{"doi":"10.1371/journal.pone.0275274","title":"Post-acute sequelae of COVID-19 symptom phenotypes and therapeutic strategies: A prospective, observational study","abstract":"BACKGROUND: Post-acute sequelae of COVID-19 (PASC) includes a heterogeneous group of patients with variable symptomatology, who may respond to different therapeutic interventions. Identifying phenotypes of PASC and therapeutic strategies for different subgroups would be a major step forward in management. METHODS: In a prospective cohort study of patients hospitalized with COVID-19, 12-month symptoms and quantitative outcome metrics were collected. Unsupervised hierarchical cluster analyses were performed to identify patients with: (1) similar symptoms lasting ≥4 weeks after acute SARS-CoV-2 infection, and (2) similar therapeutic interventions. Logistic regression analyses were used to evaluate the association of these symptom and therapy clusters with quantitative 12-month outcome metrics (modified Rankin Scale, Barthel Index, NIH NeuroQoL). RESULTS: Among 242 patients, 122 (50%) reported ≥1 PASC symptom (median 3, IQR 1-5) lasting a median of 12-months (range 1-15) post-COVID diagnosis. Cluster analysis generated three symptom groups: Cluster1 had few symptoms (most commonly headache); Cluster2 had many symptoms including high levels of anxiety and depression; and Cluster3 primarily included shortness of breath, headache and cognitive symptoms. Cluster1 received few therapeutic interventions (OR 2.6, 95% CI 1.1-5.9), Cluster2 received several interventions, including antidepressants, anti-anxiety medications and psychological therapy (OR 15.7, 95% CI 4.1-59.7) and Cluster3 primarily received physical and occupational therapy (OR 3.1, 95%CI 1.3-7.1). The most severely affected patients (Symptom Cluster 2) had higher rates of disability (worse modified Rankin scores), worse NeuroQoL measures of anxiety, depression, fatigue and sleep disorder, and a higher number of stressors (all P<0.05). 100% of those who received a treatment strategy that included psychiatric therapies reported symptom improvement, compared to 97% who received primarily physical/occupational therapy, and 83% who received few interventions (P = 0.042). CONCLUSIONS: We identified three clinically relevant PASC symptom-based phenotypes, which received different therapeutic interventions with varying response rates. These data may be helpful in tailoring individual treatment programs.","journal":"PLoS ONE","year":2022,"id":238723,"datarank":0.6010999777848708,"base_score":4.007333185232471,"endowment":4.007333185232471,"self_citation_contribution":0.6010999777848708,"citation_network_contribution":0.0,"self_endowment_contribution":0.6010999777848708,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":54,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.7762,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":389936,"name":"Lorna E. Thorpe","orcid":"0000-0002-5535-2674","position":1,"is_corresponding":false},{"id":366662,"name":"Naomi M. Simon","orcid":"0000-0002-8867-889X","position":2,"is_corresponding":false},{"id":421725,"name":"Adam de Havenon","orcid":"0000-0001-8178-8597","position":3,"is_corresponding":false},{"id":627688,"name":"Shadi Yaghi","orcid":"0000-0001-5974-4336","position":4,"is_corresponding":false},{"id":863915,"name":"Sakinah Sabadia","orcid":null,"position":5,"is_corresponding":false},{"id":623567,"name":"Dixon Yang","orcid":"0000-0002-7155-8904","position":6,"is_corresponding":false},{"id":409232,"name":"Ariane Lewis","orcid":"0000-0002-0756-7320","position":7,"is_corresponding":false},{"id":623582,"name":"Kara Melmed","orcid":"0000-0003-4084-8586","position":8,"is_corresponding":false},{"id":476807,"name":"Laura J. Balcer","orcid":"0000-0002-5136-4539","position":9,"is_corresponding":false},{"id":231338,"name":"Thomas Wısnıewskı","orcid":"0000-0002-3379-8966","position":10,"is_corresponding":false},{"id":623584,"name":"Steven Galetta","orcid":"0000-0003-3781-7324","position":11,"is_corresponding":false},{"id":108633,"name":"Jennifer Frontera","orcid":"0000-0002-0719-2522","position":0,"is_corresponding":true}],"reference_count":41,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:22:31.741535Z","pmid":"36174032","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}