Seasonality of Respiratory Viruses Including SARS-CoV-2

We propose that a reservoir of respiratory viruses in clumps of micro-sized dust exists in tropospheric clouds from which virions can be seasonally released into the lower atmosphere and thence to ground level. Respiratory Syncytial Virus (RSV), Seasonal Influenza and Human Para Influenza Virus (HPIV) are all diseases that fall in this category, including SARS-CoV-2. The seasonal incidence of disease at ground level would appear to be patchy over distance scales that are largely dictated by viral-laden dust cloud size modulated by scales of atmospheric turbulence. This could produce clustering of cases in space and time that has given rise to ‘contagion' concepts of community spread and of superspreaders. © 2022 by World Scientific Publishing Co. Pte. Ltd.

Overview SARS-CoV-2 Pandemic as January-February 2022: Likely Cometary Origin, Global Spread, Prospects for Future Vaccine Efficacy

As the SARS-CoV-2 pandemic is nearing its eventual end we focus on what we believe are two key omissions from the mainstream scientific literature and which have significant implications for how mankind manages the next global pandemic. We therefore review data, observations, analyses and conclusions from our series of papers published through 2020 and 2021 on its likely cometary origin and global spread. We also revisit our long held understanding of the superior effectiveness of intra-nasal vaccines against respiratory tract pathogens that involve induction of dimeric secretory IgA antibodies. While these two oversights seem disparate, together they provide us with new insights into our collective awareness of how we might view and address the next global pandemic. We begin with our hypothesis of the likely cometary origin of the SARS-CoV-2 virus via a bolide strike in the stratosphere on the night of October 11 2019 on the 40o N line over Jilin in NE China. Further global spread most likely occurred via prevailing wind systems transporting both the pristine cometary virus followed by continuing strikes from the same primary source as well as prior human-passaged virus transmitted by person to person spread and through contaminated dust in global wind systems. We also include a discussion of our prior work on data relating to vaccine protective efficacy. Finally we review the totality of evidence concerning the likely origin and global spread of the predominant variants of the virus ‘Omicron' (+Delta mix?) from early to mid-December 2021 and extending into the first week January 2022. We describe the striking data showing the large numbers of infectious cases per day and outline the scale of what appears to be a global pandemic phenomenon, the causes of which are unclear and not completely understood. Firstly, these essentially simultaneous and sudden global-wide epidemic COVID-19 out breaks, appear to be largely correlated with events external to the Earth, probably causing globally correlated precipitation events. They appear related broadly to "Space Weather” events that render the Earth vulnerable to cosmic pandemic pathogen attack particularly during times of the minima of the Sunspot Solar Cycle which we are now currently passing through. Secondly, we argue that these sudden global-wide epidemic outbreaks of COVID-19 are specifically largely influenced by global wind transport and deposition mechanisms, the physics of which we need to further explore and comprehend. We conclude on an optimistic note for mankind. Given our prior knowledge of the effectiveness against respiratory tract pathogens of mucosal immunity involving induction of dimeric secretory IgA antibodies, we consider that the recently published intra-nasal vaccine data from laboratories based at the University of California, San Francisco and, independently at Yale University. These latter studies hold out great promise for the future development of both panspecific and specific immunity against future pandemics caused by suddenly emergent respiratory pathogens, whether viral, bacterial or fungal. © 2022 by World Scientific Publishing Co. Pte. Ltd.

COVID-19 Sudden Outbreak of Mystery Case Transmissions in Victoria, Australia, May-June 2021: Strong Evidence of Tropospheric Transport of Human Passaged Infective Virions from the Indian Epidemic

A sudden yet very small outbreak of COVID-19 mystery community transmissions occurred in a defined arc across the inner Western and outer Northern suburbs of Melbourne in May-June 2021. An infection zone that could be 1000 km2 in size. These sudden outbreaks of genuine mystery cases could not be traced to any direct infected contacts nor could they be directly genomically linked to any known infection clusters (e.g. among infected international travellers in hotel quarantine). In response the Government of Victoria on the recommendation of the Chief Medical Officer and the Victorian Department of Health locked down the entire State of Victoria in an extreme Stage 4 emergency. As a consequence, large numbers of PCR COVID-19 tests on oro-nasal swabs were conducted (> 30, 000 per day at peak) and all positives quarantined at home, a directive enforced by police and in some cases the Australian Army. Citizens were neither allowed to leave Melbourne nor from Victoria to any other State of Australia. Contact tracing was conducted on a very large scale by teams of experienced tracers. Several sudden mystery outbreaks continued to occur despite the lock-down on people movements. This included restriction of numbers of visitors at homes, crowd-size limitations, curtailment of sporting events, school closures, mandatory mask wearing, and personal tracking of all individuals in shops and supermarkets (via a personal "QR” digital tracking system linked to mobile phones or via written personal contact statements at store or shop entry). Many of the COVID-19 variants of concern (PANGO classification) were clearly mature human-passaged virions, many of which have been identified in the current and very large 2nd Wave Indian epidemic. We show here there is plausible strong evidence that a heterogeneous set of these "Indian” variants may have been transported by prevailing tropospheric global wind systems via the Indian Ocean and Southern Ocean (Roaring Forties West to East on the 40o S Latitude line) to Victoria, Australia. There is much precedent for such global wind transportations in the history of past Influenza virus pandemics in the last 100 years and the present observations relating to COVID-19 events in Australia are discussed in that context. © 2022 by World Scientific Publishing Co. Pte. Ltd.

