Ventilation Techniques and Risk for Transmission of Coronavirus Disease, Including COVID-19: A Living Systematic Review of Multiple Streams of Evidence.

BACKGROUND: Mechanical ventilation is used to treat respiratory failure in coronavirus disease 2019 (COVID-19). PURPOSE: To review multiple streams of evidence regarding the benefits and harms of ventilation techniques for coronavirus infections, including that causing COVID-19. DATA SOURCES: 21 standard, World Health Organization-specific and COVID-19-specific databases, without language restrictions, until 1 May 2020. STUDY SELECTION: Studies of any design and language comparing different oxygenation approaches in patients with coronavirus infections, including severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS), or with hypoxemic respiratory failure. Animal, mechanistic, laboratory, and preclinical evidence was gathered regarding aerosol dispersion of coronavirus. Studies evaluating risk for virus transmission to health care workers from aerosol-generating procedures (AGPs) were included. DATA EXTRACTION: Independent and duplicate screening, data abstraction, and risk-of-bias assessment (GRADE for certainty of evidence and AMSTAR 2 for included systematic reviews). DATA SYNTHESIS: 123 studies were eligible (45 on COVID-19, 70 on SARS, 8 on MERS), but only 5 studies (1 on COVID-19, 3 on SARS, 1 on MERS) adjusted for important confounders. A study in hospitalized patients with COVID-19 reported slightly higher mortality with noninvasive ventilation (NIV) than with invasive mechanical ventilation (IMV), but 2 opposing studies, 1 in patients with MERS and 1 in patients with SARS, suggest a reduction in mortality with NIV (very-low-certainty evidence). Two studies in patients with SARS report a reduction in mortality with NIV compared with no mechanical ventilation (low-certainty evidence). Two systematic reviews suggest a large reduction in mortality with NIV compared with conventional oxygen therapy. Other included studies suggest increased odds of transmission from AGPs. LIMITATION: Direct studies in COVID-19 are limited and poorly reported. CONCLUSION: Indirect and low-certainty evidence suggests that use of NIV, similar to IMV, probably reduces mortality but may increase the risk for transmission of COVID-19 to health care workers. PRIMARY FUNDING SOURCE: World Health Organization. (PROSPERO: CRD42020178187).

Interspecies Jumping of Bat Coronaviruses.

In the last two decades, several coronavirus (CoV) interspecies jumping events have occurred between bats and other animals/humans, leading to major epidemics/pandemics and high fatalities. The SARS epidemic in 2002/2003 had a ~10% fatality. The discovery of SARS-related CoVs in horseshoe bats and civets and genomic studies have confirmed bat-to-civet-to-human transmission. The MERS epidemic that emerged in 2012 had a ~35% mortality, with dromedaries as the reservoir. Although CoVs with the same genome organization (e.g., Tylonycteris BatCoV HKU4 and Pipistrellus BatCoV HKU5) were also detected in bats, there is still a phylogenetic gap between these bat CoVs and MERS-CoV. In 2016, 10 years after the discovery of Rhinolophus BatCoV HKU2 in Chinese horseshoe bats, fatal swine disease outbreaks caused by this virus were reported in southern China. In late 2019, an outbreak of pneumonia emerged in Wuhan, China, and rapidly spread globally, leading to >4,000,000 fatalities so far. Although the genome of SARS-CoV-2 is highly similar to that of SARS-CoV, patient zero and the original source of the pandemic are still unknown. To protect humans from future public health threats, measures should be taken to monitor and reduce the chance of interspecies jumping events, either occurring naturally or through recombineering experiments.

Facemask use in community settings to prevent respiratory infection transmission: A rapid review and meta-analysis.

