key: cord-0822671-dluheryz
authors: Yusuf Mohamud, Mohamed Farah; Mukhtar, Mahad Sadik
title: Epidemiological characteristics, clinical relevance, and risk factors of thromboembolic complications among patients with COVID-19 pneumonia at A teaching hospital: Retrospective observational study
date: 2022-04-23
journal: Ann Med Surg (Lond)
DOI: 10.1016/j.amsu.2022.103660
sha: 9fd9d115405f44c971225deca0a0974fd1ed6331
doc_id: 822671
cord_uid: dluheryz

BACKGROUND: Thromboembolism is the third most common cardiovascular disorders and substantial worldwide health burden, with 1–2 instances per 1000 persons each year. This study aimed to describe the epidemiological characteristics, clinical relevance, risk factor and outcome of thromboembolic complications among COVID-19 infected patients. METHOD: This is a retrospective, single-center, observational study using a hospital information system (HIS). The study included 46-patients with a confirmed diagnosis of pneumonia by SARS-CoV-2 admitted to a tertiary hospital. RESULTS: The incidence of cardiovascular thromboembolic events among COVID-19 infected patients was 41.3% (n = 19). Cerebrovascular accident was the most common thromboembolic events among COVID-19 infected patients about 15.2%, flowed by pulmonary embolism (13%), acute myocardial infract (8.7%), and deep venous thrombosis (4.4%). In generally, 63% (n = 29) were males, while 37% (n = 17) were females. The majority of those who suffered thromboembolic events were over 65 years old (p < 0.000**). Patients with thromboembolic event were also more likely to have IHD (13.0% vs 0%, p = 0.003), diabetes (24% vs 13.0%, p = 0.025) and CL (10.9% vs 2.2%, p = 0.03) as precipitating factors when compared those without thromboembolic events. According to the outcome, 19 examinees had thrombotic events: 11 (24%) patients had admitted to non ICU inpatient ward, 2 (43%) had admitted to ICU and remaining 6 (13%) patients had dead. There was significant statistical difference in the proportion of examinees with thrombotic and non-thrombotic events in relation to outcome (p = 0.000). CONCLUSION: The incidence of thromboembolic complications among COVID19 infected patients were associated with elder (>65years), IHD, diabetes and CLD.

In December 2019, people in Wuhan, China, had reported patients presented with pneumonia like symptoms which was later on described as corona virus disease of 2019 (COVID-19) pneumonia caused by the severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) (1). In March 2020, World Health Organization (WHO) was officially declared a pandemic (2) .

Thromboembolism is the third most common cardiovascular disorders and substantial worldwide health burden, with 1 to 2 instances per 1000 persons each year (3) .

Acute respiratory distress syndrome (ARDS) and end-organ failure are the most common causes of morbidity and mortality in COVID-19 patients, also cardiovascular complications such as myocardial infarction (MI), ischemic stroke, and pulmonary embolism (PE) can also cause disability and death in these patients (4, 5, 6) .

In critically ill patients, the risk of thromboembolic is increased in the presence of COVID -19 infection. In addition to multiple mechanisms such as asystemic inflammatory condition, mechanical ventilation, central catheters, immobility, hemostatic abnormalities, and hepatic alterations enhance the risk of thromboembolic events (7, 8, 9) . A high prevalence of in situ microthrombosis suspected to be due to endothelial injury from direct viral infection has also been described (10, 11, 12) .

Until now, in our knowledge there is no study explored the role of incidence, risk factors and outcome of thromboembolic diseases among patients with SARSCoV-2 infection in Somalia.

Similarly, limited data are currently available about the incidence of thromboembolic in Sub-Sahara African countries. This study aimed to describe the epidemiological characteristics, clinical relevance, risk factor and outcome of cardiovascular thromboembolic complications among COVID-19 infected patients.

This is a retrospective, single-center, observational, cohort study using a hospital information system (HIS). The study included 46 patients with a confirmed diagnosis of pneumonia by SARS-CoV-2 admitted to Mogadishu Somali Turkish Training and Research Hospital located in Mogadishu Somalia during the second wave of COVID-19 between January to February, 2020.

