The association of mortality with vaccination and underlying disease among COVID-19 patients in long term care hospitals at Daegu and Gyeonsangbuk-do in Korea
et al., Research Square, doi:10.21203/rs.3.rs-3003449/v1, Jun 2023
Retrospective 2,507 COVID-19 patients at 18 long term care hospitals with COVID-19 outbreaks in Korea, showing no significant difference in mortality with paxlovid treatment. Note that this study is less affected by the typical confounding in paxlovid population studies since the standard of care and treatment propensity for additional treatments is likely to be more similar for this population. Treatment delay is unknown and authors note that treatment may have been delayed.
In most population studies patients receiving paxlovid may have more contact with the medical system, be more likely to follow other recommendations, be more likely to receive additional care, and be more likely to take additional treatments that are not tracked in the data (e.g., nasal/oral hygiene1,2, vitamin D3, etc.).
Resistance. Variants may be resistant to paxlovid4-11. Use may promote the emergence of variants that weaken host immunity and potentially contribute to long COVID12. Confounding by contraindication. Hoertel et al. find that over 50% of patients that died had a contraindication for the use of Paxlovid13. Retrospective studies that do not exclude contraindicated patients may significantly overestimate efficacy. Black box warning. The FDA notes that severe, life-threatening, and/or fatal adverse reactions due to drug interactions have been reported in patients treated with paxlovid14. Kidney and liver injury. Studies show significantly increased risk of acute kidney injury15 and liver injury16.
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risk of death, 5.0% lower, RR 0.95, p = 0.86, treatment 940, control 1,567, adjusted per study, multivariable.
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| Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates |
4.
Zhou et al., Nirmatrelvir-resistant SARS-CoV-2 variants with high fitness in an infectious cell culture system, Science Advances, doi:10.1126/sciadv.add7197.
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Moghadasi et al., Rapid resistance profiling of SARS-CoV-2 protease inhibitors, npj Antimicrobials and Resistance, doi:10.1038/s44259-023-00009-0.
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Jochmans et al., The Substitutions L50F, E166A, and L167F in SARS-CoV-2 3CLpro Are Selected by a Protease Inhibitor In Vitro and Confer Resistance To Nirmatrelvir, mBio, doi:10.1128/mbio.02815-22.
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Lopez et al., SARS-CoV-2 Resistance to Small Molecule Inhibitors, Current Clinical Microbiology Reports, doi:10.1007/s40588-024-00229-6.
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Zvornicanin et al., Molecular Mechanisms of Drug Resistance and Compensation in SARS-CoV-2 Main Protease: The Interplay Between E166 and L50, bioRxiv, doi:10.1101/2025.01.24.634813.
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Vukovikj et al., Impact of SARS-CoV-2 variant mutations on susceptibility to monoclonal antibodies and antiviral drugs: a non-systematic review, April 2022 to October 2024, Eurosurveillance, doi:10.2807/1560-7917.ES.2025.30.10.2400252.
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Deschenes et al., Functional and structural characterization of treatment-emergent nirmatrelvir resistance mutations at low frequencies in the main protease (Mpro) reveals a unique evolutionary route for SARS-CoV-2 to gain resistance, The Journal of Infectious Diseases, doi:10.1093/infdis/jiaf294.
11.
Zhou (B) et al., SARS-CoV-2 Mpro inhibitor ensitrelvir: asymmetrical cross-resistance with nirmatrelvir and emerging resistance hotspots, Emerging Microbes & Infections, doi:10.1080/22221751.2025.2552716.
12.
Thomas et al., Nirmatrelvir-Resistant Mutations in SARS-CoV-2 Mpro Enhance Host Immune Evasion via Cleavage of NF-κB Essential Modulator, bioRxiv, doi:10.1101/2024.10.18.619137.
13.
