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.

Life stressors significantly impact long-term outcomes and post-acute symptoms 12-months after COVID-19 hospitalization

“…However, patients who completed only 6-month follow-up (and were then lost to follow-up) were significantly older than those who completed 12-month follow-up (median age 69 years versus 65 years, P < 0.001) and had slightly higher body mass index ( Table 1 ). Among those who completed 12-month follow-up, the most common neurological post-COVID-19 symptoms reported were headache (22%), cognitive abnormalities (20%), anxiety (12%), depression (11%,), sleep disturbance (11%) and fatigue (10%, Supplemental Table 2) [ 23 ].…”

Subtypes of Post–COVID-19 Condition: A Review of the Emerging Evidence

“…At the time of editing this report, a prospective cohort study that examined hospitalized patients 12 months after their initial diagnosis was identified. 62 The study reported that symptoms clusters among their cohort also mapped to therapy clusters. For example, people within the symptoms cluster that reported shortness of breath and cognitive symptoms were more likely to receive physical and occupations therapy, while the cluster of those who reported higher anxiety and depression symptoms were more likely to receive anti-depressants, anti-anxiety, and psychological therapy interventions.…”

“…For example, people within the symptoms cluster that reported shortness of breath and cognitive symptoms were more likely to receive physical and occupations therapy, while the cluster of those who reported higher anxiety and depression symptoms were more likely to receive anti-depressants, anti-anxiety, and psychological therapy interventions. 62 It is likely that future studies will continue to identify other ways that assessing and identifying subtypes may guide health systems planning for delivering appropriate interventions.…”

Long COVID: Clinical Framing, Biomarkers, and Therapeutic Approaches

“…In another observational study that enrolled 242 patients, Frontera et al evaluated more than 100 patients reporting clinical manifestations more than 3 months after the diagnosis of COVID-19 and identified three main symptom groups, one with continuous symptoms, most commonly headache, one with many relevant symptoms, including high levels of anxiety and depression, and one reporting shortness of breath, headache, and cognitive symptoms [ 68 ]. In a cohort study, a higher prevalence of self-reported memory problems was found at eight months after SARS-CoV-2 positivity than in the control group represented by untested or negative test subjects [ 69 ].…”