Virological analysis of bronchoalveolar lavage fluid in patients with respiratory disease in Wuhan (preprint)

Purpose Identifying the cause of respiratory tract infections is important to reduce the burden of diagnosis and treatment. However, defining viral pneumonia based on viral detection in upper respiratory tract specimens gives ambiguous results. Thus, this study aimed to assess viral etiologies via bronchoalveolar lavage fluid (BALF) specimens from patients with different respiratory diseases.Methods BALF specimens (n = 335) from adult patients with respiratory disease were sampled between November 2020 and November 2021, and 22 respiratory viruses were detected using multiplex reverse-transcription polymerase chain reaction. Clinical data were collected from the hospital information system.Results At least one virus was identified in 118 (35.22%) cases. The most common viruses identified were influenza (33.13%), parainfluenza (3.28%), coronavirus (2.99%), rhinoviruses (2.09%), and respiratory syncytial (1.49%) viruses. No variations were observed in clinical symptoms between the viral and non-viral groups or among the different respiratory disease groups. The highest viral detection rate was observed in the tuberculosis group. Viral load was higher in co-infection than in single infection. In addition to influenza viruses, other viruses listed above are important in the etiology of lower respiratory tract infections in adults.Conclusion The findings suggest that rapid and accurate laboratory respiratory virus diagnosis is necessary for disease diagnosis and avoiding unnecessary antimicrobial drug use.

The changing pattern of common respiratory viruses among children from 2018-2021 in Wuhan, China (preprint)

Background Acute respiratory infections in children are a global public health challenge. Owing to the coronavirus disease (COVID-19) pandemic, non-pharmaceutical interventions, including patient isolation, social distancing, handwashing, and mask wearing, have been widely implemented, impacting the transmission of common respiratory viruses. We aimed to clarify the epidemiological features of respiratory viruses in children aged under 14 years in Wuhan before and after COVID-19.Methods Respiratory specimens were collected from patients aged < 14 years at two hospitals in Wuhan, China, from January 2018 to December 2021. Seven respiratory viruses were identified using immunofluorescence. Pathogen profiles and seasonality were analysed.Results The number of visits and virus detection rate decreased dramatically after February 2020. The respiratory virus detection rate peaked in January and December and decreased dramatically in February and August. The detection rate was lower in 2021 than in 2018 and 2019. Respiratory syncytial virus (RSV) was identified as the leading pathogen in children aged < 1 year and 1–4 years before and after the COVID-19 pandemic. In children aged 5–14 years, influenza virus was detected with the highest rate before, and RSV after, the COVID-19 pandemic. RSV was the most common coinfection virus.Conclusions This study revealed the epidemiological patterns of common respiratory viruses from 2018 to 2021. The spectrum of pathogens involved in paediatric respiratory infection partly changed. Non-pharmaceutical interventions offered fewer opportunities for spread of common viruses, also induced an “immunity debt” and could have negative consequences when the pandemic is under control in Wuhan.

The changing pattern of common respiratory viruses among children from 2018-2021 in Wuhan, China (preprint)

Background Acute respiratory infections in children are a global public health challenge. Owing to the coronavirus disease (COVID-19) pandemic, non-pharmaceutical interventions, including patient isolation, social distancing, handwashing, and mask wearing, have been widely implemented, impacting the transmission of common respiratory viruses. We aimed to clarify the epidemiological features of respiratory viruses in children aged under 14 years in Wuhan before and after COVID-19.Methods Respiratory specimens were collected from patients aged < 14 years at two hospitals in Wuhan, China, from January 2018 to December 2021. Seven respiratory viruses were identified using immunofluorescence. Pathogen profiles and seasonality were analysed.Results The number of visits and virus detection rate decreased dramatically after February 2020. The respiratory virus detection rate peaked in January and December and decreased dramatically in February and August. The detection rate was lower in 2021 than in 2018 and 2019. Respiratory syncytial virus (RSV) was identified as the leading pathogen in children aged < 1 year and 1–4 years before and after the COVID-19 pandemic. In children aged 5–14 years, influenza virus was detected with the highest rate before, and RSV after, the COVID-19 pandemic. RSV was the most common coinfection virus.Conclusions This study revealed the epidemiological patterns of common respiratory viruses from 2018 to 2021. The spectrum of pathogens involved in paediatric respiratory infection partly changed. Non-pharmaceutical interventions offered fewer opportunities for spread of common viruses, also induced an “immunity debt” and could have negative consequences when the pandemic is under control in Wuhan.

