The Impact of Medical Resources and Oral Antiviral Drugs on SARS-CoV-2 Mortality - Hong Kong SAR, China, 2022.

Introduction: The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) demonstrates increased transmissibility compared to earlier strains, contributing to a significant number of fatalities in Hong Kong Special Administrative Region (HKSAR), China. Adequate medical resources and medications are essential in mitigating these deaths. This study evaluates the effects of supplementary resources from the Chinese mainland during the fifth wave of the pandemic in HKSAR. Methods: Vector autoregression (VAR) was employed to analyze data from the Oxford coronavirus disease 2019 (COVID-19) Government Response Tracker to assess the effectiveness of control measures during five waves of the pandemic in HKSAR. Additionally, a transmission dynamics model was created to investigate the influence of supplementary medical resources from the Chinese mainland and oral medications on mortality. Results: In the initial four waves, workplace closures, restrictions on public events, international travel bans, and shielding the elderly significantly influenced pandemic management. Contrarily, during the fifth wave, these measures showed no notable effects. When comparing a situation without extra medical resources or COVID-19 oral medication, there was a 17.7% decrease in COVID-19 fatalities with mainland medical resources and an additional 10.2% reduction with oral medications. Together, they contributed to a 26.6% decline in fatalities. Discussion: With the rapid spread of the virus, regional reallocation of medical resources may reduce mortality even when the local healthcare system is overstretched.

Adaptive Fourier Decomposition of the First Three SARS-CoV-2 Infection Waves with Epidemic Intervention - London, UK, 2020-2022.

Background: This study provides a detailed analysis of the daily fluctuations in coronavirus disease 2019 (COVID-19) case numbers in London from January 31, 2020 to February 24, 2022. The primary objective was to enhance understanding of the interactions among government pandemic responses, viral mutations, and the subsequent changes in COVID-19 case incidences. Methods: We employed the adaptive Fourier decomposition (AFD) method to analyze diurnal changes and further segmented the AFD into novel multi-component groups consisting of one to three elements. These restructured components were rigorously evaluated using Pearson correlation, and their effectiveness was compared with other signal analysis techniques. This study introduced a novel approach to differentiate individual components across various time-frequency scales using basis decomposition methods. Results: Analysis of London's daily COVID-19 data using AFD revealed a strong correlation between the "stay at home" directive and high-frequency components during the first epidemic wave. This indicates the need for sustained implementation of vaccination policies to maintain their effectiveness. Discussion: The AFD component method provides a comprehensive analysis of the immediate and prolonged impact of governmental policies on the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This robust tool has proven invaluable for analyzing COVID-19 pandemic data, offering critical insights that guide the formulation of future preventive and public health strategies.

Relationship of various COVID-19 antibody titer with individual characteristics and prediction of future epidemic trend in Xiamen City, China.

Background: Reinfection of coronavirus disease 2019 (COVID-19) has raised concerns about how reliable immunity from infection and vaccination is. With mass testing for the virus halted, understanding the current prevalence of COVID-19 is crucial. This study investigated 1,191 public health workers at the Xiamen Center for Disease Control, focusing on changes in antibody titers and their relationship with individual characteristics. Methods: The study began by describing the epidemiological characteristics of the study participants. Multilinear regression (MLR) models were employed to explore the associations between individual attributes and antibody titers. Additionally, group-based trajectory models (GBTMs) were utilized to identify trajectories in antibody titer changes. To predict and simulate future epidemic trends and examine the correlation of antibody decay with epidemics, a high-dimensional transmission dynamics model was constructed. Results: Analysis of epidemiological characteristics revealed significant differences in vaccination status between infected and non-infected groups (χ2=376.706, P<0.05). However, the distribution of antibody titers among the infected and vaccinated populations was not significantly different. The MLR model identified age as a common factor affecting titers of immunoglobulin G (IgG), immunoglobulin M (IgM), and neutralizing antibody (NAb), while other factors showed varying impacts. History of pulmonary disease and hospitalization influenced IgG titer, and factors such as gender, smoking, family history of pulmonary diseases, and hospitalization impacted NAb titers. Age was the sole determinant of IgM titers in this study. GBTM analysis indicated a "gradual decline type" trajectory for IgG (95.65%), while IgM and NAb titers remained stable over the study period. The high-dimensional transmission dynamics model predicted and simulated peak epidemic periods in Xiamen City, which correlated with IgG decay. Age-group-specific simulations revealed a higher incidence and infection rate among individuals aged 30-39 years during both the second and third peaks, followed by those aged 40-49, 50-59, 18-29, and 70-79 years. Conclusions: Our study shows that antibody titer could be influenced by age, previous pulmonary diseases as well as smoking. Furthermore, the decline in IgG titers is consistent with epidemic trends. These findings emphasize the need for further exploration of these factors and the development of optimized self-protection countermeasures against reinfection.

