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1.
Commun Dis Intell (2018) ; 442020 Sep 09.
Article in English | MEDLINE | ID: covidwho-750281

ABSTRACT

Cumulatively to 30 August there have been 25,686 case notifications and 577 deaths. The number of new cases reported nationally this fortnight was 1,751, a 61% decrease from the previous fortnight (4,501). On average this represented 125 cases diagnosed each day over the reporting period, a decrease from 322 cases per day over the previous reporting period. 94% (1,640) of all cases were reported in Victoria, with a smaller number of cases reported from New South Wales (86), Queensland (19), Western Australia (5) and South Australia (1). In Victoria, the majority of cases (1,528; 93%) were locally acquired, with a further 112 (7%) under investigation at the time of analysis, but likely also to be locally acquired. Of the remaining 111 cases reported, 22 (20%) were overseas acquired; 82 (74%) were locally acquired, predominantly in NSW, and 7 (6%) were reported as under investigation. The continued decrease in new cases observed this fortnight in Victoria is likely associated with the enhanced public health measures that are currently in place in Victoria. Locally acquired cases which were predominantly associated with several interconnected clusters continued to be reported in NSW. In Qld a cluster of cases associated with a youth detention centre was identified. A total of 26 deaths were reported from cases diagnosed in this reporting period, all from Victoria and aged 75 years or older. Testing rates remain high across all jurisdictions, with an overall positivity rate for the reporting period of 0.27%. Victoria reported a positivity rate of 0.90% for this reporting period; in all other jurisdictions the positivity rate was 0.03% or lower.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Australia/epidemiology , Betacoronavirus/genetics , Child , Child, Preschool , Cluster Analysis , Coronavirus Infections/mortality , Global Health , Humans , Infant , Middle Aged , Oceanic Ancestry Group , Pandemics , Pneumonia, Viral/mortality , Public Health Administration , Young Adult
2.
Commun Dis Intell (2018) ; 442020 Aug 26.
Article in English | MEDLINE | ID: covidwho-743198

ABSTRACT

Cumulatively to 16 August there have been 23,696 case notifications and 428 deaths. The number of new cases reported nationally this fortnight (3-16 August 2020) was 3,767, a 37% decrease from the previous fortnight (5,944). On average this represented 269 cases diagnosed each day over the reporting period, a decrease from 425 cases per day over the previous reporting period. 3,628 (96%) of all cases were reported in Victoria, with a smaller number of cases reported from NSW (125), Qld (2), WA (5), SA (6) and Tas (1). In Victoria, the majority of cases (3,284; 90%) were locally acquired, with a further 344 (10%) under investigation at the time of analysis, but likely also to be locally acquired. Of the remaining 139 cases reported, 26 (19%) were overseas acquired; 110 (80%) were locally acquired, predominantly in NSW, and 3 (2%) were reported as under investigation. The decrease in new cases observed this fortnight in Victoria is likely associated with the enhanced public health measures that are currently in place in Victoria. A total of 54 deaths were reported, all from Victoria: 52 (96%) were aged 70 years and over, and 2 (4%) were aged 30 to 69 years. Testing rates remain high across all jurisdictions, with an overall positivity rate for the reporting period of 0.6%. Victoria reported a positivity rate of 1.7% for this reporting period; in all other jurisdictions the positivity rate was 0.05% or lower.


Subject(s)
Betacoronavirus , Coronavirus Infections/epidemiology , Pneumonia, Viral/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Australia/epidemiology , Child , Child, Preschool , Cluster Analysis , Coronavirus Infections/mortality , Coronavirus Infections/pathology , Disease Notification , Female , Humans , Infant , Male , Middle Aged , Pandemics , Pneumonia, Viral/mortality , Pneumonia, Viral/pathology , Population Surveillance , Young Adult
3.
Rev Soc Bras Med Trop ; 53: e20200494, 2020.
Article in English | MEDLINE | ID: covidwho-740419

ABSTRACT

Diagnosing cases of coronavirus disease (COVID-19) with only non-respiratory symptoms has been challenging. We reported the diagnosis of a child who tested positive for COVID-19 with abdominal pain/diarrhea and tracked his family cluster. One member of the family tested positive for COVID-19 on real-time reverse-transcription polymerase chain reaction assay and three other family members had anti-SARS-CoV-2 antibodies.


Subject(s)
Coronavirus Infections/diagnosis , Coronavirus/isolation & purification , Diarrhea/diagnosis , Pandemics , Pneumonia, Viral/diagnosis , Abdominal Pain/etiology , Betacoronavirus , Child, Preschool , Clinical Laboratory Techniques , Cluster Analysis , Contact Tracing , Diarrhea/etiology , Fever/etiology , Humans , Male , Pharyngitis/etiology
4.
BMJ Open ; 10(9): e039886, 2020 Sep 01.
Article in English | MEDLINE | ID: covidwho-740288

