bluuebunny/crossref_metadata_2025 huggingface dataset:
The Infection Rate of the Coronavirus Disease 2019 (COVID-19) in Wuhan, China
Authors: Qu Hui-Qi , Cheng Zhangkai J. , Duan Zhifeng , Tian Lifeng , Hakonarson Hakon
Published: May 2020

Summary Box

What is already known about this subject?

The Wuhan city in China had a much higher mortality rate (Feb 10th statistics: 748 death/18,454 diagnosis =4.05%; Apr 24th statistics: 3,869 death/50,333 diagnosis=7.69%) than the rest of China.

What are the new findings?

Based on our analysis, the number of infected people in Wuhan is estimated to be 143,000 (88,000 to 242,000) in late January and early February, significantly higher than the published number of diagnosed cases.

What are the recommendations for policy and practice?

Increased awareness of the original infection rates in Wuhan, China is critically important for proper public health measures at all levels, as well as to eliminate panic caused by overestimated mortality rate that may bias health policy actions by the authorities
Estimative of real number of infections by COVID-19 on Brazil and possible scenarios
Authors: Cintra H. P. C , Fontinele F. N.
Published: May 2020

This paper attempts to provide methods to estimate the real scenario of the novel coronavirus pandemic crisis on Brazil and the states of Sao Paulo, Pernambuco, Espirito Santo, Amazonas and Distrito Federal. By the use of a SEIRD mathematical model with age division, we predict the infection and death curve, stating the peak date for Brazil and these states. We also carry out a prediction for the ICU demand on these states for a visualization of the size of a possible collapse on the local health system. By the end, we establish some future scenarios including the stopping of social isolation and the introduction of vaccines and efficient medicine against the virus.
Etiologic Subtypes of Ischemic Stroke in SARS-COV-2 Virus patients in a cohort of New York City hospitals
Authors: Berekashvili Ketevan , Dmytriw Adam A , Vulkanov Volodomyr , Agarwal Shashank , Khaneja Amit , Turkel-Parella David , Liff Jeremy , Farkas Jeffrey , Nandakumar Thambinajar , Zhou Ting , Frontera Jennnifer , Kahn David E , Kim Sun , Humbert Kelly A , Sanger Matthew D , Yaghi Shadi , Lord Aaron , Arcot Karthikeyan , Tiwari Ambooj
Published: May 2020

Objective

To describe the ischemic stroke subtypes related to COVID-19 in a cohort of NYC hospitals and explore their etiopathogenesis.

Background

Extra-pulmonary involvement of COVID-19 has been reported in the hepatic, renal and hematological systems. Most neurological manifestations are non-focal, but few have reported the characteristics of ischemic strokes or investigated its pathophysiology.

Methods

Data were collected prospectively from March 15 to April 15, 2020 from four centers in New York City to review possible ischemic stroke types seen in COVID-19 positive patients. Patient presentation, demographics, other related vascular risk factors, associated laboratory and coagulation markers, as well as imaging and outcomes for consecutive stroke patients positive for SARS-COV2 infection over the period studied were collected.

Results

In our study, the age range of patients was 25-75 with no significant male preponderance. The median age of LVO patients was 48. Stroke was the presenting and hospitalizing event in 70%. One fifth of patients did not have common risk factors for ischemic stroke and none had atrial fibrillation, coronary or cerebrovascular disease, or were smokers. Half had a poor outcome with 40% ending in mortality (60% in LVO group) and one in a critical condition due ARDS. All had high neutrophil/lymphocyte ratio except one who demonstrated some neurological recovery. D-dimer levels showed mild to severe elevation when collected. None of the LVO cases had known cardiac risk factors but two out of five were found to have cardiac abnormalities during their hospitalization. All LVOs had hypercoagulable lab markers especially elevated D-dimer and/or fibrinogen. The LVO patients were younger and sicker with a median age of 46 and mean NIHSS of 24 as opposed to non-LVOs with a median age of 62 and mean NIHSS of 6 respectively.

Conclusion

COVID-19 related ischemic events can be small vessel, branch emboli or large vessel occlusions. The latter is often associated with either a hypercoagulable state or cardio-embolism. Patient outcomes were worse when multi-organ or pulmonary system failure prevailed.
Occurrence and Timing of Subsequent SARS-CoV-2 RT-PCR Positivity Among Initially Negative Patients
Authors: Long Dustin R. , Gombar Saurabh , Hogan Catherine A. , Greninger Alexander L. , Shah Vikas O’Reilly , Bryson-Cahn Chloe , Stevens Bryan , Rustagi Arjun , Jerome Keith R. , Kong Christina S. , Zehnder James , Shah Nigam H. , Weiss Noel S. , Pinsky Benjamin A. , Sunshine Jacob
Published: May 2020

Background

SARS-CoV-2 reverse transcriptase polymerase chain reaction (RT-PCR) testing remains the cornerstone of laboratory-based identification of patients with COVID-19. As the availability and speed of SARS-CoV-2 testing platforms improve, results are increasingly relied upon to inform critical decisions related to therapy, use of personal protective equipment, and workforce readiness. However, early reports of RT-PCR test performance have left clinicians and the public with concerns regarding the reliability of this predominant testing modality and the interpretation of negative results. In this work, two independent research teams report the frequency of discordant SARS-CoV-2 test results among initially negative, repeatedly tested patients in regions of the United States with early community transmission and access to testing.

