Trombocitopenia imune associada à COVID-19: relato de caso e revisão de literatura / Immune thrombocytopenia associated to Covid-19: case report and literature review

Pacientes com COVID-19 podem apresentar trombocitopenia grave. Esse achado tem importante impacto no aumento de desfechos negativos e mortalidade, representando um importante fator prognóstico da doença. Vários mecanismos etiopatogênicos foram descritos, sendo a trombocitopenia imune um dos fatores mais frequentes. A abordagem terapêutica inclui como opções: corticoterapia, imunoglobulina, transfusão de plaquetas e análogos da trombopoietina. Este estudo tem como objetivo apresentar o relato de caso de uma paciente com PCR positivo para SARS-CoV-2, que desenvolveu queda acentuada e abrupta das plaquetas no 20º dia de internação. Além disso, casos semelhantes na literatura foram analisados e as possibilidades terapêuticas elencadas. Por fim, conclui-se que há a necessidade de estudos mais amplos para auxiliar a criação de protocolos sistematizados para o diagnóstico e abordagem dessa condição.

COVID-19 patients may experience severe thrombocytopenia. Such finding has an important impact on the increase in negative outcomes and mortality, representing an important prognostic factor of the disease. Several etiopathogenetic mechanisms have been described, in which immune thrombocytopenia is one of the most frequent. The therapeutic approach includes as options: corticosteroid therapy, immunoglobulin, platelet transfusion and thrombopoietin analogs. The following study aims to present a case report of a patient with positive PCR for SARSCoV-2 who developed a severe and abrupt drop in platelets on the 20th day of hospitalization. In addition, similar cases reports in the literature were analyzed and the therapeutic possibilities were listed. Finally, it is concluded that there is a need for broader studies to help create systematic protocols for the diagnosis and approach of this condition.

Phage-fused epitopes from Leishmania infantum used as immunogenic vaccines confer partial protection against Leishmania amazonensis infection.

Two mimotopes of Leishmania infantum identified by phage display were evaluated as vaccine candidates in BALB/c mice against Leishmania amazonensis infection. The epitope-based immunogens, namely B10 and C01, presented as phage-fused peptides; were used without association of a Th1 adjuvant, and they were administered isolated or in combination into animals. Both clones showed a specific production of interferon-gamma (IFN-γ), interleukin-12 (IL-12) and granulocyte/macrophage colony-stimulating factor (GM-CSF) after in vitro spleen cells stimulation, and they were able to induce a partial protection against infection. Significant reductions of parasite load in the infected footpads, liver, spleen, bone marrow and paws' draining lymph nodes were observed in the immunized mice, in comparison with the control groups (saline, saponin, wild-type and non-relevant clones). Protection was associated with an IL-12-dependent production of IFN-γ, mediated mainly by CD8(+) T cells, against parasite proteins. Protected mice also presented low levels of IL-4 and IL-10, as well as increased levels of parasite-specific IgG2a antibodies. The association of both clones resulted in an improved protection in relation to their individual use. More importantly, the absence of adjuvant did not diminish the cross-protective efficacy against Leishmania spp. infection. This study describes for the first time two epitope-based immunogens selected by phage display technology against L. infantum infected dogs sera, which induced a partial protection in BALB/c mice infected with L. amazonensis.

Mimotope-based vaccines of Leishmania infantum antigens and their protective efficacy against visceral leishmaniasis.

BACKGROUND: The development of cost-effective prophylactic strategies to prevent leishmaniasis has become a high-priority. The present study has used the phage display technology to identify new immunogens, which were evaluated as vaccines in the murine model of visceral leishmaniasis (VL). Epitope-based immunogens, represented by phage-fused peptides that mimic Leishmania infantum antigens, were selected according to their affinity to antibodies from asymptomatic and symptomatic VL dogs' sera. METHODOLOGY/MAIN FINDINGS: Twenty phage clones were selected after three selection cycles, and were evaluated by means of in vitro assays of the immune stimulation of spleen cells derived from naive and chronically infected with L. infantum BALB/c mice. Clones that were able to induce specific Th1 immune response, represented by high levels of IFN-γ and low levels of IL-4 were selected, and based on their selectivity and specificity, two clones, namely B10 and C01, were further employed in the vaccination protocols. BALB/c mice vaccinated with clones plus saponin showed both a high and specific production of IFN-γ, IL-12, and GM-CSF after in vitro stimulation with individual clones or L. infantum extracts. Additionally, these animals, when compared to control groups (saline, saponin, wild-type phage plus saponin, or non-relevant phage clone plus saponin), showed significant reductions in the parasite burden in the liver, spleen, bone marrow, and paws' draining lymph nodes. Protection was associated with an IL-12-dependent production of IFN-γ, mainly by CD8+ T cells, against parasite proteins. These animals also presented decreased parasite-mediated IL-4 and IL-10 responses, and increased levels of parasite-specific IgG2a antibodies. CONCLUSIONS/SIGNIFICANCE: This study describes two phage clones that mimic L. infantum antigens, which were directly used as immunogens in vaccines and presented Th1-type immune responses, and that significantly reduced the parasite burden. This is the first study that describes phage-displayed peptides as successful immunogens in vaccine formulations against VL.