Autoimmune anti-DNA and anti-phosphatidylserine antibodies predict development of severe COVID-19.

High levels of autoimmune antibodies are observed in COVID-19 patients but their specific contribution to disease severity and clinical manifestations remains poorly understood. We performed a retrospective study of 115 COVID-19 hospitalized patients with different degrees of severity to analyze the generation of autoimmune antibodies to common antigens: a lysate of erythrocytes, the lipid phosphatidylserine (PS) and DNA. High levels of IgG autoantibodies against erythrocyte lysates were observed in a large percentage (up to 36%) of patients. Anti-DNA and anti-PS antibodies determined upon hospital admission correlated strongly with later development of severe disease, showing a positive predictive value of 85.7% and 92.8%, respectively. Patients with positive values for at least one of the two autoantibodies accounted for 24% of total severe cases. Statistical analysis identified strong correlations between anti-DNA antibodies and markers of cell injury, coagulation, neutrophil levels and erythrocyte size. Anti-DNA and anti-PS autoantibodies may play an important role in the pathogenesis of COVID-19 and could be developed as predictive biomarkers for disease severity and specific clinical manifestations.

The Search of a Malaria Vaccine: The Time for Modified Immuno-Potentiating Probes.

Malaria is a deadly disease that takes the lives of more than 420,000 people a year and is responsible for more than 229 million clinical cases globally. In 2019, 95% of malaria morbidity occurred in African countries. The development of a highly protective vaccine is an urgent task that remains to be solved. Many vaccine candidates have been developed, from the use of the entire attenuated and irradiated pre-erythrocytic parasite forms (or recombinantly expressed antigens thereof) to synthetic candidates formulated in a variety of adjuvants and delivery systems, however these have unfortunately proven a limited efficacy. At present, some vaccine candidates are finishing safety and protective efficacy trials, such as the PfSPZ and the RTS,S/AS01 which are being introduced in Africa. We propose a strategy for introducing non-natural elements into target antigens representing key epitopes of Plasmodium spp. Accordingly, chemical strategies and knowledge of host immunity to Plasmodium spp. have served as the basis. Evidence is obtained after being tested in experimental rodent models for malaria infection and recognized for human sera from malaria-endemic regions. This encourages us to propose such an immune-potentiating strategy to be further considered in the search for new vaccine candidates.

Liver and kidney dysfunction, hypoglycemia, and thrombocytopenia in Plasmodium vivax malaria patients at a Colombian Northwest region.

Plasmodium vivax has high morbidity, it is the Plasmodium species with the greatest worldwide distribution, and its ability to trigger severe symptoms is currently recognized. The present study aims to compare the clinical and epidemiological characteristics of patients with P. vivax malaria, with and without complication criteria, in an endemic area for malaria transmission in northwest Colombia. A descriptive cross-sectional study was carried out between 2017 and 2019, patients with P.vivax severe malaria (n = 50), non-severe malaria (n = 56) and healthy controls (n = 50) were included. Sociodemographic, clinical, hematological, and biochemical characteristics were analyzed. Clinical follow-up was carried out in a group of patients with severe malaria. The statistical analysis was carried out in GraphPad Prism; the Chi-square test analyzed categorical variables, comparisons of variables for the three groups were carried out by the Kruskal-Wallis test and comparison between two groups by the Mann-Whitney test. A multiple correspondence analysis described the relationship between variables, which was carried out through the R software. One hundred fifty-six individuals were linked to the study, 76 women and 80 men, between 3 and 71 years old. For 50% of the patients, it was their first malaria episode; 42% of the patients classified with severe malaria required hospitalization, compared to 7.1% of the patients with non-severe malaria. Parasitaemia was similar in both clinical groups; however, 10% of severe patients presented high parasitemia, between 20,000-135,000. The most frequent clinical characteristics in patients with severe malaria were severe thrombocytopenia in 54%, hypoglycemia in 48%, and liver and kidney failure in 30%. Biochemical and hematological parameters returned to normal in 90% of the patients with severe malaria on the third day after starting treatment. Thrombocytopenia, hypoglycemia, and liver and kidney dysfunctions were the most frequent P. vivax malaria complications in this study. Hemoglobin concentration and parasite count were not related to the clinical condition of patients. Thrombocytopenia was the most frequent finding in patients with malaria, and its severity presented an inverse relationship with the number of previous malaria episodes.

Atypical memory B-cells and autoantibodies correlate with anemia during Plasmodium vivax complicated infections.

Malaria caused by Plasmodium vivax is a highly prevalent infection world-wide, that was previously considered mild, but complications such as anemia have been highly reported in the past years. In mice models of malaria, anti-phosphatidylserine (anti-PS) autoantibodies, produced by atypical B-cells, bind to uninfected erythrocytes and contribute to anemia. In human patients with P. falciparum malaria, the levels of anti-PS, atypical B-cells and anemia are strongly correlated to each other. In this study, we focused on assessing the relationship between autoantibodies, different B-cell populations and hemoglobin levels in two different cohorts of P. vivax patients from Colombia, South America. In a first longitudinal cohort, our results show a strong inverse correlation between different IgG autoantibodies tested (anti-PS, anti-DNA and anti-erythrocyte) and atypical memory B-cells (atMBCs) with hemoglobin in both P. vivax and P. falciparum patients over time. In a second cross-sectional cohort, we observed a stronger relation between hemoglobin levels, atMBCs and autoantibodies in complicated P. vivax patients compared to uncomplicated ones. Altogether, these data constitute the first evidence of autoimmunity associating with anemia and complicated P. vivax infections, suggesting a role for its etiology through the expansion of autoantibody-secreting atMBCs.