Exhaled Aerosols in PCR-confirmed SARS-CoV-2-infected Children

Background Available data on aerosol emisions in children and adolescents during spontaneous breathing are limited. Our aim was to gain insight into the role of children in the spread of SARS-CoV-2 and whether aerosol measurements in children can be used to help detect so-called superspreaders - infected individuals with extremely high numbers of exhaled aerosol particles. Methods In this prospective study, the aerosol concentration of SARS-CoV-2 PCR-positive and SARS-CoV-2 PCR-negative children and adolescents (2-17 years) was investigated. All subjects were asked about their current health status and medical history. The exhaled aerosol particle counts of PCR-negative and PCR-positive subjects were measured using the Resp-Aer-Meter (Palas GmbH, Karlsruhe, Germany) and compared using linear regresion. The study was registered in the German Register of Clinical Studies (DRKS), DRKS00028539. Results A total of 250 children and adolescents were included in the study, 105 of whom were SARS-CoV-2 positive and 145 of whom were SARS-CoV-2 negative. The median age acros both groups was nine years (IQR 7-11). A total of 124 (49.6%) participants were female, and 126 (50.4%) participants were male. A total of 81.9% of the SARS-CoV-2-positive group had symptoms of viral infection. The median particle count of all individuals was 79.55 p/l (IQR 44.55-141.15). There was a tendency for older children to exhale more particles (1-5 years: 79.54 p/l;6-11 years: 77.96 p/l;12-17 years: 98.63 p/l). SARS-CoV-2 PCR status was not a bivariate predictor (t=.82, p=.415) for the exhaled aerosol particle count;however, the SARS-CoV-2 status was shown to be a significant predictor in a multiple regresion model together with age, body mas index (BMI), covid vaccination, and past SARS-CoV-2 infection (t=.2.81 p=.005). Covid vaccination status was a highly significant predictor of exhaled aerosol particles (p <.001).Conclusion During SARS-CoV-2 infection, children and adolescents do not have elevated aerosol levels. In addition, no superspreaders were found. Children and adolescents are not the main driver of the SARS-CoV-2 pandemic. .

Identifying the Superspreader in Proactive Backward Contact Tracing by Deep Learning

The goal of proactive contact tracing is to diminish the spread of an epidemic by means of contact tracing mobile apps and big data analysis. Finding superspreaders as has been used in Japan and Australia during the early days of the COVID-19 pandemic has proven effective as backward contact tracing can pick up infections that might otherwise be missed. In this paper, we formulate a proactive contact tracing problem to identify the superspreaders using maximum-likelihood estimation, graph traversal and deep learning algorithms. This problem is challenging due to its sheer combinatorial complexity, problem scale and the fact that the underlying infection network topology is rarely known. We propose a deep learning-based framework using Graph Neural Networks to iteratively refine the supervised learning of proactive contact tracing networks using smaller infection networks and to identify the superspreader. By optimizing the graph traversal and topological features for deep learning, proactive contact tracing strategies can be developed to contain superspreading in an epidemic outbreak.

Do Markets Price CEOs Health Hazards? Evidence from the COVID-19 Pandemic

We find evidence that markets anticipate the potential loss of firm value in the event of the CEO falling sick and eventually dying of COVID-19 in a sample of almost 3000 listed firms from across 137 regions in 10 European countries. First, we use soccer games as "super-spreader"events. The instrumented number of infected cases per capita in the region where company headquarters are located predicts a significant drop in stock returns during March and April 2020 for firms managed by CEOs with a higher probability of dying from COVID-19. Second, we show that the stock price of these firms increases significantly the day on which positive news on the development of COVID-19 vaccines are released in the market. © 2022 World Scientific Publishing Company. Midwest Finance Association.

Detailed analysis of in-hospital transmission of SARS-CoV-2 using whole genome sequencing.

