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Purpose The purpose of this review is to quantify the landscape of current clinical trials ongoing for therapies in the treatment of COVID-19. A secondary purpose is to examine the relationship between public and scientific interests in potential therapies for COVID-19. Methods A systematic search of clinicaltrials.gov was undertaken on April 22, 2020, to identify all currently registered clinical trials investigating potential therapies for patients with COVID-19. Public interest in the various therapies was quantified utilizing Google Trends. Public interest in hydroxychloroquine and chloroquine was plotted against the cumulative number of active clinical trials evaluating antimalarials as potential COVID-19 therapies over time. Results There were 341 interventional studies and 208 different therapies actively registered on clinicaltrials.gov whose primary aim is the treatment of COVID-19. The median sample size was 120 patients (range 4–6000) with 154 (45%) trials reporting a planned sample size of 100 patients or less. There was a strong positive correlation (r = 0.76, p = 0.01) between the number of registered clinical trials and the public interest in the top ten proposed therapies. Following the spike in public interest, the average number of new trials increased tenfold with respect to antimalarial therapies. Conclusions The relatively small sample sizes and the number of independent trials investigating similar therapies are concerning. Resources may not be being allocated based on scientific merit and may be driven by public consciousness and speculation. Moving forward, a concerted effort focused on implementing large, well-coordinated and carefully designed multi-armed clinical trials will help to ensure that the most promising therapeutic options are rigorously studied and clinically meaningful results produced.

Purpose The COVID-19 pandemic is importantly affecting the orthopaedic practice all over the world with Northern Italy being the first European area that faced the worst scenario. In this study, the changes in clinical practice occurred in an orthopaedic center in Milan are described. Methods Number and type of admissions, outpatients cancelled and preserved, emergency room, and intensive care unit activities have been analyzed in the timeframe of seven weeks since the beginning of the pandemic (from February 24th to April 10th) and compared with the same period in 2019. Results The planned surgical admissions declined from 2172 in 2019 to 664 in 2020 (69.42%, p

Since its outbreak in Wuhan, Hubei Province China, 2019-coronavirus infected disease (COVID-19) had been widely spread all over the world, the control of which calls for a better understanding of its epidemiology and clinical characteristics. We included 12 confirmed cases of COVID-19 in First Affiliated Hospital of Jilin University from 23 January 2020 to 11 February 2020, which were retrospectively analyzed for epidemiological, demographic, clinical, laboratory, and radiological features. All the patients were confirmed by nucleic acid detection, the average age of whom was 45.25 years (range, 23–79 years). Most patients had a history of Wuhan traveling or had contact with Wuhan travelers or infected cases. Obvious family cluster was observed. Clinical manifestations included fever (12/12), fatigue (10/12), cough (6/12), sore throat (4/12), headache (3/12), and diarrhea (2/12). Only three out of eight patients had pneumonia manifestation on radiography. Most patients had a normal white blood cell (WBC) count and normal or reduced lymphocyte (LY) count. Pneumonia changes were observed in all the four patients who underwent a chest CT scan. Only one elderly patient developed severe pneumonia, while all the rest were mild disease and had a self-limiting course.

Summary and Background Data: VV ECMO can be utilized as an advanced therapy in select patients with COVID-19 respiratory failure refractory to traditional critical care management and optimal mechanical ventilation. Anticipating a need for such therapies during the pandemic, our center created a targeted protocol for ECMO therapy in COVID-19 patients that allows us to provide this life-saving therapy to our sickest patients without overburdening already stretched resources or excessively exposing healthcare staff to infection risk. Methods: As a major regional referral program, we used the framework of our well-established ECMO service-line to outline specific team structures, modified patient eligibility criteria, cannulation strategies, and management protocols for the COVID-19 ECMO program. Results: During the first month of the COVID-19 outbreak in Massachusetts, 6 patients were placed on VV ECMO for refractory hypoxemic respiratory failure. The median (interquartile range) age was 47 years (43–53) with most patients being male (83%) and obese (67%). All cannulations were performed at the bedside in the intensive care unit in patients who had undergone a trial of rescue therapies for acute respiratory distress syndrome including lung protective ventilation, paralysis, prone positioning, and inhaled nitric oxide. At the time of this report, 83% (5/6) of the patients are still alive with 1 death on ECMO, attributed to hemorrhagic stroke. 67% of patients (4/6) have been successfully decannulated, including 2 that have been successfully extubated and one who was discharged from the hospital. The median duration of VV ECMO therapy for patients who have been decannulated is 12 days (4–18 days). Conclusions: This is 1 the first case series describing VV ECMO outcomes in COVID-19 patients. Our initial data suggest that VV ECMO can be successfully utilized in appropriately selected COVID-19 patients with advanced respiratory failure.

Objective: The COVID-19 pandemic requires to conscientiously weigh “timely surgical intervention” for colorectal cancer against efforts to conserve hospital resources and protect patients and health care providers. Summary Background Data: Professional societies provided ad-hoc guidance at the outset of the COVID-19 pandemic on deferral of surgical and perioperative interventions, but these lack specific parameters to determine the optimal timing of surgery. Methods: Using the GRADE system, published evidence was analyzed to generate weighted statements for stage, site, acuity of presentation, and hospital setting to specify when surgery should be pursued, the time and duration of oncologically acceptable delays, and when to utilize nonsurgical modalities to bridge the waiting period. Results: Colorectal cancer surgeries—prioritized as emergency, urgent with imminent emergency or oncologically urgent, or elective—were matched against the phases of the pandemic. Surgery in COVID-19-positive patients must be avoided. Emergent and imminent emergent cases should mostly proceed unless resources are exhausted. Standard practices allow for postponement of elective cases and deferral to nonsurgical modalities of stage II/III rectal and metastatic colorectal cancer. Oncologically urgent cases may be delayed for 6(–12) weeks without jeopardizing oncological outcomes. Outside established principles, administration of nonsurgical modalities is not justified and increases the vulnerability of patients. Conclusions: The COVID-19 pandemic has stressed already limited health care resources and forced rationing, triage, and prioritization of care in general, specifically of surgical interventions. Established guidelines allow for modifications of optimal timing and type of surgery for colorectal cancer during an unrelated pandemic.

Objectives We aimed to develop a simple algorithm helps early identification of SARS-CoV-2 infection patients with severe progression tendency. Methods 322 SARS-COV-2 infection patients were respectively enrolled. The univariable and multivariable analysis were computed to identify the independent predictors of severe progression, and the prediction model was established based on independent predictors. The areas under the ROC curves (AUROCs) were used to evaluate the diagnostic performances. Results Of 322 confirmed SARS-COV-2 infection patients, 11 were diagnosed as severe cases on admission, 15 developed to severe cases after admission, and 296 were non-severe cases. The multivariable analysis identified age (OR=1.061, p=0.028), lactate dehydrogenase (LDH) (OR=1.006, p=0.037), and CD4 count (OR=0.993, p=0.006) as the independent predictors of severe progression. Consequently, the age-LDH-CD4 algorithm was derived as (age×LDH)/CD4. The AUROC of the age-LDH-CD4 model was significantly higher than that of single CD4 count, LDH, or age (0.92, 0.85, 0.80, and 0.75, respectively). The age-LDH-CD4 model ≥ 82 has high sensitive (81%) and specific (93%) for the early identification of patients with severe progression tendency following SARS-CoV-2 infection. Conclusions The age-LDH-CD4 model is a simple algorithm for early identifying cases with severe progression tendency in SARS-CoV-2 infection patients, and warrants further validation.

Purpose Timing of surgery for orthopaedic injuries continues to evolve, as an improved understanding of biology, healing, and technological advances continues to challenge historical norms. With the growing COVID-19 pandemic stretching limited healthcare resources, postponing surgery becomes an inevitable and unenviable task for most orthopaedic surgeons, and a shift in outpatient paradigms is required to mitigate poor outcomes in patients. Methods A scoping review of five databases on surgical timing and orthopaedic soft-tissue injuries was performed. All randomized controlled trials, longitudinal cohort studies, retrospective case series, systematic reviews, meta-analyses, and expert opinions were included for review, with 65 studies meeting the inclusion criteria. Results Better outcomes appear to be associated with early surgery for subluxations (< 1 week), recurrent dislocations (> 2 episodes), ligamentous and tendinous injuries (< 2 weeks), and bony avulsion injuries (< 3 weeks). Spinal conditions with neurological compromise should be operated on within 24 hours and spinal instability within 72 hours to reduce the risk of complications and poor outcomes. Conclusion Most soft-tissue orthopaedic injuries can be managed with outpatient ambulatory surgery in a semi-elective setting. As the paradigm for outpatient surgery shifts due to technological advances and the COVID-19 pandemic, it is critical for surgeons to time their surgery appropriately to maintain the high standards of orthopaedic practice.