Testing and Treatments in Children with Severe Neurologic Manifestations and Sars-Cov-2 Conditions

INTRODUCTION: Our objective was to characterize testing and treatments provided for hospitalized children with and without severe neurologic manifestations with acute SARSCoV- 2 infection or Multisystem Inflammatory Syndrome in Children (MIS-C). METHOD(S): Multinational cross-sectional study of children age < 18 y hospitalized with SARS-CoV-2-related condition between January 2020-July 2021. Admission laboratory, neurologic testing, and treatments related to SARS-CoV-2 conditions were analyzed by severe neurologic manifestation status, a composite of those with univariate logistic regression p< 0.05 for unfavorable outcome (Pediatric Cerebral Performance Category Score 3-6 at hospital discharge). Multivariable logistic regression to identify laboratory values associated with severe neurologic manifestation was performed. RESULT(S): Of 3,556 children, 818 (23%) had severe neurologic manifestation. Children with severe neurologic manifestation were younger (median 5 interquartile range [1-12] vs. 9 [1.1-14] y) and had more MIS-C vs. acute SARSCoV- 2 (35% vs. 22%), pre-existing disease (68% vs. 48%), and death (5% vs. 0.5%), all p< 0.001. Blood fibrinogen was lower in children with (341 [230, 500]) vs. without (410 [274, 537] mg/dl) severe neurologic manifestation, p< 0.001. More children with severe neurologic manifestations had electroencephalography (23% vs. 2.7%), head CT (24% vs. 6%), and brain MRI (16% vs. 4%) performed, p< 0.001, but results were not more frequently abnormal between groups. Cerebrospinal fluid was sampled in 19% vs. 9%, p< 0.001, and intracranial pressure monitors were placed in 5 (1%) vs. 14 (0.5%), p=0.179. Children with severe neurologic manifestation received more steroids (25% vs. 16%) and remdesivir (15% vs. 7%), p< 0.001. After adjustment, higher lymphocytes (odds ratio 1.0003 [95% confidence interval 1.00009, 1.0005]) and lower fibrinogen (0.998 [0.996, 0.999]), p< 0.05, were associated with severe neurologic manifestation status. CONCLUSION(S): Modest laboratory signatures of severe neurologic manifestations in children hospitalized with SARSCoV- 2 related conditions were found. Despite association with worse outcomes, relatively few children received contemporary neurological testing and SARS-CoV-2 related treatments.

Neurologic Outcomes in Hospitalized Children with Acute Sars-Cov-2 or Mis-C

INTRODUCTION: We aimed to describe neurologic outcomes in hospitalized children diagnosed with acute SARS-CoV-2 infection or Multisystem Inflammatory Syndrome in Children (MIS-C). METHOD(S): Multinational (n=50 centers), cross-sectional study of neurologic manifestations in children < 18 y old hospitalized with a positive SARS-CoV-2 test or clinical diagnosis of a SARS-CoV-2-related condition between January 2020-July 2021. Multivariable logistic regression to identify risk factors for unfavorable outcome at hospital discharge (Pediatric Cerebral Performance Category Score 3-6) was performed. Severe neurologic manifestation included those with univariate logistic regression significant to p< 0.05 for unfavorable outcome: dysautonomia, stroke, encephalopathy, cardiac arrest, meningitis/encephalitis, coma, seizures, weakness, and delirium. RESULT(S): Of 3,556 children (46% female), 3333 (94%) had acute SARS-CoV-2 and 223 (6%) had MIS-C. Unfavorable outcome occurred in 368 (11%) children and 39 (1.1%) died. Children with unfavorable outcome were older (median 9 interquartile range [4-14] vs. 8 [1-14] y, p< 0.001), and more likely to have neurologic comorbidity (72% vs. 10%, p< 0.001), worse Glasgow coma scale score (GCS) group (19% with combined GCS 9-15 vs. 1.7% with GCS< 9, p< 0.001), any neurologic manifestation (52% vs. 37%, p< 0.001), and severe neurologic manifestation (48% vs. 20%, p< 0.001) compared to children with favorable outcome. In multivariate logistic regression, older age (odds ratio 1.1 95% confidence interval [1.0, 1.1], total pre-existing conditions (2.1 [1.8, 2.5]), severe neurologic manifestation (3.4 [2.0, 6.0], and worse GCS group (4.0 [2.6, 5.9]) were associated with unfavorable outcome. CONCLUSION(S): Children with severe neurologic manifestation, pre-existing conditions, and children of older age hospitalized with acute SARS-CoV-2 infection or MIS-C have worse hospital discharge outcomes. Follow-up of these children is necessary to identify and manage neurologic and functional impairment.