Structural basis of Acinetobacter type IV pili targeting by an RNA virus.

Acinetobacters pose a significant threat to human health, especially those with weakened immune systems. Type IV pili of acinetobacters play crucial roles in virulence and antibiotic resistance. Single-stranded RNA bacteriophages target the bacterial retractile pili, including type IV. Our study delves into the interaction between Acinetobacter phage AP205 and type IV pili. Using cryo-electron microscopy, we solve structures of the AP205 virion with an asymmetric dimer of maturation proteins, the native Acinetobacter type IV pili bearing a distinct post-translational pilin cleavage, and the pili-bound AP205 showing its maturation proteins adapted to pilin modifications, allowing each phage to bind to one or two pili. Leveraging these results, we develop a 20-kilodalton AP205-derived protein scaffold targeting type IV pili in situ, with potential for research and diagnostics.

Influenza and COVID-19 co-infection and vaccine effectiveness against severe cases: a mathematical modeling study.

Background: Influenza A virus have a distinctive ability to exacerbate SARS-CoV-2 infection proven by in vitro studies. Furthermore, clinical evidence suggests that co-infection with COVID-19 and influenza not only increases mortality but also prolongs the hospitalization of patients. COVID-19 is in a small-scale recurrent epidemic, increasing the likelihood of co-epidemic with seasonal influenza. The impact of co-infection with influenza virus and SARS-CoV-2 on the population remains unstudied. Method: Here, we developed an age-specific compartmental model to simulate the co-circulation of COVID-19 and influenza and estimate the number of co-infected patients under different scenarios of prevalent virus type and vaccine coverage. To decrease the risk of the population developing severity, we investigated the minimum coverage required for the COVID-19 vaccine in conjunction with the influenza vaccine, particularly during co-epidemic seasons. Result: Compared to the single epidemic, the transmission of the SARS-CoV-2 exhibits a lower trend and a delayed peak when co-epidemic with influenza. Number of co-infection cases is higher when SARS-CoV-2 co-epidemic with Influenza A virus than that with Influenza B virus. The number of co-infected cases increases as SARS-CoV-2 becomes more transmissible. As the proportion of individuals vaccinated with the COVID-19 vaccine and influenza vaccines increases, the peak number of co-infected severe illnesses and the number of severe illness cases decreases and the peak time is delayed, especially for those >60 years old. Conclusion: To minimize the number of severe illnesses arising from co-infection of influenza and COVID-19, in conjunction vaccinations in the population are important, especially priority for the elderly.

Text analysis of Macao's COVID-19 prevention and control policies: discussion on strategy evolution and public health capabilities.

Background: The global impact of the coronavirus disease 2019 (COVID-19) pandemic has been profound. Macao Special Administrative Region (SAR), renowned as an international hub for tourism and entertainment, has actively responded to the crisis. However, a comprehensive analysis detailing the evolution of Macao SAR's policies throughout this period is currently lacking. Methods: This study aims to comprehensively understand the decision-making processes, policy formulation, and implementation strategies of the Macao SAR government amidst the pandemic through the analysis of speeches and inquiries made by legislative council members and other relevant documents. Employing both quantitative and qualitative analytical methods, including word frequency analysis and word vector models, we identify key themes and patterns. Additionally, we conducted a comparative analysis of keyword frequencies during the two waves of the pandemic using radar charts. Results: The results indicate a heightened focus by the Macao SAR government on pandemic control measures and economic impacts. In response, the government formulated and implemented policies, provided support initiatives, and managed port clearance, all while focusing on enhancing healthcare infrastructure and community services. Conclusions: The government persistently amends its policies in response to the evolving challenges posed by the pandemic. The evolution of the dynamic Zero-COVID strategy highlights the government's adaptability and comprehensive consideration, ensuring public health and societal stability.

Real-time assessment of COVID-19 epidemic in Guangdong Province, China using mathematical models.

