LCAC treatment and trial tracker — twenty-one-treatment beta

Editorial update: 16 October 2026. Added two sleep-research summaries and pacing guidance; earlier entries retain their recorded evidence and recruitment checks.

Source checks: Original eight summaries: 13 October 2026. Nine additions: 14 October 2026 (America/Toronto). Status: public beta; independent clinical review not performed.

This public beta records what selected primary sources support. It is not an exhaustive review, prescribing guide or clinical recommendation. Candidate therapies and institutional campaigns are assessed separately.

Ensitrelvir — established Long COVID

Evidence source check: 13 October 2026. Independent clinical review not performed.

Public summary: PREVAIL-LC has posted results from 40 participants. The posted primary outcome values alone do not establish a statistically reliable treatment benefit.

Confirmed study facts

PREVAIL-LC (NCT06161688) randomized 40 adults at one US centre to a five-day regimen or placebo. The registry is active, not recruiting; UCSF also says it is not accepting new patients. Results were first posted 2 April 2026. Primary completion is actual; overall completion remains estimated.

The day-10 PROMIS-29 physical health summary values are 43.6 (95% CI 41.7–45.4) for ensitrelvir and 41.6 (39.7–43.4) for placebo, with 20 participants per group. No between-group analysis is supplied in that outcome record. These arm values must not be presented as demonstrating statistical significance or clinical benefit. No serious adverse events are reported in either 20-person group through the stated two-month reporting window; that small observation does not establish safety.

Sources: Registry and results; UCSF.

Limits and evidence checks

The posted analysis plan is now checked: primary comparison uses ANCOVA with the mean screening/baseline score as covariate. The registry describes baseline-adjusted day-10 means but does not supply the primary between-group CI or p-value. The primary-outcome description contains an unresolved placeholder. A full results publication was not identified in the recorded searches; this is not proof that none exists. The plan was finalized 21 February 2025, after the registry's 20 December 2024 primary-completion date. Unblinding timing is unknown; dates alone do not establish outcome switching. The protocol includes PEM assessment and exertional tests; severe/housebound applicability and safeguards remain unresolved. Protocol and SAP, SAP section 4.1.

Canadian marketing authorization, coverage, supply and a drug-specific supported access process remain unverified. Health Canada's general SAP process involves practitioner requests and manufacturer supply; it is not a confirmation of access to this drug. SAP guidance.

Related LCAC campaign should remain separate from the evidence summary.

Obeldesivir — acute-COVID evidence, direct Long COVID question unresolved

Evidence source check: 13 October 2026. Independent clinical review not performed.

Public summary: The identified randomized trials treated acute COVID-19. Their findings do not demonstrate benefit for people with established Long COVID.

Confirmed findings and search boundary

A ClinicalTrials.gov API query combining intervention “obeldesivir” and condition “Long COVID” returned zero matches on the check date. A broader intervention-only search returned six records: NCT06682234, NCT06585150, NCT05996744, NCT05715528, NCT06784973 and NCT05603143. Their listed conditions concerned filovirus, RSV or acute COVID; none was identified as established Long COVID treatment. Wording and single-registry coverage limit this finding. Reproducible all-condition query.

OAKTREE (NCT05715528), a completed acute-COVID trial, reported median symptom-alleviation times of 5.9 versus 6.0 days; hazard ratio 1.099, 95% CI 0.997–1.211, p=0.068. The primary clinical endpoint did not reach statistical significance. A reduction in viral RNA was reported as a secondary outcome. That physiological observation must not be converted into a Long COVID treatment claim.

Sources: Published abstract; Registry.

BIRCH (NCT05603143) is terminated, not simply completed. Published primary-analysis events were 0/211 versus 1/207 for acute-COVID hospitalization or all-cause death by day 29 (p=0.32). The study stopped early with few events; the authors describe it as underpowered.

Sources: Published abstract; Registry.

Limits and evidence checks

Keep both trials in a clearly labelled contextual section, outside counts of established Long COVID treatment trials. The all-condition registry search is complete for the named intervention; aliases, other registries and unpublished plans can still be missed.

Gilead still described obeldesivir as investigational in its 12 June 2026 statement. Canadian marketing, Long COVID supply and coverage remain unverified. Acute-COVID trial authorization must not be confused with marketing approval. No manufacturer message has been sent in this task.

Related LCAC campaign asks a research question; the tracker does not presume benefit.

Ivabradine — Long COVID-associated POTS

Evidence source check: 13 October 2026. Independent clinical review not performed.

Public summary: In RECOVER-AUTONOMIC, ivabradine did not significantly improve the main orthostatic symptom score overall. It reduced the heart-rate rise on standing. Conference results also suggest the symptom effect differed by care assignment.

Confirmed evidence distinctions

RECOVER-AUTONOMIC's ivabradine appendix (NCT06305806) lists 181 participants and completed status. Investigators described three months of treatment and another three months of follow-up, with factorial assignment to coordinated or usual care. Their announcement and seminar report distinguish heart-rate reduction from symptom outcomes. Numerical estimates are now verified in the investigator's ACC.26 slides, slides 14 and 16: primary symptom difference −0.14 (95% CI −0.72 to 0.43), p=0.63; standing-minus-supine heart-rate change difference −3.95 beats/min (−6.78 to −1.12), p=0.007. These remain conference evidence; the full journal efficacy report and comparative harms were not identified in this scoped check.

The slides describe a prespecified interaction (p=0.004): drug versus placebo difference −1.03 (−1.83 to −0.23) under coordinated care, versus 0.72 (−0.09 to 1.52) under usual care. Those contrasts compare drug with placebo within care assignments; they are not direct comparisons between two ivabradine groups.

Sources: Appendix registry; RECOVER announcement; July seminar.

The parent NCT06305780 has posted results, but the reviewed primary result is enrolment: 200 IVIG plus 181 ivabradine participants. It is not a separate efficacy result or an independent ivabradine trial. Its safety rows with zero participants at risk are not interpretable as zero-event safety estimates. Platform results.

An earlier uncontrolled 55-person study reported that 43 participants felt better within seven days. Without a comparator, that percentage cannot estimate treatment benefit beyond placebo, fluctuation or other influences. Its “COVID-associated POTS” population also requires applicability review against an established Long COVID definition. Study abstract.

