Clinical study of antibody cocktail therapy for COVID-19

Background: Randomized phase III clinical trials suggest that the antibody cocktail containing casirivimab and imdevimab reduces the risk of hospitalization/death in high-risk COVID-19 patients. However, the efficacy of the cocktail in daily clinical practice remains unknown.

The impact of COVID-19 on urban agriculture in Sao Paulo, Brazil

During the initial months of the COVID-19 pandemic, farmers worldwide were greatly affected by disruptions in the food chain. In 2020, Sao Paulo city experienced most of the effects of the pandemic in Brazil, with 15,587 deaths through December 2020. Here, we describe the impacts of COVID-19 on urban agriculture (UA) in Sao Paulo from April to August 2020. We analyzed two governmental surveys of 2100 farmers from Sao Paulo state and 148 from Sao Paulo city and two qualitative surveys of volunteers from ten community gardens and seven urban farmers. Our data showed that 50% of the farmers were impacted by the pandemic with drops in sales, especially those that depended on intermediaries. Some farmers in the city adapted to novel sales channels, but 22% claimed that obtaining inputs became difficult. No municipal support was provided to UA in Sao Paulo, and pre-existing issues were exacerbated. Work on community gardens decreased, but no garden permanently closed. Post COVID-19, UA will have the challenge of maintaining local food chains established during the pandemic. Due to the increase in the price of inputs and the lack of technical assistance, governmental efforts should be implemented to support UA.

A Case of Encephalitis and Adrenal Insufficiency in a Patient With Panhypopituitarism After COVID-19 Vaccination

Background: Since COVID-19 vaccination was introduced, various adverse effects have been linked to the vaccines. In patients with hypopituitarism, adrenal insufficiency due to the side reactions including fever of COVID-19 vaccination is concerned. Clinical Case: A 33-year woman was on medical therapy including hydrocortisone (HC) for panhypopituitarism arising from surgical treatment of a pituitary adenoma in 2006. She received a COVID-19 vaccination on day X-3. On day X-2, she developed fever in the morning and became unconscious in the evening. She was brought to our hospital by her family at night on day X. She had fever of 40.5°C, low blood pressure, and Glasgow Coma Scale (GCS) of 11. Her neck was supple and she had no quadriplegia. A COVID-19 PCR test was negative. Blood tests showed elevated white blood cell count (8900/μL;reference range: 3300–8600/µL) and C-reactive protein (138.3 mg/l;reference range: 0-1.44 mg/l). Blood glucose (81 mg/dL), ACTH (<3. 00 pg/mL;reference range: 7.2–63.3 pg/mL), and cortisol (1.9 μg/dL;reference range: 2.9–19.4 µg/dL) were low. Serum electrolytes were normal. A computed tomography scan showed no abnormality. Adrenal insufficiency was suspected, and she received HC intravenously. Her blood glucose and blood pressure increased, but her disorientation persisted. Lumbar puncture with cerebrospinal fluid (CSF) examination revealed slightly elevated cell counts (8 μ/L;reference range ≤4 μ/L) with average protein and glucose levels. Magnetic resonance imaging (MRI) of the brain revealed abnormal hyperintensity in the splenium of the corpus callosum on diffusion-weighted images and decreased apparent diffusion coefficient in the lesion, suggesting clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS). During her hospital stay, she received a 7-day course of meropenem and acyclovir for suspected meningoencephalitis. Her consciousness disturbance improved to GCS of 15 on day X+1 and her fever decreased on day X+2. HSV and VZV PCR tests were negative on CSF examination, and antibiotics and antivirals were discontinued on day X+7. On day X+8, brain MRI showed complete resolution of the corpus callosum lesion. She discharged on day X+18 without any neurological sequelae. Conclusions: For most vaccines, the incidence rates of encephalitis are low at 0.1–0.2 per 100,000 vaccinated individuals (1). The present patient developed fever and adrenal insufficiency after COVID-19 vaccination, and her prolonged disturbance of consciousness after HC administration led to the diagnosis of MERS. MERS should be considered in patients with adrenocortical insufficiency who show delayed recovery from unconsciousness with HC administration after COVID-19 vaccination. Reference: (1) Huynh W, Cordato DJ, Kehdi E, Masters LT, Dedousis C. Post-vaccination encephalomyelitis: literature review and illustrative case. J Clin Neurosci. 2008 Dec;15(12): 1315-22.Presentation: No date and time listed

A crystallographic snapshot of SARS-CoV-2 main protease maturation process

SARS-CoV-2 is the causative agent of COVID-19. The dimeric form of the viral Mpro is responsible for the cleavage of the viral polyprotein in 11 sites, including its own N- and C-terminus. The lack of structural information for intermediary forms of Mpro is a setback for the understanding its self-maturation process. Herein, we used X-ray crystallography combined with biochemical data to characterize multiple forms of SARS-CoV-2 Mpro. For the immature form, we show that extra N-terminal residues caused conformational changes in the positioning of domainthree over the active site, hampering the dimerization and diminishing its activity. We propose that this form preludes the cis and trans-cleavage of N-terminal residues. Using fragment screening, we probe new cavities in this form which can be used to guide therapeutic development. Furthermore, we characterized a serine site-directed mutant of the Mpro bound to its endogenous Nand C-terminal residues during dimeric association stage of the maturation process. We suggest this form is a transitional state during the C-terminal trans-cleavage. This data sheds light in the structural modifications of the SARS-CoV-2 main protease during its self-maturation process.

A Crystallographic Snapshot of SARS-CoV-2 Main Protease Maturation Process.

SARS-CoV-2 is the causative agent of COVID-19. The dimeric form of the viral Mpro is responsible for the cleavage of the viral polyprotein in 11 sites, including its own N and C-terminus. The lack of structural information for intermediary forms of Mpro is a setback for the understanding its self-maturation process. Herein, we used X-ray crystallography combined with biochemical data to characterize multiple forms of SARS-CoV-2 Mpro. For the immature form, we show that extra N-terminal residues caused conformational changes in the positioning of domain-three over the active site, hampering the dimerization and diminishing its activity. We propose that this form preludes the cis and trans-cleavage of N-terminal residues. Using fragment screening, we probe new cavities in this form which can be used to guide therapeutic development. Furthermore, we characterized a serine site-directed mutant of the Mpro bound to its endogenous N and C-terminal residues during dimeric association stage of the maturation process. We suggest this form is a transitional state during the C-terminal trans-cleavage. This data sheds light in the structural modifications of the SARS-CoV-2 main protease during its self-maturation process.