Virulence Profiles of Wild-Type, P.1 and Delta SARS-CoV-2 Variants in K18-hACE2 Transgenic Mice.

Since December 2019, the world has been experiencing the COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and we now face the emergence of several variants. We aimed to assess the differences between the wild-type (Wt) (Wuhan) strain and the P.1 (Gamma) and Delta variants using infected K18-hACE2 mice. The clinical manifestations, behavior, virus load, pulmonary capacity, and histopathological alterations were analyzed. The P.1-infected mice showed weight loss and more severe clinical manifestations of COVID-19 than the Wt and Delta-infected mice. The respiratory capacity was reduced in the P.1-infected mice compared to the other groups. Pulmonary histological findings demonstrated that a more aggressive disease was generated by the P.1 and Delta variants compared to the Wt strain of the virus. The quantification of the SARS-CoV-2 viral copies varied greatly among the infected mice although it was higher in P.1-infected mice on the day of death. Our data revealed that K18-hACE2 mice infected with the P.1 variant develop a more severe infectious disease than those infected with the other variants, despite the significant heterogeneity among the mice.

Long-term effect of uncomplicated Plasmodium berghei ANKA malaria on memory and anxiety-like behaviour in C57BL/6 mice.

BACKGROUND: Cerebral malaria, the main complication of Plasmodium falciparum infection in humans, is associated with persistent neurocognitive sequels both in human disease and the murine experimental model. In recent years, cognitive deficits related to uncomplicated (non-cerebral) malaria have also been reported in chronically exposed residents of endemic areas, but not in some murine experimental models of non-cerebral malaria. This study aimed at evaluating the influence of uncomplicated malaria on different behavioural paradigms associated with memory and anxiety-like parameters in a murine model that has the ability to develop cerebral malaria. METHODS: Plasmodium berghei ANKA-infected and non-infected C57BL/6 mice were used. Development of cerebral malaria was prevented by chloroquine treatment starting on the fourth day of infection. The control group (non-infected mice) were treated with PBS. The effect of uncomplicated malaria infection on locomotor habituation, short and long-term memory and anxious-like behaviour was evaluated 64 days after parasite clearance in assays including open field, object recognition, Y-maze and light/dark tasks. RESULTS: Plasmodium berghei ANKA-infected mice showed significant long-lasting disturbances reflected by a long-term memory-related behaviour on open field and object recognition tasks, accompanied by an anxious-like phenotype availed on open field and light-dark tasks. CONCLUSIONS: Long-term neurocognitive sequels may follow an uncomplicated malaria episode in an experimental model prone to develop cerebral malaria, even if the infection is treated before the appearance of clinical signs of cerebral impairment.

Sera of patients with systemic lupus erythematosus react with plasmodial antigens and can inhibit the in vitro growth of Plasmodium falciparum.

The acquisition of protective immunity in malaria is a slow process during which autoantibodies are produced. The present work aimed at studying a possible interference of autoimmune responses on malaria immune protection. This was done by investigating the presence of autoantibodies in the sera of malarious patients, by searching for reactivity of autoantibodies from autoimmune patients against plasmodial antigens, and by studying the effect of such antibodies on the in vitro growth of Plasmodium falciparum. Sera from systemic lupus erythematosus (SLE) and malaria patients were tested against autologous and plasmodial antigens. Out of the 109 SLE sera tested, 48 (44%) reacted against the parasite. In addition, 26 (47%) out of 55 randomly selected sera, mainly those containing anti-DNA and antinuclear autoantibodies, were able to inhibit parasite growth to some extent. Conversely, a high frequency (81%) of sera of malaria patients exhibited reactivity against autoantigens. The results show that patients with autoimmune processes can produce antibodies that recognize plasmodial antigens in the absence of plasmodial infection, that malaria patients can produce autoantibodies, that SLE sera can inhibit plasmodial growth in vitro, and that the presence of anti-DNA and antinuclear antibodies may be important in such anti-plasmodial activity. It is concluded that autoimmune responses may have influence on the protective immunity against malaria.