The impact of intervention to the incidence of natural focus diseases during the outbreak of COVID-19 in Jiangsu Province, China (preprint)

Doxorubicin (DOX) is a well-known chemotherapeutic drug for most malgnencies including breast cancer and leukemia whilst the usage of DOX is limited owing to its cardiotoxicity. The present study analyzed the effects of crocin on doxorubicin’s cardiotoxic efect in rat myocardium and searched their mechanistic interaction in the pathogenesis of DOX-induced myocardial toxicity. Forty rats were divided into four groups; (a) control (received normal saline as a dose of 1 ml/kg by ip for 15 days), (b) Crocin (received crocin as a dose of 40 mg/kg/24h by ip for 15 days), (c) DOX (received DOX as a dose of 2 mg/kg/48h by ip in six injection, cumulative dose 12 mg/kg), and (d) DOX+Crocin (received DOX as a dose of 2 mg/kg/48h by ip in six injection and crocin as a dose of 40 mg/kg/24h ip for 15 days). According to the present study, DOX administration caused significant increases in lipid indices (triglyseride, low-dencity lipoproteins and very low-dencity lipoproteins) as well as cardiac markers (Creatine kinase-muscle/brain and Cardiac Troponin I). Morever, DOX caused significant increases in oxidative stress parameters (malondialdehyde and total oxidant status) as well as decreases in antioxidant defense systems (glutathione, superoxide dismutase, catalase and total antioxidant status). The present study also demonstrated that co-administration of crocin with DOX significantly ameliorated the lipid profile and biochemical parameters in rats receiving DOX. The results were supported by histopathological and immunohistochemical evaluations. Taken together, our results reveal that crocin might be a cardioprotective agent in DOX treated patients for cancer.

Control Measures During the COVID-19 Outbreak Reduced the Transmission of Hand, Foot, and Mouth Disease (preprint)

Background: Control measures during the coronavirus disease 2019 (COVID-19) outbreak may have limited the spread of infectious diseases. This study aimed to analyse the impact of COVID-19 on the spread of hand, foot, and mouth disease (HFMD) in China. Methods: A mathematical model was established to fit the reported data of HFMD in six selected cities in mainland China from 2015 to 2020. The absolute difference (AD) and relative difference (RD) between the reported incidence in 2020, and simulated maximum, minimum, or median incidence of HFMD in 2015-2019 were calculated. Findings: The incidence and Reff of HFMD have decreased in six selected cities since the outbreak of COVID-19, and in the second half of 2020, the incidence and R eff of HFMD have rebounded. The results show that the total attack rate (TAR) in 2020 was lower than the maximum, minimum, and median TAR fitted in previous years in six selected cities (except Changsha city). For the maximum, median, minimum fitted TAR, the range of RD (%) is 42·20-99·20%, 36·35-98·41% 48·35-96·23% (except Changsha city) respectively. Interpretation: Based on the incidence data of six cities from 2015 to 2019, the SEIAR model demonstrated a significant effect on the incidence of HFMD. During the period of COVID-19, the incidence and R eff of HFMD decreased, the prevention and control measures taken during the period of COVID-19, such as school suspension, home quarantine, closing all kinds of leisure places, wearing masks, advocating frequent hand washing, etc., have not only effectively suppressed the spread of COVID-19 epidemic, but also have significantly contributed to the containment of HFMD transmission.Funding Statement: This study was partly supported by the Bill & Melinda Gates Foundation (INV-005834).Declaration of Interests: The authors declare no conflicts of interests.

