Introduction
Definitions of Long COVID
Prevalence of Long-COVID syndrome after the acute SARS-CoV-2 infection
Susceptibility to Long COVID
Potential preventive options of Long COVID
Vaccines
Antiviral compounds
Oral | Parenteral |
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Paxlovid: nirmatrelvir (protease inhibitor, inhibition of the virus replication) + ritonavir (slows the breakdown of nirmatrelvir by inhibiting CYP3A4) | Remdesivir: prodrug of an adenosine analogue, the active metabolite of remdesivir interferes with the action of viral RNA-dependent RNA polymerase and inhibits viral replication (Recommended for both non-hospitalized and hospitalized patients (WHO, September, 2022) |
Molnupiravir: prodrug of N-hydroxycytidine (NHC). After phosphorylation in the cell to NHC triphosphate, it is incorporated into viral RNA and misdirects the viral polymerase and inhibits viral replication | Bebtelovimab: monoclonal antibody, isolated from a patient recovered from the COVID-19 disease, directed against the spike protein of the virus. (For the treatment of high-risk outpatients with mild-to-moderate COVID-19, if Paxlovid and remdesivir are not available.) |
Glucocorticoids
Ongoing and recently completed clinical trials with drugs and dietary supplements for the management of Long Covid syndrome
NCT number | Title | Interventions | |
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1 | NCT05618587 | Effect of Lithium Therapy on Long COVID Symptoms | Drug: Lithium Drug: Placebo |
2 | NCT04997395 | Feasibility of Cannabidiol for the Treatment of Long COVID | Drug: MediCabilis Cannabis sativa 50 |
3 | NCT05595369 | SARS CoV-2 Viral Persistence Study (PASC)—Study of Long COVID-19 | Drug: Paxlovid Drug: Placebo |
4 | NCT05576662 | Paxlovid for Treatment of Long Covid | Drug: Nirmatrelvir + Ritonavir Drug: Placebo + Ritonavir |
5 | NCT05220280 | SOLIDARITY Finland Plus Long-COVID | Drug: Imatinib Drug: Infliximab |
6 | NCT05513560 | Canadian Adaptive Platform Trial for Long COVID-19 | Drug: Ibudilast Drug: Pentoxifylline Other: Placebo |
7 | NCT04978259 | SOLIDARITY Finland Long-COVID (Remdesivir Long-term Follow-up Study of COVID Patients) | Drug: Remdesivir |
8 | NCT05592418 | Study to Evaluate the Efficacy and Safety of Ampligen in Patients With Post-COVID Conditions | Drug: Rintatolimod Other: Placebo/Normal Saline |
9 | NCT04604704 | Pilot Study Into LDN and NAD + for Treatment of Patients With Post-COVID-19 Syndrome | Drug: Naltrexone Dietary Supplement: NAD + |
10 | NCT05216614 | Fluvoxamine to Augment Olfactory Recovery For Long COVID-19 Parosmia | Drug: Fluvoxamine Drug: Placebo |
11 | NCT04695704 | Efficacy of Montelukast in Mild-moderate Respiratory Symptoms in Patients With Long-COVID-19: | Drug: Montelukast Other: placebo |
12 | NCT04948203 | Assessing the Efficacy of Sirolimus in Patients With COVID-19 Pneumonia for Prevention of Post-COVID Fibrosis | Drug: Sirolimus |
13 | NCT05507372 | Treatment for post acute COVID-19 Syndrome | Drug: Pimozide |
14 | NCT04904536 | Statin TReatment for COVID-19 to Optimise NeuroloGical recovERy | Drug: Atorvastatin Other: Standard Care |
15 | NCT05497089 | Temelimab as a Disease Modifying Therapy in Patients With Neuropsychiatric Symptoms in Post-COVID 19 or PASC Syndrome | Drug: Temelimab Drug: Placebo |
16 | NCT05350774 | Immunotherapy for Neurological Post-Acute Sequelae of SARS-CoV-2 | Drug: IV immunoglobulin Drug: IV normal saline Drug: IV methylprednisolone |
17 | NCT05430152 | Low-dose Naltrexone for Post-COVID Fatigue Syndrome | Drug: Low-Dose Naltrexone Other: Placebo |
18 | NCT05096884 | Post-Acute Sequelae of Coronavirus-19 (COVID-19) With Dyspnea on Exertion And Associated TaChycardia TrEatment Study | Drug: Metoprolol Succinate |
19 | NCT05047952 | Vortioxetine for post-COVID-19 Condition | Drug: Vortioxetine Drug: Placebo |
20 | NCT05228899 | Zofin to Treat COVID-19 Long Haulers | Drug: Zofin Other: Placebo |
21 | NCT05052307 | A Real-world Evidence Study of BNT162b2 mRNA Covid-19 Vaccine in Brazil | Drug: Pfizer/BioNTech BNT162b2 mRNA COVID-19 vaccine, CoronaVac COVID-19 vaccine, ChAdOx1 nCoV-19 vid-19 Vaccine, Janssen COVID-19 Vaccine |
