Nirmatrelvir and Molnupiravir and Post–COVID-19 Condition in Older Patients
Retrospective 8,089 molnupiravir patients in the USA showing a small reduction in long COVID with treatment.
Confounding is likely significant as below, and may eliminate the benefit. Results specific to the COVID-19 code should be closer to the actual efficacy due to likely lower average severity of the additional treatment patients included based on home tests.
Confounding by treatment propensity. This study analyzes a population
where only a fraction of eligible patients received the treatment. Patients
receiving treatment may be more likely to follow other recommendations, more
likely to receive additional care, and more likely to use additional
treatments that are not tracked in the data (e.g., nasal/oral hygiene
c19early.org, c19early.org (B), vitamin D
c19early.org (C), etc.) — either because the physician
recommending molnupiravir also recommended them, or
because the patient seeking out molnupiravir is more
likely to be familiar with the efficacy of additional treatments and more
likely to take the time to use them.
Therefore, these kind of studies may
overestimate the efficacy of treatments.
Concerns have been raised that the mutagenic mechanism of action may create dangerous variants or cause cancer Chamod, Hadj Hassine, Huntsman, Marikawa, Swanstrom, Waters, Zhou, Zibat. Multiple analyses have identified variants potentially created by molnupiravir Fountain-Jones, Kosakovsky Pond, Sanderson, .
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risk of PASC, 4.0% lower, HR 0.96, p = 0.001, COVID-19 only, Cox proportional hazards.
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risk of PASC, 8.0% lower, HR 0.92, p < 0.001, including patients without COVID-19 code, Cox proportional hazards.
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Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
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Fung et al., 23 Oct 2023, retrospective, USA, peer-reviewed, 4 authors, study period January 2022 - September 2022.
Contact:
kfung@mail.nih.gov.
Abstract: Letters
RESEARCH LETTER
Nirmatrelvir and Molnupiravir and Post–COVID-19
Condition in Older Patients
While the COVID-19 pandemic appears to be winding down, its
effects are still felt by the millions of people worldwide experiencing post–COVID-19 condition (PCC, or long COVID).1 The
antiviral drug nirmatrelvir (marketed as Paxlovid [Pfizer], in
combination with ritonavir)
and molnupiravir (Lagevrio
Supplemental content
[Merch]) are recommended as
first- and second-line treatments for acute illness in patients with
specific risk factors (eg, diabetes).2 However, there are still no
US Food and Drug Administration–approved drugs for the treatment or prevention of PCC. Recent studies among US veterans
(mostly male) suggest that nirmatrelvir and molnupiravir reduce the risk of some sequelae of COVID-19.3,4 We performed a
cohort study of the 2 drugs in PCC in older patients who were
Medicare enrollees.
Methods | The cohort came from Medicare enrollees aged 65
years or older diagnosed with COVID-19 between January
and September 2022. COVID-19 was identified with an
outpatient International Statistical Classif ication of
Diseases, Tenth Revision, Clinical Modification code of
U07.1. In January 2022, free home COVID-19 tests became
available and not all positive self-tests were captured in
Medicare data. Therefore, we also considered the prescription of nirmatrelvir or molnupiravir to be indicative of
COVID-19 because no other indications existed. Following
previous work, 5 we identified PCC based on the World
Health Organization (WHO) consensus clinical definition.6
Any new occurrence (not present prior to COVID-19 diagnosis) of the 11 symptoms between 4 to 12 weeks after infection was considered as PCC. We used an extended Cox
regression with propensity score adjustment to examine the
2 drugs and the incidence of PCC. We included age, sex,
race, geographic region, dual eligibility, low-income subsidy, and 51 chronic comorbidities as covariates as included
Table 1. Hazard Ratio Based on Cox Regression Modela
Event rate, % (95% CI)
Index variable
Reference
No. (%)
Hazard ratio (95% CI)
Index group
Reference group
Absolute risk
reductionb
Nirmatrelvir
None
439 134 (19.5)
0.87 (0.86 to 0.88)
11.8 (11.7 to 11.9)
14.5 (14.4 to 14.6)
2.7
Molnupiravir
None
58 914 (2.6)
0.92 (0.90 to 0.94)
13.7 (13.5 to 14.0)
14.5 (14.4 to 14.6)
0.8
Female
Male
1 313 415 (58.5)
1.17 (1.16 to 1.18)
14.5 (14.4 to 14.6)
13.2 (13.1 to 13.2)
−1.3
70-74
65-69
656 324 (29.2)
0.78 (0.77 to 0.79)
12.7 (12.7 to 12.8)
12.0 (11.9 to 12.1)
−0.7
75-79
65-69
509 291 (22.7)
0.70 (0.69 to 0.71)
14.2 (14.1 to 14.3)
12.0 (11.9 to 12.1)
−2.2
80-84
65-69
324 008 (14.4)
0.64 (0.63 to 0.66)
15.8 (15.7 to 16.0)
12.0 (11.9 to 12.1)
−3.8
≥85
65-69
313 754 (14.0)
0.61 (0.60 to 0.63)
16.9 (16.7 to 17.0)
12.0 (11.9 to 12.1)
−4.9
Asian
White
81 073 (3.6)
1.10 (1.07 to 1.12)
13.3 (13.0 to 13.5)
13.9 (13.9 to 14.0)
0.6
Black
White
82 249 (3.7)
1.24 (1.22 to 1.27)
15.3 (15.0 to 15.5)
13.9 (13.9 to 14.0)
−1.4
Hispanic
White
93 325 (4.2)
1.02 (1.00 to 1.04)
15.4 (15.1 to 15.6)
13.9 (13.9 to 14.0)
−1.5
Otherd
White
93 011 (4.1)
1.04 (1.02 to 1.06)
12.4 (12.1 to 12.6)
13.9 (13.9 to 14.0)
1.5
Dual eligibility
Nondual
244 874 (10.9)
1.06 (1.05 to 1.08)
16.6 (16.5 to 16.8)
13.6 (13.5 to 13.6)
−3.0
Low-income subsidy
Nondual
21 049 (0.9)
1.07 (1.03 to 1.10)
16.4 (15.9 to 16.9)
13.6 (13.5 to..
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