Background
The novel coronavirus, also known as severe acute respiratory syndrome coronavirus 2 or SARS-CoV-2, was reported in Wuhan province, China, in December 2019, and since then it has expanded worldwide due to its high infectivity [1]. Coronaviruses are single-stranded RNA enveloped viruses that transmit mainly through aerosolized droplets expelled from the respiratory tract of the primary patient. The clinical spectrum of COVID-19 infection ranges from asymptomatic states to critically ill cases. SARS-CoV-2 has been implicated in a wide spectrum of cardiovascular complications, from mild elevation in troponins to more severe cases such as pericarditis, cardiac tamponade, and myocarditis [2,3].
We present a case of cardiac involvement as a late complication of SARS-CoV-2 infection.
| TIMELINE | DESCRIPTION |
|---|---|
| Day 3 of illness | Telehealth consult with primary care physician. Prescribed antibiotic course and COVID-19 testing. |
| Day 5 of illness | Presented to the Emergency Room due to worsening symptoms. |
| Day 9 of illness | Patient developed rapidly progressive hypoxemia and new retrocardiac opacity in chest X-ray. |
| Day 12 of illness | Increase in inflammatory markers; started on high dose steroids. |
| Day 17 of illness | Required intubation for worsening hypoxia and pressors for hypotension. |
| Day 18 of illness | Started on Continuous renal replacement therapy (CRRT) for renal failure. |
| Day 27 | Peak T wave elevation diffusely in telemetry. EKG revealed diffuse ST wave elevation in most leads, with PR interval depression. Given high dose aspirin and continued with steroids. |
| Day 28 | New right-sided tension in pneumothorax treated with thoacotomy tube insertion. |
| Day 30 | Died from worsening respiratory function and sepsis. |
Case Presentation
A 68-year-old woman presented to the emergency department with fever for 5 days, weakness, and fatigue. She was asymptomatic otherwise with no respiratory symptoms and no sick contacts. Prior to admission, she consulted her primary care physician who prescribed her doxycycline, aceta- minophen, and a SARS-CoV2 nasopharyngeal polymerase chain reaction (PCR) test that came back positive. Her past medical history was significant for ulcerative colitis treated with total colectomy and ileostomy, autonomic neuropathy, chronic kidney disease stage 3, and depression. Home medications included midodrine and sertraline.
On admission, the patient was tachycardic and tachyp- neic with a SpO2%: 96% on ambient air.
Initial laboratory studies showed elevated C-Reactive Protein (CRP), lactate dehydrogenase (LDH), and ferritin, with low lymphocyte count (Table 1). Patient received treatment with ceftriaxone 1 g/d, enoxaparin 40 mg sq daily and received transfusion with one unit of convales- cent plasma for COVID-19. On day 4, the patient developed worsening hypoxia requiring high flow nasal cannula at 40 l and FiO2: 100%. A repeat chest X-ray showed new retrocardiac opacity.
| LABORATORY | ADMISSION DAY | DAY 7* | DAY 22** |
|---|---|---|---|
| White blood cell count (WBC) (4.0-11.0 × 103/μl) | 7.1 | 19.2 | 33.1 |
| Absolute (ABS) lymphocytes | 0.57 | 0.76 | 2.33 |
| Hemoglobin (HGB) (12.0-16.0 g/dl) | 14.7 | 13.8 | 9.6 |
| Platelet (150-400 × 103/μl) | 157 | 283 | 153 |
| D-Dimer (0.00-211.00 ng/ml) | 209 | 1,183 | |
| Blood urea nitrogen (BUN) (9-28 mg/dl) | 63 | 46 | 49 |
| Creatinine (0.52-1.04 mg/dl) | 3.48 | 2.32 | 1.62 |
| Aspartate aminotransferase (AST) (14-36 U/l) | 36 | 20 | 57 |
| Alanine aminotransferase (ALT) (9-52 U/l) | 20 | 19 | 37 |
| CO2 (21-33 mmol/l) | 18 | 21 | 25 |
| LDH (140-271 U/l) | 337 | 501 | |
| Lactic acid (0.5-2.0 mmol/l) | 1.1 | 1.9 | |
| C-reactive protein (0.0-5.0 mg/l) | 38 | 259 | |
| Ferritin | 1,172 | 1,438 | |
| Troponin-I (<0.12 ng/ml) | <0.03 | 1.8 |
*Day 7: Notorious increase in the inflammatory markers which may correlate with an increase in cytokine release (cytokine storm).
**Day 22: Development of diffuse ST elevation on the cardiac monitor and elevation of cardiac enzymes.
On day 7, the patient developed leukocytosis and increase in inflammatory markers including CRP, LDH, and ferritin (Table 1). She was given tocilizumab 4 mg/ kg for 2 days, and methylprednisolone 30 mg every 12 hours for a total of 10 days. Full anticoagulation with hep- arin infusion was started in view of significant elevation in D dimer. By day 12 the patient developed septic shock and was transferred to the intensive care unit where she underwent orotracheal intubation and vasopressors nor-epinephrine and vasopressin were started. She became oliguric with worsening renal failure and continuous renal replacement therapy was installed. Micafungin was added empirically due to isolation of yeasts on sputum culture.
