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1.
JMIR Public Health Surveill ; 8(11): e36424, 2022 Nov 08.
Article in English | MEDLINE | ID: covidwho-2109550

ABSTRACT

BACKGROUND: The distribution of population-level real-time reverse transcription-polymerase chain reaction (RT-PCR) cycle threshold (Ct) values as a proxy of viral load may be a useful indicator for predicting COVID-19 dynamics. OBJECTIVE: The aim of this study was to determine the relationship between the daily trend of average Ct values and COVID-19 dynamics, calculated as the daily number of hospitalized patients with COVID-19, daily number of new positive tests, daily number of COVID-19 deaths, and number of hospitalized patients with COVID-19 by age. We further sought to determine the lag between these data series. METHODS: The samples included in this study were collected from March 21, 2021, to December 1, 2021. Daily Ct values of all patients who were referred to the Molecular Diagnostic Laboratory of Iran University of Medical Sciences in Tehran, Iran, for RT-PCR tests were recorded. The daily number of positive tests and the number of hospitalized patients by age group were extracted from the COVID-19 patient information registration system in Tehran province, Iran. An autoregressive integrated moving average (ARIMA) model was constructed for the time series of variables. Cross-correlation analysis was then performed to determine the best lag and correlations between the average daily Ct value and other COVID-19 dynamics-related variables. Finally, the best-selected lag of Ct identified through cross-correlation was incorporated as a covariate into the autoregressive integrated moving average with exogenous variables (ARIMAX) model to calculate the coefficients. RESULTS: Daily average Ct values showed a significant negative correlation (23-day time delay) with the daily number of newly hospitalized patients (P=.02), 30-day time delay with the daily number of new positive tests (P=.02), and daily number of COVID-19 deaths (P=.02). The daily average Ct value with a 30-day delay could impact the daily number of positive tests for COVID-19 (ß=-16.87, P<.001) and the daily number of deaths from COVID-19 (ß=-1.52, P=.03). There was a significant association between Ct lag (23 days) and the number of COVID-19 hospitalizations (ß=-24.12, P=.005). Cross-correlation analysis showed significant time delays in the average Ct values and daily hospitalized patients between 18-59 years (23-day time delay, P=.02) and in patients over 60 years old (23-day time delay, P<.001). No statistically significant relation was detected in the number of daily hospitalized patients under 5 years old (9-day time delay, P=.27) and aged 5-17 years (13-day time delay, P=.39). CONCLUSIONS: It is important for surveillance of COVID-19 to find a good indicator that can predict epidemic surges in the community. Our results suggest that the average daily Ct value with a 30-day delay can predict increases in the number of positive confirmed COVID-19 cases, which may be a useful indicator for the health system.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Middle Aged , Child, Preschool , COVID-19/epidemiology , Longitudinal Studies , Iran/epidemiology , Hospitalization
2.
Int J Environ Res Public Health ; 19(22)2022 Nov 08.
Article in English | MEDLINE | ID: covidwho-2110064

ABSTRACT

This study aimed to evaluate the effect of hand hygiene interventions on the overall hand hygiene (HH) status of teaching instruction of hand hygiene in kindergartens, given the vulnerability of kindergarten children and their high risk due to infectious diseases and the current COVID-19 epidemic. We investigated the HH status of teachers from two kindergartens in the same community. The participants were recruited from 28 classes in both kindergartens. After completing the baseline survey, the intervention program consisted of three components: lectures on infectious diseases, lectures on HH, and seven-step hand washing techniques conducted in two kindergartens. The intervention program effectively increased teachers' perceived disease susceptibility (p < 0.05), reduced the total bacterial colonization of children's hands (p < 0.001), and improved the HH environment (p < 0.01). We recommend that health authorities or kindergartens adopt this HH intervention program to effectively improve the HH status in kindergartens and allow for preventive responses to the COVID-19 epidemic or other emerging infectious diseases.