Background Disasters, crises and pandemics are emergencies which impact on businesses severely. The COVID-19 pandemic reached its peak in mid-April 2020 in the UK. During this period, NHS Occupational Health Services (OHS) were stretched to their limit along with other health services. OHS may have had to change their pattern of operation, operating times, services offered, etc. to cope with the pandemic. Data about business model modifications, services offered by the OHS businesses during the pandemic could help in better utilization of OHS resources in the future. Aims To understand the behaviour of OHS in different parts of the country during the COVID-19 pandemic. Methods An online survey link was sent to both accredited and unaccredited UK Occupational Health Physicians (OHPs). Results Sixty-two OHPs responded to the survey. In the current pandemic, 51% of the OHS (95% CI 0.38–0.62) offered weekend or out-of-hours (OOH) services, 21% had to employ extra staff (95% CI 0.13–0.33) and 54% had to change their working hours (95% CI 0.41–0.65). Ninety per cent of the OHS (95% CI 0.78–0.94) continued to offer routine services; however, there was a decline in offering vaccination services. Fifty-six per cent of the OHS (95% CI 0.42–0.67) offered a dedicated telephone line and 46% of the OHS (95% CI 0.32–0.56) started a dedicated COVID-19 queries inbox. Conclusions There was a change in the behaviour of the OHS to cope with the pandemic. Having a dedicated helpline to manage the crisis situation seemed a logical step whilst offering routine services.

The objective of the study was to assess the knowledge and perception of COVID-19 and relevant universal safety measures among the Nepalese population. A web-based cross-sectional study was conducted among Nepalese adults from March 29 to April 07, 2020. A 13- and 15- items structured questionnaire assessed the COVID-19 related knowledge and perception of the universal safety measure. Kruskal–Wallis test and Mann–Whitney U test evaluated the differences in knowledge between the groups. Data analysis was performed using IBM SPSS Statistics for Windows Version 21.0 (IBM Corp. Armonk, NY, USA). Of the 884 surveys accessed, a total of 871 consented (electronically) and completed the online survey (response rate 98.52%). The median knowledge score of the participants was 10.0 (± 3.0 IQR). Although participants’ overall knowledge score was high, only about half of the participants knew about the concept of quarantine and the ideal distance to be maintained between individuals to prevent the transmission. Though the majority of the participants had positive perception towards universal safety measure of COVID-19, about 18% perceived that coronavirus infected only older people, 11% opined that the infection was highly fatal with no chances of survival and 70% considered that limiting consumptions of poultry and meat would prevent the spread of COVID-19. A statistically significant difference in knowledge was noted by participants’ age, educational status, occupational type, and household monthly income. This study found optimal knowledge and perception of universal safety measures of COVID-19 among the Nepalese population, but misinformation and misunderstanding prevailed. Electronic supplementary material The online version of this article (10.1007/s10900-020-00839-3) contains supplementary material, which is available to authorized users.

The WHO has announced the novel coronavirus disease (COVID-19) outbreak to be a global pandemic. The distribution of community outbreaks shows seasonal patterns along certain latitude, temperature and humidity, that is, similar to the behaviour of seasonal viral respiratory tract infections. COVID-19 displays significant spread in northern mid-latitude countries with an average temperature of 5–11°C and low humidity. Vitamin D deficiency has also been described as pandemic, especially in Europe. Regardless of age, ethnicity and latitude, recent data showed that 40 % of Europeans are vitamin D deficient (25-hydroxyvitamin D (25(OH)D) levels

Motivation The outbreak of COVID-2019 initiated at Wuhan, China has become a global threat by rapid transmission and severe fatalities. Recent studies have uncovered whole genome sequence of SARS-CoV-2 (causing COVID-2019). In addition, lung metagenomic studies on infected patients revealed overrepresented Prevotella spp. producing certain proteins in abundance. We performed host–pathogen protein–protein interaction analysis between SARS-CoV-2 and overrepresented Prevotella proteins with human proteome. We also performed functional overrepresentation analysis of interacting proteins to understand their role in COVID-2019 severity. Results It was found that overexpressed Prevotella proteins can promote viral infection. As per the results, Prevotella proteins, but not viral proteins, are involved in multiple interactions with NF-kB, which is involved in increasing clinical severity of COVID-2019. Prevotella may have role in COVID-2019 outbreak and should be given importance for understanding disease mechanisms and improving treatment outcomes. Supplementary information Supplementary data are available at Bioinformatics online.

Currently, we are on a global pandemic of Coronavirus disease-2019 (COVID-19) which causes fever, dry cough, fatigue and acute respiratory distress syndrome (ARDS) that may ultimately lead to the death of the infected. Current researches on COVID-19 continue to highlight the necessity for further understanding the virus-host synergies. In this study, we have highlighted the key cytokines induced by coronavirus infections. We have demonstrated that genes coding interleukins (Il-1α, Il-1β, Il-6, Il-10), chemokine (Ccl2, Ccl3, Ccl5, Ccl10), and interferon (Ifn-α2, Ifn-β1, Ifn2) upsurge significantly which in line with the elevated infiltration of T cells, NK cells and monocytes in SARS-Cov treated group at 24 hours. Also, interleukins (IL-6, IL-23α, IL-10, IL-7, IL-1α, IL-1β) and interferon (IFN-α2, IFN2, IFN-γ) have increased dramatically in MERS-Cov at 24 hours. A similar cytokine profile showed the cytokine storm served a critical role in the infection process. Subsequent investigation of 463 patients with COVID-19 disease revealed the decreased amount of total lymphocytes, CD3+, CD4+, and CD8+ T lymphocytes in the severe type patients which indicated COVID-19 can impose hard blows on human lymphocyte resulting in lethal pneumonia. Thus, taking control of changes in immune factors could be critical in the treatment of COVID-19.

Purpose We aimed to report the clinical characteristics of 194 cases coronavirus disease-19 (COVID-19) in Huanggang, Hubei and Taian, Shandong. Methods We retrospectively investigated the clinical, laboratory characteristics and CT imaging of confirmed cases of COVID-19 from January 22 to February 28, 2020 in Huanggang Central Hospital and The Second Affiliated Hospital of Shandong First Medical University. Real time PCR was used to detect the new coronavirus in respiratory samples. Immunohistochemical staining was used to detect the expressions of ACE2 in tissues. Results Among the 194 patients infected with COVID-19, 108 patients were male, with a median age of 48.3 years. The average preclinical period was 7.44 day. Except for 37 severe or critically ill patients, the rest of the 157 patients exhibited mild or moderate symptoms. 190 (97.94%) patients were confirmed during the three times nucleic acid test. The main clinical symptom of the patients were fever, sore throat and cough, which accounted for 146 cases (75.26%), 98 (50.52%) and 86 cases (44.33%), respectively. 30 patients (15.46%) showed liver dysfunction. Imaging examination showed that 141 patients (72.68%) showed abnormal density shadow, while 53 cases (27.32%) had no obvious abnormality in the parenchyma of both lungs. Up to now, 109 cases have been discharged from the hospital, and 9 patients died. The ACE2 expression levels were up-regulated in patients of severe type and critically ill type. Conclusion Clinical symptoms, laboratory tests and CT imaging should be combined for comprehensive analysis to diagnose COVID-19. ACE2 may be the receptor of COVID-19. Electronic supplementary material The online version of this article (10.1007/s15010-020-01440-5) contains supplementary material, which is available to authorized users.

