SARS coronavirus 2 (SARS-CoV-2) in the viral spike (S) encoding a SARS-COV-2 SPIKE D614G mutation protein predominate over time in locales revealing the dynamic aspects of its key viral processes where it is found, implying that this change enhances viral transmission. It has also been observed that retroviruses infected ACE2-expressing cells pseudotyped with SG614 that is presently affecting a growing number of countries markedly more efficiently than those with SD614. The availability of newer powerful computational resources, molecular modeling techniques, and cheminformatics quality data have made it feasible to generate reliable algebraic calculations to design new chemical entities, merging chemicals, recoring natural products, and a lot of other substances fuelling further development and growth of this AI-quantum based drug design field to balance the trade-off between the structural complexity and the quality of such biophysics predictions that cannot be obtained by any other method. In this paper, we strongly combine topology geometric methods targeting at the atomistic level the protein apparatus of the SARS-COV-2 virus that are simple in machine learning anti-viral characteristics, to propose computer-aided rational drug design strategies efficient in computing docking usage, and powerful enough to achieve very high accuracy levels for this in-silico effort for the generation of the AI-Quantum designed molecule the RoccustyrnaTM small molecule, a multi-targeting druggable scaffold (1S,2R,3S)‐2‐({[(1S,2S,4S,5R)‐4‐ethenyl‐4‐sulfonylbicyclo[3.2.0]heptan‐2‐yl]oxy}amino)‐3‐[(2R,5R)‐5‐(2‐methyl‐6‐methylidene‐6,9‐dihydro‐3H‐purin‐9‐yl)‐3‐methylideneoxolan‐2‐yl]phosphirane‐1‐carbonitrile targeting the COVID-19-SARS-COV-2 SPIKE D614G mutation using Chern-Simons Topology Euclidean Geometric in a Lindenbaum-Tarski generated QSAR automating modeling and Artificial Intelligence-Driven Predictive Neural Networks.

Νovel SARS coronavirus 2 (SARS-CoV-2) of the family Coronaviridae starting in China and spreading around the world is an enveloped, positive-sense, single-stranded RNA of the genus betacoronavirus encoding the SARS-COV-2 (2019-NCOV, Coronavirus Disease 2019. Remdesivir drug, or GS-5734 lead compound, first described in 2016 as a potential anti-viral agent for Ebola diseade and has also being researched as a potential therapeutic agent against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the coronavirus that causes coronavirus disease 2019 (COVID-19). Computer-aided drug design (CADD), Structure and Ligand based Drug Repositioning strategies based on parallel docking methodologies have been widely used for both modern drug development and drug repurposing to find effective treatments against this disease. Quantum mechanics, molecular mechanics, molecular dynamics (MD), and combinations have shown superior performance to other drug design approaches providing an unprecedented opportunity in the rational drug development fields and for the developing of innovative drug repositioning methods. We tested 18 phytochemical small molecule libraries and predicted their synergies in COVID-19 (2019- NCOV), to devise therapeutic strategies, repurpose existing ones in order to counteract highly pathogenic SARS-CoV-2 infection. We anticipate that our geometry hashing driven quantum deep learing similarity approaches which is based on separated pairs of short consecutive matching fragments, can be used for the development of anticoronaviral drug combinations in large scale HTS screenings, and to maximize the safety and efficacy of the Remdesivir, Colchicine and Ursolic acid drugs already known to induce synergy with potential therapeutic value or drug repositioning to COVID-19 patients.

For the treatment of Covid-19 patients with remdesivir, poor renal- and liver function were both exclusion criteria in randomized clinical trials (RCTs) and contra-indication for treatment. Also, nephrotoxicity and hepatotoxicity are reported as adverse events. We retrospectively reviewed renal- and liver functions of covid-19 patients who received remdesivir in the 15 days after treatment initiation. Approximately 20% of the patient population met RCT exclusion criteria. In total, 11% of the patients had a decrease in estimated glomerular filtration rate larger than 10 ml/min/1.73m2. Also, 25% and 35% had increased alanine transaminase and aspartate transaminase levels, respectively. However, serious adverse events were limited. Therefore, contra-indications based on kidney- and liver function should not be absolute for remdesivir treatment in patients with Covid-19 if these functions are monitored regularly.