Subject(s)
COVID-19 , Hand Hygiene , Child , Humans , COVID-19/epidemiology , COVID-19/prevention & control , Guideline Adherence , Hand Disinfection , Schools
3.
Viral Infections and Antiviral Therapies ; : 69-83, 2023.
Article in English | ScienceDirect | ID: covidwho-2104205

ABSTRACT

Infectious pathogens are a threat to global healthcare and the socioeconomic progress of the world. Since December 2019, the world has battled with the 2019-novel coronavirus disease (COVID-19), a zoonotic viral infection caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has resulted in high rates of infection and deaths across continents. Coronaviruses, due to their genetic nomenclature of being RNA viruses, easily undergo genetic mutation during their replication cycle. This has resulted in several SARS-CoV-2 variants of concern. The current state and what the future of COVID-19 holds for mankind is an unresolved question hanging on. Recently, there has been great improvement in the fight against the COVID-19 pandemic. Vaccines have been developed to reduce the risk of infection. Also, insights from the study of previous coronaviruses and previous pandemics have been helpful in the quick development of different effective vaccines and the deployment of various effective interventions. In this chapter, discussions on the genesis of COVID-19, its transmission, impact, preventive measures, and therapeutic advancements are presented.

4.
Droplets of Life ; : 681-698, 2023.
Article in English | ScienceDirect | ID: covidwho-2104198

ABSTRACT

Infectious diseases continue to represent a major threat to the humankind. This is reiterated by the current COVID-19 pandemic that affected almost 550 million people worldwide and caused more than 6.35 million deaths. It is clear that in addition to the existing preventive measures and treatments for various pathogens, better understanding is needed of the relationship between pathogen infection and the human antiinfection immune response and of the specific mechanisms underlying these complex processes. There is a constant warfare between the hosts and infectious pathogens, where humans have evolved a very effective and broadly amended antiinfection immune system, but, in their turn, pathogens have evolved a multitude of immune escape mechanisms to efficiently oppose it. It is recognized now that liquid–liquid phase separation (LLPS) occupies a special place among the important molecular mechanisms of the antiinfection immune response. Some illustrative examples of the roles of LLPS in the antiinfection immune response are considered in this chapter.

5.
Biosaf Health ; 2022 Nov 09.
Article in English | MEDLINE | ID: covidwho-2104460

ABSTRACT

Monkeypox is a zoonotic disease caused by the monkeypox virus (MPXV), which is a potential biological warfare agent of bioterrorism and poses the greatest threat to the world's public biosafety and health after variola virus (VARV). While the coronavirus disease 2019 (COVID-19) pandemic has not ended yet, monkeypox is spreading menacingly. The first case of monkeypox in a nonendemic country was confirmed on May 6th, 2022, while the first imported case from Asia was found on June 21st. There were more than 16 thousand reported cases as of July 23rd, the day the World Health Organization (WHO) declared the global monkeypox outbreak a public health emergency of international concern (PHEIC) at the same level as smallpox and COVID-19; while there were more than 53 thousand cases as of September 1st. Therefore, we will propose relevant biosafety prevention and control strategies after analyzing the etiology of the 2022 multi-country monkeypox outbreak from the biological feature, transmissibility, epidemic, and variability of MPXV.

6.
Front Med (Lausanne) ; 9: 937732, 2022.
Article in English | MEDLINE | ID: covidwho-2099171

ABSTRACT

Background: Public health and social measures (PHSM) against COVID-19 in Japan involve requesting the public to voluntarily reduce social contact; these measures are not legally binding. The effectiveness of such PHSM has been questioned with emergence of the SARS-CoV-2 Alpha variant (B.1.1.7), which exhibited elevated transmissibility. Materials and Methods: We investigated the epidemic dynamics during the fourth epidemic wave in Japan from March to June 2021 involving pre-emergency measures and declaration of a state of emergency (SoE). We estimated the effective reproduction number (R t ) before and after these interventions, and then analyzed the relationship between lower R t values and each PHSM. Results: With implementation of pre-emergency measures (PEM) in 16 prefectures, the R t was estimated to be < 1 in six prefectures; its average relative reduction ranged from 2 to 19%. During the SoE, 8 of 10 prefectures had an estimated R t < 1, and the average relative reduction was 26%-39%. No single intervention was identified that uniquely resulted in an R t value < 1. Conclusion: An SoE can substantially reduce the R t and may be required to curb a surge in cases caused by future SARS-CoV-2 variants of concern with elevated transmissibility. More customized interventions did not reduce the R t value to < 1 in this study, but that may be partly attributable to the greater transmissibility of the Alpha variant.