We aimed to describe typical radiological features and progression of Coronavirus disease 2019 (COVID-19) patients. We reviewed the chest CT scans, laboratory findings, and clinical records of 66 COVID-19 patients who were admitted to affiliated hospitals of Nanchang university, Nanchang, China, from Jan 21 to Feb 2, 2020. CT was used to evaluate the radiological characteristics of COVID-19 patients. Only 4 patients (4/66, 6%) claimed their exposure to COVID-19 pneumonia patients. The major symptoms were fever (60/66, 91%) and cough (37/66, 56%). The predominant features of lesion were scattered (43/66, 65%), bilateral (50/66, 76%), ground-glass opacity (64/66, 97%), and air bronchogram sign (47/66, 71%). Forty-eight patients (48/66, 73%) had more than two lobes involved. Right lower lobe (58/66, 88%) and left lower lobe (49/66, 74%) were most likely invaded. Twelve patients (12/66, 18%) had at least one comorbid condition. Pleural traction (29/66, 44%), crazy paving (15/66, 23%), interlobular septal thickening (11/66, 17%), and consolidation (7/66, 11%) were also observed. The typical radiology features of COVID-19 patients are scattered ground-glass opacity in the bilateral lobes. Fever and cough are the major symptoms. Evaluating chest CT, clinical symptoms, and laboratory results could facilitate the early diagnosis of COVID-19, and judge disease progression.

Being infected by SARS-CoV-2 may cause damage to multiple organs in patients, such as the lung, liver and heart. Angiotensin-converting enzyme 2 (ACE2), reported as a SARS-CoV-2 receptor, is also expressed in human male testes. This suggests a potential risk in human male reproductive system. However, the characteristics of ACE2-positive cells and the expression of other SARS-CoV-2 process-related genes are still worthy of further investigation. Here, we performed singlecell RNA seq (scRNA-seq) analysis on 853 male embryo primordial germ cells (PGCs) and 2,854 normal testis cells to assess the effects of the SARS-CoV-2 virus on the male reproductive system from embryonic stage to adulthood. We also collected and constructed the scRNA-seq library on 228 Sertoli cells from three non-obstructive azoospermia (NOA) patients to assess the effects at disease state. We found that ACE2 expressing cells existed in almost all testis cell types and Sertoli cells had highest expression level and positive cells ratio. Moreover, ACE2 was also expressed in human male PGCs. In adulthood, the level of ACE2 expression decreased with the increase of age. We also found that ACE2 positive cells had high expressions of stress response and immune activation-related genes. Interestingly, some potential SARS-CoV-2 process-related genes such as TMPRSS2, BSG, CTSL and CTSB had different expression patterns in the same cell type. Furthermore, ACE2 expression level in NOA donors’ Sertoli cells was significantly decreased. Our work would help to assess the risk of SARS-CoV-2 infection in the male reproductive system. Electronic Supplementary Material Supplementary material is available for this article at 10.1007/s11427-020-1705-0 and is accessible for authorized users.

Purpose This study aimed to describe the epidemiologic characteristics of fracture in the elderly during the COVID-19. Methods This was a retrospective multi-centre study, which included patients who sustained fractures between 20 January and 19 February 2020. The collected data included patients' demographics (age and gender), injury-related (injury type, fracture location, injury mechanism, places where fracture occurred), and treatment modality. SPSS 23.0 was used to describe the data and perform some analysis. Results A total of 436 patients with 453 fractures were included; there were 153 males and 283 females, with an average age of 76.2 years (standard deviation, SD, 7.7 years; 65 to 105). For either males or females, 70-74 years was the most commonly involved age group. A total of 317 (72.7%) patients had their fractures occurring at home. Among 453 fractures, there were 264 (58.3%) hip fractures, accounting for 58.3%. Fall from standing height was the most common cause of fracture, making a proportion of 89.4% (405/453). Most fractures (95.8%, 434/453) were treated surgically, and 4.2% (19/453) were treated by plaster fixation or traction. Open reduction and internal fixation (ORIF) was the most used surgical method, taking a proportion of 49.2% (223/453). Conclusion These findings highlighted the importance of primary prevention (home prevention) measures and could be used for references for individuals, health care providers, or health administrative department during the global pandemic of COVID-19.

Background: Anti-SARS-CoV-2 virus antibody levels in convalescent plasma (CP), which may be useful in severe Anti-SARS-CoV-2 virus infections, have been rarely reported. Results: A total of eight donors were considered for enrollment; two of them were excluded because of ineligible routine check. Of the six remaining participants, five samples were tested weakly positive by the IgM ELISA. Meanwhile, high titers of IgG were observed in five samples. The patient treated with CP did not require mechanical ventilation 11 days after plasma transfusion, and was then transferred to a general ward. Conclusions: Our serological findings in convalescent plasma from recovered patients may help facilitate understanding of the SARS-CoV-2 infection and establish CP donor screening protocol in COVID-19 outbreak. Methods: Anti-SARS-CoV-2 antibodies including IgM and IgG were measured by two enzyme-linked immunosorbent assays (ELISA) in convalescent plasma from six donors who have recovered from coronavirus disease 2019 (COVID-19) in Nanjing, China. CP was also utilized for the treatment of one severe COVID-19 patient.

Since the beginning of the COVID-19 epidemic in Italy, the Italian Government implemented several restrictive measures to contain the spread of the infection. Data shows that, among these measures, the lockdown implemented as of 9 March had a positive impact, in particular the central and southern regions of Italy, while other actions appeared to be less effective. When the true prevalence of a disease is unknown, it is possible estimate it, based on mortality data and the assumptive case-fatality rate of the disease. Given these assumptions, the estimated period-prevalence of COVID-19 in Italy varies from 0.35% in Sicity to 13.3% in Lombardy.

With the current trajectory of the 2019‐nCoV outbreak unknown, public health and medicinal measures will both be needed to contain spreading of the virus and to optimize patient outcomes. Although little is known about the virus, an examination of the genome sequence shows strong homology with its better‐studied cousin, SARS‐CoV. The spike protein used for host cell infection shows key nonsynonymous mutations that might hamper the efficacy of previously developed therapeutics but remains a viable target for the development of biologics and macrocyclic peptides. Other key drug targets, including RNA‐dependent RNA polymerase and coronavirus main proteinase (3CLpro), share a strikingly high (>95 %) homology to SARS‐CoV. Herein, we suggest four potential drug candidates (an ACE2‐based peptide, remdesivir, 3CLpro‐1 and a novel vinylsulfone protease inhibitor) that could be used to treat patients suffering with the 2019‐nCoV. We also summarize previous efforts into drugging these targets and hope to help in the development of broad‐spectrum anti‐coronaviral agents for future epidemics., What′s sauce for the goose? Little is known about the coronavirus causing the current outbreak; however, it shares strong sequence homology with its better‐studied cousin SARS‐CoV. Based on previous studies of targeting SARS‐CoV, we suggest four potential candidates that could be used to drug the viral spike protein, RNA‐dependent RNA polymerase, and coronavirus main proteinase.

The use of multipronged measures, including traditional Chinese medicine (TCM), has greatly increased in response to the COVID-19 pandemic, and we found the use of TCM and is positively correlated with the regional cure rate in China (R=0.77, P

Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2, with acute respiratory failure as the most significant symptom, has led to a global pandemic. Angiotensin-converting enzyme 2 (ACE2) is considered as the most important receptor of SARS-CoV-2 and wildly expressed in human tissues. Whereas, the extremely low expression of ACE2 in lung could hardly interpret the severe symptom of pneumonia in COVID-19 patients. Here we profiled two SARS-CoV-2 infection related genes, the transmembrane serine protease 2 (TMPRSS2) and the interferon-inducible transmembrane protein 3 (IFITM3), in human tissues and organs. Consistent with the expression and distribution of ACE2, TMPRSS2 was also highly expressed in digestive, urinary and reproductive systems, but low expressed in lung. Notably, the anti-virus protein IFITM3 also expressed much lower in lung than other tissues, which might be related to the severe lung symptoms of COVID-19. In addition, the low expression of IFITM3 in immune cells suggested that SARS-CoV-2 might attack lymphocytes and induce the cytokine release syndrome (CRS). Furthermore, cancer patients were considered as more susceptible to SARS-CoV-2 infection. Our data supposed that fourteen types of tumors might have different susceptibility to the virus according to ACE2, TMPRSS2 and IFITM3 expression patterns. Interestingly the prognosis of six types of cancers including breast carcinoma (BRCA), lung adenocarcinoma (LUAD), uterine corpus endometrial carcinoma (UCEC), renal clear cell carcinoma (KIRC), prostate adenocarcinoma (PRAD), and hepatocellular carcinoma (LIHC) were closely related to these gene expressions. Our study explored the expression and distribution profiles of two potential novel molecules that might participate in SARS-CoV-2 infection and involved in immunity, which may provide a functional basis for preventing infection of SARS-CoV-2.