Hoertel et al., Prevalence of Contraindications to Nirmatrelvir-Ritonavir Among Hospitalized Patients With COVID-19 at Risk for Progression to Severe Disease, JAMA Network Open, doi:10.1001/jamanetworkopen.2022.42140.
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FDA, Fact sheet for healthcare providers: emergency use authorization for paxlovid, www.fda.gov/media/155050/download.
Park et al., 16 Jun 2023, retrospective, South Korea, peer-reviewed, 11 authors, study period January 2022 - August 2022.
The association of mortality with vaccination and underlying disease among COVID-19 patients in long term care hospitals at Daegu and Gyeonsangbuk-do in Korea
doi:10.21203/rs.3.rs-3003449/v1
Background This study aimed to estimate the effects of vaccine on reducing the mortality rate and the relationship between underlying diseases and death among long term care hospital residents during the Omicron epidemic.
Methods This study included 2,507 inpatients at 18 long term care hospitals that experienced COVID-19 outbreaks more than twice in Daegu Metropolitan City and Gyeongsangbuk-do in Korea, from January 2022 to August 2022. Descriptive statistics were used to analyze participants' demographic characteristics and mortality, which were expressed as percentages (%). Logistic regression analysis was performed to compare mortality, and the crude risk ratio (cRR) and adjusted risk risk (aRR) were estimated. The analysis model was adjusted for sex, age, region, history of Paxlovid priscription, vaccine status, reinfection, and presence, type, and number of underlying diseases.
Results In terms of vaccination status, the aRR in the group with < 90 days after the 3 doses was 0.20 (CI:0.09-0.45) and ≥ 90 days was 0.14 (CI:0.06-0.32), that in the group with < 90 days after 4 doses was 0.18 (CI:0.06-0.43), compared with the non-vaccinated group. The fatality rate in the group prescribed Paxlovid was higher than that in the non-prescribed group. However, the difference was not statistically signi cant. The aRR of hypothyroidism was 5.75 (CI:1.10-30.13) and that of COPD and asthma were 2.84 (CI:1.15-6.99), compared with the group that did not have each underlying disease.
Conclusion We con rmed the preventive effects of vaccination on death and the high risk of death from hypothyroidism, COPD, and asthma in COVID-19-con rmed patients in long term care hospitals.
Abbreviations
References
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"abstract": "<jats:title>Abstract</jats:title>\n <jats:p>Background\n This study aimed to estimate the effects of vaccine on reducing the mortality rate and the relationship between underlying diseases and death among long term care hospital residents during the Omicron epidemic.\nMethods\n This study included 2,507 inpatients at 18 long term care hospitals that experienced COVID-19 outbreaks more than twice in Daegu Metropolitan City and Gyeongsangbuk-do in Korea, from January 2022 to August 2022. Descriptive statistics were used to analyze participants’ demographic characteristics and mortality, which were expressed as percentages (%). Logistic regression analysis was performed to compare mortality, and the crude risk ratio (cRR) and adjusted risk risk (aRR) were estimated. The analysis model was adjusted for sex, age, region, history of Paxlovid priscription, vaccine status, reinfection, and presence, type, and number of underlying diseases.\nResults\n In terms of vaccination status, the aRR in the group with < 90 days after the 3 doses was 0.20 (CI:0.09–0.45) and ≥ 90 days was 0.14 (CI:0.06–0.32), that in the group with < 90 days after 4 doses was 0.18 (CI:0.06–0.43), compared with the non-vaccinated group. The fatality rate in the group prescribed Paxlovid was higher than that in the non-prescribed group. However, the difference was not statistically significant. The aRR of hypothyroidism was 5.75 (CI:1.10–30.13) and that of COPD and asthma were 2.84 (CI:1.15–6.99), compared with the group that did not have each underlying disease.\nConclusion\n We confirmed the preventive effects of vaccination on death and the high risk of death from hypothyroidism, COPD, and asthma in COVID-19-confirmed patients in long term care hospitals.</jats:p>",
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