Methods

All patients at the University of Washington (UW) and Stanford Health Care undergoing initial testing by nasopharyngeal (NP) swab between March 2nd and April 7th, 2020 were included. SARS-CoV-2 RT-PCR was performed targeting the N, RdRp, S, and E genes and ORF1ab, using a combination of Emergency Use Authorization laboratory-developed tests and commercial assays. Results through April 14th were extracted to allow for a complete 7-day observation period and an additional day for reporting.

Results

A total of 23,126 SARS-CoV-2 RT-PCR tests (10,583 UW, 12,543 Stanford) were performed in 20,912 eligible patients (8,977 UW, 11,935 Stanford) undergoing initial testing by NP swab; 626 initially test-negative patients were re-tested within 7 days. Among this group, repeat testing within 7 days yielded a positive result in 3.5% (4.3% UW, 2.8% Stanford) of cases, suggesting an initial false negative RT-PCR result; the majority (96.5%) of patients with an initial negative result who warranted reevaluation for any reason remained negative on all subsequent tests performed within this window.

Conclusions

Two independent research teams report the similar finding that, among initially negative patients subjected to repeat SARS-CoV-2 RT-PCR testing, the occurrence of a newly positive result within 7 days is uncommon. These observations suggest that false negative results at the time of initial presentation do occur, but potentially at a lower frequency than is currently believed. Although it is not possible to infer the clinical sensitivity of NP SARS-CoV-2 RT-PCR testing using these data, they may be used in combination with other reports to guide the use and interpretation of this common testing modality.
Reduced mortality and shortened ICU stay in SARS-COV-2 patients: a low PEEP strategy
Authors: Ceruti Samuele , Roncador Marco , Gié Olivier , Bona Giovanni , Iattoni Martina , Biggiogero Maira , Maida Pier Andrea ,   COVID-19 Clinical Management Team, Garzoni Christian , Mauri Romano ,   COVID-19 Clinical Management Team, Biondi Carola , Canovi Sara , Cavagna Mattia , Di Mari Bruno , Horvath Zsofia , Leo Rosambra , Lo Presti Giorgia , Luvini Giorgia , Meloni Dario , Orlando Francesca , Ravasi Sara , Sonzini Roberta , Tinessa Giuseppe
Published: May 2020

Background

Intensive Care Unit (ICU) management of COVID-19 patients with severe hypoxemia is associated with high mortality. We implemented a ‘care map’, as a standardized multidisciplinary approach to improve patients monitoring using: uniform patient selection for ICU admission, a low-PEEP strategy and a pharmacologic strategic thromboembolism management.

Methods

A standardized protocol for managing COVID-19 patients and ICU admissions was implemented through accurate Early Warning Score (EWS) monitoring and thromboembolism prophylaxis at hospital admission. Dyspnea, mental confusion or SpO2 less than 85% were criteria for ICU admission. Ventilation approach employed low PEEP values (about 10 cmH2O in presence of lung compliance > 40 mL/cmH2O) and FiO2 as needed. In presence of lower lung compliance (< 40 mL/cmH2O) PEEP value was increased to about 14 cmH2O.

Findings

From March 16th to April 12nd 2020, 41 COVID-19 patients were admitted to our ICU from a total of 310 patients. 83% (34) of them needed mechanical ventilation. The ventilation approach chosen employed low PEEP value based on BMI (PEEP 11± 3.8 (10-12) cmH2O if BMI < 30 Kg/m2; PEEP 15± 3.26 (12-18) cmH2O if BMI >30 Kg/m2). To date, ten patients (24%) died, four (9.7%) received mechanical ventilation, two were transferred to another hospital and 25 (60.9%) were discharged from ICU after a median of nine days.

Interpretation

A multimodal approach for COVID-19 patients is mandatory. The knowledge of this multi-organ disease is growing rapidly, requiring improvements in the standard of care. Our approach implements an accurate pre-ICU monitoring and strict selection for ICU admission, and allows to reduce mechanical ventilation, ICU stay and mortality.

Funding

No funding has been required.
Temperature and relative humidity are not major contributing factor on the occurrence of COVID-19 pandemic: An observational study in 57 countries (2020-05-08)
Authors: Sobur Md. Abdus , Islam Md. Saiful , Haque Md. Emdadul , Rahman AMM Taufiquer , Islam Md. Taohidul , Toniolo Antonio , Rahman Md. Tanvir
Published: May 2020

The world searching for hope has already experienced a huge loss of lives due to COVID-19 caused by SARS-CoV-2 started in Wuhan, China. There are speculations that climatic conditions can slowdown the transmission of COVID-19. Findings from the early outbreak indicated the possible association of air temperature and relative humidity in COVID-19 occurrence in China. Current study focused on whether climatic conditions (temperature and relative humidity) are having any influence in the occurrence of COVID-19 when the outbreak has been classified as pandemic. To determine the effect of daily average temperature and average relative humidity on log-transformed total daily cases of COVID-19, polynomial regression as a quadratic term and linear regression were done. Linear regression analysis was also carried out to explore the same effect on selected countries. Present study observed no correlation between the climatic conditions (the daily average temperature and relative humidity) and the number of cases of COVID-19. Similar result was found in relation between daily average temperature and average number of cases per day in country-wise analysis. However, about 93.5% cases of COVID-19 occurred between 1°C to 16°C and the average number of cases per day was lower in high temperature country than low temperature country with exceptions. The minimum effect of summer temperature may not be effective to control the pandemic rather need to apply the control measures of COVID-19.
A seven-day cycle in COVID-19 infection, hospitalization, and mortality rates: Do weekend social interactions kill susceptible people?
Authors: Ricon-Becker Itay , Tarrasch Ricardo , Blinder Pablo , Ben-Eliyahu Shamgar
Published: May 2020

