Skip to main content
SearchLoginLogin or Signup

Review 2: "Assessing the Effect of Selective Serotonin Reuptake Inhibitors in the Prevention of Post-Acute Sequelae of COVID-19"

This preprint discusses the importance of SSRIs and their effect on long-COVID.. Reviewers find this study to be potentially informative and strong, highlighting the study’s contribution to new treatments for PASC.

Published onJan 05, 2023
Review 2: "Assessing the Effect of Selective Serotonin Reuptake Inhibitors in the Prevention of Post-Acute Sequelae of COVID-19"
1 of 2
key-enterThis Pub is a Review of
Assessing the Effect of Selective Serotonin Reuptake Inhibitors in the Prevention of Post-Acute Sequelae of COVID-19
Description

AbstractImportancePost-acute sequelae of COVID-19 (PASC) produce significant morbidity, prompting evaluation of interventions that might lower risk. Selective serotonin reuptake inhibitors (SSRIs) potentially could modulate risk of PASC via their central, hypothesized immunomodulatory, and/or antiplatelet properties and therefore may be postulated to be of benefit in patients with PASC, although clinical trial data are lacking.ObjectivesThe main objective was to evaluate whether SSRIs with agonist activity at the sigma-1 receptor lower the risk of PASC, since agonism at this receptor may serve as a mechanism by which SSRIs attenuate an inflammatory response. A secondary objective was to determine whether potential benefit could be traced to sigma-1 agonism by evaluating the risk of PASC among recipients of SSRIs that are not S1R agonists.DesignRetrospective study leveraging real-world clinical data within the National COVID Cohort Collaborative (N3C), a large centralized multi-institutional de-identified EHR database. Presumed PASC was defined based on a computable PASC phenotype trained on the U09.9 ICD-10 diagnosis code to more comprehensively identify patients likely to have the condition, since the ICD code has come into wide-spread use only recently.SettingPopulation-based study at US medical centers.ParticipantsAdults (≥ 18 years of age) with a confirmed COVID-19 diagnosis date between October 1, 2021 and April 7, 2022 and at least one follow up visit 45 days post-diagnosis. Of the 17 933 patients identified, 2021 were exposed at baseline to a S1R agonist SSRI, 1328 to a non-S1R agonist SSRI, and 14 584 to neither.ExposuresExposure at baseline (at or prior to COVID-19 diagnosis) to an SSRI with documented or presumed agonist activity at the S1R (fluvoxamine, fluoxetine, escitalopram, or citalopram), an SSRI without agonist activity at S1R (sertraline, an antagonist, or paroxetine, which does not appreciably bind to the S1R), or none of these agents.Main Outcome and MeasurementDevelopment of PASC based on a previously validated XGBoost-trained algorithm. Using inverse probability weighting and Poisson regression, relative risk (RR) of PASC was assessed.ResultsA 26% reduction in the RR of PASC (0.74 [95% CI, 0.63-0.88]; P = 5 × 10−4) was seen among patients who received an S1R agonist SSRI compared to SSRI unexposed patients and a 25% reduction in the RR of PASC was seen among those receiving an SSRI without S1R agonist activity (0.75 [95% CI, 0.62 - 0.90]; P = 0.003) compared to SSRI unexposed patients.Conclusions and RelevanceSSRIs with and without reported agonist activity at the S1R were associated with a significant decrease in the risk of PASC. Future prospective studies are warranted.Key pointsQuestionDo Selective Serotonin Reuptake Inhibitors with and without agonist activity at the sigma-1 receptor (S1R) prevent Post-Acute Sequelae of COVID-19?FindingsIn this retrospective study leveraging real-world clinical data that included 17 933 patients, a 28% reduction in risk of PASC was observed for S1R agonist SSRIs and a 25% reduction in risk of PASC was observed for non-S1R agonist SSRIs, both versus controls, using a computable phenotype to define PASC.MeaningSSRIs may play a role in managing the long term disease burden of COVID-19. Future prospective studies are warranted to confirm these findings and evaluate potential mechanisms of action.