BACKGROUND: Hospital transmission of SARS-CoV-2 has proved difficult to control, with healthcare-associated infections troublesome throughout. AIM: To understand factors contributing to hospital transmission of infections, which is necessary for containing spread. METHODS: An outbreak of 56 staff and patient cases of COVID-19 over a 31-day period in a tertiary referral unit is presented, with at least a further 29 cases identified outside of the unit and the hospital by whole genome sequencing (WGS). FINDINGS: Transmission is documented from staff to staff, staff to patients, and patients to staff, showing disruption of a tertiary referral service, despite implementation of nationally recommended control measures, superior ventilation, and use of personal protective equipment. There was extensive spread from the index case, despite this patient spending only 10 h bed bound on the ward in strict cubicle isolation and with an initial single target low level (CT = 32) polymerase chain reaction test. CONCLUSION: This investigation highlights how effectively and rapidly SARS-CoV-2 can spread in certain circumstances. It raises questions about infection control measures in place at the time and calls into question the premise that transmissibility can be reliably detected by using lower sensitivity rapid antigen lateral flow tests. We also highlight the value of early intervention in reducing impact as well as the value of WGS in understanding outbreaks.

Contact tracing & super-spreaders in the branching-process model.

In recent years, it became clear that super-spreader events play an important role, particularly in the spread of airborne infections. We investigate a novel model for super-spreader events, not based on a heterogeneous contact graph but on a random contact rate: Many individuals become infected synchronously in single contact events. We use the branching-process approach for contact tracing to analyze the impact of super-spreader events on the effect of contact tracing. Here we neglect a tracing delay. Roughly speaking, we find that contact tracing is more efficient in the presence of super-spreaders if the fraction of symptomatics is small, the tracing probability is high, or the latency period is distinctively larger than the incubation period. In other cases, the effect of contact tracing can be decreased by super-spreaders. Numerical analysis with parameters suited for SARS-CoV-2 indicates that super-spreaders do not decrease the effect of contact tracing crucially in case of that infection.

Accounting for super-spreader events and algebraic decay in SIR models

A central feature of pandemics is the emergence and decay of localized infection waves. While traditional SIR models for infectious diseases can reproduce such waves, they fail to capture two key features. First, SIR models are unable to represent short-duration super-spreader events which often trigger infection waves in a community. Second, SIR models predict exponential decay to an asymptotic state after the infection wave peaks. In contrast, observations suggest a slower algebraic decay. In this paper, we develop models for the basic reproduction number R0 to capture these features. To generate quantitative estimates for R0 during super-spreader events, we reconcile the SIR framework with the Wells-Riley model for airborne disease transmission. We also show that algebraic decay emerges naturally if models are modified to account for the behavioral tendency towards relaxing precautions as the infected fraction decreases. This approach merges for the first time behavioral with physicochemical aspects.(c) 2022 Elsevier B.V. All rights reserved.

Immunity in Omicron SARS-CoV-2 breakthrough infection in vaccinated adults

The new SARS-CoV-2 Omicron variant has more than 15 mutations in the receptor binding domain of the Spike protein enabling increased transmissibility and viral escape from antibodies in vaccinated individuals. It is unclear how vaccine immunity protects against Omicron infection. Here we show that vaccinated participants at a super-spreader event had robust recall response of humoral and pre-existing cellular immunity induced by the vaccines, and an emergent de novo T cell response to non-Spike antigens. Omicron SARS-CoV-2-infected individuals had significantly increased activated SARS-CoV-2 Wild type Spike-specific (vaccine) cytotoxic T cells, activated follicular helper (TFH) cells, functional T cell responses, boosted humoral responses, rapid release of Spike and RBD-specific IgG+ B cell plasmablasts and memory B cells into circulation. Omicron SARS-CoV-2 infected individuals had significantly induced de novo memory T cell responses to non-Spike viral antigens. This concerted T and B cell immunity may provide durable and broad immunity.

Advanced Genetic Methodologies in Tracking Evolution and Spread of SARS-CoV-2.

A newly emerged coronavirus, SARS-CoV-2, caused severe pneumonia outbreaks in China in December 2019 and has since spread to various countries around the world. Here, we describe genetic methods to trace the evolution route and probe the transmission dynamics of this virus.

Contact tracing-induced Allee effect in disease dynamics.