ABSTRACT

OBJECTIVES: To illustrate the intersections of, and intercounty variation in, individual, household and community factors that influence the impact of COVID-19 on US counties and their ability to respond. DESIGN: We identified key individual, household and community characteristics influencing COVID-19 risks of infection and survival, guided by international experiences and consideration of epidemiological parameters of importance. Using publicly available data, we developed an open-access online tool that allows county-specific querying and mapping of risk factors. As an illustrative example, we assess the pairwise intersections of age (individual level), poverty (household level) and prevalence of group homes (community-level) in US counties. We also examine how these factors intersect with the proportion of the population that is people of colour (ie, not non-Hispanic white), a metric that reflects histories of US race relations. We defined 'high' risk counties as those above the 75th percentile. This threshold can be changed using the online tool. SETTING: US counties. PARTICIPANTS: Analyses are based on publicly available county-level data from the Area Health Resources Files, American Community Survey, Centers for Disease Control and Prevention Atlas file, National Center for Health Statistic and RWJF Community Health Rankings. RESULTS: Our findings demonstrate significant intercounty variation in the distribution of individual, household and community characteristics that affect risks of infection, severe disease or mortality from COVID-19. About 9% of counties, affecting 10 million residents, are in higher risk categories for both age and group quarters. About 14% of counties, affecting 31 million residents, have both high levels of poverty and a high proportion of people of colour. CONCLUSION: Federal and state governments will benefit from recognising high intrastate, intercounty variation in population risks and response capacity. Equitable responses to the pandemic require strategies to protect those in counties at highest risk of adverse COVID-19 outcomes and their social and economic impacts.


Subject(s)
Age Factors , Coronavirus Infections , Ethnic Groups/statistics & numerical data , Family Characteristics , Pandemics , Pneumonia, Viral , Poverty/statistics & numerical data , Public Health , Survival Analysis , Adult , Aged , Betacoronavirus , Cluster Analysis , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Cross-Sectional Studies , Female , Humans , Male , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Prevalence , Public Health/methods , Public Health/statistics & numerical data , Risk Assessment/methods , Risk Assessment/statistics & numerical data , Risk Factors , Severity of Illness Index , United States
5.
Zhonghua Yu Fang Yi Xue Za Zhi ; 54(7): 720-725, 2020 Jul 06.
Article in Chinese | MEDLINE | ID: covidwho-731282

ABSTRACT

Objective: Analysis of clustering characteristics of coronavirus disease 2019 (COVID-19) in Guangdong Province. Methods: The COVID-19 cases in Guangdong Province onset from January 1 to February 29, 2020 were collected from Chinese information system for disease control and prevention and Emergency Public Reporting System. Obtain the epidemiological survey data of the cluster epidemic situation, and clarify the scale of cluster epidemic situation, the characteristics of the index cases, family and non-family subsequent cases. Calculate serial interval according to the onset time of the index cases and subsequent cases, secondary attack rate based on the close contacts tracking results, the characteristics of different cases in the clustered epidemic were compared. Results: A total of 283 cluster were collected, including 633 index cases, 239 subsequent cases. Families are mainly clustered, the total number involved in each cluster is in the range of 2-27, M (P25, P75) are 2.0 (2.0, 4.0). During January 15 to February 29, the secondary attack rate is 2.86% (239/8 363) in Guangdong Province, the family secondary attack rate was 4.84% (276/3 697), and the non-family secondary attack rate was 1.32% (61/4 632). According to the reporting trend of the number of cases in Guangdong Province, it can be divided into four stages, the rising stage, the high platform stage, the descending stage and the low level fluctuation period. The secondary attack rate of the four stages were 3.5% (140/3 987), 2.3% (55/2 399), 2.6% (37/1 435), 1.3% (7/542), respectively. The difference was statistically significant (P=0.003). Conclusion: COVID-19 cluster mainly occurs in families in Guangdong Province. The scale of the clustered epidemic was small; the serial interval was short; and the overall secondary attack rate was low.


Subject(s)
Coronavirus Infections/epidemiology , Epidemics , Pneumonia, Viral/epidemiology , China/epidemiology , Cluster Analysis , Humans , Pandemics
6.
J Alzheimers Dis ; 77(1): 67-73, 2020.
Article in English | MEDLINE | ID: covidwho-721452

ABSTRACT

BACKGROUND: Facing the novel coronavirus disease 2019 (COVID-19), most vulnerable individuals are seniors, especially those with comorbidities. More attention needs to been paid to the COVID-19 patients with Alzheimer's disease (AD), which is the top age-related neurodegenerative disease. OBJECTIVE: Since it is unclear whether AD patients are prone to COVID-19 infection and progression to severe stages, we report for the first time a retrospective analysis of the clinical characteristics of AD patients with COVID-19 pneumonia. METHODS: We conducted a retrospective cohort study of the clinical data of 19 AD patients with COVID-19 pneumonia, compared with 23 non-AD COVID-19 patients admitted at the same time to our hospital. Demographic, clinical, laboratory, radiological, and treatment data were collected and analyzed. RESULTS: Between AD patients and non-AD patients with COVID-19 pneumonia, the pneumonia severity was not significantly different. AD patients had a higher clustering onset than non-AD patients. The median duration from symptom onset to hospitalization were shorter in AD patients than non-AD patients, indicating the former were sent to the hospital by their family or from nursing home earlier than the later. The median duration from hospitalization to discharge seemed shorter in AD patients than non-AD patients. Dementia patients seemed less likely to report fatigue. It is noticed that more AD patients might have pericardial effusion than the non-AD patients. CONCLUSION: AD patients with COVID-19 were in milder conditions with a better prognosis than non-AD patients. AD patients who had adequate access to healthcare showed resilience to COVID-19 with shorter hospital stays.