NCT number | Title | Aim | Interventions | Study design | Population | Results | |
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1 | NCT04871815 | Effects of Sodium Pyruvate Nasal Spray in COVID-19 Long Haulers | To examine the effects of N115 (Sodium pyruvate nasal spray) treatment on the symptoms associated with COVID-19 Long Haulers | Drug: sodium pyruvate nasal spray | Allocation: N/A Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment | Enrollment: 22 Age: 18 Years to 40 Years (Adult) Sex: All | Primary outcome data are available |
2 | NCT04795557 | Efficacy of Adaptogens in Patients With Long COVID-19 | To demonstrate possible efficacy of adjuvant treatment with ADAPT-232 in decreasing the duration of the convalescence, alleviation of fatigue, headache, attention deficit, difficult and rapid respiration, depression, anxiety and other symptoms of Long COVID-19 during rehabilitation period | Dietary Supplement: ADAPT-232 oral solution Other: Placebo oral solution | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) Primary Purpose: Treatment | Enrollment: 100 Age: 18 Years and older (Adult, Older Adult Sex: All | No results |
3 | NCT04880161 | A Study to Evaluate Ampion in Patients With Prolonged Respiratory Symptoms Due to COVID-19 (Long COVID) | To evaluate the safety of Ampion (low molecular weight filtrate of human serum albumin with the in vitro ability to modulate inflammatory cytokine levels) and the clinical outcomes in patients with Long COVID | Biological: Inhaled Ampion Other: Inhaled Placebo | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) Primary Purpose: Treatment | Enrollment: 32 Age: 18 Years and older (Adult, Older Adult) Sex: All | Results Submitted, but is not yet publicly available |
4 | NCT05311852 | Effects of PEA-LUT on Frontal Lobe Functions and GABAergic Transmission in Long-Covid Patients | To test the possible therapeutic effects of an 8-week therapy with PEA-LUT on GABAB-ergic neurotransmission, LTP-like synaptic plasticity, indexed with transient potentiation of motor evoked potentials (MEP) amplitude after repetitive TMS given as intermittent theta burst stimulation (iTBS) in Long COVID patients with cognitive complaints and fatigue | Dietary Supplement: palmitoylethanolami co-ultramicronized with antioxidant flavonoid luteolin (PEA-LUT) Dietary Supplement: Placebo | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double (Participant, Investigator) Primary Purpose: Treatment | Enrollment: 34 Age: 18 Years and older (Adult, Older Adult) Sex: All | No results |
5 | NCT04828668 | Study to Evaluate Benefits and Safety of Endourage Formula C™ Oral Drops in People With Post-Acute COVID-19 Syndrome | To evaluate the clinical benefits of Formula C on symptoms in adults who have documented PACS or persistence of effects consistent with COVID-19 and to assess the impact of Formula C on quality-of-life (QOL) in persons with PACS. The secondary objective was to assess the safety of Formula C in persons with PACS | Dietary Supplement: Targeted Wellness Formula C™ Sublingual Drops- 1200 mg–30 mL (Formula C) Dietary Supplement: Placebo | Allocation: Randomized Intervention Model: Crossover Assignment Masking: Single (Participant) Primary Purpose: Other | Enrollment: 32 Age: 18 Years to 75 Years (Adult, Older Adult) Sex: All | Given that both groups demonstrated improvement, both formulations may be contributing to these findings. Limitations include the small number of participants, the lack of a true placebo, and limited time on study products (Young et al. 2022) |
6 | NCT05152849 | Efficacy, Safety, Tolerability of AXA1125 in Fatigue After COVID-19 Infection | To compare the effects of AXA1125, an orally active mixture of amino acids, compared to placebo, on improving muscle function (metabolism) following moderate exercise in subjects with fatigue-Predominant Post-Acute Sequelae of SARS-CoV-2 as well as the safety and tolerability of AXA1125. Subjects will take one dose of AXA1125 or a placebo twice daily for 28 days | Drug: AXA1125 Drug: Placebo | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Triple (Participant, Care Provider, Investigator) Primary Purpose: Treatment | Enrollment: 41 Age: 18 Years to 64 Years (Adult) Sex: All | No results |