Viral entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) via the spike protein enables endocytosis into host cells using the ACE2 receptor and TMPRSS2. The frequent upper respiratory tract symptoms of COVID-19 and the localization of the virus to the nasopharynx, the most common site of swabbing, indicate that the sinonasal mucosa may play an important role in SARS-CoV2 infection and viral replication. This paper investigates the presence of ACE2 Receptor and TMPRESS2 expression in the primary human nasal epithelial cells (HNECs) from Control, CRSsNP, and CRSwNP and maps the expression changes when exposed to Th1, Th2, Th17 associated cytokines. We found that ACE2 and TMPRSS2 expression is higher in control HNECs than CRSwNP HNECs, and that both ACE2 and TMPRSS2 are downregulated further by Th2 cytokines in CRSwNP HNECs. This indicates an immune dysregulated state of CRSwNP mucosa, which normally contributes to a chronic inflammatory state, might support an altered susceptibility to SARS-CoV2 infection and transmission.

Objective: We hypothesized that omega-3 fatty acids would be an appropriate adjunct therapy for alleviating the inflammatory response and clinical manifestation in hospitalized patients with covid-19 disease. Methods: This was a single-blind randomized controlled trial in Amir-Alam hospital in Tehran. Thirty adult men and women diagnosed with covid-19 were allocated to either control group (receiving Hydroxychloroquine) or intervention group (receiving Hydroxychloroquine plus 2 grams of DHA+EPA) for 2 weeks. Primary outcome of the intervention including CRP, ESR as well as clinical symptoms including body pain, fatigue, appetite and olfactory and secondary outcomes including liver enzymes were determined at the baseline and after omega-3 supplementation. Clinical signs were measured using self-reported questionnaires. There were commercial kits for determination of CRP and liver enzymes concentrations in the serum of patients. For determination of ESR automated hematology analyzer was applied. Results: In comparison to control group, patients receiving omega-3 indicated favorable changes in all clinical symptoms except for olfactory ((p<0.001 for body pain and fatigue, p= 0.03 for appetite and p=0.21 for olfactory). Reducing effects of omega-3 supplementation compared to control group were also observed in the levels of ESR and CRP after treatment (p<0.001 for CRP and p=0.02 for ESR). However, no between group differences in the liver enzymes serum concentrations were observed after supplementation (p>0.05). Conclusion: Current observations are very promising and indicate that supplementation with moderate dosages of omega-3 fatty acids may be beneficial in the management of inflammation-mediated clinical symptoms in covid-19 patients. Key words: Covid-19, omega-3, inflammation, clinical symptoms

The recent emergence of Severe Acute Respiratory Syndrome-Corona Virus 2 (SARS-CoV-2) in late 2019 and its spread worldwide caused an acute pandemic of Coronavirus disease 19 (COVID-19). COVID-19 pathologies are currently under intense scrutiny as its outbreak led to immense and urgent changes worldwide. Although many theories have been introduced on how SARS-CoV-2 enters the host, the ACE-2 receptor is shown to be the primary mechanism of SARS-CoV-2 entry. However, the mechanism behind the establishment and pathology of infection is poorly understood. As recent studies show that host mitochondria play an essential role in virus-mediated innate immune response, in this review, we will discuss, in detail, the entry and progression of SARS-CoV-2 and how mitochondria play a role in the establishment of viral infection and the development of an immune response, whether it is beneficial or not. We will also review the possible treatments that could be used to prevent the surgency of COVID-19 infection with respect to the role of mitochondria. Understanding the mitochondria-mediated SARS-CoV-2 establishment may provide a unique mechanism and conceptual advancement in finding a novel treatment for COVID-19.

