Pathogenesis, Symptomatology, and Transmission of SARS-CoV-2 through Analysis of Viral Genomics and Structure

The novel coronavirus SARS-CoV-2, which emerged in late 2019, has since spread around the world and infected hundreds of millions of people with coronavirus disease 2019 (COVID-19). While this viral species was unknown prior to January 2020, its similarity to other coronaviruses that infect humans has allowed for rapid insight into the mechanisms that it uses to infect human hosts, as well as the ways in which the human immune system can respond. Here, we contextualize SARS-CoV-2 among other coronaviruses and identify what is known and what can be inferred about its behavior once inside a human host. Because the genomic content of coronaviruses, which specifies the virus's structure, is highly conserved, early genomic analysis provided a significant head start in predicting viral pathogenesis and in understanding potential differences among variants. The pathogenesis of the virus offers insights into symptomatology, transmission, and individual susceptibility. Additionally, prior research into interactions between the human immune system and coronaviruses has identified how these viruses can evade the immune system's protective mechanisms. We also explore systems-level research into the regulatory and proteomic effects of SARS-CoV-2 infection and the immune response. Understanding the structure and behavior of the virus serves to contextualize the many facets of the COVID-19 pandemic and can influence efforts to control the virus and treat the disease. IMPORTANCE COVID-19 involves a number of organ systems and can present with a wide range of symptoms. From how the virus infects cells to how it spreads between people, the available research suggests that these patterns are very similar to those seen in the closely related viruses SARS-CoV-1 and possibly Middle East respiratory syndrome-related CoV (MERS-CoV). Understanding the pathogenesis of the SARS-CoV-2 virus also contextualizes how the different biological systems affected by COVID-19 connect. Exploring the structure, phylogeny, and pathogenesis of the virus therefore helps to guide interpretation of the broader impacts of the virus on the human body and on human populations. For this reason, an in-depth exploration of viral mechanisms is critical to a robust understanding of SARS-CoV-2 and, potentially, future emergent human CoVs (HCoVs).Copyright © 2021 Rando et al.

The role of pandemic planning in the management of COVID-19 in England from an infection prevention and control perspective: results of a national survey.

OBJECTIVES: This national survey aimed to explore how existing pandemic preparedness plans (PPP) accounted for the demands placed on infection prevention and control (IPC) services in acute and community settings in England during the first wave of the COVID-19 pandemic. STUDY DESIGN: This was a cross-sectional survey of IPC leaders working within National Health Service Trusts or clinical commissioning groups/integrated care systems in England. METHODS: The survey questions related to organisational COVID-19 preparedness pre-pandemic and the response provided during the first wave of the pandemic (January to July 2020). The survey ran from September to November 2021, and participation was voluntary. RESULTS: In total, 50 organisations responded. Seventy-one percent (n = 34/48) reported having a current PPP in December 2019, with 81% (n = 21/26) indicating their plan was updated within the previous 3 years. Around half of IPC teams were involved in previous testing of these plans via internal and multi-agency tabletop exercises. Successful aspects of pandemic planning were identified as command structures, clear channels of communication, COVID-19 testing, and patient pathways. Key deficiencies were lack of personal protective equipment, difficulties with fit testing, keeping up to date with guidance, and insufficient staffing. CONCLUSIONS: Pandemic plans need to consider the capability and capacity of IPC services to ensure they can contribute their critical knowledge and expertise to the pandemic response. This survey provides a detailed evaluation of how IPC services were impacted during the first wave of the pandemic and identifies key areas, which need to be included in future PPP to better manage the impact on IPC services.

Coronavirus disease 2019: International public health considerations

On December 31, 2019, the Chinese government announced an outbreak of a novel coronavirus, recently named COVID-19. During the following weeks the international medical community has witnessed with unprecedented coverage the public health response both domestically by the Chinese government, and on an international scale as cases have spread to dozens of countries. While much regarding the virus and the Chinese public health response is still unknown, national and public health institutions globally are preparing for a pandemic. As cases and spread of the virus grow, emergency and other front-line providers may become more anxious about the possibility of encountering a potential case. This review describes the tenets of a public health response to an infectious outbreak by using recent historical examples and also by characterizing what is known about the ongoing response to the COVID-19 outbreak. The intent of the review is to empower the practitioner to monitor and evaluate the local, national and global public health response to an emerging infectious disease.