7.
J Multidiscip Healthc ; 15: 2481-2492, 2022.
Article in English | MEDLINE | ID: covidwho-2098948

ABSTRACT

Objective: To find out how well healthcare workers (HCWs) in Saudi Arabia's eastern region knew about the novel coronavirus illness 2019 (COVID-19) in terms of its symptoms, transmission, and treatment. Methods: This is a cross-sectional study conducted in the Saudi Arabian region of Al-Ahsa. Between December 2020 and March 2021, a questionnaire was distributed in the main hospitals in the eastern region: King Fahad Hospital, Prince Saud Bin Jalawi Hospital, Prince Sultan Cardiac Center, and Maternity and Children's Hospital. Participants' knowledge of COVID-19 symptoms, transmission, and treatment was assessed using our developed questionnaire tool. The Student's t-test/ANOVA test was used to compare the mean knowledge scores of different demographic groups. Results: A total of 300 HCWs participated in this study. Our study sample's mean knowledge score was 6.9 (SD = 2.1) out of 13 (53.1%), indicating a marginal degree of understanding. The duration of practice had a significant effect on the participants' knowledge of COVID-19. Senior and non-Saudi HCWs had a higher knowledge score than the rest of the groups (p ≤ 0.05). The majority of the participants were able to identify that COVID-19 is transmitted from human to human through respiratory droplets, populations at higher risk of developing severe complications, populations needing screening for COVID-19, main clinical symptoms of COVID-19, and were following the WHO guidelines for the treatment of COVID-19. Conclusion: According to our findings, HCWs only had marginal knowledge about the symptoms, transmission, and treatment of COVID-19. As our findings represent early investigation at the start of the pandemic, more research is needed to evaluate the degree of information gathered two years after the outbreak began. Furthermore, future research should identify knowledge gaps in the targeted population of HCWs and provide strategies to address them.

8.
Ir J Psychol Med ; 38(3): 192-207, 2021 09.
Article in English | MEDLINE | ID: covidwho-2096536

ABSTRACT

OBJECTIVES: In March 2020, the World Health Organization (WHO) officially declared the spread of coronavirus disease 2019 (COVID-19) as a pandemic. Adolescence and early adulthood are peak times for the onset of mental health difficulties. Exposure to a pandemic during this vulnerable developmental period places young people at significant risk of negative psychological experiences. The objective of this research was to summarise existing evidence on the potential impact of a pandemic on the mental health of 12-25 year olds. METHODS: A rapid review of the published peer-reviewed literature, published between 1985 and 2020, using PsycINFO (Proquest) and Medline (Proquest) was conducted. Narrative synthesis was used across studies to identify key themes and concepts. RESULTS: This review found 3,359 papers, which was reduced to 12 papers for data extraction. Results regarding the prevalence of psychological difficulties in youth were mixed, with some studies finding this group experience heightened distress during an infectious disease outbreak, and others finding no age differences or higher distress among adults. Gender, coping, self-reported physical health and adoption of precautionary measures appear to play a role in moderating the psychological impact of an infectious disease outbreak. Most studies were conducted after the peak of an epidemic/pandemic or in the recovery period. CONCLUSIONS: More longitudinal research with young people, particularly adolescents in the general population, before and during the early stages of an infectious disease outbreak is needed to obtain a clear understanding of how best to support young people during these events.


