Polyserositis as a Post–Covid-19 Complication

INTRODUCTION Polyserositis is described as inﬂ ammation with eﬀ usion of more than one serous membrane. There is very little published literature linking it to COVID-19 as a late complication. OBJECTIVE Present and describe a case of post–COVID-19 polyserositis. METHODS Data were collected from the medical record of a female patient admitted for fainting spells and marked weakness. The patient underwent a clinical evaluation, additional hematology, imaging and histopathology tests, and a surgical procedure. RESULTS We present the case of a 57-year-old female patient admitted to hospital for fainting spells and marked weakness, four months after COVID-19 infection. She also had a history of obesity, asthma, type 2 diabetes mellitus and a cholecystectomy in December 1992 for gallstones. Clinical assessment revealed pericardial eﬀ usion and bilateral pleural eﬀ usion, in addition to a tumor-like lesion outside the pericardium, proximal to the right ventricular wall. A surgical procedure and ﬁ ndings from additional tests led to diagnoses of thymic remnants and polyserositis. CONCLUSIONS This is a case of polyserositis in a post– COVID-19 patient. After other causes of polyserositis were ruled out, and since there is a likely physiological and pathogenic mechanism operating between the two diseases, the polyserositis was determined to be a late complication of COVID-19. To date, it is the second case reported in the world and the ﬁ rst reported in Cuba.


INTRODUCTION
COVID-19 has presented extraordinary global challenges in virtually all aspects of public and private life, prompting continuing debate and research. [1] On the medical front, complications of this viral infection have included reports of isolated infl ammation of the pericardium, pleura and peritoneum. [2][3][4] The medical community has also focused on the persistent symptoms identifi ed after resolution of acute COVID-19. These symptoms have been called by diff erent names: post-COVID conditions, long COVID, and post-acute COVID syndrome. Most of these descriptions involve onset of symptoms one to three months after the patient recovers from acute infection. [5,6] After reviewing acute and late COVID-19 conditions, we found very few reports of polyserositis in adults not attributable to another comorbidity.
The objective of this report was to present and describe a case of post-COVID-19 polyserositis-the fi rst in Cuba and the second in the world considered as a post-COVID-19 complication. [7] METHODS The patient's medical record included data collected from the patient interview, the physical exam, additional blood and imaging test results and surgeries, as well as the histopathology test of pleural and pericardial fl uid samples and tissue bordering the pericardium. All research was conducted by technicians and professionals in laboratories and hospital departments, following good clinical and laboratory practices.
We searched the Scielo, MedCarib, PubMed, LiLacs, and Google Scholar databases for previous reports of polyserositis as a post-COVID-19 complication.
We also conducted an interdisciplinary review of the case.

Ethics
The patient voluntarily provided her written informed consent to be studied for her health condition, as part of her healthcare regimen. We took special care to respect the patient's privacy and anonymity and ensured the integrity and accuracy of the data disclosed.

RESULTS
This is the case of a 57-year-old female patient with obesity (body mass index 34.4 kg/m 2 ), a history of bronchial asthma and a 10-year history of type 2 diabetes mellitus regularly controlled with oral hypoglycemic agents. The patient underwent a cholecystectomy in December 1992 for gallstones.
In July 2021, the patient completed her SARS-CoV-2 vaccination series with three doses of Abdala, a Cuban COVID-19 vaccine. On September 15, 2021, she received a diagnosis of COVID-19; she had a mild case, and recovered quickly.

COVID-19 Case Study
Peer Reviewed admission, with progressive worsening in intensity and frequency. The spells were accompanied by noticeable weakness.
In the interview, the patient reported dyspnea on moderate physical exertion and when attempting supine position.
Physical examination revealed decreased vesicular breath sounds in both lung bases, rhythmic and somewhat muffl ed heart sounds, heart rate at 80 beats per minute, blood pressure (in the right arm) at 110/70 mmHg and soft and rounded abdomen. The rest of the physical examination was normal.
Additional tests showed abnormally high blood glucose (>20 mmol/L), requiring a change in diabetes treatment (discontinuation of oral hypoglycemic agents in favor of insulin), which brought the symptoms under control. Laboratory tests also revealed high levels of high-sensitivity troponin T, aspartate aminotransferase, alanine aminotransferase and gamma-glutamyl transpeptidase. The results of the remaining blood tests were unremarkable ( Table 1).
The electrocardiogram was normal.
Other fi ndings were as follows: Abdominal ultrasound The liver had increased echogenicity due to steatosis; both kidneys were normal; the pancreas was normal; the uterus was small and involuted with thin endometrial lining; and a small amount of fl uid was found at the bottom of the pouch of Douglas.

Computed tomography (CT)
The noncontrast study showed pericardial thickening on the outer border of the right atrium, pericardial eff usion and bilateral pleural eff usion, more evident on the right side. There was no mediastinal lymphadenopathy. The liver showed uniform density. A small amount of fl uid was observed in the bottom of the pouch of Douglas. The spleen measured 128 mm. Kidneys were normal in appearance, without stones. The pancreas was normal. There was no retroperitoneal lymphadenopathy. There were incipient degenerative changes in the lumbosacral spine.