Many studies have reported the risk factors for exacerbations in patients with 2019 novel coronavirus (2019-nCoV). This study aims to perform the meta-analysis of risk factors for the exacerbation of the novel coronavirus-infected pneumonia (NCIP). PubMed, Embase and Google scholar have been searched. We included the cohort studies involving risk factors for the exacerbation of NCIP. This meta-analysis compared the risk factors of patients between intensive care (ICU) group and non-ICU group. Two cohort studies were included in this study. After comparing the patients between intensive care (ICU) group and non-ICU group, several important factors were found to significantly increase the risk of exacerbations in patients with NCIP, and they included hypertension (RR=2.34; 95% CI=1.21 to 4.51; P=0.01), cardiovascular diseases (RR=2.28; 95% CI=1.13 to 4.58; P=0.02), COPD (RR=7.65; 95% CI=1.24 to 47.13; P=0.03), dyspnea (RR=2.89; 95% CI=2.05 to 4.08; P

The SARS-CoV-2 spread quickly across the globe. The World Health Organization (WHO) on March 11 declared COVID-19 a pandemic. The mortality rate, hospital disorders and incalculable economic and social damages, besides the unproven efficacy of the treatments evaluated against COVID-19, raised the need for immediate control of this disease. Therefore, the current study employed in silico tools to rationally identify new possible SARS-CoV-2 main protease (Mpro) inhibitors. That is an enzyme conserved among the coronavirus species; hence, the identification of an Mpro inhibitor is to make it a broad-spectrum drug. Molecular docking studies described the binding sites and the interaction energies of 74 Mpro-ligand complexes deposited in the Protein Data Bank (PDB). A structural similarity screening was carried out in order to identify possible Mpro ligands that show additional pharmacological properties against COVID-19. We identified 59 hit compounds and among them, melatonin stood out due to its prominent immunomodulatory and anti-inflammatory activities; it can reduce oxidative stress, defence cell mobility and efficiently combat the cytokine storm and sepsis. In addition, melatonin is an inhibitor of calmodulin, an essential intracellular component to maintain angiotensin-converting enzyme 2 (ACE-2) on the cell surface. Interestingly, one of the most promising hits in our docking study was melatonin. It revealed better interaction energy with Mpro compared to ligands in complexes from PDB. Consequently, melatonin can have response potential in early stages for its possible effects on ACE-2 and Mpro, although it is also promising in more severe stages of the disease for its action against hyper-inflammation. These results definitely do not confirm antiviral activity, but can rather be used as a basis for further preclinical and clinical trials.

The outbreak of pneumonia caused by SARS-CoV-2 posed a great threat to global human health, which urgently requires us to understand comprehensively the mechanism of SARS-CoV-2 infection. Angiotensin-converting enzyme 2 (ACE2) was identified as a functional receptor for SARS-CoV-2, distribution of which may indicate the risk of different human organs vulnerable to SARS-CoV-2 infection. Previous studies investigating the distribution of ACE2 mRNA in human tissues only involved a limited size of the samples and a lack of determination for ACE2 protein. Given the heterogeneity among humans, the datasets covering more tissues with a larger size of samples should be analyzed. Indeed, ACE2 is a membrane and secreted protein, while the expression of ACE2 in blood and common blood cells remains unknown. Herein, the proteomic data in HIPED and the antibody-based immunochemistry result in HPA were collected to analyze the distribution of ACE2 protein in human tissues. The bulk RNA-seq profiles from three separate public datasets including HPA tissue Atlas, GTEx, and FANTOM5 CAGE were also obtained to determine the expression of ACE2 in human tissues. Moreover, the abundance of ACE2 in human blood and blood cells was determined by analyzing the data in the PeptideAtlas and the HPA Blood Atlas. We found that the mRNA expression cannot reflect the abundance of ACE2 factor due to the strong differences between mRNA and protein quantities of ACE2 within and across tissues. Our results suggested that ACE2 protein is mainly expressed in the small intestine, kidney, gallbladder, and testis, while the abundance of which in brain-associated tissues and blood common cells is low. HIPED revealed enrichment of ACE2 protein in the placenta and ovary despite a low mRNA level. Further, human secretome shows that the average concentration of ACE2 protein in the plasma of males is higher than those in females. Our research will be beneficial for understanding the transmission routes and sex-based differences in susceptibility of SARS-CoV-2 infection.

Rationale: Some patients with coronavirus disease 2019 (COVID-19) rapidly develop respiratory failure or even die, underscoring the need for early identification of patients at elevated risk of severe illness. This study aims to quantify pneumonia lesions by computed tomography (CT) in the early days to predict progression to severe illness in a cohort of COVID-19 patients. Methods: This retrospective cohort study included confirmed COVID-19 patients. Three quantitative CT features of pneumonia lesions were automatically calculated using artificial intelligence algorithms, representing the percentages of ground-glass opacity volume (PGV), semi-consolidation volume (PSV), and consolidation volume (PCV) in both lungs. CT features, acute physiology and chronic health evaluation II (APACHE-II) score, neutrophil-to-lymphocyte ratio (NLR), and d-dimer, on day 0 (hospital admission) and day 4, were collected to predict the occurrence of severe illness within a 28-day follow-up using both logistic regression and Cox proportional hazard models. Results: We included 134 patients, of whom 19 (14.2%) developed any severe illness. CT features on day 0 and day 4, as well as their changes from day 0 to day 4, showed predictive capability. Changes in CT features from day 0 to day 4 performed the best in the prediction (area under the receiver operating characteristic curve = 0.93, 95% confidence interval [CI] 0.87~0.99; C-index=0.88, 95% CI 0.81~0.95). The hazard ratios of PGV and PCV were 1.39 (95% CI 1.05~1.84, P=0.023) and 1.67 (95% CI 1.17~2.38, P=0.005), respectively. CT features, adjusted for age and gender, on day 4 and in terms of changes from day 0 to day 4 outperformed APACHE-II, NLR, and d-dimer. Conclusions: CT quantification of pneumonia lesions can early and non-invasively predict the progression to severe illness, providing a promising prognostic indicator for clinical management of COVID-19.

The COVID-19 pandemic has stressed patients and healthcare givers alike and challenged our practice of antenatal care, including fetal diagnosis and therapy. This document aims to review relevant recent information to allow us to optimize prenatal care delivery. We discuss potential modifications to obstetric management and fetal procedures in SARS-CoV2-negative and SARS-CoV2-positive patients with fetal anomalies or disorders. Most fetal therapies are time sensitive and cannot be delayed. If personnel and resources are available, we should continue to offer procedures of proven benefit, acknowledging any fetal and maternal risks, including those to health care workers. There is, to date, minimal, unconfirmed evidence of spontaneous vertical transmission, though it may theoretically be increased with some procedures. Knowing a mother’s preoperative SARS-CoV-2 status would enable us to avoid or defer certain procedures while she is contagious and to protect health care workers appropriately. Some fetal conditions may alternatively be managed neonatally. Counseling regarding fetal interventions which have a possibility of additional intra- or postoperative morbidity must be performed in the context of local resource availability. Procedures of unproven benefit should not be offered. We encourage participation in registries and trials that may help us to understand the impact of COVID-19 on pregnant women, their fetuses, and neonates.

During the novel coronavirus disease 2019 (COVID-19) outbreak, traditional face-to-face psychological interventions have been suspended due to high risks of rapid transmission. Developing an effective online model of psychological intervention is deemed necessary to deal with the mental health challenges brought up by this disease. An integrated psychological intervention model coined 'COVID-19 Psychological Resilience Model' was developed in Chengdu, China including live media, 24-hour hotline consultations, online video intervention and on-site crisis intervention sessions to provide services to those in need. A total of 45 episodes of live media programs on COVID-19 outbreak-related psychological problems were broadcasted with over 10 million views. A total of 4,236 hotline consultations were completed. More than 50% of the clients had positive feedback about the hotline consultations. A total of 223 cases received online video intervention, of which 84.97% were redirected from the hotline consultation and 15.03% from COVID-19-designated hospital and community-based observation spots. Seventy one-on-one psychological interventions were conducted with 39 COVID-19 patients, and one-third were treated with medication. Additionally, 5 training sessions were conducted to 98 frontline medical staff. This 'COVID-19 Psychological Resilience Model' is proven effective to the general population during the COVID-19 pandemic. We have greatly improved the overall mental health of our target population during the COVID-19 pandemic. This model could provide valuable experiences and serve as a reference guide for other countries to offer effective psychological intervention, and reduce detrimental negative mental health outcomes in public health emergency.

