To The Editor
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a novel coronavirus
first identified in Wuhan, China, at the end of 2019. Since then it has caused more
than 1,700,000 confirmed cases of Coronavirus Disease 2019 (COVID-19) worldwide and
almost 110,000 deaths [1]. It is responsible for a respiratory syndrome ranging from
mild flu-like symptoms to severe respiratory failure (due to acute respiratory distress
syndrome), shock, multiorgan failure and death. [2]. SARS-CoV-2 has been first identified
in a bronchoalveolar-lavage fluid collected from patients with pneumonia admitted
in a hospital of Wuhan on late December [3] and a real-time reverse transcriptase–polymerase
chain reaction (rRT-PCR) of nasopharyngeal swabs is currently used to confirm the
clinical diagnosis [4]. From its isolation, SARS-CoV-2 has been detected in the respiratory
tract, in feces, conjunctiva and in blood [5, 6] but its localization in other sites
has not been reported so far. We reported here the first isolation of SARS-CoV-2 in
the pericardial fluid of a patient affected with COVID19 and cardiac tamponade undergoing
pericardiocentesis.
On February 15, 2020, a 59-year old man was admitted to our Emergency Department for
acute chest pain. Non-ST Elevation Acute Coronary Syndrome was diagnosed with coronary
angiography showing multivessel disease. The following day the patient underwent Coronary
Artery Bypass Surgery with left internal mammary artery to the left anterior descending,
right internal mammary artery to first obtuse marginal and left radial artery to right
coronary. He was extubated on the third day and echocardiography showed mild pericardial
effusion without hemodynamic impairment. On March 5, the patient complained of fever;
blood and urine culture were performed resulting negative. After three days, a new
episode of fever associated with dyspnoea occurred; considering the increasing number
of cases affected with COVID19 at our hospital, a nose-pharyngeal swab for SARS-CoV-2
research was performed with positive result; at the same time serological tests for
Mycoplasma Pneumoniae and Chlamydia Pneumoniae, A/B Influenza viruses research on
respiratory specimens, urinary antigens for Legionella Pneumophila and Streptococcus
Pneumoniae were performed and all resulted negative. Patient underwent high-resolution
lung CT scan showing “ground glass” areas with “crazy paving” pattern in both lungs,
especially in the left lung, suggesting COVID19-related interstitial pneumonia. Therapy
with lopinavir/ritonavir and hydroxychloroquine was started. Blood samples trend showed
increasing inflammatory markers (C-reactive protein and fibrinogen), lactic dehydrogenase
and D-dimer (Table 1
); in the light of emerging evidence that suggested a role for low-molecular-weight-heparin
(LMWH) to decrease mortality in COVID19 patients with markedly elevated D-dimer, enoxaparin
was also started [7]. In the subsequent days, the patient was treated with helmet
c-PAP for hypoxic respiratory insufficiency with a favourable clinical response. On
March 17, we started antibiotic therapy with ampicillin and ceftriaxone because of
a second blood culture showing the presence of Enterococcus Faecalis. After some days,
global clinical conditions improved with progressive reduction in inflammatory markers
(Table 1). On March 31, he complained of dyspnoea and chest pain: temperature was
36.5°C, blood pressure 100/65 mmHg, the pulse 130 beats per minute, the respiratory
rate 24 beats per minute and the oxygen saturation 98% while he was breathing room
air. An echocardiography was performed and documented severe circumferential pericardial
effusion conditioning collapse of the right heart sections. As shown in Table 1, high
sensitivity Troponin-I elevation was minimal. An echo-guided pericardiocentesis from
subcostal approach was performed, draining 250 cc of sero-haemorragic fluid; a sample
was sent to our laboratory for physico-chemical, cytological, microbiological and
molecular analysis. A second nasopharyngeal swab and a blood sample for viral RNA
detection were performed. Pericardial drainage was maintained in situ for two days
and a total of 400 cc of fluid was aspired. Given the progressive improvement of clinical
conditions and laboratory results, patient was discharged on April, 6, in fiduciary
isolation.
Table 1
Laboratory Results.
