Can ship travel contain COVID-19 outbreak after re-opening: a Bayesian meta-analysis.

Large gatherings of people on cruise ships and warships are often at high risk of COVID-19 infections. To assess the transmissibility of SARS-CoV-2 on warships and cruise ships and to quantify the effectiveness of the containment measures, the transmission coefficient (ß), basic reproductive number (R0), and time to deploy containment measures were estimated by the Bayesian Susceptible-Exposed-Infected-Recovered model. A meta-analysis was conducted to predict vaccine protection with or without non-pharmaceutical interventions (NPIs). The analysis showed that implementing NPIs during voyages could reduce the transmission coefficients of SARS-CoV-2 by 50%. Two weeks into the voyage of a cruise that begins with 1 infected passenger out of a total of 3,711 passengers, we estimate there would be 45 (95% CI:25-71), 33 (95% CI:20-52), 18 (95% CI:11-26), 9 (95% CI:6-12), 4 (95% CI:3-5), and 2 (95% CI:2-2) final cases under 0%, 10%, 30%, 50%, 70%, and 90% vaccine protection, respectively, without NPIs. The timeliness of strict NPIs along with implementing strict quarantine and isolation measures is imperative to contain COVID-19 cases in cruise ships. The spread of COVID-19 on ships was predicted to be limited in scenarios corresponding to at least 70% protection from prior vaccination, across all passengers and crew.

A new approach to modeling pre-symptomatic incidence and transmission time of imported COVID-19 cases evolving with SARS-CoV-2 variants.

There is paucity of the statistical model that is specified for data on imported COVID-19 cases with the unique global information on infectious properties of SARS-CoV-2 variant different from local outbreak data used for estimating transmission and infectiousness parameters via the established epidemic models. To this end, a new approach with a four-state stochastic model was proposed to formulate these well-established infectious parameters with three new parameters, including the pre-symptomatic incidence rate, the median of pre-symptomatic transmission time (MPTT) to symptomatic state, and the incidence (proportion) of asymptomatic cases using imported COVID-19 data. We fitted the proposed stochastic model to empirical data on imported COVID-19 cases from D614G to Omicron with the corresponding calendar periods according to the classification GISAID information on the evolution of SARS-CoV-2 variant between March 2020 and Jan 2022 in Taiwan. The pre-symptomatic incidence rate was the highest for Omicron followed by Alpha, Delta, and D614G. The MPTT (in days) increased from 3.45 (first period) ~ 4.02 (second period) of D614G until 3.94-4.65 of VOC Alpha but dropped to 3.93-3.49 of Delta and 2 days (only first period) of Omicron. The proportion of asymptomatic cases increased from 29% of D-614G period to 59.2% of Omicron. Modeling data on imported cases across strains of SARS-CoV-2 not only bridges the link between the underlying natural infectious properties elucidated in the previous epidemic models and different disease phenotypes of COVID-19 but also provides precision quarantine and isolation policy for border control in the face of various emerging SRAS-CoV-2 variants globally.

Review of epidemic, containment strategies, clinical management, and economic evaluation of COVID-19 pandemic.

The spread of the emerging pathogen, named as SARS-CoV-2, has led to an unprecedented COVID-19 pandemic since 1918 influenza pandemic. This review first sheds light on the similarity on global transmission, surges of pandemics, and the disparity of prevention between two pandemics. Such a brief comparison also provides an insight into the potential sequelae of COVID-19 based on the inference drawn from the fact that a cascade of successive influenza pandemic occurred after 1918 and also the previous experience on the epidemic of SARS and MERS occurring in 2003 and 2015, respectively. We then propose a systematic framework for elucidating emerging infectious disease (EID) such as COVID-19 with a panorama viewpoint from natural infection and disease process, public health interventions (non-pharmaceutical interventions (NPIs) and vaccine), clinical treatments and therapies (antivirals), until global aspects of health and economic loss, and economic evaluation of interventions with emphasis on mass vaccination. This review not only concisely delves for evidence-based scientific literatures from the origin of outbreak, the spread of SARS-CoV-2 to three surges of pandemic, and NPIs and vaccine uptakes but also provides a new insight into how to apply big data analytics to identify unprecedented discoveries through COVID-19 pandemic scenario embracing from biomedical to economic viewpoints.

Continental transmission of emerging COVID-19 on the 38° north latitude.

BACKGROUND: As COVID-19 has become a pandemic emerging infectious disease it is important to examine whether there was a spatiotemporal clustering phenomenon in the globe during the rapid spread after the first outbreak reported from southern China. MATERIALS AND METHODS: The open data on the number of COVID-19 cases reported at daily basis form the globe were used to assess the evolution of outbreaks with international air link on the same latitude and also including Taiwan. The dynamic Susceptible-Infected-Recovered model was used to evaluate continental transmission from December 2019 to March 2020 before the declaration of COVID-19 pandemic with basic reproductive number and effective reproductive number before and after containment measurements. RESULTS: For the initial COVID-19 outbreak in China, the estimated reproductive number was reduced from 2.84 during the overwhelming outbreaks in early January to 0.43 after the strict lockdown policy. It is very surprising to find there were three countries (including South Korea, Iran, and Italy) and the Washington state of the USA on the 38° North Latitude involved with large-scale community-acquired outbreaks since the first imported COVID-19 cases from China. The propagation of continental transmission was augmented from hotspot to hotspot with higher reproductive number immediately before the declaration of pandemic. By contrast, there was not any large community-acquired outbreak in Taiwan. CONCLUSION: The propagated spatiotemporal transmission from China to other hotspots may explain the emerging pandemic that can only be exempted by timely border control and preparedness of containment measurements according to Taiwan experience.

