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. 2022 Dec 2;71(48):1531–1537. doi: 10.15585/mmwr.mm7148e2

TABLE 2. Adjusted hazard ratios for COVID-19–associated hospitalization based on Paxlovid prescription receipt (exposure) — Cosmos,* United States, April–September 2022.

Characteristic Adjusted HR (95% CI) No. of participants No. hospitalized Events per 100,000 person-days
Overall Exposed§ Unexposed§
Total
0.49 (0.46–0.53)
693,084
5,229
25.31
15.88
29.05
COVID-19 vaccination status
Vaccinated (≥3 mRNA doses)
0.50 (0.45–0.55)
310,196
2,126
22.98
14.30
27.87
Vaccinated (2 mRNA doses)
0.50 (0.42–0.58)
149,498
1,086
24.37
16.37
26.92
Unvaccinated
0.50 (0.43–0.59)
170,789
1,477
29.05
19.60
31.08
UHC**
0
0.89 (0.58–1.36)
52,592
106
6.73
6.51
6.83
1
0.57 (0.45–0.71)
200,116
503
8.40
6.46
9.03
≥2
0.47 (0.44–0.51)
440,376
4,620
35.29
20.56
41.57
Previous infection ††
No
0.48 (0.44–0.51)
589,147
4,715
26.86
16.12
31.53
Yes
0.76 (0.60–0.98)
103,937
514
16.56
13.54
17.20
Immunocompromised§§
No
0.49 (0.45–0.53)
628,706
3,770
20.09
12.61
23.03
Yes
0.50 (0.44–0.58)
64,378
1,459
77.01
45.99
90.49
Month of COVID-19 diagnosis
Apr 2022
0.54 (0.40–0.71)
60,001
450
25.16
17.77
26.71
May 2022
0.57 (0.48–0.67)
139,062
979
23.61
17.06
25.88
Jun 2022
0.51 (0.43–0.60)
143,706
1,006
23.48
15.02
26.76
Jul 2022
0.46 (0.40–0.53)
184,153
1,432
26.09
15.65
30.94
Aug 2022
0.44 (0.38–0.51)
166,162
1,362
27.52
15.60
32.93
Age group, yrs
18–49
0.59 (0.48–0.71)
275,930
886
10.73
6.99
11.68
50–64
0.40 (0.34–0.48)
211,940
1,032
16.30
7.90
20.10
≥65
0.53 (0.48–0.58)
205,214
3,311
54.56
29.72
68.80
By age group, yrs
18–49
Vaccinated (≥3 mRNA doses)
0.75 (0.53–1.06)
84,054
178
7.07
6.10
7.46
Vaccinated (2 mRNA doses)
0.53 (0.35–0.82)
70,159
198
9.43
6.20
10.16
Unvaccinated
0.54 (0.39–0.76)
97,637
417
14.29
9.09
15.13
1 UHC
0.91 (0.58–1.44)
109,620
157
4.78
4.11
4.91
≥2 UHC
0.54 (0.43–0.67)
166,310
729
14.67
8.35
16.54
50–64
Vaccinated (≥3 mRNA doses)
0.41 (0.30–0.55)
98,699
284
9.61
5.28
12.11
Vaccinated (2 mRNA doses)
0.46 (0.33–0.63)
47,111
265
18.84
10.96
21.89
Unvaccinated
0.38 (0.27–0.53)
45,154
355
26.39
12.43
30.35
No UHC
1.11 (0.46–2.68)
32,519
25
2.56
2.87
2.46
1 UHC
0.30 (0.17–0.55)
53,493
109
6.80
2.45
8.72
≥2 UHC
0.40 (0.33–0.48)
125,928
898
23.91
11.04
30.26
≥65
Vaccinated (≥3 mRNA doses)
0.51 (0.46–0.57)
127,443
1,664
44.02
24.51
57.35
Vaccinated (2 mRNA doses)
0.53 (0.43–0.65)
32,228
623
65.58
36.83
78.59
Unvaccinated
0.58 (0.47–0.72)
27,998
705
85.92
52.75
96.15
No UHC
0.84 (0.51–1.36)
20,073
81
13.50
10.34
15.49
1 UHC
0.63 (0.47–0.85)
37,003
237
21.47
13.66
26.77
≥2 UHC 0.51 (0.47–0.56) 148,138 2,993 68.58 37.33 85.48

Abbreviations: HR = hazard ratio; UHC = underlying health condition.

* Cosmos is an electronic health record dataset that includes information from >160 million persons in U.S. health systems covered by Epic. https://cosmos.epic.com

95% CIs that exclude 1 were considered to be statistically significant. Multivariable models were adjusted for age, sex, race and ethnicity, social vulnerability index, number of underlying health conditions, U.S. Census Bureau region of residence, previous infection, and COVID-19 vaccination status, excluding the stratum of interest.

§ Persons receiving Paxlovid contributed unexposed time until the prescription date and exposed time after the prescription date; those not receiving Paxlovid contributed unexposed time. Follow-up time ended when a hospitalization occurred or at 30-days after diagnosis, whichever came first.

Vaccination categories included 1) unvaccinated if no COVID-19 vaccine had been received; 2) 2 mRNA-dose recipients if ≥14 days had elapsed after the second dose and no subsequent doses had been received or <7 days since receipt of third dose; 3) ≥3 mRNA-dose recipients if ≥7 days had elapsed since receipt of the third dose; and 4) other recipient if any Janssen (Johnson & Johnson) vaccine, other vaccine, or 1 mRNA vaccine dose had been received any time before COVID-19 diagnosis.

** https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/underlyingconditions.html (Accessed October 24, 2022).

†† Previous infection was defined as a COVID-19 diagnosis code or positive COVID-19 nucleic acid amplification test result or antigen test result >90 days before the current diagnosis.

§§ Immunocompromised status was defined using International Classification of Diseases, Tenth Revision codes (adapted from https://academic.oup.com/cid/article/73/11/e4353/6060064 or immunocompromising medication prescribed during the past 6 months (adapted from https://www.atsjournals.org/doi/10.1513/AnnalsATS.201507-415BC).

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