5 replies to this topic

[smithx]

I have been avoiding regular weekly or monthly doses of rapamycin for fear that it could weaken my immune response, even though it's been found that intermittent dosing reduces that effect or eliminates it (see https://www.ncbi.nlm...les/PMC4906329/ and others).

 

Rapamycin (also called sirolimus) has also been theorized to be of value in the treatment of covid-19:

 

Previous studies have confirmed the mammalian target of rapamycin complex 1 (mTORC1) as the key factor in regulating various viruses’ replications, including Andes orthohantavirus and coronavirus^48,49. Sirolimus (Z = –2.35 and GSEA score = 3), an inhibitor of mammalian target of rapamycin (mTOR), was reported to effectively block viral protein expression and virion release effectively⁵⁰. Indeed, the latest study revealed the clinical application: sirolimus reduced MERS-CoV infection by over 60%⁵¹. Moreover, sirolimus usage in managing patients with severe H1N1 pneumonia and acute respiratory failure can improve those patients’ prognosis significantly⁵⁰.

 

 

 

https://www.nature.c...1421-020-0153-3

 

But this is for active cases where suppression of an overactive immune response could also be valuable.

 

I would like to start taking rapamycin again once a week or a larger dose once a month, but have not so far found any references that would help understand if doing this is more or less likely to predispose me to COVID-19 disease. Immune suppression is limited in intermittent dosing, but is there still a bit of it? Rapamycin may inhibit the infection once started, but is this effect likely to be bigger than the immune suppression, if there is some?

 

Does anyone have references that would inform the decision of whether to take or not take rapamycin during this pandemic (if not yet infected)?

 

 

 

 

[The Capybara]

I can only relay a very unscientific observation.

I took rapamycin once a week to boost my immune response to antigens (such as the Coronavirus) since I'm in my 50's.

My roommate appears to have gotten the virus early, sometime in February. In hindsight it was a pretty classic presentation, but there were no cases reported in the general population, so I dismissed it as a bad cold.

I continued taking rapamycin.

About 7 weeks later the virus began to present in the general population here, though it was rare (there was no testing, so rare likely meant few critical presentations to the ER).

I then stopped the rapamycin and was sick with Covid-19 about 2 weeks later.

The questions that I will never know are:

Did I hold down an infection from the Covidvirus my roommate had for 9 weeks because of rapamycin, only to set it free when I stopped taking it?

Did I totally suppress the virus, only to catch it almost two months later from another source? (unlikely in my opinion, since I probably would have formed antibodies by that time due to the chronic roommate exposure).

Did my roommate really have just a bad cold that resembled Covid? (always a possibility, however she never caught my Covid-19 when she cared for me while sick for several weeks).

 

Food for thought.

[geo12the]

of interest to this topic:

 

https://clinicaltria...how/NCT04341675

 

Does anyone have references that would inform the decision of whether to take or not take rapamycin during this pandemic (if not yet infected)?

 

 

You can find papers that show that at low doses immunity is not suppressed. I don't have the time to dig them out but they exist. What dosage are you taking? Personally I take 1 mg every two weeks and have not stopped because everything I have read suggests immune response is not hampered at such low doses. 

[geo12the]

 

Exp Gerontol. 2018 May;105:53-69. doi: 10.1016/j.exger.2017.12.026. Epub 2018 Feb 3.

A randomized control trial to establish the feasibility and safety of rapamycin treatment in an older human cohort: Immunological, physical performance, and cognitive effects.  

Kraig E1, Linehan LA2, Liang H3, Romo TQ4, Liu Q5, Wu Y6, Benavides AD7, Curiel TJ8, Javors MA9, Musi N10, Chiodo L11, Koek W12, Gelfond JAL13, Kellogg DL Jr10.

Author information  

 

Abstract  

Inhibition of the mechanistic target of rapamycin (mTOR) pathway by rapamycin (RAPA), an FDA-approved immunosuppressive drug used as a clinical therapy to prevent solid organ allograft rejection, enhances longevity in mice. Importantly, RAPA was efficacious even when initiated in relatively old animals, suggesting that mTOR inhibition could potentially slow the progression of aging-associated pathologies in older humans (Harrison et al., 2009; Miller et al., 2011). However, the safety and tolerability of RAPA in older human subjects have not yet been demonstrated. Towards this end, we undertook a placebo-controlled pilot study in 25 generally healthy older adults (aged 70-95 years); subjects were randomized to receive either 1 mg RAPA or placebo daily. Although three subjects withdrew, 11 RAPA and 14 controls completed at least 8 weeks of treatment and were included in the analysis. We monitored for changes that would indicate detrimental effects of RAPA treatment on metabolism, including both standard clinical laboratory assays (CBC, CMP, HbA1c) and oral glucose tolerance tests (OGTTs). We also monitored parameters typically associated with aging that could potentially be modified by RAPA; these included cognitive function which was assessed by three different tools: Executive Interview-25 (EXIT25); Saint Louis University Mental Status Exam (SLUMS); and Texas Assessment of Processing Speed (TAPS). In addition, physical performance was measured by handgrip strength and 40-foot timed walks. Lastly, changes in general parameters of healthy immune aging, including serum pro-inflammatory cytokine levels and blood cell subsets, were assessed. Five subjects reported potential adverse side effects; in the RAPA group, these were limited to facial rash (1 subject), stomatitis (1 subject) and gastrointestinal issues (2 subjects) whereas placebo treated subjects only reported stomatitis (1 subject). Although no other adverse events were reported, statistically significant decrements in several erythrocyte parameters including hemoglobin (HgB) and hematocrit (Hct) as well as in red blood cell count (RBC), red blood cell distribution width (RDW), mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH) were observed in the RAPA-treatment group. None of these changes manifested clinically significant effects during the short duration of this study. Similarly, no changes were noted in any other clinical laboratory, cognitive, physical performance, or self-perceived health status measure over the study period. Immune parameters were largely unchanged as well, possibly due to the advanced ages of the cohort (70-93 years; mean age 80.5). RAPA-associated increases in a myeloid cell subset and in TREGS were detected, but changes in most other PBMC cell subsets were not statistically significant. Importantly, the OGTTs revealed no RAPA-induced change in blood glucose concentration, insulin secretion, and insulin sensitivity. Thus, based on the results of our pilot study, it appears that short-term RAPA treatment can be used safely in older persons who are otherwise healthy; a trial with a larger sample size and longer treatment duration is warranted.

 

[poonja]

Does not seem to be germane as most of us are taking a larger does at intervals much longer that one day.

[geo12the]

My understanding is that for the longevity benefits what is suggested from the data is intermittent low dosing. At low doses the data suggest  immunity is strengthened as opposed to suppressed from the high doses.