Identification and Development of Therapeutics for COVID-19

After emerging in China in late 2019, the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread worldwide, and as of mid-2021, it remains a significant threat globally. Only a few coronaviruses are known to infect humans, and only two cause infections similar in severity to SARS-CoV-2: Severe acute respiratory syndrome-related coronavirus, a species closely related to SARS-CoV-2 that emerged in 2002, and Middle East respiratory syndrome-related coronavirus, which emerged in 2012. Unlike the current pandemic, previous epidemics were controlled rapidly through public health measures, but the body of research investigating severe acute respiratory syndrome and Middle East respiratory syndrome has proven valuable for identifying approaches to treating and preventing novel coronavirus disease 2019 (COVID-19). Building on this research, the medical and scientific communities have responded rapidly to the COVID-19 crisis and identified many candidate therapeutics. The approaches used to identify candidates fall into four main categories: adaptation of clinical approaches to diseases with related pathologies, adaptation based on virological properties, adaptation based on host response, and data-driven identification (ID) of candidates based on physical properties or on pharmacological compendia. To date, a small number of therapeutics have already been authorized by regulatory agencies such as the Food and Drug Administration (FDA), while most remain under investigation. The scale of the COVID-19 crisis offers a rare opportunity to collect data on the effects of candidate therapeutics. This information provides insight not only into the management of coronavirus diseases but also into the relative success of different approaches to identifying candidate therapeutics against an emerging disease. IMPORTANCE The COVID-19 pandemic is a rapidly evolving crisis. With the worldwide scientific community shifting focus onto the SARS-CoV-2 virus and COVID-19, a large number of possible pharmaceutical approaches for treatment and prevention have been proposed. What was known about each of these potential interventions evolved rapidly throughout 2020 and 2021. This fast-paced area of research provides important insight into how the ongoing pandemic can be managed and also demonstrates the power of interdisciplinary collaboration to rapidly understand a virus and match its characteristics with existing or novel pharmaceuticals. As illustrated by the continued threat of viral epidemics during the current millennium, a rapid and strategic response to emerging viral threats can save lives. In this review, we explore how different modes of identifying candidate therapeutics have borne out during COVID-19.

Unusual neurological manifestations in children during the COVID-19 pandemic

Objective: To present paediatric cases of unusual neuroinflammatory conditions encountered during the COVID-19 pandemic in Trinidad & Tobago. Methods: Retrospective study design. Inpatient paediatric patients (aged 0-16 years) hospitalized for neurological complaints from June 2020 - August 2021 at EWMSC. Outcome measures were age at presentation, sex, ethnicity, diagnosis, radiological findings, blood/CSF findings, COVID-19 PCR and antibodies testing, treatment, outcomes and other systems involved. Results: Twenty (20) patients (aged 4-months-old to 15-years-old) had documented neurological involvement. 50% had a diagnosis of ADEM/ADS/AHNE;45% had a diagnosis of either CNS vasculitis (n=3), autoimmune encephalitis (n=3) or GBS (n=3);5% had a diagnosis of acute COVID-19 encephalitis. 70% were of African descent. The youngest age group (0-4 years) (n=11) constituted more males (82%) whereas the eldest age group (10-15 years) (n=3) were all females. Neuroimaging findings were corpus callosal lesions;deep white matter T2 hyperintensities;cerebellar involvement;area postrema and brainstem/C-spine involvement;microhaemorrhages and necrotizing/haemorrhagic lesions (peripheral/central). 70% of patients were either SARS-CoV-2 PCR or COVID-19 antibodies positive. Other systems were involved in 40% to 62.5% (n=5) had cardiac involvement (myocarditis, coronary arteries dilatation, valve regurgitation) and 37.5% (n=3) had pancreatic involvement (autoimmune pancreatitis, type 1 diabetes mellitus). Treatment modalities for CNS manifestations (n=17) were clinically based - 24% (n=4) 3rd line treatment, 29% (n=5) 2nd line treatment, 41% (n=7) 1st line treatment and 6% (n=1) requiring no treatment. All 3 patients with a diagnosis of GBS responded appropriately to IVIG. Developmental outcomes were worst in patients with a diagnosis of autoimmune encephalitis. Conclusion: We have had an explosion of neuro-inflammatory cases since the COVID-19 pandemic began. The range of neuroradiological diagnoses and other systemic involvement (including criteria for PIMS) are interesting, alluding to a neuroinflammatory mechanism. Effects on long-term sequelae and developmental outcomes are concerning in some cases, however, still unknown at this stage.

