• 
• 

Three Part Question

In [adults with COVID-19 where pulmonary embolism is considered as a possible diagnosis] are [decision aids] valid in [stratifying risk]?

Clinical Scenario

A 55-year-old woman presents with shortness of breath, sinus tachycardia and low oxygen saturations. She is COVID-19 positive.

Search Strategy

({exp Clinical Decision-Making OR exp Clinical Decision Rules OR exp Coronavirus Disease 2019 OR exp COVID-19 OR exp Decision Making OR exp Decision Support System OR exp Decision Support Systems, Clinical OR exp Decision Support Techniques OR exp Decision Trees}) LIMIT to human AND English.

Search Outcome

53 papers found. 18 were relevant.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Fang C et al. 2020 UK	93 patients with COVID-19 underwent CTPA imaging. 41 had a PE.	Retrospective Observational Cohort study	Wells Score	A high Wells’ score did not differentiate between pulmonary thromboembolic disease (PTD) and non-PTD groups (p=0.801). 3.42% of participants had confirmed COVID-19 and PE (above test threshold).	Small sample size from a single institution. Majority of patients were referred for a CTPA from inpatient wards.
Whyte MB et al. 2020 UK	1477 patients were admitted with COVID-19 and 214 CTPA scans were performed and 80 (37%) confirmed PE	Retrospective Observational Cohort study	To examine the utility of D-dimer and conventional pre-test probability for diagnosis of PE in COVID-19	The Wells score was not different between those with and without PE. The numbers and proportions with Wells score of more than or equal to 4 (‘PE likely’) were 33/134 (25%) without PE vs 20/80 (25%) with PE (P = 0.951). 5.41% of participants had confirmed COVID-19 and PE (above test threshold).	Single institution. Small sample size
Monfardini L et al. 2020 Italy	1,207 confirmed COVID-19 patients. 34 of which underwent CTPA and 26 of these had PE	Retrospective Observational Cohort study	Wells Score	Patients with a moderate to high-risk Wells Score were found to have a two- to fivefold increase compared to the prevalence reported by the original study by Wells et al. 2.15% of participants had confirmed COVID-19 and PE (above test threshold).	Small sample size. May not be generalisable to the ED setting.
Kampouri E et al. 2020 Switzerland	443 COVID positive patients. 28 PEs with 18 on ITU.	Retrospective Cohort study	Predicting Venous Thromboembolic Events in Patients with Coronavirus Disease 2019	The presence of either a Wells score of more than or equal to 2 points or a D-dimer value of more or equal to 1,000 ng/mlis was the most sensitive for PE diagnosis (sensitivity 92.9%, specificity 46.9%). D-dimer values of more or equal to 3,000 ng/l combined with a Wells score for PE of more or equal to 2 was associated with the highest specificity (sensitivity 57.1%, specificity 91.6%, accuracy 0.905) 6.32% of participants had confirmed COVID-19 and PE (above test threshold).	Retrospective data and small sample size.
Rogers A et al. 2021 UK	468 patients were included, with 47 diagnosed with PE on CTPA. All patients were COVID positive and had an onset of symptoms of less than 30 days.	Retrospective Observational study. Conference abstract.	To establish whether there is a role for D-dimer, CRP and Wells’ score to risk stratify patients with COVID-19 to guide CTPA imaging and enable early diagnosis of PE.	The Wells criteria, if used according to NICE guidance, would not indicate CTPA and potentially lead to delayed diagnosis in this patient group. 10.04% of participants had confirmed COVID-19 and PE (above test threshold).	Abstract only found. Small Sample Size
Kirsch B et al. 2021 USA	459 patients with COVID-19. Age over 17 years old. 64 had a CTPA and 12 had evidence of pulmonary embolism.	Retrospective Observational study	To evaluate the ability of the Wells score to predict pulmonary embolism in patients with COVID-19	A Wells score above 4 was significantly associated with PE, but the sensitivity and specificity of the score were unreliable. 12 confirmed PEs out of 459 patients gives a 2.6% test threshold. This is over the test threshold.	Single centre retrospective study. Admitted patients only
Raj K et al. 2021 USA	1000 COVID-19 patients. 88 with suspected PE. PE was confirmed in 18 of the 88 patients.	Retrospective Cohort Study	Reliability of the Wells score	Wells PE score (P=0.02, CI 1.26-16.3). PE and DVT, clinical gestalt and Wells scores are inferior to D-dimer. 1.8% of participants had confirmed COVID-19 and PE.	Retrospective and single institution. Cannot access full paper.
Stals et al. 2021 Netherlands	Patients with COVID-19	Narrative Review	Review of the available literature and guidelines on current diagnostic algorithms for suspected PE	Diagnostic algorithms for ruling out PE might be considered safe in patients with COVID-19, although efficiency could be diminished.	Lack of clear methodology on search strategy and inclusion criteria. Only retrospective studies were included.Not specific to the emergency department setting.