Contact tracing, case isolation, quarantine, social distancing, and other non-pharmaceutical interventions (NPIs) have been a cornerstone in managing the COVID-19 pandemic. However, their effects on disease dynamics are not fully understood. Saturation of contact tracing caused by the increase of infected individuals has been recognized as a crucial variable by healthcare systems worldwide. Here, we model this saturation process with a mechanistic and a phenomenological model and show that it induces an Allee effect which could determine an infection threshold between two alternative states-containment and outbreak. This transition was considered elsewhere as a response to the strength of NPIs, but here we show that they may be also determined by the number of infected individuals. As a consequence, timing of NPIs implementation and relaxation after containment is critical to their effectiveness. Containment strategies such as vaccination or mobility restriction may interact with contact tracing-induced Allee effect. Each strategy in isolation tends to show diminishing returns, with a less than proportional effect of the intervention on disease containment. However, when combined, their suppressing potential is enhanced. Relaxation of NPIs after disease containment--e.g. because vaccination--have to be performed in attention to avoid crossing the infection threshold required to a novel outbreak. The recognition of a contact tracing-induced Allee effect, its interaction with other NPIs and vaccination, and the existence of tipping points contributes to the understanding of several features of disease dynamics and its response to containment interventions. This knowledge may be of relevance for explaining the dynamics of diseases in different regions and, more importantly, as input for guiding the use of NPIs, vaccination campaigns, and its combination for the management of epidemic outbreaks.

A Systematic Review of COVID-19 Transmission Dynamics and Clinical Response on Cruise Ships Globally between January and October 2020

Background. Cruise ships provide an ideal setting for efficient transmission of SARS-CoV- 2 given a socially dense exposure environment. No systematic review of transmission of COVID-19 on cruise ships to date has been completed. Methods. MEDLINE was searched in accordance with PRIMSA guidelines for COVID-19 cases associated with cruise ships. A list of cruise ships with COVID-19 was crossed referenced with the Centers for Disease Controls' list of cruise ships that had at least one COVID-19 case associated with them within 14 days of disembarkation. News articles were also searched for epidemiologic information. 43 full text articles from MEDLINE and 177 from news sources were included in the final analysis. Narratives of the outbreak in ships with over 100 cases are presented. Results. A total of 80 ships and 104 unique voyages on cruise ships were identified with at least one COVID-19 case before 30 October 2020. Nineteen ships had more than one voyage with a case of COVID-19. The median number of cases per ship was three (intraquartile range (IQR) 1-17.8), with two notable outliers the Diamond Princess and Ruby Princess which had 712 and 907 cases respectively. The median attack rate for COVID-19 was 0.2% (IQR 0.03% -1.5%), though this distribution was skewed to the right with a mean attack rate of 3.7%. 25.9% of voyages had at least one associated death. Outbreaks involving only crew were later than outbreaks with guests and crew. Conclusion. COVID-19 can spread easily on cruise ships in a susceptible population when there is an absence of mitigation measures due to the confined space and high-density of contact networks. This can not only create super spreader events but also facilitate international spread.

Superspreading in the emergence of COVID-19 variants.

Superspreading and variants of concern (VOC) of the human pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are the main catalyzers of the coronavirus disease 2019 (COVID-19) pandemic. However, measuring their individual impact is challenging. By examining the largest database of SARS-CoV-2 genomes The Global Initiative on Sharing Avian Influenza Data [GISAID; n >1.2 million high-quality (HQ) sequences], we present evidence suggesting that superspreading has had a key role in the epidemiological predominance of VOC. There are clear signatures in the database compatible with large superspreading events (SSEs) coinciding chronologically with the worst epidemiological scenarios triggered by VOC. The data suggest that, without the randomness effect of the genetic drift facilitated by superspreading, new VOC of SARS-CoV-2 would have had more limited chance of success.

Merits and Demerits of Selective Isolation of Superspreaders: A Mathematical Modeling Study Based upon West Bengal (India) SARS-COV 2 Data.