The Impact of Intervention to Routine Surveillance of Natural Focal Diseases During the Outbreak of COVID-19 in Jiangsu Province, China (preprint)

Background: With the strength intervention of China, the outbreak of Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) had a great control effect. The measures may influence the development and progression of others infectious diseases.Method: The data of daily coronavirus virus disease 2019 (COVID-19) confirmed cases from January 3, 2020 to April 30, 2020 and natural focal disease cases from January, 2005 to April, 2020 were collected from Jiangsu Provincial Center for Disease Control and Prevention (Jiangsu Provincial CDC). We describe and compare the data of natural focal diseases from January to April, 2020 with the same months from 2015 to 2019 in the four aspects: trend of incidence, regional, age and sex distribution. Nonparametric tests were used to analyzed to the difference between the duration from onset of illness to date of diagnosis of natural focal diseases and the same period of the previous year. Results: The incidence of malaria in February (0.9 per 10,000,000 people), March (0.3 per 10,000,000 people) and April (0.1 per 10,000,000 people) 2020 less than the lower limit for range of February (1.6-4.5 per 10,000,000 people), March (0.8-3.3 per 10,000,000 people) and April (1.0-2.9 per 10,000,000 people) from 2015 to 2019 respectively. The incidence of brucellosis in February was 0.9 (per 10,000,000 people), less than the lower limit for the range from 2015 to 2019 (1.6-4.5 per 10,000,000 people). The incidence of hemorrhagic fever (HF) in March was 1.0 (per 10,000,000 people), less than the lower limit for the range from 2015 to 2019 (1.4-2.6 per 10,000,000 people). However, the incidence of Severe Fever with Thrombocytopenia Syndrome (SEFT) in March was 0.3 (per 10,000,000 people), higher than the upper limit for the range from 2015 to 2019 (0.0-0.1 per 10,000,000 people). Furthermore, we respectively observed the incidence with various degree of reduction in male, 20-60 years old and both rural and urban areas. Conclusions: In Jiangsu province, the incidence of natural focal diseases decreased during the outbreak of COVID-19 in 2020, especially malaria, HF and SEFT. The impact of interventions were felt most by male individuals within the age group of 20-50 years. The interventions for COVID-19 may control the epidemics of natural focal diseases.

Forecasting the Effectiveness of Interventions to Control the Second Wave of COVID-19 Outbreaks: A Modelling Study in 12 Countries of 6 Regions (preprint)

Background: In most countries, it is hard to effectively control coronavirus disease 2019 (COVID-19). This study conducted the most comprehensive evaluation of the effects of pharmacological (like vaccination, pharmacotherapy ) and non-pharmacological (like isolation, social distancing and mask-wearing) interventions taken singly or in combination for the first time globally.Methods: We estimate that across these 12 countries that are different but presentative, interventions prevented or delayed roughly millions of confirmed cases. This study constructs mathematical model, which interventions includes vaccination, pharmacotherapy, isolation, social distancing and mask-wearing , and analyses the effect of these interventions used alone and in combination.Findings: The basic reproduction number (R0) of each country mostly range from 3 to 5. In terms of the effect of single intervention, for countries such as China, South Korea, Thailand, US, South Africa and Algeria, it is preferred to recommend these countries to adopt isolation to prevent and control the second wave of COVID-19 outbreak, while for countries such as Russia, UK, Saudi Arabia, India and Brazil, wearing masks is the best choice. Especially pharmacotherapy can play a good role in Iran. When combinations with different interventions were taken, the situation was different. For US, Brazil and Algeria, the combination of “Vaccination & Isolation & Wearing mask” is recommended in these countries to prevent and control the development of COVID-19, and the combination of “Isolation & Social distancing & Wearing mask” is recommended in UK and China. For the rest, we suggest that Russia, Iran, Saudi Arabia, India, Thailand and South Africa take the intervention measures of “Vaccination & Medical treatment & Isolation & Wearing mask”, “Vaccination & Medical treatment”, “Vaccination & Social distancing & Wearing mask”, “Medical treatment & Social distancing & Wearing mask”, “Vaccination & Medical Treatment & Isolation”, “Vaccination & Medical Treatment & Wearing mask”, respectively to deal with the second wave of outbreaks that may come by the end of this year.Interpretation: Our model is operable and selective for the prevention and control of epidemic situations in various countries. These findings may help policy makers in the 180+ countries where COVID-19 has been reported around the world to identify the most effective and socioeconomically acceptable measures to prevent and control the second wave of COVID-19 epidemic, and inform if when these policies should be deployed, intensified or replaced.Funding: This study was partly supported by the Bill & Melinda Gates Foundation (INV-005834), the Science and Technology Program of Fujian Province (No: 2020Y0002), the Xiamen New Coronavirus Prevention and Control Emergency Tackling Special Topic Program (No: 3502Z2020YJ03), and the Open Research Fund of State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics (SKLVD2019KF005).Declaration of Interests: The authors declare no competing interests.