Objective: To analyze the blood test indicators of patients after infection of COVID-19 in Chongqing and analyze the clinical indicators of 8 patients with diarrhea. Materials and Methods: From January 26, 2019 to February 13, 2020, 70 patients diagnosed with 2019-nCoV according to the World Health Organization interim guidance for NCP and divided into diarrhea and non-diarrhea groups. The laboratory tests liver and kidney function, blood routine, coagulation function, and immune status. Results: The study population included 70 hospitalized patients with confirmed CONV-2019. NCP patients (43males and 27 females) with a mean age of 48.57±17.80 (9~82) years and only 4.3% of patients have lung-related diseases. The positive rate of ESR, CRP, PT, IL6, lymphocyte count, GGT, Prealbumin and CD4 was more than 50%. We further analyzed the differences between 8 diarrhea patients and 62 non-diarrhea patients. Among these indicators, only Lymphocyte, CRP, Prealbumin and Cystatin C positive rate is more than 50%. Although there is no statistical difference in GGT, 100% of the 7 patients tested decreased. Conclusion: Our data recommended that the ESR, CRP, PT, IL6, lymphocyte count, GGT, prealbumin and CD4 have important value in the diagnosis of COVID-19, and the decrease of GGT may be an important indicator for judging the intestinal dysfunction of patients.

Rationale: To retrospectively analyze serial chest CT and clinical features in patients with coronavirus disease 2019 (COVID-19) for the assessment of temporal changes and to investigate how the changes differ in survivors and nonsurvivors. Methods: The consecutive records of 93 patients with confirmed COVID-19 who were admitted to Wuhan Union Hospital from January 10, 2020, to February 22, 2020, were retrospectively reviewed. A series of chest CT findings and clinical data were collected and analyzed. The serial chest CT scans were scored on a semiquantitative basis according to the extent of pulmonary abnormalities. Chest CT scores in different periods (0 - 5 days, 6 - 10 days, 11 - 15 days, 16 - 20 days, and > 20 days) since symptom onset were compared between survivors and nonsurvivors, and the temporal trend of the radiographic-clinical features was analyzed. Results: The final cohort consisted of 93 patients: 68 survivors and 25 nonsurvivors. Nonsurvivors were significantly older than survivors. For both survivors and nonsurvivors, the chest CT scores were not different in the first period (0 - 5 days) but diverged afterwards. The mortality rate of COVID-19 monotonously increased with chest CT scores, which positively correlated with the neutrophil-to-lymphocyte ratio, neutrophil percentage, D-dimer level, lactate dehydrogenase level and erythrocyte sedimentation rate, while negatively correlated with the lymphocyte percentage and lymphocyte count. Conclusions: Chest CT scores correlate well with risk factors for mortality over periods, thus they may be used as a prognostic indicator in COVID-19. While higher chest CT scores are associated with a higher mortality rate, CT images taken at least 6 days since symptom onset may contain more prognostic information than images taken at an earlier period.

Rationale: Chest computed tomography (CT) has been used for the coronavirus disease 2019 (COVID-19) monitoring. However, the imaging risk factors for poor clinical outcomes remain unclear. In this study, we aimed to assess the imaging characteristics and risk factors associated with adverse composite endpoints in patients with COVID-19 pneumonia. Methods: This retrospective cohort study enrolled patients with laboratory-confirmed COVID-19 from 24 designated hospitals in Jiangsu province, China, between 10 January and 18 February 2020. Clinical and initial CT findings at admission were extracted from medical records. Patients aged < 18 years or without available clinical or CT records were excluded. The composite endpoints were admission to ICU, acute respiratory failure occurrence, or shock during hospitalization. The volume, density, and location of lesions, including ground-glass opacity (GGO) and consolidation, were quantitatively analyzed in each patient. Multivariable logistic regression models were used to identify the risk factors among age and CT parameters associated with the composite endpoints. Results: In this study, 625 laboratory-confirmed COVID-19 patients were enrolled; among them, 179 patients without an initial CT at admission and 25 patients aged < 18 years old were excluded and 421 patients were included in analysis. The median age was 48.0 years and the male proportion was 53% (224/421). During the follow-up period, 64 (15%) patients had a composite endpoint. There was an association of older age (odds ratio [OR], 1.04; 95% confidence interval [CI]: 1.01-1.06; P = 0.003), larger consolidation lesions in the upper lung (Right: OR, 1.13; 95%CI: 1.03-1.25, P =0.01; Left: OR,1.15; 95%CI: 1.01-1.32; P = 0.04) with increased odds of adverse endpoints. Conclusion: There was an association of older age and larger consolidation in upper lungs on admission with higher odds of poor outcomes in patients with COVID-19.

Rationale: The clinical data and corresponding dynamic CT findings were investigated in detail to describe the clinical and imaging profiles of COVID-19 pneumonia disease progression. Methods: Forty HCWs with COVID-19 were included in this study and 30 enrolled for imaging assessment. Disease was divided into four stages based on time from onset: stage 1 (1-6 days), stage 2 (7-13 days), stage 3 (14-22 days), and stage 4 (> 22 days). Clinical wand imaging data were analyzed retrospectively. Results: The cohort included 33 female and 7 male cases, with a median age of 40 years. Six had underlying comorbidities. More than half of the cases were nurses (22, 55%). Each stage included 39, 37, 34 and 32 CTs, respectively. Bilateral lesions, multifocal lesions and lesions with GGO pattern occurred in both lower lobes at all stages. The crazy-paving pattern (20, 54%), air bronchogram (13, 35%), and pleural effusion (2, 5%) were the most common CT features in stage 2. Consolidation score peaked in stage 2 whereas total lesions score peaked in stage 3. Conclusions: COVID-19 pneumonia in HCWs has a potential predilection for younger female workers. Stage 2 of COVID-19 pneumonia may be the key period for controlling progression of the disease, and consolidation scores may be an objective reflection of the severity of lung involvement.

Background: Lactate dehydrogenase (LDH) has been proved to be a prognostic factor for the severity and poor outcomes of coronavirus disease 2019 (COVID-19). In most studies, patients with various levels of COVID-19 severity were pooled and analyzed which may prevent accurate evaluation of the relationship between LDH and disease progression and in-hospital death. In this study, we aimed to evaluate the association of LDH with in-hospital mortality in severe and critically ill patients with COVID-19. Methods: This single-center retrospective study enrolled 119 patients. Survival curves were plotted using Kaplan-Meier method and compared by log-rank test. Multivariate Cox regression models were used to determine the independent risk factors for in-hospital mortality. Receiver-operator curves (ROCs) were constructed to evaluate the predictive accuracy of LDH and other prognostic biomarkers. Results: Compared to the survival group, LDH levels in the dead group were significantly higher [559.5 (172, 7575) U/L vs 228 (117, 490) U/L, (P < 0.001)]. In Multivariate Cox regression, it remained an independent risk factor for in-hospital mortality (Hazard ratio 5.985, 95.0%CI: 1.498-23.905; P=0.011). A cutoff value of 353.5 U/L predicted the in-hospital mortality with a sensitivity of 94.4% and a specificity of 89.2% respectively. Conclusion: LDH is a favorable prognostic biomarker with high accuracy for predicting in-hospital mortality in severe and critically ill patients with COVID-19. This may direct physicians worldwide to effectively prioritize resources for patients at high risk of death and to implement more aggressive treatments at an earlier phase to save patients' lives.

