long COVID-19

Summary

long COVID-19 (MONDO:0100233) is a disease with 1 cohort gene and 76 clinical trials. Top therapeutic interventions include solriamfetol, nirmatrelvir, and ivabradine.

At a glance

• Cohort genes: 1
• ClinVar variants: 1
• Clinical trials: 76

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	long COVID-19
Mondo ID	MONDO:0100233
MeSH	D000094024
DOID	DOID:0080848
NCIT	C179263
UMLS	C5433293
MedGen	1735839
MedDRA	10085503, 10085504
Is cancer (heuristic)	no

Also known as: long haul COVID-19 · long-haul COVID-19 · PASC · post-acute sequelae of COVID-19 · post-acute sequelae of SARS-CoV-2 infection · sequelae of COVID-19

Data availability: 1 ClinVar variant · 1 cell line.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of primarily extrinsic mechanism › post-infectious disorder › post-viral disorder › post-COVID-19 disorder › long COVID-19

Related subtypes (1): multisystem inflammatory syndrome in children and adults

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

1 retrieved; paginated sample, class counts are floors:

1 likely risk allele

ClinVar	Variant (HGVS)	Gene	Classification	Review
2687869	NM_001243133.2(NLRP3):c.278-1889G>C	NLRP3	Likely risk allele	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 4 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NLRP3	Orphanet:1451	CINCA syndrome
NLRP3	Orphanet:47045	Familial cold urticaria
NLRP3	Orphanet:575	Muckle-Wells syndrome
NLRP3	Orphanet:647815	Keratitis fugax hereditaria

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
NLRP3	HGNC:16400	ENSG00000162711	Q96P20	NACHT, LRR and PYD domains-containing protein 3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NLRP3	NACHT, LRR and PYD domains-containing protein 3	Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyroptosis.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
NLRP3	Other/Unknown	no		Leu-rich_rpt, DAPIN, NACHT_NTPase

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
leukocyte	1
monocyte	1
mononuclear cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NLRP3	172	broad	marker	monocyte, mononuclear cell, leukocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NLRP3	3,797

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NLRP3	Q96P20	24

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
The NLRP3 inflammasome	1	671.8×	0.005	NLRP3
Purinergic signaling in leishmaniasis infection	1	423.0×	0.005	NLRP3
Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells	1	356.9×	0.005	NLRP3
Metalloprotease DUBs	1	300.5×	0.005	NLRP3
SARS-CoV-1 activates/modulates innate immune responses	1	271.9×	0.005	NLRP3
Cytoprotection by HMOX1	1	184.2×	0.006	NLRP3
SARS-CoV-2 activates/modulates innate and adaptive immune responses	1	89.2×	0.011	NLRP3

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
detection of biotic stimulus	1	4213.0×	0.003	NLRP3
negative regulation of acute inflammatory response	1	2407.4×	0.003	NLRP3
positive regulation of type 2 immune response	1	2407.4×	0.003	NLRP3
NLRP3 inflammasome complex assembly	1	2407.4×	0.003	NLRP3
positive regulation of T-helper 2 cell differentiation	1	2106.5×	0.003	NLRP3
osmosensory signaling pathway	1	1532.0×	0.003	NLRP3
positive regulation of T-helper 2 cell cytokine production	1	1532.0×	0.003	NLRP3
pattern recognition receptor signaling pathway	1	991.3×	0.004	NLRP3
positive regulation of interleukin-4 production	1	561.7×	0.005	NLRP3
negative regulation of interleukin-1 beta production	1	510.7×	0.005	NLRP3
pyroptotic inflammatory response	1	510.7×	0.005	NLRP3
negative regulation of non-canonical NF-kappaB signal transduction	1	510.7×	0.005	NLRP3
positive regulation of interleukin-1 beta production	1	259.3×	0.008	NLRP3
positive regulation of non-canonical NF-kappaB signal transduction	1	255.3×	0.008	NLRP3
defense response	1	216.1×	0.008	NLRP3
obsolete positive regulation of NF-kappaB transcription factor activity	1	205.5×	0.008	NLRP3
cellular response to virus	1	200.6×	0.008	NLRP3
regulation of inflammatory response	1	168.5×	0.009	NLRP3
protein maturation	1	163.6×	0.009	NLRP3
positive regulation of inflammatory response	1	145.3×	0.010	NLRP3
negative regulation of inflammatory response	1	137.0×	0.010	NLRP3
protein homooligomerization	1	122.1×	0.010	NLRP3
cellular response to lipopolysaccharide	1	98.0×	0.012	NLRP3
inflammatory response	1	37.7×	0.031	NLRP3
innate immune response	1	33.6×	0.033	NLRP3
apoptotic process	1	28.7×	0.038	NLRP3
signal transduction	1	16.1×	0.065	NLRP3
positive regulation of transcription by RNA polymerase II	1	14.9×	0.067	NLRP3

