Detection of SARS-CoV-2 Nucleocapsid and Microvascular Disease in the Brain: A Case Report.

BACKGROUND AND OBJECTIVES: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause a wide range of neurologic complications; however, its neuropenetrance during the acute phase of the illness is unknown. METHODS: Extracellular vesicles were isolated from brain biopsy tissue from a patient undergoing epilepsy surgery using ultracentrifugation and analyzed by Western blot and qPCR for the presence of virus protein and RNA, respectively. Biopsy tissue was assessed by immunohistochemistry for the presence of microvascular damage and compared with 3 other non-COVID surgical epilepsy brain tissues. RESULTS: We demonstrate the presence of viral nucleocapsid protein in extracellular vesicles and microvascular disease in the brain of a patient undergoing epilepsy surgery shortly after SARS-CoV-2 infection. Endothelial cell activation was indicated by increased levels of platelet endothelial cell adhesion molecule-1 and was associated with fibrinogen leakage and immune cell infiltration in the biopsy tissue as compared with control non-COVID surgical epilepsy brain tissues. DISCUSSION: Despite the lack of evidence of viral replication within the brain, the presence of the nucleocapsid protein was associated with disease-specific endothelial cell activation, fibrinogen leakage, and immune cell infiltration.

Safety of the utilization of telemedicine for brain tumor neurosurgery follow-up.

Background: There is a need to evaluate the outcomes of patients who underwent brain tumor surgery with subsequent telemedicine or in-person follow-up during the COVID-19 pandemic. Methods: We retrospectively included all patients who underwent surgery for brain tumor resection by a single neurosurgeon at our Institution from the beginning of the COVID-19 pandemic restrictions (March 2020) to August 2021. Outcomes were assessed by stratifying the patients using their preference for follow-up method (telemedicine or in-person). Results: Three-hundred and eighteen (318) brain tumor patients who were included. The follow-up method of choice was telemedicine (TM) in 185 patients (58.17%), and in-person (IP) consults in 133 patients. We found that patients followed by TM lived significantly farther, with a median of 36.34 miles, compared to a median of 22.23 miles in the IP cohort (P = .0025). We found no statistical difference between the TM and the IP group, when comparing visits to the emergency department (ED) within 30 days after surgery (7.3% vs 6.01%, P = .72). Readmission rates, wound infections, and 30-day mortality were similar in both cohorts. These findings were also consistent after matching cohorts using a propensity score. The percentage of telemedicine follow-up consults was higher in the first semester (73.17%) of the COVID-19 pandemic, compared to the second (46.21%), and third semesters (47.86%). Conclusions: Telehealth follow-up alternatives may be safely offered to patients after brain tumor surgery, thereby reducing patient burden in those with longer distances to the hospital or special situations as the COVID-19 pandemic.

COVID-19 pandemic effects on the distribution of healthcare services in India: A systematic review.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has brought fundamental changes to our problems and priorities, especially those related to the healthcare sector. India was one of the countries severely affected by the harsh consequences of the COVID-19 pandemic. AIM: To understand the challenges faced by the healthcare system during a pandemic. METHODS: The literature search for this review was conducted using PubMed, EMBASE, Scopus, Web of Science, and Google Scholar. We also used Reference Citation Analysis (RCA) to search and improve the results. We focused on the published scientific articles concerned with two major vital areas: (1) The Indian healthcare system; and (2) COVID-19 pandemic effects on the Indian healthcare system. RESULTS: The Indian healthcare system was suffering even before the pandemic. The pandemic has further stretched the healthcare services in India. The main obstacle in the healthcare system was to combat the rising number of communicable as well as noncommunicable diseases. Besides the pandemic measures, there was a diversion of focus of the already established healthcare services away from the chronic conditions and vaccinations. The disruption of the vaccination services may have more severe short and long-term consequences than the pandemic's adverse effects. CONCLUSION: Severely restricted resources limited the interaction of the Indian healthcare system with the COVID-19 pandemic. Re-establishment of primary healthcare services, maternal and child health services, noncommunicable diseases programs, National Tuberculosis Elimination Program, etc. are important to prevent serious long-term consequences of this pandemic.