Background and Purpose: Based on in vitro data, ivermectin (IVM) has been proposed for the prevention and treatment of COVID-19, a condition for which obesity is a major risk factor. IVM dosage is based on total body weight and there are no recommendations to adjust dosage in obese patients. The objective of this study was to establish, in a canine model, the influence of obesity on the clearance and steady-state volume of distribution of IVM and two analog compounds, moxidectin (MOX) and eprinomectin (EPR). Experimental Approach: An experimental model of obesity in dogs was based on a high calorie diet. IVM, MOX and EPR were administered intravenously, simultaneously in combination, to a single group of dogs in two circumstances, during a control period and when body weight had been increased by 50%. Key Results: In obese dogs, clearance, expressed in absolute values (L/day), was not modified for MOX and reduced for IVM and EPR, compared to the initial control state. When scaled by body weight (L/day/kg), plasma clearance was reduced by 42, 55 and 63%, for MOX, IVM and EPR, respectively. In contrast, the steady-state volume of distribution was markedly increased in absolute values (L) by obesity. Conclusion and Implications: For IVM and MOX, the obese dog model suggests that the maintenance dose should not be adjusted by total body weight in the obese subject but should be based on lean body weight. On the other hand, the loading dose should be computed based on the total body weight of the obese subject.

COVID-19 has an unpredictable course with substantial percentage of infected patients developing clinical deterioration and increasing health care burden. With no specific treatment or vaccination, the current search is for drugs that can limit the disease progression. Recently Fluvoxamine has been reported to have disease modifying effects in COVID-19. We suggest the hypothesis that short term routine use of Selective Serotonin Reuptake Inhibitors (SSRIs) can prevent clinical deterioration of asymptomatic or mild COVID-19 cases by the following ways: a) anti-inflammatory actions through sigma-1 agonism and reducing release of pro-inflammatory cytokines, b) anti-coagulant action by reducing platelet aggregation, c) specific antiviral and antibacterial effects, d) Immunomodulation through Serotonin pathway and anti-oxidation. The routine short term use of SSRIs can also alleviate the psychological impact of the disease. We hope our hypothesis will encourage future clinical trials to validate the routine use of SSRIs against COVID-19.

The Vero cell line is the most used continuous cell line in viral vaccine manufacturing. This adherent cell culture platform requires the use of surfaces to support cell growth, typically roller bottles or microcarriers. We have recently compared the production of rVSV-ZEBOV on Vero cells between microcarrier and fixed-bed bioreactors. However, suspension cultures are considered superior with regards to process scalability. Therefore, we further explore the Vero suspension system for rVSV-vectored vaccine production. Previously, this suspension cell line was only able to be cultivated in a proprietary medium. Here, we expand the adaptation and bioreactor cultivation to a serum-free commercial medium. Following small scale optimization and screening studies, we demonstrate bioreactor productions of highly relevant vaccines and vaccine candidates against Ebola virus disease, HIV and COVID-19 in the Vero suspension system. rVSV-ZEBOV, rVSV-HIV and rVSVInd-msp-SF-Gtc can replicate to high titers in the bioreactor, reaching 3.87 × 107 TCID50/mL, 2.12 × 107 TCID50/mL and 3.59 × 109 TCID50/mL, respectively. Further, we compare cell specific productivities, and the quality of the produced viruses by determining the ratio of total viral particles to infectious viral particles

