Emergency response for evaluating SARS-CoV-2 immune status,seroprevalence and convalescent plasma in Argentina

We report the emergency development and application of a robust serologic test to evaluate acute and convalescent antibody responses to SARS-CoV-2 in Argentina. The assays, COVIDAR IgG and IgM, which were produced and provided for free to health authorities, private and public health institutions and nursing homes, use a combination of a trimer stabilized spike protein and the receptor binding domain (RBD) in a single enzyme-linked immunosorbent assay (ELISA) plate. Over half million tests have already been distributed to detect and quantify antibodies for multiple purposes, including assessment of immune responses in hospitalized patients and large seroprevalence studies in neighborhoods, slums and health care workers, which resulted in a powerful tool for asymptomatic detection and policy making in the country. Analysis of antibody levels and longitudinal studies of symptomatic and asymptomatic SARS-CoV-2 infections in over one thousand patient samples provided insightful information about IgM and IgG seroconversion time and kinetics, and IgM waning profiles. At least 35% of patients showed seroconversion within 7 days, and 95% within 45 days of symptoms onset, with simultaneous or close sequential IgM and IgG detection. Longitudinal studies of asymptomatic cases showed a wide range of antibody responses with median levels below those observed in symptomatic patients. Regarding convalescent plasma applications, a protocol was standardized for the assessment of end point IgG antibody titers with COVIDAR with more than 500 plasma donors. The protocol showed a positive correlation with neutralizing antibody titers, and was used for clinical trials and therapies across the country. Using this protocol, about 80% of convalescent donor plasmas were potentially suitable for therapies. Here, we demonstrate the importance of providing a robust and specific serologic assay for generating new information about antibody kinetics in infected individuals and mitigation policies to cope with pandemic needs.     

The maximal body mass–area relationship in island mammals

Aim A positive power relationship between maximal body mass and land area has previously been reported of the form M_max ∝ Area^0.5 whilst allometric scaling theory predicts either M_max ∝ Area^1.33 or M_max ∝ Area¹. We provide an analysis of the maximal mass–area relationship for four island systems, to test the hypothesis that community relaxation following isolation converges in each case to a slope of Area^0.5. Location Islands of the Japanese archipelago, the western Mediterranean, the Sea of Cortés and Southeast Asia. Methods We calculated the relationship between island area and the maximal body mass of the largest mammal species on the island using linear regression models with log‐transformed variables, and tested the hypothesis that the slopes were not significantly different from 0.5. Results We found a slope of 0.47 within the Japanese archipelago, 0.42 for western Mediterranean islands, 0.73 for the Sea of Cortés islands and 0.50 for Southeast Asian islands. None of these slopes were significantly different from 0.5. Main conclusions Our results provide further empirical support for previous findings of a general maximal body mass–area relationship of M_max ∝ Area^0.5, but they deviate from theoretical predictions. We hypothesize that this mass–area relationship was the ultimate end point of community relaxation initiated by the isolation of the mammal communities. Maximal body mass on each island today probably reflects the interaction between energetic constraints, home range size and island area.     

Adeno-Associated Viral Vector Serotype 5 Poorly Transduces Liver in Rat Models

Preclinical studies in mice and non-human primates showed that AAV serotype 5 provides efficient liver transduction and as such seems a promising vector for liver directed gene therapy. An advantage of AAV5 compared to serotype 8 already shown to provide efficient correction in a phase 1 trial in patients suffering from hemophilia B, is its lower seroprevalence in the general population. Our goal is liver directed gene therapy for Crigler-Najjar syndrome type I, inherited severe unconjugated hyperbilirubinemia caused by UGT1A1 deficiency. In a relevant animal model, the Gunn rat, we compared the efficacy of AAV 5 and 8 to that of AAV1 previously shown to be effective. Ferrying a construct driving hepatocyte specific expression of UGT1A1, both AAV8 and AAV1 provided an efficient correction of hyperbilirubinemia. In contrast to these two and to other animal models AAV5 failed to provide any correction. To clarify whether this unexpected finding was due to the rat model used or due to a problem with AAV5, the efficacy of this serotype was compared in a mouse and two additional rat strains. Administration of an AAV5 vector expressing luciferase under the control of a liver specific promoter confirmed that this serotype poorly performed in rat liver, rendering it not suitable for proof of concept studies in this species.