Subject(s)
COVID-19 , Pandemics , Adaptation, Psychological , Adolescent , Adult , Humans , Mental Health , SARS-CoV-2
9.
Health Secur ; 20(S1): S54-S59, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-2097248

ABSTRACT

Staff safety is paramount when managing an infectious disease event. However, early data from the COVID-19 pandemic suggested that staff compliance with personal protective equipment and other safety protocols was poor. In response to patient surges, many hospitals created dedicated "biomode" units to provide care for patients infected with SARS-CoV-2, the virus that causes COVID-19. To enhance staff safety on biomode units and during patient transports, our hospital created a safety officer/transport safety officer (SO/TSO) program. The first SOs/TSOs were nurses, clinical technicians, and other support staff who were redeployed from their home units when the units closed during the initial surge. During subsequent COVID-19 surges, dedicated SOs/TSOs were hired to maintain the program. SOs/TSOs provided just-in-time personal protective equipment training and helped staff safely enter and exit COVID-19 clinical units. SOs/TSOs participated in the transport of over 1,000 COVID-19 patients with no safety incidents reported. SOs/TSOs conducted safety audits throughout the hospital and observed 86% compliance with COVID-19 precautions across 32,500 activities. During contact tracing of frontline staff who became infected with SARS-CoV-2, potential deviations from COVID-19 precautions were identified in only 7.7% of cases. The SO/TSO program contributed to a culture of safety in the biomode units and helped to enhance infection prevention throughout the hospital. This program can serve as a model for other health systems during the response to the current pandemic and during future infectious disease threats.


Subject(s)
COVID-19 , COVID-19/prevention & control , Hospitals , Humans , Pandemics/prevention & control , Personal Protective Equipment , SARS-CoV-2
10.
Prev Med Rep ; 30: 102049, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2095896

ABSTRACT

Proactive management of SARS-CoV-2 requires timely and complete population data to track the evolution of the virus and identify at risk populations. However, many cases are asymptomatic and are not easily discovered through traditional testing efforts. Sentinel surveillance can be used to estimate the prevalence of infections for geographical areas but requires identification of sentinels who are representative of the larger population. Our goal is to evaluate applicability of a population of labor and delivery patients for sentinel surveillance system for monitoring the prevalence of SARS-CoV-2 infection. We tested 5307 labor and delivery patients from two hospitals in Phoenix, Arizona, finding 195 SARS-CoV-2 positive. Most positive cases were associated with people who were asymptomatic (79.44%), similar to statewide rates. Our results add to the growing body of evidence that SARS-CoV-2 disproportionately impacts people of color, with Black people having the highest positive rates (5.92%). People with private medical insurance had the lowest positive rates (2.53%), while Medicaid patients had a positive rate of 5.54% and people without insurance had the highest positive rates (6.12%). With diverse people reporting for care and being tested regardless of symptoms, labor and delivery patients may serve as ideal sentinels for asymptomatic detection of SARS-CoV-2 and monitoring impacts across a wide range of social and economic classes. A more robust system for infectious disease management requires the expanded participation of additional hospitals so that the sentinels are more representative of the population at large, reflecting geographic and neighborhood level patterns of infection and risk.

11.
J Psychosom Res ; 164: 111076, 2022 Nov 02.
Article in English | MEDLINE | ID: covidwho-2095696

ABSTRACT

OBJECTIVES: Few countries required people living in collective facilities to undergo quarantine during the COVID-19 pandemic, which could lead to more psychological effects than quarantine at home or hotels. This study assessed the changes in depression, anxiety, and quality of life (QOL) among residents of a collective quarantine facility in central Taiwan. METHODS: Between April and November 2020, 660 collective quarantine facility residents participated in the survey conducted on the first and last days of the 14-day quarantine period. Questionnaires of Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder (GAD-7), and WHO quality of life (WHOQOL)-BREF were used to measure depression and anxiety symptoms, and QOL, respectively. Linear regression model with generalization estimation equation method was for estimating the differences in depression, anxiety, and QOL between two surveys and to test the changes of associations between them over time. RESULTS: PHQ-9 and WHOQOL-BREF scores showed no significant changes, but GAD-7 score decreased during quarantine (p = 0.011, Cohen's d = -0.11). Both PHQ-9 and GAD-7 were negatively associated with overall and domain-specific WHOQOL-BREF scores on both the first and last days of quarantine. Such associations did not significantly vary with time, except for the association between PHQ-9 and environmental domain WHOQOL-BREF score, being stronger on the first day than on the last day of quarantine (p = 0.041, η2 = 0.0021). CONCLUSION: A significant decrease in anxiety among quarantined individuals over a 14-day quarantine period was found. While depression was negatively associated with overall QOL, the strength of association between depression and environmental domain QOL decreased over the period.