Rationale: Up to date, the exploration of clinical features in severe COVID-19 patients were mostly from the same center in Wuhan, China. The clinical data in other centers is limited. This study aims to explore the feasible parameters which could be used in clinical practice to predict the prognosis in hospitalized patients with severe coronavirus disease-19 (COVID-19). Methods: In this case-control study, patients with severe COVID-19 in this newly established isolation center on admission between 27 January 2020 to 19 March 2020 were divided to discharge group and death event group. Clinical information was collected and analyzed for the following objectives: 1. Comparisons of basic characteristics between two groups; 2. Risk factors for death on admission using logistic regression; 3. Dynamic changes of radiographic and laboratory parameters between two groups in the course. Results: 124 patients with severe COVID-19 on admission were included and divided into discharge group (n=35) and death event group (n=89). Sex, SpO2, breath rate, diastolic pressure, neutrophil, lymphocyte, C-reactive protein (CRP), procalcitonin (PCT), lactate dehydrogenase (LDH), and D-dimer were significantly correlated with death events identified using bivariate logistic regression. Further multivariate logistic regression demonstrated a significant model fitting with C-index of 0.845 (p77.35mg/L, PCT>0.20μg/L, and LDH>481U/L were the independent risk factors with the ORs of 2.959, 4.015, 2.852, 3.554, and 3.185, respectively (p

Rationale: Coronavirus disease 2019 (COVID-19) was first announced in Wuhan, and has rapidly evolved into a pandemic. However, the risk factors associated with the severity and mortality of COVID-19 are yet to be described in detail. Methods: We retrospectively reviewed the information of 1525 cases from the Leishenshan Hospital in Wuhan. Univariate and multivariate Cox regression analyses were generated to explore the relationship between procalcitonin (PCT) level and the progression and prognosis of COVID-19. Univariate and multivariate logistic regression analyses were performed to explore the relationship between disease severity in hospitalized patients and their PCT levels. Survival curves and the cumulative hazard function for COVID-19 progression were conducted in the two groups. To further detect the relationship between the computed tomography score and survival days, curve-fitting analyses were performed. Results: Patients in the elevated PCT group had a higher incidence of severe and critical severity conditions (P < 0.001), death, and higher computed tomography (CT) scores. There was an association between elevated PCT levels and mortality in the univariate ((hazard ratio [1], 3.377; 95% confidence interval [2], 1.012-10.344; P = 0.033) and multivariate Cox regression analysis (HR, 4.933; 95% CI, 1.170-20.788; P = 0.030). Similarly, patients with elevated PCT were more likely to have critically severe disease conditions in the univariate (odds ratio [2], 7.247; 95% CI, 3.559-14.757; P < 0.001) and multivariate logistic regression analysis (OR, 10.679; 95% CI, 4.562-25.000; P < 0.001). Kaplan-Meier curves showed poorer prognosis for patients with elevated PCT (P = 0.024). The CT score 1 for patients with elevated PCT peaked at day 40 following the onset of symptoms then decreased gradually, while their total CT score was relatively stable. Conclusion: PCT level was shown as an independent risk factor of in-hospital mortality among COVID-19 patients. Compared with inpatients with normal PCT levels, inpatients with elevated PCT levels had a higher risk for overall mortality and critically severe disease. These findings may provide guidance for improving the prognosis of patients with critically severe COVID-19.

The emerging coronavirus diseases such as COVID-19, MERS, and SARS indicated that animal coronaviruses (CoVs) spillover to humans are a huge threat to public health. Therefore, we needed to understand the CoVs carried by various animals. Wild hedgehogs were collected from rural areas in Wuhan and Xianning cities in Hubei Province for analysis of CoVs. PCR results showed that 5 out of 51 (9.8%) hedgehogs (Erinaceus amurensis) were positive to CoVs in Hubei Province with 3 samples from Wuhan City and 2 samples from Xianning City. Phylogenetic analysis based on the partial sequence of RNA-dependent RNA polymerase showed that the CoVs from hedgehogs are classified into Merbecovirus of the genus Betacoronavirus; the hedgehog CoVs formed a phylogenetic sister cluster with human MERS-CoVs and bat MERS-related CoVs. Among the 12 most critical residues of receptor binding domain in MERS-CoV for binding human Dipeptidyl peptidase 4, 3 residuals were conserved between the hedgehog MERS-related CoV obtained in this study and the human MERS-CoV. We concluded that hedgehogs from Hubei Province carried MERS-related CoVs, indicating that hedgehogs might be important in the evolution and transmission of MERS-CoVs, and continuous surveillance of CoVs in hedgehogs was important.

Background As the COVID-19 epidemic increases in severity, the burden of quarantine stations outside emergency departments (EDs) at hospitals is increasing daily. To address the high screening workload at quarantine stations, all staff members with medical licenses are required to work shifts in these stations. Therefore, it is necessary to simplify the workflow and decision-making process for physicians and surgeons from all subspecialties. Objective The aim of this paper is to demonstrate how the National Cheng Kung University Hospital artificial intelligence (AI) trilogy of diversion to a smart quarantine station, AI-assisted image interpretation, and a built-in clinical decision-making algorithm improves medical care and reduces quarantine processing times. Methods This observational study on the emerging COVID-19 pandemic included 643 patients. An “AI trilogy” of diversion to a smart quarantine station, AI-assisted image interpretation, and a built-in clinical decision-making algorithm on a tablet computer was applied to shorten the quarantine survey process and reduce processing time during the COVID-19 pandemic. Results The use of the AI trilogy facilitated the processing of suspected cases of COVID-19 with or without symptoms; also, travel, occupation, contact, and clustering histories were obtained with the tablet computer device. A separate AI-mode function that could quickly recognize pulmonary infiltrates on chest x-rays was merged into the smart clinical assisting system (SCAS), and this model was subsequently trained with COVID-19 pneumonia cases from the GitHub open source data set. The detection rates for posteroanterior and anteroposterior chest x-rays were 55/59 (93%) and 5/11 (45%), respectively. The SCAS algorithm was continuously adjusted based on updates to the Taiwan Centers for Disease Control public safety guidelines for faster clinical decision making. Our ex vivo study demonstrated the efficiency of disinfecting the tablet computer surface by wiping it twice with 75% alcohol sanitizer. To further analyze the impact of the AI application in the quarantine station, we subdivided the station group into groups with or without AI. Compared with the conventional ED (n=281), the survey time at the quarantine station (n=1520) was significantly shortened; the median survey time at the ED was 153 minutes (95% CI 108.5-205.0), vs 35 minutes at the quarantine station (95% CI 24-56; P Conclusions The AI trilogy improved our medical care workflow by shortening the quarantine survey process and reducing the processing time, which is especially important during an emerging infectious disease epidemic.

The COVID-19 pandemic has modified organisation and processes of primary care. In this paper, we aim to summarise experiences of international primary care systems. We explored personal accounts and findings in reporting on the early experiences from primary care during the pandemic, through the online Global Forum on Universal Health Coverage and Primary Health Care. During the early stage of the pandemic, primary care continued as the first point of contact to the health system but was poorly informed by policy makers on how to fulfil its role and ill equipped to provide care while protecting staff and patients against further spread of the infection. In many countries, the creativity and initiatives of local health professionals led to the introduction or extension of the use of telephone, e-mail and virtual consulting, and introduced triaging to separate ‘suspected)’ COVID-19 from non-COVID-19 care. There were substantial concerns of collateral damage to the health of the population due to abandoned or postponed routine care. The pandemic presents important lessons to strengthen health systems through better connection between public health, primary care, and secondary care to cope better with future waves of this and other pandemics. KEY MESSAGES It was fairly easy to convince the population to postpone contact with primary care in the first days when practices had to carry out a reorganisation and innovate to the new situation. The bigger problem was encouraging people to resume seeking care as usual as quickly as possible.

The objective of this study was to describe the epidemiology of COVID-19 in Nigeria with a view of generating evidence to enhance planning and response strategies. A national surveillance dataset between 27 February and 6 June 2020 was retrospectively analysed, with confirmatory testing for COVID-19 done by real-time polymerase chain reaction (RT-PCR). The primary outcomes were cumulative incidence (CI) and case fatality (CF). A total of 40 926 persons (67% of total 60 839) had complete records of RT-PCR test across 35 states and the Federal Capital Territory, 12 289 (30.0%) of whom were confirmed COVID-19 cases. Of those confirmed cases, 3467 (28.2%) had complete records of clinical outcome (alive or dead), 342 (9.9%) of which died. The overall CI and CF were 5.6 per 100 000 population and 2.8%, respectively. The highest proportion of COVID-19 cases and deaths were recorded in persons aged 31–40 years (25.5%) and 61–70 years (26.6%), respectively; and males accounted for a higher proportion of confirmed cases (65.8%) and deaths (79.0%). Sixty-six per cent of confirmed COVID-19 cases were asymptomatic at diagnosis. In conclusion, this paper has provided an insight into the early epidemiology of COVID-19 in Nigeria, which could be useful for contextualising public health planning.

