Coinfection of SARS-CoV-2 and Influenza: A Catastrophic Coexistence

Introduction

SARS-CoV-2 is a major public health burden causing morbidity and mortality in the global community and leading to respiratory sequelae, and cardiovascular, neurological, and digestive complications.^1,2 Myocardial and cerebral infarction are thromboembolic complications found in patients with COVID-19 with estimated incidence of 0.88 and 4.9%, respectively.³ Apart from COIVD-19, influenza A infection could also induce vascular inflammation and a hypercoagulable state.⁴ Epidemiological studies have shown increased risks of myocardial infarction and stroke following influenza infection.⁵ Simultaneous acute myocardial and cerebral infarction, known as cardio-cerebral infarction, is a rare medical emergency, with a reported incidence of 0.0009%.⁶ Few cases of cardio-cerebral infarction have been reported in those with COVID-19.⁷ Sharing a common transmission route, SARS-CoV-2 and influenza have the potential to cause a coinfection within the population with an incidence reported as 2.45%.⁸ In patients with COVID-19, coinfection with influenza is associated with increased in-hospital mortality.⁹ In this study, we reported a case of a patient with cardio-cerebral infarction after coinfection with SARS-CoV-2 and influenza A. The patient survived following coronary artery intervention and medical treatment. Institutional approval was required and obtained from the Tri-Service General Hospital Institutional Review Board to publish the case details.

Case Presentation

A 75-year-old nonsmoking Taiwanese female with a history of hypertension and type 2 diabetes mellitus presented to the emergency department with a five-day duration of fever, general weakness, and productive coughing in July, 2024 (Omicron wave of COVID-19 in Taiwan). Her vital signs were as follows: temperature, 36.5°C; blood pressure, 103/55 mmHg; heart rate, 86 beats/min; respiratory rate, 20 breaths/min; and oxygen saturation, 92% under 3 L/min of oxygen support. She denied contact with sick person and nor vaccination of COVID-19 and influenza previously. On physical examination, the patient appeared acutely ill with rales heard in both lungs. The laboratory results revealed white blood cell counts within the normal range (6600 per microliter), elevated C-reactive protein levels (28.07 mg/dL), and elevated D-dimer leves (6.98 µg/mL). Nasopharyngeal swabs tested positive for SARS-CoV-2 and influenza A antigens. The diagnosis of coinfection of SARS-CoV-2 and influenza A was then made. A Computed tomography (CT) of chest revealed multiple peripheral ground‒glass opacities with multi-lobar involvement and consolidation in both lungs with a CT severity score of 13 (Figure 1A).

Figure 1 (A) A computed tomography of chest revealed multiple ground-glass opacities and consolidation in bilateral lungs. (B) Coronary angiography demonstrates moderate to severe (70–80%) stenosis (arrow) of the proximal to mid LAD. (C) A T2-weighted magnetic resonance imaging of brain revealed focal hyperintensities in the left Corona radiata and left basal ganglia.

The patient was treated with intravenous methylprednisolone, remdesivir, peramivir, and levofloxacin. Dyspnea, right-sided limb weakness, desaturation, and decreased consciousness developed on the second day of hospitalization. The patient underwent endotracheal intubation with mechanical ventilation for acute respiratory failure. Elevated troponin I levels (7469 pg/mL) accompanied by ST elevation and inverted T waves in the precordial lead electrocardiogram were noted. Angioplasty with stenting was performed for moderate-to-severe stenosis of the proximal middle left anterior descending artery on day four of hospitalization (Figure 1B). Brain computed tomography revealed focal hypodensities in the left corona radiata and left basal ganglia, along with mild passive dilation of the left lateral ventricle on the fifth day of hospitalization. T2-weighted magnetic resonance imaging (MRI) of the brain revealed hyperintensity over the left corona radiata and basal ganglion, indicating acute cerebral infarction (Figure 1C). The patient received dual antiplatelet therapy with careful neurological monitoring after multidisciplinary team discussion between the cardiologist and neurologist. She had rehabilitation programs and was successfully weaned from mechanical ventilation after management. The patient was discharged one month later and recovered well, with mild right hemiparesis. The patient’s laboratory findings during the hospitalization, are summarized in Table 1.