One research resident collected data on demographics, comorbidities, clinical symptoms, laborat ory and radiological analyses retrospectively. All patient Nineteen patients had fulfilled arterio-venous thromboembolic criteria of our study. The criteria The baseline characteristics of the cases included age and sex, and comorbidities included diabetes mellitus, hypertension, dyslipidemia, CAD, and organ failure. Pregnant women, patients having coagulopathies, patients taking anti-cancer drugs, and children (those younger than 18 years of age) were excluded from the study. The prevalence of cardiovascular thromboembolic events among COVID-19 infected patients was 41.3% (n=19). Characteristics and risk factors of both thromboembolic and non-thromboembolic patients hospitalized for COVID-19 pneumonia are shown in Table 1 In generally, 63% (n=29) were males, while 37% (n=17) were females. According to the thromboembolic and thromboembolic events no difference between the two genders (male=52.6%;n=10, vs female=47.4%;n=9). There was no significant statistical difference in the proportion of examinees with thromboembolic events and non-thromboembolic events in relation to gender (p=0.180).

The majority of the overall participants (34.8%) were in the age group of 25-39 years old. There are more non-thromboembolic COVID-19 pneumonia patients in this age group than thromboembolic COVID-19 pneumonia patients. Among COVID-19 infected individuals, the majority of those who suffered thromboembolic events were over 65 years old (p<0.000**).

Thromboembolic event among COVID-19 infected patients were also more likely to have ischemic heart disease (IHD) (13.0% vs 0%, p=0.003), diabetes (24 % vs 13.0%, p=0.025) and chronic liver disease (CLD) (10.9% vs 2.2%, p=0.03) as precipitating factors of thromboembolic events among COVID-19 infected patients. This cohort had also more frequently comorbidities, such as hypertension, smoker, malignancy, as well as, heart failure and chronic renal disease.

As compared to those with thromboembolic events, participants with non-thromboembolic events mostly had presented headache ( 

Regarding laboratory findings on admission, COVID-19 infected patients with thromboembolic events were presented more often with WBC, platelets, CRP, AST, D-dimer, and Troponin levels and less frequently with urea, creatinine, ALT, D-dimer, and troponin than their nonthromboembolic counterpart ( Table 2) . In accordance with therapeutic modalities, patients with thromboembolic event had higher prevalence for administration of anticoagulant (41.3%, n=19, p<0.000), oxygen 19.6%, n=9, p=0.118 and invasive mechanical ventilation (19.6%, n=9, p<0,008) when compared to the patients with non-thromboembolic events (Table 4 ).

According to the outcome, most of the patients with non-thromboembolic events had been discharged to home (46.7%, n=21), flowed by 3 (6.5 %) patients admitted to non ICU inpatient ward, 2 (4.3%) patients admitted to ICU, and 1 (2.2%) patients had dead, while 19 examinees had thrombotic events: 11 (24 %) patients had admitted to non ICU inpatient ward, 2 (4.3%) had admitted to ICU and remaining 6 (13%) patients had dead. There was significant statistical difference in the proportion of examinees with thrombotic and non-thrombotic events in relation to outcome (p=0.000).

Limited data are currently available about the incidence of thromboembolic in Sub-Sahara African countries and in our knowledge there is no study explored the role of incidence, risk factors and outcome of thromboembolic diseases among patients with SARSCoV-2 infection in Somalia. This study aimed to describe the epidemiological characteristics, clinical relevance, risk factor and outcome of thromboembolic complications among COVID-19 infected patients.

Recent studies have found a significant frequency of thrombotic events in viral infections including corona-virus (13, 14, 15) . A meta-analysis included 8271 cases have reported thromboembolic rates in the range of 20-30% while others have reported rates as high as 40-70% (16).

In an evaluation of 184 severely ill COVID-19 patients, 31% of the patients suffered thrombotic complications, the most common of which was pulmonary embolism (17). Similarly, another retrospective cohort study of 388 cases found that COVID-19 patients had a significant rate of venous thromboembolism (21%) (18) .

The present study showed that the incidence of thrombotic events among hospitalized patients with COVID-19 was 41.3% (n=19). This significant variability is likely attributable to differences in the clinical and socio-demographic features of the study participants, as well as sample size and study design. The inflammatory process, cytokine storm, lung injury, and endothelial injury that enhance the risk of hypercoagulable condition in hospitalized COVID-19 patients are likely to be the cause of this high prevalence of thrombotic events (19) .

In the current study, cerebrovascular accident was the most common thromboembolic events among COVID-19 infected patients about 15.2%, flowed by pulmonary embolism (PE) (13%), acute myocardial infract (AMI) (8.7%), and deep venous thrombosis (4.4%).