COVIVA (NCT05481177) now has unknown overall status; its last registry verification was November 2023, although a location still says recruiting. Do not advertise it as open. The institutional MiCOR project listing names COVIVA but supplies no current recruitment confirmation. The 2025 linked article is a protocol, not efficacy results. Registry; Protocol.

Canadian access and evidence checks

Health Canada lists Lancora as marketed; the reviewed monograph indication is specified chronic heart failure, not Long COVID/POTS. Ontario limited-use code 538 has heart-failure eligibility criteria; Long COVID/POTS alone does not meet this listed indication. Other routes/provinces are unverified. Product record; Monograph.

Retrieve the complete randomized efficacy report and safety data; reconcile the prespecified care interaction with a full report and do not substitute it for the overall result. Confirm COVIVA's current recruitment from an institution/investigator before listing it as open.

Paxlovid

Evidence source check: 13 October 2026. Independent clinical review not performed.

Evidence status: Three published randomized trials; no significant primary benefit.

STOP-PASC, PAX LC and RECOVER-VITAL did not show statistically significant improvement on their primary Long COVID outcomes with the tested regimens. These findings concern established Long COVID, not treatment of a new acute infection.

STOP-PASC: symptoms at 10 weeks

A 15-day course did not significantly improve the pooled six-symptom primary outcome versus placebo plus ritonavir. The publication randomized 155 people; the registry count of 168 includes those who consented and were screened.

Sources: STOP-PASC randomized trial (2024); STOP-PASC registry.

PAX LC: physical health at day 28

Adjusted difference −0.55 PROMIS-29 points (95% CI −2.32 to 1.21; p=0.54), after 15 days of treatment. No significant primary benefit.

Sources: PAX LC randomized trial (2025).

RECOVER-VITAL: symptoms at day 90

The August 2026 publication reported no significant primary benefit with either 15 or 25 days in cognitive, autonomic or exercise/PEM phenotypes. For 25 days, adjusted differences in clinically significant improvement were 3.2 percentage points (95% CI −10.4 to 16.8), −6.4 (−18.5 to 5.7) and −7.8 (−19.5 to 3.8), respectively.

Sources: RECOVER-VITAL randomized trial (August 2026).

Reported harms

PAX LC reported drug-related events in 35/46 treated participants versus 27/49 controls, commonly altered taste; no serious events through six weeks. RECOVER-VITAL Table 3 reports any adverse event in 212/323 (25-day), 204/320 (15-day) and 185/320 (placebo–ritonavir). Treatment-related serious events affected one participant per group. These descriptive counts do not establish equivalent safety.

Sources: PAX LC randomized trial (2025); RECOVER-VITAL randomized trial (August 2026); RECOVER-VITAL full report.

Trial records and burden

• STOP-PASC (NCT05576662): COMPLETED; registry updated 2025-09-04, checked 2026-10-13. Trial completed; not recruiting. 15 days; primary assessment at 10 weeks. Five clinic visits over 15 weeks. Registry enrolment 168 corresponds to consent and screening in the publication; 155 were randomized. Registry.
• PAX LC (NCT05668091): COMPLETED; registry updated 2024-12-02, checked 2026-10-13. Trial completed; not recruiting. 15 days; primary assessment at day 28. Decentralized US trial with no required site visits. Registry.
• RECOVER-VITAL (NCT05965726): COMPLETED; registry updated 2026-03-27, checked 2026-10-13. Trial completed; not recruiting. 15 or 25 days; primary assessment at day 90. Symptom and performance assessments. Registry.

Limitations

• Results concern the studied regimens and populations; they do not rule out every antiviral strategy or subgroup.
• Full-report review confirms that 31 participants belonged to multiple symptom clusters; the phenotype counts must not be summed as unique people. Table 3 supplies arm-level safety counts. Independent clinical interpretation remains pending.
• Acute treatment and prevention trials are excluded from the Canadian Long COVID treatment recruitment filter.

Canada

Health Canada authorized Paxlovid for acute COVID-19 in people at high risk of severe disease. That does not establish a Long COVID indication or coverage for extended courses. Important drug interactions require clinician/pharmacist review.

Sources: Health Canada: Paxlovid acute-COVID authorization; Health Canada: Paxlovid interactions.

Next evidence check: Monitor corrections and new outcome or harms reports; independent clinical review can be added later.

Low-dose naltrexone (LDN)

Evidence source check: 13 October 2026. Independent clinical review not performed.

Evidence status: Observational findings; randomized results pending.

A small retrospective study reported symptom improvements, but it cannot establish treatment benefit. The Canadian randomized trial is completed with no registry results posted; LIFT also studies LDN.

Retrospective symptom and function changes

Among 59 people with paired questionnaires, LDN use was associated with improvements in fatigue, PEM, sleep and function. Composite symptom scores improved in 32 and worsened in 19. This selected, uncontrolled analysis cannot separate medication effects from other changes.

Sources: Bonilla et al.: retrospective LDN cohort (2023).

Canadian randomized evidence

The BC trial enrolled 160 participants and completed in February 2026. Its primary outcome measures fatigue at 16 weeks. No registry results were posted when checked; completion and the published protocol are not outcome evidence.

Sources: BC low-dose naltrexone trial registry.

LIFT: shared trial with pyridostigmine

One four-arm trial tests LDN, pyridostigmine, their combination and placebo in ME/CFS with orthostatic intolerance, including eligible Long COVID patients. No results posted. The planned 160 participants are shared across the trial. An August 2026 peer-reviewed protocol describes the study design, not treatment results or confirmed current recruitment.

Sources: LIFT registry; LIFT protocol (August 2026).

Trial records and burden

• BC low-dose naltrexone trial (NCT05430152): COMPLETED; registry updated 2026-03-20, checked 2026-10-13. Trial completed; not recruiting. 16-week trial with fatigue questionnaires and blood measures. Completed. Registry.
• LIFT (NCT06366724): RECRUITING; registry updated 2025-10-22, checked 2026-10-13. Registry says recruiting but was last updated October 2025; estimated September 2026 primary completion has passed. Current availability requires confirmation. Approximately three months, three in-person Boston visits and four virtual visits; two submaximal cardiopulmonary exercise tests, blood and urine collection. Exertional testing can be burdensome with PEM; discuss accommodations and suitability with the study team. 160 total across four arms shared between LDN and pyridostigmine; not 160 per drug. Registry.

