Regulatory Cross Talk Between SARS-CoV-2 Receptor Binding and Replication Machinery in the Human Host.

We dissect the mechanism of SARS-CoV-2 in human lung host from the initial phase of receptor binding to viral replication machinery. Two independent lung protein interactome were constructed to reveal the signaling process on receptor activation and host protein hijacking machinery in the pathogenesis of virus. Further, we test the functional role of the hubs derived from the interactome. Most hubs proteins were differentially regulated on SARS-CoV-2 infection. Also, the proteins in viral replication hubs were related with cardiovascular disease, diabetes and hypertension confirming the vulnerability and severity of infection in the risk individual. Additionally, the hub proteins were closely linked with other viral infection, including MERS and HCoVs which suggest similar infection pattern in SARS-CoV-2. We identified five hubs that interconnect both networks that show the preparation of optimal environment in the host for viral replication process upon receptor attachment. Interestingly, we propose that seven potential miRNAs, targeting the intermediate phase that connects receptor and viral replication process a better choice as a drug for SARS-CoV-2.

Safety of major reconstructive surgery during the peak of the COVID-19 pandemic in the United Kingdom and Ireland - multicentre national cohort study.

BACKGROUND: The safety of surgery during and after the coronavirus disease-2019 (COVID-19) pandemic is paramount. Early reports of excessive perioperative mortality in COVID-positive patients promoted the widespread avoidance of operations. However, cancelling or delaying operations for cancer, trauma, or functional restitution has resulted in increased morbidity and mortality. METHODS: A national multicentre cohort study of all major reconstructive operations carried out over a 12-week period of the 'COVID-19 surge' in the United Kingdom and Ireland was performed. Primary outcome was 30-day mortality and secondary outcome measures were major complications (Clavien-Dindo grade ≥3) and COVID-19 status of patients and healthcare professionals before and after surgery. RESULTS: A total of 418 patients underwent major reconstructive surgery with a mean operating time of 7.5 hours and 12 days' inpatient stay. Cancer (59.8%) and trauma (29.4%) were the most common indications. COVID-19 infection was present in 4.5% of patients. The 30-day post-operative mortality was 0.2%, reflecting the death of one patient who was COVID-negative. Overall complication rate was 20.8%. COVID status did not correlate with major or minor complications. Eight healthcare professionals developed post-operative COVID-19 infection, seven of which occurred within the first three weeks. CONCLUSIONS: Major reconstructive operations performed during the COVID-19 crisis have been mostly urgent cases involving all surgical specialties. This cohort is a surrogate for all major operations across all surgical specialties. Patient safety and surgical outcomes have been the same as in the pre-COVID era. With adequate precautions, major reconstructive surgery is safe for patients and staff. This study helps counsel patients of COVID-19 risks in the perioperative period.

Rapidly progressive dementia in the COVID-19 era

Abstract Background Rapidly progressive dementias(RPD) are conditions that typically cause dementia over weeks or months.1 Due to the current COVID-19 pandemic, it has become difficult for dementia caregivers on the one hand, and relevant detailed examination and management in the hospitals worldwide, on the other. Recent studies shows that ApoE e4 genotype is associated with both dementia and delirium2. Hence further research into the possible genetic link between dementia and COVID-19 is the need of the hour. Method We studied two elderly male patients, aged 66 and 68 years, presenting with memory decline of recent events, untimely and non-sequential Activities of Daily Living and apathetic alongwith way finding difficulty and errors in money transactions. One patient also had forgetfulness of handwashing and face hygiene measures, and of using preventive face masks in public places as advised for public health during COVID-19 outbreak. On examination, vitals were stable and normal fundus examination with no fever, dry cough or tiredness, and no evidence of Increased Intracranial Pressure(ICP). MMSE score was 16/30 and 17/30 respectively, recent memory and visuospatial skills were impaired and slowness of activities were present. Motor examination was normal, with no focal or non-focal neurological deficit or sensory impairment. All routine tests were normal. Neuroimaging with contrast in one patient showed well defined hyperdense mass lesion of size 4.0*3.5*3.0 cms. showing heterogenous contrast enhancement in left parieto-occipital lobes with moderate perilesional edema suggestive of astrocytoma (intermediate type). Result High index of suspicion of Space occupying lesions should be made in the background of RPD even in the absence of focal or non focal neurological deficit or without signs of raised ICP. Conclusion Most of the etiologies causing RPD especially surgical causes, if diagnosed early and promptly are reversible and treatable. The double hit of dementia and COVID-19 pandemic necessitates further research globally. References: 1) Paterson RW, Takada LT, Geschwind MD. Diagnosis and treatment of rapidly progressive dementias. Neurol Clin Pract. 2012;2(3):187?200. 2) Kuo C-L, Pilling LC, Atkins JL, Kuchel GA, Melzer D. ApoE e2 and aging-related outcomes in 379,000 UK Biobank participants. medRxiv [Internet]. 2020: 2020.02.12.20022459.

St Andrew's COVID-19 surgery safety (StACS) study: Elective plastic surgery, trauma & burns.

INTRODUCTION: This study evaluates COVID-19 related patient risk, when undergoing management within one of the largest specialist centres in Europe, which rapidly implemented national COVID-19 safety guidelines. METHOD: A prospective cohort study was undertaken in all patients who underwent surgical (n = 1429) or non-operative (n = 191) management during the UK COVID-19 pandemic peak (April-May 2020); all were evaluated for 30-day COVID-19 related death. A representative sample of elective/trauma/burns patients (surgery group, n = 729) were selected and also sub-analysed within a controlled cohort study design. Comparison was made to a random selection of non-operatively managed (non-operative group, n = 100) or waiting list (control group, n = 250) patients. These groups were prospectively followed-up and telephoned from the end of June (control group) or at 30 days post-first assessment (non-operative group)/post-operatively (surgery group). RESULTS: Complex general (9.2%, 136/1483) or regional (5.0%, 74/1483) anaesthesia cases represented 14.2% (210/1483) of operations undertaken. There were no 30-day post-operative (0/1429)/first assessment (0/191) COVID-19 related deaths. Neither the three sub-speciality plastic surgery, or non-operative groups, displayed increases in post-operative/first assessment symptoms in comparison to each other, or to control. The proportion of COVID-19 positive tests were: 7.1% (1/14) (non-operative), 5.9% (2/34) (burns) and 3.0% (3/99) (trauma); there were however no significant differences between these groups, the elective (0%, 0/54) and control (0%, 0/24) groups (p = 0.236). CONCLUSION: We demonstrate that even heterogeneous sub-speciality patient groups, who required operative/non-operative management, did not incur an increased COVID-19 risk compared to each other or to control. These highly encouraging results were achieved with described, rapidly implemented service changes that were tailored to protect each patient group and staff.