Safety of the Utilization of Telemedicine for Brain Tumor Neurosurgery Follow-Up

Background There is a need to evaluate the outcomes of patients who underwent brain tumor surgery with subsequent telemedicine or in-person follow-up during the COVID-19 pandemic. Methods We retrospectively included all patients who underwent surgery for brain tumor resection by a single neurosurgeon at our Institution from the beginning of the COVID-19 pandemic restrictions (March 2020) to August 2021. Outcomes were assessed by stratifying the patients using their preference for follow-up method (telemedicine or in-person). Results Three-hundred and eighteen (318) brain tumor patients who were included. The follow-up method of choice was telemedicine (TM) in 185 patients (58.17%), and in-person (IP) consults in 133 patients. We found that patients followed by TM lived significantly farther, with a median of 36.34 miles, compared to a median of 22.23 miles in the IP cohort (p = 0.0025). We found no statistical difference between the TM and the IP group, when comparing visits to the emergency department (ED) within 30 days after surgery (7.3% vs 6.01%, p=0.72). Readmission rates, wound infections and 30-day mortality were similar in both cohorts. These findings were also consistent after matching cohorts using a propensity score. The percentage of telemedicine follow-up consults was higher in the first semester (73.17%) of the COVID-19 pandemic, compared to the second (46.21%) and third semesters (47.86%). Conclusions Telehealth follow-up alternatives may be safely offered to patients after brain tumor surgery, thereby reducing patient burden in those with longer distances to the hospital or special situations as the COVID-19 pandemic.

In‐silico Computational Investigations of AntiViral Lignan Derivatives as Potent Inhibitors of SARS CoV‐2

Due to alarming outbreak of pandemic COVID‐19 in recent times, there is a strong need to discover and identify new antiviral agents acting against SARS CoV‐2. Among natural products, lignan derivatives have been found effective against several viral strains including SARS CoV‐2. Total of twenty‐seven reported antiviral lignan derivatives of plant origin have been selected for computational studies to identify the potent inhibitors of SARS CoV‐2. Molecular docking study has been carried out in order to predict and describe molecular interaction between active site of enzyme and lignan derivatives. Out of identified hits, clemastatin B and erythro‐strebluslignanol G demonstrated stronger binding and high affinity with all selected proteins. Molecular dynamics simulation studies of clemastin B and savinin against promising targets of SARS CoV‐2 have revealed their inhibitory potential against SARS CoV‐2. In fine, in‐silico computational studies have provided initial breakthrough in design and discovery of potential SARS CoV‐2 inhibitors. The present work involve the in‐silico discovery of liganan derivatives as SARS CoV‐2 inhibitors against more than one promising antiviral targets invovling the study of ligand binding strength through molecular docking, assessment of drug likeliness using Lipinski's filters and MD simulations‐based assessment of the stability of the ligands within active sites of antiviral targets.

The impact of public health interventions on critical illness in the pediatric emergency department during the SARS-CoV-2 pandemic.

Study objective: The impact of public health interventions during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic on critical illness in children has not been studied. We seek to determine the impact of SARS-CoV-2 related public health interventions on emergency healthcare utilization and frequency of critical illness in children. Methods: This was an interrupted time series analysis conducted at a single tertiary pediatric emergency department (PED). All patients evaluated by a provider from December 31 through May 14 of 6 consecutive years (2015-2020) were included. Total patient visits (ED and urgent care), shock trauma suite (STS) volume, and measures of critical illness were compared between the SARS-CoV-2 period (December 31, 2019 to May 14, 2020) and the same period for the previous 5 years combined. A segmented regression model was used to explore differences in the 3 outcomes between the study and control period. Results: Total visits, STS volume, and volume of critical illness were all significantly lower during the SARS-CoV-2 period. During the height of public health interventions, per day there were 151 fewer total visits and 7 fewer patients evaluated in the STS. The odds of having a 24-hour period without a single critical patient were >5 times higher. Trends appeared to start before the statewide shelter-in-place order and lasted for at least 8 weeks. Conclusions: In a metropolitan area without significant SARS-CoV-2 seeding, the pandemic was associated with a marked reduction in PED visits for critical pediatric illness.