Transthoracic echocardiogram (TTE)
Valve apparatuses were normal. The right atrium and right ventricle were collapsed due to eff usion. The echocardiogram identifi ed a tumor, proximal to the right atrium, which seemed to be attached to the pericardium, but could not be further pinpointed with this study.

Contrasted heart CT
The arterial phase showed a hyperdense lesion measuring 1.7 x 4.3 cm, oval in shape, enhanced with a contrast agent, located in close contact with the outer border of the right atrium ( Figure 1). This lesion coincides with the pericardial thickening reported in the noncontrast study.
Thoracoscopy Considering the previous fi ndings and especially the tumor-like lesion in the pericardial region, a thoracoscopy was performed to pinpoint whether there were pleural abnormalities and to urgently study the pleural COVID-19 Case Study  During the same surgical procedure, a median sternotomy was performed to study the pericardium and remove the lesion reported in the imaging tests. Moderate pericardial eff usion was confi rmed. The gross characteristics of the pericardial fl uid extracted were similar to those described in the pleural fl uid.
A lesion with fatty appearance outside the pericardium at the right pericardiophrenic angle was identifi ed and completely removed. A pericardial window was also performed as a therapeutic measure to prevent recurrence of pericardial eff usion and to prevent risk of developing cardiac tamponade.
Histopathology A cytopathology test of the pericardial fl uid confi rmed absence of malignant neoplasm and presence of isolated lymphocytes.
Anatomic pathology report Analysis of the specimen removed during surgery yielded a determination of fi broadipose tissue with Hassall's corpuscles, leading to the conclusion that this tissue was related to thymic remnants and that this condition is not associated with development of pericardial eff usion in this case. [8] Followup The patient recovered quickly and started treatment with colchicine at low doses (0.5 mg every 12 hours). In the followup conducted one month after the procedure, the patient did not have pleural or pericardial eff usion, and she maintained normal cardiac function and diabetes control.

Final diagnosis
The patient received a diagnosis of polyserositis, possibly as part of a post-COVID-19 complication.

DISCUSSION
The imaging finding of a pericardial lesion with pericardial effusion, along with manifestations of right ventricular failure, led to several possible diagnoses.
Pericardial conditions are variable in clinical practice and may occur as an isolated process or associated with certain systemic conditions. Different benign or malignant diseases can also be established in the pericardium. [9,10] Initial identification of a pericardial mass, with the aid of TTE and CT, led to different presumptive diagnoses. First, pericardial metastases had to be considered because they are the most common malignant neoplasms of the pericardium.
The most common metastases are those from malignant lung, breast and kidney tumors. [10] Primary pericardial neoplasms are extremely rare. Mesothelioma is the most frequent, followed by fibrosarcomas and other types of sarcomas, lymphomas, neuroectodermal tumors and other benign lesions such as lymphangiomas, hemoangiomas, teratomas, neurofibromas and lipomas. [10] For these reasons, doctors initially turned to a thoracoscopy to evaluate the nature of the pleural effusions and rule out a malignant pleural effusion. [11] Identifying fatty-like tissue bordering the pericardium with thymic remnants fully ruled out the primary nature of a pericardial lesion, as well as a primary or metastatic malignant lesion. While it may be an uncommon finding, thymic remnants are present in more than half of adults. [12] After ruling out thymic remnants and neoplastic, infectious and autoimmune diseases as plausible causes for polyserositis in this case, a diagnosis of polyserositis associated with COVID-19 was proposed, a condition that to date has been reported in only one case in a scientific publication. [7] Nevertheless, the characteristics of the pleural and pericardial fluids (exudate) and the high levels of high-sensitivity troponin T support such a diagnosis. Evidence has also emerged indicating that SARS-CoV-2 can cause direct damage to the heart, either affecting the myocardium (myocarditis) or the pericardium (pericarditis). [13] Polyserositis is a condition characterized by inflammation and effusion in more than one site, including the pericardium, pleura and the peritoneum. Because of the rarity of polyserositis in medical practice, the diagnosis is based on clinical recognition and subsequent screening of probable causes. [9] It has been suggested that polyserositis onset in these patients occurs as a result of immunological phenomena caused by COVID-19, characterized by a disregulated cytokine and chemokine production. [14] Experience using colchicine to treat acute pericarditis and prevent recurrences indicates that this drug is safe for patients with COVID-19 and can be used during the early phases of the disease and for complications such as pericarditis and pleuritis. [15,16] The previous report of polyserositis as a post-COVID complication also documented successful treatment with colchicine. [7] COVID-19 Case Study Figure 1: Axial slice of heart CT scan during arterial phase CT: computed tomography; pe: pleural eff usion The arrow points to the contrast-enhanced lesion projected out from the pericardium, with oval appearance, located in close contact with the outer border of the right atrium. The study was conducted with a 128-slice SOMATOM Defi nition AS scanner (Siemens, Germany).

CONCLUSION
This report described a patient with clinical symptoms consistent with post-COVID-19 polyserositis, which occurred three months after infection by SARS-CoV-2. While it is not possible to establish a defi nitive causal relationship between polyserositis and history of COVID-19, this link cannot be ignored, especially after ruling out other possible causes of polyserositis and fi nding a plausible physiological and pathological mechanism between these two diseases. Thus, the studies conducted in this patient led us to conclude that polyserositis may be a late complication of COVID-19. This case is the second reported in the world and the fi rst in Cuba describing such a nosological association.