Aim: There is an emerging role of steroids in the management of COVID-19. We aimed to compare the outcome of COVID-19 patients (recovery versus mortality) who were treated with steroids with those who were not treated with steroids during their course of hospital stay. Methods: A retrospective analysis of all moderately to severely ill COVID-19 patients, meeting the inclusion and exclusion criteria, admitted to our center during the study period of four months, was performed. The patients were categorized into two groups: Group I included 25 patients who were given steroids, and Group II also included 25 patients who were not given any steroids during their hospital stay. The primary outcome (recovery versus mortality), length of hospital stay as well as other features were compared between the two groups. Results: The mean length of hospital stay was 9.3 days in the steroids group and 10.9 days in the non-steroids group with a p value of 0.249. None of the patients was shifted to a ventilator in either group. One patient in the steroids group (4%) and two patients in the non-steroids group (8%) needed to be put on high flow nasal cannula. One patient died in the steroids group with a recovery rate of 96%, while two patients died in the non-steroids group with a recovery rate of 92% (p value 0.552). Conclusion: Treatment with steroids in moderately to severely ill COVID-19 patients did not decrease the length of hospital stay or mortality in our study.

Introduction: Extracorporeal membrane oxygenation (ECMO) has been used as a refractory treatment for acute respiratory distress syndrome (ARDS) due to COVID-19, but there has been little evidence of its efficacy. We conducted this study to share our experience using ECMO as a bridge to recovery for ARDS due to COVID-19. Methods: All adult patients who were placed on ECMO for ARDS due to COVID -19 between April 2020 and June 2020 (during the first wave of COVID-19) were identified. The clinical characteristics and outcomes of these patients were analyzed with a specific focus on the differences between patients who survived to hospital discharge and those who did not. Results: 20 COVID-19 patients were included in this study. All patients were placed on veno-veno ECMO. Comparing between survivors and non-survivors, older age was associated with hospital mortality (p=0.02). The following complications were observed: renal failure requiring renal replacement therapy (35%, n=7), bacteremia during ECMO (20%, n=4),coinfection with bacterial pneumonia (15%, n=3), cannula site bleeding (15%, n=3), stroke (10%, n=2), gastrointestinal bleeding (10%, n=2), and liver failure (5%, n=1). The complications associated with patient mortality were culture positive septic shock (p=0.01), culture-negative systemic inflammatory response syndrome (p=0.01), and renal failure (p=0.01). The causes of death were septic shock (44%, n=4), culture-negative systemic inflammatory response syndrome (44%, n=4), and stroke (11%, n=1). Conclusions: Based on our experience, ECMO can improve refractory ARDS due to COVID-19 in select patients. Proper control of bacterial infections during COVID-19 immunomodulation therapy may be critical to improving survival.

The world is currently facing the COVID-19 pandemic that is taking a heavy toll on several countries. While many infected patients have a good prognosis, in some cases the progression can be serious and even lead to death. The commonly seen complications are a cytokine storm and multi-organ failure that require intensive care. The mortality of critically ill patients depends on age (> 65 years), sex (male) or co-morbidities. There is an urgent need to discover a biomarker to identify early on patients at risk of developing serious complications, and to find an effective treatment that could prevent disease progression and critical states. Recent investigations have pointed to the possible contribution of intestinal dysbiosis to the pathophysiology of COVID-19. Herein, we hypothesize that butyrate, a short-chain fatty acid produced by the gut microbiota, can prevent immune system activation and disease progression.

Paediatric multisystem inflammatory syndrome: temporally associated with SARS-COV-2 (PIMS-TS) is a well described rare but severe COVID-19 related syndrome. PIMS-TS have been reported in children from geographical areas of high COVID-19 infection. Most children with PIMS-TS require management in an intensive care unit with variable respiratory involvement. Adults recovering from COVID-19 infection have been reported to suffer from respiratory morbidity but such outcomes are unknown in children. We present the first report of normal short term respiratory outcomes as measured by spirometry in children with SARS-COV-2 antibody positive, PIMS-TS syndrome managed at a specialist children’s hospital in the UK.