Limitations

• Observational findings are vulnerable to selection bias, missing follow-up and confounding.
• LIFT’s population is narrower than Long COVID as a whole.
• Comprehensive comparative harms and formal certainty assessment are pending.

Canada

The BC trial used compounded low-dose capsules and is completed. Routine Canadian access, compounding costs and coverage are unverified. LIFT is based in Boston; Canadian participation is not established.

Sources: BC low-dose naltrexone trial registry; LIFT registry.

Next evidence check: Check for BC trial results and obtain a current LIFT recruitment update; assess randomized harms alongside benefit.

Intravenous immunoglobulin (IVIG)

Evidence source check: 13 October 2026. Independent clinical review not performed.

Evidence status: Small observational signal; randomized results pending.

A small nonrandomized study reported improvement in post-COVID small-fibre neuropathy. RECOVER-AUTONOMIC’s IVIG trial is completed with no posted results. An NIH neurological study enrols by invitation.

Small-fibre neuropathy case-control study

Neuropathic symptom response was reported in 9/9 IVIG-treated patients versus 3/7 untreated patients (p=0.02). This small retrospective, nonrandomized comparison cannot establish efficacy for Long COVID broadly.

Sources: McAlpine et al.: post-COVID small-fibre neuropathy (2024).

RECOVER-AUTONOMIC IVIG

The randomized IVIG appendix enrolled 200 people and completed in June 2026. No results posted when checked. The shared platform’s enrolment totals are not efficacy or usable comparative safety findings.

Sources: RECOVER-AUTONOMIC IVIG registry; RECOVER-AUTONOMIC platform results — enrolment.

NIH neurological trial

The registry lists enrolment by invitation with 45 planned participants and requires prior study participation. It is not an open Canadian recruitment opportunity. No results posted.

Sources: NIH neurological Long COVID IVIG study registry.

Trial records and burden

• RECOVER-AUTONOMIC IVIG (NCT06305793): COMPLETED; registry updated 2026-07-31, checked 2026-10-13. Trial completed; not recruiting. Repeated IV infusions over nine months, followed by three months of follow-up; orthostatic symptoms assessed at nine months. Registry.
• NIH neurological Long COVID IVIG study (NCT05350774): ENROLLING_BY_INVITATION; registry updated 2026-10-13, checked 2026-10-13. No Canadian site listed; cross-border eligibility not established. Invitation-only NIH study requiring prior protocol participation. Procedures include infusion courses, lumbar puncture, tilt testing and neurological assessments; up to four months. Registry.

Limitations

• Biopsy-confirmed small-fibre neuropathy and selected trial populations do not represent all Long COVID.
• An observational response comparison is not a randomized treatment effect.
• Full comparative harms are pending; absent results do not establish safety.

Canada

No Canadian site is listed in these two selected trials. Routine Canadian eligibility, product access and provincial funding for Long COVID are not established in this review.

Sources: RECOVER-AUTONOMIC IVIG registry; NIH neurological Long COVID IVIG study registry.

Next evidence check: Check for RECOVER IVIG results and assess efficacy, adverse events and subgroup applicability together.

Pyridostigmine

Evidence source check: 13 October 2026. Independent clinical review not performed.

Evidence status: Trial listed as recruiting; current availability unconfirmed.

LIFT tests pyridostigmine alone and with LDN in people with ME/CFS and orthostatic intolerance, including qualifying Long COVID patients. No results are posted. Current recruitment needs confirmation.

LIFT factorial trial

The planned 160-person, four-arm trial measures function and exercise-related physiology. It is shared with the LDN entry, not a second independent trial. Registry status says recruiting, but its October 2025 update is old and estimated primary completion has passed. An August 2026 peer-reviewed protocol describes the study design, not treatment results or confirmed current recruitment.

Sources: LIFT registry; LIFT protocol (August 2026).

Trial records and burden

• LIFT (NCT06366724): RECRUITING; registry updated 2025-10-22, checked 2026-10-13. Registry says recruiting but was last updated October 2025; estimated September 2026 primary completion has passed. Current availability requires confirmation. Approximately three months, three in-person Boston visits and four virtual visits; two submaximal cardiopulmonary exercise tests, blood and urine collection. Exertional testing can be burdensome with PEM; discuss accommodations and suitability with the study team. 160 total across four arms shared between LDN and pyridostigmine; not 160 per drug. Registry.

Limitations

• Trial registration cannot establish benefit.
• Eligibility requires ME/CFS and orthostatic intolerance; applicability to all Long COVID is uncertain.
• Exercise testing and travel may limit participation for people with PEM or severe illness.

Canada

LIFT is based in Boston with no Canadian site listed. Cross-border eligibility, routine Canadian prescribing access and coverage are not verified here.

Sources: LIFT registry.

Next evidence check: Confirm whether LIFT is accepting participants and check for results; count this shared trial once.

Upadacitinib

Evidence source check: 13 October 2026. Independent clinical review not performed.

Evidence status: Canadian sites listed as recruiting; no results posted.

LC-REVITALIZE tests upadacitinib and pirfenidone against matched placebo. Its registry lists recruiting sites in Montreal and Sherbrooke. No results are posted; availability of the upadacitinib arm needs confirmation.

LC-REVITALIZE platform

The initial phase plans 348 participants across two drugs and placebo groups. The primary outcome tracks the worst baseline symptom domain during follow-up; the registry specifies enrolment through month six. This is not an upadacitinib-only sample, and authorization to run a trial is not evidence of benefit.

Sources: LC-REVITALIZE registry; Health Canada: LC-REVITALIZE authorization.

Trial records and burden

• LC-REVITALIZE (NCT06928272): RECRUITING; registry updated 2026-10-06, checked 2026-10-14. Registry lists Canadian sites as recruiting; site and specific drug-arm availability require confirmation. Three months of study medication with follow-up to six months. Confirm eligibility, visits, monitoring and the locally available drug arm with the study team. 348 across upadacitinib, pirfenidone and matched placebo groups in the initial platform phase; not 348 on upadacitinib. Registry. Canadian study details and contacts.