RR:C19 Evidence Scale rating by reviewer:

  • Potentially informative. The main claims made are not strongly justified by the methods and data, but may yield some insight. The results and conclusions of the study may resemble those from the hypothetical ideal study, but there is substantial room for doubt. Decision-makers should consider this evidence only with a thorough understanding of its weaknesses, alongside other evidence and theory. Decision-makers should not consider this actionable, unless the weaknesses are clearly understood and there is other theory and evidence to further support it.

***************************************

Review:

The use of Selective Serotonin Reuptake Inhibitors (SSRIs) has been widely examined in cohort studies and randomized trials for the treatment of acute COVID symptoms and recovery. Specifically, fluvoxamine has been examined in several randomized trials and demonstrated treatment benefits for both prevention of clinical progression and time to recovery. Observational studies have examined whether patients already on SSRIs had a greater risk of hospitalization or death and have found protective effects. It should come as only logical then, to examine whether these drugs have a role in long COVID. For that reason, this study is very timely and potentially important. 

The methods are sound and use a typical nested case-control approach. There is a sufficient number of patients that if they detect a treatment effect, it is likely sufficiently powered. The effect size detected also appears to be in line with the therapeutic studies of SSRIs in acute COVID. 

Some of the text is overly long; for example the introduction and some of the reporting of results are inconsistent. There is no reason, for example, to report a p-value as P = 5 x 10-4. I am not convinced that the mechanism of action is understood about antidepressants in COVID and it is entirely speculative that they may have antiviral or anti-inflammatory properties. The study is interesting and will probably lead to a lot of off-label prescribing and use by a population of patients that otherwise have nothing else. However, we ultimately need a large randomized trial to inform whether this is an agent that can be widely recommended.

Comments
2
Abhishek Kumar:

Jubilant Biosys is a global CRO/CDMO that provides comprehensive drug discovery, contract research, and manufacturing services in partnership with leading worldwide pharmaceutical and healthcare companies.

Vape Factory:

https://brooklyninc.ru/2022/12/26/elementor-12269/

https://ekids.edu.vn/brustschwimmen-muskelaufbau/

https://ekids.edu.vn/anabola-clenbuterol/

https://ekids.edu.vn/ejercicio-bosu/

https://ekids.edu.vn/aecn/

https://ekids.edu.vn/anabola-equipoise/

https://ekids.edu.vn/test-title6289/

https://ekids.edu.vn/test-title7170/

https://www.hurmio.fi/node/557668

https://www.hurmio.fi/node/557669

https://rcid.tums.ac.ir/?q=en/content/benefits-disposable-vaping-over-traditional-cigarettes

https://rcid.tums.ac.ir/?q=en/content/latest-innovations-disposable-vaping-technology

https://ysidhu.wixsite.com/website-1/forum/education-forum/how-to-use-a-vape

https://ysidhu.wixsite.com/website-1/forum/education-forum/vape-shape-and-atomizer-mechanism

https://www.smore.com/n60bj-how-to-use-a-vape

https://www.agentpet.com/forum/discussion/general/advantages-of-using-a-vape

https://forum.medmap.io/d/3356-advantages-of-using-a-vape

https://www.blockdit.com/posts/63e281eac0fd04717c87e45e

http://forum.gold-forum.ru/index.php?showtopic=59613

https://www.bitsdujour.com/view/advantages-of-using-a-vape

https://www.tickaroo.com/ticker/637f8657a720689dbb6849d5

https://fucksocial.net/events/721b0354-d587-4016-aed4-b64a5bf5fca5

https://typevape.splashthat.com/

https://gettogether.community/events/27412/vape-factory/

http://www.corrections.com/events/12022

https://eventregist.com/e/s8nIsLNzViWd

https://ticketbud.com/events/3f54ec5c-a39a-11ed-a537-42010a71701e

https://www.mixily.com/event/3676460065141150314

https://events.ydr.com/event/fc661db5a92ca57364a992b82e3c3896

https://events.ydr.com/event/cb9de660a4c8066a4f492db1e5a62d7c

https://d.io/vaperisk/afefd3

http://dom-nam.ru/index.php/forum/stroitelnye-kompanii/17886-what-is-the-healthiest-vape

