Low dispersion in the infectiousness of COVID-19 cases implies difficulty in control.

The individual infectiousness of coronavirus disease 2019 (COVID-19), quantified by the number of secondary cases of a typical index case, is conventionally modelled by a negative-binomial (NB) distribution. Based on patient data of 9120 confirmed cases in China, we calculated the variation of the individual infectiousness, i.e., the dispersion parameter k of the NB distribution, at 0.70 (95% confidence interval: 0.59, 0.98). This suggests that the dispersion in the individual infectiousness is probably low, thus COVID-19 infection is relatively easy to sustain in the population and more challenging to control. Instead of focusing on the much fewer super spreading events, we also need to focus on almost every case to effectively reduce transmission.

Age-period-cohort analysis and projection of cancer mortality in Hong Kong, 1998-2030.

OBJECTIVES: To explore the relationship between immigration groups and cancer mortality, this study aimed to explore age, period, birth cohort effects and effects across genders and immigration groups on mortality rates of lung, pancreatic, colon, liver, prostate and stomach cancers and their projections. DESIGN, SETTING, AND PARTICIPANTS: Death registry data in Hong Kong between 1998 and 2021, which were stratified by age, sex and immigration status. Immigration status was classified into three groups: locals born in Hong Kong, long-stay immigrants and short-stay immigrants. METHODS: Age-period-cohort (APC) analysis was used to examine age, period, and birth cohort effects for genders and immigration groups from 1998 to 2021. Bayesian APC models were applied to predict the mortality rates from 2022 to 2030. RESULTS: Short-stay immigrants revealed pronounced fluctuations of mortality rates by age and of relative risks by cohort and period effects for six types of cancers than those of long-stay immigrants and locals. Immigrants for each type of cancer and gender will be at a higher mortality risk than locals. After 2021, decreasing trends (p<0.05) or plateau (p>0.05) of forecasting mortality rates of cancers occur for all immigration groups, except for increasing trends for short-stay male immigrants with colon cancer (p<0.05, Avg+0.30 deaths/100 000 per annum from 15.47 to 18.50 deaths/100 000) and long-stay male immigrants with pancreatic cancer (p<0.05, Avg+0.72 deaths/100 000 per annum from 16.30 to 23.49 deaths/100 000). CONCLUSIONS: Findings underscore the effect of gender and immigration status in Hong Kong on mortality risks of cancers that immigrants for each type of cancer and gender will be at a higher mortality risk than locals.

Modelling COVID-19 outbreak on the Diamond Princess ship using the public surveillance data.

The novel coronavirus disease 2019 (COVID-19) outbreak on the Diamond Princess (DP) ship has caused over 634 cases as of February 20, 2020. We model the transmission process on DP ship as a stochastic branching process, and estimate the reproduction number at the innitial phase of 2.9 (95%CrI: 1.7-7.7). The epidemic doubling time is 3.4 days, and thus timely actions on COVID-19 control were crucial. We estimate the COVID-19 transmissibility reduced 34% after the quarantine program on the DP ship which was implemented on February 5. According to the model simulation, relocating the population at risk may sustainably decrease the epidemic size, postpone the timing of epidemic peak, and thus relieve the tensive demands in the healthcare. The lesson learnt on the ship should be considered in other similar settings.

The shortage of hospital beds for COVID-19 and non-COVID-19 patients during the lockdown of Wuhan, China.

BACKGROUND: The 76-day lockdown of Wuhan city has successfully contained the first wave of the coronavirus disease 2019 (COVID-19) outbreak. However, to date few studies have evaluated the hospital bed shortage for COVID-19 during the lockdown and none for non-COVID-19 patients, although such data are important for better preparedness of the future outbreak. METHODS: We built a compartmental model to estimate the daily numbers of hospital bed shortage for patients with mild, severe and critical COVID-19, taking account of underreport and diagnosis delay. RESULTS: The maximal daily shortage of inpatient beds for mild, severe and critical COVID-19 patients was 43,960 (95% confidence interval: 35,246, 52,929), 2,779 (1,395, 4,163) and 196 (143, 250) beds in early February 2020. An earlier or later lockdown would have greatly increased the shortage of hospital beds in Wuhan. The overwhelmed healthcare system might have delayed the provision of health care to both COVID-19 and non-COVID-19 patients during the lockdown. The second wave in Wuhan could have occurred in June 2020 if social distancing measures had waned in early March 2020. The hospital bed shortage was estimated much smaller in the potential second wave than in the first one. CONCLUSIONS: Our findings suggest that the timing and strength of lockdown is important for the containment of the COVID-19 outbreaks. The healthcare needs of non-COVID-19 patients in the pandemic warrant more investigations.