CONTEXT: All COVID cases and their contacts are considered highly infectious requiring isolation, which blocks the COVID isolation beds and disrupts life in the community. AIM: To find out the effect of selective isolation and contact tracing of superspreaders as compared with the conventional ongoing protocol. SETTINGS AND DESIGN: A mathematical model was designed to look at the effect of isolation and contact tracing of only those with high viral loads (superspreaders) on COVID-19 bed occupancy and overall mortality, in comparison with conventional protocol of isolation and contact tracing of all cases. MATERIALS AND METHODS: An agent-based model, calibrated to the ongoing West Bengal COVID-19 data, was run for a total of 178 days to find out the effect of the interventions on COVID-19 bed occupancy and mortality. RESULTS: There is an impressive reduction in the occupancy of COVID isolation beds, even with the preintervention testing rate with no negative impact on mortality. CONCLUSIONS: Strict isolation of superspreaders only, maybe highly effective in reducing the burden on health care and solving the COVID isolation bed crises if the testing rate is significantly increased.

Clinical characteristics and outcomes of patients with haematologic malignancies and COVID-19 suggest that prolonged SARS-CoV-2 carriage is an important issue.

Specificities of COVID-19 disease course in patients with haematologic malignancies are still poorly studied. So, we aimed to compare patients with haematologic malignancies to patients without malignancies, matched by sex and age and hospitalised for COVID-19 at the same time and in the same centre. Among 25 patients with haematologic malignancies, we found that mortality (40% versus 4%, p < 0.01), number of days with RT-PCR positivity (21.2 ± 15.9 days [range, 3-57] versus 7.4 ± 5.6 days [range, 1-24], p < 0.01), maximal viral load (mean minimal Ct, 17.2 ± 5.2 [range, 10-30] versus 26.5 ± 5.1 [range, 15-33], p < 0.0001) and the delay between symptom onset and clinical worsening (mean time duration between symptom onset and first day of maximum requirement in inspired oxygen fraction, 14.3 ± 10.7 days versus 9.6 ± 3.7 days, p = 0.0485) were higher than in other patients. COVID-19 course in patients with haematologic malignancies has a delayed onset and is more severe with a higher mortality, and patients may be considered as super-spreaders. Clinicians and intensivists need to be trained to understand the specificity of COVID-19 courses in patients with haematological malignancies.

Superspreaders drive the largest outbreaks of hospital onset COVID-19 infections.

SARS-CoV-2 is notable both for its rapid spread, and for the heterogeneity of its patterns of transmission, with multiple published incidences of superspreading behaviour. Here, we applied a novel network reconstruction algorithm to infer patterns of viral transmission occurring between patients and health care workers (HCWs) in the largest clusters of COVID-19 infection identified during the first wave of the epidemic at Cambridge University Hospitals NHS Foundation Trust, UK. Based upon dates of individuals reporting symptoms, recorded individual locations, and viral genome sequence data, we show an uneven pattern of transmission between individuals, with patients being much more likely to be infected by other patients than by HCWs. Further, the data were consistent with a pattern of superspreading, whereby 21% of individuals caused 80% of transmission events. Our study provides a detailed retrospective analysis of nosocomial SARS-CoV-2 transmission, and sheds light on the need for intensive and pervasive infection control procedures.

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, presents a global public health challenge. Hospitals have been at the forefront of this battle, treating large numbers of sick patients over several waves of infection. Finding ways to manage the spread of the virus in hospitals is key to protecting vulnerable patients and workers, while keeping hospitals running, but to generate effective infection control, researchers must understand how SARS-CoV-2 spreads. A range of factors make studying the transmission of SARS-CoV-2 in hospitals tricky. For instance, some people do not present any symptoms, and, amongst those who do, it can be difficult to determine whether they caught the virus in the hospital or somewhere else. However, comparing the genetic information of the SARS-CoV-2 virus from different people in a hospital could allow scientists to understand how it spreads. Samples of the genetic material of SARS-CoV-2 can be obtained by swabbing infected individuals. If the genetic sequences of two samples are very different, it is unlikely that the individuals who provided the samples transmitted the virus to one another. Illingworth, Hamilton et al. used this information, along with other data about how SARS-CoV-2 is transmitted, to develop an algorithm that can determine how the virus spreads from person to person in different hospital wards. To build their algorithm, Illingworth, Hamilton et al. collected SARS-CoV-2 genetic data from patients and staff in a hospital, and combined it with information about how SARS-CoV-2 spreads and how these people moved in the hospital . The algorithm showed that, for the most part, patients were infected by other patients (20 out of 22 cases), while staff were infected equally by patients and staff. By further probing these data, Illingworth, Hamilton et al. revealed that 80% of hospital-acquired infections were caused by a group of just 21% of individuals in the study, identifying a 'superspreader' pattern. These findings may help to inform SARS-CoV-2 infection control measures to reduce spread within hospitals, and could potentially be used to improve infection control in other contexts.