Seven-day cycles in numbers of COVID-19 new-cases and deaths are markedly evident in most public databases (e.g. Worldometer, ECDC), but it is unclear whether they reflect systematic artifacts of delays in information reporting/gathering, or have a more profound basis. To address this question we located 11 databases of US states that provide date- authenticated information (actual date of symptom onset and/or specimen collection, or actual hospitalization or death date) that reported more than 1,000 deaths each. Numbers of new cases showed a weekly cyclic pattern in 10 out of 11 states, commonly peaking on weekdays, 2-6 days after the weekend, corresponding with a reported median 5-day lag between infection and the manifestation of clinical symptoms. We postulate that this pattern emerges from interactions with different and/or extended social-circles during weekends, including increased inter-generational meetings, which in turn facilitate transfer of COVID-19 from younger people to older vulnerable individuals. Furthermore, we found weekly periodicity in hospitalizations in 2 out of 2 authenticated databases providing this information. Actual death date, which is more difficult to attribute to individual choice, and is expected to occur approximately 2-3 weeks following hospitalization, showed significant 7-day periodicity in 1 out of 11 states, and a trend in 2 additional states. If weekly peaks in new cases can be truncated by physical/social distancing, especially during weekends, the mortality of COVID-19 may be reduced, or at least hospitalization and mortality curves may be flattened.

Significance Statement

We believe our findings are significant, as it appears that it is difficult for people to grasp an ambiguous “price” for visiting their friends and family, when they cannot be certain that they are not carrying and spreading the virus. Our findings could be used as an effective “tool” to demonstrate such a cost, clearly presented in terms of number of excessive infections. During these days of uncertainly, we believe it is fundamental to provide scientific facts that could illuminate this connection and make it tangible for the general. The amplitude of the cycles we describe here is such that many thousands of infections could be averted by carefully scrutinizing local policies, medical practice, and social norms.
The relatively young and rural population may limit the spread and severity of Covid-19 in Africa: a modelling study
Authors: Diop Binta Zahra , Ngom Marième , Biyong Clémence Pougué , Biyong John N. Pougué
Published: May 2020

Introduction

A novel coronavirus disease 2019 (COVID-19) has spread to all regions of the world. There is great uncertainty regarding how countries characteristics will affect the spread of the epidemic; to date, there are few studies that attempt to predict the spread of the epidemic in African countries. In this paper, we investigate the role of demographic patterns, urbanization and co-morbidities on the possible trajectories of COVID-19 in Ghana, Kenya, and Senegal.

Methods

We use an augmented deterministic SIR model to predict the true spread of the disease, under the containment measures taken so far. We dis-aggregate the infected compartment into asymptomatic, mildly symptomatic, and severely symptomatic to match observed clinical development of COVID-19. We also account for age structures, urbanization, and co-morbidities (HIV, tuberculosis, anemia).

Results

In our baseline model, we project that the peak of active cases will occur in July, subject to the effectiveness of policy measures. When accounting for the urbanization, and factoring-in co-morbidities, the peak may occur between June 2ndand June 17th(Ghana), July 22ndand August 29th(Kenya), and finally May 28thand June 15th(Senegal). Successful containment policies could lead to lower rates of severe infections. While most cases will be mild, we project in the absence of policies further containing the spread, that between 0.78 and 1.03%, 0.61 and 1.22%, and 0.60 and 0.84% of individuals in Ghana, Kenya, and Senegal respectively may develop severe symptoms at the time of the peak of the epidemic.

Conclusion

Compared to Europe, Africa’s younger and rural population may modify the severity of the epidemic. The large youth population may lead to more infections but most of these infections will be asymptomatic or mild, and will probably go undetected. The higher prevalence of underlying conditions must be considered.

What is known?

While most COVID-19 studies focus on western and Asian countries, very few are concerned with the spread of the virus in African countries.

Most African countries have relatively low urbanization rates, a young population and context-specific co-morbidities that are still to be explored in the spread of COVID-19.

What are the new findings?

In our baseline predictions 33 to 50% of the public will be actively infected at the peak of the epidemic and 1 in 36 (Ghana), 1 in 40 (Kenya) and 1 in 42 (Senegal) of these active cases may be severe.

With rural areas, infection may be lowered to 65-73% (Ghana), 48-71% (Kenya) and 61-69% (Senegal) of the baseline infections.

Comorbidities may however increase the ratio of severe infections among the active cases at the peak of the epidemic.

What do the new findings imply?

Rural areas and large youth population may limit the spread and severity of the epidemic and outweigh the negative impact of HIV, tuberculosis and anemia.
The Impact of Coronavirus Disease 2019 (COVID-19) on Liver Injury in China: A Systematic Review and Meta-analysis
Authors: Zhao Xin , Lei Zehua , Gao Fengwei , Xie Qingyun , Jang Kangyi , Wu Jianping , Fu Jinqiang , Du Bo , Wang Zhixu
Published: May 2020

Background

The evidence for the incidence and severity of liver injury in Chinese patients with COVID-19 is still controversial.

Aims

The purpose of this study was to summarize the incidence of liver injury and the differences between liver injury markers among different patients with COVID-19 in China.