Limitations

• No randomized efficacy or safety results posted when checked.
• Eligibility criteria and exclusions limit who can participate.
• A recruiting site listing does not guarantee an open local drug arm, eligibility or enrolment.

Canada

Health Canada lists an authorized LC-REVITALIZE trial. ClinicalTrials.gov lists IRCM in Montreal and CRCHUS in Sherbrooke as recruiting (updated 6 October 2026). Confirm the site, eligibility and upadacitinib arm with the study team. Routine Long COVID access and coverage are not established. Recherche Santé Québec also lists these locations as open but identifies ClinicalTrials.gov as its data source; this is not independent site confirmation.

Sources: LC-REVITALIZE registry; Health Canada: LC-REVITALIZE authorization; Quebec listing — registry-derived.

Next evidence check: Confirm Canadian site and drug-arm availability; monitor registry changes and first results.

Famotidine + loratadine

Evidence source check: 14 October 2026. Independent clinical review not performed.

Summary: The tested antihistamine combination produced a small additional fatigue-score improvement at 12 weeks. The difference was not sustained at 24 weeks, and sensitivity analyses weakened confidence in the finding.

Fatigue at 12 weeks

Adjusted difference versus no study drug: −1.48 FAS points (95% CI −2.88 to −0.08). Lower scores mean less fatigue; a statistically detectable difference is not necessarily a meaningful improvement.

Sources: STIMULATE-ICP drug trial — full published report (2026).

Reported adverse events

51/193 participants in the combination group versus 21/196 receiving no study drug reported an adverse event. Open-label reporting and the sample size limit safety conclusions.

Sources: STIMULATE-ICP drug trial — full published report (2026).

Limitations

• Open-label study with self-reported fatigue; expectations and missing data can affect estimates.
• Sensitivity analyses addressing missing data or full treatment completion did not retain statistical significance for the small colchicine and antihistamine differences.
• No sustained between-group fatigue difference at 24 weeks. This does not establish a cure or benefit for every Long COVID symptom.
• This trial tested famotidine and loratadine together. It cannot establish either component's independent effect or benefit from all antihistamines.

Canada

Canadian authorization for this use, supply, cost and coverage were not verified in this update. Availability for another condition would not establish benefit for Long COVID.

Linked studies

• STIMULATE-ICP drug trial (ISRCTN10665760): COMPLETED; checked 2026-10-14. Study drugs for 12 weeks; fatigue questionnaires at baseline, 12 and 24 weeks. Published trial regimens are research descriptions, not prescribing instructions.

Next check: Check subsequent trials, corrections and longer-term results; assess Canadian access separately.

Colchicine

Evidence source check: 14 October 2026. Independent clinical review not performed.

Summary: A UK trial found a small, short-term fatigue difference. A separate placebo-controlled trial in India did not demonstrate better walking-distance improvement at 52 weeks. These findings do not establish a broadly effective treatment.

STIMULATE-ICP: fatigue at 12 weeks

Adjusted difference versus no study drug: −1.49 FAS points (95% CI −2.92 to −0.06). The difference was not sustained at 24 weeks.

Sources: STIMULATE-ICP drug trial — full published report (2026).

India: walking-distance change at 52 weeks

Difference: 5.59 metres (95% CI −9.00 to 20.18), after 26 weeks of treatment. The trial randomized 350 people; the primary outcome model included 319.

Sources: Colchicine randomized trial — India (2025).

Reported harms

In STIMULATE-ICP, 57/192 versus 21/196 reported adverse events; 27 colchicine participants had gastrointestinal events. In India, adverse events were reported by 35/176 versus 30/170, and medication was stopped because of events by 3 versus 1. Two deaths occurred in the colchicine group (suicide and miliary tuberculosis); these counts alone do not establish drug causation.

Sources: STIMULATE-ICP drug trial — full published report (2026); Colchicine randomized trial — India (2025).

Limitations

• Open-label study with self-reported fatigue; expectations and missing data can affect estimates.
• Sensitivity analyses addressing missing data or full treatment completion did not retain statistical significance for the small colchicine and antihistamine differences.
• No sustained between-group fatigue difference at 24 weeks. This does not establish a cure or benefit for every Long COVID symptom.
• The trials used different regimens, populations, comparators and outcomes; their estimates should not be pooled casually.
• The Indian study permitted enrollment from 22 days after infection, although the median interval was much longer. The report uses 346 for the treated population and 319 for the primary outcome analysis.

Canada

Canadian authorization for this use, supply, cost and coverage were not verified in this update. Availability for another condition would not establish benefit for Long COVID.

Linked studies

• STIMULATE-ICP drug trial (ISRCTN10665760): COMPLETED; checked 2026-10-14. Study drugs for 12 weeks; fatigue questionnaires at baseline, 12 and 24 weeks. Published trial regimens are research descriptions, not prescribing instructions.
• Colchicine trial — India (CTRI/2021/11/038234): COMPLETED; checked 2026-10-14. 26 weeks of study medication; primary walking-distance outcome at 52 weeks. Walking assessments may not represent what severely affected or housebound patients can tolerate.

Next check: Check further randomized reports and corrections; retain distinct fatigue and functional outcomes.

Rivaroxaban

Evidence source check: 14 October 2026. Independent clinical review not performed.

Summary: STIMULATE-ICP did not demonstrate a fatigue benefit over no study drug at 12 weeks. Bleeding events were reported. This trial does not support a general claim that anticoagulation treats Long COVID.

Fatigue at 12 weeks

Adjusted difference: −1.06 FAS points (95% CI −2.47 to 0.35); the interval includes no difference. No between-group fatigue difference was demonstrated at 24 weeks.

Sources: STIMULATE-ICP drug trial — full published report (2026).

Reported harms

70/197 participants versus 21/196 receiving no study drug reported adverse events. Minor bleeding or heavy menstrual bleeding was reported in 26/197 rivaroxaban participants. Five serious events in three rivaroxaban participants were judged unrelated to the study drug by investigators.

Sources: STIMULATE-ICP drug trial — full published report (2026).

Limitations

• Open-label trial; fatigue and adverse-event reporting can be affected by knowledge of treatment.
• A confidence interval crossing zero does not prove every possible regimen has no effect.
• This is one rivaroxaban regimen, not evidence about every anticoagulant or treatment combination.

