Thrombotic and hemorrhagic complications of COVID-19 in adults hospitalized in high-income countries compared with those in adults hospitalized in low- and middle-income countries in an international registry

Abstract

Background: COVID-19 has been associated with a broad range of thromboembolic, ischemic, and hemorrhagic complications (coagulopathy complications). Most studies have focused on patients with severe disease from high-income countries (HICs).

Objectives: The main aims were to compare the frequency of coagulopathy complications in developing countries (low- and middle-income countries [LMICs]) with those in HICs, delineate the frequency across a range of treatment levels, and determine associations with in-hospital mortality.

Methods: Adult patients enrolled in an observational, multinational registry, the International Severe Acute Respiratory and Emerging Infections COVID-19 study, between January 1, 2020, and September 15, 2021, met inclusion criteria, including admission to a hospital for laboratory-confirmed, acute COVID-19 and data on complications and survival. The advanced-treatment cohort received care, such as admission to the intensive care unit, mechanical ventilation, or inotropes or vasopressors; the basic-treatment cohort did not receive any of these interventions.

Results: The study population included 495,682 patients from 52 countries, with 63% from LMICs and 85% in the basic treatment cohort. The frequency of coagulopathy complications was higher in HICs (0.76%-3.4%) than in LMICs (0.09%-1.22%). Complications were more frequent in the advanced-treatment cohort than in the basic-treatment cohort. Coagulopathy complications were associated with increased in-hospital mortality (odds ratio, 1.58; 95% CI, 1.52-1.64). The increased mortality associated with these complications was higher in LMICs (58.5%) than in HICs (35.4%). After controlling for coagulopathy complications, treatment intensity, and multiple other factors, the mortality was higher among patients in LMICs than among patients in HICs (odds ratio, 1.45; 95% CI, 1.39-1.51).

Conclusion: In a large, international registry of patients hospitalized for COVID-19, coagulopathy complications were more frequent in HICs than in LMICs (developing countries). Increased mortality associated with coagulopathy complications was of a greater magnitude among patients in LMICs. Additional research is needed regarding timely diagnosis of and intervention for coagulation derangements associated with COVID-19, particularly for limited-resource settings.

Keywords: COVID-19; SARS-CoV-2; developing countries; disseminated intravascular coagulation; hemorrhage; ischemic stroke; thromboembolism; thrombosis.

Graphical abstract

Figure 1

Patient Flow Diagram, showing exclusion steps and final cohorts by treatment intensity for LMIC and HIC.

Figure 2

(A) Trends in coagulopathy complications over time for LMICs. Months specified along x-axis; "coagulation" stands for "coagulopathy/DIC"; "venous thromboembolic complication" is the combination of deep venous thrombosis and pulmonary embolism. (B) Trends in coagulopathy complications over time for HICs. Months specified along x-axis. "Coagulation/DIC" stands for "Coagulopathy/Disseminated intravascular coagulopathy"; Venous thromboembolic complication is the combination of both deep venous thrombosis and pulmonary embolism. (C) Cumulative Number of COVID-19 Cases and Complications: The x-axis displays the study period, dark blue line: cumulative number of COVID-cases in the registry over time; light blue line: cumulative number of coagulopathy complications over time. (D) Mortality over time by Income Cohort. The x-axis specifies month of study period, the monthly mortality rate is green for HICs and lavender for LMICs.

Figure 3

(A) Frequency of complications in low- and middle-income countries. Light blue bars: patients receiving basic treatment, dark blue bars: patients receiving advanced treatments; green bars: patients treated with extracorporeal membrane oxygenation. (B) Frequency of complications in high-income countries. Light blue bars: patients receiving basic treatment, dark blue bars: patients receiving advanced treatments; green bars: patients treated with extracorporeal membrane oxygenation. Coag/DIC, coagulopathy/disseminated intravascular coagulation; DVT, deep venous thrombosis; ECMO, extracorporeal membrane oxygenation; GI, gastrointestinal; MI, myocardial infarction; PE, pulmonary embolism.

Figure 4

In-hospital mortality by the presence of coagulopathy complications (dark blue) vs no such complications (light blue), for low- and middle-income countries (LMICs) and high-income countries (HICs). (B) Mortality by treatment intensity, light blue for cohorts without coagulopathy complications, dark blue for cohorts with coagulopathy complications, patient fractions specified along x-axis. (C) Mortality by income category (LMIC on left and HIC on right), coagulopathy free (light blue), coagulopathy complications (dark blue). (D) Mortality by treatment intensity, economic stratification (HIC, open rectangles; LMIC, cross-hatched rectangles), and treatment intensity.

Figure 5

(A) Multivariable analysis of risk factors for coagulopathy complications. Odds ratios and 95% CIs are indicated along the margin. (B) Multivariable analysis of risk factors for mortality. Odds ratios and 95% CIs are indicated along the margin.

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