Effects of environmental variability on superspreading transmission events in stochastic epidemic models.

Superspreaders (individuals with a high propensity for disease spread) have played a pivotal role in recent emerging and re-emerging diseases. In disease outbreak studies, host heterogeneity based on demographic (e.g. age, sex, vaccination status) and environmental (e.g. climate, urban/rural residence, clinics) factors are critical for the spread of infectious diseases, such as Ebola and Middle East Respiratory Syndrome (MERS). Transmission rates can vary as demographic and environmental factors are altered naturally or due to modified behaviors in response to the implementation of public health strategies. In this work, we develop stochastic models to explore the effects of demographic and environmental variability on human-to-human disease transmission rates among superspreaders in the case of Ebola and MERS. We show that the addition of environmental variability results in reduced probability of outbreak occurrence, however the severity of outbreaks that do occur increases. These observations have implications for public health strategies that aim to control environmental variables.

Viral Load of Severe Acute Respiratory Syndrome Coronavirus 2 in Adults During the First and Second Wave of Coronavirus Disease 2019 Pandemic in Houston, Texas: The Potential of the Superspreader.

BACKGROUND: During the coronavirus disease 2019 pandemic, a minority of index cases are associated with a majority of secondary cases suggesting that superspreaders could drive the pandemic. We identified a phenotype in individuals with extremely high viral load who could act as superspreaders. METHODS: Data were analyzed from individuals tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from 18 March through 15 August 2020. Outcomes were compared using contingency table and quantile regression to test the equality of medians between the pandemic waves and by viral load groups. RESULTS: Of the 11 564 samples tested, 1319 (11.4%) were positive for SARS-CoV-2. An increase in weekly median viral load occurred in the second wave of the SARS-CoV2 pandemic. This population was more likely to be women, outpatients, and symptomatic and to have an extremely high or high viral load. In patients with multiple reverse-transcription polymerase chain reaction-positive test results, the durations of viral shedding were comparable between individuals with asymptomatic/mild and mild/moderate illness severity. CONCLUSIONS: We detected a small group of individuals with extremely high SARS-CoV-2 viral loads and mild illness. We believe that these individuals' characteristics could be consistent with the superspreader phenomenon and that greater awareness of the social dynamics of these individuals is needed to understand the spread of SARS-CoV-2.

Epidemiology and Clinical Course of First Wave Coronavirus Disease Cases, Faroe Islands.

The Faroe Islands was one of the first countries in the Western Hemisphere to eliminate coronavirus disease (COVID-19). During the first epidemic wave in the country, 187 cases were reported between March 3 and April 22, 2020. Large-scale testing and thorough contact tracing were implemented early on, along with lockdown measures. Transmission chains were mapped through patient history and knowledge of contact with prior cases. The most common reported COVID-19 symptoms were fever, headache, and cough, but 11.2% of cases were asymptomatic. Among 187 cases, 8 patients were admitted to hospitals but none were admitted to intensive care units and no deaths occurred. Superspreading was evident during the epidemic because most secondary cases were attributed to just 3 infectors. Even with the high incidence rate in early March, the Faroe Islands successfully eliminated the first wave of COVID-19 through the early use of contact tracing, quarantine, social distancing, and large-scale testing.

