University of São Paulo: Organ damage reveals effects of severe covid-linked syndrome in children
Pthe first time, a survey conducted by the USP School of Medicine (FMUSP) identified the full extent of the effects of severe covid-19 on the tissues of children who died of the disease. The analyzes prove the presence of lesions caused by the sars-cov-2 virus in all vital organs of the body, associated with Pediatric Multisystemic Inflammatory Syndrome (SIM-P), responsible for cardiac, gastrointestinal and neurological complications. According to the authors of the study, the result reinforces the importance of researching the diagnosis of covid-19 in children with persistent fever, even if they have different clinical manifestations. The research also points out that all patients with SIM-P had obstructions in the blood vessels of the lungs (microtombroses), even with mild pneumonia.
The results of the work are presented in an article published in the most recent edition of the scientific journal EClinical Medicine , of the Lancet group . According to Professor Marisa Dolhnikoff, from FMUSP, who coordinated the research, autopsy studies of covid-19 in children are rare, because, fortunately, deaths in this age group are less frequent when compared to the numbers recorded among adults. “Our objective was to study the effects of covid-19 on the organs and tissues of children who died with the severe form of the disease”, he points out, “and to bring information that can help to understand the complications resulting from the infection, especially from the Multisystemic Inflammatory Syndrome Pediatric (SIM-P), which is a particular form of clinical presentation of covid-19 in children and adolescents. ”
Using a minimally invasive autopsy (postmortem diagnosis without opening the body and exposing the organs, using imaging techniques and biopsies), the researchers analyzed five patients, of various ages, from under one year old to adolescents over 15 years. “The three patients with SIM-P were more than eight years old”, reports the professor. “Changes in the tissues of all vital organs, that is, lungs, heart, kidneys, brain, liver and spleen, were analyzed using light microscopy and electron microscopy, in addition to the search for the sars-cov-2 virus by three methods different types, RT-PCR of tissues, immunohistochemistry and electron microscopy ”, explains the professor to Jornal da USP.
Autopsy findings in a child with covid-19, pediatric multisystem inflammatory syndrome (SIM-P) and encephalitis; the figure shows the presence of coronavirus in the brain (A), virus antigens (B) and viral particles (C, DE, and F) – Image provided by the researchers
Two patients had previous serious illnesses: one with congenital genetic disease and malformations, and the other with a neoplasm. “These two patients developed the most classic form of covid-19, with predominantly pulmonary disease, associated with complications from previous diseases”, describes Marisa. The other three were previously healthy and developed SIM-P, with different manifestations: myocarditis and heart failure; acute abdominal condition, simulating appendicitis; and predominantly neurological condition, with multiple and constant seizures. “These three patients had overweight or obesity in common, often associated with an increased risk of severe covid-19, both among adults and children.”
Electron microscopy image artificially colored of the cross section of a nerve fiber; inside there is a vesicle containing sars-cov-2 (pointed by the arrow) – Image provided by the researchers
Tissue viruses
“Identified for the first time, these findings indicate that viral tissue damage also plays an important role in causing complications from the disease.”
The research shows that patients with SIM-P had mild pneumonia caused by the sars-cov-2 virus with obstruction of blood vessels in the lungs (microthrombosis), necrosis of cardiac tissue (in two cases) and viral infection of blood vessel cells, showing the spread of the virus. “A viral myocarditis was the main cause of heart failure and a diffuse intestinal inflammation, also of viral cause, was responsible for the acute abdominal condition”, points out the professor. The virus was detected in the tissues of all patients, including the heart and lungs, the intestine of the patient with intestinal injury and the brain of the patient with seizures. “Identified for the first time, these findings indicate that viral tissue damage also plays an important role in causing complications from the disease.”
According to the professor, the results of the research reinforce that, although rare, severe covid-19 can affect children and lead to death. “Two main patterns of severe covid may exist, one of which is that of a disease with a predominance of pulmonary impairment (severe pneumonia caused by sars-cov-2, with diffuse alveolar damage), similarly to what is observed in adults”, he points out. The other is SIM-P, which can cause myocarditis and heart failure; colitis with important intestinal manifestations (severe abdominal pain, diarrhea, vomiting), simulating inflammation from other causes (appendicitis, for example); and acute neurological condition (acute encephalopathy) with seizures. “Different clinical manifestations can make the diagnosis of SIM-P very difficult, so it is very important that,
Pulmonary microthrombosis, already described in adults with severe covid-19, is also present in children with severe SIM-P, even if pneumonia by the sars-cov-2 virus is mild. “Furthermore, electron microscopy studies show the presence of vessels capillaries clogged by an accumulation of erythrocytes, leukocytes, cellular, and fibrin debris, indicating an impairment of microcirculation in all analyzed organs of five children” describes the Journal USP to professor Elia Caldini, from FMUSP, who also participated in the research. “These observations also have an impact on the treatment of children with severe SIM-P.”
According to the professor, the literature shows that SIM-P is characterized by a systemic and exacerbated inflammatory reaction, which can occur several days and even weeks after infection by sars-cov-2. “However, our findings indicate that SIM-P is not just an abnormal inflammatory reaction in response to the passage of the virus in the body”, he emphasizes. “We have shown that, in these severe cases, there is an intense viral invasion in different tissues, including blood vessels, heart, lungs, intestine and brain, leading to tissue damage by direct action of the virus. Persistent and systemic infection, with the spread of the virus to various organs, is likely to play a central role in the pathogenesis of SIM-P. ”
Elia Caldini – Photo provided by the researcher
“Different clinical manifestations can make the diagnosis of SIM-P very difficult, so it is very important that, in children with persistent fever who present any of these clinical presentations, the diagnosis of sars-cov-2 infection is considered and investigated, so that treatment can be started properly. ”
In order to understand the damage that the covid-19 virus causes to cells of different organs, studies in electron microscopy are essential. “Magnifications greater than 50,000 times are used to observe changes in the cells in which the virus is present, in order to relate them to the clinical manifestations of patients”, concludes Professor Elia.
The work’s findings are described in the article An autopsy study of the spectrum of severe COVID-19 in children: From SARS to different phenotypes of MIS-C , published in the scientific journal EClinical Medicine . The first authors of the text are the pathologist Amaro Nunes Duarte-Neto and professor Elia Caldini, from FMUSP, responsible for the study by electron microscopy.