Canada

Canadian authorization for this use, supply, cost and coverage were not verified in this update. Availability for another condition would not establish benefit for Long COVID.

Linked studies

• STIMULATE-ICP drug trial (ISRCTN10665760): COMPLETED; checked 2026-10-14. Study drugs for 12 weeks; fatigue questionnaires at baseline, 12 and 24 weeks. Published trial regimens are research descriptions, not prescribing instructions.

Next check: Check new controlled trials and harms; keep claims specific to the tested regimen and outcome.

Hyperbaric oxygen therapy (HBOT)

Evidence source check: 14 October 2026. Independent clinical review not performed.

Summary: A 40-session trial reported short-term cognitive improvement. Two later 10-session trials did not demonstrate benefit on their main comparisons. Different protocols and outcomes prevent a simple conclusion that more sessions work better.

40 sessions: cognitive outcome

The 2022 trial reported a group-by-time difference in global cognition (effect size d=0.495; p=0.038), assessed 1–3 weeks after treatment. Its Results section reports 79 randomized and 73 analyzed.

Sources: HBOT 40-session randomized trial (2022).

10 sessions: HOT-LoCO

Among 80 randomized participants, the 13-week between-group differences were 0.63 points for physical functioning (95% CI −7.04 to 8.29) and 2.35 for physical role limitations (−5.95 to 10.66). Neither primary comparison demonstrated benefit.

Sources: HOT-LoCO 10-session randomized trial (2025).

10 sessions: Belgian four-group trial

101 participants were randomized to different oxygen/pressure conditions. No significant between-group differences in symptoms, function or cognitive performance were reported after treatment.

Sources: Belgian four-group oxygen trial (2025).

Reported harms and burden

The 2022 report recorded side effects in 35.1% of HBOT and 38.9% of control participants. HOT-LoCO reported adverse events in 19 HBOT and 18 placebo participants, including a seizure judged probably related to HBOT and a placebo-group death judged unrelated. Four Belgian-trial participants stopped because of middle-ear pressure injury. These findings do not establish that HBOT is safe for everyone.

Sources: HBOT 40-session randomized trial (2022); HOT-LoCO 10-session randomized trial (2025); Belgian four-group oxygen trial (2025).

Limitations

• Small studies, differing oxygen pressures, sham procedures, populations and outcomes limit comparison.
• The 2022 abstract and Results section differ on the randomized count; this summary uses the Results section and keeps analyzed participants separate.
• Short-term results do not establish durable benefit. The 2022 authors disclosed commercial relationships with AVIV Scientific.
• Repeated chamber visits and testing can be burdensome. Applicability to severe, housebound or PEM-affected patients needs assessment.
• HOT-LoCO also reported a later secondary responder finding at 52 weeks; this is distinct from its negative primary 13-week comparisons and requires cautious interpretation.

Canada

The Canadian directory lists RECLAIM HBOT at UHN in Toronto as recruiting and the Sunnybrook study as ongoing without recruitment (registry checks: 13 October 2026). Confirm openings, visits, eligibility and accommodations with the team. Routine Canadian coverage and treatment costs were not verified.

Sources: RECLAIM HBOT registry; Sunnybrook HBOT registry; RECLAIM investigator intervention page.

Linked studies

• HBOT 40-session trial — Israel (NCT04647656): COMPLETED; checked 2026-10-14. 40 chamber sessions; outcomes assessed 1–3 weeks after treatment. The Results section reports 79 randomized and 73 analyzed; the abstract calls 73 randomized.
• HOT-LoCO — Sweden (NCT04842448): COMPLETED; checked 2026-10-14. 10 chamber sessions over six weeks; primary physical-health outcomes at 13 weeks.
• Four-group oxygen trial — Belgium (HBOT-BELGIUM-2025): COMPLETED; checked 2026-10-14. 10 chamber sessions with four oxygen/pressure conditions; repeated cognitive and walking tests. Travel and attendance burden were reported.
• RECLAIM — hyperbaric oxygen (NCT06452095): RECRUITING; checked 2026-10-13. Tests hyperbaric oxygen for Long COVID cognitive symptoms. Ask the team about chamber visits, travel and the assessment schedule. Ask the study team about visits, time, travel, compensation, accessibility and any exertion or testing requirements. Canadian listing.
• Hyperbaric oxygen for post-COVID symptoms (NCT06082518): ACTIVE_NOT_RECRUITING; checked 2026-10-13. Studies hyperbaric oxygen treatment for post-COVID symptoms. Follow-up is ongoing; the registry says new participants are not being accepted. Ask the study team about visits, time, travel, compensation, accessibility and any exertion or testing requirements. Canadian listing.

Next check: Monitor Canadian trial results and recruitment; check long-term controlled outcomes and protocol-specific harms.

Taurine

Evidence source check: 14 October 2026. Independent clinical review not performed.

Public summary: Blood taurine levels have been associated with symptom burden, but this does not show that taking taurine improves Long COVID. Canadian adult and adolescent studies are testing different questions; neither registry has posted results.

Evidence: Biomarker association; treatment results pending.

• Observational biomarker evidence: A study of 117 people initially hospitalized with COVID-19, with 28 healthy controls, linked taurine trajectories to later symptoms and outcomes. It did not randomize people to taurine supplements, so its associations cannot establish treatment benefit. Sources: Taurine biomarker study — observational (2024)
• Adult randomized trial: TaurineLC plans 300 participants. Primary outcomes assess fatigue and cognitive performance at three months. No registry results were posted when checked. Sources: Taurine Supplementation in Long COVID — registry
• Adolescent study: TaurineLCPeds plans 30 participants aged 10–17 in a single-group, open-label study. The primary outcome is blood taurine change at three months; this is different from demonstrating symptom benefit versus placebo. Sources: Taurine Supplementation in Adolescents With Post-COVID Condition — registry
• Safety evidence: The biomarker study does not establish supplement safety. Comparative Long COVID harms results from these Canadian studies are not yet available in their registry records. Sources: Taurine biomarker study — observational (2024); Taurine Supplementation in Long COVID — registry; Taurine Supplementation in Adolescents With Post-COVID Condition — registry

Limitations:

• Association does not establish that a deficiency causes symptoms or that supplementation reverses them.
• Findings from adults initially hospitalized with COVID-19 may not apply to all Long COVID populations.
• The adolescent study has no placebo group. Blood-level change is not equivalent to clinical improvement.