Stals MA et al. 2021 Netherlands	707 patients with (suspected) COVID-19 and suspected of acute PE. PE was detected in 197 patients (28%), of whom 151 patients were ultimately diagnosed with COVID-19 (77%) and in 46 patients COVID-19 diagnosis could ultimately not be confirmed (23%).	Prospective multi-centred cohort study	Evaluation of diagnostic strategies for suspected pulmonary embolism (PE)	One-hundred seventeen patients (46%) managed according to YEARS had a negative CTPA, of whom 10 were diagnosed with nonfatal VTE during follow-up (failure rate 8.8%, 95% CI 4.3–16). In patients managed by CTPA only, 66% had an initial negative CTPA, of whom eight patients were diagnosed with a nonfatal VTE during follow-up (failure rate 3.6%, 95% CI 1.6–7.0). 28% of participants had confirmed COVID-19 and PE (above test threshold)	Not all patients were COVID-19 positive. Not specific to the ED setting.
Porfidia A et al. 2021 Italy	93 adults over 18 years old with COVID-19. 28 patients underwent CTPA and 10 had PE.	Retrospective Observational Study	To evaluate the Geneva score, Wells score, PERC, and YEARS algorithm	Current recommendations for diagnosing PE don’t discriminate between PE and non-PE patients in the COVID-19 population 10.8% of participants had confirmed COVID-19 and PE (above test threshold).	Retrospective study. Single centre design and a small sample size.
Raj K et al. 2021 USA	210 COVID-19 positive patients with 109 underwent a CTPA. 26 had a confirmed PE.	Retrospective Cohort Study	Sensitivity and specificity of Wells Score	A Wells PE score of 4 had a specificity of 100% and a sensitivity of 20% for the diagnosis of PE. 23.8% of participants had a CTPA and confirmed COVID-19 and PE.	Measurement bias due to Wells score being calculated retrospectively
Luu IH et al. 2021 Netherlands	666 patients admitted via ED who were suspected to have COVID-19. Of the 393 patients who underwent CTPA, PE was confirmed in 51 (13%).	Prospective Cohort study	To prospectively evaluate diagnostic strategies such as YEARS for suspected PE in COVID-19 patients.	CTPA could be avoided in 29% of patients managed by YEARS, with a low failure rate. 13% of participants had confirmed COVID-19 and PE (above test threshold).	Small sample size. It excluded 15 patients with contraindications to CTPA or anticoagulant therapy.
Quezada-Feijoo M et al. 2021 Spain	305 patients over 75 years old, hospitalised with COVID-19 and with a clinical suspicion of PE. 50 patients had suspected PE based on CTPA. 17 patients were confirmed to have a diagnosis of PE.	Longitudinal observational study	To assess the Wells and revised Geneva scoring systems as predictors of PE and their relationships with D-dimer in this population.	D dimer and the clinical probability scales increases the specificity and negative predictive value. The modified Geneva scale was more accurate than the Wells scale for classifying patients with suspected PE 5.57% of participants had confirmed COVID-19 and PE (above test threshold).	Hospitalised patients and not specific to the ED setting. Specific to elderly patients.
Rindi LV et al. 2021 Italy	12 cohort studies were included in this review with a total of 4569 hospitalised covid positive patients. 8 of the trials used Wells Score, 2 Padua, 1 CHOD score and 1 Revised Geneva	Systematic Review	Summary of the literature on predicting rules for PE in hospitalized COVID-19 patients	New prediction rules, specifically developed estimating the risk of PE in HCP, differentiating ICU from non-ICU patients, and taking into account anticoagulation prophylaxis, comorbidities, and the time from COVID-19 diagnosis are needed.	Only three studies were prospective included and no randomised control trials. One study is 2/3 of the patients and assesses non-traditional risk scores such as CHAD-VASC 2. Review included ICU and non-ICU patients.
Silva BV et al. 2021 Portugal	300 adult patients with COVID-19 and suspected PE. All patients had diagnostic CTPA.	Retrospective Observation study.	To compare the diagnostic accuracy of the standard approach based on Wells and Geneva scores combined with a standard D-dimer cut-off of 500 ng/mL with three alternative strategies (age-adjusted, YEARS and PEGeD algorithms) in COVID-19 patients.	None of the diagnostic prediction rules are reliable predictors of PE in COVID-19. PE was detected in 15% and 13% of patients considered as having low probability by Wells and Geneva scores, respectively, 15% of participants had confirmed COVID-19 and PE (above test threshold).	Retrospective single-centre and chart review study.
Martens ES et al. 2022 Netherlands	Three studies including 1713 COVID-19 positive patients with suspected PE.	Narrative Review	To evaluate the diagnostic algorithms for acute PE	This review supports the use of the standard diagnostic algorithms for all patients with suspected PE and specifically for COVID-19 patients. YEAR can be used in patients with COVID-19, although the number of patients who can be managed without CTPA is lower than in the non-COVID-19 population and the failure rate is higher than in non-COVID-19 patients.	Unclear methodology and search strategy. Not specific to the ED setting.