Modeling the impact of delaying transcatheter aortic valve replacement for the treatment of aortic stenosis in the era of COVID-19.

OBJECTIVE: The aim of this study was to model the short term and 2-year overall survival (OS) for intermediate-risk and low-risk patients with severe symptomatic aortic stenosis (AS) undergoing timely or delayed transcatheter aortic valve replacement (TAVR) during the 2019 novel coronavirus (COVID-19) pandemic. METHODS: We developed a decision analysis model to evaluate 2 treatment strategies for both low-risk and intermediate-risk patients with AS during the COVID-19 novel coronavirus pandemic. RESULTS: Prompt TAVR resulted in improved 2-year OS compared with delayed intervention for intermediate-risk patients (0.81 vs 0.67) and low-risk patients (0.95 vs 0.85), owing to the risk of death or the need for urgent/emergent TAVR in the waiting period. However, if the probability of acquiring COVID-19 novel coronavirus is >55% (intermediate-risk patients) or 47% (low-risk patients), delayed TAVR is favored over prompt intervention (0.66 vs 0.67 for intermediate risk; 0.84 vs 0.85 for low risk). CONCLUSIONS: Prompt transcatheter aortic valve replacement for both intermediate-risk and low-risk patients with symptomatic severe AS results in improved 2-year survival when local healthcare system resources are not significantly constrained by the COVID-19.

Unfolding trends of COVID-19 transmission in India: critical review of available Mathematical models. (Special Issue: The epidemiologist and the pandemic.)

Background: There is a surge in epidemiological modeling research due to sudden onset of COVID-19 pandemic across the globe. In the absence of any pharmaceutical interventions to control the epidemic, nonpharmaceutical interventions like containment, mitigation and suppression are tried and tested partners in epidemiological theories. But policy and planning needs estimates of disease burden in various scenarios in absence of real data and epidemiological models helps to fill this gap. Aims and Objectives: To review the models of COVID-19 prediction in Indian scenario, critically evaluate the range, concepts, strength and limitations of these prediction models and its potential policy implications.

Discovery of Some Antiviral Natural Products to Fight Against Novel Coronavirus (SARS-CoV-2) Using an In silico Approach.

BACKGROUND: Novel coronavirus is a type of enveloped viruses with a single-stranded RNA enclosing helical nucleocapsid. The envelope consists of spikes on the surface which are made up of proteins through which virus enters into human cells. Until now, there is no specific drug or vaccine available to treat COVID-19 infection. In this scenario, reposting of drug or active molecules may provide rapid solution to fight against this deadly disease. OBJECTIVE: We selected 30 phytoconstituents from the different plants which are reported for antiviral activities against coronavirus (CoVs) and performed in silico screening to find out phytoconstituents which have potency to inhibit specific target of the novel coronavirus. METHODS: We performed molecular docking studies on three different proteins of novel coronavirus, namely COVID-19 main protease (3CL pro), papain-like protease (PL pro) and spike protein (S) attached to ACE2 binding domain. The screening of the phytoconstituents on the basis of binding affinity compared to standard drugs. The validations of screened compounds were done using ADMET and bioactivity prediction. RESULTS: We screened five compounds biscoclaurine, norreticuline, amentoflavone, licoricidin and myricetin, using in silico approach. All compounds were found safe in In silico toxicity studies. Bioactivity prediction reveals that these compounds may act through protease or enzyme inhibition. Results of compound biscoclaurine norreticuline were more interesting as this biscoclaurine had higher binding affinity for the target 3CLpro and PLpro targets and norreticuline had a higher binding affinity for the target PLpro and Spike protein. CONCLUSION: Our study concludes that these compounds could be further explored rapidly as it may have potential to fight against COVID-19.