First Reported Nosocomial Outbreak of Severe Acute Respiratory Syndrome Coronavirus 2 in a Pediatric Dialysis Unit.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a life-threatening respiratory condition caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and was initially detected in China in December 2019. Currently, in Germany >140 000 cases of COVID-19 are confirmed. Here we report a nosocomial outbreak of SARS-CoV-2 infections in the pediatric dialysis unit of the University Hospital Münster (UHM). METHODS: Single-step real-time reverse-transcription polymerase chain reaction (rRT-PCR) from nasopharyngeal swabs was used to diagnose the index patient and identify infected contacts. Epidemiological links were analyzed by patient interviews and medical record reviews. In addition, each contact was assessed for exposure to the index case and monitored for clinical symptoms. Cycle threshold (Ct) values of all positive test results were compared between symptomatic and asymptomatic cases. RESULTS: Forty-eight cases were involved in this nosocomial outbreak. Nine contact cases developed laboratory-confirmed COVID-19 infections. Two SARS-CoV-2-positive cases remained clinically asymptomatic. Eleven cases reported flulike symptoms without positive results. Ct values were significantly lower in cases presenting typical COVID-19 symptoms, suggesting high viral shedding (P = .007). CONCLUSIONS: Person-to-person transmission was at the heart of a hospital outbreak of SARS-CoV-2 between healthcare workers (HCWs) and patients in the pediatric dialysis unit at UHM. Semiquantitative rRT-PCR results suggest that individuals with high viral load pose a risk to spread SARS-CoV-2 in the hospital setting. Our epidemiological observation highlights the need to develop strategies to trace and monitor SARS-CoV-2-infected HCWs to prevent COVID-19 outbreaks in the hospital setting.

Superspreaders: A Lurking Danger in the Community.

A "superspreader" refers to an unusually contagious organism infected with a disease. With respect to a human borne illnesses, a superspreader is someone who is more likely to infect other humans when compared to a typically infected person. The existence of human superspreaders is deeply entrenched in history; the most famous case being that of Typhoid Mary. Through contact tracing, epidemiologists have identified human superspreaders in measles, tuberculosis, rubella, monkeypox, smallpox, Ebola hemorrhagic fever, and SARS. The recent outbreak of Coronavirus disease (COVID-19) has shifted the focus back on the superspreaders. We herein present a case report of a COVID-19 superspreader with a hitherto unusually high number of infected contacts. The index case was a 33 year old male who resided in a low income settlement comprising of rehabilitated slum dwellers and worked as a healthcare worker (HCW) in a tertiary care hospital and had tested positive for COVID-19.On contact tracing, he had a total of 125 contacts, of which 49 COVID-19 infections had direct or indirect contact with the index case, qualifying him as a "superspreader." This propagated infection led to an outbreak in the community. Contact tracing, testing and isolation of such superspreaders from the other members of the community is essential to stop the spread of this disease and contain the COVID-19 pandemic.

Observations on the Occurrence, Transmission and Management of the COVID-19 Pandemic Derived from Physics.

Three important observations derived from the ongoing COVID-19 pandemic could result in the development of novel approaches to deal with it and avoid or at least minimize the occurrence and impact of future outbreaks. First, the dramatic increase in pandemics in the past decade alone suggests that the current relationship of humans with the environment is quickly becoming unstable, with potentially catastrophic consequences. In order to reduce the toll in life and property, we would need to shift our emphasis from control of nature to a symbiosis with nature. This, then, can become the new framework for dealing effectively with environmental issues such as climate change, whereby properly applied medical science would provide the necessary impetus for action. Second, the existence of superspreaders of infection among populations in this pandemic requires that we develop objective tests, most likely of a genetic nature, to identify them rather than apply indiscriminate and draconian controls across the board. Not identifying superspreaders in a timely fashion could allow this pandemic to turn into a black swan event, with a catastrophic impact on society. Third, we need to refocus our efforts in dealing with this pandemic from the virus itself to the human hosts. An objective morbidity risk index can be developed such that most of us can go about our daily business without the fear of becoming seriously ill, while measures can be implemented to protect those who are most vulnerable to this virus. These observations point clearly to a need for a paradigm shift.