Incidence of Symptoms Associated with Post-Acute Sequelae of SARS-CoV-2 infection in Non-Hospitalized Vaccinated Patients Receiving Nirmatrelvir-Ritonavir

  1. Rushin Patel
  2. Sourbha Dani
  3. Sumanth Khadke
  4. Javaria Ahmad
  5. Jui Shah
  6. Neev Mehta
  7. Kenneth Wener
  8. Daniel P McQuillen
  9. George Abraham
  10. Jeremy Faust
  11. Jason Maley
  12. Smita Patel
  13. Janet Mullington
  14. Robert M. Wachter
  15. Anne Mosenthal
  16. Paul E. Sax
  17. Sarju Ganatra

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Abstract

Background

The role of Nirmatrelvir plus ritonavir (NMV-r) in preventing post-acute sequelae of SARS-CoV-2 infection (PASC) is unknown. The objective of this study is to assess the effect of NMV-r in non-hospitalized, vaccinated patients on the occurrence of PASC.

Methods

We performed a comparative retrospective cohort study utilizing data from the TriNetX research network, including vaccinated patients ≥18 years old who subsequently developed Covid-19 between December 2021-April 2022. Cohorts were based on NMV-r administration within five days of diagnosis. Based on previously validated broad and narrow definitions, the main outcome was the presence of symptoms associated with PASC. Outcomes were assessed between 30-180 days and 90-180 days after the index Covid-19 infection.

Results

1,004 patients remained in each cohort after propensity-score matching. PASC (broad definition) occurred in 425 patients (42%) in the NMV-r cohort, vs. 480 patients (48%) in the control cohort (OR 0.8 CI 0.67-0.96; p=0.01) from 30-180 days and in 273 patients (27%) in the NMV-r cohort, as compared to 347 patients (35%) in the control cohort (OR 0.707, CI 0.59-0.86; p<0.001) from 90-180 days. Narrowly defined PASC was reported in 337 (34%) patients in the NMV-r and 404 (40%) in the control cohort between 30-180 days (OR=0.75, CI 0.62-0.9, p=0.002) and in 221 (22%) in the NMV-r cohort as compared to in 278 (28%) patients in the control cohort (OR=0.7, CI 0.63-0.9, p=0.003) between 90 -180 days.

Conclusions

NMV-r treatment in non-hospitalized vaccinated patients with Covid-19 was associated with a reduction in the development of symptoms commonly observed with PASC and healthcare utilization.

Key Points

Assessment of Nirmatrelvir plus ritonavir (NMV-r) in preventing post-acute sequelae of SARS-CoV-2 infection (PASC), based on broad and narrow definitions in non-hospitalized, vaccinated patients between 30-180 days and 90-180 days.

Article activity feed

  1. PREreview

    This Zenodo record is a permanently preserved version of a PREreview. You can view the complete PREreview at https://prereview.org/reviews/7933773.

    Covid 19 presented a varied range of symptoms in different infected individuals. Effects range from nonsymptomatic to severe symptoms leading to even death of individuals. In this study, authors have shown the effect of NMV-r (antiviral drugs) on post-acute sequelae of SARS-CoV-2 (PASC) in vaccinated individuals. The authors observed that there was a reduction in PASC in non-hospitalized vaccinated patients after NMV-r treatment (during the first 5 days of diagnosis).

    The authors have discussed the methods and statistical analysis in detail and have also talked about limitations at each point. The study is novel and can lead to future research with reduced limitations of data acquisition and the use of predefined definitions during patient data acquisition. Their conclusion is supported by data that shows 11-21% of reduction in PASC.

    Limitations of the study can be listed below, and the authors have also discussed most of them:

    As the data come from an EHR-based TNX research network so the accuracy of data entered by the clinical providers during the whole acquisition becomes a cause of concern.

    As there is no accounting of differences that can influence the results independently. As the groups are significantly different from each other and lack of placebo-controlled trials is a limitation.

    As the severity of PASC is defined by the statement of patients and not a readout by the clinical test so that can cause variability.

    Only the reduction of symptoms has been targeted and rebound symptoms/increased risk has not been accounted for.

    As vaccinated patients have been used in the study and vaccination has been shown to reduce risk itself by 15-50% so that also becomes a variable.

    Overall, the study is novel, and it sets up the platform for future studies. Authors have bravely talked about the limitations to keep it more open to readers. This article can help in further studies to design and define well leading to the least variability and more robust results and conclusions.

    Competing interests

    The author declares that they have no competing interests.

  2. PREreview

    This Zenodo record is a permanently preserved version of a PREreview. You can view the complete PREreview at https://prereview.org/reviews/7820084.

    The main question that this preprint seeks to answer is whether or not Nirmatrelvir plus ritonavir, used as a treatment for non-hospitalized vaccinated patients, was effective at preventing long COVID symptoms. Overall, the paper found that NMV-r was indeed associated with a reduction in symptoms of long COVID. The findings of this paper are novel, as there has been research conducted on NMV-r's effect on COVID symptoms, but this is the first time its effect on long COVID has been investigated. The results are likely to lead to future research, as the findings are novel and relevant to helping solve a large issue in long COVID. I would say that sufficient detail is provided to allow reproduction of the study. Where the data was taken from and how it was analyzed is described in great detail. I do not have the expertise needed to determine if the methods and statistics are appropriate for the analysis, so I am unsure but they seem logical and is an area that other reviewers could check. The principal conclusions are supported by the data and analysis. The manuscript does discuss limitations. It highlights that there could be significant biases in the data due to differences between the groups receiving and not receiving treatment. The authors claim that they used propensity matching to control for these limitations in the data, but admit that there could still be residual confounding. In addition, the authors also point out that the findings could change depending on the definition of long COVID used. The authors say that their definitions of long COVID may have lacked precision and been too inclusive. The authors say that a more accurate result could be obtained from data from original placebo-controlled trials. The authors have not discussed ethical concerns. The manuscript does not include new data. It gets its data from the TriNetX Analytics Network. The authors say that more can be found about this database online. I would recommend this manuscript to others due to its novel findings and its potential contributions to finding effective treatments for long COVID. I highly recommend this manuscript for peer review.

    My only concerns with this manuscript would be that the data does not come from placebo-controlled trials and only from electronic health records. However, the authors have already addressed this concern.

    I do not have any competing interests.

    Competing interests

    The author declares that they have no competing interests.

  3. Version published to 10.1101/2023.04.05.23288196v1 on medRxiv