7 | NCT04652518 | LYT-100 in Post-acute COVID-19 Respiratory Disease | To evaluate the Safety and Efficacy of Deupirfenidone (LYT-100) in Post-acute COVID-19 Respiratory Disease | Drug: LYT-100 Other: Placebo | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Triple (Participant, Investigator, Outcomes Assessor) Primary Purpose: Treatment | Enrollment: 185 Age: 18 Years to 80 Years (Adult, Older Adult) Sex: All | No results |
8 | NCT04960215 | Coenzyme Q10 as Treatment for Long Term COVID-19 | To investigate the effect of high-dose Coenzyme Q10 on number and severity of self-reported symptoms in patients with Long Term COVID-19 | Drug: Coenzyme Q10 Drug: Placebo | Allocation: Randomized Intervention Model: Crossover Assignment Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) Primary Purpose: Treatment | Enrollment: 121 Age: 18 Years and older (Adult, Older Adult) Sex: All | No results |
9 | NCT04699097 | The Effect of Azithromycin Use on Conduction System of Heart in COVID-19 Positive Children | To evaluate the effect of Azithromycin on ventricular repolarization in COVID-19 positive pediatric patients | Drug: Azithromycin | Observational Model: Case-Only Time Perspective: Prospective | Enrollment: 105 Age: 1 Year to 18 Years (Child, Adult) Sex: All | No results |
10 | NCT04814914 | An observational clinical study to evaluate COVID-19 symptoms in “Long Hauler” patients who participated in K031-120 or K032-120 | To evaluate the presence of symptoms of COVID-19 infection in patients who participated in K031-120 or K032-120 (“long hauler”) | Other: KB109 is a novel glycan + Self Supportive Care Other: Self Supportive Care (SSC) Alone | Observational Model: Cohort Time Perspective: Prospective | Enrollment: 333 Age: 18 Years and older (Adult, Older Adult) Sex: All | No results |
11 | NCT04382755 | Zilucoplan® in improving oxygenation and short- and long-term outcome of COVID-19 patients with acute hypoxic respiratory failure | The hypothesis of the proposed intervention is that Zilucoplan® (complement C5 inhibitor) has profound effects on inhibiting acute lung injury post-COVID-19, and can promote lung repair mechanisms, that lead to a 25% improvement in lung oxygenation parameters. This hypothesis is based on experiments performed in mice showing that C5a blockade can prevent mortality and prevent ARDS in mice with post-viral acute lung injury | Drug: Zilucoplan® Drug: Placebo | Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Treatment | Enrollment: 81 Age: 18 Years and older (Adult, Older Adult) Sex: All | Complement C5 inhibition with zilucoplan led to numerically relevant respiratory and clinical improvements in hypoxemic COVID-19 patients with systemic inflammation, Zilucoplan lowered serum C5b-9 (p < 0.001) and interleukin-8 (p = 0.03) concentration compared with control. No relevant safety differences between the zilucoplan and control group were identified (De Leeuw et al. 2022) |
12 | NCT04678830 | COVID-19 Long-Haulers Study | To assess the safety and efficacy of leronlimab (PRO 140) administered as weekly subcutaneous injections in subjects experiencing prolonged symptoms (> 12 weeks) of COVID-19 | Drug: Placebos Drug: Leronlimab (700 mg) | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) Primary Purpose: Treatment | Enrollment: 56 Age: 18 Years and older (Adult, Older Adult) Sex: All | The mean symptom score changes from baseline to the latest available time point from day 30–56 for leronlimab vs placebo were –16.0 and –12.0, respectively; adjusting for prespecified covariates, the adjusted mean difference was –1.0 (not statistically significant). For several symptoms, there was a numerically higher percentage of participants with reduced raw symptom scores for leronlimab compared with placebo treatment reaching borderline statistical significance without correction for multiple comparisons due to the exploratory nature of this pilot study (Gaylis et al. 2022) |