Methods

Computer searches of PubMed, Embase, CNKI and medRxiv were used to obtain reports on the incidence and markers of liver injury in Chinese patients with COVID-19, from January 1, 2020 to April 10, 2020. (No. CRD42020181350)

Results

A total of 57 reports from China were included, including 9889 confirmed cases of COVID-19 infection. The results of the meta-analysis showed that among the patients with early COVID-19 infection in China, the incidence of liver injury events was 24.7% (95% CI, 23.4%-26.4%). Liver injury in severe patients was more common than that in non-severe patients, with a risk ratio of 2.07 (95% CI, 1.77 to 2.43). Quantitative analysis showed that the severe the coronavirus infection, the higher the level of AST, ALT, TB, ALP, GGT and the lower the level of ALB. The changing trend of the appeal index was similar in ICU patients and dead patients.

Conclusion

There is a certain risk of liver injury in Chinese patients with COVID-19, and the risk and degree of liver injury are related to the severity of COVID-19.
Social determinants of COVID-19 mortality at the county level
Authors: Fielding-Miller Rebecca K. , Sundaram Maria E. , Brouwer Kimberly
Published: May 2020

The United States is currently the global epicenter of the COVID-19 pandemic. Emerging data suggests that social determinants of health may be key drivers of the epidemic, and that minorities, migrants, and essential workers may bear a disproportionate degree of risk. We used publicly accessible datasets to build a series of spatial autoregressive models assessing county level associations between COVID- 19 mortality and (1) Percentage of Non-English speaking households, (2) percentage of individuals engaged in hired farm work, (3) percentage of uninsured individuals under the age of 65, and (3) percentage of individuals living at or below the poverty line. Across all counties (n=2940), counties with more farmworkers, more residents living in poverty, higher density, and more residents over the age of 65 had significantly higher levels of mortality. In urban counties (n=114), only county density was significantly associated with mortality. In non-urban counties (n=2826), counties with more non- English speaking households and more farm workers had significantly higher levels of mortality, as did counties with higher levels of poverty and more residents over the age of 65. More uninsured residents was significantly associated with decreased reported COVID-19 mortality. Individuals who do not speak English, individuals engaged in farm work, and individuals living in poverty may be at heightened risk for COVID-19 mortality in non-urban counties. Mortality among the uninsured may be being systematically undercounted in county and national level surveillance.
Cocooning is essential to relaxing social distancing
Authors: Wang Xutong , Du Zhanwei , Huang George , Pasco Remy F , Fox Spencer J , Galvani Alison P , Pignone Michael , Johnston S. Claiborne , Meyers Lauren Ancel
Published: May 2020

As the first wave of COVID-19 recedes, policymakers are contemplating the relaxation of shelter-in-place orders. Using a model capturing high-risk populations and transmission rates estimated from hospitalization data, we find that postponing relaxation will only delay a second wave and cocooning vulnerable populations is needed to prevent overwhelming medical surges.
Reentrant liquid condensate phase of proteins is stabilized by hydrophobic and non-ionic interactions
Authors: Krainer Georg , Welsh Timothy J. , Joseph Jerelle A. , Espinosa Jorge R. , Wittmann Sina , Csilléry Ella de , Sridhar Akshay , Toprakcioglu Zenon , Gudiškytė Giedre , Czekalska Magdalena A. , Arter William E. , George-Hyslop Peter St , Hyman Anthony A. , Collepardo-Guevara Rosana , Alberti Simon , Knowles Tuomas P.J.
Published: May 2020

Many cellular proteins demix spontaneously from solution to form liquid condensates. These phase-separated systems have wide-ranging roles in health and disease. Elucidating the molecular driving forces underlying liquid–liquid phase separation (LLPS) is therefore a key objective for understanding biological function and malfunction. Here we show that proteins implicated in cellular LLPS, including FUS, TDP-43, Brd4, Sox2, and Annexin A11, which form condensates at low salt concentrations, can reenter a phase-separated regime at high salt concentrations. By bringing together experiments and simulations, we demonstrate that phase separation in the high-salt regime is driven by hydrophobic and non-ionic interactions, and is mechanistically distinct from the low-salt regime, where condensates are additionally stabilized by electrostatic forces. Our work thus provides a new view on the cooperation of hydrophobicity and non-ionic interactions as non-specific driving forces for the condensation process, with important implications for aberrant function, druggability, and material properties of biomolecular condensates.
COVID-19 and homelessness in England: a modelling study of the COVID-19 pandemic among people experiencing homelessness, and the impact of a residential intervention to isolate vulnerable people and care for people with symptoms
Authors: Lewer Dan , Braithwaite Isobel , Bullock Miriam , Eyre Max T , Aldridge Robert W , Story Alistair , Hayward Andrew
Published: May 2020

Background

There is an ongoing pandemic of the viral respiratory disease COVID-19. People experiencing homelessness are vulnerable to infection and severe disease. Health and housing authorities in England have developed a residential intervention that aims to isolate those vulnerable to severe disease (COVID-PROTECT) and care for people with symptoms (COVID-CARE).

Methods

We used a discrete-time Markov chain model to forecast COVID-19 infections among people experiencing homelessness, given strong containment measures in the general population and some transmission among 35,817 people living in 1,065 hostels, and 11,748 people sleeping rough (the ’do nothing’ scenario). We then estimated demand for beds if those eligible are offered COVID-PROTECT and COVID-CARE. We estimated the reduction in the number of COVID-19 cases, deaths, and hospital admissions that could be achieved by these interventions. We also conducted sensitivity and scenario analyses to identify programme success factors.

