NCT05618587

Effect of Lithium Therapy on Long COVID Symptoms

Completed Phase 2 Results posted Last updated 5 March 2025

What this trial tests

Phase 2 trial testing Lithium in Long COVID in 52 participants. Completed in 21 July 2023.

Timeline

28 November 2022

Primary endpoint
21 July 2023

21 July 2023

Quick facts

Lead sponsor	State University of New York at Buffalo
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	52
Start date	28 November 2022
Primary completion	21 July 2023
Estimated completion	21 July 2023
Sites	1 location across United States

Drugs / interventions tested

• Lithium
• Placebo

Conditions studied

• Long COVID — all drugs for Long COVID →

Sponsor

State University of New York at Buffalo

Who can join

Adults 18 to 80, any sex, with Long COVID. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Fatigue Severity Scale Primary · Change from baseline to day 21

7-item questionnaire assessing fatigue severity. Score range 1-49 with higher values signifying worse outcome

Group	Value	95% CI
Lithium	-11.3	± 12.6
Placebo	-8.6	± 12.3

Brain Fog Severity Scale Primary · Change from baseline to day 21

7-item questionnaire assessing brain fog severity. Score range 1-49 with higher values signifying worse outcome

Group	Value	95% CI
Lithium	-9.0	± 13.8
Placebo	-8.1	± 10.6

Patient Global Impression of Change (PGIC) Secondary · Day 21

Change in symptoms on 7-point scale. Single-item scale. Score range 1-7 with higher values signifying better outcome

Group	Value	95% CI
Lithium	4.7	± 1.1
Placebo	4.6	± 1.2

Well-Being Scale Secondary · Change from baseline to day 21

Sense of well-being over past week on 10-point scale. Score range 0-10 with higher values signifying better outcome.

Group	Value	95% CI
Lithium	1.0	± 2.0
Placebo	0.9	± 2.1

Short Form-12 Health Survey (1-week Modification) Secondary · Change from baseline to day 21

Quality of life assessment over past week, PCS-subscale. 12-item quality of life scale. Score range 0-100 for both the Physical Component Score and the Mental Component Score with higher values signifying better outcomes.

Group	Value	95% CI
Lithium	5.1	± 8.5
Placebo	4.2	± 11.1

Desire to Continue Therapy Secondary · Day 21

Single Yes/No question. Single-item scale. Score range 1-2 with higher value signifying better outcome. Reported as % of respondents recording "yes".

Group	Value	95% CI
Lithium	12
Placebo	13

Generalized Anxiety Disorder-2 Scale Secondary · Change from baseline to day 21

2-item questionnaire assessing anxiety frequency over the past week. 2-item scale. Score range 0-6 with higher values signifying worse outcome

Group	Value	95% CI
Lithium	-0.8	± 1.7
Placebo	-1.4	± 1.7

Headache and Body Pain Bother Scale Secondary · Change from baseline to day 21

2-item questionnaire assessing frequency of headaches and body pain over the past week, Headache score. 2-item scale. Score range 2-10 with higher values signifying worse outcome

Group	Value	95% CI
Lithium	-0.6	± 0.7
Placebo	-0.7	± 1.2

Insomnia Severity Index Secondary · Change from baseline to day 21

7-item questionnaire assessing insomnia severity over the past week. 7-item scale. Score range 0-28 with higher values signifying worse outcome.

Group	Value	95% CI
Lithium	-6.0	± 6.7
Placebo	-4.4	± 4.8

Sense of Smell and Taste Change Scale Secondary · Day 21

Subjective change from baseline on a 7-point scale (score range: 1-7) with higher scores indicating better outcomes. Scores of 1 and 7 indicate sense of smell and taste were "very much worse" or "very much improved", respectively, since the start of study treatment.

Group	Value	95% CI
Lithium	4.1	± 0.3
Placebo	4.2	± 0.4

Digit Symbol Substitution Test Secondary · Change from baseline to day 21

Validated cognitive test. Score range 0-100 with higher scores indicating a better outcome.

Group	Value	95% CI
Lithium	4.3	± 5.9
Placebo	6.6	± 9.0

Delayed Recall Test Secondary · Change from baseline to day 21

Validated cognitive test. Score range 0-5 with higher scores indicating better outcomes.

Group	Value	95% CI
Lithium	0.46	± 1.02
Placebo	0.35	± 0.80

Sponsor's own description

This study will assess low-dose lithium's effects on several different symptoms experienced by long COVID patients.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Pathogenesis Underlying Neurological Manifestations of Long COVID Syndrome and Potential Therapeutics.
   Leng A, Shah M, Ahmad SA, Premraj L, et al · · 2023 · cited 124× · PMID 36899952 · DOI 10.3390/cells12050816
2. The long-term health outcomes, pathophysiological mechanisms and multidisciplinary management of long COVID.
   Li J, Zhou Y, Ma J, Zhang Q, et al · · 2023 · cited 91× · PMID 37907497 · DOI 10.1038/s41392-023-01640-z
3. Therapeutic trials for long COVID-19: A call to action from the interventions taskforce of the RECOVER initiative.
   Bonilla H, Peluso MJ, Rodgers K, Aberg JA, et al · · 2023 · cited 72× · PMID 36969241 · DOI 10.3389/fimmu.2023.1129459
4. Fighting Post-COVID and ME/CFS - development of curative therapies.
   Scheibenbogen C, Bellmann-Strobl JT, Heindrich C, Wittke K, et al · · 2023 · cited 32× · PMID 37396922 · DOI 10.3389/fmed.2023.1194754
5. Long COVID and possible preventive options.
   Sebők S, Gyires K. · · 2023 · cited 19× · PMID 37344737 · DOI 10.1007/s10787-023-01204-1
6. Lithium Aspartate for Long COVID Fatigue and Cognitive Dysfunction: A Randomized Clinical Trial.
   Guttuso T, Zhu J, Wilding GE. · · 2024 · cited 7× · PMID 39356507 · DOI 10.1001/jamanetworkopen.2024.36874
7. The current landscape of long COVID clinical trials: NIH's RECOVER to Stanford Medicine's STOP-PASC initiative.
   Chakraborty C, Bhattacharya M. · · 2023 · cited 7× · PMID 37680987 · DOI 10.1016/j.omtn.2023.08.016
8. SARS-Cov2 seasonality and adaptation are driven by solar activity.
   Gonzalez-Lugo O. · · 2023 · DOI 10.21203/rs.3.rs-2797280/v3