INTRODUCTION: Synthesis of the available evidence on the effectiveness of medical and cloth facemask use by the general public in community settings is required to learn lessons for future respiratory epidemics/pandemics. METHOD: Search terms relating to facemasks, infection and community settings were used for PubMed, the Cochrane Library Database and Google Scholar. A meta-analysis was conducted using a random-effects model. RESULTS: The review included 12 primary studies on the effectiveness of medical facemask use to prevent influenza, influenza-like illness, SARS-CoV, and SARS-CoV-2 transmission. The meta-analysis demonstrated that facemask use significantly reduces the risk of transmitting these respiratory infections (pooled OR = 0.66, 95% CI 0.54-0.81). Of the 12 studies, 10 clinical trials suggested that respiratory infection incidence is lower with high medical facemask compliance, early use and use in combination with intensive hand hygiene. One cohort study conducted during the SARS-CoV-2 pandemic demonstrated that facemasks are effective in reducing SARS-CoV-2 transmission when used before those who are infected develop symptoms. One case-control study reported that controls used medical facemasks more often than cases infected with SARS-CoV (p < 0.05). No primary study on cloth facemask effectiveness to prevent respiratory infection transmission was found. CONCLUSION: Based on the available evidence, medical facemask use by healthy and sick individuals is recommended for preventing respiratory infection transmission in community settings. Medical facemask effectiveness is dependent on compliance and utilization in combination with preventive measures such as intensive hand hygiene. No direct evidence is currently available in humans supporting the recommendation of cloth facemask use to prevent respiratory infection transmission.

Oxygen Therapy and Risk of Infection for Health Care Workers Caring for Patients With Viral Severe Acute Respiratory Infection: A Systematic Review and Meta-analysis.

STUDY OBJECTIVE: To synthesize the evidence regarding the infection risk associated with different modalities of oxygen therapy used in treating patients with severe acute respiratory infection. Health care workers face significant risk of infection when treating patients with a viral severe acute respiratory infection. To ensure health care worker safety and limit nosocomial transmission of such infection, it is crucial to synthesize the evidence regarding the infection risk associated with different modalities of oxygen therapy used in treating patients with severe acute respiratory infection. METHODS: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched from January 1, 2000, to April 1, 2020, for studies describing the risk of infection associated with the modalities of oxygen therapy used for patients with severe acute respiratory infection. The study selection, data extraction, and quality assessment were performed by independent reviewers. The primary outcome measure was the infection of health care workers with a severe acute respiratory infection. Random-effect models were used to synthesize the extracted data. RESULTS: Of 22,123 citations, 50 studies were eligible for qualitative synthesis and 16 for meta-analysis. Globally, the quality of the included studies provided a very low certainty of evidence. Being exposed or performing an intubation (odds ratio 6.48; 95% confidence interval 2.90 to 14.44), bag-valve-mask ventilation (odds ratio 2.70; 95% confidence interval 1.31 to 5.36), and noninvasive ventilation (odds ratio 3.96; 95% confidence interval 2.12 to 7.40) were associated with an increased risk of infection. All modalities of oxygen therapy generate air dispersion. CONCLUSION: Most modalities of oxygen therapy are associated with an increased risk of infection and none have been demonstrated as safe. The lowest flow of oxygen should be used to maintain an adequate oxygen saturation for patients with severe acute respiratory infection, and manipulation of oxygen delivery equipment should be minimized.

Potential Factors Influencing Repeated SARS Outbreaks in China.

Within last 17 years two widespread epidemics of severe acute respiratory syndrome (SARS) occurred in China, which were caused by related coronaviruses (CoVs): SARS-CoV and SARS-CoV-2. Although the origin(s) of these viruses are still unknown and their occurrences in nature are mysterious, some general patterns of their pathogenesis and epidemics are noticeable. Both viruses utilize the same receptor-angiotensin-converting enzyme 2 (ACE2)-for invading human bodies. Both epidemics occurred in cold dry winter seasons celebrated with major holidays, and started in regions where dietary consumption of wildlife is a fashion. Thus, if bats were the natural hosts of SARS-CoVs, cold temperature and low humidity in these times might provide conducive environmental conditions for prolonged viral survival in these regions concentrated with bats. The widespread existence of these bat-carried or -released viruses might have an easier time in breaking through human defenses when harsh winter makes human bodies more vulnerable. Once succeeding in making some initial human infections, spreading of the disease was made convenient with increased social gathering and holiday travel. These natural and social factors influenced the general progression and trajectory of the SARS epidemiology. However, some unique factors might also contribute to the origination of SARS in Wuhan. These factors are discussed in different scenarios in order to promote more research for achieving final validation.