Canada: The adult trial lists recruiting sites in Alberta, British Columbia, Ontario and Quebec. The adolescent registry says not yet recruiting, has no posted sites and retains an estimated September 2026 start date that has passed. Confirm openings and eligibility with the team. Retail availability does not establish Long COVID benefit; Canadian product authorization and coverage were not assessed. Sources: Taurine Supplementation in Long COVID — registry; Taurine Supplementation in Adolescents With Post-COVID Condition — registry

• RECLAIM — taurine (NCT06721949): recruiting. Registry updated 2026-09-18; checked 2026-10-14. 12 weeks of taurine or placebo followed by 12 weeks of follow-up; fatigue and cognitive testing plus other assessments. Confirm visit and exertion requirements with the team. Canadian listing
• TaurineLCPeds (NCT07682402): not yet recruiting. Registry updated 2026-08-13; checked 2026-10-14. Three months of supplementation with blood sampling and symptom/cognitive assessments. Ask about study locations, visit schedule, accessibility, travel and current opening date. The primary outcome is change in blood taurine, not proof of symptom benefit. Canadian listing

Next check: Check adult randomized results and the adolescent opening date/site list; assess symptom outcomes and harms separately from taurine blood levels.

Pirfenidone

Evidence source check: 14 October 2026. Independent clinical review not performed.

Public summary: A trial after severe COVID-19 pneumonia did not demonstrate better lung recovery with pirfenidone than placebo. That population differs from Long COVID more broadly. LC-REVITALIZE is testing symptom outcomes and has no posted registry results.

Evidence: Related-condition randomized results; Long COVID platform results pending.

• FIBRO-COVID: primary outcome: Of 113 randomized participants, 103 were analyzed. At 24 weeks, the composite improvement outcome occurred in 79.7% receiving pirfenidone and 82.3% receiving placebo. The trial did not demonstrate superiority. Sources: FIBRO-COVID randomized trial — post-pneumonia lung fibrosis
• Reported harms: Four pirfenidone participants and three placebo participants stopped because of toxicity. The report described similar adverse-event and hospitalization rates and no deaths. This does not establish safety for every patient. Sources: FIBRO-COVID randomized trial — post-pneumonia lung fibrosis
• LC-REVITALIZE: The planned 348 participants span upadacitinib, pirfenidone and matched placebo groups. This is one shared platform, not 348 people receiving pirfenidone. No registry results were posted when checked. Sources: LC-REVITALIZE registry

Limitations:

• FIBRO-COVID enrolled people with CT lung changes after severe hospitalized pneumonia, 30–90 days after recovery/discharge; it is not a general Long COVID fatigue or brain-fog trial.
• Most participants were also receiving low-dose prednisone. Improvement within both groups does not establish a drug effect.
• The 2026 correction adds an author affiliation; it does not change the reported outcomes. Read the correction.

Canada: LC-REVITALIZE lists Montreal and Sherbrooke as recruiting. Confirm whether the pirfenidone arm is available locally. Authorization to run a study does not establish treatment benefit or routine Long COVID access; coverage and supply were not verified. Sources: LC-REVITALIZE registry

• FIBRO-COVID (NCT04607928): completed. Published completed-trial report; not a new registry-status check; checked 2026-10-14. 24 weeks of treatment with lung function, CT imaging and other assessments; enrolled after severe COVID-19 pneumonia.
• LC-REVITALIZE (NCT06928272): recruiting. Registry updated 2026-10-06; checked 2026-10-14. Three months of study medication with follow-up to six months. Confirm eligibility, visits, monitoring and the locally available drug arm with the study team. Canadian listing

Next check: Check LC-REVITALIZE arm-specific results and Canadian availability; retain the distinction between lung-fibrosis and broader Long COVID outcomes.

Hi-OxSR breathing device

Evidence source check: 14 October 2026. Independent clinical review not performed.

Public summary: A small open-label pilot reported cognitive and symptom improvements, but without a control group it cannot establish benefit. A Canadian randomized study is testing the device; no results are posted in its registry.

Evidence: Uncontrolled pilot abstract; randomized results pending.

• Pilot report: The abstract reports 36 completers with improvements after device use. Repeat testing, expectations, natural changes and selection could contribute. This is a brief abstract hosted by the manufacturer, not a fully assessed randomized report. Sources: Hi-OxSR open-label pilot abstract — manufacturer-hosted copy
• Reported pilot harms: The abstract reports shortness of breath, nausea and headaches, with no severe adverse effects reported. A small uncontrolled study cannot establish safety or reliably detect uncommon harms. Sources: Hi-OxSR open-label pilot abstract — manufacturer-hosted copy
• Canadian randomized study: The planned 120 participants are divided among three groups testing device-use duration and oxygen/rebreathing conditions. Primary cognitive tests are assessed through two months. No registry results were posted when checked. Sources: Effect of Hi-OxSR for the Treatment of Post COVID Condition — registry

Limitations:

• The pilot's claims of safety and effectiveness exceed what an uncontrolled abstract can establish.
• The registry describes participants as knowing group allocation while being masked to the study hypothesis; this should not be presented as a fully blinded trial.
• Hi-OxSR is distinct from hyperbaric oxygen. Findings from HBOT cannot be transferred to this device.

Canada: The registry lists UHN Toronto as recruiting, while Edmonton and Sherbrooke remain not yet recruiting in the older record. RECLAIM's website lists enrollment open; confirm the specific site. Routine device access, cost and coverage were not verified. Sources: Effect of Hi-OxSR for the Treatment of Post COVID Condition — registry; RECLAIM investigator intervention page

• RECLAIM-HiOxSR (NCT06928506): recruiting. Registry updated 2025-09-15; checked 2026-10-14. Three device-use groups over two or four weeks with cognitive follow-up to two months. Device training, monitoring and site visits require confirmation. This is not HBOT or a home-use instruction. Canadian listing

Next check: Seek a full pilot report and randomized outcomes; reconcile site openings and assess device-specific harms and participation burden.