Subject(s)
Alzheimer Disease/complications , Alzheimer Disease/psychology , Coronavirus Infections/complications , Coronavirus Infections/psychology , Pneumonia, Viral/complications , Pneumonia, Viral/psychology , Resilience, Psychological , Aged , Aged, 80 and over , Cluster Analysis , Cohort Studies , Disease Progression , Fatigue/etiology , Fatigue/psychology , Female , Humans , Length of Stay , Male , Middle Aged , Pandemics , Patient Discharge/statistics & numerical data , Pleural Effusion/epidemiology , Pleural Effusion/etiology , Pneumonia/complications , Pneumonia/therapy , Prognosis
7.
Int J Environ Res Public Health ; 17(16)2020 08 14.
Article in English | MEDLINE | ID: covidwho-717739

ABSTRACT

The novel coronavirus (COVID-19) pandemic continues to be a significant public health threat worldwide, particularly in densely populated countries such as Bangladesh with inadequate health care facilities. While early detection and isolation were identified as important non-pharmaceutical intervention (NPI) measures for containing the disease spread, this may not have been pragmatically implementable in developing countries due to social and economic reasons (i.e., poor education, less public awareness, massive unemployment). Hence, to elucidate COVID-19 transmission dynamics with respect to the NPI status-e.g., social distancing-this study conducted spatio-temporal analysis using the prospective scanning statistic at district and sub-district levels in Bangladesh and its capital, Dhaka city, respectively. Dhaka megacity has remained the highest-risk "active" cluster since early April. Lately, the central and south eastern regions in Bangladesh have been exhibiting a high risk of COVID-19 transmission. The detected space-time progression of COVID-19 infection suggests that Bangladesh has experienced a community-level transmission at the early phase (i.e., March, 2020), primarily introduced by Bangladeshi citizens returning from coronavirus epicenters in Europe and the Middle East. Potential linkages exist between the violation of NPIs and the emergence of new higher-risk clusters over the post-incubation periods around Bangladesh. Novel insights into the COVID-19 transmission dynamics derived in this study on Bangladesh provide important policy guidelines for early preparations and pragmatic NPI measures to effectively deal with infectious diseases in resource-scarce countries worldwide.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections/epidemiology , Pneumonia, Viral/epidemiology , Bangladesh/epidemiology , Cluster Analysis , Coronavirus Infections/diagnosis , Coronavirus Infections/transmission , Coronavirus Infections/virology , Early Diagnosis , Humans , Pandemics , Patient Isolation , Pneumonia, Viral/diagnosis , Pneumonia, Viral/transmission , Pneumonia, Viral/virology , Prospective Studies , Public Health , Risk
8.
Infect Dis Poverty ; 9(1): 112, 2020 Aug 12.
Article in English | MEDLINE | ID: covidwho-708847

ABSTRACT

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) had spread worldwide. Although the world has intensively focused on the epidemic center during this period of time, it is imperative to emphasize that more attention should also be paid to some impoverished areas in China since they are more vulnerable to disease outbreak due to their weak health service capacities. Therefore, this study took Liangshan Yi Autonomous Prefecture as an example to analyze the COVID-19 epidemic in the impoverished area, evaluate the control effect and explore future control strategies. METHODS: In this study, we collected information including age, gender, nationality, occupation, and address of all COVID-19 cases reported from 25 January 2020 to 23 April 2020 in Liangshan Prefecture from the Nationwide Notifiable Infectious Diseases Reporting Information System (NIDRIS), which were used under license and not publicly available. Additionally, we retrieved other information of cases through epidemiological investigation reports reviewing. Data were analyzed using the software Excel 2010 and SPSS 17.0. The geographic distribution of cases was mapped using ArcGIS10.2. RESULTS: By 23 April 2020, a total of 13 COVID-19 cases and two asymptomatic SARS-CoV-2 carriers were reported in Liangshan, in three family clusters. Among the cases, eight cases had a history of sojourning in Hubei Province (61.54%), of which six were related to Wuhan. Cases aged under 44 years accounted for 61.54%, with no child case. The delay of patients' hospital visiting, and the low degree of cooperation in epidemiological investigation are problems. CONCLUSIONS: During the study period, Liangshan was well under control. This was mainly contributed to strict preventive strategies aimed at local culture, inter-sectoral coordination and highly degree of public cooperation. Besides, some possible environmentally and culturally preventive factors (e.g., rapid air flow and family concept) would affect disease prevention and control. In the next step, the health education about COVID-19 should be strengthened and carried out according to the special culture of ethnic minorities to enhance public awareness of timely medical treatment.


Subject(s)
Coronavirus Infections/epidemiology , Pneumonia, Viral/epidemiology , Poverty Areas , Adult , Age Distribution , Aged , Carrier State/epidemiology , Carrier State/transmission , Carrier State/virology , China/epidemiology , Cluster Analysis , Contact Tracing , Coronavirus Infections/prevention & control , Coronavirus Infections/transmission , Female , Humans , Male , Middle Aged , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Pneumonia, Viral/transmission , Quarantine , Spatial Analysis , Time Factors , Young Adult
9.
Am J Trop Med Hyg ; 103(3): 1207-1210, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-695539

ABSTRACT

The SARS-CoV-2 pandemic is now expanding into the developing world with devastating consequences. Departing from a population-based study in rural Ecuador where all adult individuals (aged 40 years or older) were tested for SARS-CoV-2 IgG and IgM antibodies, we expanded it to include a house-based case-control component assessing in-house clustering and other variables potentially associated with infection. We selected houses where exactly two study participants lived and were both seropositive (case-houses), and matched 1:1 to control-houses where both were seronegative. Younger household members had an antibody test performed. Infected household members were found in 33 (92%) case-houses and in only six (17%) control-houses. In 28/29 discordant house pairs, the case-house had seropositive household members and the control-house did not (odds ratio: 28; 95% CI: 4.6-1,144). Our data demonstrate strong in-house clustering of infection in community settings, stressing the importance of early case ascertainment and isolation for SARS-CoV-2 control.


