Brain Abscess in a Patient with Congenital Cardiopathy in Association with COVID-19: A Case Report

    


    


    Figure 2: Histological features observed with Masson’s trichrome stain showed (a) extensive areas of fibrosis, perivascular fibrosis with dissection of the vessels (x200). Reticular fibers stain in (b) the great production of fibers surrounding the blood vessels, they are made in the shape of onion cloth, but aneurysmal formations (x200), and in (c) a close-up, showed reticular fibers dissect diffusely in the form of fishing nets (x400). (d) GFAP staining, observed areas of perivascular fibrous eschar (x400). (e) CD31 positive immunoreaction in blood vessels with swollen endocervical cells and in a loose form (x200), (f) virus spice protein showed immunoreaction in endothelial and in inflammatory cells (x200). Transmission Electron Microscopy analysis. Endothelial cells showed large pathologic vacuoles (arrows) in and some cytoplasmic lamellar bodies were found in (g). Free viral particles and visible along the plasma membrane were found in (h).

    

Immunohistochemical stain was performed showing a proliferation of T cells (CD3 +, CD8 +), focally CD20 +, increased macrophages (CD68 +++ and CD163 +), IL6 +, IL10 +, IL13 +, HIF1a +, TNFa +). GFAP staining, showed positive immunoexpression in perivascular fibrous eschar and hypertrophic perivascular astrocytes (Figure 2d). CD31 was positive in swollen endocervical cells and in a loose form, and in EC outside the vessel. ECs loss in larger vessels were observed (Figure 2e). The ACE2 was positive in endothelial cells and virus spike protein was positive in endothelial, as well as inflammatory cells (Figure 2f).

Electron microscopy analysis of CoV-2 infected cells shows destruction and extensive degeneration of brain tissue. Large vacuoles in endothelial and neuron cell were found in cytoplasm (Figure 2g). Viral particles were also observed in infected cells which induce stress on the endoplasmic reticulum, arranging themselves in lamellar bodies. Single viral particles resembled the “spherules” and viral particles visible along the plasma membrane were observed (Figure 2h).

Initially, a diagnosis of abscess was made in the process of resolution. And once the stains for COVID were performed, the diagnosis of brain abscess associated with COVD19 was made in an immunosuppressed cardiac patient, with negative COVID19 serology and no lung damage.

Discussion

COVID-19 predominantly affects the respiratory system and advanced age, cardiovascular disease, patients with chronic inflammatory conditions including hypertension, diabetes mellitus, and obesity, chronic respiratory disease, smoking, and cancer are risk factors may be disproportionally be affected by SARS-CoV-2 and experience a bigger severity of disease [6]. However, Bacterial co-infection or fungal infection in the ongoing pandemic of COVID-19 is associated with poor outcomes, mainly attacks hosts who have compromised immune systems [3,4]. Though, Microbial coinfection exacerbates the occurrence processes, development and prognosis of COVID-19, and the difficulties of clinical diagnosis and treatment [8]. Several authors believe that an area of infarction in the brain precedes the development of an abscess although this process alone has not been reported in congenital heart disease. The paradoxic emboli, as a result of thrombosis of the cerebral arteries. Especially in COVID-19 patients at high risk of mortality and brain abscess formation.

The virus is detectable by PCR, immunohistochemistry IHQ, In Situ Hybridization (ISH), RNA-Dependent Reverse transcriptase (RdRp) genes, identifying of virus in frozen or formalin-fixed paraffin-embedded brain tissue or Electron Microscopy (EM) [6]. COVID-19 RT-PCR testing may produce false-negative results in the initial phase of infection [7]. SARS-CoV-2 immunohistochemistry, using antibodies that recognize the viral Nucleocapsid (N) or spike (S) proteins, have been reported as negative in most attempted human cases of autopsy [7]. The use of immunostaining can be very useful, especially when there are not enough clinical data or when serological positivity for PCR has been confirmed; however, the lack of controls in most of these studies limits the interpretation of these findings. Finally, it is noteworthy that inflammation does not always coincide with the location of the virus, raising concerns that the virus may be evading the immune response in the CNS. SARS-CoV-2 has not been detected in Cerebrospinal Fluid (CBF) in the majority of patients tested [7].