China government has relaxed the response measures of COVID-19 in early December 2022. In this report, we assessed the number of infections, the number of severe cases based on the current epidemic trend (October 22, 2022 to November 30, 2022) using a transmission dynamics model, called modified susceptible-exposed-infectious-removed (SEIR) to provide valuable information to ensure the medical operation of the healthcare system under the new situation. Our model showed that the present outbreak in Guangdong Province peaked during December 21, 2022 to December 25, 2022 with about 14.98 million new infections (95% CI: 14.23-15.73 million). The cumulative number of infections will reach about 70% of the province's population from December 24, 2022 to December 26, 2022. The number of existing severe cases is expected to peak during January 1, 2023 to January 5, 2023 with a peak number of approximately 101.45 thousand (95% CI: 96.38-106.52 thousand). In addition, the epidemic in Guangzhou which is the capital city of Guangdong Province is expected to have peaked around December 22, 2022 to December 23, 2022 with the number of new infections at the peak being about 2.45 million (95% CI: 2.33-2.57 million). The cumulative number of infected people will reach about 70% of the city's population from December 24, 2022 to December 25, 2022 and the number of existing severe cases is expected to peak around January 4, 2023 to January 6, 2023 with the number of existing severe cases at the peak being about 6.32 thousand (95% CI: 6.00-6.64 thousand). Predicted results enable the government to prepare medically and plan for potential risks in advance.

An ultra-sensitive one-pot RNA-templated DNA ligation rolling circle amplification-assisted CRISPR/Cas12a detector assay for rapid detection of SARS-CoV-2.

Rapid, sensitive, and one-pot diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays an extremely important role in point-of-care testing (POCT). Herein, we report an ultra-sensitive and rapid one-pot enzyme-catalyzed rolling circle amplification-assisted CRISPR/FnCas12a assay, termed OPERATOR. OPERATOR employs a single well-designed single-strand padlock DNA, containing a protospacer adjacent motif (PAM) site and a sequence complementary to the target RNA which procedure converts and amplifies genomic RNA to DNA by RNA-templated DNA ligation and multiply-primed rolling circle amplification (MRCA). The MRCA amplicon of single-stranded DNA is cleaved by the FnCas12a/crRNA complex and detected via a fluorescence reader or lateral flow strip. OPERATOR presents outstanding advantages including ultra-sensitivity (1.625 copies per reaction), high specificity (100%), rapid reaction speed (∼30 min), easy operation, low cost, and on-spot visualization. Furthermore, we established a POCT platform by combining OPERATOR with rapid RNA release and a lateral flow strip without professional equipment. The high performance of OPERATOR in SARS-CoV-2 tests was confirmed using both reference materials and clinical samples, and the results suggest that is readily adaptable for point-of-care testing of other RNA viruses.

Culturing Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) for Diagnosis and Genome Sequencing.

OBJECTIVE: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid detection "re-positive" phenomenon is encountered clinically. The accuracy of a viral nucleic acid test is crucial to prevent reintroduction of the virus into the community. This study evaluated the effect of virus culturing on increasing the sensitivity and specificity of real-time polymerase chain reaction (RT-PCR) detection and viral genomic sequencing. METHODS: A series of tenfold dilutions of a SARS-CoV-2 viral stock were conducted and cultured for either 24 or 48 hours. The viral load of cultured samples was determined by RT-PCR. The cultured and non-cultured samples of 1x 50% tissue culture infectious dose (TCID50) were sequenced using metagenomic next-generation sequencing. The depth and coverage of SARS-CoV-2 genome were measured. RESULTS: The lowest viral load detectable in a sample with RT-PCR was 0.01 TCID50. After a 24-h culture, the viral ORF 1ab and N-gene cycle threshold (CT) values were reduced by 4.4 points and 1 point, respectively. One TCID50 viral load of post 24-h culture revealed the sequence depth reached an average of 752 reads, compared with 0.15 in the nonculture; furthermore, the coverage was 99.99% while 6.42% in the nonculture. CONCLUSION: These results indicate that virus culturing can significantly increase the viral load, which can increase the certainty of true-positive detection of the viral nucleic acids, and improve the quality of virus genomic sequencing.

Containment of SARS-CoV-2 Delta strain in Guangzhou, China by quarantine and social distancing: a modelling study.

China detected the first case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with Delta variant in May 2021. We assessed control strategies against this variant of concern. We constructed a robust transmission model to assess the effectiveness of interventions against the Delta variant in Guangzhou with initial quarantine/isolation, followed by social distancing. We also assessed the effectiveness of alternative strategies and that against potentially more infectious variants. The effective reproduction number (Rt) fell below 1 when the average daily number of close contacts was reduced to ≤ 7 and quarantine/isolation was implemented on average at the same day of symptom onset in Guangzhou. Simulations showed that the outbreak could still be contained when quarantine is implemented on average 1 day after symptom onset while the average daily number of close contacts was reduced to ≤ 9 per person one week after the outbreak's beginning. Early quarantine and reduction of close contacts were found to be important for containment of the outbreaks. Early implementation of quarantine/isolation along with social distancing measures could effectively suppress spread of the Delta and more infectious variants.