Prioritizing heart transplantation during the COVID-19 pandemic.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has significantly impacted the healthcare landscape in the United States in a variety of ways including a nation-wide reduction in operative volume. The impact of COVID-19 on the availability of donor organs and the impact on solid organ transplant remains unclear. We examine the impact of COVID-19 on a single, large-volume heart transplant program. METHODS: A retrospective chart review was performed examining all adult heart transplants performed at a single institution between March 2020 and June 2020. This was compared to the same time frame in 2019. We examined incidence of primary graft dysfunction, continuous renal replacement therapy (CRRT) and 30-day survival. RESULTS: From March to June 2020, 43 orthotopic heart transplants were performed compared to 31 performed during 2019. Donor and recipient demographics demonstrated no differences. There was no difference in 30-day survival. There was a statistically significant difference in incidence of postoperative CRRT (9/31 vs. 3/43; p = .01). There was a statistically significant difference in race (23 W/8B/1AA vs. 30 W/13B; p = .029). CONCLUSION: We demonstrate that a single, large-volume transplant program was able to grow volume with little difference in donor variables and clinical outcomes following transplant. While multiple reasons are possible, most likely the reduction of volume at other programs allowed us to utilize organs to which we would not have previously had access. More significantly, our growth in volume was coupled with no instances of COVID-19 infection or transmission amongst patients or staff due to an aggressive testing and surveillance program.

Telemedicine in Neurosurgery: Lessons Learned from a Systematic Review of the Literature for the COVID-19 Era and Beyond.

BACKGROUND: Evolving requirements for patient and physician safety and rapid regulatory changes have stimulated interest in neurosurgical telemedicine in the COVID-19 era. OBJECTIVE: To conduct a systematic literature review investigating treatment of neurosurgical patients via telemedicine, and to evaluate barriers and challenges. Additionally, we review recent regulatory changes that affect telemedicine in neurosurgery, and our institution's initial experience. METHODS: A systematic review was performed including all studies investigating success regarding treatment of neurosurgical patients via telemedicine. We reviewed our department's outpatient clinic billing records after telemedicine was implemented from 3/23/2020 to 4/6/2020 and reviewed modifier 95 inclusion to determine the number of face-to-face and telemedicine visits, as well as breakdown of weekly telemedicine clinic visits by subspecialty. RESULTS: A total of 52 studies (25 prospective and 27 retrospective) with 45 801 patients were analyzed. A total of 13 studies were conducted in the United States and 39 in foreign countries. Patient management was successful via telemedicine in 99.6% of cases. Telemedicine visits failed in 162 cases, 81.5% of which were due to technology failure, and 18.5% of which were due to patients requiring further face-to-face evaluation or treatment. A total of 16 studies compared telemedicine encounters to alternative patient encounter mediums; telemedicine was equivalent or superior in 15 studies. From 3/23/2020 to 4/6/2020, our department had 122 telemedicine visits (65.9%) and 63 face-to-face visits (34.1%). About 94.3% of telemedicine visits were billed using face-to-face procedural codes. CONCLUSION: Neurosurgical telemedicine encounters appear promising in resource-scarce times, such as during global pandemics.

Virtual screening of curcumin and its analogs against the spike surface glycoprotein of SARS-CoV-2 and SARS-CoV.