Various pathophysiologic mechanisms of neurologic sequelae have been proposed, including injury to the vascular wall and epithelial cells, resulting in disruption of the blood brain barrier; hypoxic injury and prolonged period of ventilation [6,7]. The entry of SARS-CoV-2 into human cells is commonly supposed to be mediated by the communication and interaction between the spike protein with the Angiotensin Converting Enzyme 2 (ACE2) receptor, an important regulator of the Renin-Angiotensin System (RAS) [6]. ACE2 receptor–facilitated entry of the virus into neural tissue cells; and immune cell and injury is secondary to cytokine storm syndrome [1]. SARS-CoV-2–induced coagulopathy significantly contributes to the development of neurologic manifestations and brain injury in patients with COVID-19 disease [7].

The classical neuropathology findings of COVID19 viral CNS infections including; perivascular mononuclear cell cuffing, neuropil infiltration by polymorphonuclear leukocyte lymphocytic leptomeningitis and encephalitis, microglial nodules, perivascular lymphocytic cuffing, focal demyelination and viral inclusions [6-8]. Perivascular-activated microglia, macrophage infiltrates, and hypertrophic astrocytes are also seen [6-8].

Talaminti et al [10], reported 6 cases of primary bacterial spinal epidural abscess in association with COVID19 infection. That they were surgically managed over a 2-month period. Clinically none had evidence of septic infection. All cases were apyretic and never they presented signs of sepsis, and only leukopenia. In the 6 patients, the cultures identified methicillin-sensitive staphylococcus aureus. And they hypothesized that epidural abscess may develop because asymptomatic bacterial colonization coexisted with COVID19-induced damage to the endothelial cells and that this could favor retrograde spinal invasion at the corresponding level, vs a probable nosocomial infection [10].

Diagnosis of coronavirus particles by EM is challenging due to similar appearance normal cellular structures, which has shaped substantial controversy in the literature [12,13]. The EM changes that SARS-CoV-2 induces in infected cells, including; focused on the membranous replication organelles that support viral RNA fusion and, cytoplasmatic vacuoles, similar to endosomes on the meeting, and release of new virions, various distinct membrane alterations and multisystemic Cellular Tropism of SARS-CoV-2 have been described [12,13]. Double-membrane vesicles, convoluted membranes, while zippered endoplasmic reticulum [13].

CRP, and d-dimer (d-D) has been found as an important marker that changes significantly in severe patients with COVID-19, which serves as an initial marker of infection and inflammation in predicting the possibility of disease progression [14].

Conclusion

We present a rare case of difficult diagnosis not due to the fact of having a simple brain abscess associated with streptococcal infection, with COV- protein positive in some inflammatory cells and in endothelial cells and ACE2 was also positive in ECs, and CD8, Il6, Il10, Il20 and Il23 positive immunoreaction. And by EM in embedded tissue showed a viridions like particles. Also, leukopenia, lymphopenia, al serum increases of CRP and D-dimer, all together suggesting COVID19 disease. But because the vascular pathology observed in this case does not appear in the simple brain abscesses reported. Because it was also positive for ACE2, angiotensin, and COVD19 viral proteins, in an asymptomatic patient for covid19 but with high risk factors such as congenital heart disease, and presenting a cachectic state, a state of immunodeficiency. The co-expression of two or more causative agents of a brain abscess. We should encounter much more patients with BA since the degree of the pandemic. False positives, false negatives and negative patients are increasingly reported.

Author Statements

Footnotes

Declaration of interest: We declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Author Contributions

Conceptualization: MLTS; Data curation: MLTS; Funding acquisition: MLTS; Investigation: MLTS, CSL; Methodology: MLTS; Project administration: MLTS; Resources: MLTS, AOP; Software: MLTS.GC; JLSH; Supervision: MLTS.GC; JLSH, CSL; Validation: MLTS, MCR, AOP, SM, CSL; Visualization: MLTS.GC; JLSH, JL; AOP; Writing – original draft: MLTS.GC; JLSH, JL; Writing – review & editing: MLTS.GC; JLSH, JL.

Conflict of Interest Statement

The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Ethics

Where we don’t require, informed consent four each patient procedure.

Funding

We had no funding for this study.

Disclosure

We have no conflict of interest to disclose.

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