Plant-derived single domain COVID-19 antibodies.

Data show a decrease in the risk of hospitalization and death from COVID-19. To date, global vaccinations for SARS-CoV-2 protections are underway, but additional treatments are urgently needed to prevent and cure infection among naïve and even vaccinated people. Neutralizing monoclonal antibodies are very promising for prophylaxis and therapy of SARS-CoV-2 infections. However, traditional large-scale methods of producing such antibodies are slow, extremely expensive and possess a high risk of contamination with viruses, prions, oncogenic DNA and other pollutants. The present study is aimed at developing an approach of producing monoclonal antibodies (mAbs) against SARS-CoV-2 spike (S) protein in plant systems which offers unique advantages, such as the lack of human and animal pathogens or bacterial toxins, relatively low-cost manufacturing, and ease of production scale-up. We selected a single N-terminal domain functional camelid-derived heavy (H)-chain antibody fragments (VHH, AKA nanobodies) targeted to receptor binding domain of SARS-CoV-2 spike protein and developed methods of their rapid production using transgenic plants and plant cell suspensions. Isolated and purified plant-derived VHH antibodies were compared with mAbs produced in traditional mammalian and bacterial expression systems. It was found that plant generated VHH using the proposed methods of transformation and purification possess the ability to bind to SARS-CoV-2 spike protein comparable to that of monoclonal antibodies derived from bacterial and mammalian cell cultures. The results of the present studies confirm the visibility of producing monoclonal single-chain antibodies with a high ability to bind the targeted COVID-19 spike protein in plant systems within a relatively shorter time span and at a lower cost when compared with traditional methods. Moreover, similar plant biotechnology approaches can be used for producing monoclonal neutralizing antibodies against other types of viruses.

Diazoxide in the Treatment of Asymptomatic Refractory Hypoglycemia in End Stage Renal Disease

Introduction: Diabetic patients with end-stage renal disease (ESRD) treated with insulin or any other diabetic agent show high variations in their glucose metabolism, lower insulin clearance level, and uncertain accuracy of glycemic control measurements. Therefore, these patients are at a greater risk of developing hypoglycemia. Diazoxide use in the treatment of spontaneous and refractory hypoglycemia in this population has not been well documented. We report a case of a young diabetic male that has been successfully treated with diazoxide for his asymptomatic refractory hypoglycemic episodes. Case Description: A young man with type 2 diabetes mellitus complicated by diabetic nephropathy, on hemodialysis for ESRD, presented with shortness of breath due to COVID pneumonia. After resolution of his infection, he was noted to have recurrent asymptomatic hypoglycemic episodes, although he has been off his diabetes medications for the past few years due to worsening of his kidney function. His oral intake was adequate and there was no concern for malnutrition, or any substance use. From the testing performed, we were able to exclude exogenous insulin or insulin secretagogues use and the presence of insulin antibodies. Insulin and noninsulin (insulin-like growth factor) mediated mechanisms were also ruled out. Since he was having recurrent and refractory asymptomatic hypoglycemic episodes and to minimize the need for supplemental dextrose containing fluids, he was started on diazoxide at 3 mg/kg/day. Knowing the risk of fluid retention with diazoxide, this patient on hemodialysis tolerated it well. Diazoxide helped reduce his episodes of hypoglycemia and he was then safely discharged on it. Discussion(s): In ESRD, hypoglycemia can be explained by the impaired contribution of the kidneys to gluconeogenesis and glucose release, as well as the higher insulin levels caused by insulin resistance and decrease in insulin clearance. When his hypoglycemia persisted even after the resolution of his infection, further testing and work-up was done and other causes of hypoglycemia were ruled out. Generally, diazoxide is used as a treatment to manage the symptoms of hypoglycemia in congenital hyperinsulinism, insulinomas and post bariatric surgery cases of hyperinsulinemic hypoglycemia. However, it has not been the optimal treatment when it comes to treating hypoglycemia in ESRD patients because of its side effects;specifically, fluid retention, and electrolyte imbalances. In our case, the patient was treated with diazoxide as a last resort, despite its known side effects and the limited documentation of its use in ESRD patients. Actually, a few other case reports, have also shown promising results with the use of diazoxide for that purpose with no or minimal side effects. However, there are not enough studies that have shown the benefits or risks of long-term treatment of diazoxide in ESRD patients, an area of growing interest.Copyright © 2023

A review of COVID-19 vaccines strategies and anti-vaxxers theories

In what is a global record time of getting the COVID-19 vaccines available within 11 months, the world has equally been faced with several myths and conspiracy theories dissuading the public from accepting vaccination as an important measure in the response to the pandemic. We reviewed the leading conspiracy theories and balanced these with the scientific basis of viral transmission and replication and the broad role of vaccination in tackling this challenge. We briefly examined the design of the leading vaccines, and provided recommendations for worldwide COVID-19 distribution, acceptance and use.

Safety monitoring of adjuvant 2 weekly durvalumab for patients with stage III NSCLC: Implications for a 4 weekly regimen during the COVID-19 pandemic and beyond

Background: Durvalumab, an anti-PD-L1 agent, is approved for use as an adjuvant treatment of patients with stage III NSCLC previously treated with concurrent chemoradiotherapy scheduled as two-weekly infusions for one year. The COVID-19 pandemic has necessitated a move to remote monitoring of patients via telephone consultations, and a need to reduce hospital visits for patient treatment. It is however, imperative that drug safety is not compromised. Methods: We carried out a retrospective study of 40 patients treated with 2 weekly infusions of durvalumab at The Royal Marsden Hospital between November 2018 and March 2020, prior to the COVID-19 pandemic. A total of 216 hospital visits were analysed. The number of adverse events requiring investigation or intervention were reviewed and the clinical consult documentation analysed. Results: All 40 patients included in the study were diagnosed with Stage III NSCLC (adenocarcinoma 25/40, squamous 9/40, other 6/40) and were previously treated with chemoradiotherapy. The median number of hospital visits analysed per patient was 5. An adverse event leading to a medical intervention (concomitant medication commenced or altered, further unplanned imaging booked, referral to a non-oncology specialist) occurred in 24 out of 216 (11.1%) hospital visits. We observed a clinically significant abnormal blood test result in 8/216 (3.7%) visits. In 10/216 (4.6%) visits, durvalumab was either discontinued due to significant toxicity (5/10) or due to disease progression (5/10). On review of the doctors documentation from each clinic visit we assessed that the majority 184/216 (85.2%) of face-to-face consultations could have been safely performed via telephone with signs and symptoms elicited via verbal conversation rather than clinical examination. Conclusions: In conclusion, patients receiving two weekly durvalumab can safely be assessed via a telephone consultation with a face-to-face consultation and blood test required in a minority of patients. Given our findings, we have now moved to 4 weekly infusions of durvalumab as permitted during the COVID-19 pandemic without a mid-cycle consultation or blood test, thereby minimising the number of hospital visits for patients with cancer. Legal entity responsible for the study: The Royal Marsden NHS Foundation Trust. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.