Effectiveness of non-pharmaceutical interventions and vaccine for containing the spread of COVID-19: Three illustrations before and after vaccination periods.

BACKGROUND: There are few studies demonstrating how the effectiveness of various extents of non-pharmaceutical interventions (NPIs) before and after vaccination periods. The study aimed to demonstrate such an effectiveness in the alteration of the epidemic curves from theory to practice. METHODS: The empirical data on the daily reported COVID-19 cases were extracted from open source. A computer simulation design in conjunction with the susceptible-exposed-infected-recovered (SEIR) type model was applied to evaluating confinement measures in Italy with adjustment for underreported cases; isolation and quarantine in Taiwan; and NPIs and vaccination in Israel. RESULTS: In Italy scenario, the extents of confinement measures were 34% before the end of March and then scaled up to 70% after then. Both figures were reduced to 22-69% after adjusting for underreported cases. Approximately 44% of confinement measures were implemented in the second surge of pandemic in Italy. Fitting the observational data on Taiwan assuming the initial outbreak similar to Wuhan, China, 44% of isolation and quarantine were estimated before March 23rd, 2020. Isolation and quarantine were scaled up to 90% and at least 60% to contain community-acquired outbreaks from March 24th, 2020 onwards. Given 15% monthly vaccination rate from December 2020 in Israel, the effectiveness estimates of reducing the infected toll were 36%, 56%, and 85% for NPIs alone, vaccination alone, and both combined, respectively. CONCLUSION: We demonstrated how various NPIs stamp out and delay the epidemic curve of COVID-19. The optimal implementation of these NPIs has to be planned before wide vaccine uptake worldwide.

Efficacy and safety of umbilical cord mesenchymal stem cells for the treatment of patients with COVID-19.

OBJECTIVES: The coronavirus disease (COVID-19) outbreak has catastrophically threatened public health worldwide and presented great challenges for clinicians. To date, no specific drugs are available against severe acute respiratory syndrome coronavirus 2. Mesenchymal stem cells (MSCs) appear to be a promising cell therapy owing to their potent modulatory effects on reducing and healing inflammation-induced lung and other tissue injuries. The present pilot study aimed to explore the therapeutic potential and safety of MSCs isolated from healthy cord tissues in the treatment of patients with COVID-19. METHODS: Twelve patients with COVID-19 treated with MSCs plus conventional therapy and 13 treated with conventional therapy alone (control) were included. The efficacy of MSC infusion was evaluated by changes in oxygenation index, clinical chemistry and hematology tests, immunoglobulin (Ig) levels, and pulmonary computerized tomography (CT) imaging. The safety of MSC infusion was evaluated based on the occurrence of allergic reactions and serious adverse events. RESULTS: The MSC-treated group demonstrated significantly improved oxygenation index. The area of pulmonary inflammation decreased significantly, and the CT number in the inflammatory area tended to be restored. Decreased IgM levels were also observed after MSC therapy. Laboratory biomarker levels at baseline and after therapy showed no significant changes in either the MSC-treated or control group. CONCLUSION: Intravenous infusion of MSCs in patients with COVID-19 was effective and well tolerated. Further studies involving a large cohort or randomized controlled trials are warranted.

Evaluating Clinical Efficacy of Antiviral Therapy for COVID-19: A Surrogate Endpoint Approach.

INTRODUCTION: Efficient evaluation with an early surrogate endpoint, taking into account the process of disease evolution, may not only clarify inconsistent or underpowered results but also provide a new insight into the exploration of a new antiviral therapy for treating COVID-19 patients. METHODS: We assessed the dynamics of COVID-19 disease spectrum, commencing from low-risk (no or low oxygen supplement), medium-risk (non-invasive ventilator or high oxygen supplement), and high-risk (extracorporeal membrane oxygenation or invasive ventilator) risk state on enrollment, and then the subsequent progression and regression of risk states until discharge or death. The efficacy of antiviral therapy in altering the dynamics was assessed by using the high-risk state as a surrogate endpoint based on the data retrieved from the two-arm Adaptive Covid-19 Treatment Trial. RESULTS: Using the high-risk state as a surrogate endpoint, remdesivir treatment led to a decrease in the high-risk COVID-19 state by 34.8% (95% CI 26.7-42.0%) for a 14-day period and 29.3% (95% CI 28.8-29.8%) up to 28 days, which were consistent with a statistically significant reduction of death by 30.5% (95% CI 6.6, 50.9%) up to a 28-day period. The estimates of numbers needed to be treated were 100.9 (95% CI 88.1, 115.7) for using the high-risk COVID-19 state as a surrogate endpoint for a 14-day period and 133.3 (95% CI 112.5, 158.0) were required for averting one death from COVID-19 up to 28 days. CONCLUSIONS: We demonstrate the expedient use of the high-risk COVID-19 disease status as a surrogate endpoint for evaluating the primary outcome of the earliest death.