Predicting Antituberculosis Drug-Induced Liver Injury Using an Interpretable Machine Learning Method: Model Development and Validation Study.

BACKGROUND: Tuberculosis (TB) is a pandemic, being one of the top 10 causes of death and the main cause of death from a single source of infection. Drug-induced liver injury (DILI) is the most common and serious side effect during the treatment of TB. OBJECTIVE: We aim to predict the status of liver injury in patients with TB at the clinical treatment stage. METHODS: We designed an interpretable prediction model based on the XGBoost algorithm and identified the most robust and meaningful predictors of the risk of TB-DILI on the basis of clinical data extracted from the Hospital Information System of Shenzhen Nanshan Center for Chronic Disease Control from 2014 to 2019. RESULTS: In total, 757 patients were included, and 287 (38%) had developed TB-DILI. Based on values of relative importance and area under the receiver operating characteristic curve, machine learning tools selected patients' most recent alanine transaminase levels, average rate of change of patients' last 2 measures of alanine transaminase levels, cumulative dose of pyrazinamide, and cumulative dose of ethambutol as the best predictors for assessing the risk of TB-DILI. In the validation data set, the model had a precision of 90%, recall of 74%, classification accuracy of 76%, and balanced error rate of 77% in predicting cases of TB-DILI. The area under the receiver operating characteristic curve score upon 10-fold cross-validation was 0.912 (95% CI 0.890-0.935). In addition, the model provided warnings of high risk for patients in advance of DILI onset for a median of 15 (IQR 7.3-27.5) days. CONCLUSIONS: Our model shows high accuracy and interpretability in predicting cases of TB-DILI, which can provide useful information to clinicians to adjust the medication regimen and avoid more serious liver injury in patients.

Correction: Predicting Antituberculosis Drug-Induced Liver Injury Using an Interpretable Machine Learning Method: Model Development and Validation Study.

[This corrects the article DOI: 10.2196/29226.].

Superspreading and heterogeneity in transmission of SARS, MERS, and COVID-19: A systematic review.

BACKGROUND: Severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and coronavirus disease 2019 (COVID-19) have caused substantial public health burdens and global health threats. Understanding the superspreading potentials of these viruses are important for characterizing transmission patterns and informing strategic decision-making in disease control. This systematic review aimed to summarize the existing evidence on superspreading features and to compare the heterogeneity in transmission within and among various betacoronavirus epidemics of SARS, MERS and COVID-19. METHODS: PubMed, MEDLINE, and Embase databases were extensively searched for original studies on the transmission heterogeneity of SARS, MERS, and COVID-19 published in English between January 1, 2003, and February 10, 2021. After screening the articles, we extracted data pertaining to the estimated dispersion parameter (k) which has been a commonly-used measurement for superspreading potential. FINDINGS: We included a total of 60 estimates of transmission heterogeneity from 26 studies on outbreaks in 22 regions. The majority (90%) of the k estimates were small, with values less than 1, indicating an over-dispersed transmission pattern. The point estimates of k for SARS and MERS ranged from 0.12 to 0.20 and from 0.06 to 2.94, respectively. Among 45 estimates of individual-level transmission heterogeneity for COVID-19 from 17 articles, 91% were derived from Asian regions. The point estimates of k for COVID-19 ranged between 0.1 and 5.0. CONCLUSIONS: We detected a substantial over-dispersed transmission pattern in all three coronaviruses, while the k estimates varied by differences in study design and public health capacity. Our findings suggested that even with a reduced R value, the epidemic still has a high resurgence potential due to transmission heterogeneity.

Obesity and COVID-19 in Adult Patients With Diabetes.