SARS CoV-2 (COVID-19) Current Pharmacotherapy for Mother and Infant.

The novel coronavirus disease 2019 (COVID-19), appeared in the United States over 1 year ago. This virus has a wide range of presentations, from being asymptomatic to causing severe acute respiratory syndrome, which can lead to death. It has led to a worldwide effort to find effective treatments, from repurposed medications to new discoveries, as well as the push to develop effective vaccines. As the race to fight this pandemic unfolds, this column provides what is currently available to combat this virus, how it has been utilized in the pregnant population, and what data have been made available about how these treatments affect fetal development and the neonate.

Analyzing the vast coronavirus literature with CoronaCentral.

The SARS-CoV-2 pandemic has caused a surge in research exploring all aspects of the virus and its effects on human health. The overwhelming publication rate means that researchers are unable to keep abreast of the literature. To ameliorate this, we present the CoronaCentral resource that uses machine learning to process the research literature on SARS-CoV-2 together with SARS-CoV and MERS-CoV. We categorize the literature into useful topics and article types and enable analysis of the contents, pace, and emphasis of research during the crisis with integration of Altmetric data. These topics include therapeutics, disease forecasting, as well as growing areas such as "long COVID" and studies of inequality. This resource, available at https://coronacentral.ai, is updated daily.

Risk of Transmitting Coronavirus Disease 2019 During Nebulizer Treatment: A Systematic Review.

Rationale: There is an urgent need to understand the risk of viral transmission during nebulizer treatment of patients with coronavirus disease 2019 (COVID-19). Objectives: To assess the risk of transmitting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), SARS, Middle East respiratory syndrome (MERS), and influenza with administration of drugs via nebulizer. Methods: We searched multiple electronic databases, including PubMed®, China National Knowledge Infrastructure, Wanfang, preprint databases, and clinicaltrials.gov through December 1, 2020. Any study design in any language describing the risk of viral transmission with nebulizer treatment was eligible. Data were abstracted by one investigator and verified by a second. Results: We identified 22 articles: 1 systematic review, 7 cohort/case-control studies, 7 case series, and 7 simulation-based studies. Eight individual studies involved patients with SARS, five involved MERS, and one involved SARS-CoV-2. The seven cohort/case-control studies (four high risk of bias [ROB], three unclear ROB) found mixed results (median odds ratio 3.91, range 0.08-20.67) based on very weak data among a small number of health care workers (HCWs) with variable use of personal protective equipment (PPE). Case series had multiple potential contributors to transmission. Simulation studies found evidence for droplet dispersion after saline nebulization and measureable influenza viral particles up to 1.7 m from the source after 10 minutes of nebulization with a patient simulator. Study heterogeneity prevented meta-analysis. Conclusions: Case series raise concern of transmission risk, and simulation studies demonstrate droplet dispersion with virus recovery, but specific evidence that exposure to nebulizer treatment increases transmission of coronaviruses similar to COVID-19 is inconclusive. Tradeoffs balancing HCW safety and patient appropriateness can potentially minimize risk, including choice of delivery method for inhaled medications (e.g., nebulizer vs. metered dose inhaler) and PPE (e.g., N95 vs. surgical mask).

Heterogeneity in transmissibility and shedding SARS-CoV-2 via droplets and aerosols.