Table 1:
Variable
Reference Range
February, 15
March, 11
March, 17
March, 23
March, 29
April, 5
Hemoglobin (g/dl)
14-18
13
11.9
12.5
12.2
11.8
11.3
Hematocrit (%)
42-50
40.6
36.5
38.7
39.4
38.3
35.6
Platelet Count (per mm2)
150,000-400,000
150
106
202
460
324
215
White Cell Count (per mm2)
4000-10000
5.8
1.9
5.6
8.5
4.7
5.2
Absolute Neutrophil Count (per mm2)
2000-7000
4.02
1.25
4.8
6.95
2.84
3.47
Absolute Lymphocyte Count (per mm2)
1500-4000
0.95
0.5
0.35
0.6
0.86
0.83
C-Reactive Protein (mg/liter)
<1
1.34
2.43
11
4.76
0.58
2.76
Troponin I (ng/L)
<15
4580
<15
<15
22
20
D-dimer (ng/ml)
<400
1956
1966
4566
1607
Fibrinogen (mg/dl)
150-350
775
631
Sodium (mmol/liter)
135145
141
136
136
138
140
Potassium (mmol/liter)
3,5-5
3.8
4.3
4.2
4.1
4.4
Albumin (g/dl)
3.5-5.2
2.72
2.84
Creatinine (mg/dl)
0.6-1.17
0.92
0.76
0.68
0.74
0.82
NT-proBNP (ng/L)
<300
2705
Glucose (mg/dl)
65-110
131
93
128
100
86
Aspartate aminotransferase (U/liter)
<35
65
31
34
37
36
Alanine aminotransferase (U/liter)
<45
27
25
65
53
68
Lactate dehydrogenase (U/liter)
125-250
204
648
264
206
162
Procalcitonin (ng/ml)
<0.49
0.10
0.11
Pericardial Fluid Analysis
Chemical and cytological analysis of pericardial sample documented presence of inflammatory
cells: erythrocyte, mononucleates elements and lymphocytes were predominant, neoplastic
cells were not found. The presence of was detected by a rRT-PCR amplification of SARS-CoV-2
RNA through the GeneFinder COVID-19 PLUS RealAmp Kit (OSANG Healthcare Co, Ltd., Korea)
on the ELITe InGenius platform (ELITech Group, Puteaux, France), which integrates
extraction and amplification. The rRT-PCR kit detects in the same PCR reaction the
presence of three SARS-CoV-2 targets: the envelope protein (E), the nucleocapsid protein
(N) and RNA-dependent RNA polymerase (RdRp) genes. An endogenous internal control
based on the amplification of human beta-globin gene allows to confirm the quality
of the sample material extracted and the execution of the test. The rRT-PCR analysis
revealed the presence of SARS-CoV-2 N gene with a cycle threshold (Ct) value of 37.07
(the test is considered positive if Ct <43). No amplification was detected for the
other two SARS-CoV-2 genes, thus suggesting the presence of a low viral load; the
value of single positive target gene has already been postulated in a suggestive clinical
context [8]. Our patient had a previous nasopharyngeal swab positive for all three
target genes and a suggestive lung CT scan; after about three weeks and a full course
of antiviral therapy, the second nasopharyngeal swab and viral RNA research in the
blood were both negative: this data are in agreement with the bland positivity in
the pericardial sample. In our opinion the absence of viral RNA in blood and nasopharyngeal
secretions and its presence in pericardial fluid could suggest a persistence site;
whether this has pathogenic implications is still unknown.
COVID-19 pathogenesis is still being characterized. Until now, virus has been detected
only in sites corresponding to clinical manifestations: respiratory, gastro-intestinal
and ocular involvement are well known. However, although cardiac involvement has been
described [9], pericardial and myocardial tropism of SARS-COV-2 was only assumed.
The present data provide a new piece in the complex puzzle of this emerging disease,
suggesting a possible direct virus involvement in cardiologic manifestations. Further
studies in this direction are necessary.
Declaration of Competing Interest
All authors declare that they have no known competing financial interests or personal
relationships that could have appeared to influence the work reported in this paper.