Subject(s)
Betacoronavirus , Coronavirus Infections/epidemiology , Pneumonia, Viral/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Viral/blood , Case-Control Studies , Child , Cluster Analysis , Ecuador/epidemiology , Family Characteristics , Female , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Male , Middle Aged , Pandemics , Young Adult
10.
BMC Public Health ; 20(1): 1202, 2020 Aug 05.
Article in English | MEDLINE | ID: covidwho-696961

ABSTRACT

BACKGROUND: More than 2 months have passed since the novel coronavirus disease 2019 (COVID-19) first emerged in Wuhan, China. With the migration of people, the epidemic has rapidly spread within China and throughout the world. Due to the severity of the epidemic, undiscovered transmission of COVID-19 deserves further investigation. The aim of our study hypothesized possible modes of SARS-CoV-2 transmission and how the virus may have spread between two family clusters within a residential building in Guangzhou, China. METHODS: In a cross-sectional study, we monitored and traced confirmed patients and their close contacts from January 11 to February 5, 2020 in Guangzhou, China, including 2 family cluster cases and 61 residents within one residential building. The environmental samples of the building and the throat swabs from the patients and from their related individuals were collected for SARS-CoV-2 and tested with real-time reverse transcriptase polymerase chain reaction (RT-PCR). The relevant information was collected and reported using big data tools. RESULTS: There were two notable family cluster cases in Guangzhou, which included 3 confirmed patients (family No.1: patient A, B, C) and 2 confirmed patients (family No.2: patient D, E), respectively. None of patients had contact with other confirmed patients before the onset of symptoms, and only patient A and patient B made a short stop in Wuhan by train. Home environment inspection results showed that the door handle of family No.1 was positive of SARS-CoV-2. The close contacts of the 5 patients all tested negative of SARS-CoV-2 and in good health, and therefore were released after the official medical observation period of 14-days. Finally, according to the traceability investigation through applying big data analysis, we found an epidemiological association between family No.1 and family No.2, in which patient D (family No.2) was infected through touching an elevator button contaminated by snot with virus from patient A (family No.1) on the same day. CONCLUSIONS: Contaminants with virus from confirmed patients can pollute the environment of public places, and the virus can survive on the surface of objects for a short period of time. Therefore, in addition to the conventional droplet transmission, there is also indirect contact transmission such as snot-oral transmission that plays a crucial role in community spread of the virus.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Family , Pneumonia, Viral/epidemiology , Pneumonia, Viral/transmission , Adult , Aged , China/epidemiology , Cluster Analysis , Contact Tracing , Cross-Sectional Studies , Environmental Microbiology , Female , Humans , Male , Middle Aged , Pandemics , Real-Time Polymerase Chain Reaction , Residence Characteristics
11.
J Transl Med ; 18(1): 297, 2020 08 03.
Article in English | MEDLINE | ID: covidwho-692007

ABSTRACT

BACKGROUND: The severe acute respiratory syndrome virus SARS-CoV-2, a close relative of the SARS-CoV virus, is the cause of the recent COVID-19 pandemic affecting, to date, over 14 million individuals across the globe and demonstrating relatively high rates of infection and mortality. A third virus, the H5N1, responsible for avian influenza, has caused infection with some clinical similarities to those in COVID-19 infections. Cytokines, small proteins that modulate immune responses, have been directly implicated in some of the severe responses seen in COVID-19 patients, e.g. cytokine storms. Understanding the immune processes related to COVID-19, and other similar infections, could help identify diagnostic markers and therapeutic targets. METHODS: Here we examine data of cytokine, immune cell types, and disease associations captured from biomedical literature associated with COVID-19, Coronavirus in general, SARS, and H5N1 influenza, with the objective of identifying potentially useful relationships and areas for future research. RESULTS: Cytokine and cell-type associations captured from Medical Subject Heading (MeSH) terms linked to thousands of PubMed records, has identified differing patterns of associations between the four corpuses of publications (COVID-19, Coronavirus, SARS, or H5N1 influenza). Clustering of cytokine-disease co-occurrences in the context of Coronavirus has identified compelling clusters of co-morbidities and symptoms, some of which already known to be linked to COVID-19. Finally, network analysis identified sub-networks of cytokines and immune cell types associated with different manifestations, co-morbidities and symptoms of Coronavirus, SARS, and H5N1. CONCLUSION: Systematic review of research in medicine is essential to facilitate evidence-based choices about health interventions. In a fast moving pandemic the approach taken here will identify trends and enable rapid comparison to the literature of related diseases.


Subject(s)
Betacoronavirus , Coronavirus Infections/immunology , Lung Diseases/immunology , Pneumonia, Viral/immunology , Publications , Cluster Analysis , Comorbidity , Cytokine Release Syndrome/virology , Cytokines/immunology , Hematopoietic Stem Cells/cytology , Humans , Immune System , Influenza A Virus, H5N1 Subtype , Influenza, Human/immunology , Pandemics , PubMed , Severe Acute Respiratory Syndrome/immunology
12.
Transl Psychiatry ; 10(1): 263, 2020 07 31.
Article in English | MEDLINE | ID: covidwho-691246

ABSTRACT

The current study aimed to explore mental health problems in patients diagnosed with cancer during the COVID-19 pandemic. A cluster sampling, cross-sectional survey with 6213 cancer patients was conducted in one of the largest cancer centers in China. The socio-demographic and clinical characteristics, psychosomatic conditions, interpersonal relationships and social support, COVID-19 infection-related psychological stress, and mental health status were measured. Medical conditions were extracted from patients' electronic healthcare records. Among the 6213 cancer patients, 23.4% had depression, 17.7% had anxiety, 9.3% had PTSD, and 13.5% had hostility. Hierarchical liner regression models showed that having a history of mental disorder, excessive alcohol consumption, having a higher frequency of worrying about cancer management due to COVID-19, having a higher frequency feeling of overwhelming psychological pressure from COVID-19, and having a higher level of fatigue and pain were the predominant risk factors for mental health problems in cancer patients. However, there were only 1.6% of them were seeking psychological counseling during COVID-19. We also revealed the protective factors associated with lower risk of mental health problems among cancer patients. The present study revealed a high prevalence of mental health problems and gaps in mental health services for cancer patients, which also indicated high distress from COVID-19-elevated risks. We call for systematic screening of mental health status for all cancer patients, and developing specific psychological interventions for this vulnerable population.