Therapeutics

Drugs indicated for this disease

0 approved, 3 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Metformin	Phase 3 (in late-stage trials)
Microcrystalline Cellulose	Phase 3 (in late-stage trials)
Oxygen	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Cannabidiol, Celecoxib, Fluvoxamine, Human Immunoglobulin G, Ibudilast, Ivabradine, Lithium Carbonate, Naltrexone, Nicotinamide Riboside, Nirmatrelvir, Pentoxifylline, Rintatolimod, Ritonavir, Sodium Chloride, Valacyclovir.

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 0

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
NLRP3	CLOMIPHENE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
NLRP3	11	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CLOMIPHENE	4	NLRP3
GLYBURIDE	4	NLRP3
CURCUMIN	3	NLRP3
JT-001	3	NLRP3
TRICLOCARBAN	2	NLRP3
CLIOXANIDE	2	NLRP3
DAPANSUTRILE	2	NLRP3
USNOFLAST	2	NLRP3
INZOMELID	1	NLRP3
BMS-986299	1	NLRP3
NT-0796	1	NLRP3

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
NLRP3	534	Binding:527, Functional:6, ADMET:1

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
NLRP3	534

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

11 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
CLOMIPHENE	4	NLRP3
GLYBURIDE	4	NLRP3
CURCUMIN	3	NLRP3
JT-001	3	NLRP3
TRICLOCARBAN	2	NLRP3
CLIOXANIDE	2	NLRP3
DAPANSUTRILE	2	NLRP3
USNOFLAST	2	NLRP3
INZOMELID	1	NLRP3
BMS-986299	1	NLRP3
NT-0796	1	NLRP3

