosteron system
2 In addition to codes in CCI: chronic kidney disease, N18; and dependence on renal dialysis, Z99.2
|
|
Observed RR (95%CrI) |
|
Bias-corrected RR (95%CrI) |
Study 1 |
|
|
|
|
Cohort A vs. Cohort B |
|
|
|
|
COVID-19-related hospitalization |
|
1.15 (0.66-2.11) |
|
1.02 (0.58-1.86) |
All-cause 30-day hospitalization |
|
1.76 (1.39-2.25) |
|
1.55 (1.23-1.99) |
COVID-19-related mortality |
|
0.93 (0.53-1.76) |
|
0.82 (0.47-1.55) |
Study 2 |
|
|
|
|
Fluvoxamine vs. Paroxetine |
|
|
|
|
COVID-19-related hospitalization |
|
1.21 (0.60-2.36) |
|
1.07 (0.52-2.08) |
All-cause 30-day hospitalization |
|
1.13 (0.73-1.73) |
|
1.00 (0.64-1.53) |
COVID-19-related mortality |
|
0.91 (0.46-1.72) |
|
0.80 (0.41-1.52) |