Rationale, aims, and objectives The current strategy of searching for an effective drug to treat COVID-19 relies mainly on repurposing existing therapies developed to target other diseases. There are currently more than four thousand active studies assessing the efficacy of existing drugs as therapies for COVID-19. The number of ongoing trials and the urgent need for a treatment poses the risk that false-positive results will be incorrectly interpreted as evidence for treatments’ efficacy and a ground for drug approval. Our purpose is to assess the risk of false-positive outcomes by analyzing the mechanistic evidence for the efficacy of exemplary candidates for repurposing, estimate false discovery rate, and discuss solutions to the problem of excessive hypothesis testing. Methods We estimate the expected number of false-positive results and probability of at least one false-positive result under the assumption that all tested compounds have no effect on the course of the disease. Later, we relax this assumption and analyze the sensitivity of the expected number of true-positive results to changes in the prior probability (π) that tested compounds are effective. Finally, we calculate False Positive Report Probability and expected numbers of false-positive and true-positive results for different thresholds of statistical significance, power of studies, and ratios of effective to non-effective compounds. We also review mechanistic evidence for the efficacy of two exemplary repurposing candidates (hydroxychloroquine and ACE2 inhibitors) and assess its quality to choose the plausible values of the prior probability (π) that tested compounds are effective against COVID-19. Results Our analysis shows that, due to the excessive number of statistical tests in the field of drug repurposing for COVID-19 and low prior probability (π) of the efficacy of tested compounds, positive results are far more likely to result from type-I error than reflect the effects of pharmaceutical interventions.

This report describes the case of a 53-year-old man with SARS-CoV-2 infection and occurrence of complete unilateral sensorineural hearing loss, adding new evidence to the association between COVID-19 and hearing loss. Whether this is the result of endothelial cell dysfunction in the cochlea or central auditory pathways remains unclear.

As the clinical course of COVID-19 infection in SCD patients is not clear, close monitoring is essential. We emphasize that RBC exchange should be offered early to avoid possible deterioration. We present a case of COVID-19 infection in a SCD patient causing severe hemolysis, that improved after RBC exchange.

Background Indomethacin, a well-known non-steroidal anti-inflammatory drug (NSAID), with effective broad spectrum anti-viral activity, was evaluated for efficacy and safety of indomethacin in treating RT-PCR positive covid-19 patients Materials and Methods Patients with RT-PCR positive covid-19 who were admitted to hospital were offered the option to receive indomethacin 50 to 75mg daily in addition to the Indian council of medical research (ICMR) standard covid-19 treatment. Patients who declined the indomethacin option were offered paracetamol for pain and fever. The endpoint was the development of hypoxia. Secondary endpoints were time to become afebrile and time to resolution of cough and myalgia. Propensity Score Matching was used to compare indomethacin and paracetamol treatments. A separate group of severely ill patients who were admitted with hypoxia were treated with indomethacin 75mg; the endpoint was the requirement for mechanical ventilation or admission to the intensive care unit (ICU). Blood chemistry was collected before and after the treatment. The patients were monitored every day for clinical parameters. . Results A total of 104 patients received indomethacin, 82 with mild-moderate disease and 22 with severe disease. Matching reduced the number of patients to 72. In the indomethacin mild-moderate disease group, one patient out of 72 in the matched group developed hypoxia and required oxygen compared with 28 out of 72 patients in the matched group who received paracetamol. Patients who received indomethacin also experienced more rapid symptomatic relief compared to paracetamol arm. In the indomethacin severe disease group no patient deteriorated enough to require mechanical ventilation. There were no adverse reactions to indomethacin or deterioration of renal or liver function. Conclusion The use of indomethacin compared with paracetamol, in addition to the standard ICMR treatment in hospitalised covid-19 patients was associated with marked reductions in the severity and duration of illness, without any adverse effects.