12.
J Pediatric Infect Dis Soc ; 2022 Nov 01.
Article in English | MEDLINE | ID: covidwho-2097391

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has driven a significant increase in the use of telehealth (TH) but little is published about changes in TH usage by pediatric infectious disease (PID) providers. We assessed their pre- and intra-pandemic TH usage and experience. METHODS: The Pediatric Infectious Diseases Society (PIDS) Telehealth Work Group surveyed PID specialists in the United States and Canada from 12/6/2020 until 2/26/2021. Data collected included TH modalities, barriers and satisfaction. RESULTS: The survey response rate was 11.3% (288 of 2,550 PID clinicians) with 243 (96% of 253 analysis-eligible responses) managing children only. Women accounted for 62.1% (n = 157), 51.4% (130) of respondents devoted 50-99% of their time to direct patient care, and 93.3% (236) were located in the US. The greatest increase in TH usage during the pandemic was in synchronous provider-patient communications (3.9-fold increase). During the pandemic, provider-provider TH increased by less than 10%, comfort with TH usage doubled from 42% to 91%, and satisfaction grew from 74% to 93.3% with different aspects of TH. The top challenge was incomplete or no physical examination (182, 71.9%). Multivariate analysis showed that pre-pandemic TH usage and lack of barriers, but not reimbursement, were significantly associated with higher intra-pandemic usage. EMR-integrated TH was associated with significantly higher usage and satisfaction. Over 70% of respondents anticipate continuing TH usage after the pandemic. CONCLUSIONS: There was high intra-pandemic usage of, and increased comfort and satisfaction with telehealth by PID specialists. Our data help inform post-pandemic TH expectations and strategies.

13.
Engineering (Beijing) ; 15: 126-132, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-2095307

ABSTRACT

By providing a means of separating the airborne emissions of patients from the air breathed by healthcare workers (HCWs), vented individual patient (VIP) hoods, a form of local exhaust ventilation (LEV), offer a new approach to reduce hospital-acquired infection (HAI). Results from recent studies have demonstrated that, for typical patient-emitted aerosols, VIP hoods provide protection at least equivalent to that of an N95 mask. Unlike a mask, hood performance can be easily monitored and HCWs can be alerted to failure by alarms. The appropriate use of these relatively simple devices could both reduce the reliance on personal protective equipment (PPE) for infection control and provide a low-cost and energy-efficient form of protection for hospitals and clinics. Although the development and deployment of VIP hoods has been accelerated by the coronavirus disease 2019 (COVID-19) pandemic, these devices are currently an immature technology. In this review, we describe the state of the art of VIP hoods and identify aspects in need of further development, both in terms of device design and the protocols associated with their use. The broader concept of individual patient hoods has the potential to be expanded beyond ventilation to the provision of clean conditions for individual patients and personalized control over other environmental factors such as temperature and humidity.

15.
Cureus ; 14(9): e29455, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-2090852

ABSTRACT

Listeria monocytogenes (LM) is a gram-positive intracellular pathogen that can cause central nervous system infections such as meningitis, meningoencephalitis, rhombencephalitis, or cerebritis. It rarely causes a brain abscess. Listerial meningitis and brain abscess most commonly occur in immunocompromised individuals, neonates, pregnant females, alcoholics, and the elderly. We present a unique case of a young immunocompetent male who presented with listerial meningitis and brain abscess. Coexisting coronavirus disease 2019 (COVID-19) infection was also present. Since LM was not included in the differentials, the standard antibiotic regimen started for the meningitis therapy was ineffective. Remdesivir was administered to treat the coexisting COVID-19 infection. When the lumbar tap polymerase chain reaction pointed out that the causative agent was Listeria, we shifted to ampicillin and gentamicin therapy, to which the patient responded very effectively.LM is an atypical cause of meningitis and brain abscesses. A high index of suspicion is therefore required for early detection and effective treatment of listerial meningitis and brain abscess.