Footprints of Past Pandemics in the Human Genome

Viral pandemics over centuries and millennia have left indelible signatures on our genomes. Deciphering these signatures could give us profoundly important information on our evolutionary history that appears to have been directed by the arrival of new viruses from the deep cosmos. A recent study that shows a residual signature of SARS-CoV-2 (in the form of multiple generational expression of host-specific SARS-CoV targeting viral interacting proteins known as VIPs) in the genomes of a South Asian population suggests that a major COVID-19 type infectious episode may have occurred about 25, 000 years ago. The need to monitor the stratosphere for the arrival of new pathogenic viruses, or even the return of old viruses such as Small Pox, is stressed. © 2022 by World Scientific Publishing Co. Pte. Ltd.

Pediatric Neurology Patient Disparitiesin Use of and Accessto Rapid Telehealth Implementation during the COVID-19 Pandemic

Objective: To compare telehealth (telemedicine (video) and telephone) utilization pre-COVID-19 (10/6/2019-2/29/2020) and during the COVID-19 pandemic (3/1/2020-5/1/2021) among the diverse patient populations served by child neurology clinics at Seattle Children's Hospital (SCH). Background: SCH serves a five-state geographic area comprising 27% of the United States' landmass, of which 25% is rural. Prior to the COVID-19 pandemic, the Neurology department utilized telemedicine visits infrequently (0.001% visits). COVID-19 demanded rapid implementation of telehealth with variable demographic use. Utilization of telephone versus telemedicine visits may indicate populations at risk of a care gap with increased telehealth use. Design/Methods: We tracked telemedicine, telephone, and in-person neurology visit utilization based on race/ethnicity, English proficiency, insurance type, interpreter utilization, broadband status, area deprivation index (ADI), and zip code of residence. While broadband status, ADI, and zip code data included only patients from the state of Washington, other measures included all patients seen. Results: Prior to the pandemic, telemedicine was used primarily for remote patient populations with a higher frequency of Hispanic and non-English proficient household patients. During the COVID-19 pandemic, we found a trend toward increased telephone visit utilization for patients of Hispanic ethnicity (14.7% vs 6.9% overall), patients from non-English proficient households (18.5% vs 10.1% overall), and those who reside in a cluster of four zip codes in Eastern Washington (11.9% of all phone visits). Areas with less broadband access or a higher ADI utilized telephone visits more compared to telemedicine visits. Conclusions: Given Seattle Children's Hospital's long-term goal of increased telemedicine use to improve access to care for underserved populations, further interventions are necessary to close the access to care gap for patients and families who reside in areas with lower broadband internet access, possess limited socioeconomic resources, Hispanic families, and those with limited English proficiency.

GCS-neuro-COVID: Neurologic manifestations and outcomes in children with and without comorbidities

INTRODUCTION: Children with comorbidities are at increased risk of severe disease due to SARS-CoV-2 (COVID-19) infection and Multisystem Inflammatory Syndrome-Children (MIS-C). We hypothesized that children with comorbidities hospitalized with COVID-19 or MIS-C will experience more neurologic manifestations and worse outcomes compared to children without comorbidities. METHODS: Secondary study of the Global Consortium Study of Neurological Dysfunction in COVID-19 (GCS-NeuroCOVID) study, a multinational study enrolling children < 18 years of age hospitalized with confirmed/presumed COVID-19 or MIS-C. Neurological manifestations, lengths of hospital and intensive care unit (ICU) stay, hospital disposition and mortality were analyzed by comorbidity status. A multivariable logistic regression was performed to analyze the association of comorbidity with neurologic manifestation. RESULTS: Overall, 824 (55%) children had any comorbidity and 646 (43%) had any neurologic manifestation. Children with comorbidity were older (median [interquartile range] 9.5 [4-15] vs. 6.4 [0.5-12], had more COVID-19 (58%) vs. MIS-C (32%) and ICU admissions (39% vs. 29%), and longer hospital length of stay (9 [2-9] vs. 5 [2-6] days), all p< .001;mortality was similar (1.5% vs. 0.5%, p=.067). The most common comorbidities were neurologic and respiratory (20% each). Children with comorbidity more frequently had any neurologic manifestation (61% vs. 39%), and seizures/status epilepticus (11% vs. 4%), p< .001). There were no differences between comorbidity vs no comorbidity groups for the most common neurologic manifestations including headache (21% vs. 20%) and acute encephalopathy (17% vs. 15%). Older age (odds ratio 1.1 [95% confidence interval 1.1-1.1]), ICU stay (2.6 [1.9-3.4]), MIS-C (2.2 [1.5-3.2]), and neurologic (2.8 [1.9-4.1]) comorbidity were associated with neurologic manifestation while cardiovascular morbidity was protective for neurologic manifestation (.5 [.3-.8]), all p< .05. CONCLUSIONS: Children with comorbidity, especially neurologic, who are hospitalized with COVID-19 related conditions are at increased risk of neurologic manifestations. Assessment of post-hospital neurodevelopmental outcomes to determine the impact of neurologic manifestations in children with comorbidity and COVID-19 related conditions is critically needed.