Results

In a ’do nothing’ scenario, we estimate that 34% of the homeless population could get COVID-19 between March and August 2020, with 364 deaths, 4,074 hospital admissions and 572 critical care admissions. In our ’base intervention’ scenario, demand for COVID-PROTECT peaks at 9,934 beds, and demand for COVID-CARE peaks at 1,366 beds. The intervention could reduce transmission by removing symptomatic individuals from the community, and preventing vulnerable individuals from being infected. This could lead to a reduction of 164 deaths, 2,624 hospital admissions, and 248 critical care admissions over this period. Sensitivity analyses showed that the number of deaths is sensitive to transmission of COVID-19 in COVID-PROTECT. If COVID-PROTECT capacity is limited, scenario analyses show the benefit of prioritising people who are vulnerable to severe disease.

Conclusion

Supportive accommodation can mitigate the impact of the COVID-19 pandemic on the homeless population of England, and reduce the burden on acute hospitals.
IDentif.AI: Artificial Intelligence Pinpoints Remdesivir in Combination with Ritonavir and Lopinavir as an Optimal Regimen Against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)
Authors: Blasiak Agata , Lim Jhin Jieh , Seah Shirley Gek Kheng , Kee Theodore , Remus Alexandria , Chye De Hoe , Wong Pui San , Hooi Lissa , Truong Anh T.L. , Le Nguyen , Chan Conrad E.Z. , Desai Rishi , Ding Xianting , Hanson Brendon J. , Chow Edward Kai-Hua , Ho Dean
Published: May 2020

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 2019 (COVID-19) has led to the rapid initiation of urgently needed clinical trials of repurposed drug combinations and monotherapies. These regimens were primarily relying on mechanism-of-action based selection of drugs, many of which have yielded positive in vitro but largely negative clinical outcomes. To overcome this challenge, we report the use of IDentif.AI, a platform that rapidly optimizes infectious disease (ID) combination therapy design using artificial intelligence (AI). In this study, IDentif.AI was implemented on a 12-drug candidate therapy search set representing over 530,000 possible drug combinations. IDentif.AI demonstrated that the optimal combination therapy against SARS-CoV-2 was comprised of remdesivir, ritonavir, and lopinavir, which mediated a 6.5-fold improvement in efficacy over remdesivir alone. Additionally, IDentif.AI showed hydroxychloroquine and azithromycin to be relatively ineffective. The identification of a clinically actionable optimal drug combination was completed within two weeks, with a 3-order of magnitude reduction in the number of tests typically needed. IDentif.AI analysis was also able to independently confirm clinical trial outcomes to date without requiring any data from these trials. The robustness of the IDentif.AI platform suggests that it may be applicable towards rapid development of optimal drug regimens to address current and future outbreaks.
The prevalence of common and stress-related mental health disorders in healthcare workers based in pandemic-affected hospitals: a rapid systematic review and meta-analysis
Authors: Allan Sophie M. , Bealey Rebecca , Birch Jennifer , Cushing Toby , Parke Sheryl , Sergi Georgina , Bloomfield Michael , Meiser-Stedman Richard
Published: May 2020

Background

Healthcare workers (HCWs) are considered at elevated risk of experiencing mental health disorders in working with patients with COVID-19.

Aims

To estimate the prevalence of common mental health disorders in HCWs based in hospitals where pandemic-affected patients were treated.

Method

Databases were searched for studies published before 30th March 2020. Quantitative synthesis was used to obtain estimates of the prevalence of mental health disorders in four time windows, determined a priori (the acute phase, i.e. during and up to 1.5 months post-pandemic; 1.5-5.9 months; 6-11.9 months; 12 months and later).

Results

Nineteen studies met the review criteria. They predominantly addressed the acute phase of the SARS outbreak in Asia. The most studied outcomes were clinically-significant post-traumatic stress symptoms (PTSS) and general psychiatric caseness. For clinically significant PTSS in the acute phase, the prevalence estimate was 23.4% (95% CI 16.3, 31.2; N=4147; I2=96.2%); in the 12 months plus window, the estimate was 11.9% (8.4, 15.8; N=1136; I2=74.3%). For general psychiatric caseness, prevalence estimates were: acute phase, 34.1% (18.7, 51.4; N=3971; I2=99.1%); 6-12 months, 17.9% (13.1, 23.2; N=223; I2=0.0%); 12 months plus, 29.3% (6.0, 61.0; N=710; I2=97.8%).

Conclusions

Mental health disorders are particularly common in HCWs working with pandemic-afflicted patients immediately following a pandemic, but the course of disorders following this period is poorly understood. PTSS remained elevated compared to the general population at 12 months, despite there being some evidence for natural recovery. There was considerable heterogeneity, likely linked to methodological differences. More extended follow up of HCWs is needed.
Association of previous medications with the risk of COVID-19: a nationwide claims-based study from South Korea
Authors: Huh Kyungmin , Ji Wonjun , Kang Minsun , Hong Jinwook , Bae Gi Hwan , Lee Rugyeom , Na Yewon , Choi Hyoseon , Gong Seon Yeong , Jung Jaehun
Published: May 2020

Background

Identifying the association between medications taken prior to the infection of coronavirus disease (COVID-19) might be useful during the current pandemic until a proven treatment is developed. We aimed to determine whether the risk of developing COVID-19 was associated with the use of various drugs that may increase or decrease susceptibility to severe acute respiratory syndrome coronavirus 2 infection and COVID-19.