Background. There is an emergency need for early ambulatory treatment of COVID-19 in acutely ill patients in an attempt to reduce disease progression and the risks of hospitalization and death. Methods and Results. We recently reported results on 320 high-risk (age > 50 with ≥ 1 comorbidity) COVID-19 cases and have updated our results with 549 additional cases in period ending December 16, 2020. Our protocol utilizes at least two agents with antiviral activity against SARS-CoV-2 (zinc, hydroxychloroquine, ivermectin) and one antibiotic (azithromycin, doxycycline, ceftriaxone) along with inhaled budesonide and/or intramuscular dexamethasone. Albuterol nebulizer, inhaled budesonide, intravenous volume expansion with supplemental parenteral thiamine 500 mg, magnesium sulfate 4 grams, folic acid 1 gram, vitamin B12 1 mg, are administered for severely ill patients who either present or return to the clinic with severe symptoms. In period 1 (April-September, 2020) 6/320 (1.9%) and 1/320 (0.3%) patients were hospitalized and died, respectively. In period 2, (September-December, 2020) 14/549 (2.6%) and 1/549 (0.18%) were hospitalized and died, respectively. For comparison, we used the Cleveland Clinic COVID-19 hospitalization calculator and based on average age and comorbidities the expected rate of hospitalization for both periods was 18.5%. The cumulative mortality among confirmed and suspected COVID-19 in Collin, Dallas, Denton, and Tarrant counties was 0.76, 1.04, 0.90, and 0.97. As a result, our early ambulatory treatment regimen was associated with estimated 87.6% and 74.9% reductions in hospitalization and death respectively, p<0.0001. Conclusions. We conclude that early ambulatory, multidrug therapy is associated with substantial reductions in hospitalization and death compared to available rates in the community. Prompt ambulatory treatment should be offered to high-risk patients with COVID-19 instead of watchful watching and late-stage hospitalization for salvage therapies.

Objective: The present study aimed to investigate the possible cardioprotective effects of ketotifen and to assess its activity as an iron-chelating agent in patients receiving anthracyclines for the treatment of breast cancer. Patients & Methods: This was a randomized, prospective, controlled clinical trial. 111 eligible patients with breast cancer (age range, 30-60 year) were scheduled to receive anthracycline chemotherapy. The patients divided into two groups: Patients (n=56) assigned to The ketotifen group received ketotifen 1 mg three times daily for six consecutive cycles of treatment, and patients assigned to The control group (n= 55) without ketotifen treatment. The echocardiogram for each patient was recorded two times at baseline and at the end of the study. As well, blood samples were collected from all patients. Results: The findings showed a statistically significant reduction in the mean serum levels of common cardiotoxicity accompanied biomarkers in The ketotifen group compared with The control group (P ≤ 0.05). The mean serum levels of total iron-binding capacity was significantly elevated in The ketotifen group (P ≤ 0.001). There was a direct correlation between the mean serum levels of iron and that of lactate dehydrogenase (LDH) (r = + 0.79). On the other hand, there were indirect correlations between mean serum levels of LDH and both the percentage of ejection fraction and the total iron-binding capacity (r = - 0.69 and -0.697, respectively). Conclusion: Oral administration of ketotifen appears to be efficient and safe as a novel cardioprotective agent for the prevention of anthracyclines induced cardiotoxicity. Additionally, ketotifen suggested a beneficial effect in iron overload inducing diseases such as COVID-19.

Background: A rapid outbreak of novel coronavirus, COVID-19, made it a global pandemic. This study focused on the possible association between lymphopenia and Computed tomography (CT) scan features and COVID-19 patient mortality. Method: The clinical data of 596 COVID-19 patients were collected from February 2020 to September 2020. The patients’ serological survey and CT scan features were retrospectively explored. Results: The median age of the patients was 56.7±16.4 years old. Lung involvement was more than 50% in 214 COVID-19 patients (35.9%). The average blood lymphocyte percentage was 20.35 ±10.16. The levels of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and platelet-to-lymphocyte ratio (PLR) may not indicate the severity and prognosis of COVID-19. Patients with severe lung involvement and lymphopenia were found to be significantly associated with increased odds of death (odds ratio [OR], 9.24; 95% confidence interval [95 CI%], 4.32- 19.78). These results indicated that lymphopenia <20% along with pulmonary involvement >50% impose a multiplicative effect on the risk of mortality. The in-hospital mortality rate of this group was significantly higher than other COVID-19 hospitalized cases. Furthermore, they meaningfully experienced a prolonged stay in the hospital (P= 0.00). Conclusion: The Lymphocyte count less than 20% and chest CT scan findings with more than 50% involvement might be related to the patient’s mortality. It could act as laboratory and clinical indicators of disease severity and mortality.