http://dom-nam.ru/media/kunena/attachments/153139/Whatsthebestbrandofvape.pdf

https://vapecig.footeo.com/

https://vapecig.footeo.com/news/2022/11/24/types-of-vape

http://toparticlesubmissionsites.com/types-of-vape/

https://theomnibuzz.com/tips-to-quit-smoking-with-vape/

https://writeupcafe.com/the-vape-market-in-europe-and-the-u-s-and-europe/

https://articlepedia.xyz/can-i-sell-vapes-on-amazon/

https://randomarticle.xyz/how-do-i-quit-smoking-perfectly/

https://www.articlebowl.com/how-do-start-a-vape-business/

https://www.articleshood.com/how-to-find-a-reliable-vape-supplier/

https://www.articlefloor.com/how-to-start-a-vape-business-online/

https://www.articlequarter.com/the-top-5-vape-manufacturers/

https://www.articledistrict.com/what-is-the-best-way-to-start-a-vape-business/

https://www.articlewood.com/what-is-better-disposable-pods-or-vape/

https://www.peopleofarticle.com/are-there-any-benefits-of-switching-from-cigarettes-to-vaping/

https://www.articlemela.com/what-does-vaping-feel-like/

https://www.articleshore.com/can-you-buy-vape-devices-from-amazon/

https://www.articladihatti.com/the-risks-of-vaping-inside-a-casino/

https://www.articlescluster.com/is-it-safe-to-vape-with-no-nicotine/

https://articlezone.xyz/why-did-you-start-vaping/

https://articlezine.xyz/why-shouldnt-you-vape/

https://articlemag.xyz/should-i-start-vaping-if-i-m-a-smoker/

https://articleroom.xyz/should-i-start-vaping-if-i-m-a-smoker/

https://articlewrap.xyz/can-vaping-ever-be-safe/

https://articlepost.xyz/are-vape-devices-useful/

https://articlemania.xyz/what-are-the-pros-and-cons-of-disposable-vape/

https://dailybusinesspost.com/does-vaping-make-you-lose-weight/

https://dailybusinesspost.com/is-vaping-more-addictive-than-cigarette/

https://linkhay.com/link/5849728/vape-factory-from-china

https://linkhay.com/link/5849729/diposable-vapes

https://linkhay.com/u/vapecig

https://linkhay.com/blog/436082/features-and-benefits-of-e-cigarettes

https://flipboard.com/@VapeFactory

https://www.gapo.vn/1368661816

https://fr.quora.com/profile/Ecigator-New

https://vapecig.skyrock.com/

https://vapecig.skyrock.com/3352939636-How-to-choose-a-vape-manufacturer.html

https://www.sqworl.com/6aj0jg

https://www.strava.com/athletes/111060038/posts/22608893

https://www.cakeresume.com/matthew-ma

https://www.doyoubuzz.com/ma-matthew

https://diigo.com/0qto52

https://www.diigo.com/item/note/sb5u/skvt?k=0d91af8ef0c48dfe7f4fb3362f95dee3

https://fundrazr.com/profiles/ecigator-new

https://journal.thierry-pelle.eu/vapecig/vape-situation-in-indonesia

https://journal.thierry-pelle.eu/vapecig/

https://journal.thierry-pelle.eu/vapecig/whats-a-pod-vape

https://dribbble.com/shots/20002064-Armo-Bunny

https://www.bloggalot.com/lifestyle/do-e-cigarettes-help-you-quit-smoking

https://www.bloggalot.com/lifestyle/2-recommended-e-liquids

https://www.evernote.com/shard/s488/sh/209ad964-4871-0160-0e3a-8140ff7444e3/fdaacc077990b5718156a686043887d2