16.
Elife ; 112022 Oct 21.
Article in English | MEDLINE | ID: covidwho-2090829

ABSTRACT

The role of schools in the spread of SARS-CoV-2 is controversial, with some claiming they are an important driver of the pandemic and others arguing that transmission in schools is negligible. School cluster reports that have been collected in various jurisdictions are a source of data about transmission in schools. These reports consist of the name of a school, a date, and the number of students known to be infected. We provide a simple model for the frequency and size of clusters in this data, based on random arrivals of index cases at schools who then infect their classmates with a highly variable rate, fitting the overdispersion evident in the data. We fit our model to reports from four Canadian provinces, providing estimates of mean and dispersion for cluster size, as well as the distribution of the instantaneous transmission parameter ß, whilst factoring in imperfect ascertainment. According to our model with parameters estimated from the data, in all four provinces (i) more than 65% of non-index cases occur in the 20% largest clusters, and (ii) reducing instantaneous transmission rate and the number of contacts a student has at any given time are effective in reducing the total number of cases, whereas strict bubbling (keeping contacts consistent over time) does not contribute much to reduce cluster sizes. We predict strict bubbling to be more valuable in scenarios with substantially higher transmission rates.


During the COVID-19 pandemic, public health officials promoted social distancing as a way to reduce SARS-CoV-2 transmission. The goal of social distancing is to reduce the number, proximity, and duration of face-to-face interactions between people. To achieve this, people shifted many activities online or canceled events outright. In education, some schools closed and shifted to online learning, while others continued classes in person with safety precautions. Better information about SARS-CoV-2 transmission in schools could help public health officials to make decisions of what activities to keep in person and when to suspend classes. If safety measures lower transmission in schools considerably, then closing schools may not be worth online education's social, educational, and economic costs. However, if transmission of SARS-CoV-2 in schools remains high despite measures, closing schools may be essential, despite the costs. Tupper et al. used data about COVID-19 cases in children attending in-person school in four Canadian provinces between 2020 and 2021 to fit a computer model of school transmission. On average, their analysis shows that one infected person in a school leads to between two and three further cases. Most of the time, no more students are infected, indicating that normally infection clusters are small; and only rarely does one infected person set off a large outbreak. The model also showed that measures to reduce transmission, like masking or small class sizes, were more effective than interventions such as keeping students with the same cohort all day (bubbling). Tupper et al. caution that their findings apply to the variants of SARS-CoV-2 circulating in Canada during the 2020-2021 school year, and may not apply to newer, highly transmissible strains like Omicron. However, the model could always be adapted to assess school or workplace transmission of more recent strains of SARS-CoV-2, and more generally of other diseases. Thus, Tupper et al. provide a new approach to estimating the rate of disease transmission and comparing the impact of different prevention strategies.

17.
Front Cardiovasc Med ; 9: 1001780, 2022.
Article in English | MEDLINE | ID: covidwho-2089824

ABSTRACT

Objective: To analyze the clinical characteristics and prognostic factors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant infections in children with congenital heart disease (CHD). Methods: A retrospective analysis was performed on SARS-CoV-2 Omicron-infected children with CHD who were admitted to Shanghai Children's Medical Center from April 1, 2022 to May 31, 2022. The clinical, laboratory and imaging data, and the nucleic acid conversion time of the children in this group were collected and analyzed. Results: Thirteen patients were included in this study and had an average age of 1.1 (0.16-14) years. Among the patients, 3 patients were preoperatively treated, and 10 were postoperatively treated. According to the severity of the disease, 1 patient was diagnosed with the moderate type, and the remaining 12 patients were diagnosed with the mild type. The clinical symptoms were mostly associated with upper respiratory tract infections, including 13 with fever (100%), 8 with cough (61.8%), 5 with sputum production (38.5%), 1 of shortness of breath (7.7%), etc. All patients were successfully discharged from the hospital, with 16.4 ± 2.9 days needed to obtain cycle threshold (CT) values ≥35 in nucleic acid testing and 17.5 ± 3.6 days of hospitalization. Conclusions: For vulnerable patients such as children with CHD, SARS-CoV-2 Omicron variant infections mostly present with mild upper respiratory tract symptoms with negative or mildly changed chest imaging. Through appropriate treatment of the underlying disease in the quarantine ward, patients might obtain good outcomes, even after long periods of hospitalization.