Subject(s)
Betacoronavirus , Coronavirus Infections/psychology , Mental Disorders/epidemiology , Mental Disorders/psychology , Neoplasms/epidemiology , Neoplasms/psychology , Pneumonia, Viral/psychology , China/epidemiology , Cluster Analysis , Comorbidity , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Pandemics , Prevalence , Risk Factors , Social Support , Stress, Psychological/epidemiology , Stress, Psychological/psychology
13.
Trials ; 21(1): 689, 2020 Jul 31.
Article in English | MEDLINE | ID: covidwho-690891

ABSTRACT

OBJECTIVES: Hydroxychloroquine has shown to have antiviral activity in vitro against coronaviruses, specifically SARS-CoV-2. It is believed to block virus infection by increasing endosomal pH required for virus cell fusion and glycosylation of viral surface proteins. In addition to its antiviral activity, hydroxychloroquine has an immune-modulating activity that may synergistically enhance its antiviral effect in vivo, making it a potentially promising drug for the prevention and the cure of SARS-CoV-19. However, randomized controlled trials are needed to assess whether it can be used safely to treat COVID-19 patients or to prevent infection. The main objective of the present study is to evaluate the efficacy of hydroxychloroquine for (I) the prevention of COVID-19 or related symptoms in SARS-CoV-2-exposed subjects, such as as household members/contacts of COVID-19 patients and (II) the treatment of early-phase asymptomatic or paucisymptomatic COVID-19 patients. TRIAL DESIGN: This is a controlled, open label, cluster-randomized, superiority trial with parallel group design. Subjects will be randomized either to receive hydroxychloroquine or to observation (2:1). PARTICIPANTS: SARS-CoV-2-exposed subjects, including household members and/or contacts of COVID-19 patients and healthcare professionals (Group 1) or patients with COVID-19 (positive PCR test on a rhinopharyngeal or oropharyngeal swab for SARS-CoV-2), asymptomatic or paucisymptomatic in home situations who are not undergoing treatment with any anti COVID-19 medication (Group 2), will be enrolled. Paucisymptomatic patients are defined as patients with a low number of mild symptoms. All subjects must be aged ≥18 years, male or female, must be willing and able to give informed consent and must not have any contraindications to take hydroxychloroquine (intolerance or previous toxicity for hydroxychloroquine/chloroquine, bradycardia or reduction in heart rhythm with arrhythmia, ischemic heart disease, retinopathy, congestive heart failure with use of diuretics, favism or glucose-6-phosphate dehydrogenase (G6PD) deficiency, diabetes type 1, major comorbidities such as advanced chronic kidney disease or dialysis therapy, known history of ventricular arrhythmia, any oncologic/hematologic malignancy, severe neurological and mental illness, current use of medications with known significant drug-drug interactions, and known prolonged QT syndrome or current use of drugs with known QT prolongation). The study is monocentric and will be conducted at Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS. Subjects will be enrolled from a large epidemic region (North-Central Italy). The Public Health Departments of several Italian regions will collaborate by identifying potentially eligible subjects. INTERVENTION AND COMPARATOR: The participants will be randomized (2:1 randomization) to receive either hydroxychloroquine (Arm A) or to Observation (Arm B). Hydroxychloroquine will be administered with the following schedule: Group1: A loading dose hydroxychloroquine 400 mg twice daily on day 1, followed by a weekly dose of hydroxychloroquine 200 mg twice daily on days 8, 15 and 22, for a total of one month of treatment. Group 2: A loading dose hydroxychloroquine 400 mg twice daily on day 1 followed by 200 mg twice daily for a total of 5-7 days. The comparator in this trial is observation given that currently neither treatment is administered to asymptomatic or paucisymptomatic subjects, nor prophylaxis is available for contacts. Hydroxychloroquine will be shipped to subjects within 24 hours of randomization. Given the extraordinary nature of the COVID-19 pandemic, only telephonic interviews will be carried out and electronic Patient Reported Outcomes (ePRO) completed. During treatment, each subject will be contacted every other day for the first week and weekly thereafter (Group 2) or weekly (Group 1) by a study physician to assess early onset of any COVID-19 symptom or any adverse reaction to hydroxychloroquine and to check subject compliance. Furthermore, all subjects will receive periodic ePROs which may be completed through smartphone or tablets to record drug self-administration and onset of any symptom or adverse event. All subjects will be followed up for a total of 6 months by periodic telephonic interviews and ePROs. MAIN OUTCOMES: The primary endpoint/outcome measure for this trial is: for Group 1, the proportion of subjects who become symptomatic and/or swab-positive in each arm within one month of randomization; for Group 2, the proportion of subjects who become swab-negative in each arm within 14 days of randomization. RANDOMIZATION: All household members and/or contacts of each COVID-19 index case, and the COVID-19 patient himself/herself, fulfilling all inclusion criteria will be grouped into a single cluster and this cluster will be randomized (2:1) to either arm A or arm B. Information on each subject will be recorded in specific data records. Randomization lists will be stratified according to the following factors regarding COVID-19 index cases: 1. COVID-19 risk level on the basis of province of residence (high vs. low/intermediate); 2. Index case is a healthcare professional (yes vs.no) 3. Index case with COVID-19 treatment (yes vs. no) An independent statistician not otherwise involved in the trial will generate the allocation sequence, and COVID-19 response teams will be unaware of the allocation of clusters. Randomization will be performed through an interactive web-based electronic data-capturing database. An Independent Data Monitoring Committee has been established. BLINDING (MASKING): This study is open label. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): For Group 1, a sample size of about 2000 SARS-CoV-2-exposed subjects such as household members and/or contacts of COVID-19 patients will take part in the study. Assuming around 1.5-2.0 asymptomatic household members and/or contacts for each COVID-19 patient, we expect to identify approximately 1000-1300 COVID-19 index cases to be randomized. An interim analysis on efficacy is planned using standard alpha-spending function. For Group 2, sufficient power for primary objective (negative swab within 14 days of randomization) will be reached given a sample size of 300 asymptomatic or paucisymptomatic COVID-19 subjects in home situations not treated for COVID-19 (25%-30% of about 1000-1300 expected index cases). Since up to date reduced evidence about COVID-19 infection epidemiology, the continuous update of diagnostic and therapeutic approaches, the sample size estimation could be updated after a one third of population will be recruited and eventually modified according to a substantial protocol amendment. An interim analysis at 100 enrolled COVID-19 patients is planned. We have planned a Generalized Estimating Equation analysis, which is more efficient than a cluster level analysis, to take advantage of subject-specific covariates. The above reported sample size analysis is therefore to be considered conservative. TRIAL STATUS: The current version of the PROTECT trial protocol is 'Final version, 15 April 2020'. The study started on 9th May 2020. The first patient was enrolled on 14th May 2020. Recruitment is expected to last through September 2020. TRIAL REGISTRATION: The PROTECT trial is registered in the EudraCT database (no. 2020-001501-24) and in ClinicalTrials.gov ( NCT04363827 ), date of registration 24 April 2020. FULL PROTOCOL: The full PROTECT protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interests of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol (Protocol final version, 15th April 2020). The study protocol has been reported in accordance with Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).