https://wise-atmosphere-86e.notion.site/Basic-knowledge-of-vape-83a033045ae94868a8c6db8e6e18bfa2

https://gotartwork.com/Blog/why-is-my-disposable-vape-pen-not-working/107257/

https://gotartwork.com/Blog/how-to-use-disposable-vape/107267/

https://click4r.com/posts/g/7525385/how-to-make-a-disposable-vape-hit-again

https://click4r.com/posts/g/7525703/how-to-make-disposable-vape-last-longer

https://www.kityfeed.com/hobbies/is-disposable-vape-safe.html

https://www.kityfeed.com/hobbies/are-disposable-vapes-safe.html

https://jobhop.co.uk/profile/184879

https://jobhop.co.uk/blog/184879

https://jobhop.co.uk/blog/184879/basic-knowledge-of-vape

http://jobhop.co.uk/company/ecigatorvape

https://onmogul.com/vapecig

https://onmogul.com/stories/basic-knowledge-of-vape

https://onmogul.com/stories/how-to-start-a-vape-business-in-2023

https://tbpchan.cz/biz/res/19.html

https://tbpchan.cz/biz/src/1669644398549.pdf

https://wakelet.com/@MatthewMa521

https://wakelet.com/wake/gTUjZ3eQ8dlEf66nu_kv3

https://www.storeboard.com/ecigatorvapewholesale

https://www.storeboard.com/blogs/health/tips-to-quit-smoking-with-vape/5544333

https://www.storeboard.com/blogs/health/are-disposable-vapes-cost-effective/5576342

https://www.thecityclassified.com/ads/vape-wholesale/

http://www.classtize.com/view/2-recommended-eliquids-1399682

https://freead1.net/ad/4019644/vape-wholesale.html

https://vatgia.com/raovat/9957/16968116/cach-chon-vape-dung-mot-lan.html

http://www.xcomplaints.com/complaint/vape-wholesale-c130226.html

https://vape.deno.dev/

https://melaninterest.com/user/vapecig/

https://xtibia.com/forum/topic/255532-what-is-a-vape/

https://pluginindia.freeforums.net/thread/2196/vape

https://pluginindia.freeforums.net/thread/2197/enjoy-vape-box

https://xtibia.com/forum/topic/255533-what-flavors-are-available-in-vape-liquids/

https://clubvapeadoresmexico.boards.net/thread/1381/ecigator-vape-wholesale-factory

https://clubvapeadoresmexico.boards.net/thread/1380/ecigator-sticky-prefilled-vape-starter

https://www.dagaldan.co.il/forum/general-discussion/what-is-a-vape

https://www.padelforum.org/threads/how-to-choose-the-right-battery-to-enjoy-vaping.115707/

https://civilqa.com/en/how-to-choose-a-vape-battery/

https://www.mastersindia.co/q/question/how-to-choose-a-vape-battery/

https://www.zupyak.com/p/3377746/t/lets-get-the-basics-of-vape

https://www.zupyak.com/p/3377749/t/vape-wholesale-directly-from-china-vape-factory

https://community.gtarcade.com/thread/1388232-1-1.html

https://www.truxgo.net/blogs/391817/1201180/how-to-choose-an-e-cigarette

https://www.truxgo.net/blogs/391817/1201185/what-is-a-vape

https://www.truxgo.net/blogs/391817/1201187/i-want-to-enjoy-vape-in-a-box

https://bloggalot.com/lifestyle/2-recommended-e-liquids

https://bloggalot.com/lifestyle/do-e-cigarettes-help-you-quit-smoking

https://bloggalot.com/lifestyle/how-to-choose-the-right-battery-to-enjoy-vaping

https://dailygram.com/blog/1177995/what-is-vitamin-e-cigarette/

https://dailygram.com/blog/1177996/points-to-consider-when-choosing-a-vitamin-e-cigarette/

https://dailygram.com/blog/1186153/why-should-i-choose-a-disposable-vape-pen/

https://dailygram.com/blog/1198149/how-to-get-the-most-out-of-your-disposable-vaping-device/