Effectiveness of Pharmacological Interventions to Control COVID-19: An Age-Specific Modelling Study (preprint)

Background: Novel coronavirus disease 2019 (COVID-19) causes an immense disease burden. Only drugs or vaccines can eliminate the virus. Methods: We adopted our age-specific transmission model by susceptible-exposed-infectious -critically ill-asymptomatic-removed (SEICAR) model. Effects of different drug types were simulated by changing transmission rate (β), critical case fatality rate (fc), and disease duration of each age group. Evaluation indexes were based on outbreak duration(OD), cumulative number of cases(CNC), total attack rate(TAR), peak date(PD), number of peak cases(NPC), and case fatality rate(f). Findings: When without intervention, changing in β and disease duration, as the age increased, OD decreased, TAR increased, PD advanced, CCN and NPC initially increased and then decreased, while f decreased first and then increased. When disease duration and β remained unchanged, changing fc did not affect the epidemic. All age groups had 40% shorter disease duration but unchanged fc, while β was reduced by 60%, which reduced TAR of group 1 (≤14 years) from 2·35% to 0·09%; f of group 4 (≥65 years) was reduced from 1·04% to 0·05%. Interpretation: Drugs had different age-dependent effects. If a drug can control the disease duration or β of all age groups, younger people would have the fastest transmission control and seniors will have the best improvement in disease severity. Funding: The Bill & Melinda Gates Foundation (INV-005834); the Science and Technology Program of Fujian Province (No: 2020Y0002), and the Xiamen New Coronavirus Prevention and Control Emergency Tackling Special Topic Program (No: 3502Z2020YJ03).Declaration of Interests: The authors declare no competing interests.

Children with COVID-19 behaving milder may challenge the public policies: A Systematic Review and Meta-Analysis (preprint)

Background: The emerging virus is rampaging globally. Great efforts are needed to cut down the transmission. Clinical characteristics of infected children have been described previously. No meta-analysis on this subgroup have been published.Methods: A single-arm meta-analysis was conducted. We searched PubMed, Google Scholar, Web of Science, three preprints websites and other Chinese database for studies presenting characteristics of children confirmed with Coronavirus Disease 2019 (COVID-19) from December 1 2019 to March 28 2020. Quality Appraisal of Case Series Studies Checklist was used to assess quality and publication bias was analyzed by Egger’s test. Random-effect model was used to calculate the pooled incidence rate (IR) or mean difference (MD) with 95% confidence intervals (CI), or a fixed model instead when I2<50%. We conducted subgroup analysis according to geographic region. Additionally, we searched United Nations Educational Scientific and Cultural Organization to see how different countries act to the education disruption in COVID-19.Results: 14 studies (two unpublished) with 361 pediatric patients were included. The mean age was 5.5 (95% CI: 0.344–0.765) years old. 23.4% of children were asymptomatic (95%CI: 0.112-0.377). 32.3% (95%CI: 0.163-0.503) showed normal computed tomography imaging, besides, four children were admitted in intensive care units (0, 95%CI: 0.000-0.001) and one death was reported (0, 95%CI: 0.000-0.001). Up to 191 countries have implemented nationwide school closures, affecting over 91% of the world’s students.Conclusion: Children were also susceptible to SARS-CoV-2, while critical cases or death were rare. Characterized by mild presentation, the dilemma that children may become a potential spreader in the pandemic, while strict managements like prolonged school closures, may undermine their well-beings. Thus, the public policies are facing challenge.