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	NLRP3
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 76.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	52
PHASE2	20
PHASE1	2
PHASE2/PHASE3	1
PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06960928	PHASE3	RECRUITING	Low Dose Sirolimus in People With Post-Acute Sequelae of COVID-19 (PASC) Long COVID-19
NCT05513560	PHASE2/PHASE3	COMPLETED	RECLAIM: Recovering From COVID-19 Lingering Symptoms Adaptive Integrative Medicine
NCT05690503	PHASE2	ACTIVE_NOT_RECRUITING	Glutamatergic Modulation as a Treatment for Depressive Symptoms Among Patients With Post-acute Sequelae of COVID (PASC): A Pilot Trial
NCT05747534	PHASE2	ACTIVE_NOT_RECRUITING	AT1001 for the Treatment of Long COVID
NCT06161688	PHASE2	ACTIVE_NOT_RECRUITING	Ensitrelvir for Viral Persistence and Inflammation in People Experiencing Long COVID
NCT06204432	PHASE2	ACTIVE_NOT_RECRUITING	Sodium Citrate in Smell Retraining for People With Post-COVID-19 Olfactory Dysfunction
NCT06305793	PHASE2	ACTIVE_NOT_RECRUITING	RECOVER-AUTONOMIC: Platform Protocol, Appendix A (IVIG)
NCT06366724	PHASE2	RECRUITING	LIFT: Life Improvement Trial
NCT06404099	PHASE2	ACTIVE_NOT_RECRUITING	RECOVER-SLEEP: Platform Protocol, Appendix_A (Hypersomnia)
NCT06404112	PHASE2	ACTIVE_NOT_RECRUITING	RECOVER-SLEEP: Platform Protocol, Appendix_B (CPSD)
NCT06940609	PHASE2	RECRUITING	Magnetic Resonance Analysis of Neural Inflammatory Factors and External Stimulation
NCT07123727	PHASE2	RECRUITING	A Study to Examine Anktiva for the Treatment of COVID-19.
NCT07597902	PHASE2	NOT_YET_RECRUITING	SARS-CoV-2 and Herpesvirus Inhibition for Ending Long COVID Dysfunction
NCT04604704	PHASE2	COMPLETED	Pilot Study Into LDN and NAD+ for Treatment of Patients With Post-COVID-19 Syndrome
NCT05152849	PHASE2	COMPLETED	Efficacy, Safety, Tolerability of AXA1125 in Fatigue After COVID-19 Infection
NCT05472090	PHASE2	COMPLETED	A Phase 2 Study to Evaluate the Efficacy and Safety of TNX-102 SL in Patients With Multi-Site Pain Associated With Post-Acute Sequelae of SARS-CoV-2 Infection
NCT05576662	PHASE2	COMPLETED	Paxlovid for Treatment of Long Covid
NCT05719012	PHASE2	WITHDRAWN	Efficacy and Safety of Umbilical Cord Mesenchymal Stem Cells in the Treatment of Long COVID-19
NCT05965726	PHASE2	COMPLETED	RECOVER-VITAL: Platform Protocol, Appendix to Measure the Effects of Paxlovid on Long COVID Symptoms
NCT06305780	PHASE2	COMPLETED	RECOVER-AUTONOMIC Platform Protocol
NCT06305806	PHASE2	COMPLETED	RECOVER-AUTONOMIC: Platform Protocol, Appendix B (Ivabradine)
NCT06404086	PHASE2	COMPLETED	RECOVER-SLEEP: Platform Protocol
NCT06920628	PHASE1	RECRUITING	PET Imaging of Cyclooxygenase-1 in Participants With Neurological Manifestations of Post-Acute Sequelae of SARS-CoV-2 Infection (PASC)
NCT05638620	PHASE1	COMPLETED	Dual Sympathetic Blocks for Patients Experiencing Sympathetically-Mediated Symptoms From Long COVID
NCT05057676	Not specified	RECRUITING	Autoimmune Intervention Mastery Course Study
NCT05092516	Not specified	ACTIVE_NOT_RECRUITING	Home-based Brain Stimulation Treatment for Post-acute Sequelae of COVID-19 (PASC)
NCT05167227	Not specified	ACTIVE_NOT_RECRUITING	Does a Technology Enabled Multi-disciplinary Team-based Care Model for the Management of Long COVID and Other Fatiguing Illnesses Improve Clinical Care of Patients and Represent a Sustainable Approach Within a Federally Qualified Health Center?
NCT05190718	Not specified	RECRUITING	Register Study: Implementation of Pharyngeal Electrostimulation Therapy for the Treatment of Acute Neurogenic Dysphagia
NCT05225688	Not specified	ACTIVE_NOT_RECRUITING	Skeletal Muscle in PASC and ME/CFS Patients
NCT05293366	Not specified	RECRUITING	LOng COvid COmorbidities: Endocrine,Metabolic,Neuropsychiatric,Muscle,Cardiovascular,Pulmonary,Dermatologic Dysfunctions
NCT05379556	Not specified	RECRUITING	LOng COvid COmorbidities: Andrological, Reproductive, Sexual Dysfunctions in Patients Recovered From COVID-19
NCT05471011	Not specified	ACTIVE_NOT_RECRUITING	COVID-19 Outcome Prediction Algorithm
NCT05566483	Not specified	RECRUITING	Physiology of Long COVID-19 and the Impact of Cardiopulmonary Rehabilitation on Quality-of-Life and Functional Capacity
NCT05914649	Not specified	RECRUITING	NC Testing in LC & POTS
NCT06045338	Not specified	RECRUITING	Mind Body Intervention for Long COVID-19
NCT06073002	Not specified	ACTIVE_NOT_RECRUITING	Effects of a Home-Based Exercise Intervention in Subjects with Long COVID
NCT06156176	Not specified	RECRUITING	Pursuing Reduction in Fatigue After COVID-19 Via Exercise and Rehabilitation (PREFACER): A Randomized Feasibility Trial
NCT06159309	Not specified	ACTIVE_NOT_RECRUITING	Quality of Life After Hyperbaric Oxygen Therapy in Post-COVID Patients
NCT06291870	Not specified	RECRUITING	Predictors of Post-COVID-19 Clinical and Cognitive Consequences
NCT06404060	Not specified	ACTIVE_NOT_RECRUITING	RECOVER-ENERGIZE Platform Protocol_Appendix A (Exercise Intolerance)

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
SOLRIAMFETOL	4	6
NIRMATRELVIR	4	3
IVABRADINE	4	2
MODAFINIL	4	2
IBUDILAST	4	1
NOGAPENDEKIN ALFA INBAKICEPT	4	1
PENTOXIFYLLINE	4	1
PYRIDOSTIGMINE	4	1
SODIUM CITRATE	4	1
VALACYCLOVIR	4	1
ENSITRELVIR	3	1
LARAZOTIDE ACETATE	3	1
NADIDE	2	1
CHEMBL4204890	0	1
CHEMBL5201264	0	1
CHEMBL6145506	0	1