Comment(s)

There is limited evidence available on this topic. Only two relevant prospective papers were reviewed. The majority of patients included were hospitalised and from a single centre, thus the results may not be generalisable to the emergency department setting. Confounding factors such as vaccination status and subjective decision-making tools may have influenced results. Of the 16 cohort studies, the prevalence of PE identified on CTPA in COVID-19 positive hospitalised patients ranged from 1.8% to 60%. However, the test threshold for the investigation of PEs is known to be 1.8% (1). This BestBets review suggests that COVID-19 may increase the probability of PEs to above the test threshold and therefore new COVID specific algorithms are required. New COVID-19 algorithms may incorporate varying d-dimer cut-off levels. Reference: Kline JA, Mitchell AM, Kabrhel C, Richman PB, Courtney DM. Clinical criteria to prevent unnecessary diagnostic testing in emergency department patients with suspected pulmonary embolism. Journal of Thrombosis and Haemostasis. 2004; 2(8):1247-1255

Clinical Bottom Line

This question has not been answered adequately due to the limited high-quality evidence available on pulmonary embolism decision aids in patients with COVID-19 and no studies directly answered this three-part question. The limited evidence suggests that new decision aids will need to be developed and validated for COVID-19 patients.

References

1. Fang C, Garzillo G, Batohi B, Teo JT, Berovic M, Sidhu PS, Robbie H. Extent of pulmonary thromboembolic disease in patients with COVID-19 on CT: relationship with pulmonary parenchymal disease. Clinical Radiology 2020; 780-8.
2. Whyte MB, Kelly PA, Gonzalez E, Arya R, Roberts LN. Pulmonary embolism in hospitalised patients with COVID-19. Thrombosis research 2020; 95–99
3. Monfardini L, Morassi M, Botti P, Stellini R, Bettari L, Pezzotti S, Alì M, Monaco CG, Magni V, Cozzi A, Schiaffino S. Pulmonary thromboembolism in hospitalised COVID-19 patients at moderate to high risk by Wells score: a report from Lombardy, Italy. The British Journal of radiology 2020; 1113
4. Zotzmann V, Lang CN, Wengenmayer T, Bemtgen X, Schmid B, Mueller-Peltzer K, Supady A, Bode C, Duerschmied D, Staudacher DL. Combining lung ultrasound and Wells score for diagnosing pulmonary embolism in critically ill COVID-19 patients. Journal of thrombosis and thrombolysis. 2020; 76-84
5. Kampouri E, Filippidis P, Viala B, Méan M, Pantet O, Desgranges F, Tschopp J, Regina J, Karachalias E, Bianchi C, Zermatten MG. Predicting venous thromboembolic events in patients with coronavirus disease 2019 requiring hospitalization: an observational retrospective study by the COVIDIC Initiative in a Swiss University Hospit BioMed research international. 2020;