Subject(s)
Betacoronavirus , Coronavirus Infections/prevention & control , Hydroxychloroquine/therapeutic use , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Randomized Controlled Trials as Topic , Cluster Analysis , Female , Humans , Male , Patient Reported Outcome Measures , Telemedicine
14.
Geriatr Gerontol Int ; 20(7): 715-719, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-682347

ABSTRACT

AIM: To clarify the association of cluster number and size of coronavirus disease 2019 (COVID-19) in long-term care (LTC) hospitals/facilities, general medical/welfare facilities and non-medical/welfare facilities with morbidity and mortality in 47 prefectures during 16 January to 9 May 2020 in Japan. METHODS: Information on COVID-19 clusters (n ≥2), and morbidity and mortality of COVID-19 was collected. RESULTS: A total of 381 clusters with 3786 infected cases were collected, accounting for 23.9% of 15 852 cumulated cases on 9 May 2020. Although the cluster number (/107 subjects) in LTC hospitals/facilities was significantly smaller compared with those in the other two groups, the cluster size in LTC hospitals/facilities was significantly larger than that in non-medical/welfare facilities. Cluster numbers in general medical/welfare facilities and in non-medical/welfare facilities were significantly positively correlated with morbidity (/105 ), indicating relatively early identification of clusters in these facilities. Unlike in these facilities, cluster size in LTC hospitals/facilities was significantly positively correlated with morbidity, indicating that clusters in LTC hospitals/facilities were finally identified after already having grown to a large size in areas where infection was prevalent. Multivariate logistic regression analysis showed that both cluster number and cluster size only in LTC hospitals/facilities were independently associated with higher mortality (≥median 0.64/105 subjects) after adjustment. CONCLUSIONS: Preventive efforts against COVID-19 outbreaks even at the early phase of the epidemic are critically important in LTC hospitals/facilities, as both the larger number and size of clusters only in LTC hospitals/facilities were independently linked to higher mortality in prefectures in Japan. Geriatr Gerontol Int 2020; 20: 715-719.


Subject(s)
Coronavirus Infections , Hospitals, Chronic Disease/statistics & numerical data , Long-Term Care , Pandemics , Pneumonia, Viral , Skilled Nursing Facilities/statistics & numerical data , Aged , Betacoronavirus/isolation & purification , Cluster Analysis , Coronavirus Infections/mortality , Coronavirus Infections/prevention & control , Female , Humans , Infection Control/organization & administration , Japan/epidemiology , Long-Term Care/methods , Long-Term Care/organization & administration , Long-Term Care/trends , Male , Mortality , Pandemics/prevention & control , Pneumonia, Viral/mortality , Pneumonia, Viral/prevention & control
15.
Nature ; 584(7821): 463-469, 2020 08.
Article in English | MEDLINE | ID: covidwho-677004