Objective: To date, over 7 million people have been infected in the COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2 which emerged in Wuhan, China in December 2019. This study examined the relationships between serum monocyte chemoattractant protein-1 (MCP-1) and surfactant protein-A (SP-A) levels and the clinical course and prognosis of COVID-19. Method: The study included a total of 108 subjects. Those in the patient group (n=88) were diagnosed with COVID-19 using real-time PCR analysis of nasopharyngeal swab samples and treated in the Atatürk University Pulmonary Diseases and the City Hospital Infectious Diseases department between March 24 and April 15. The control group (n=20) included asymptomatic healthcare workers whose real-time PCR results during routine COVID-19 screening in our hospital were negative. Results: The COVID-19 patient group had significantly higher MCP-1 and SP-A levels compared to the control group (p=0.001, p=0.001). Patients who developed macrophage activation syndrome had significantly higher MCP-1 and SP-A levels than those who did not both at admission (p=0.001, p=0.001) and on day 5 of treatment (p=0.05, p=0.04). Similarly, MCP-1 and SP-A levels were significantly higher in patients who developed acute respiratory distress syndrome compared to those who did not at both time points (p=0.001 for all). Both parameters were significantly higher in nonsurviving COVID-19 patients compared to survivors (p=0.001 for both). Conclusion: MCP-1 and SP-A are on opposing sides of the inflammatory balance, and SP-A may be a pneumoprotein of importance in the presentation, course, prognosis, and possibly the treatment of COVID-19 in the future.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Wuhan, China, and rapidly spread worldwide. This new emerging pathogen is highly transmittable and can cause fatal disease. More than 35 million cases have been confirmed and the fatality was about 2.9% up to October 9 2020. However, the original and intermediate hosts of SARS-CoV-2 remain unknown. Here, a total of 3160 poultry samples collected from 14 provinces between September and December 2019 in China were tested for the purpose of traceable surveillance for SARS-CoV-2 infection. The results indicated that all samples were SARS-CoV-2 negative, and a total of 593 avian coronaviruses were detected, including 485 avian infectious bronchitis viruses, 72 duck coronaviruses and 36 pigeon coronaviruses. The positive rates of avian infectious bronchitis virus, duck coronavirus, and pigeon coronavirus were 15.35%, 2.28% and 1.14%, respectively. Our surveillance demonstrated the diversities of avian coronaviruses in China, and higher prevalence were also recognized in some regions. The possibility of SARS-CoV-2 originating from the known avian-origin coronaviruses can be preliminarily ruled out. More surveillance and research on avian coronaviruses should be strengthened for better understanding the diversity, distribution, cross-species transmission and clinical significance of these viruses.