18.
J Clin Invest ; 2022 Oct 27.
Article in English | MEDLINE | ID: covidwho-2089016

ABSTRACT

The SARS-CoV-2 spike (S) glycoprotein is synthesized as large precursor protein and must be activated by proteolytic cleavage into S1 and S2. A recombinant modified vaccinia virus Ankara (MVA) expressing native, full-length S protein (MVA-SARS-2-S) is currently under investigation as candidate vaccine in phase I clinical studies. Initial results from immunogenicity monitoring revealed induction of S-specific antibodies binding to S2, but low-level antibody responses to the S1 domain. Follow-up investigations of native S antigen synthesis in MVA-SARS-2-S infected cells revealed limited levels of S1 protein on the cell surface. In contrast, we found superior S1 cell surface presentation upon infection with a recombinant MVA expressing a stabilized version of SARS-CoV-2 S protein with an inactivated S1/2 cleavage site and K986→P and V987→P mutations (MVA-SARS-2-ST). When comparing immunogenicity of MVA vector vaccines, mice vaccinated with MVA-SARS-2-ST mounted substantial levels of S broadly reactive antibodies that effectively neutralized different SARS-CoV-2 variants. Importantly, intramuscular MVA-SARS-2-ST immunization of hamsters and mice resulted in potent immune responses upon challenge infection and protected from disease and severe lung pathology. Our results suggest that MVA-SARS-2-ST represents an improved clinical candidate vaccine and that the presence of plasma membrane-bound S1 is highly beneficial to induce protective antibody levels.

19.
Disaster Med Public Health Prep ; : 1-2, 2021 Dec 09.
Article in English | MEDLINE | ID: covidwho-2087000
20.
Pathogenic Coronaviruses of Humans and Animals ; : 417-454, 2023.
Article in English | ScienceDirect | ID: covidwho-2082819

ABSTRACT

Coronaviruses are Baltimore Class I viruses of the family Coronaviridae. Similarities and differences to other members of these groups are discussed. Proposed reservoir/intermediate hosts of severe acute respiratory system coronavirus (SARS-CoV), Middle Eastern respiratory system coronavirus, and SARS-CoV-2 are presented. Bats appear to be reservoir hosts for these and some animal coronaviruses. Other potential reservoir/intermediate hosts of pathogenic coronaviruses are presented, with particular emphasis on rodents and birds. Potential methods to predict or prevent future pandemics include the One Health Approach and SpillOver. Factors driving epidemics and pandemics are discussed, particularly microbial, host-related, and environmental factors as well as ‘The Human Factor,’ medical and behavioral interventions that decrease disease spread and severity. The author’s vision for Infectious Disease Centers (IDCs), similar to Ebola Centers, is presented. IDCs would respond to a broad range of infectious diseases, utilizing separated, negative-pressure areas of existing hospitals with specialized, trained healthcare personnel, microbiologists, public health officials, and lab technicians on call. The proposed IDCs would have stockpiles of personal protective equipment (PPE), equipment, and laboratory facilities on hand to respond to a range of infections. Equipment could include ventilators, autoclaves, dialysis equipment, and three-dimensional printers. The latter was used to produce PPE and ventilators during the COVID-19 pandemic. Other innovative plans would be encouraged, such as the conversions of a deck of a long-distance Italian ferry for patients needing an intermediate level of care during the COVID-19 pandemic. Problems associated with infectious disease epidemics in developing countries are examined, with suggestions for the inclusion of appropriate personnel, such as local cultural experts and interpreters, as well as innovative planners and, perhaps, 3-D printers.

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