Stellate ganglion block (SGB)

Evidence source check: 14 October 2026. Independent clinical review not performed.

Public summary: A placebo-controlled trial did not demonstrate benefit for persistent post-COVID smell distortion. Uncontrolled studies report broader symptom improvements but cannot establish causation. Canadian trials are testing symptom and functional outcomes.

Evidence: Parosmia randomized trial negative; broader symptom evidence uncontrolled.

• Randomized parosmia trial: At three months, 13/30 SGB participants and 6/16 placebo participants met the prespecified response threshold. The study did not demonstrate superiority. This finding concerns smell distortion and the tested procedure, not every Long COVID symptom or block regimen. Sources: Stellate ganglion block randomized parosmia trial (2025)
• Broader symptoms: retrospective cohort: A survey-based study of 52 patients reported improvements after treatment. There was no untreated or placebo comparison, and recall and selection bias limit causal interpretation. Sources: Stellate ganglion block retrospective cohort (2025)
• Reported harms: The randomized trial reported transient hoarseness, congestion, headache and dizziness, with no serious or unexpected events reported. In the retrospective cohort, 13/52 reported adverse effects, including worsened post-exertional malaise; reported duration ranged from hours to months. Sources: Stellate ganglion block randomized parosmia trial (2025); Stellate ganglion block retrospective cohort (2025)
• Canadian studies: STAR-CO in Trois-Rivières and a Toronto cervicothoracic sympathetic block trial have no posted registry results. Their protocols and symptom targets differ from the published parosmia trial. Sources: Stellate Ganglion Block for Long COVID Symptoms: A Randomized Controlled Trial — registry; Cervicothoracic Sympathetic Block Evaluation for Post COVID Condition — registry

Limitations:

• Small, symptom-specific randomized evidence cannot settle effectiveness for every Long COVID presentation.
• Uncontrolled improvement does not separate treatment effects from other changes.
• The parosmia paper's abstract and Table 2 differ in the reported response-difference confidence interval. This summary reports the Table 2 counts and does not reproduce a disputed contrast.
• No serious event reported in a small trial is not proof that an invasive procedure is risk-free.

Canada: STAR-CO lists Trois-Rivières as recruiting. The Toronto registry lists Toronto Western recruiting and Women's College not yet recruiting. Confirm the site, protocol, eligibility and procedural risks with the study team. Routine Long COVID access and coverage were not verified. Sources: Stellate Ganglion Block for Long COVID Symptoms: A Randomized Controlled Trial — registry; Cervicothoracic Sympathetic Block Evaluation for Post COVID Condition — registry

• Stellate ganglion block for post-COVID parosmia (NCT06253806): completed. Published completed-trial report; not a new registry-status check; checked 2026-10-14. A single ultrasound-guided injection, with symptom follow-up at one and three months. Canadian protocols differ.
• STAR-CO (NCT07374562): recruiting. Registry updated 2026-02-09; checked 2026-10-14. Injection procedure with primary symptom/function assessments at four weeks and follow-up through 26 weeks. Ask about procedural risks, monitoring and travel. Canadian listing
• CeASE (NCT07468604): recruiting. Registry updated 2026-10-09; checked 2026-10-14. Two injection procedures over six weeks; symptom and autonomic assessments afterward. Toronto Western is listed recruiting; Women's College is not yet recruiting. Canadian listing

Next check: Monitor Canadian randomized outcomes and harms; reconcile the parosmia report's numerical discrepancy before adding a confidence-interval estimate.

Guanfacine + N-acetylcysteine (NAC)

Evidence source check: 14 October 2026. Independent clinical review not performed.

Evidence status: Uncontrolled reports; benefit remains uncertain.

Public summary: A small uncontrolled report described cognitive improvements with guanfacine plus NAC. It does not establish that the combination caused the improvement. Low blood pressure and dizziness led some patients to stop treatment.

Combination: 12-patient case series

Eight of 12 patients reported cognitive improvement. Four discontinued: two for unspecified reasons and two because of low blood pressure and/or dizziness. There was no control group or blinded assessment.

Sources: Guanfacine + NAC: 12-patient case series (online 2022).

Guanfacine alone: separate case report

A 2024 report described improved symptoms and cognitive test performance in one patient over six months. NAC was not part of that treatment. This is not confirmation of the combination or evidence of an average treatment effect.

Sources: Guanfacine alone: single-patient report (2024).

Patient survey: research context

A 2025 ME/CFS and Long COVID survey included the combination. Self-selected, retrospective treatment experiences can inform research questions but do not establish efficacy; concurrent treatments, recall and selection bias limit interpretation.

Sources: Patient-reported treatment survey (2025).

Limits

• Eight reported improvements out of 12 is not a reliable success rate for future patients. Without a comparison group, natural changes, expectations and other treatments cannot be separated from a drug effect.
• The case series does not isolate the contribution of guanfacine from NAC. The separate guanfacine-only case must not be pooled as another combination recipient.
• These small reports cannot establish safety, lasting benefit, or applicability to people with severe disease or post-exertional malaise.
• No controlled trial of this combination for Long COVID cognition was identified in the recorded search. This targeted search is not proof that none exists.

Trial search and Canada

The live condition-specific registry query returned zero records; the broader guanfacine query returned 97 records whose titles, conditions and intervention fields were screened. No trial specifically testing this combination for Long COVID cognition was identified. The POTS guanfacine/cromolyn record is a different intervention question. Search terminology and single-registry coverage can miss studies.

No Canadian trial of this combination was identified in this targeted registry search. Canadian authorization for this use, availability and coverage have not been verified. This entry provides no dosing or prescribing instructions.

Sources: ClinicalTrials.gov: guanfacine and Long COVID search; ClinicalTrials.gov: guanfacine across conditions.

Next check: Check for controlled cognitive-outcome studies, comparative harms and Canadian access information. Keep guanfacine-only and combination findings separate.

Dapagliflozin

Evidence source check: 15 October 2026. Independent clinical review not performed.

Evidence status: Upcoming Canadian trial; no posted registry results.

Public summary: The planned Canadian DALCO trial will compare dapagliflozin with placebo in adults with Long COVID. The registry still says not yet recruiting and has no posted results; it does not establish a Long COVID treatment benefit.