6. Rogers A, Brend J, Pitt D, Parker A. 803 Characteristics of patients with COVID-19 undergoing CT pulmonary angiography in the emergency department: a retrospective observational study BMJ 2021;
7. Kirsch B, Aziz M, Kumar S, Burke M, Webster T, Immadi A, Sam M, Lal A, Estrada-Y-Martin RM, Cherian S, Aisenberg GM. Wells score to predict pulmonary embolism in patients with coronavirus disease 2019 The American Journal of Medicine. 2021; 688-90:
8. Raj K, Chandna S, Watts A, Anandam A, Sankaramangalam K, Oluwatoba M. Incidence and diagnosis of deep vein thrombosis and pulmonary embolism In COVID-19-A retrospective cohort study of 1000 patients in a community hospital in Central New Jersey. Journal of the American College of Cardiology. 2021
9. Stals MA, Kaptein FH, Kroft LJ, Klok FA, Huisman MV. Challenges in the diagnostic approach of suspected pulmonary embolism in COVID-19 patients. Postgraduate Medicine. 2021; :36-41
10. Stals MA, Kaptein FH, Bemelmans RH, van Bemmel T, Boukema IC, Braeken DC, Braken SJ, Bresser C, Ten Cate H, Deenstra DD, van Dooren YP. Ruling out Pulmonary Embolism in Patients with (Suspected) COVID-19—A Prospective Cohort Study. Thieme Open 2021; 387-99
11. Porfidia A, Mosoni C, Talerico R, Porceddu E, Lupascu A, Tondi P, Landi F, Pola R. Pulmonary Embolism in COVID-19 Patients: Which Diagnostic Algorithm Should We Use? Frontiers in Cardiovascular Medicine. 2021
12. Raj K, Chandna S, Doukas SG, Watts A, Pillai KJ, Anandam A, Singh D, Nagarakanti R, Sankaramangalam K Combined Use of Wells Scores and D-dimer Levels for the Diagnosis of Deep Vein Thrombosis and Pulmonary Embolism in COVID-19: A Retrospective Cohort Study. Cureus 2021
13. Luu IH, Kroon FP, Buijs J, Krdzalic J, de Kruif MD, Leers MP, Mostard GJ, Martens RJ, Mostard RL, van Twist DJ. Systematic screening for pulmonary embolism using the YEARS algorithm in patients with suspected COVID-19 in the Emergency Department. Thrombosis research. 2021; 113-5
14. Quezada-Feijoo M, Ramos M, Lozano-Montoya I, Sarró M, Cabo Muiños V, Ayala R, Gómez-Pavón FJ, Toro R. Elderly Population with COVID-19 and the Accuracy of Clinical Scales and D-Dimer for Pulmonary Embolism: The OCTA-COVID Study. Journal of Clinical Medicine. 2021; , 5433:
15. Rindi LV, Al Moghazi S, Donno DR, Cataldo MA, Petrosillo N. Predictive scores for the diagnosis of Pulmonary Embolism in COVID-19: A systematic review. International Journal of Infectious Diseases. 2021; 93-100
16. Silva BV, Jorge C, Plácido R, Mendonça C, Urbano ML, Rodrigues T, Brito J, da Silva PA, Rigueira J, Pinto FJ. Pulmonary embolism and COVID-19: A comparative analysis of different diagnostic models performance. The American journal of emergency medicine. 2021; 526-31:
17. Martens ES, Huisman MV, Klok FA. Diagnostic Management of Acute Pulmonary Embolism in COVID-19 and Other Special Patient Populations. Diagnostics 2022