https://webyourself.eu/vapecig

https://webyourself.eu/posts/53387

https://webyourself.eu/pages/vapecig

https://webyourself.eu/blogs/53389/What-is-vitamin-e-cigarette

https://webyourself.eu/blogs/53390/Points-to-consider-when-choosing-a-vitamin-e-cigarette

https://webyourself.eu/blogs/53391/What-vapde-devices-do-you-recommend

https://geto.space/vapecig

https://geto.space/vaporecig

https://geto.space/read-blog/88780

https://geto.space/read-blog/88781

https://geto.space/read-blog/88782

https://www.ethiovisit.com/myplace/posts/158254

https://www.ethiovisit.com/myplace/vapecig

https://www.ethiovisit.com/myplace/pages/vapecignew

https://www.promorapid.com/6352a2417

https://www.promorapid.com/post/568061_ecigator-is-one-of-the-well-known-vape-brands-spun-off-from-giftsoar-technology.html

https://www.sachamberrapidresponse.org/forum/general-discussions/the-pros-and-cons-of-using-disposable-vapes

https://www.blogulr.com/vapecig/convenient-and-cost-effective-disposable-vapes-explained-72277

https://www.blogulr.com/vapecig/discover-the-convenience-of-disposable-vape-72279

https://www.pickmemo.com/vapecig

https://www.pickmemo.com/post/197402_ecigator-is-one-of-the-well-known-vape-brands-spun-off-from-giftsoar-technology.html

https://www.pickmemo.com/read-blog/126285

https://www.pickmemo.com/read-blog/126286

https://www.pickmemo.com/read-blog/126287

https://www.social-vape.com/1676813311955772_10839

https://www.social-vape.com/post/49369_ecigator-is-one-of-the-well-known-vape-brands-spun-off-from-giftsoar-technology.html

https://www.social-vape.com/read-blog/21617

https://www.social-vape.com/read-blog/21618

https://www.social-vape.com/read-blog/21620

https://frustratedgamers.com/vapenew

https://frustratedgamers.com/post/315499_ecigator-is-one-of-the-well-known-vape-brands-spun-off-from-giftsoar-technology.html

https://frustratedgamers.com/read-blog/250741

https://frustratedgamers.com/read-blog/250743

https://frustratedgamers.com/read-blog/250744

https://bresdel.com/vapecig

https://bresdel.com/posts/273285

https://bresdel.com/pages/ecignew

https://bresdel.com/blogs/273287/What-is-vitamin-e-cigarette

https://bresdel.com/blogs/273288/Points-to-consider-when-choosing-a-vitamin-e-cigarette

https://bresdel.com/blogs/273289/What-vapde-devices-do-you-recommend

https://kyourc.com/vapecig

https://kyourc.com/post/59288_ecigator-is-one-of-the-well-known-vape-brands-spun-off-from-giftsoar-technology.html

https://kyourc.com/read-blog/59682

https://kyourc.com/read-blog/59683

https://kyourc.com/read-blog/59684

https://www.trackthattravel.com/travelblog/39963

https://www.trackthattravel.com/travelblog/39966

https://www.trackthattravel.com/travelblog/39969

https://naijacontacts.com/topics/view/94584

https://naijacontacts.com/topics/view/95636

https://hackmd.io/@vapecig/r1nAz_8wo

https://hackmd.io/@vapecig/HyU7X_Ivs

https://hackmd.io/@vapecig/HJ8HQ_LDs

https://getinkspired.com/en/story/297724/pod-type-vape-is-a-hot-item/

https://git.guildofwriters.org/DoobesURU/moul-assets-doobes/issues/336

https://i2pgit.org/Vapecig/vape

https://vapelife.unicornplatform.page/

http://vapelife.rf.gd/

http://vape123.42web.io/

http://nicevape.great-site.net/

https://www.gocrowdera.com/campaign/where-can-i-purchase-pod-type-vape

https://sajhi.com/vapecig

https://sajhi.com/posts/49503

https://sajhi.com/posts/49504

https://sajhi.com/blogs/49505/Where-can-I-purchase-POD-type-vape

https://sajhi.com/blogs/49506/POD-type-vape-is-a-hot-item

https://sajhi.com/blogs/49507/What-vapde-devices-do-you-recommend

https://www.bonfire.com/vape-factory/

http://nigerianwiki.com/User:Vapefactory

https://shortest.activeboard.com/forum.spark?aBID=160356&p=83&topicID=68983403&commentID=68983403