Table 1 Laboratory Findings

Discussion

To the best of our knowledge, this is the first report of concurrent cardio-cerebral infarction during coinfection with SARS-CoV-2 and influenza A. The patient received antiviral treatment for the infection. The patient recovered well after coronary angioplasty and dual antiplatelet therapy.

Patients with COVID-19 are at an increased risk of thrombosis, including deep vein thrombosis, pulmonary embolism, and arterial thrombosis, with an overall thrombosis rate of 21%.^10,11 The risk factors are multifactorial, and include advanced age, male sex, a history of cardiovascular disease, and elevated D-dimer levels.¹² While the exact mechanism of thrombosis events has not been elucidated, several features, including cytokines, endothelial injury, and complement activation, have been documented as possible attributable factors.^13,14

Some respiratory tract viruses, such as influenza¹⁵ and respiratory syncytial virus¹⁶ have also been found to cause thrombosis. The coexistence of influenza and SARS-CoV-2 pneumonia is clinically significant and difficult to be differentiated from each other. Pneumonia due to either virus alone can result in diffuse alveolar damage, bilateral ground-glass opacities on CT images. Influenza pneumonia is more frequently associated with bacterial superinfection and higher initial fever and neutrophil counts,¹⁷ whereas SARS-CoV-2 pneumonia is characterized by lymphopenia, endothelial injury and prolonged ventilation duration.^18,19 Our patient’s presentation amplified features typical of both pathogens—highlighting the need for heightened vigilance in coinfection scenarios. The incidence of thrombosis caused by different varieties varies.¹⁵ Compared with influenza infection, COVID-19 is associated with a greater risk of venous thromboembolism, but not arterial thromboembolism.^15,20 Myocardial infarction is the most common arterial thrombosis event followed by cerebral infarction in patients with COVID-19.¹² In very rare instances, patients with COVID-19 may have simultaneous myocardial and cerebral infarction, namely, concurrent cardio-cerebral infarction.⁷

Concurrent cardio-cerebral infarction is an extraordinary medical emergency condition resulting in morbidity and mortality.²¹ Cardiocerebral infarction in patients with respiratory viral infection is very rare. Although the exact mechanism of cardio-cerebral infarction has not been well identified, several factors have been postulated, including cardiac thromboembolism, sudden hemodynamic compromise, and insular infarction-induced arrhythmia.²¹ In patients with COVID-19, coinfection with influenza may aggravate thrombotic events²² and lead to cardiac injury²³ and a high mortality rate.²⁴ This may be a possible reason for the development of concurrent cardio-cerebral infarction in our case. While the patient we described had significant pre-existing risk factors—including advanced age, hypertension, and diabetes mellitus—for both cerebral and myocardial infarctions, coinfection with SARS-CoV-2 and influenza A may have acted as a potential trigger or aggravating factor for the concurrent cardio-cerebral infarction in this susceptible individual. In addition, the patient did not receive enoxaparin despite an elevated D-dimer level, and this potential clinical oversight may have contributed to subsequent thrombotic events. The cerebral ischemia observed may also have been secondary to brain hypoperfusion resulting from cardiac ischemia in this case. However, this causal relationship cannot be definitively established based on a single case.

The management of myocardial and cerebral infarctions has been well established in the literature. Antiplatelet agents, anticoagulants, and other supportive medications are recommended for patients with arterial thrombosis. However, no clear evidence-based guidelines or clinical studies have addressed the optimal management of concurrent cerebral infarctions. Deciding the appropriate treatment for this condition often places physicians in a dilemma. Delayed intervention for each arterial thrombosis may lead to irreversible disability or even death. However, the use of thrombolytics and anticoagulants may lead to intracranial hemorrhage and myocardial rupture. Further research is needed to address these clinical issues.

In conclusion, we report a rare case of concurrent cerebral infarction in a patient coinfected with SARS-CoV-2 and influenza A. The patient’s condition improved after coronary intervention and dual antiplatelet agent treatment.Although the World Health Organization (WHO) has downgraded the COVID-19 pandemic, different respiratory viruses remain, leading to a global health burden. Clinicians should pay attention to the complex conditions of patients coinfected with SARS-CoV-2 and other respiratory viruses and the importance of early thrombosis prevention in coinfections.