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

Abstract

Introduction

Vaccination strongly reduces the risk of hospitalization and death due to coronavirus disease 2019 (COVID-19). However, the severity of the acute respiratory syndrome coronavirus-2 (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.

Methods

We report a case series of nine hospitalized vulnerable patients who developed a SARS-CoV-2 infection during a cardiac rehabilitation inpatient program.

Results

Age ranged from 50 to 81 years. 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. After the confirmed diagnosis of SARS-CoV-2 infection, all patients developed symptoms. Eight patients developed at least one SARS-CoV-2-related complication, including a significant increase in high-sensitivity troponin I levels, new-onset hypoxemia, persistent atrial fibrillation, non-sustained ventricular tachycardia and recurrent sinus arrest, pericardial effusion, and a persistent increase in blood pressure.

Conclusion

Almost all patients developed complications which, however, did not evolve towards more severe expressions of the disease. These data suggest that even in this new phase of the pandemic, vaccination may exert a potential role to reduce the risk of progression towards more severe disease of SARS-CoV-2 infection in vulnerable patients with cardiovascular comorbidities.

Key Summary Points

The severity of the acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in this new phase of the pandemic remains to be clarified. It is not entirely clear to what extent coronavirus disease 2019 (COVID-19) vaccination modifies the clinical outcome of COVID-19 in hospitalized vulnerable patients.

We report a descriptive series of hospitalized patients with acute COVID-19 infection and several cardiovascular comorbidities. All patients had been previously vaccinated.

These patients developed hospital complications, including hypoxemia, arrhythmias, pericardial effusion, troponin elevation, and increased blood pressure.

The degree of protection exerted over time by COVID-19 vaccination against progression towards severe COVID-19 phenotypes remains to be fully elucidated among comorbid and vulnerable patients with SARS-CoV-2 infection.

Introduction

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].

Methods

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.

Results

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.

Table 1.

Main characteristic of patients and cardiopulmonary complications recorded during the acute phase of SARS-CoV-2 infection

	Case 1	Case 2	Case 3	Case 4	Case 5	Case 6	Case 7	Case 8	Case 9
Age (years)	73	72	81	50	77	80	73	67	66
Sex	Male	Male	Male	Male	Male	Male	Male	Male	Male
Admitted after	NSTEMI	Heart valve surgery	Heart valve surgery	CABG	STEMI	CHF	CABG	NSTEMI	CABG
Days from index event	8	9	10	16	9	14	8	6	10
History
Hypertension	No	Yes	No	Yes	Yes	Yes	Yes	No	Yes
Diabetes	No	Yes	No	No	No	No	No	No	Yes
Obesity	No	No	No	No	No	No	No	No	Yes
Previous SARS-CoV-2 infection	No	Yes	No	No	No	No	No	No	No
Number of anti-COVID-19 doses	3	3	4	2	3	3	3	3	3
Date of last vaccination	December 2021	July 2021	July 2021	December 2020	December 2021	December 2021	December 2021	December 2021	December 2021
Time from last vaccination (> 4 months)	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes
Complications
Troponin elevation	Yes (73 pg/ml)	No	No	No	No	Yes (65 pg/ml)	Yes (52 pg/ml)	No	No
ECG changes	No	No	Yes	No	No	No	No	No	Yes
Pericardial disease	No	Yes	No	Yes	No	No	No	No	No
Hypoxemia	No	Yes	No	Yes	No	No	Yes	Yes	Yes
BP increase	No	No	Yes	No	No	No	No	Yes	Yes

CABG coronary artery bypass graft, BP blood pressure, CHF congestive heart failure, NSTEMI non-ST elevation myocardial infarction, STEMI ST elevation myocardial infarction

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.

Discussion

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].

Conclusions

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.