Methods and Findings

A case-control study was performed using a nationwide claims database of South Korea, where a large testing capacity has been available throughout the pandemic. Exposure was defined as the prescription of study drugs that would have been continued until ≤7 days before the testing for COVID-19. Adults were considered eligible if they were ≥18 years old and tested for COVID-19. Among the 65,149 eligible subjects (mean age, 48.3 years; 49.4% male), 5,172 (7.9%) were diagnosed with COVID-19. Hydroxychloroquine was not significantly associated with the risk of COVID-19 (adjusted odds ratio [aOR], 1.48; 95% CI, 0.95–2.31). In the overall population, lower risks of COVID-19 were associated with the use of camostat (aOR, 0.45; 95% CI, 0.20–1.02) and amiodarone (aOR, 0.54; 95% CI, 0.33–0.89), although the differences were not significant in the subgroup analyses. Angiotensin receptor blockers were also associated with a slightly increased risk of COVID-19 (aOR, 1.13; 95% CI, 1.01–1.26), which was also not observed in the subgroup analysis. The study limitations include potential bias regarding the controls’ characteristics, inability to determine prescription compliance, and a lack of information regarding the severity of underlying conditions.

Conclusions

No medications were consistently associated with increased or decreased risks of COVID-19. These findings suggest that a more cautious approach is warranted for the clinical use of re-purposed drugs until the results are available from clinical trials.
Hospitalization and 30-day fatality in 121,263 COVID-19 outpatient cases
Authors: Prieto-Alhambra Daniel , Balló Elisabet , Coma Ermengol , Mora Núria , Aragón María , Prats-Uribe Albert , Fina Francesc , Benítez Mència , Guiriguet Carolina , Fàbregas Mireia , Medina-Peralta Manuel , Duarte-Salles Talita
Published: May 2020

Background

To date, characterisation studies of COVID-19 have focussed on hospitalised or intensive care patients. We report for the first time on the natural history of COVID-19 disease from first diagnosis, including both outpatient and hospital care.

Methods

Data was obtained from SIDIAP, a primary care records database covering >6 million people (>80% of the population of Catalonia), linked to COVID-19 RT-PCR tests, hospital emergency and inpatient, and mortality registers. All participants >=15 years, diagnosed with COVID-19 in outpatient between 15th March and 24th April 2020 (10thApril for outcome studies) were included. Baseline characteristics, testing, and 30-day outcomes (hospitalisation for COVID-19 and all-cause fatality) were analysed.

Results

A total of 121,263 and 95,467 COVID-19 patients were identified for characterisation and outcome studies, respectively. Women (57.8%) and age 45-54 (20.2%) were predominant. 44,709 were tested, with 32,976 (73.8%) PCR+. From 95,467 cases, a 14.6% [14.4–14.9] were hospitalised in the month after diagnosis, with male predominance (19.2% vs 11.3%), peaking at age 75-84. Overall 30-day fatality was 4.0% [95%CI 3.9%-4.2%], higher in men (4.8%) than women (3.4%), increasing with age, and highest in those residing in nursing homes (25.3% [24.2% to 26.4%]).

Conclusions

COVID-19 is seen in all age-sex strata, but severe forms of disease cluster in older men and nursing home residents. Although initially managed in primary care, 15% of cases require hospitalization within a month, with overall fatality of 4%.
Respiratory infection during lithium and valproate medication: a within-individual prospective study of 50,000 patients with bipolar disorder
Authors: Landén Mikael , Lichtenstein Paul , Larsson Henrik , Song Jie
Published: May 2020

Objective

In vitrostudies have demonstrated that lithium has antiviral properties, but evidence from human studies is scarce. Lithium is used as a mood stabilizer to treat patients with bipolar disorder. Here, the aim was to investigate the association between lithium use and the risk of respiratory infections in patients with bipolar disorder. To rule out the possibility that a potential association could be due to lithium’s effect on psychiatric symptoms, we also studied the effect of the most common alternative to lithium to prevent mood episodes in bipolar disorder, valproate.

Method

We followed 51,509 individuals diagnosed with bipolar disorder in the Swedish Patient register 2005–2013. We applied a with-individual design using stratified Cox regression to estimate the hazard ratios (HRs) of respiratory infections during treated periods compared with untreated periods.

Results

During follow-up, 5,760 respiratory infections were documented in the Swedish Patient Register. The incidence rate was 28% lower during lithium treatment (HR 0.73, 95% CI 0.61–0.86) and 35% higher during valproate treatment (HR 1.35, 95% CI 1.06–1.73) compared with periods off treatment.

Conclusions

This study provides real-world evidence that lithium protects against respiratory infections and suggests that the repurposing potential of lithium for antiviral effects is worthy of investigation.
Multivariable prediction model of intensive care unit transfer and death: a French prospective cohort study of COVID-19 patients
Authors: Allenbach Yves , Saadoun David , Maalouf Georgina , Vieira Matheus , Hellio Alexandra , Boddaert Jacques , Gros Hélène , Salem Joe Elie , Rigon Matthieu Resche , Biard Lucie , Benveniste Olivier , Cacoub Patrice
Published: May 2020

Background

Prognostic factors of coronavirus disease 2019 (COVID-19) patients among European population are lacking. Our objective was to identify early prognostic factors upon admission to optimize the management of COVID-19 patients hospitalized in a medical ward.

Methods

French single-center prospective cohort study of 152 patients with positive Severe acute respiratory syndrome coronavirus 2 (SARS-Cov2) real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay, hospitalized in a medical ward. Multivariable models and a simplified scoring system assessed predictive factors of intensive care unit (ICU) transfer or death at day 14 (D14), of being discharge alive and severe status at D14 (remaining with ventilation, or death). A validation was performed on an external sample of 132 patients.