The genetic characterization of hemagglutinin (HA), neuraminidase (NA) and polymerase acidic (PA) genes of H3N2 influenza viruses circulated in Guangdong Province of China during 2019-2020.

The evolution of seasonal influenza viruses, which can cause virus antigenic drift to escape human herd immunity, is a significant public health problem. Here, we obtained hemagglutinin (HA), neuraminidase (NA), and polymerase acidic protein (PA) the gene sequences of 84 influenza virus isolates collected in Guangdong Province during the 2019-2020 influenza season. Phylogenetic analyses revealed all these isolates were genetically similar to the viruses of clade 3C2a A1b, specifically those within subclades of A1b 137F (59 cases), A1b 186D (19 cases), and A1b 94 N (6 cases). The influenza virus isolates were distinct from the World Health Organization recommended influenza A vaccine virus for the 2019-2020 Northern Hemisphere season (A/Kansas/14/2017; H3N2). Phylogenies inferred from the individual gene segment sequences revealed that one reassortment event occurred among these clades. The genetic variation involved mutations within viral antigenic epitopes and two N-glycosylation site alterations. The novel mutation sites of G202D and D206N in the HA gene, E344K in the NA gene, and K626R in the PA gene which may affect the spread of the virus were observed. We investigated the evolution of these genes and found that the HA and NA genes were under greater pressure than PA gene. Mutations associated with conferring resistance to NA inhibitors or baloxavir acid were not found. Our results suggest that a rapid evolution of the H3N2 influenza virus occurred, thus continuous monitoring is critical for establishing appropriate vaccine formulations or drug delivery for targeting influenza.

Quantifying the Effect of Public Activity Intervention Policies on COVID-19 Pandemic Containment Using Epidemiologic Data From 145 Countries.

OBJECTIVES: Most countries have adopted public activity intervention policies to control the coronavirus disease 2019 (COVID-19) pandemic. Nevertheless, empirical evidence of the effectiveness of different interventions on the containment of the epidemic was inconsistent. METHODS: We retrieved time-series intervention policy data for 145 countries from the Oxford COVID-19 Government Response Tracker from December 31, 2019, to July 1, 2020, which included 8 containment and closure policies. We investigated the association of timeliness, stringency, and duration of intervention with cumulative infections per million population on July 1, 2020. We introduced a novel counterfactual estimator to estimate the effects of these interventions on COVID-19 time-varying reproduction number (Rt). RESULTS: There is some evidence that earlier implementation, longer durations, and more strictness of intervention policies at the early but not middle stage were associated with reduced infections of COVID-19. The counterfactual model proved to have controlled for unobserved time-varying confounders and established a valid causal relationship between policy intervention and Rt reduction. The average intervention effect revealed that all interventions significantly decrease Rt after their implementation. Rt decreased by 30% (22%-41%) in 25 to 32 days after policy intervention. Among the 8 interventions, school closing, workplace closing, and public events cancellation demonstrated the strongest and most consistent evidence of associations. CONCLUSIONS: Our study provides more reliable evidence of the quantitative effects of policy interventions on the COVID-19 epidemic and suggested that stricter public activity interventions should be implemented at the early stage of the epidemic for improved containment.

Crucial control measures to contain China's first Delta variant outbreak.

The SARS-CoV-2 B.1.617.2 (Delta) variant flared up in late May in Guangzhou, China. Transmission characteristics of Delta variant were analysed for 153 confirmed cases and two complete transmission chains with seven generations were fully presented. A rapid transmission occurred in five generations within 10 days. The basic reproduction number (R0) was 3.60 (95% confidence interval: 2.50-5.30). After redefining the concept of close contact, the proportion of confirmed cases discovered from close contacts increased from 43% to 100%. With the usage of a yellow health code, the potential exposed individuals were self-motivated to take a nucleic acid test and regained public access with a negative testing result. Facing the massive requirement of screening, novel facilities like makeshift inflatable laboratories were promptly set up as a vital supplement and 17 cases were found, with 1 pre-symptomatic. The dynamic adjustment of these three interventions resulted in the decline of Rt from 5.00 to 1.00 within 9 days. By breaking the transmission chain and eliminating the transmission source through extending the scope of the close-contact tracing, health-code usage and mass testing, the Guangzhou Delta epidemic was effectively contained.

