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Published on: August 4, 2023
Exploring Coagulation Abnormalities and Functional Impairment in Long COVID: Relevance to Primary Care Practice
Rama Krishna Prasad Chikkala1, Sandeep Garre1, A Chaitanya Pratyusha1
1Anaesthesiology, All India Institute of Medical Sciences, Bibinagar, Bibinagar, IND.
Insights
Elevated D-dimer and fibrinogen levels correlate with severe long COVID symptoms. Basic coagulation tests and the Six-Minute Walk Test (6MWT) can help primary care identify patients with ongoing thrombo-inflammatory activity.
Area of Science:
- Medical research
- Clinical diagnostics
- Pulmonology
Background:
- Long COVID, a post-viral syndrome, presents persistent symptoms potentially linked to ongoing coagulation abnormalities.
- Early identification in primary care necessitates simple, cost-effective diagnostic tools.
- This study assesses basic coagulation markers and the Six-Minute Walk Test (6MWT) for long COVID evaluation.
Purpose of the Study:
- To evaluate the association between coagulation abnormalities and long COVID symptom severity.
- To assess functional impairment using the 6MWT in long COVID patients.
- To determine the persistence of coagulation abnormalities at three-month follow-up.
Main Methods:
- An observational study involving 197 adults over six weeks post-COVID-19.
- Baseline assessments included C-reactive protein (CRP), prothrombin time (PT)/international normalized ratio (INR), activated partial thromboplastin time (aPTT), D-dimer, fibrinogen, platelet count, and the 6MWT.
- Patients with abnormal parameters (n=63) were re-evaluated at three months.
Main Results:
- Reduced effort tolerance was the most common symptom (76.7%).
- Baseline abnormalities included D-dimer (25.4%), fibrinogen (21.8%), and CRP (17.3%).
- Elevated D-dimer and fibrinogen significantly correlated with severe symptoms (p < 0.001) and showed persistent elevation at three months in 50.8% and 47.6% of patients, respectively.
Conclusions:
- Significant association exists between elevated D-dimer/fibrinogen and long COVID symptom severity.
- Basic coagulation tests and the 6MWT are valuable adjunctive tools for primary care physicians.
- These accessible assessments can aid in identifying patients with probable ongoing thrombo-inflammatory activity for timely referral and management.
Abstract:
Background The long-term sequelae of COVID-19, collectively termed long COVID, manifest as persistent symptoms that may be driven by ongoing coagulation abnormalities. Early identification, particularly in primary care, requires simple, low-cost tools that do not rely on advanced diagnostics. This study evaluated the usefulness of basic coagulation markers and the Six-Minute Walk Test (6MWT) in assessing symptom severity and functional limitation among individuals with long COVID. Methodology A two-phase observational study was conducted from July 2022 to January 2024. Phase I enrolled 197 adults more than six weeks post-COVID-19 who presented with fatigue, breathlessness, reduced exercise tolerance, cough, or musculoskeletal pain. Baseline investigations included C-reactive protein (CRP), prothrombin time (PT)/international normalized ratio (INR), activated partial thromboplastin time (aPTT), D-dimer, fibrinogen, and platelet count, alongside the 6MWT. The primary objective was to evaluate the association between coagulation abnormalities and the severity of long COVID symptoms. Secondary objectives included assessment of functional impairment using the 6MWT and evaluation of persistence of coagulation abnormalities at the three-month follow-up. Patients with abnormal baseline coagulation or inflammatory parameters (n = 63) underwent repeat evaluation after three months. Results The study included 197 participants with a mean age of 37.3 ± 11.97 years, of whom 87 (44.2%) were male. Reduced effort tolerance was the most common presenting symptom, observed in 151 (76.7%) patients. At baseline, abnormalities were noted in D-dimer (50 (25.4%)), fibrinogen (43 (21.8%)), CRP (34 (17.3%)), aPTT (23 (11.7%)), PT/INR (21 (10.7%)), and platelet count (10 (5.1%)). Patients with severe symptoms demonstrated significantly higher levels of D-dimer and fibrinogen (p < 0.001 for both). Elevated D-dimer (50 (25.4%)) and fibrinogen (43 (21.8%)) were associated with an increased risk of severe symptomatology, with relative risks of 3.0 and 2.34, respectively. At the three-month follow-up, persistent elevation of D-dimer (32 (50.8%)) and fibrinogen (30 (47.6%)) was observed, indicating sustained coagulation abnormalities in a substantial subset of individuals with long COVID. Conclusions This study demonstrates a significant association between elevated D-dimer and fibrinogen levels and symptom severity in patients with long COVID. Simple, accessible tools, particularly basic coagulation tests and the 6MWT, may serve as useful adjunctive assessments for primary care physicians to identify long COVID patients with probable ongoing thrombo-inflammatory activity. Integrating these assessments into routine follow-up may improve early detection, monitoring, and targeted referral.
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