https://bigcitydreamz.com/blog/how-do-you-use-a-pod-vape

https://bigcitydreamz.com/blog/vapde-devices-recommend

https://paperpage.in/vapecig

https://paperpage.in/posts/2219

https://paperpage.in/blogs/2222/What-is-electronic-cigarette-and-the-type

https://paperpage.in/blogs/2223/Advantages-of-Vaping-to-Quit-Smoking

https://www.gamerlaunch.com/community/users/blog/6273360/?mode=view&gid=535

https://www.party.biz/profile/vapecig

https://www.party.biz/blogs/144469/187303/what-is-plume-tech

https://mcspartners.ning.com/forum/topics/what-are-the-various-types-and-varieties

https://mcspartners.ning.com/photo/albums/vape-factory

https://www.onfeetnation.com/profiles/blogs/what-is-the-cheapest-way-to-vape

https://www.onfeetnation.com/profiles/blogs/what-websites-sell-vapes-without-id

https://www.onfeetnation.com/profiles/blogs/can-you-legally-ship-a-vape

https://www.esurveyspro.com/Survey.aspx?id=e31f8b4c-06a4-434b-96d8-afcbcea7a387

https://questionpro.com/t/AXQY1Zwvy6

https://dopostings.com/5-disposable-vapes-recommended/

https://dopostings.com/author/vapecig/

https://peatix.com/group/11911636/view

https://peatix.com/event/3438786/view

https://www.tipga.com/e/63930af33286fe44e333dab7

https://www.liveinternet.ru/users/vapelife/

https://www.liveinternet.ru/users/vapelife/post496870078/

https://www.liveinternet.ru/users/vapelife/post496870207/

https://jemi.so/vapecig

https://jemi.so/vapecig/blog

https://www.loom.com/share/7407cbe13dfe4daa82f161c9dcc0aef3

https://note.com/vapecig/n/n95210e1b965f

https://vocus.cc/article/63df9c71fd89780001447e14

https://cafe.cfma.org/viewdocument/some-popular-e-cigarette-recommenda

https://www.arkbar.com/network/members/profile?UserKey=11424fed-d020-4c03-96c1-018511c77d35

https://www.common.org/network/members/profile?UserKey=7102028f-c7ed-4250-ae23-c42daba08162

https://community.arubainstanton.com/network/members/profile?UserKey=c1e39f78-fa78-4ea8-a188-837b96cd76ea

https://collaborate.amcp.org/network/members/profile?UserKey=256bca7b-ffa6-4d91-ae05-2936c359e53c

https://community.acsi.org/network/members/profile?UserKey=e3e04907-bcba-4707-a2d0-77c3f15cf7b2

https://community.acec.org/network/members/profile?UserKey=467a789c-74f4-49d5-8f84-c126b1282f8d

https://raindrop.io/vapelife/disposable-vape-29809666

https://web.ggather.com/vapecig

https://www.lasso.net/go/link/eWZoBK

https://disposablevape.notion.site/

https://www.clipix.com/9/share-4iaxQ-Dm

https://vapelife-f911a.web.app/

https://storage.googleapis.com/podvape/index.html

https://t.me/s/dispovape

https://discussions.apple.com/thread/254471492

https://vapelife.mobirisesite.com/

https://vapecig.take.app/

https://phs.vn/faqDetail?id=3145

https://phs.vn/faqDetail?id=3146

https://vapecig-disposablevape.pbworks.com/w/file/152285106/What%27s%20the%20best%20brand%20of%20vape.pdf