Complications of SARS-CoV-2 Infection During Cardiac Rehabilitation: A Case Series

Worldwide, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused more than 758,390,564 cases of infection and 6,859,093 deaths to date (https://​covid19.​who.​int/​). Despite the structural evolution of the virus [1‐4], the crude case fatality rate (CFR, number of deaths in the population of diagnosed and reported cases) has progressively decreased, most likely as a result of vaccines [5], which proved to be a highly effective measure to curb the pandemic [5, 6].

Although the impact of anti-coronavirus disease 2019 (COVID-19) vaccination on the risk of hospitalization and death is well recognized, the severity of SARS-CoV-2 infection and the degree of protection exerted over time by vaccination remains to be fully elucidated among hospitalized comorbid and vulnerable patients with SARS-CoV-2 infection [1‐3, 7].

In the setting of an ongoing registry of patients with COVID-19 [8], we report a case series of nine hospitalized patients who developed a SARS-CoV-2 infection during a cardiac rehabilitation inpatient program (from November 1 to November 30, 2022) in the Department of Internal Medicine of the Maugeri Care and Research Institute of Tradate (VA), Italy. The authors received approval for the conduct of this study from the ICS Maugeri Ethical Committee (protocol number 2415), and patients gave their written informed consent to participate [9].

The presence of comorbidities was defined according to documented medical history, as collected by physicians at the study site level. This assessment was performed during the clinical interview with the patient and by searching through medical records. An electrocardiogram (ECG) was also recorded at admission and when worsening clinical conditions or significant changes in laboratory tests occurred. ECG tracings were coded and were analyzed offline. Laboratory parameters were assessed using standard techniques.

Diagnosis of SARS-CoV-2 infection was confirmed by RNA reverse transcriptase polymerase chain reaction (PCR) assays from nasopharyngeal swab specimens.

All patients were male, asymptomatic, and with hemodynamic stability and negative PCR results at hospital admission. Table 1 shows the main characteristics of patients. Age ranged from 50 to 81 years. Six and two of the nine patients had a history of arterial hypertension and diabetes, respectively. All but one patient had received at least three doses of anti-COVID-19 vaccine more than 4 months before the cardiac event. Indications for cardiac rehabilitation included acute coronary syndromes, congestive heart failure, heart valve surgery, and coronary artery bypass graft. At admission, all patients had a baseline echocardiographic evaluation. A new evaluation was also performed after the diagnosis of SARS-CoV-2 infection.

After the confirmed diagnosis of SARS-CoV-2 infection, all patients developed symptoms, including fever, cough, dyspnea, fatigue, and headache. Eight of nine patients developed at least one SARS-CoV-2-related complication. Three of the patients reported a significant increase in high-sensitivity troponin I levels and five patients required supplemental oxygen therapy for new-onset hypoxemia (patient no. 4 required several hours of monitoring at a tertiary center emergency department). Persistent atrial fibrillation was recorded in one patient, without evidence of electrolyte imbalance (Case 3). Non-sustained ventricular tachycardia and recurrent sinus arrests were documented in one patient, who was not taking atrioventricular nodal blocking agents (Case 9). Two patients developed new-onset circumferential pericardial effusion (12 mm). During hospitalization and according to our protocol [10], three patients exhibited a persistent increase in blood pressure (BP), with values ≥ 140 mmHg systolic or 90 mmHg diastolic for at least two consecutive days, which required intensification of antihypertensive treatment.

After the acute phase of infection with evidence of two consecutive negative results of nasopharyngeal swab samples, all patients completed the rehabilitation cycle and were discharged from the hospital.

Our case series suggests that the majority of vulnerable patients may exhibit cardiopulmonary complications during the acute phase of SARS-CoV-2 infection contracted during hospitalization. Of note, these cardiac complications appear to be comparable to those noted in the early phase of the pandemic [8, 9, 11‐15]. A non-negligible proportion of patients may react with a significant increase in BP. As recently reported by a prospective study including hospitalized patients with confirmed diagnosis of SARS-CoV-2 infection, a non-negligible proportion of patients may develop a persistent increase in BP (as defined by BP values ≥ 140 mmHg systolic or 90 mmHg diastolic for at least two consecutive days) requiring new or intensified antihypertensive treatment during hospitalization [10]. Furthermore, estimating the effects of covariates with multivariable regression models, COVID-19 was associated with a sevenfold higher risk of uncontrolled hypertension when compared with bacterial pneumonia (p = 0.004), even after adjustment for confounders [10].

This phenomenon has been associated with angiotensin-converting enzyme 2 (ACE₂) receptor deficiency, potentially linked to reduced generation of the potent vasodilator angiotensin_1-7, during the active phase of the infection [10, 16‐26].

Almost all of our patients with important cardiovascular comorbidities and COVID-19 infection during hospitalization developed complications which, however, did not evolve towards more severe expressions of the disease. All patients had received COVID-19 vaccination over the past months, exerting a potential effect on reducing the risk of progression towards more severe disease of SARS-CoV-2 infection in vulnerable patients with cardiovascular comorbidities.