Background: Which virological factors mediate overdispersion in the transmissibility of emerging viruses remains a long-standing question in infectious disease epidemiology. Methods: Here, we use systematic review to develop a comprehensive dataset of respiratory viral loads (rVLs) of SARS-CoV-2, SARS-CoV-1 and influenza A(H1N1)pdm09. We then comparatively meta-analyze the data and model individual infectiousness by shedding viable virus via respiratory droplets and aerosols. Results: The analyses indicate heterogeneity in rVL as an intrinsic virological factor facilitating greater overdispersion for SARS-CoV-2 in the COVID-19 pandemic than A(H1N1)pdm09 in the 2009 influenza pandemic. For COVID-19, case heterogeneity remains broad throughout the infectious period, including for pediatric and asymptomatic infections. Hence, many COVID-19 cases inherently present minimal transmission risk, whereas highly infectious individuals shed tens to thousands of SARS-CoV-2 virions/min via droplets and aerosols while breathing, talking and singing. Coughing increases the contagiousness, especially in close contact, of symptomatic cases relative to asymptomatic ones. Infectiousness tends to be elevated between 1 and 5 days post-symptom onset. Conclusions: Intrinsic case variation in rVL facilitates overdispersion in the transmissibility of emerging respiratory viruses. Our findings present considerations for disease control in the COVID-19 pandemic as well as future outbreaks of novel viruses. Funding: Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant program, NSERC Senior Industrial Research Chair program and the Toronto COVID-19 Action Fund.

To understand how viruses spread scientists look at two things. One is ­ on average ­ how many other people each infected person spreads the virus to. The other is how much variability there is in the number of people each person with the virus infects. Some viruses like the 2009 influenza H1N1, a new strain of influenza that caused a pandemic beginning in 2009, spread pretty uniformly, with many people with the virus infecting around two other people. Other viruses like SARS-CoV-2, the one that causes COVID-19, are more variable. About 10 to 20% of people with COVID-19 cause 80% of subsequent infections ­ which may lead to so-called superspreading events ­ while 60-75% of people with COVID-19 infect no one else. Learning more about these differences can help public health officials create better ways to curb the spread of the virus. Chen et al. show that differences in the concentration of virus particles in the respiratory tract may help to explain why superspreaders play such a big role in transmitting SARS-CoV-2, but not the 2009 influenza H1N1 virus. Chen et al. reviewed and extracted data from studies that have collected how much virus is present in people infected with either SARS-CoV-2, a similar virus called SARS-CoV-1 that caused the SARS outbreak in 2003, or with 2009 influenza H1N1. Chen et al. found that as the variability in the concentration of the virus in the airways increased, so did the variability in the number of people each person with the virus infects. Chen et al. further used mathematical models to estimate how many virus particles individuals with each infection would expel via droplets or aerosols, based on the differences in virus concentrations from their analyses. The models showed that most people with COVID-19 infect no one because they expel little ­ if any ­ infectious SARS-CoV-2 when they talk, breathe, sing or cough. Highly infectious individuals on the other hand have high concentrations of the virus in their airways, particularly the first few days after developing symptoms, and can expel tens to thousands of infectious virus particles per minute. By contrast, a greater proportion of people with 2009 influenza H1N1 were potentially infectious but tended to expel relatively little infectious virus when the talk, sing, breathe or cough. These results help explain why superspreaders play such a key role in the ongoing pandemic. This information suggests that to stop this virus from spreading it is important to limit crowd sizes, shorten the duration of visits or gatherings, maintain social distancing, talk in low volumes around others, wear masks, and hold gatherings in well-ventilated settings. In addition, contact tracing can prioritize the contacts of people with high concentrations of virus in their airways.

Review of infective dose, routes of transmission and outcome of COVID-19 caused by the SARS-COV-2: comparison with other respiratory viruses.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is pandemic. Prevention and control strategies require an improved understanding of SARS-CoV-2 dynamics. We did a rapid review of the literature on SARS-CoV-2 viral dynamics with a focus on infective dose. We sought comparisons of SARS-CoV-2 with other respiratory viruses including SARS-CoV-1 and Middle East respiratory syndrome coronavirus. We examined laboratory animal and human studies. The literature on infective dose, transmission and routes of exposure was limited specially in humans, and varying endpoints were used for measurement of infection. Despite variability in animal studies, there was some evidence that increased dose at exposure correlated with higher viral load clinically, and severe symptoms. Higher viral load measures did not reflect coronavirus disease 2019 severity. Aerosol transmission seemed to raise the risk of more severe respiratory complications in animals. An accurate quantitative estimate of the infective dose of SARS-CoV-2 in humans is not currently feasible and needs further research. Our review suggests that it is small, perhaps about 100 particles. Further work is also required on the relationship between routes of transmission, infective dose, co-infection and outcomes.