Obesity has caused wide concerns due to its high prevalence in patients with severe coronavirus disease 2019 (COVID-19). Coexistence of diabetes and obesity could cause an even higher risk of severe outcomes due to immunity dysfunction. We conducted a retrospective study in 1,637 adult patients who were admitted into an acute hospital in Wuhan, China. Propensity score-matched logistic regression was used to estimate the risks of severe pneumonia and requiring in-hospital oxygen therapy associated with obesity. After adjustment for age, sex, and comorbidities, obesity was significantly associated with higher odds of severe pneumonia (odds ratio [OR] 1.47 [95% CI 1.15-1.88]; P = 0.002) and oxygen therapy (OR 1.40 [95% CI 1.10-1.79]; P = 0.007). Higher ORs of severe pneumonia due to obesity were observed in men, older adults, and those with diabetes. Among patients with diabetes, overweight increased the odds of requiring in-hospital oxygen therapy by 0.68 times (P = 0.014) and obesity increased the odds by 1.06 times (P = 0.028). A linear dose-response curve between BMI and severe outcomes was observed in all patients, whereas a U-shaped curve was observed in those with diabetes. Our findings provide important evidence to support obesity as an independent risk factor for severe outcomes of COVID-19 infection in the early phase of the ongoing pandemic.

Unexpected positive correlation between human development index and risk of infections and deaths of COVID-19 in Italy.

In this analysis, we observed that human development index (an integrated index of life expectation, education and living standard) correlates with infection rate (proportion of confirmed cases among the population) and the fatality rate of COVID-19 in Italy based on data as of May 15, 2020. Further analysis showed that HDI is negatively correlated with cigarette consumption, whereas it is positively correlated with chronic disease and average annual gross salary. These factors may partially explain why unexpected positive correlation is observed between human development index and risk of infections and deaths of COVID-19 in Italy.

Four-tier response system and spatial propagation of COVID-19 in China by a network model.

In order to investigate the effectiveness of lockdown and social distancing restrictions, which have been widely carried out as policy choice to curb the ongoing COVID-19 pandemic around the world, we formulate and discuss a staged and weighted network system based on a classical SEAIR epidemiological model. Five stages have been taken into consideration according to four-tier response to Public Health Crisis, which comes from the National Contingency Plan in China. Staggered basic reproduction number has been derived and we evaluate the effectiveness of lockdown and social distancing policies under different scenarios among 19 cities/regions in mainland China. Further, we estimate the infection risk associated with the sequential release based on population mobility between cities and the intensity of some non-pharmaceutical interventions. Our results reveal that Level I public health emergency response is necessary for high-risk cities, which can flatten the COVID-19 curve effectively and quickly. Moreover, properly designed staggered-release policies are extremely significant for the prevention and control of COVID-19, furthermore, beneficial to economic activities and social stability and development.

Preliminary estimation of the novel coronavirus disease (COVID-19) cases in Iran: A modelling analysis based on overseas cases and air travel data.

As of March 1, 2020, Iran had reported 987 novel coronavirus disease (COVID-19) cases, including 54 associated deaths. At least six neighboring countries (Bahrain, Iraq, Kuwait, Oman, Afghanistan, and Pakistan) had reported imported COVID-19 cases from Iran. In this study, air travel data and the numbers of cases from Iran imported into other Middle Eastern countries were used to estimate the number of COVID-19 cases in Iran. It was estimated that the total number of cases in Iran was 16 533 (95% confidence interval: 5925-35 538) by February 25, 2020, before the UAE and other Gulf Cooperation Council countries suspended inbound and outbound flights from Iran.

The relative transmissibility of asymptomatic COVID-19 infections among close contacts.

Asymptomatic transmission of the coronavirus disease 2019 is an important topic. A recent study in China showed that transmissibility of the asymptomatic cases is comparable to that of symptomatic cases. Here, we discuss that the conclusion may depend on how we interpret the data. To the best of our knowledge, this is the first time the relative transmissibility of asymptomatic COVID-19 infections is quantified.

Preliminary estimates of the reproduction number of the coronavirus disease (COVID-19) outbreak in Republic of Korea and Italy by 5 March 2020.

The novel coronavirus disease 2019 (COVID-19) outbreak has caused 6088 cases and 41 deaths in Republic of Korea, and 3144 cases and 107 death in Italy by 5 March 2020, respectively. We modelled the transmission process in the Republic of Korea and Italy with a stochastic model, and estimated the basic reproduction number R0 as 2.6 (95% CI: 2.3-2.9) or 3.2 (95% CI: 2.9-3.5) in the Republic of Korea, under the assumption that the exponential growth starting on 31 January or 5 February 2020, and 2.6 (95% CI: 2.3-2.9) or 3.3 (95% CI: 3.0-3.6) in Italy, under the assumption that the exponential growth starting on 5 February or 10 February 2020, respectively.

