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Paxlovid may cut chances of Long Covid by up to 26%: study [1]

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Date: 2022-11-08

Significant news about the possibilities of Paxlovid: a newly published study suggests that Paxlovid may cut the risk of contracting Long Covid (also referred to as PASC) by up to 26%.

The study, which used data collected by the Veterans Administration, utilized two cohorts which “consisted of 56,340 participants, of which 9217 were in nirmatrelvir [Paxlovid] group, and 47,123 in control group” (p. 5). These cohorts were followed from the initial period (between March 1 and June 30 of this year) until August 31.

This analysis was conducted on existing data sets; this was not an experimental study. However, one primary constraining variable was that participants “were treated in the acute phase with a 5-day course of nirmatrelvir”. This comprised the basis of the investigation.

PASC is defined by the researchers as “having at least one sequela from a set of sequelae based on prior evidence,” where “[i]ndividual sequelae were defined based on inpatient and outpatient ICD-10 diagnosis codes and laboratory results”. Sequelae you can think of something that comes as a material outcome of a consequence. In the lay schema of cause→ effect → consequence → contingency, sequelae are contingencies: something that may happen as a result of some other instance (in this case, coming down with Covid in the first place). Common sequelae in Long Covid include fatigue, pain, shortness, and loss of smell (anosmia), as well as mental confusion and other cognitive dysfunction.

The variables examined in the statistical analysis included such data as

age (≤ 60 years, >60-≤70 years, or >70 years),

race (White, Black, or other),

sex,

smoking status (current smoker, former smoker, someone who never smoked),

systemic and/or chronic diseases (i.e., cancer, cardiovascular disease, chronic kidney disease, chronic lung disease, diabetes, Immune dysfunction and hypertension)

vaccination status (unvaccinated, 1-2 doses of vaccine, and boosted)

infection status (primary SARS-CoV2 infection and reinfection)

the number of baseline risk factors (1-2, 3-4 or ≥5) of progression to severe acute COVID-19 illness, where risk factors included age > 60, BMI > 25km/m2, current smoker, or possessing any of the above mentioned systemic or chronic conditions. (p. 7)



The researchers found that Paxlovid “was associated with reduced risk of 10 of the 12 pre-specified post-acute sequelae evaluated”:

Nirmatrelvir was associated with reduced risk of sequelae in the cardiovascular system (dysrhythmia and ischemic heart disease), coagulation and hematologic disorders (deep vein thombosis, and pulmonary embolism), fatigue, liver disease, acute kidney disease, muscle pain, neurocognitive impairment, and shortness of breath[.] (p. 9)

No statistically significant association was found with regards to the symptoms of new onset diabetes or cough.

Survival probability over a 90-day interval. Nirmatrelvir (Paxlovid) in purple. Shaded areas are 95% confidence intervals.

In addition to the above findings, they also found that Paxlovid “was associated with the reduced risk of PASC in people with 1 to 2, 3 to 4, and 5 or more baseline risk factors”, “in people who were unvaccinated, vaccinated, and those who received a booster vaccine”, and also “in people with primary SARS-CoV-2 infection and in people with reinfection” (p. 10).

This is great news. Of course, there are caveats. First, as this is a study based on retrospective data from the Veterans Administration, the patient population skews overwhelmingly male (87.64% vs 12.36% female). This is not typical for a general population of Long Covid patients in the main (whereas acute Covid is more lethal in males, Long Covid is more prevalent in females). So the population that this study was based on is not reflective of actual, random distributions of persons in the general population. (The study authors note also that the population skews strongly White as well—74.59%, as compared to Black [19.06%], as well as 6.35% of the unspecified “other” group.)

Second, the paper is a medRxiv pre-print, meaning it has yet to be peer-reviewed. Lisa Schnirring, writing on behalf of the Center for Infectious Disease Research and Policy (CIDRAP) out of the University of Minnesota, quoted Dr. Eric Topol, a noted epidemiologist who in his estimation “said the results will need to be independently replicated to ensure that they hold up,” but that, “if they do, Paxlovid would provide a third way to prevent long COVID, alongside avoiding infection and getting vaccinated [and] that a mechanism behind the benefit might be reducing the likelihood of the virus from establishing a reservoir or leaving behind remnants.”

Survival probability with death (as a sequela of COVID-19) as its own measure. Coloring and shading as above.

Acknowledging these limiting factors, the study’s authors note that “it remains unclear whether longer duration or higher dose or both may have resulted in more reduced risk of post-acute sequelae. It is also unclear whether the initiation of treatment in the post-acute phase of COVID-19 reduces the risk of Long Covid” (p. 13). I interpret this as a tacit recommendation for follow-up study to address these open questions.

The authors conclude:

In sum, we provide evidence in this study that in people with SARS-CoV-2 infection who had at least 1 risk factor for progression to severe disease, treatment with nirmatrelvir within 5 days of a positive SARS-CoV-2 test was associated with reduced risk of PASC across the risk spectrum in this cohort and regardless of vaccination status and history of prior infection. The findings suggest that the salutary benefit of nirmatrelvir extends to the post-acute phase of COVID-19. (p. 14, my emphasis)

If these results are borne out in further studies, then Paxlovid will be a welcome and potent weapon in our anti-Long Covid arsenal.

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[1] Url: https://www.dailykos.com/stories/2022/11/8/2134508/-Paxlovid-may-cut-chances-of-Long-Covid-by-up-to-26-study

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