COVA1-18 neutralizing antibody protects against SARS-CoV-2 in three preclinical models.

Effective treatments against Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) are urgently needed. Monoclonal antibodies have shown promising results in patients. Here, we evaluate the in vivo prophylactic and therapeutic effect of COVA1-18, a neutralizing antibody highly potent against the B.1.1.7 isolate. In both prophylactic and therapeutic settings, SARS-CoV-2 remains undetectable in the lungs of treated hACE2 mice. Therapeutic treatment also causes a reduction in viral loads in the lungs of Syrian hamsters. When administered at 10 mg kg-1 one day prior to a high dose SARS-CoV-2 challenge in cynomolgus macaques, COVA1-18 shows very strong antiviral activity in the upper respiratory compartments. Using a mathematical model, we estimate that COVA1-18 reduces viral infectivity by more than 95% in these compartments, preventing lymphopenia and extensive lung lesions. Our findings demonstrate that COVA1-18 has a strong antiviral activity in three preclinical models and could be a valuable candidate for further clinical evaluation.

Success of prophylactic antiviral therapy for SARS-CoV-2: Predicted critical efficacies and impact of different drug-specific mechanisms of action.

Repurposed drugs that are safe and immediately available constitute a first line of defense against new viral infections. Despite limited antiviral activity against SARS-CoV-2, several drugs are being tested as medication or as prophylaxis to prevent infection. Using a stochastic model of early phase infection, we evaluate the success of prophylactic treatment with different drug types to prevent viral infection. We find that there exists a critical efficacy that a treatment must reach in order to block viral establishment. Treatment by a combination of drugs reduces the critical efficacy, most effectively by the combination of a drug blocking viral entry into cells and a drug increasing viral clearance. Below the critical efficacy, the risk of infection can nonetheless be reduced. Drugs blocking viral entry into cells or enhancing viral clearance reduce the risk of infection more than drugs that reduce viral production in infected cells. The larger the initial inoculum of infectious virus, the less likely is prevention of an infection. In our model, we find that as long as the viral inoculum is smaller than 10 infectious virus particles, viral infection can be prevented almost certainly with drugs of 90% efficacy (or more). Even when a viral infection cannot be prevented, antivirals delay the time to detectable viral loads. The largest delay of viral infection is achieved by drugs reducing viral production in infected cells. A delay of virus infection flattens the within-host viral dynamic curve, possibly reducing transmission and symptom severity. Thus, antiviral prophylaxis, even with reduced efficacy, could be efficiently used to prevent or alleviate infection in people at high risk.

Tratamento seletivo do hipoparatireoidismo após tireoidectomia total baseado nos valores de PTH / Selective treatment for hypoparathyroidism after total thyroidectomy based on PTH levels

Introdução: A hipocalcemia é a complicação mais comum após a tireoidectomia total e responsável por um maior tempo de internação. A fim de evitar manifestações da hipocalcemia, alguns autores rotineiramente fazem suplementação oral de cálcio, outros, por sua vez, prolongam a estadia do doente aguardando dosagens séricas de cálcio para indicar a reposição. Objetivo: Avaliar a eficácia da suplementação de cálcio/calcitriol baseado em valores pós operatórios de paratormônio(PTH) , afim de evitar manifestações clínicas de hipocalcemia em pacientes submetidos à tireoidectomia total. Materiais e Métodos: Estudo prospectivo com 31 pacientes submetidos à tireoidectomia total ou totalização, com ou sem esvaziamento recorrencial. O PTH foi colhido após 1 hora de pós operatório. A suplementação seletiva foi determinada pelo valor do PTH com cálcio (PTH >5 e <15pg/ml), cálcio e calcitriol (PTH <5pg/ml) e foram correlacionadas com sintomas de hipocalcemia durante 10 dias de pós operatório. Resultados: Nenhum paciente com PTH>15pg/ml desenvolveu sintomas (p=0,007). Dentre os pacientes com PTH <15pg/ml, 9 (52,84%) permaneceram assintomáticos com uso da medicação. Cinco pacientes (29,41%) não fizeram uso da suplementação prescrita e todos apresentaram sintomas. Três pacientes apresentaram sintomas, apesar do uso correto da suplementação.(p=0,009). Conclusão: A suplementação seletiva de cálcio ou cálcio associada ao calcitriol, baseada no PTH, é eficaz para evitar os sintomas de hipocalcemia.

Background: Hypocalcemia is the most common complication after total thyroidectomy and the major determinant in delay of discharge. Because of this, some authors routinely use oral supplementation of oral calcium, while others postpone hospital discharge waiting of multiple calcium dosages. Objectives: To test a selective oral calcium/calcitriol supplementation to avoid clinical manifestations of hypocalcemia based on parathyroid hormone levels after total thyroidectomy. Methods: Prospective study with 31 patients undergoing total thyroidectomy or completion, with or without central neck dissection. Parathyroid hormone (PTH) was measured 1 hour postoperative period. Selective supplementation was determined by serum PTH levels with oral calcium (PTH>5pg/ ml and <15pg/ml) or oral calcium plus calcitriol (PTH<5pg/ml) and correlated with symptoms of hypocalcemia during 10 days postthyroidectomy. Results: None of the patients (14/31) with PTH levels > 15pg/ml developed symptoms (p=0,007). Among seventeen patients with PTH<15pg/ml, 9 (52,84%) patients had adequate supplementation and remained asymptomatic. Five patients (29,41%) had clinical manifestations without correct supplementation. Three patients developed symptoms taking correct supplementation. (p=0,009). Conclusions: The selective supplementation based on postthyroidectomy PTH levels can be used safely to avoid clinical manifestations of hypocalcemia.

Gestão da capacidade de atendimento em hospitais de câncer

Em um centro de tratamento de câncer, um dos fatores críticos de sucesso é o diagnóstico precoce. A agilidade no encaminhamento do paciente a adequadas condutas terapêuticas, com a redução do tempo de espera é fundamental para o aumento da sobrevida, melhoria da qualidade de vida e chances de cura. Neste contexto, o objetivo desse trabalho é a formulação de um modelo para gestão da capacidade de atendimento em hospitais de câncer, apresentando contribuições ao entendimento e identificação de melhores alternativas de acesso, agendamento, utilização de recursos humanos e do parque de equipamentos disponíveis. A metodologia adotada foi analisar o fluxo de tratamento reduzindo o intervalo de tempo entre o registro do paciente e a execução de procedimentos terapêuticos

One of the critical success factors in a cancer treatment center is an early diagnosis. The rapidness in guiding patients to adequate therapeutic conduct, along with wait time reduction is basic for the increase of life span and the improvement of the quality of life and possibilities of cure. Under these circumstances, the objective of this work is the formulation of a model for capacity management of attendance in cancer hospitals, demonstrating contributions to the comprehension and identification of better alternatives of access, appointment scheduling, use of human resources and the availability of equipment. The methodology adopted was to analyze the treatment patient flow and accelerate the beginning of the cancer treatment, thus reducing the wait time between the patient’s enrolment and the execution of therapeutic procedures