How fast and how well the Omicron epidemic was curtailed. A Guangzhou experience to share.

Introduction: SARS-CoV-2 has ravaged the world and undergone multiple mutations during the course of the COVID-19 pandemic. On 7 April 2022, an epidemic caused by SARS-CoV-2 Omicron (BA.2) variant broke out in Guangzhou, China, one of the largest transportation and logistical hubs of the country. Methods: To fast curtained the Omicron epidemic, based on the routine surveillance on the risk population of SARS-CoV-2 infection, we identify key places of the epidemic and implement enhanced control measures against Omicron. Results: Transmission characteristics of the Omicron variant were analyzed for 273 confirmed cases, and key places involved in this epidemic were fully presented. The median incubation time and the generation time were 3 days, and the reproduction number Rt was sharply increased with a peak of 4.20 within 2 days. We tried an all-out effort to tackle the epidemic in key places, and the proportion of confirmed cases increased from 61.17% at Stage 2 to 88.89% at Stage 4. Through delimited risk area management, 99 cases were found, and the cases were isolated in advance for 2.61 ± 2.76 days in a lockdown zone, 0.44 ± 1.08 days in a controlled zone, and 0.27 ± 0.62 days in a precautionary zone. People assigned with yellow code accounted for 30.32% (84/277) of confirmed COVID-19 cases, and 83.33% of them were detected positive over 3 days since code assignment. For the districts outside the epicenter, the implementation duration of NPIs was much shorter compared with the Delta epidemic last year. Conclusion: By blocking out transmission risks and adjusting measures to local epidemic conditions through the all-out effort to tackle the epidemic in key places, by delimiting risk area management, and by conducting health code management of the at-risk population, the Omicron epidemic could be contained quickly.

Antigenic Drift of the Hemagglutinin from an Influenza A (H1N1) pdm09 Clinical Isolate Increases its Pathogenicity In Vitro.

The influenza A (H1N1) pdm09 virus emerged in 2009 and has been continuously circulating in humans for over ten years. Here, we analyzed a clinical influenza A (H1N1) pdm09-infected patient case hospitalized for two months in Guangdong (from December 14, 2019 to February 15, 2020). This isolate, named A/Guangdong/LCF/2019 (LCF/19), was genetically sequenced, rescued by reverse genetics, and phylogenetically analyzed in the context of other relevant pdm09 isolates. Compared with earlier isolates, this pdm09 virus's genetic sequence contains four substitutions, S186P, T188I, D190A, and Q192E, of the hemagglutinin (HA) segment at position 186-192 (H3 numbering) in the epitope Sb, and two of which are located at the 190-helix. Phylogenetic analysis indicated that the epitope Sb started undergoing a rapid antigenic change in 2018. To characterize the pathogenicity of this novel substitution motif, a panel of reassortant viruses containing the LCF/2019 HA segment or the chimeric HA segment with the four substitutions were rescued. Kinetic growth data revealed that the reassortant viruses, including the LCF/2019 with the PTIAAQE substitution, propagated faster than those rescued ones having the STTADQQ motif in the epitope Sb in Madin-Darby Canine Kidney (MDCK) cells. The HI test showed that the binding activity of escape mutant to 2018 pdm09 sera was weaker than GLW/2018, suggesting that old vaccines might not effectively protect people from infection. Due to the difference in the selection of vaccine strains, people vaccinated in the southern hemisphere could still suffer a severe infection if infected with this antigenic drift pdm09 virus.

Different Circulation Pattern of Multiple Respiratory Viruses in Southern China During the COVID-19 Pandemic.

China implemented stringent non-pharmaceutical interventions (NPIs) in spring 2020, which has effectively suppressed SARS-CoV-2. In this study, we utilized data from routine respiratory virus testing requests from physicians and examined circulation of 11 other respiratory viruses in Southern China, from January 1, 2018 to December 31, 2020. A total of 58,169 throat swabs from patients with acute respiratory tract infections (ARTIs) were collected and tested. We found that while the overall activity of respiratory viruses was lower during the period with stringent NPIs, virus activity rebounded shortly after the NPIs were relaxed and social activities resumed. Only influenza was effectively suppressed with very low circulation which extended to the end of 2020. Circulation of other respiratory viruses in the community was maintained even during the period of stringent interventions, especially for rhinovirus. Our study shows that NPIs against COVID-19 have different impacts on respiratory viruses.