SARS-CoV and SARS-CoV-2 are transmitted through the air between ferrets over more than one meter distance.

SARS-CoV-2 emerged in late 2019 and caused a pandemic, whereas the closely related SARS-CoV was contained rapidly in 2003. Here, an experimental set-up is used to study transmission of SARS-CoV and SARS-CoV-2 through the air between ferrets over more than a meter distance. Both viruses cause a robust productive respiratory tract infection resulting in transmission of SARS-CoV-2 to two of four indirect recipient ferrets and SARS-CoV to all four. A control pandemic A/H1N1 influenza virus also transmits efficiently. Serological assays confirm all virus transmission events. Although the experiments do not discriminate between transmission via small aerosols, large droplets and fomites, these results demonstrate that SARS-CoV and SARS-CoV-2 can remain infectious while traveling through the air. Efficient virus transmission between ferrets is in agreement with frequent SARS-CoV-2 outbreaks in mink farms. Although the evidence for virus transmission via the air between humans under natural conditions is absent or weak for SARS-CoV and SARS-CoV-2, ferrets may represent a sensitive model to study interventions aimed at preventing virus transmission.

Infection precautions for severe acute respiratory syndrome coronavirus 2 in assisted reproduction centers: dodging an invisible bullet.

The coronavirus disease 2019 pandemic has resulted in many changes in how we interact in society, requiring that we protect ourselves and others from an invisible, airborne enemy called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Until a vaccine is developed, and it reaches high levels of distribution, everyone must continue to be diligent to limit the viral spread. The practice of assisted reproduction during this pandemic presents unique challenges in addition to the risks identified in general clinical care. The established good tissue practices employed in laboratories are not designed to protect gametes and embryos from an airborne virus, particularly one that may be shed by an asymptomatic staff member. Armed with theoretical risks but lacking direct evidence, assisted-reproduction teams must examine every aspect of their practice, identify areas at a risk of exposure to SARS-CoV-2, and develop a mitigation plan. Several professional fertility societies have created guidelines for the best practices in patient care during the coronavirus disease 2019 pandemic. As we learn more about SARS-CoV-2, updates have been issued to help adapt infection-control and -prevention protocols. This review discusses what is currently known about SARS-CoV-2 infection risks in assisted reproductive centers and recommends the implementation of specific mitigation strategies.

Lethal zoonotic coronavirus infections of humans - comparative phylogenetics, epidemiology, transmission, and clinical features of coronavirus disease 2019, The Middle East respiratory syndrome and severe acute respiratory syndrome.

PURPOSE OF REVIEW: Severe acute respiratory syndrome-coronaviruses-2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged as a new zoonotic pathogen of humans at the end of 2019 and rapidly developed into a global pandemic. Over 106 million COVID-19 cases including 2.3 million deaths have been reported to the WHO as of February 9, 2021. This review examines the epidemiology, transmission, clinical features, and phylogenetics of three lethal zoonotic coronavirus infections of humans: SARS-CoV-1, SARS-CoV-2, and The Middle East respiratory syndrome coronavirus (MERS-COV). RECENT FINDINGS: Bats appear to be the common natural source of SARS-like CoV including SARS-CoV-1 but their role in SARS-CoV-2 and MERS-CoV remains unclear. Civet cats and dromedary camels are the intermediary animal sources for SARS-CoV-1 and MERS-CoV infection, respectively whereas that of SARS-CoV-2 remains unclear. SARS-CoV-2 viral loads peak early on days 2-4 of symptom onset and thus high transmission occurs in the community, and asymptomatic and presymptomatic transmission occurs commonly. Nosocomial outbreaks are hallmarks of SARS-CoV-1 and MERS-CoV infections whereas these are less common in COVID-19. Several COVID-19 vaccines are now available. SUMMARY: Of the three lethal zoonotic coronavirus infections of humans, SARS-CoV-2 has caused a devastating global pandemic with over a million deaths. The emergence of genetic variants, such as D614G, N501Y (variants 1 and 2), has led to an increase in transmissibility and raises concern about the possibility of re-infection and impaired vaccine response. Continued global surveillance is essential for both SARS-CoV-2 and MERS-CoV, to monitor changing epidemiology due to viral variants.