The clinical features of COVID-19 pneumonia range from a mild illness to patients with a very severe illness with acute hypoxemic respiratory failure requiring ventilation and Intensive Care Unit admission.To provide a brief overview of the existing evidence for such differences in host response and outcome, and generate hypotheses for divergent patterns and avenues for future research, by highlighting similarities and differences in histopathological appearance between COVID-19 and influenza as well as previous coronavirus outbreaks, and by discussing predisposition through genetics and underlying disease.We assessed the available early literature for histopathological patterns of COVID-19 pneumonia and underlying risk factors.The histopathological spectrum of COVID-19 pneumonia includes variable patterns of epithelial damage, vascular complications, fibrosis and inflammation. Risk factors for a fatal disease include older age, respiratory disease, diabetes mellitus, obesity and hypertension.While some risk factors and their potential role in COVID-19 pneumonia are increasingly recognized, little is known about the mechanisms behind episodes of sudden deterioration or the infrequent idiosyncratic clinical demise in otherwise healthy and young subjects.The answer to many of the remaining questions regarding COVID-19 pneumonia pathogenesis may in time be provided by genotyping as well careful clinical, serological, radiological and histopathological phenotyping.

Background The COVID-19 pandemic has necessitated a rapid increase of space in highly infectious disease intensive care units (ICUs). At Houston Methodist Hospital (HMH), a virtual intensive care unit (vICU) was used amid the COVID-19 outbreak. Objective The aim of this paper was to detail the novel adaptations and rapid expansion of the vICU that were applied to achieve patient-centric solutions while protecting staff and patients’ families during the pandemic. Methods The planned vICU implementation was redirected to meet the emerging needs of conversion of COVID-19 ICUs, including alterations to staged rollout timing, virtual and in-person staffing, and scope of application. With the majority of the hospital critical care physician workforce redirected to rapidly expanded COVID-19 ICUs, the non–COVID-19 ICUs were managed by cardiovascular surgeons, cardiologists, neurosurgeons, and acute care surgeons. HMH expanded the vICU program to fill the newly depleted critical care expertise in the non–COVID-19 units to provide urgent, emergent, and code blue support to all ICUs. Results Virtual family visitation via the Consultant Bridge application, palliative care delivery, and specialist consultation for patients with COVID-19 exemplify the successful adaptation of the vICU implementation. Patients with COVID-19, who were isolated and separated from their families to prevent the spread of infection, were able to virtually see and hear their loved ones, which bolstered the mental and emotional status of those patients. Many families expressed gratitude for the ability to see and speak with their loved ones. The vICU also protected medical staff and specialists assigned to COVID-19 units, reducing exposure and conserving personal protective equipment. Conclusions Telecritical care has been established as an advantageous mechanism for the delivery of critical care expertise during the expedited rollout of the vICU at Houston Methodist Hospital. Overall responses from patients, families, and physicians are in favor of continued vICU care; however, further research is required to examine the impact of innovative applications of telecritical care in the treatment of critically ill patients.

The COVID-19 pandemic has led to an exponential increase in SARS-CoV-2 infections and associated deaths, and represents a significant challenge to healthcare professionals and facilities. Individual countries have taken several prevention and containment actions to control the spread of infection, including measures to guarantee safety of both healthcare professionals and patients who are at increased risk of infection from COVID-19. Faecal microbiota transplantation (FMT) has a well-established role in the treatment of Clostridioides difficile infection. In the time of the pandemic, FMT centres and stool banks are required to adopt a workflow that continues to ensure reliable patient access to FMT while maintaining safety and quality of procedures. In this position paper, based on the best available evidence, worldwide FMT experts provide guidance on issues relating to the impact of COVID-19 on FMT, including patient selection, donor recruitment and selection, stool manufacturing, FMT procedures, patient follow-up and research activities.

The unpredictability and uncertainty of the COVID-19 pandemic; the associated lockdowns, physical distancing, and other containment strategies; and the resulting economic breakdown could increase the risk of mental health problems and exacerbate health inequalities. Preliminary findings suggest adverse mental health effects in previously healthy people and especially in people with pre-existing mental health disorders. Despite the heterogeneity of worldwide health systems, efforts have been made to adapt the delivery of mental health care to the demands of COVID-19. Mental health concerns have been addressed via the public mental health response and by adapting mental health services, mostly focusing on infection control, modifying access to diagnosis and treatment, ensuring continuity of care for mental health service users, and paying attention to new cases of mental ill health and populations at high risk of mental health problems. Sustainable adaptations of delivery systems for mental health care should be developed by experts, clinicians, and service users, and should be specifically designed to mitigate disparities in health-care provision. Thorough and continuous assessment of health and service-use outcomes in mental health clinical practice will be crucial for defining which practices should be further developed and which discontinued. For this Position Paper, an international group of clinicians, mental health experts, and users of mental health services has come together to reflect on the challenges for mental health that COVID-19 poses. The interconnectedness of the world made society vulnerable to this infection, but it also provides the infrastructure to address previous system failings by disseminating good practices that can result in sustained, efficient, and equitable delivery of mental health-care delivery. Thus, the COVID-19 pandemic could be an opportunity to improve mental health services. CM and CA are co-financed by the European Regional Development Fund; have received support from the Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III (SAM16PE07CP1, PI16/02012, PI17/02227, and PI19/024), the European Commission; CIBERSAM, the Madrid Regional Government (B2017/BMD-3740 AGES-CM-2), Fundación Familia Alonso, Fundación Alicia Koplowitz, and Fundación Mutua Madrileña; and have received European Union Structural Funds via the European Union Seventh Framework (FP7-4-HEALTH-2009-2.2.1-2-241909, FP7-HEALTH-2013-2.2.1-2-603196, and FP7-HEALTH-2013-2.2.1-2-602478) and the European Union H2020 programme under the Innovative Medicines Initiative 2 Joint Undertaking (115916 and 777394). TW acknowledges support from the National Institute for Health Research Maudsley Biomedical Research Centre at the South London and Maudsley NHS Foundation Trust and King’s College London (IS-BRC-1215-20018) and the National Institute for Health Research Senior Investigator Award (NF-SI-0514-10028). MRP acknowledges support from the National Natural Science Foundation of China (81371502 and 81761128031). EV acknowledges the support of the Spanish Ministry of Science and Innovation (PI15/00283 and PI18/00805), funding that was integrated into the Plan Nacional de I+D+I and co-financed by the ISCIII—Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional; the Instituto de Salud Carlos III; CIBERSAM; the Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement (2017 SGR 1365); the CERCA Programme; and the Departament de Salut de la Generalitat de Catalunya (PERIS grant SLT006/17/00357). MC is supported by a European Research Council Consolidator Award (iHear 724809). We acknowledge Giulia Maria Giordano (University of Campania “Luigi Vanvitelli”, Naples, Italy) and Pasquale Pezzella (University of Campania “Luigi Vanvitelli”, Naples, Italy).

Background COVID-19 has disproportionately affected older people. Objective The objective of this paper to investigate whether frailty is associated with all-cause mortality in older hospital inpatients, with COVID-19. Design Cohort study. Setting Secondary care acute hospital. Participants Participants included are 677 consecutive inpatients aged 65 years and over. Methods Cox proportional hazards models were used to examine the association of frailty with mortality. Frailty was assessed at baseline, according to the Clinical Frailty Scale (CFS), where higher categories indicate worse frailty. Analyses were adjusted for age, sex, deprivation, ethnicity, previous admissions and acute illness severity. Results Six hundred and sixty-four patients were classified according to CFS. Two hundred and seventy-one died, during a mean follow-up of 34.3 days. Worse frailty at baseline was associated with increased mortality risk, even after full adjustment (P = 0.004). Patients with CFS 4 and CFS 5 had non-significant increased mortality risks, compared to those with CFS 1–3. Patients with CFS 6 had a 2.13-fold (95% CI 1.34–3.38) and those with CFS 7–9 had a 1.79-fold (95% CI 1.12–2.88) increased mortality risk, compared to those with CFS 1–3 (P = 0.001 and 0.016, respectively). Older age, male sex and acute illness severity were also associated with increased mortality risk. Conclusions Frailty is associated with all-cause mortality risk in older inpatients with COVID-19.