On day 22 of hospitalization, the cardiac monitor showed peak T wave elevation diffusely. An Electrocardiogram (EKG) was done and revealed diffuse ST Segment wave ele- vation with PR segment interval depression in lead II and PR segment elevation on AVR (Figure 1). Initial troponin was <0.03 ng/ml (i.e., normal) and repeated one increased to 1.8 ng/ml (upper limit of normal: 0.12 ng/ml in our laboratory). A transthoracic 2D echo was obtained showing ejection fraction of 60% impaired relaxation and right ventricle systolic pressure of 31 mmHg with no pericardial effusion.
Electrocardiogram showing diffuse ST elevation and PR depressions most noticeable in leads I, II, AVF, and V3-V6, with no reciprocal changes.
Cardiology was consulted and recommended starting high dose aspirin 650 mg oral daily. Repeat set of troponin downtrended to normal values <0.03 ng/ml. Given the iso- lation status of the patient, no cardiac Magnetic resonance imaging (MRI) or echocardiogram was performed. The next day the patient developed right-sided pneumothorax treated with thoracostomy tube insertion. Eventually, the patient expired on day 25 of her illness due to worsening shock.
Discussion
COVID-19 patients are likely to develop multiple cardio- vascular complications. This was seen in the first studies conducted by Huang et al. [1] in which 5 out of 41 patients (i.e., 12%) diagnosed with COVID-19 had a high-sensi- tivity troponin above the threshold of 28 pg/ml.
The ECG abnormalities found in patients with COVID-19 may range from non-specific ST segment-T wave abnormalities to full-blown ST-Segment Elevation Myocardial Infarction (STEMI), and differentiating acute coronary syndromes from type 2 myocardial infarction may be challenging. Consequently, cardiology consulta- tion is encouraged if available on managing these cases [4].
The pathogenesis for the development of pericarditis in COVID-19 patients has not been defined yet. One mech- anism is the systemic inflammation mediated through cytokine release (cytokine storm) during the 2nd week of symptoms, which are considered one of the major causes for complications including acute respiratory distress syndrome (ARDS) and thoughtfully myocardial injury [5]. Direct infection of the virus has also been identified in a recent study through the presence of positive results for the SARS-CoV-2 genome by PCR in endomyocardial biopsies [6]. Other authors suggest that the development of fulminant myocarditis and severe cardiac damage expe- rience a 10-15-day delay following the onset of symptoms from COVID-19 pneumonia, presumably after activated T cells and macrophages infiltrating myocardial cells [7,8]. This becomes important in evaluating therapeutic options for these patients, including the decrease in leukocyte motility and phagocytosis from colchicine through inhi- bition of microtubule formation. Colchicine has also been proven to decrease symptoms in patients with pericarditis and has a favorable safety profile, appearing as a reason- able option for treatment of COVID-19 pericarditis [7].
The use of corticosteroids for treatment of viral per- icarditis has been controversial. Interestingly, steroids in COVID-19 pneumonia have shown good evidence for reduction of mortality in recent meta-analysis [9]. However, currently there is only anecdotal data for steroid use in COVID-19 pericarditis.
Regarding the use of Non-steroidal anti-inflammatory drugs (NSAIDs), there is no clear indication of harm, but some authors consider them pertinent for symptom con- trol in patients with COVID-19 pericarditis [10].
Other interventions such as the use of azathioprine, non-human immunoglobulins, and anakinra have been described as well, but there is lack of solid evidence for their benefits [10-13].
We present a case of a late development of pericarditis in a patient with COVID-19 pneumonia and ARDS. To this date, the prevalence of this condition remains unquantified, and a targeted treatment strategy remains indefinable for cases of myocardial injury and pericarditis, and a broad supportive strategy is key.
We over score the need for more clinical research regarding safety and efficacy of the treatment options available, as well as the prognosis of these patients.
Limitations
This study is limited by the lack of objective evidence of cardiac involvement in MRI or echocardiogram, given the restrictions for personnel exposure during the peak of the pandemic.
Conclusion
Mortality from COVID-19 may arise from complications related to cytokine storm syndrome including ARDS, pneumothorax, and a vast number of cardiovascular insults.
Patients with COVID-19 pneumonias commonly have elevated cardiac enzymes that seldom indicate myocardial injury. Using diagnostic tools such as ECG and echocardi- ography may aid in this distinction.
Preliminary information about the mechanisms of developing COVID-19 pericarditis may indicate that colchicine and steroids would be a reasonable treatment option. The efficacy and safety of these medications are to be elucidated.