Findings

At D14, the probability of ICU transfer or death was 32% (95% CI 25-40). Older age (OR 2·61, 95% CI 0·96-7·10), poorer respiratory presentation (OR 4·04 per 1-point increment on World Health Organization (WHO) clinical scale, 95% CI 1·76-9·25), higher CRP-level (OR 1·63 per 100mg/L increment, 95% CI 0·98-2·71) and lower lymphocytes count (OR 0·36 per 1000/mm3 increment, 95% CI 0·13-0·99) were associated with an increased risk of ICU requirement or death. A 8-point ordinal scale scoring system defined low (score 0-2), moderate (score 3-5), and high (score 6-8) risk patients, with predicted respectively 2%, 25% and 81% risk of ICU transfer or death at D14.

Interpretation

In this prospective cohort study of laboratory-confirmed COVID-19 patients hospitalized in a medical ward in France, 32% were transferred to ICU or died. A simplified scoring system at admission predicted the outcome at D14.

Funding

No funding.
Safe Blues: A Method for Estimation and Control in the Fight Against COVID-19
Authors: Dandekar Raj , Henderson Shane G. , Jansen Marijn , Moka Sarat , Nazarathy Yoni , Rackauckas Christopher , Taylor Peter G. , Vuorinen Aapeli
Published: May 2020

How do fine modifications to social distancing measures really affect COVID-19 spread? A major problem for health authorities is that we do not know.

In an imaginary world, we might develop a harmless biological virus that spreads just like COVID-19, but is traceable via a cheap and reliable diagnosis. By introducing such an imaginary virus into the population and observing how it spreads, we would have a way of learning about COVID-19 because the benign virus would respond to population behaviour and social distancing measures in a similar manner. Such a benign biological virus does not exist. Instead, we propose a safe and privacy-preserving digital alternative.

Our solution is to mimic the benign virus by passing virtual tokens between electronic devices when they move into close proximity. As Bluetooth transmission is the most likely method used for such inter-device communication, and as our suggested “virtual viruses” do not harm individuals’ software or intrude on privacy, we call these Safe Blues.

In contrast to many app-based methods that inform individuals or governments about actual COVID-19 patients or hazards, Safe Blues does not provide information about individuals’ locations or contacts. Hence the privacy concerns associated with Safe Blues are much lower than other methods. However, from the point of view of data collection, Safe Blues has two major advantages:

Data about the spread of Safe Blues is uploaded to a central server in real time, which can give authorities a more up-to-date picture in comparison to actual COVID-19 data, which is only available retrospectively.

Sampling of Safe Blues data is not biased by being applied only to people who have shown symptoms or who have come into contact with known positive cases.

These features mean that there would be real statistical value in introducing Safe Blues. In the medium term and end game of COVID-19, information from Safe Blues could aid health authorities to make informed decisions with respect to social distancing and other measures.

In this paper we outline the general principles of Safe Blues and we illustrate how Safe Blues data together with neural networks may be used to infer characteristics of the progress of the COVID-19 pandemic in real time. Further information is on the Safe Blues website: https://safeblues.org/.
The genetic analysis of a founder Northern American population of European descent identifiesFANCIas a candidate familial ovarian cancer risk gene
Authors: Fierheller Caitlin T , Guitton-Sert Laure , Alenezi Wejdan M , Revil Timothée , Oros Kathleen K , Bedard Karine , Arcand Suzanna L , Serruya Corinne , Behl Supriya , Meunier Liliane , Fleury Hubert , Fewings Eleanor , Subramanian Deepak N , Nadaf Javad , Provencher Diane , Foulkes William D , El Haffaf Zaki , Mes-Masson Anne-Marie , Majewski Jacek , Tischkowitz Marc , James Paul A , Campbell Ian G , Greenwood Celia M T , Ragoussis Jiannis , Masson Jean-Yves , Tonin Patricia N
Published: May 2020

Some familial ovarian cancer (OC) could be due to rare risk alleles in genes that each account for a relatively small proportion of cases not due toBRCA1andBRCA2, major risk genes in the homologous recombination (HR) DNA repair pathway. We report a new candidate OC risk allele,FANCIc.1813C>T in a Fanconi anemia (FA) gene that plays a role upstream of the HR DNA repair pathway. This variant was identified by whole exome sequencing of aBRCA1andBRCA2mutation-negative French Canadian (FC) OC family from a population exhibiting founder effects. In FCs, the c.1813C>T allele was detected in 7% (3/43) of familial and 1.6% (7/439) of sporadic OC cases; and in 3.7% (3/82) of familial breast cancer (BC) cases with a family history of OC and in 1.9% (3/158) of BC only families. This allele was significantly associated with FCBRCA1andBRCA2mutation-negative OC families (OR=5.6; 95%CI=1.6-19; p=0.006). AlthoughFANCIc.1813C>T was detected in 2.5% (74/2950) of cancer-free FC females, carriers had a personal history of known OC risk reducing factors, and female/male carriers were more likely to have reported a first-degree relative with OC (ρ=0.037; p=0.011). Eight rare potentially pathogenicFANCIvariants were identified in 3.3% (17/516) of Australian OC cases, including 10 carriers ofFANCIc.1813C>T. Potentially pathogenicFANCIvariants were significantly more common in AUS OC cases with a family history of OC than in isolated OC cases (p=0.027). The odds ratios (OR) were >3 for carriers of any of the seven rarestFANCIalleles, and 1.5 for c.1813C>T. Data from the OC Association Consortium revealed that the ORs for the c.1813C>T allele were highest for the most common OC subtypes. Localization of FANCD2, part of the FANCI-FANCD2 (ID2) binding complex in the FA pathway, to sites of induced DNA damage was severely impeded in cells expressing the p.L605F isoform. This isoform was expressed at a reduced level; unstable by formaldehyde or mitomycin C treatment; and exhibited sensitivity to cisplatin but not to olaparib (a poly [ADP-ribose] polymerase inhibitor). By tissue microarray analyses, FANCI protein was robustly expressed in fallopian tube epithelial cells but expressed at low-to-moderate levels in 88% (83/94) of high-grade serous carcinoma OC samples. This is the first study to describe potentially pathogenic variants in OC in a member of the ID2 complex of the FA DNA repair pathway. Our data suggest that potentially pathogenicFANCIvariants may modify OC risk in cancer families.
Assessing the impact of non-pharmaceutical interventions on SARS-CoV-2 transmission in Switzerland
Authors: Lemaitre Joseph. C. , Perez-Saez Javier , Azman Andrew S. , Rinaldo Andrea , Fellay Jacques
Published: May 2020