COVID-19, a new pandemic caused by SARS-CoV-2, was first identified in 2019 in Wuhan, China. The novel corona virus SARS-CoV-2 and the 2002 SARS-CoV have 74% identity and use similar mechanisms to gain entry into the cell. Both the viruses enter the host cell by binding of the viral spike glycoprotein to the host receptor, angiotensin converting enzyme 2 (ACE2). Targeting entry of the virus has a better advantage than inhibiting the later stages of the viral life cycle. The crystal structure of the SARS-CoV (6CRV: full length S protein) and SARS-CoV-2 Spike proteins (6M0J: Receptor binding domain, RBD) was used to determine potential small molecule inhibitors. Curcumin, a naturally occurring phytochemical in Curcuma longa, is known to have broad pharmacological properties. In the present study, curcumin and its derivatives were docked, using Autodock 4.2, onto the 6CRV and 6M0J to study their capability to act as inhibitors of the spike protein and thereby, viral entry. The curcumin and its derivatives displayed binding energies, ΔG, ranging from -10.98 to -5.12 kcal/mol (6CRV) and -10.01 to -5.33 kcal/mol (6M0J). The least binding energy was seen in bis-demethoxycurcumin with: ΔG = -10.98 kcal/mol (6CRV) and -10.01 kcal/mol (6M0J). A good binding energy, drug likeness and efficient pharmacokinetic parameters suggest the potential of curcumin and few of its derivatives as SARS-CoV-2 spike protein inhibitors. However, further research is necessary to investigate the ability of these compounds as viral entry inhibitors.Communicated by Ramaswamy H. Sarma.

Neuro-oncology practice guidelines from a high-volume surgeon at the COVID-19 epicenter.

BACKGROUND: During the coronavirus 19 (COVID-19) pandemic, physicians have begun adapting their daily practices to prevent transmissions. In this study we aimed to provide surgical neuro-oncologists with practice guidelines during the COVID-19 pandemic based on objective data from a high-volume brain tumor surgeon at the current COVID-19 epicenter. METHODS: All outpatient visits and surgeries performed by the senior author during the COVID-19 pandemic were compared between the initial quarantine (3/23/20-5/4/20), the plateau period following quarantine (5/5/20-6/27/20), and the second peak (6/28/20-7/20/20). In-person and telemedicine visits were evaluated for crossovers. Surgeries were subdivided based on lesion type and evaluated across the same time period. RESULTS: From 3/23/20-7/20/20, 469 clinic visits and 196 surgeries were identified. After quarantine was lifted, face-to-face visits increased (P < 0.01) yet no change in telehealth visits occurred. Of 327 telehealth visits, only 5.8% converted to in-person during the 4-month period with the most cited reason being patient preference (68.4%). Of the 196 surgeries performed during the pandemic, 29.1% occurred during quarantine, 49.0% during the plateau, and 21.9% occurred in the second peak. No COVID negative patients developed symptoms at follow-up. 55.6% were performed on malignant tumors and 31.6% were benign with no difference in case volumes throughout the pandemic. CONCLUSIONS: Despite exceptional challenges, we have maintained a high-volume surgical neuro-oncology practice at the epicenter of the COVID-19 pandemic. We provide the protocols implemented at our institution in order to maximize neuro-oncology care while mitigating risk of COVID-19 exposure to both patients and providers.

Early Changes to Neurosurgery Resident Training During the COVID-19 Pandemic at a Large U.S. Academic Medical Center.

BACKGROUND: The coronavirus disease 2019 pandemic has led to sweeping changes in residency programs across the world, including cancellation of elective cases. The effects of safety measures on neurosurgical training remain unclear. To understand how neurosurgical residents have been affected, we analyzed the operative experience in the months leading up to and during the pandemic. METHODS: The resident and institutional case totals were tallied for a single residency program in Miami-Dade County from January 1, 2019 to June 30, 2020. A matched cohort analysis was performed before and during the pandemic to assess the effects on resident surgical training. RESULTS: The case totals for all levels of training were lower when restrictions were placed on elective surgeries. An average of 11 cases was logged in April 2020, a decrease from 26 cases in April 2019 (95% confidence interval, 8.7-22; P < 0.01). An average of 20 cases was logged in May 2020, a decrease from 25 cases in May 2019 (95% confidence interval, 1.2-8.8; P = 0.01). In April and May 2020, 299 (66%) and 148 (50%) fewer cases had been performed at our institution compared with April and May 2109. CONCLUSIONS: Operative experience was reduced for residents during the months when the performance of elective cases was restricted. Our data suggest experience in some areas of neurosurgery were more affected than were others, and residents at different levels of training were also affected differently. However, the extent of the coronavirus disease 2019 pandemic on neurosurgical training is unlikely to be understood in the short term.