A study done by Lodigiani et al. conducted that the incidence of PE, AMI and acute stroke were 33%, 2.5% and 1.1%, respectively (17). Of 221 patients with COVID-19 at a hospital in Wuhan, 11 (5%) developed acute ischemic stroke (20) .

PE was found to have an incidence rate of 8.3% in a major French retrospective multicentre observational investigation, which is lower than the current research (21) . These results are contrast to those of Li et al (22) . A cross-sectional survey of 143 hospitalized patients with J o u r n a l P r e -p r o o f COVID-19 in Wuhan, China, found that 46% developed lower extremity deep venous thrombosis (23) .

Since the outbreak of the corona-virus, only one case of thromboembolic complication has been reported in Somalia (24) .

In this study, males were higher frequently affected, which is contrast to the previous studies (25, 26) . A prospective multicenter observational study of 812 patients reported that thromboembolic events were high prevalence female sex (27) .

According to the age, the majority of COVID-19 infected individuals those who suffered thromboembolic events were over 65 years old (p<0.000**). A recent analysis from an academic hospital in Italy showed that the median age of thromboembolic complications in 388COVID-19 patients were 66 years (18) .

Similarly to our study, diabetes (9.7%), cardiovascular disease (16.4%), and hypertension (17.1%) were among the prevalent comorbid illnesses described in a meta-analysis of six published Chinese studies involving 1527 COVID-19 patients (20) . Unfractionated heparin and low molecular weight heparin (LMWH) have both been used prophylactically and therapeutically in these patients (28, 29) . Patients with COVID-19 who have a severe thromboembolic event, such as PE, without any additional risk factors should be regarded to have had a "provoked thromboembolic event" and may require anticoagulation for 3-6 months (30) . In the present study, COVID-19 infected patients with thromboembolic events had been administered anticoagulants were100%, while those without thromboembolic complication had administered 30%.

However, we found that presence of major cardiovascular thromboembolism had the strongest association with adverse outcomes, including symptomatic VTE, worsening chest CT findings, required invasive mechanical ventilation, and death.

There are several limitations in our report. First, this is a retrospective, single-center, and small sample study. Second, in the absence of data on thromboembolic testing at the national level because there may be cases of hidden thromboembolic that could not be detected in this study. No satisfied or specific number on the incidence of thromboembolic events in patients with COVID-J o u r n a l P r e -p r o o f 

A pneumonia outbreak associated with a new coronavirus of probable bat origin

WHO. WHO Director-General's opening remarks at the media briefing on COVID-19 -11

Deep vein thrombosis and pulmonary embolism. The Lancet

COVID-19 and thrombotic or thromboembolic disease: implications for prevention, antithrombotic therapy, and follow-up: JACC stateof-the-art review

Association of coronavirus disease 2019 (COVID-19) with myocardial injury and mortality

Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy

Pulmonary embolism or pulmonary thrombosis in COVID-19? Is the recommendation to use high-dose heparin for thromboprophylaxis justified

Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19

Endothelial cell infection and endotheliitis in COVID-19. The Lancet

Autopsy findings and venous thromboembolism in patients with COVID-19: a prospective cohort study. Annals of internal medicine

Risk of developing antiphospholipid antibodies following viral infection: a systematic review and metaanalysis. Lupus

Hepatitis C virus infection and risk of venous thromboembolism: a systematic review and meta-analysis. Annals of hepatology

ill ICU patients with COVID-19. Thrombosis research

Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in

The need to manage the risk of thromboembolism in COVID-19 patients

Prevalence and impact of cardiovascular metabolic diseases on COVID-19 in China

Pulmonary embolism in COVID-19 patients: a French multicentre cohort study

Acute cerebrovascular disease following COVID-19: a single center, retrospective, observational study. Stroke and vascular neurology

Deep vein thrombosis in hospitalized patients with COVID-19 in Wuhan, China: prevalence, risk factors, and outcome

Incidental finding of mild COVID-19 pneumonia with multiple thromboembolic disease: A case report

Cerebral venous thrombosis associated with COVID-19 infection: an observational, multicenter study

Asian study of cerebral venous thrombosis

A multicenter study of 1144 patients with cerebral venous thrombosis: the VENOST study

Asian study of cerebral venous thrombosis

The versatile heparin in COVID-19

The old but new: Can unfractioned heparin and low molecular weight heparins inhibit proteolytic activation and cellular internalization of SARS-CoV2 by inhibition of host cell proteases

Guidance for the treatment of deep vein thrombosis and pulmonary embolism