Planned randomized comparison

The registry plans 192 participants, with dapagliflozin or placebo over 12 months. Its primary outcome is the six-month change in an EQ-5D-derived health utility score. These are design details, not results.

Recruitment and evidence status

The record remained not yet recruiting when checked on 15 October 2026. The estimated September 2026 start date has passed, but an estimated date does not establish that recruitment opened. No results are posted in this registry record.

Limits

• This entry describes one registered planned study, not a completed evidence review of all dapagliflozin research.
• There are no posted trial outcome or adverse-event results to interpret. Absence of results is not evidence of safety or benefit.
• The study excludes several groups, including people with diabetes, prior heart failure or severe renal impairment. Applicability outside the eligibility criteria cannot be assumed.

Canada

The University of Ottawa Heart Institute is the listed Canadian site. Confirm recruitment with the study team. This trial listing does not establish approval for Long COVID, coverage or routine treatment access.

Source: DALCO registry. Canadian study details.

Next check: Check for recruitment updates and posted or published outcomes. Review comparative benefit and harms before drawing a treatment conclusion.

Modafinil or solriamfetol

Evidence source check: 16 October 2026. Independent clinical review not performed.

Public summary: RECOVER-SLEEP tested wakefulness medicines for excessive daytime sleepiness after COVID. The trial is completed, but its registry has no posted results. Long COVID benefit remains unestablished.

Participants received modafinil or placebo; people unable to take modafinil could receive solriamfetol or placebo. The medicines form one wakefulness-treatment comparison, not two independent trials.

No results are posted in this registry record as of 16 October 2026. Completion and enrolment counts are not evidence of benefit or safety.

This is a scoped registry summary, not an exhaustive publication review.

Effects on PEM, severe Long COVID and long-term functioning cannot be inferred from the study design.

Sleepiness, fatigue and post-exertional symptom worsening are different problems; these findings cannot be assumed to apply to all three.

This completed study lists US sites only. Canadian Long COVID authorization, supply and coverage have not been verified; a research listing is not a prescribing recommendation.

Sources: RECOVER-SLEEP Modafinil or solriamfetol registry.

Melatonin + light therapy

Evidence source check: 16 October 2026. Independent clinical review not performed.

Public summary: RECOVER-SLEEP tested melatonin and tailored light for sleep problems after COVID. The completed trial has no posted registry results. This does not establish a Long COVID treatment benefit.

The trial compared active or placebo melatonin and active or control light, alongside a tailored sleep schedule. It studied the treatment components within one trial.

No results are posted in this registry record as of 16 October 2026. Completion and enrolment counts are not evidence of benefit or safety.

This is a scoped registry summary, not an exhaustive publication review.

Effects on PEM, severe Long COVID and long-term functioning cannot be inferred from the study design.

Sleepiness, fatigue and post-exertional symptom worsening are different problems; these findings cannot be assumed to apply to all three.

This completed study lists US sites only. Canadian Long COVID authorization, supply and coverage have not been verified; a research listing is not a prescribing recommendation.

Sources: RECOVER-SLEEP Melatonin + light therapy registry.

Pacing and energy management

Evidence source check: 16 October 2026. Independent clinical review not performed.

Public summary: Pacing adapts activity and rest to a person’s limits to reduce post-exertional symptom flare-ups. It is supportive care, not evidence that Long COVID is cured.

CDC Long COVID guidance links to activity-management approaches for PEM. Its ME/CFS resource describes balancing rest and activity within individual limits.

Guidance does not provide a randomized Long COVID effect estimate.

Individual limits differ and can change. Physical and mental activity can both trigger delayed symptoms.

Pacing should not be turned into fixed activity increases or instructions to push through symptoms.

Discuss an individual plan and support needs with a clinician familiar with PEM. This entry does not prescribe an activity target or a graded exercise programme.

Sources: CDC Long COVID clinical guidance; CDC ME/CFS activity-management guidance.

How these notes are maintained

These notes cover all eighteen treatment summaries in the public tracker. They are a curated resource, not a systematic review. The evidence data separates interventions, trial/appendix/platform records, outcome findings, access facts, source records, recorded searches and unresolved review questions. Enrolment totals, protocols and efficacy results are distinct evidence types.

Evidence-summary check dates, registry update dates and trial-record check dates describe different things. LC-REVITALIZE's shared registry record was rechecked on 14 October; the upadacitinib evidence-summary check remains 13 October. This editorial cleanup does not refresh either date. Recruitment and access statements describe the dated checks recorded here, not confirmation of current availability.

The web and downloadable notes use the same content. All eighteen treatment summaries, their limitations and source links are readable without JavaScript. The Canadian directory separately displays recheck dates and a date-based notice after 30 days; this does not fetch registry updates or confirm recruitment.

Independent clinical review has not been performed and remains deferred. No formal certainty assessment is claimed. The optional historical reviewer worksheet covers the original eight entries; it is not a completed review of these eighteen summaries. No recurring monitoring is active. Recruitment inquiries for adolescent taurine and Hi-OxSR were sent on 14 October 2026; replies are pending and no recruitment status has been changed on that basis.

Outstanding source checks

These are unresolved questions carried forward from the recorded reviews. They are not newly verified claims that results or recruitment updates remain unavailable.

• PREVAIL-LC: obtain the adjusted between-group contrast and unblinding chronology when a full report or investigator clarification becomes available.
• RECOVER-AUTONOMIC ivabradine: reconcile conference findings, the care interaction and harms against a full efficacy report when available.
• BC LDN and RECOVER IVIG: check outcome and harms reports when new primary-source information appears.
• LIFT and COVIVA: obtain current recruitment information before describing openings as confirmed.
• Canadian participation: confirm LC-REVITALIZE drug-arm availability, adolescent taurine start/sites, and the Hi-OxSR site discrepancy when registry or study-team information changes.
• Evidence details: seek the full Hi-OxSR pilot report and resolve the parosmia paper's inconsistent response-difference intervals before adding stronger interpretations or a confidence-interval estimate.
• Canadian access: verify authorization, supply and coverage from the relevant official sources before adding an access claim.

LCAC sets editorial priorities; source checks depend on new primary-source information or study-team replies. No response deadline has been agreed. A publication, correction, registry change or team reply should trigger a scoped update.