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Master of Public Health

Symptoms, viral loads, and rebound among COVID-19 outpatients treated with nirmatrelvir/ritonavir compared to propensity score matched untreated individuals

AUTHORS

Smith-Jeffcoat SE , Biddle JE , Talbot HK , Morrisey KG , Stockwell MS , Maldonado Y , McLean HQ , Ellingson KD , Bowman NM , Asturias E , Mellis AM , Johnson S , Kirking HL , Rolfes MAR , Olivo V , Merrill L , Battan-Wraith S , Sano E , McLaren SH , Vargas CY , Goodman S , Sarnquist CC , Govindaranjan P , Petrie JG , Belongia EA , Ledezma K , Pryor K , Lutrick K , Bullock A , Yang A , Haehnel Q , Rao S , Zhu Y , Schmitz J , Hart K , Grijalva CG , Salvatore PP , . Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2023 11 14; ().

ABSTRACT

BACKGROUND: Nirmatrelvir/ritonavir (N/R) reduces severe outcomes among patients with COVID-19; however, rebound after treatment has been reported. We compared symptom and viral dynamics in community-based individuals with COVID-19 who completed N/R and similar untreated individuals.

METHODS: We identified symptomatic participants who tested SARS-CoV-2 positive and were N/R eligible from a COVID-19 household transmission study: index cases from ambulatory settings and their households were enrolled, collecting daily symptoms, medication use, and respiratory specimens for quantitative PCR for 10 days, March 2022-May 2023. Participants who completed N/R (treated) were propensity score matched to untreated participants. We compared symptom rebound, viral load (VL) rebound, average daily symptoms, and average daily VL by treatment status measured after N/R completion or, if untreated, seven days after symptom onset.

RESULTS: Treated (n=130) and untreated participants (n=241) had similar baseline characteristics. After treatment completion, treated participants had greater occurrence of symptom rebound (32% vs 20%; p=0.009) and VL rebound (27% vs 7%; p<0.001). Average daily symptoms were lower among treated participants compared to untreated participants without symptom rebound (1.0 vs 1.6; p<0.01), but not statistically lower with symptom rebound (3.0 vs 3.4; p=0.5). Treated participants had lower average daily VLs without VL rebound (0.9 vs 2.6; p<0.01), but not statistically lower with VL rebound (4.8 vs 5.1; p=0.7).

CONCLUSIONS: Individuals who completed N/R experienced fewer symptoms and lower VL but were more likely to have rebound compared to untreated individuals. Providers should still prescribe N/R, when indicated, and communicate possible increased rebound risk to patients.

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