ABSTRACT

Recent studies have provided insights into the pathogenesis of coronavirus disease 2019 (COVID-19)1-4. However, the longitudinal immunological correlates of disease outcome remain unclear. Here we serially analysed immune responses in 113 patients with moderate or severe COVID-19. Immune profiling revealed an overall increase in innate cell lineages, with a concomitant reduction in T cell number. An early elevation in cytokine levels was associated with worse disease outcomes. Following an early increase in cytokines, patients with moderate COVID-19 displayed a progressive reduction in type 1 (antiviral) and type 3 (antifungal) responses. By contrast, patients with severe COVID-19 maintained these elevated responses throughout the course of the disease. Moreover, severe COVID-19 was accompanied by an increase in multiple type 2 (anti-helminths) effectors, including interleukin-5 (IL-5), IL-13, immunoglobulin E and eosinophils. Unsupervised clustering analysis identified four immune signatures, representing growth factors (A), type-2/3 cytokines (B), mixed type-1/2/3 cytokines (C), and chemokines (D) that correlated with three distinct disease trajectories. The immune profiles of patients who recovered from moderate COVID-19 were enriched in tissue reparative growth factor signature A, whereas the profiles of those with who developed severe disease had elevated levels of all four signatures. Thus, we have identified a maladapted immune response profile associated with severe COVID-19 and poor clinical outcome, as well as early immune signatures that correlate with divergent disease trajectories.


Subject(s)
Coronavirus Infections/immunology , Coronavirus Infections/physiopathology , Cytokines/analysis , Pneumonia, Viral/immunology , Pneumonia, Viral/physiopathology , Adult , Aged , Aged, 80 and over , Cluster Analysis , Cytokines/immunology , Eosinophils/immunology , Female , Humans , Immunoglobulin E/analysis , Immunoglobulin E/immunology , Interleukin-13/analysis , Interleukin-13/immunology , Interleukin-5/analysis , Interleukin-5/immunology , Male , Middle Aged , Pandemics , T-Lymphocytes/cytology , T-Lymphocytes/immunology , Viral Load , Young Adult
16.
Int J Environ Res Public Health ; 17(15)2020 07 22.
Article in English | MEDLINE | ID: covidwho-671049

ABSTRACT

While several efforts have been made to control the epidemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Italy, differences between and within regions have made it difficult to plan the phase two management after the national lockdown. Here, we propose a simple and immediate clustering approach to categorize Italian regions working on the prevalence and trend of SARS-CoV-2 positive cases prior to the start of phase two on 4 May 2020. Applying both hierarchical and k-means clustering, we identified three regional groups: regions in cluster 1 exhibited higher prevalence and the highest trend of SARS-CoV-2 positive cases; those classified into cluster 2 constituted an intermediate group; those in cluster 3 were regions with a lower prevalence and the lowest trend of SARS-CoV-2 positive cases. At the provincial level, we used a similar approach but working on the prevalence and trend of the total SARS-CoV-2 cases. Notably, provinces in cluster 1 exhibited the highest prevalence and trend of SARS-CoV-2 cases. Provinces in clusters 2 and 3, instead, showed a median prevalence of approximately 11 cases per 10,000 residents. However, provinces in cluster 3 were those with the lowest trend of cases. K-means clustering yielded to an alternative cluster solution in terms of the prevalence and trend of SARS-CoV-2 cases. Our study described a simple and immediate approach to monitor the SARS-CoV-2 epidemic at the regional and provincial level. These findings, at present, offered a snapshot of the epidemic, which could be helpful to outline the hierarchy of needs at the subnational level. However, the integration of our approach with further indicators and characteristics could improve our findings, also allowing the application to different contexts and with additional aims.


Subject(s)
Coronavirus Infections/epidemiology , Pneumonia, Viral/epidemiology , Betacoronavirus , Cluster Analysis , Geography , Humans , Italy/epidemiology , Pandemics , Prevalence
17.
BMJ Open ; 10(7): e040999, 2020 07 14.
Article in English | MEDLINE | ID: covidwho-646582

ABSTRACT

INTRODUCTION: Advance care planning (ACP) is associated with improved health outcomes for patients with cancer, and its absence is associated with unfavourable outcomes for patients and their caregivers. However, older adults do not complete ACP at expected rates due to patient and clinician barriers. We present the original design, methods and rationale for a trial aimed at improving ACP for older patients with advanced cancer and the modified protocol in response to changes brought by the COVID-19 pandemic. METHODS AND ANALYSIS: The Advance Care Planning: Promoting Effective and Aligned Communication in the Elderly study is a pragmatic, stepped-wedge cluster randomised trial examining a Comprehensive ACP Program. The programme combines two complementary evidence-based interventions: clinician communication skills training (VitalTalk) and patient video decision aids (ACP Decisions). We will implement the programme at 36 oncology clinics across three unique US health systems. Our primary outcome is the proportion of eligible patients with ACP documentation completed in the electronic health record. Our secondary outcomes include resuscitation preferences, palliative care consultations, death, hospice use and final cancer-directed therapy. From a subset of our patient population, we will collect surveys and video-based declarations of goals and preferences. We estimate 11 000 patients from the three sites will be enrolled in the study. ETHICS AND DISSEMINATION: Regulatory and ethical aspects of this trial include Institutional Review Board (IRB) approval via single IRB of record mechanism at Dana-Farber Cancer Institute, Data Use Agreements among partners and a Data Safety and Monitoring Board. We plan to present findings at national meetings and publish the results. TRIAL REGISTRATION NUMBER: NCT03609177; Pre-results.