Zoonotic coronavirus epidemics: Severe acute respiratory syndrome, Middle East respiratory syndrome, and coronavirus disease 2019.

OBJECTIVE: To review the virology, immunology, epidemiology, clinical manifestations, and treatment of the following 3 major zoonotic coronavirus epidemics: severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and coronavirus disease 2019 (COVID-19). DATA SOURCES: Published literature obtained through PubMed database searches and reports from national and international public health agencies. STUDY SELECTIONS: Studies relevant to the basic science, epidemiology, clinical characteristics, and treatment of SARS, MERS, and COVID-19, with a focus on patients with asthma, allergy, and primary immunodeficiency. RESULTS: Although SARS and MERS each caused less than a thousand deaths, COVID-19 has caused a worldwide pandemic with nearly 1 million deaths. Diagnosing COVID-19 relies on nucleic acid amplification tests, and infection has broad clinical manifestations that can affect almost every organ system. Asthma and atopy do not seem to predispose patients to COVID-19 infection, but their effects on COVID-19 clinical outcomes remain mixed and inconclusive. It is recommended that effective therapies, including inhaled corticosteroids and biologic therapy, be continued to maintain disease control. There are no reports of COVID-19 among patients with primary innate and T-cell deficiencies. The presentation of COVID-19 among patients with primary antibody deficiencies is variable, with some experiencing mild clinical courses, whereas others experiencing a fatal disease. The landscape of treatment for COVID-19 is rapidly evolving, with both antivirals and immunomodulators demonstrating efficacy. CONCLUSION: Further data are needed to better understand the role of asthma, allergy, and primary immunodeficiency on COVID-19 infection and outcomes.

Topological Analysis for Sequence Variability: Case Study on more than 2K SARS-CoV-2 sequences of COVID-19 infected 54 countries in comparison with SARS-CoV-1 and MERS-CoV.

The pandemic due to novel coronavirus, SARS-CoV-2 is a serious global concern now. More than thousand new COVID-19 infections are getting reported daily for this virus across the globe. Thus, the medical research communities are trying to find the remedy to restrict the spreading of this virus, while the vaccine development work is still under research in parallel. In such critical situation, not only the medical research community, but also the scientists in different fields like microbiology, pharmacy, bioinformatics and data science are also sharing effort to accelerate the process of vaccine development, virus prediction, forecasting the transmissible probability and reproduction cases of virus for social awareness. With the similar context, in this article, we have studied sequence variability of the virus primarily focusing on three aspects: (a) sequence variability among SARS-CoV-1, MERS-CoV and SARS-CoV-2 in human host, which are in the same coronavirus family, (b) sequence variability of SARS-CoV-2 in human host for 54 different countries and (c) sequence variability between coronavirus family and country specific SARS-CoV-2 sequences in human host. For this purpose, as a case study, we have performed topological analysis of 2391 global genomic sequences of SARS-CoV-2 in association with SARS-CoV-1 and MERS-CoV using an integrated semi-alignment based computational technique. The results of the semi-alignment based technique are experimentally and statistically found similar to alignment based technique and computationally faster. Moreover, the outcome of this analysis can help to identify the nations with homogeneous SARS-CoV-2 sequences, so that same vaccine can be applied to their heterogeneous human population.