1. IntroductionIn the United States, the number of cases of COVID-19 is continuously increasing. Until October 28, 2020, according to John Hopkins Coronavirus Resource Center, there were 8,856,413 confirmed cases in the United States, and 72,183 cases were reported in one day. After a few months of the lockdown in March, most states are reopening, including retail stores, restaurants, and recreation. As a college student, COVID-19 is affecting everyday student life and residence life.According to the CDC, seasonal influenza viruses are expected during the late fall and peak between December to February [1]. There are some explanations about why flu season usually spreads in the winter. First, people spend more time indoors, which increases the chance to closer contact others who might be carrying the virus. Students, for example, would prefer using public transportation, such as buses, instead of walking to class. Second, in the short days of the winter, people may run low on Vitamin D and weaken our immune system [2]. UConn is located in the northeast of the United States; the temperature is low during the fall and winter. Students and the university need to be prepared and preclude the new wave from spreading. Typically, international students and out-of-state students are more vulnerable to get infected due to limited access to testing [3].The government of Connecticut announced the reopening policy phase 2 began on June 17, which up to 50% capacity indoors with 6 feet spacing for restaurants, personal services, libraries, and indoor recreation and up to 25% capacity capped at 100 people for indoor religious gatherings. Phase 3 began on October 8. Restaurants, personal services, and libraries are up to 75% capacity indoors and up to 50% capacity for indoor and outdoor religious gatherings. However, due to the increasing number of cases of COVID-19 in Connecticut, the Connecticut government updated the latest reopening rule, which was phase 2.1 started on November 6. Phase 2.1 is slightly different from the phase 2 version, in which restaurants can accommodate up to 50%, while personal service and libraries can accommodate up to 75% [6].This article focuses on a local scale, which is the UConn main campus. It is important because college campuses are places with high dense population and easily get infected. From a student’s perspective, building spatial models of campus areas are necessary and help us create a safe community. This study article focuses on building a mathematical model, the Susceptible-Infected-Recovered (SIR) model, and estimates the infectious rate and recovery rate at the University of Connecticut (UConn) Storrs. The model generates the number of cases from August 16, when students who live on campus check-in, to September 7. After finding out the parameters using SIR, we use Agent-Based Modeling (ABM) to simulate different cases to predict and evaluate the risks of different places on campus.  UConn, located in Storrs, has approximately 5,000 students living on campus. Such a population would increase the chances of interaction between students in public places such as academic buildings, dining halls, grocery stores, residential halls, and apartments. Before the semester began, UConn had already announced reopening policies. Most of the classes are moving online or distance learning to prevent the spreading of disease. In-person classes require students wearing a mask and maintaining at least six feet of physical distancing from others. Dining halls are switching to take-out and limited dining models. However, for those students who live in residential halls, even though UConn policy requires one person per dorm room, they are still sharing bathrooms. For those who live in apartments or off-campus, students have approximately one to four roommates, which increases the chance of infection. Our primary goal is to extend the SIR model into the spatial form and using QGIS and NetLogo to visualize the spreading. Because the covid-19 disease varies a great deal with places, we consider leveraging this when we estimate covid information for policy-makers to make lockdown or reopening business strategies. We extend the traditional mathematical SIR model into a spatially-explicit model to simulate the spatial dynamics of covid-19 over discrete-time and across discrete space at the Uconn Storrs campus. The spatially-explicit models may provide useful insights into the epidemiological characteristics of the disease and identification of disease hotspots across the campus, thus can inform and guide policy-makers for targeted interventions and targeted reopening the business in specific locations of the campus. This paper focuses on a specific area, rather than a state or a country, with a smaller population size. We are using the data to predict the cases and infection rates in the next few months, evaluating each building’s risk and ranking the score with a higher chance of getting infected. Based on the policies that have been implemented at UConn, we also make some suggestions to the university about forestalling the new wave coming in winter. 2. Data and MethodologyTo simulate the spreading of epidemics, we are building the SIR model. The SIR model was first introduced by Kermack and McKendrick by separating people into three different categories: susceptible (S), infected (I), and recovered (R) [4]. In this case, the population in Storrs is susceptible (S). Individuals who get infected move from susceptible stage to infected stage (I). Eventually, people who were removed from the infected status recovered (R). The SIR model using the parameters β, the infection rate, and γ, the recovery rate, can be presented by the ordinary differential equation (ODE). 

An Italian male with no link to China SARS-CoV-2 epidemic presented at Emergency Room with severe respiratory impairment. The RT-PCR on 20th February, 2020, nasopharyngeal swab revealed SARS-CoV-2 infection, confirmed with viral culture and sequencing. This was the first identified autochthonous SARS-CoV-2 transmission in Italy, that unveiled global pathogen diffusion.