Subject(s)
Advance Care Planning , Betacoronavirus , Clinical Decision-Making/methods , Coronavirus Infections/prevention & control , Health Communication/methods , Neoplasms/therapy , Pandemics/prevention & control , Patient Participation/methods , Pneumonia, Viral/prevention & control , Aged , Cluster Analysis , Humans , Program Evaluation/methods , Research Design , United States
18.
J Struct Biol ; 211(3): 107575, 2020 09 01.
Article in English | MEDLINE | ID: covidwho-640251

ABSTRACT

COVID-19 is a respiratory disease caused by the coronavirus SARS-CoV-2. SARS-CoV-2 has many similarities with SARS-CoV. Both viruses rely on a protease called the main protease, or Mpro, for replication. Therefore, inhibiting Mpro may be a successful strategy for treating COVID-19. Structures of the main proteases of SARS-CoV and SARS-CoV-2 with and without inhibitor N3 are available in the Protein Data Bank. Comparing these structures revealed residue interaction network changes associated with N3 inhibition. Comparing network clustering with and without inhibitor N3 identified the formation of a cluster of residues 17, 18, 30-33, 70, 95, 98, 103, 117, 122, and 177 as a network change in both viral proteases when bound to inhibitor N3. Betweenness and stress centrality differences as well as differences in bond energies and relative B-factors when comparing free Mpro to inhibitor-bound Mpro identified residues 131, 175, 182, and 185 as possibly conformationally relevant when bound to the inhibitor N3. Taken together, these results provide insight into conformational changes of betacoronavirus Mpros when bound to an inhibitor.


Subject(s)
Antiviral Agents/pharmacology , Betacoronavirus/enzymology , Enzyme Inhibitors/pharmacology , SARS Virus/enzymology , Viral Nonstructural Proteins/antagonists & inhibitors , Viral Proteins/antagonists & inhibitors , Catalytic Domain , Cluster Analysis , Coronavirus Infections/drug therapy , Cysteine Endopeptidases , Drug Design , Humans , Pandemics , Pneumonia, Viral/drug therapy , Protein Binding
19.
Genes (Basel) ; 11(7)2020 07 07.
Article in English | MEDLINE | ID: covidwho-640013

ABSTRACT

The global spread of COVID-19, caused by pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) underscores the need for an imminent response from medical research communities to better understand this rapidly spreading infection. Employing multiple bioinformatics and computational pipelines on transcriptome data from primary normal human bronchial epithelial cells (NHBE) during SARS-CoV-2 infection revealed activation of several mechanistic networks, including those involved in immunoglobulin G (IgG) and interferon lambda (IFNL) in host cells. Induction of acute inflammatory response and activation of tumor necrosis factor (TNF) was prominent in SARS-CoV-2 infected NHBE cells. Additionally, disease and functional analysis employing ingenuity pathway analysis (IPA) revealed activation of functional categories related to cell death, while those associated with viral infection and replication were suppressed. Several interferon (IFN) responsive gene targets (IRF9, IFIT1, IFIT2, IFIT3, IFITM1, MX1, OAS2, OAS3, IFI44 and IFI44L) were highly upregulated in SARS-CoV-2 infected NBHE cell, implying activation of antiviral IFN innate response. Gene ontology and functional annotation of differently expressed genes in patient lung tissues with COVID-19 revealed activation of antiviral response as the hallmark. Mechanistic network analysis in IPA identified 14 common activated, and 9 common suppressed networks in patient tissue, as well as in the NHBE cell model, suggesting a plausible role for these upstream regulator networks in the pathogenesis of COVID-19. Our data revealed expression of several viral proteins in vitro and in patient-derived tissue, while several host-derived long noncoding RNAs (lncRNAs) were identified. Our data highlights activation of IFN response as the main hallmark associated with SARS-CoV-2 infection in vitro and in human, and identified several differentially expressed lncRNAs during the course of infection, which could serve as disease biomarkers, while their precise role in the host response to SARS-CoV-2 remains to be investigated.


Subject(s)
Betacoronavirus/metabolism , Coronavirus Infections/pathology , Pneumonia, Viral/pathology , RNA, Long Noncoding/metabolism , Viral Proteins/metabolism , Betacoronavirus/genetics , Betacoronavirus/pathogenicity , Biomarkers/metabolism , Bronchi/cytology , Cell Death , Cell Line , Cluster Analysis , Coronavirus Infections/genetics , Coronavirus Infections/virology , Epithelial Cells/cytology , Epithelial Cells/virology , Gene Regulatory Networks , Humans , Immunity, Innate , Interferon-Stimulated Gene Factor 3, gamma Subunit/genetics , Lung/metabolism , Lung/pathology , Lung/virology , Pandemics , Pneumonia, Viral/genetics , Pneumonia, Viral/virology , RNA, Long Noncoding/genetics , Transcriptome
20.
J Public Health (Oxf) ; 42(3): 656-658, 2020 Aug 18.
Article in English | MEDLINE | ID: covidwho-639185

ABSTRACT

An ongoing outbreak of coronavirus disease 2019 (COVID-19) has rapidly spread in the world, whereas asymptomatic carriers may also play a critical role in the pandemic. We report a familial cluster of COVID-19 caused by one family member before his onset of illness, indicating that it seems to be potentially infectious during the incubation period, even earlier than we expected. Close contact, especially in a small enclosed space, might be the cause of familial transmission. The unsynchronized changes in the clinical symptoms and COVID-19 nucleic acid were found in this case, so consecutive nucleic acid detection of pretty suspected cases was recommended. Family members, especially of whom the confirmed cases contacted with since one incubation period before onset rather than 2 days before onset, should be regarded as close contact and centrally isolated in case of asymptomatic infection already existed in the family.


Subject(s)
Asymptomatic Infections/epidemiology , Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Disease Outbreaks/statistics & numerical data , Disease Transmission, Infectious/statistics & numerical data , Family/psychology , Pandemics/statistics & numerical data , Pneumonia, Viral/epidemiology , Pneumonia, Viral/transmission , Betacoronavirus , China/epidemiology , Cluster Analysis , Humans
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