Sistema Inmune, Infección por SARS-CoV-2 y Desarrollo de COVID-19

Resumen La infección por SARS-CoV-2 promueve un descontrol del sistema inmune con predominio de una respuesta inflamatoria de rápida instauración y el desencadenamiento de una tormenta de citocinas. El objetivo de esta revisión es comprender mejor los mecanismos inmunológicos y su descontrol activados por SARS-CoV-2. La activación de la inmunidad innata, contra la infección, es el factor clave para el control viral o su progresión hacia COVID-19. La respuesta inmune adaptativa, igualmente es perturbada por SARS-CoV-2 con lo cual se posibilita una mayor tasa de infección, así como también el descontrol inmunológico sistémico que puede desencadenar shock y daño tisular en diferentes órganos, muerte por COVID-19 o autoinmunidad post COVID-19.

Abstract The SARS-CoV-2 infection promotes a lack of control of the immune system with a predominance of a rapidly onset inflammatory response and the triggering of a cytokine storm. The objective of this review is to understand better the immune mechanisms and their lack of control activated by SARS-CoV-2. The activation of innate immunity against infection is the key factor for viral control or its progression towards COVID-19. The adaptive immune response is also disturbed by SARS-CoV-2, which enables a higher infection rate, as well as systemic immune lack of control that can trigger shock and tissue damage in different organs, death from COVID-19 or autoimmunity post-COVID-19.

Seroprevalence of Triatoma virus (Dicistroviridae: Cripaviridae) antibodies in Chagas disease patients.

BACKGROUND: Chagas disease is caused by Trypanosoma cruzi, and humans acquire the parasite by exposure to contaminated feces from hematophagous insect vectors known as triatomines. Triatoma virus (TrV) is the sole viral pathogen of triatomines, and is transmitted among insects through the fecal-oral route and, as it happens with T. cruzi, the infected insects release the virus when defecating during or after blood uptake. METHODS: In this work, we analysed the occurrence of anti-TrV antibodies in human sera from Chagas disease endemic and non-endemic countries, and developed a mathematical model to estimate the transmission probability of TrV from insects to man, which ranged between 0.00053 and 0.0015. RESULTS: Our results confirm that people with Chagas disease living in Bolivia, Argentina and Mexico have been exposed to TrV, and that TrV is unable to replicate in human hosts. CONCLUSIONS: We presented the first experimental evidence of antibodies against TrV structural proteins in human sera.

Maternal infection with Trypanosoma cruzi and congenital Chagas disease induce a trend to a type 1 polarization of infant immune responses to vaccines.

BACKGROUND: We previously showed that newborns congenitally infected with Trypanosoma cruzi (M+B+) display a strong type 1 parasite-specific T cell immune response, whereas uninfected newborns from T. cruzi-infected mothers (M+B-) are prone to produce higher levels of proinflammatory cytokines than control neonates (M-B-). The purpose of the present study was to determine if such fetal/neonatal immunological environments could alter the response to standard vaccines administered in early life. METHODOLOGY: Infants (6-7 months old) living in Bolivia, an area highly endemic for T. cruzi infection, and having received Bacillus Calmette Guerin (BCG), hepatitis B virus (HBV), diphtheria and tetanus vaccines, were enrolled into the M+B+, M+B-, M-B- groups mentioned above. The production of IFN-gamma and IL-13, as markers of Th1 and Th2 responses respectively, by peripherical blood mononuclear cells stimulated with tuberculin purified protein derivative of Mycobacterium tuberculosis (PPD) or the vaccinal antigens HBs, diphtheria toxoid (DT) or tetanus toxoid (TT), as well as circulating levels of IgG antibodies against HBsAg, DT and TT were analyzed in infants. Cellular responses to the superantigen SEB were also monitored in M+B+, M+B-, M-B-infants and newborns. PRINCIPAL FINDINGS: M+B+ infants developed a stronger IFN-gamma response to hepatitis B, diphtheria and tetanus vaccines than did M+B- and M-B- groups. They also displayed an enhanced antibody production to HBsAg. This was associated with a type 1-biased immune environment at birth, since cells of M+B+ newborns produced higher IFN-gamma levels in response to SEB. M+B- infants produced more IFN-gamma in response to PPD than the other groups. IL-13 production remained low and similar in all the three groups, whatever the subject's ages or vaccine status. CONCLUSION: These results show that: i) both maternal infection with T. cruzi and congenital Chagas disease do not interfere with responses to BCG, hepatitis B, diphtheria and tetanus vaccines in the neonatal period, and ii) the overcoming of immunological immaturity by T. cruzi infection in early life is not limited to the development of parasite-specific immune responses, but also tends to favour type 1 immune responses to vaccinal antigens.

Human congenital infection with Trypanosoma cruzi induces phenotypic and functional modifications of cord blood NK cells.

We studied the phenotype and activity of cord blood natural killer (NK) cells in newborns congenitally infected with Trypanosoma cruzi. We found that the proportion of CD56(bright) NK cells was significantly decreased in cord blood from these newborns, suggesting they may have been recruited to secondary lymphoid organs. The remaining CD56(bright) NK cells exhibited a defective ability in the production of interferon (IFN)-gamma following in vitro activation with interleukin (IL)-12 + IL-2 or IL-12 + IL-15 cytokines, as compared with NK cells from uninfected newborns. In addition, cord blood NK cells from congenitally infected newborns stimulated with cytokines have a decreased release of granzyme B (GrB) when incubated with K562 target cells. This defect in cytotoxic effector function is associated with a reduced surface expression of activating NK receptors (NKp30, NKp46, and NKG2D) on CD56(dim) NK cells compared with uninfected newborns. These alterations of fetal NK cells from congenitally infected newborns may reflect a down-regulation of the NK cell response after an initial peak of activation and could also be the result of T. cruzi modulating the immune response.

[Integral treatment of congenital Chagas disease: the Bolivian experience ]. / Tratamiento integral de la enfermedad de Chagas congenita: la experiencia boliviana.

We have analyzed the response to the treatment with benznidazol in newborns and nurslings in the Hospital Materno Infantil Germán Urquidi of Cochabamba, Bolivia, between 1999 and 2002. It is important an integral treatment of the nursling with a subsequent information directed to the family. The response was close to 100% when the treatment was correctly administrated. They were not adverse effects and the detected biochemical alterations did not present clinical significance.

[Serum levels for IgM and IgA antibodies to anti-trypanosoma cruzi in samples of blood from newborns from mothers with positive serology for Chagas disease]. / Dosificación de anticuerpos IgM e IgA anti-trypanosoma cruzi en sangre de recién nacidos de madres con serología positiva para Chagas.

This study compares the levels of specific antibodies IgM and IgA for Chagas in samples of blood from newborns. Three groups of cord blood samples have been analysed: a group of 42 samples from newborns, displaying positive parasitemia, of seropositive mothers (M+B+), 68 samples from newborns with negative parasitemia whose mothers were seropositive (M+B-) and a group of 45 control newborns coming from mothers with negative serology for Chagas. From the 42 M+B+ samples with congenital Chagas disease, 81 and 82.9% displayed detectable levels of IgM and IgA antibodies, respectively In the M+B- group, 70.6 and 33.8% presented antibodies of IgM and IgA classes, respectively, whereas in the control group M-B-, we detected 6% and 11.1% of IgM and IgA antibodies, respectively. The calculated sensitivity of detection of congenital cases using IgM or IgA antibodies was of 82.9% and 80.9% respectively, whereas the specificity of detection was of 29.4% for IgM antibodies and of 66.1% for IgA antibodies.