Recurrent cerebral venous sinus thromboses (CVST's) and livedo reticularis rash-a case of Sneddon syndrome

Background Sneddon syndrome is a rare, progressive small and medium-vessel vasculopathy characterized by the clinical occurrence of livedo racemosa and ischaemic cerebrovascular events. Objectives We present the clinical course and management of this rare condition. Methods An 18-year-old female of East Indian descent presented with the following: CNS involvement: Recurrent Cerebral Venous Sinus Thromboses + Cognitive impairment - Skin: Livedo reticularis rash - Eyes: Bilateral optic nerves atrophy - CVS: Mild to moderate LAD dilation (16/12/2020) - MS: Polyarticular arthritis She first presented at 8-years-old with new-onset squint, ataxia and fever and was treated as culture-negative meningitis (CSF white cells 1238 neutrophils, CSF protein 110mg/ dL). At 16-years-old, she presented with expressive aphasia, headache, fever, left earache and was treated as acute mastoiditis. Regarding the recurrent presentations of CVST's there was involvement of left transverse sinus (untreated 2 years ago), then over a 1-month period despite anticoagulation, right transverse sinus with extension into the right sigmoid sinus and left straight and posterior superior sagittal sinus. She presented with headache, vomiting and new-onset seizures (GTCS) prior to these presentations. An extension of this clot after being non-compliant with low-molecular weight heparin for 1 week resulted in a venous infarct with surrounding oedema. She presented with progressive right-sided weakness and expressive aphasia and within 24 hours, encephalopathic with decerebrate posturing in subclinical status epilepticus. She was managed in PICU for refractory status epilepticus and raised intracranial pressure. There is also a family history of early stroke (maternal cousin with CVST at 8yo on long-term anticoagulation). Results Her inflammatory markers continued to increase despite antibiotic coverage at meningitic doses and she was treated for a CNS vasculitis/Catastrophic Antiphospholipid syndrome with IV anticoagulation (UFH), high-dose steroids then IVIG. Her neurological state gradually improved (coma -> vegetative state -> minimally conscious -> conscious). This was followed by Rituximab therapy 375 mg/m2 weekly x4. Her neurological function gradually improved as she was able to verbally communicate and developed anti-gravity movement of the right side. Hypertension and fever also settled, and inflammatory markers steadily decreased post treatment. Investigations: ANA, dsDNA, ENA negative pANCA borderline positive but MPO, PR3 Antibodies negative Anticardiolipin antibodies negative (on warfarin) Infectious screen (HIV, Hepatitis, COVID-19 serology, Mantoux test, CSF Acid-fast bacilli) - negative CSF cell count - 33 white cells (neutrophils), protein 183mg/dL Skin biopsy report (26/11/2020) - Neutrophils, lymphocytes of leucocytoclasis seen in vessels of dermis. Thrombosis of fibrinoid necrosis of vessel walls and extravasated red blood cells also seen - Obstructive vasculopathy for clinical correlation;Possible Sneddon syndrome/Antiphospholipid syndrome Conclusions There are few case reports describing the clinical course and treatment of this rare syndrome. In our case, treatment for Catastrophic Antiphospholipid syndrome (steroids, IVIG, rituximab and anticoagulation) was beneficial in improving the clinical outcome.

Consumer behaviour in a health crisis: What happened to cash?

This paper uses data from the Federal Reserve Bank of Atlanta’s 2019 Survey and Diary of Consumer Payment Choice and interim rapidresponse surveys in spring and late summer 2020 to give some insights into consumer cash holdings and payments behaviour during the COVID-19 pandemic. The paper describes several key findings from the survey, most notably that US consumers increased their cash holdings at the time of the pandemic lockdowns. More consumers held at least some cash, and almost half of consumers had more than US$100 in spring and late summer 2020, compared with one-third in autumn 2019. In spring, just onethird of consumers reported making an in-person payment, compared with almost everyone in autumn 2019. People who paid in person, however, were about as likely to use cash in the spring as they had been in the previous autumn. Payments of unemployment benefits appear to have affected cash holding for some consumers. Similar to the behaviour of some consumers in advance of hurricanes, some consumers reported getting precautionary amounts of cash. © Henry Stewart Publications,.

Building Mental Health and Psychosocial Support Capacity during a Pandemic: The Process of Adapting Problem Management plus for Remote Training and Implementation during COVID-19 in New York City, Europe and East Africa

On March 11, 2020, COVID-19 was declared a pandemic by the World Health Organization. In response to the sudden rise in COVID-19-related mental health and psychosocial impacts, we embarked on a digital training (e-learning) and remote delivery adaptation for Problem Management Plus Training for Helpers (Remote PM+ Training) based in New York City, four European countries and six African countries. This paper provides an overview of the two Remote PM+ Trainings, including key adaptations and lessons learned across the contexts. Trainings were approximately 75 hours in duration, with a mix of group and individual work, in diverse contexts. Overall, remotely delivered PM+ training and intervention appear appropriate. There were a number of critical lessons learned that contributed to the efficacy of the trainings, such as technological support, digital literacy, preparation and flexibility among the trainers and the trainees. There is also a need for cultural and contextual adaptation towards the delivery of remote training and implementation of PM+. However, the outcomes from these two trainings indicate that PM+ may be adapted for remote (online) training and, if supported with additional studies, could build workforce capacity in contexts in which there is limited in-person access to mental health and psychosocial support services and staff. © 2021 Lippincott Williams and Wilkins. All rights reserved.