Background The aim of this clinical trial was to evaluate the effects of febuxostat (FBX) in comparison with hydroxychloroquine (HCQ) on clinical symptoms, laboratory tests and chest CT findings in outpatients with moderate symptoms of COVID-19 infection. Methods We conducted a clinical trial involving adult outpatients with the moderate respiratory illness following COVID-19 infection. Patients were randomly assigned to receive either FBX or HCQ for 5 days. The measured variables were needs to hospitalisation, clinical and laboratory data including fever, cough, breathing rate, C-Reactive Protein level, lymphocytes count at onset of admission and was well as at 5 days of treatments. In addition, CT findings were evaluated on admission and 14 days after initiation of treatment. Results Sixty subjects were enrolled in the study with a 1 to 1 ratio in FBX and HCQ groups. On admission, fever (66.7%), cough (87%), tachypnoea (44.4%), dyspnoea (35%), elevated CRP value (94.4%) and lung involvement according to chest CT (100%) were documented in enrolled patients with insignificant difference between FBX and HCQ groups. Fever, cough and tachypnoea were significantly mitigated in both groups after five days of treatments without any significant differences between groups. The mean percentages of lung involvement were significantly reduced to 7.3% and 8% after 14 days of treatment with FBX and HCQ, respectively. In adult outpatients with moderate COVID-19 infection, the effectiveness of FBX and HCQ was not different in terms of resolution of clinical manifestations, laboratory tests and lung CT findings. Conclusion This trial suggests that FBX is as an alternative treatment to HCQ for COVID-19 infection and may be considered in patients with a contraindication or precaution to HCQ.

The devastating effects of the coronavirus designated severe acute respiratory syndrome coronavirus 2 (SARS‐Cov‐2) has led to urgent attempts to find effective therapeutic agents for inpatient and outpatient treatment of COVID‐19. Initial enthusiasm for the combination of hydroxychloroquine and azithromycin has abated. However, as a result of positive clinical experience with azithromycin used alone during the first few days of the flu‐like illness caused by this coronavirus, we recommend formal clinical trials using azithromycin early in the course of a COVID‐19 infection. There is one clinical trial initiated, the individually‐randomized, telemedicine‐based, “Azithromycin for COVID‐19 Treatment in Outpatients Nationwide (ACTION)” based at the University of California San Francisco. This placebo‐controlled trial is designed to determine the efficacy of a single 1.2 g dose of oral azithromycin to prevent COVID‐19 patient progression to hospitalization. We recommend formal clinical trials of azithromycin in its prepackaged form at the first sign of COVID‐19 infection in adults and children, using an initial adult dose of 500 mg followed by 250 mg per day for four days, a total cumulative dose of 1.5 g, and for children 5 to 18 years of age, 10 mg/kg on the first day followed by 5 mg/kg for four days. This article is protected by copyright. All rights reserved.

SARS‐COV‐2 is a highly virulent positive‐sense single stranded RNA virus that spreads rapidly via respiratory droplets, causing severe acute respiratory syndromes with significant mortality and morbidity. Currently 210 countries and territories are affected around the world with a reported 2.6 million confirmed cases.1 The COVID 19 pandemic has changed the way patients attend their specialist appointments and receive medical care. Whilst some specialist clinics have closed we have implemented strategies and restructured our academic practice in Australia to minimize the spread of disease whilst treating patients who need urgent care. We hope to share these strategies in the hope they may be useful to the dermatology community. This article is protected by copyright. All rights reserved.

Background The outbreak of COVID-19 has profoundly influenced people’s lifestyles; these impacts have varied across subgroups of people. The pandemic-related impacts on the health outcomes of people with dermatological conditions are unknown. Objective The aim of this paper was to study the association of COVID-19 pandemic–related impacts with health-related quality of life in patients with skin diseases. Methods This was a cross-sectional study among Chinese patients with skin diseases. A self-administered web-based questionnaire was distributed through social media. Demographic and clinical data and pandemic-related impacts (isolation status, income changes, and employment status) were collected. The main outcomes included perceived stress (Visual Analog Scale), symptoms of anxiety (Generalized Anxiety Disorder-7) and depression (9-Item Patient Health Questionnaire), quality of life (Dermatology Life Quality Index), and health utility mapping based on the EQ-5D-3L descriptive system. Multivariable logistic regression was used to investigate the associations. Results A total of 506 patients with skin diseases completed the survey. The mean age of the patients was 33.5 years (SD 14.0), and 217/506 patients (42.9%) were male. Among the 506 respondents, 128 (25.3%) were quarantined, 102 (20.2%) reported unemployment, and 317 (62.6%) reported decrease or loss of income since the pandemic. The pandemic-related impacts were significantly associated with impaired mental well-being and quality of life with different effects. Unemployment and complete loss of income were associated with the highest risks of adverse outcomes, with increases of 110% to 162% in the prevalence of anxiety, depression, and impaired quality of life. Conclusions Isolation, income loss, and unemployment are associated with impaired health-related quality of life in patients with skin diseases during the COVID-19 pandemic.

The epidemiological burden of COVID-19 is a healthcare challenge throughout the world, not only in terms of testing the limits of medical capacities, but also as an enigma considering preventive strategies and methods. The upper respiratory tract mucosa is the first line of defense, as a physical barrier, as well as through multiple innate and adaptive immune mechanisms which are crucial for efficient antiviral responses. Identifying methods able to reduce or prevent colonization, viral adhesion, and promote virus shedding on mucous membranes or have the ability to inactivate pathogens and thus reduce virus dose and/or increase immune response would be essential in the management of COVID-19 outbreak and help in flattening the curve. We review the effects of propolis, an old remedy with proven antiviral properties, as a possible low-cost inhibitor of SARS-CoV-2 in the oropharyngeal niche, prophylaxis, or adjuvant therapy.

Background Coronavirus disease (COVID-19) is a type of pneumonia caused by a novel coronavirus that was discovered in 2019. As of May 6, 2020, 84,407 cases and 4643 deaths have been confirmed in China. The Chinese population has expressed great concern since the COVID-19 outbreak. Meanwhile, an average of 1 billion people per day are using the Baidu search engine to find COVID-19–related health information. Objective The aim of this paper is to analyze web search data volumes related to COVID-19 in China. Methods We conducted an infodemiological study to analyze web search data volumes related to COVID-19. Using Baidu Index data, we assessed the search frequencies of specific search terms in Baidu to describe the impact of COVID-19 on public health, psychology, behaviors, lifestyles, and social policies (from February 11, 2020, to March 17, 2020). Results The search frequency related to COVID-19 has increased significantly since February 11th. Our heat maps demonstrate that citizens in Wuhan, Hubei Province, express more concern about COVID-19 than citizens from other cities since the outbreak first occurred in Wuhan. Wuhan citizens frequently searched for content related to “medical help,” “protective materials,” and “pandemic progress.” Web searches for “return to work” and “go back to school” have increased eight-fold compared to the previous month. Searches for content related to “closed community and remote office” have continued to rise, and searches for “remote office demand” have risen by 663% from the previous quarter. Employees who have returned to work have mainly engaged in the following web searches: “return to work and prevention measures,” “return to work guarantee policy,” and “time to return to work.” Provinces with large, educated populations (eg, Henan, Hebei, and Shandong) have been focusing on “online education” whereas medium-sized cities have been paying more attention to “online medical care.” Conclusions Our findings suggest that web search data may reflect changes in health literacy, social panic, and prevention and control policies in response to COVID-19.

In the era of coronavirus disease 2019 (COVID-19), many healthcare professionals are being faced with the question of what is considered to be an essential service. This opinion paper has attempted to answer this complex question by understanding the potential relationship between dysphagia and COVID-19 and how speech-language therapists (SLTs) in South Africa should tackle this. It also aims to answer the question through the lens of a risk-benefit discussion based around practices and decision-making. Important gaps in the field relating to how SLT practices need to move forward during this challenging time have also been highlighted. Reflective questions that can assist SLTs when seeing dysphagia cases have been provided.