While respiratory issues continue to be the most common symptom of a COVID-19 infection, a meta-analysis of 42 studies indicates the disease could also be associated with hypercoagulability, according to a study published November 20, 2020 in the journal EClinical Medicine by The Lancet, researchers from University of California San Diego found that blood clots led to an increased risk of death by 74%.
Led by Dr Mahmoud Malas, division chief of Vascular and Endovascular Surgery at UC San Diego Health, researchers reviewed 42 different studies involving more than 8,000 patients diagnosed with COVID-19. Using random models, the team produced summary rates and odds ratios of mortality in COVID-19 patients with thrombo-embolism and compared them to patients without these conditions to determine what effect blood clots may have on risk of death.
"We began to notice a really unusual manifestation of venous and arterial thromboembolism in patients with COVID-19," said Malas. "In addition to higher instances of blood clots, the mortality for patients hospitalised for COVID-19 and with thrombo-embolism was much higher, compared to patients without clots. It's unusual because we have never seen anything like this with other respiratory infections."
Overall, 20 percent of the COVID-19 patients were found to have blood clots in the veins, and among patients in the intensive care unit, that statistic increased to 31 percent.
Blood clots in the vein, or deep vein thrombosis, can reach the lungs and develop into pulmonary embolism, resulting in higher risk of death. Blood clots in the arteries may lead to limb amputation if not treated surgically in a timely fashion.
In the study, Malas and colleagues performed a systemic review through meta-analysis, which is a statistical method that allowed researchers to combine multiple studies to produce a single comprehensive paper.
"The collective experience in the literature as captured in this meta-analysis study brings additional light on the importance of blood vessel clotting events in hospitalised patients with COVID-19," said Bryan Clary, MD, surgeon-in-chief at UC San Diego Health and co-author of the study. "While the frequency of these events is much higher than expected, our study likely underestimates the incidence of thromboembolism in the global population of patients with COVID-19, including non-hospitalised patients."
According to Malas, arterial blood clots developing in people with the flu is extremely rare, and the rate of clotting in patients with COVID-19 is higher than what is reported for other viral pandemics, including the H1N1 influenza of 2009.
Similar symptoms are shared between influenza and SARS-CoV-2, such as fever, cough, shortness of breath, or fatigue. Blood clotting can occur in patients hospitalised with the flu, but only in veins. For patients with COVID-19, blood clots can appear in either veins or arteries.
Typically, clotting in the arteries is caused by health factors, such as atrial fibrillation, high blood pressure, high cholesterol, diabetes, or lifestyle choices like smoking. Patients who are hospitalised for long periods of time are also more at risk for blood clots in the vein due to immobility.
Blood clots in the vein are treated or prevented with prescribed blood thinners. Proactively administering such medications to hospitalised patients can also help prevent clots from forming. Clinical trials are ongoing to determine how blood thinners can reduce the risk of clotting in patients with COVID-19.
"What we can learn from this paper is due diligence," said Malas. "We're still in the process of understanding the pathophysiology of COVID-19, so it's important to have a low index of suspicion when it comes to this infection to ensure we're doing all we can to mitigate the spread and prevent severe outcomes."
Thromboembolism risk of COVID-19 is high and associated with a higher risk of mortality: A systematic review and meta-analysis
Authors: Mahmoud B. Malas, Isaac N. Naazie, Nadin Elsayed, Asma Mathlouthi, Rebecca Marmor, Bryan Clary.
Publication details: EClinicalMedicine, 23 November 2020;
Abstract
Background
Studies have suggested that there is increased risk of thromboembolism (TE) associated with coronavirus disease 2019 (COVID-19). However, overall arterial and venous TE rates of COVID-19 and effect of TE on COVID-19 mortality is unknown.
Methods
We did a systematic review and meta-analysis of studies evaluating TE in COVID-19. We searched PubMed, Cochrane, and Embase for studies published up to June 12, 2020. Random effects models were used to produce summary TE rates and odds ratios (OR) of mortality in COVID-19 patients with TE compared to those without TE. Heterogeneity was quantified with I2.
Findings
Of 425 studies identified, 42 studies enrolling 8271 patients were included in the meta-analysis. Overall venous TE rate was 21% (95% CI:17–26%): ICU, 31% (95% CI: 23–39%). Overall deep vein thrombosis rate was 20% (95% CI: 13–28%): ICU, 28% (95% CI: 16–41%); postmortem, 35% (95% CI:15–57%). Overall pulmonary embolism rate was 13% (95% CI: 11–16%): ICU, 19% (95% CI:14–25%); postmortem, 22% (95% CI:16–28%). Overall arterial TE rate was 2% (95% CI: 1–4%): ICU, 5% (95%CI: 3–7%). Pooled mortality rate among patients with TE was 23% (95%CI:14–32%) and 13% (95% CI:6–22%) among patients without TE. The pooled odds of mortality were 74% higher among patients who developed TE compared to those who did not (OR, 1.74; 95%CI, 1.01–2.98; P = 0.04).
Interpretation
TE rates of COVID-19 are high and associated with higher risk of death. Robust evidence from ongoing clinical trials is needed to determine the impact of thromboprophylaxis on TE and mortality risk of COVID-19.
[link url="https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(20)30383-7/fulltext"]Full EClinicalMedicine study (Open access)[/link]