The Bayesian Susceptible-Exposed-Infected-Recovered model for the outbreak of COVID-19 on the Diamond Princess Cruise Ship.

The outbreak of COVID-19 on the Diamond Princess Cruise Ship provides an unprecedented opportunity to estimate its original transmissibility with basic reproductive number (R0) and the effectiveness of containment measures. We developed an ordinary differential equation-based Susceptible-Exposed-Infected-Recovery (SEIR) model with Bayesian underpinning to estimate the main parameter of R0 determined by transmission coefficients, incubation period, and the recovery rate. Bayesian Markov Chain Monte Carlo (MCMC) estimation method was used to tackle the parameters of uncertainty resulting from the outbreak of COVID-19 given a small cohort of the cruise ship. The extended stratified SEIR model was also proposed to elucidate the heterogeneity of transmission route by the level of deck with passengers and crews. With the application of the overall model, R0 was estimated as high as 5.70 (95% credible interval: 4.23-7.79). The entire epidemic period without containment measurements was approximately 47 days and reached the peak one month later after the index case. The partial containment measure reduced 63% (95% credible interval: 60-66%) infected passengers. With the deck-specific SEIR model, the heterogeneity of R0 estimates by each deck was noted. The estimated R0 figures were 5.18 for passengers (5-14 deck), mainly from the within-deck transmission, and 2.46 for crews (2-4 deck), mainly from the between-deck transmission. Modelling the dynamic of COVID-19 on the cruise ship not only provides an insight into timely evacuation and early isolation and quarantine but also elucidates the relative contributions of different transmission modes on the cruise ship though the deck-stratified SEIR model. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at (10.1007/s00477-020-01968-w).

Progression from Pneumonia to ARDS as a Predictor for Fatal COVID-19.

There is a serious concern over the variation of case fatality of COVID-19 patients that reflects the preparedness of the medical care system in response to the surge of pneumonia patients. We aimed to quantify the disease spectrum of COVID-19 on which we are based to develop a key indicator on the probability of progression from pneumonia to acute respiratory disease syndrome (ARDS) for fatal COVID-19. The retrospective cohort on 12 countries that have already experienced the epidemic of COVID-19 with available open data on the conformed cases with detailed information on mild respiratory disease (MRD), pneumonia, ARDS, and deaths were used. The pooled estimates from three countries with detailed information were 73% from MRD to pneumonia and 27% from MRD to recovery and the case-fatality rate of ARDS was 43%. The progression from pneumonia to ARDS varied from 3% to 63%. These key estimates were highly associated with the case fatality rates reported for each country with a statistically significant positive relationship (adjusted R2 = 95%). Such a quantitative model provides key messages for the optimal medical resources allocation to a spectrum of patients requiring quarantine and isolation at home, isolation wards, and intensive care unit in order to reduce deaths from COVID-19.

An Index for Lifting Social Distancing During the COVID-19 Pandemic: Algorithm Recommendation for Lifting Social Distancing.

BACKGROUND: Implementing and lifting social distancing (LSD) is an urgent global issue during the COVID-19 pandemic, particularly when the travel ban is lifted to revive international businesses and economies. However, when and whether LSD can be considered is subject to the spread of SARS-CoV-2, the recovery rate, and the case-fatality rate. It is imperative to provide real-time assessment of three factors to guide LSD. OBJECTIVE: A simple LSD index was developed for health decision makers to do real-time assessment of COVID-19 at the global, country, region, and community level. METHODS: Data on the retrospective cohort of 186 countries with three factors were retrieved from a publicly available repository from January to early July. A simple index for guiding LSD was measured by the cumulative number of COVID-19 cases and recoveries, and the case-fatality rate was envisaged. If the LSD index was less than 1, LSD can be considered. The dynamic changes of the COVID-19 pandemic were evaluated to assess whether and when health decision makers allowed for LSD and when to reimplement social distancing after resurgences of the epidemic. RESULTS: After large-scale outbreaks in a few countries before mid-March (prepandemic phase), the global weekly LSD index peaked at 4.27 in March and lasted until mid-June (pandemic phase), during which most countries were affected and needed to take various social distancing measures. Since, the value of LSD has gradually declined to 0.99 on July 5 (postpandemic phase), at which 64.7% (120/186) of countries and regions had an LSD<1 with the decile between 0 and 1 to refine risk stratification by countries. The LSD index decreased to 1 in about 115 days. In addition, we present the results of dynamic changes of the LSD index for the world and for each country and region with different time windows from January to July 5. The results of the LSD index on the resurgence of the COVID-19 epidemic in certain regions and validation by other emerging infectious diseases are presented. CONCLUSIONS: This simple LSD index provides a quantitative assessment of whether and when to ease or implement social distancing to provide advice for health decision makers and travelers.