Following the rapid dissemination of COVID-19 cases in Switzerland, large-scale non-pharmaceutical interventions (NPIs) were implemented by the cantons and the federal government between February 28 and March 20. Estimates of the impact of these interventions on SARS-CoV-2 transmission are critical for decision making in this and future outbreaks. We here aim to assess the impact of these NPIs on disease transmission by estimating changes in the basic reproduction number (R0) at national and cantonal levels in relation to the timing of these NPIs. We estimate the time-varying R0 nationally and in twelve cantons by fitting a stochastic transmission model explicitly simulating within hospital dynamics. We use individual-level data of >1,000 hospitalized patients in Switzerland and public daily reports of hospitalizations and deaths. We estimate the national R0 was 3.15 (95% CI: 2.13-3.76) at the start of the epidemic. Starting from around March 6, we find a strong reduction in R0 with a 85% median decrease (95% quantile range, QR: 83%-90%) to a value of 0.44 (95% QR: 0.27-0.65) in the period of March 29-April 5. At the cantonal-level R0 decreased over the course of the epidemic between 71% and 94%. We found that reductions in R0 were synchronous with changes in mobility patterns as estimated through smartphone activity, which started before the official implementation of NPIs. We found that most of the reduction of transmission is due to behavioural changes as opposed to natural immunity, the latter accounting for only about 3% of the total reduction in effective transmission. As Switzerland considers relaxing some of the restrictions of social mixing, current estimates of R0 well below one are promising. However most of inferred transmission reduction was due to behaviour change (<3% due to natural immunity buildup), with an estimated 97% (95% QR: 96.6%-97.2%) of the Swiss population still susceptible to SARS-CoV-2 as of April 24. These results warrant a cautious relaxation of social distance practices and close monitoring of changes in both the basic and effective reproduction numbers.
Projection of COVID-19 Cases and Deaths in the US as Individual States Re-open May 4, 2020
Authors: Yamana Teresa , Pei Sen , Kandula Sasikiran , Shaman Jeffrey
Published: May 2020

In March and April 2020, control measures enforcing social distancing and restricting individual movement and contact were adopted across the United States in an effort to slow the spread and growth of COVID-19. However, a number of states have now begun to ease these restrictions. Here, we evaluate the effects of loosening stay-at-home orders on COVID-19 incidence and related outcomes. We use a metapopulation model applied at county resolution to simulate the spread and growth of COVID-19 incidence in the United States. We calibrate the model against county-level daily case and death data collected from February 21, 2020 to May 2, 2020, and project the outbreak in 3,142 US counties for 6 weeks into the future. Projections for daily reported cases, daily new infections (both reported and unreported), new and cumulative hospital bed demand, ICU bed and ventilator demand, as well as daily mortality, are generated. We observe a rebound in COVID-19 incidence and deaths beginning in late May, approximately 2 to 4 weeks after states begin to reopen. Importantly, the lag between infection acquisition and case confirmation, coupled with insufficient broader testing and contact tracing, will mask any rebound and exponential growth of the COVID-19 until it is well underway.
COVID-19 DYNAMICS: A HETEROGENEOUS MODEL
Authors: Gerasimov Andrey , Lebedev Georgy , Lebedev Mikhail , Semenycheva Irina
Published: May 2020

The ongoing Coronavirus disease 2019 (COVID-19) epidemic is different from the previous epidemic of severe acute respiratory syndrome (SARS), which demands a rigorous analysis for the selection of anti-epidemic measures and their lifting when the epidemic subsides. Here we estimate the basic reproductive number for COVID-19 and propose a dynamical model for the time course of infection number. With this model, we assessed the effects of different measures for infection risk control. The model is different from the previous ones as it models the population as heterogeneous, with subpopulations having different infection risks. Our analyses showed that after this heterogeneity is incorporated in the model, several characteristics of the epidemic are estimated more accurately: the total number of cases and peak number of cases are lower compared to the homogeneous case, the early-stage growth rate in the number of infection cases is little affected, and the decrease in the number of infections slows down during the epidemic late stage. The comparison of our model results with the available data for COVID-19 indicates that the anti-epidemic measures undertaken in China and the rest of the world managed to decrease the basic reproductive number but did not assure an accumulation of sufficient collective immunity. Thus, the epidemic has a high likelihood to restart, which necessitates a careful approach to lifting the quarantine measures.