Blood pressure control and adverse outcomes of COVID-19 infection in patients with concomitant hypertension in Wuhan, China.

Hypertension is a common comorbidity in hospitalized patients with COVID-19 infection. This study aimed to estimate the risks of adverse events associated with in-hospital blood pressure (BP) control and the effects of angiotensin II receptor blocker (ARB) prescription in COVID-19 patients with concomitant hypertension. In this retrospective cohort study, the anonymized medical records of COVID-19 patients were retrieved from an acute field hospital in Wuhan, China. Clinical data, drug prescriptions, and laboratory investigations were collected for individual patients with diagnosed hypertension on admission. Cox proportional hazards models were used to estimate the risks of adverse outcomes associated with BP control during the hospital stay. Of 803 hypertensive patients, 67 (8.3%) were admitted to the ICU, 30 (3.7%) had respiratory failure, 26 (3.2%) had heart failure, and 35 (4.8%) died. After adjustment for confounders, the significant predictors of heart failure were average systolic blood pressure (SBP) (hazard ratio (HR) per 10 mmHg 1.89, 95% confidence interval (CI): 1.15, 3.13) and pulse pressure (HR per 10 mmHg 2.71, 95% CI: 1.39, 5.29). The standard deviations of SBP and diastolic BP were independently associated with mortality and ICU admission. The risk estimates of poor BP control were comparable between patients receiving ARBs and those not receiving ARBs, with the only exception of a high risk of heart failure in the non-ARB group. Poor BP control was independently associated with higher risks of adverse outcomes of COVID-19. ARB drugs did not increase the risks of adverse events in hypertensive patients.

Quantifying the improvement in confirmation efficiency of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the early phase of the outbreak in Hong Kong in 2020.

BACKGROUNDS: The emerging virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), caused a large outbreak of coronavirus disease, COVID-19, in Wuhan, China, since December 2019. COVID-19 soon spread to other regions of China and overseas. In Hong Kong, local mitigation measures were implemented since the first imported case was confirmed on January 23, 2020. Here we evaluated the temporal variation of detection delay from symptoms onset to laboratory confirmation of SARS-CoV-2 in Hong Kong. METHODS: A regression model is adopted to quantify the association between the SARS-CoV-2 detection delay and calendar time. The association is tested and further validated by a Cox proportional hazard model. FINDINGS: The estimated median detection delay was 9.5 days (95%CI: 6.5-11.5) in the second half of January, reduced to 6.0 days (95%CI: 5.5-9.5) in the first half of February 2020. We estimate that SARS-CoV-2 detection efficiency improved at a daily rate of 5.40% (95%CI: 2.54-8.33) in Hong Kong. CONCLUSIONS: The detection efficiency of SARS-CoV-2 was likely being improved substantially in Hong Kong since the first imported case was detected. Sustaining enforcement in timely detection and other effective control measures are recommended to prevent the SARS-CoV-2 infection.

Early estimation of the case fatality rate of COVID-19 in mainland China: a data-driven analysis.

BACKGROUND: An ongoing outbreak of pneumonia caused by a novel coronavirus [severe acute respiratory syndrome coronavirus (SARS-CoV)-2], named COVID-19, hit a major city of China, Wuhan in December 2019 and subsequently spread to other provinces/regions of China and overseas. Several studies have been done to estimate the basic reproduction number in the early phase of this outbreak, yet there are no reliable estimates of case fatality rate (CFR) for COVID-19 to date. METHODS: In this study, we used a purely data-driven statistical method to estimate the CFR in the early phase of the COVID-19 outbreak. Daily numbers of laboratory-confirmed COVID-19 cases and deaths were collected from January 10 to February 3, 2020 and divided into three clusters: Wuhan city, other cities of Hubei province, and other provinces of mainland China. Simple linear regression model was applied to estimate the CFR from each cluster. RESULTS: We estimated that CFR during the first weeks of the epidemic ranges from 0.15% (95% CI: 0.12-0.18%) in mainland China excluding Hubei through 1.41% (95% CI: 1.38-1.45%) in Hubei province excluding the city of Wuhan to 5.25% (95% CI: 4.98-5.51%) in Wuhan. CONCLUSIONS: Our early estimates suggest that the CFR of COVID-19 is lower than the previous coronavirus epidemics caused by SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV).