Glycyrrhizin as a promising kryptonite against SARS-CoV-2: Clinical, experimental, and theoretical evidences.

COVID-19 is the most devastating disease in recent times affecting most people globally. The higher rate of transmissibility and mutations of SARS-CoV-2 along with the lack of potential therapeutics has made it a global crisis. Potential molecules from natural sources could be a fruitful remedy to combat COVID-19. This systematic review highlights the detailed therapeutic implication of naturally occurring glycyrrhizin and its related derivatives against COVID-19. Glycyrrhizin has already been established for blocking different biomolecular targets related to the SARS-CoV-2 replication cycle. In this article, several experimental and theoretical evidences of glycyrrhizin and related derivatives have been discussed in detail to evaluate their potential as a promising therapeutic strategy against COVID-19. Moreover, the implication of glycyrrhizin in traditional Chinese medicines for alleviating the symptoms of COVID-19 has been reviewed. The potential role of glycyrrhizin and related compounds in affecting various stages of the SARS-CoV-2 life cycle has also been discussed in detail. Derivatization of glycyrrhizin for designing potential lead compounds along with combination therapy with other anti-SARS-CoV-2 agents followed by extensive evaluation may assist in the formulation of novel anti-coronaviral therapy for better treatment to combat COVID-19.

Equipment-free, salt-mediated immobilization of nucleic acids for nucleic acid lateral flow assays.

As the world has been facing several deadly virus crises, including Zika virus disease, Ebola virus disease, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and Coronavirus disease 2019 (COVID-19), lateral flow assays (LFAs), which require minimal equipment for point-of-care of viral infectious diseases, are garnering much attention. Accordingly, there is an increasing demand to reduce the time and cost required for manufacturing LFAs. The current study introduces an equipment-free method of salt-mediated immobilization of nucleic acids (SAIoNs) for LFAs. Compared to general DNA immobilization methods such as streptavidin-biotin, UV-irradiation, and heat treatment, our method does not require special equipment (e.g., centrifuge, UV-crosslinker, heating device); therefore, it can be applied in a resource-limited environment with reduced production costs. The immobilization process was streamlined and completed within 30 min. Our method improved the color intensity signal approximately 14 times compared to the method without using SAIoNs and exhibited reproducibility with the long-term storage stability. The proposed method can be used to detect practical targets (e.g., SARS-CoV-2) and facilitates highly sensitive and selective detection of target nucleic acids with multiplexing capability and without any cross-reactivity. This novel immobilization strategy provides a basis for easily and inexpensively developing nucleic acid LFAs combined with various types of nucleic acid amplification.

Single domain antibodies derived from ancient animals as broadly neutralizing agents for SARS-CoV-2 and other coronaviruses.

With severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as an emergent human virus since December 2019, the world population is susceptible to coronavirus disease 2019 (COVID-19). SARS-CoV-2 has higher transmissibility than the previous coronaviruses, associated by the ribonucleic acid (RNA) virus nature with high mutation rate, caused SARS-CoV-2 variants to arise while circulating worldwide. Neutralizing antibodies are identified as immediate and direct-acting therapeutic against COVID-19. Single-domain antibodies (sdAbs), as small biomolecules with non-complex structure and intrinsic stability, can acquire antigen-binding capabilities comparable to conventional antibodies, which serve as an attractive neutralizing solution. SARS-CoV-2 spike protein attaches to human angiotensin-converting enzyme 2 (ACE2) receptor on lung epithelial cells to initiate viral infection, serves as potential therapeutic target. sdAbs have shown broad neutralization towards SARS-CoV-2 with various mutations, effectively stop and prevent infection while efficiently block mutational escape. In addition, sdAbs can be developed into multivalent antibodies or inhaled biotherapeutics against COVID-19.

Telemedicine: A cornerstone of healthcare assistance during the SARS-Cov2 pandemic outbreak but also a great opportunity for the near future.

At the end of 2019, Wuhan, China, experienced an outbreak of a novel coronavirus. The SARS-CoV2 epidemiologic burden was constantly evolving, with numbers of infected persons, hospital admissions and deaths growing near exponentially. The pandemic outbreak of COVID-19 worldwide caught the health care systems in every country by storm and without a proper defense mechanism to cope and control such a pandemic, causing an overwhelming burden of illnesses that stressed the Health System capacity. In this context, telemedicine has been promoted and scaled up to reduce the risk of transmission. During the "lockdown", the AOU "Federico II" was forced to create peculiar pathways to ensure the safety of the patients and medical staff, and to keep an appropriate medical assistance, therefore it was introduced the telemedicine, wherever possible, by modifying the Information Technology (IT) related to the waiting times, rescheduling all booked visits and identifying several outpatient clinics suitable for telemedicine activities. In this paper the Authors reports their own experience with Telemedicine.

Risk factors for impaired pulmonary diffusion function in convalescent COVID-19 patients: A systematic review and meta-analysis.

Background: The long-term prognosis of COVID-19 survivors remains poorly understood. It is evidenced that the lung is the main damaged organ in COVID-19 survivors, most notably in impairment of pulmonary diffusion function. Hence, we conducted a meta-analysis of the potential risk factors for impaired diffusing capacity for carbon monoxide (DLCO) in convalescent COVID-19 patients. Methods: We performed a systematic search of PubMed, Web of Science, Embase, and Ovid databases for relevant studies from inception until January 7, 2022, limited to papers involving human subjects. Studies were reviewed for methodological quality. Fix-effects and random-effects models were used to pool results. Heterogeneity was assessed using I2. The publication bias was assessed using the Egger's test. PROSPERO registration: CRD42021265377. Findings: A total of eighteen qualified articles were identified and included in the systematic review, and twelve studies were included in the meta-analysis. Our results showed that female (OR: 4.011; 95% CI: 2.928-5.495), altered chest computerized tomography (CT) (OR: 3.002; 95% CI: 1.319-6.835), age (OR: 1.018; 95% CI: 1.007-1.030), higher D-dimer levels (OR: 1.012; 95% CI: 1.001-1.023) and urea nitrogen (OR: 1.004;95% CI: 1.002-1.007) were identified as risk factors for impaired DLCO. Interpretation: Pulmonary diffusion capacity was the most common impaired lung function in recovered patients with COVID-19. Several risk factors, such as female, altered chest CT, older age, higher D-dimer levels and urea nitrogen are associated with impairment of DLCO. Raising awareness and implementing interventions for possible modifiable risk factors may be valuable for pulmonary rehabilitation. Funding: This work was financially supported by Emergency Key Program of Guangzhou Laboratory (EKPG21-29, EKPG21-31), Incubation Program of National Science Foundation for Distinguished Young Scholars by Guangzhou Medical University (GMU2020-207).

Preventive Measures Against COVID-19 in Small- and Mid-sized Enterprises from an Early Stage of the Epidemic in Daegu and Gyeongsangbuk-do.

Background: In the early stage of the coronavirus disease 2019 (COVID-19) epidemic, small- and mid-sized enterprises (SMEs) may be an important transmission consideration. The study aimed to identify the pattern of COVID-19 prevention measures during the outbreaks in Daegu and Gyeongsangbuk-do at the early stage of COVID-19. Moreover, we investigated whether SME size and past experiences affected the preventive measures implemented in the region. Methods: A survey detailing the general characteristics and implementation of 12 preventive activities was conducted in 122 SMEs in Daegu and Gyeongsangbuk-do. The survey was analyzed by size and operation period. Results: The study subjects consisted of 53 (43.4%) workplaces with 1-5 employees, 50 (40.9%) workplaces with 6-30 employees, and 19 (15.6%) workplaces with 31-49 employees. The lowest three items among those surveyed were 'symptomatic workers to stay home for 3-4 days' (17.2%), 'work remotely' (18.9%), and 'video meetings' (20.5%). There were significant differences in the rate of several preventive measures implemented. The larger sized SMEs, the higher the number of implementations (p < 0.01). The operation period had no significant relationship with the implementation of preventive measures. The same pattern was observed in multiple generalized linear regression with covariate adjustment. Conclusion: Preventive measures among SMEs with fewer than 50 employees were identified. Even within SMEs, a gap in preventive measures according to size was confirmed. To prevent the spread of infection and protect workers' right to health, different support for different sized SMEs is necessary.

Association between thrombocytopenia and the severity of Covid-19 infection among hospitalized Egyptian patients.

Background: COVID-19, which is caused by the corona virus 2 that causes severe acute respiratory syndrome, causes a respiratory and systemic illness that in 10-15% of patients escalates to a severe form of pneumonia. Thrombocytopenia is frequent in patients with COVID-19. We aimed to evaluate the association between thrombocytopenia and the severity of COVID-19 infection in hospitalized patients. Methods: A cross-sectional study was done on 800 Egyptian patients with confirmed covid-19 infection. They were divided into Group I (Mild): 200 symptomatic patients meeting the case definition for COVID-19 without radiological evidence of pneumonia or hypoxia. Group II (Moderate): 200 patients with clinical signs of non-severe pneumonia and radiological evidence of pneumonia. Group III (Severe): 200 patients with clinical signs of pneumonia plus: respiratory or lung dysfunction. Group IV: 200 critically ill patient in ICU: Acute respiratory distress syndrome (ARDS).Results: there was a highly statistically significant difference between the studied groups regarding thrombocytopenia (p < 0.001). Thrombocytopenia was statistically higher in severe and critically ill patients. In addition, a statistically significant difference found in outcome among the studied groups (p < 0.05) {critically ill (40%), severe (17.5%)}. The most common cause of death was respiratory failure, which occurred in 28 severe patients (80%) and 65 critically ill patients (81.25%), followed by hemorrhage due to thrombocytopenia, which occurred in 7 severe patients (20%) and 15 critically ill patients, respectively (18.75%). Conclusion: The Platelet count is a straightforward, inexpensive, as well as easily available laboratory parameter that is frequently linked to severe covid-19 infection and a significant death risk.

Prospects of NIR fluorescent nanosensors for green detection of SARS-CoV-2.

The pandemic of the novel coronavirus disease 2019 (COVID-19) is continuously causing hazards for the world. Effective detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can relieve the impact, but various toxic chemicals are also released into the environment. Fluorescence sensors offer a facile analytical strategy. During fluorescence sensing, biological samples such as tissues and body fluids have autofluorescence, giving false-positive/negative results because of the interferences. Fluorescence near-infrared (NIR) nanosensors can be designed from low-toxic materials with insignificant background signals. Although this research is still in its infancy, further developments in this field have the potential for sustainable detection of SARS-CoV-2. Herein, we summarize the reported NIR fluorescent nanosensors with the potential to detect SARS-CoV-2. The green synthesis of NIR fluorescent nanomaterials, environmentally compatible sensing strategies, and possible methods to reduce the testing frequencies are discussed. Further optimization strategies for developing NIR fluorescent nanosensors to facilitate greener diagnostics of SARS-CoV-2 for pandemic control are proposed.

Caregivers' perceived changes in engaged time with preschool-aged children during COVID-19: Familial correlates and relations to children's learning behavior and emotional distress.

The COVID-19 pandemic and its resulting containment measures have forced many children and their caregivers around the world to spend unprecedented amounts of time at home. Based on a sample of 764 households with preschool-aged children in Wuhan, China, where the pandemic began, this study examined how primary caregivers perceived changes in the amount of time spent engaging with their children (i.e., engaged time) from the start of the pandemic and whether these changes were associated with children's learning behavior and emotional distress. The results showed that primary caregivers generally perceived increases in the amount of engaged time spent on indoor activities with their children but decreases in the amount of engaged time spent playing with their children outdoors. A bigger family size and greater loss of family income during the pandemic were associated with bigger perceived increases in caregivers' engaged time spent on indoor activities, whilst a higher level of parental education was associated with bigger perceived decreases in engaged time spent playing with children outdoors. The family's poorer physical health and higher levels of chaos during the pandemic were related to smaller perceived increases in caregivers' engaged time spent on educational activities. Finally, although bigger perceived increases in caregivers' indoor engaged time (e.g., time spent on educational activities) were associated with higher levels of positive learning behavior and fewer symptoms of anxiety and withdrawal in the children, bigger perceived decreases in outdoor play time were associated with fewer symptoms of anxiety and withdrawal. These findings offer valuable insights into caregivers' allocation of engaged time with their preschool-aged children during the COVID-19 pandemic.

RNAi-mediated siRNA sequences to combat the COVID-19 pandemic with the inhibition of SARS-CoV2.

The outbreak of the COVID-19 pandemic has cost five million lives to date, and was caused by a positive-sense RNA virus named SARS-CoV2. The lack of drugs specific to SARS-CoV2, leads us to search for an effective and specific therapeutic approach. Small interfering RNA (siRNA) is able to activate the RNA interference (RNAi) pathway to silence the specific targeted gene and inhibit the viral replication, and it has not yet attracted enough attention as a SARS-CoV2 antiviral agent. It could be a potential weapon to combat this pandemic until the completion of full scale, effective mass vaccination. For this study, specific siRNAs were designed using a web-based bioinformatics tool (siDirect2.0) against 14 target sequences. These might have a high probability of silencing the essential proteins of SARS-CoV2. such as: 3CLpro/Mpro/nsp5, nsp7, Rd-Rp/nsp12, ZD, NTPase/HEL or nsp13, PLpro/nsp3, envelope protein (E), spike glycoprotein (S), nucleocapsid phosphoprotein (N), membrane glycoprotein (M), ORF8, ORF3a, nsp2, and its respective 5' and 3'-UTR. Among these potential drug targets, the majority of them contain highly conserved sequences; the rest are chosen on the basis of their role in viral replication and survival. The traditional vaccine development technology using SARS-CoV2 protein takes 6-8 months; meanwhile the virus undergoes several mutations in the candidate protein chosen for vaccine development. By the time the protein-based vaccine reaches the market, the virus would have undergone several mutations, such that the antibodies against the viral sequence may not be effective in restricting the newly mutated viruses. However, siRNA technology can make sequences based on real time viral mutation status. This has the potential for suppressing SARS-CoV2 viral replication, through RNAi technology.

Enhanced endocytosis elevated virulence and severity of SARS-CoV-2 due to hyperglycemia in type 2 diabetic patients.

Diabetes mellitus is a metabolic disease that causes hyperglycemia. In COVID-19 patients the severity of the disease depends on myriad factors but diabetes mellitus is the most important comorbidity. The current review was conducted to investigate the virulence of SARS-CoV-2 and disease severity of COVID-19 in type 2 diabetes mellitus patients and relevant treatment. The literature published in PubMed, Scopus, Web of Science, and Google Scholar was reviewed up to September 2021. The keywords including SARS-CoV-2, type 2 diabetes mellitus in COVID-19, hyperglycemia in COVID-19, opportunistic infections in type 2 diabetes mellitus and COVID-19 were used in different combinations. Hyperglycemic individuals over-express ACE-2 receptors in the lungs thus increasing the SARS-CoV-2 susceptibility and replication. Although dipeptidyl peptidase-4 plays an important role in glucose homeostasis, additionally it also stimulates the production of proinflammatory cytokines such as IL-6 and TNF-α creating a cytokine storm. Cytokine storm might be responsible for respiratory insufficiency in severe COVID-19 patients. Type 2 diabetes mellitus is associated with immunosuppression and the patients are prone to get many opportunistic infections. Type 2 diabetes mellitus patients with severe COVID-19 have lymphopenia. Moreover, in type 2 diabetes mellitus patients the neutrophils exhibit decreased chemotaxis, hydrogen peroxide production, and phagocytosis. Reduction in lymphocyte count and defective neutrophil capacity renders them with COVID-19 susceptible to opportunistic bacterial and fungal infections increasing the mortality rate. The opportunistic bacterial infections in COVID-19 patients were due to Staphylococcus aureus, Streptococcus pneumonia, and coagulase-negative Staphylococci, E. coli, Pseudomonas aeruginosa, and Klebsiella sp. In COVID-19 patients with type 2 diabetes mellitus, mucormycosis was found to be the most common fungal infection with a higher predilection to males. Hyperglycemia in COVID-19 patients with type 2 diabetes mellitus enhances the SARS-CoV-2 replication with an adverse outcome. A strong correlation exists between the poor prognosis of COVID-19 and type 2 diabetes mellitus. Proper glycemic control in COVID-19 patients with diabetes mellitus might lessen the severity of the disease.

The fatty acid site is coupled to functional motifs in the SARS-CoV-2 spike protein and modulates spike allosteric behaviour.

The SARS-CoV-2 spike protein is the first contact point between the SARS-CoV-2 virus and host cells and mediates membrane fusion. Recently, a fatty acid binding site was identified in the spike (Toelzer et al. Science 2020). The presence of linoleic acid at this site modulates binding of the spike to the human ACE2 receptor, stabilizing a locked conformation of the protein. Here, dynamical-nonequilibrium molecular dynamics simulations reveal that this fatty acid site is coupled to functionally relevant regions of the spike, some of them far from the fatty acid binding pocket. Removal of a ligand from the fatty acid binding site significantly affects the dynamics of distant, functionally important regions of the spike, including the receptor-binding motif, furin cleavage site and fusion-peptide-adjacent regions. Simulations of the D614G mutant show differences in behaviour between these clinical variants of the spike: the D614G mutant shows a significantly different conformational response for some structural motifs relevant for binding and fusion. The simulations identify structural networks through which changes at the fatty acid binding site are transmitted within the protein. These communication networks significantly involve positions that are prone to mutation, indicating that observed genetic variation in the spike may alter its response to linoleate binding and associated allosteric communication.

QSAR based virtual screening derived identification of a novel hit as a SARS CoV-229E 3CLpro Inhibitor: GA-MLR QSAR modeling supported by molecular Docking, molecular dynamics simulation and MMGBSA calculation approaches.

Congruous coronavirus drug targets and analogous lead molecules must be identified as quickly as possible to produce antiviral therapeutics against human coronavirus (HCoV SARS 3CLpro) infections. In the present communication, we bear recognized a HIT candidate for HCoV SARS 3CLpro inhibition. Four Parametric GA-MLR primarily based QSAR model (R2:0.84, R2adj:0.82, Q2loo: 0.78) was once promoted using a dataset over 37 structurally diverse molecules along QSAR based virtual screening (QSAR-VS), molecular docking (MD) then molecular dynamic simulation (MDS) analysis and MMGBSA calculations. The QSAR-based virtual screening was utilized to find novel lead molecules from an in-house database of 100 molecules. The QSAR-vS successfully offered a hit molecule with an improved PEC50 value from 5.88 to 6.08. The benzene ring, phenyl ring, amide oxygen and nitrogen, and other important pharmacophoric sites are revealed via MD and MDS studies. Ile164, Pro188, Leu190, Thr25, His41, Asn46, Thr47, Ser49, Asn189, Gln191, Thr47, and Asn141 are among the key amino acid residues in the S1 and S2 pocket. A stable complex of a lead molecule with the HCoV SARS 3CLpro was discovered using MDS. MM-GBSA calculations resulted from MD simulation results well supported with the binding energies calculated from the docking results. The results of this study can be exploited to develop a novel antiviral target, such as an HCoV SARS 3CLpro Inhibitor.

Implications of WHO COVID-19 interim guideline 2020.5 on the comprehensive care for infected persons in Africa Before, during and after clinical management of cases.

The novel coronavirus disease 2019 (COVID-19) is one of the biggest public health crises globally. Although Africa did not display the worst-case scenario compared to other continents, fears were still at its peak since Africa was already suffering from a heavy load of other life-threatening infectious diseases such as HIV/AIDS and malaria. Other factors that were anticipated to complicate Africa's outcomes include the lack of resources for diagnosis and contact tracing along with the low capacity of specialized management facilities per capita. The current review aims at assessing and generating discussions on the realities, and pros and cons of the WHO COVID-19 interim guidance 2020.5 considering the known peculiarities of the African continent. A comprehensive evaluation was done for COVID-19-related data published across PubMed and Google Scholar (date of the last search: August 17, 2020) with emphasis on clinical management and psychosocial aspects. Predefined filters were then applied in data screening as detailed in the methods. Specifically, we interrogated the WHO 2020.5 guideline viz-a-viz health priority and health financing in Africa, COVID-19 case contact tracing and risk assessment, clinical management of COVID-19 cases as well as strategies for tackling stigmatization and psychosocial challenges encountered by COVID-19 survivors. The outcomes of this work provide links between these vital sub-themes which may impact the containment and management of COVID-19 cases in Africa in the long-term. The chief recommendation of the current study is the necessity of prudent filtration of the global findings along with regional modelling of the global care guidelines for acting properly in response to this health threat on the regional level without exposing our populations to further unnecessary adversities.

Differential Effect of SARS-CoV-2 Spike Glycoprotein 1 on Human Bronchial and Alveolar Lung Mucosa Models: Implications for Pathogenicity.

BACKGROUND: The SARS-CoV-2 spike protein mediates attachment of the virus to the host cell receptor and fusion between the virus and the cell membrane. The S1 subunit of the spike glycoprotein (S1 protein) contains the angiotensin converting enzyme 2 (ACE2) receptor binding domain. The SARS-CoV-2 variants of concern contain mutations in the S1 subunit. The spike protein is the primary target of neutralizing antibodies generated following infection, and constitutes the viral component of mRNA-based COVID-19 vaccines. METHODS: Therefore, in this work we assessed the effect of exposure (24 h) to 10 nM SARS-CoV-2 recombinant S1 protein on physiologically relevant human bronchial (bro) and alveolar (alv) lung mucosa models cultured at air-liquid interface (ALI) (n = 6 per exposure condition). Corresponding sham exposed samples served as a control. The bro-ALI model was developed using primary bronchial epithelial cells and the alv-ALI model using representative type II pneumocytes (NCI-H441). RESULTS: Exposure to S1 protein induced the surface expression of ACE2, toll like receptor (TLR) 2, and TLR4 in both bro-ALI and alv-ALI models. Transcript expression analysis identified 117 (bro-ALI) and 97 (alv-ALI) differentially regulated genes (p ≤ 0.01). Pathway analysis revealed enrichment of canonical pathways such as interferon (IFN) signaling, influenza, coronavirus, and anti-viral response in the bro-ALI. Secreted levels of interleukin (IL) 4 and IL12 were significantly (p < 0.05) increased, whereas IL6 decreased in the bro-ALI. In the case of alv-ALI, enriched terms involving p53, APRIL (a proliferation-inducing ligand) tight junction, integrin kinase, and IL1 signaling were identified. These terms are associated with lung fibrosis. Further, significantly (p < 0.05) increased levels of secreted pro-inflammatory cytokines IFNγ, IL1ꞵ, IL2, IL4, IL6, IL8, IL10, IL13, and tumor necrosis factor alpha were detected in alv-ALI, whereas IL12 was decreased. Altered levels of these cytokines are also associated with lung fibrotic response. CONCLUSIONS: In conclusion, we observed a typical anti-viral response in the bronchial model and a pro-fibrotic response in the alveolar model. The bro-ALI and alv-ALI models may serve as an easy and robust platform for assessing the pathogenicity of SARS-CoV-2 variants of concern at different lung regions.

Mutual Pan-African support paradigm to produce scientific evidence of traditional medical practices for use against COVID-19 and emerging pandemics.

Africa is endowed with a profoundly rich and diverse system of plants and other bio-resources out of which, by traditional medicine practice, the people have satisfied their healthcare needs right from antiquity. In contemporary times, it has become necessary to modernize this traditional medical care system via scientific studies. Validation of the efficacy of health-enhancement products and drugs from plants and other bio-resources is predicated on diligent and intensive research accompanied by rigorous and conclusive clinical trials. Africa has eminently qualified human resources but due to the finance-intensive nature of medical research, individual African states on their own cannot fund the level of research desired for dealing with such serious issues as the COVID-19 pandemic. A collaboration among African states guided by a Mutual Pan-African support paradigm (MPASP) is a unique strategy for achieving success in any such a high-impact global project as the use of traditional medicine against COVID-19 and emerging pandemics; and this is hereby advocated.

Recent developments in the medicinal chemistry of single boron atom-containing compounds.

Various boron-containing drugs have been approved for clinical use over the past two decades, and more are currently in clinical trials. The increasing interest in boron-containing compounds is due to their unique binding properties to biological targets; for example, boron substitution can be used to modulate biological activity, pharmacokinetic properties, and drug resistance. In this perspective, we aim to comprehensively review the current status of boron compounds in drug discovery, focusing especially on progress from 2015 to December 2020. We classify these compounds into groups showing anticancer, antibacterial, antiviral, antiparasitic and other activities, and discuss the biological targets associated with each activity, as well as potential future developments.

Prevalence and 30-Day Mortality in Hospitalized Patients With Covid-19 and Prior Lung Diseases.

INTRODUCTION: Patients with pre-existing respiratory diseases in the setting of COVID-19 may have a greater risk of severe complications and even death. METHODS: A retrospective, multicenter, cohort study with 5847 COVID-19 patients admitted to hospitals. Patients were separated in two groups, with/without previous lung disease. Evaluation of factors associated with survival and secondary composite end-point such as ICU admission and respiratory support, were explored. RESULTS: 1,271 patients (22%) had a previous lung disease, mostly COPD. All-cause mortality occurred in 376 patients with lung disease (29.5%) and in 819 patients without (17.9%) (p < 0.001). Kaplan-Meier curves showed that patients with lung diseases had a worse 30-day survival (HR = 1.78; 95%C.I. 1.58-2.01; p < 0.001) and COPD had almost 40% mortality. Multivariable Cox regression showed that prior lung disease remained a risk factor for mortality (HR, 1.21; 95%C.I. 1.02-1.44; p = 0.02). Variables independently associated with all-cause mortality risk in patients with lung diseases were oxygen saturation less than 92% on admission (HR, 4.35; 95% CI 3.08-6.15) and elevated D-dimer (HR, 1.84; 95% CI 1.27-2.67). Age younger than 60 years (HR 0.37; 95% CI 0.21-0.65) was associated with decreased risk of death. CONCLUSIONS: Previous lung disease is a risk factor for mortality in patients with COVID-19. Older age, male gender, home oxygen therapy, and respiratory failure on admission were associated with an increased mortality. Efforts must be done to identify respiratory patients to set measures to improve their clinical outcomes.

INTRODUCCIÓN: Los pacientes con enfermedades respiratorias preexistentes pueden tener en el contexto de la covid-19 un mayor riesgo de complicaciones graves e incluso de muerte. MÉTODOS: Estudio de cohortes multicéntrico y retrospectivo de 5.847 pacientes con covid-19 ingresados en hospitales. Los pacientes se separaron en 2 grupos, sin y con enfermedad pulmonar previa. Se evaluaron factores asociados con la supervivencia y criterios combinados de valoración secundarios, como el ingreso en la UCI y la necesidad de asistencia respiratoria. RESULTADOS: Mil doscientos setenta y un (1.271) pacientes (22%) tenían una enfermedad pulmonar previa, principalmente EPOC. La mortalidad por todas las causas ocurrió en 376 pacientes con enfermedad pulmonar (29,5%) y en 819 pacientes sin enfermedad pulmonar (17,9%; p < 0,001). Las curvas de Kaplan-Meier mostraron que los pacientes con enfermedades pulmonares tenían una peor supervivencia a los 30 días (HR: 1,78; IC del 95%: 1,58-2,01; p < 0,001) y la EPOC tenía una mortalidad de casi el 40%. La regresión de Cox multivariante mostró que la enfermedad pulmonar previa seguía siendo un factor de riesgo de mortalidad (HR: 1,21; IC del 95%: 1,02-1,44; p = 0,02). Las variables asociadas de forma independiente con el riesgo de muerte por todas las causas en pacientes con enfermedades pulmonares fueron la saturación de oxígeno inferior al 92% al ingreso (HR: 4,35; IC del 95%: 3,08-6,15) y el dímero D elevado (HR: 1,84; IC del 95%: 1,27-2,67). La edad menor de 60 años (HR: 0,37; IC del 95%: 0,21-0,65) se asoció con una disminución del riesgo de muerte. CONCLUSIONES: La enfermedad pulmonar previa es un factor de riesgo de muerte en pacientes con covid-19. La edad avanzada, el sexo masculino, la oxigenoterapia domiciliaria y la insuficiencia respiratoria al ingreso se asociaron con un aumento de la mortalidad. Se deben realizar esfuerzos para identificar a los pacientes respiratorios y establecer medidas para mejorar sus resultados clínicos.

Time series forecasting of new cases and new deaths rate for COVID-19 using deep learning methods.

The first known case of Coronavirus disease 2019 (COVID-19) was identified in December 2019. It has spread worldwide, leading to an ongoing pandemic, imposed restrictions and costs to many countries. Predicting the number of new cases and deaths during this period can be a useful step in predicting the costs and facilities required in the future. The purpose of this study is to predict new cases and deaths rate one, three and seven-day ahead during the next 100 days. The motivation for predicting every n days (instead of just every day) is the investigation of the possibility of computational cost reduction and still achieving reasonable performance. Such a scenario may be encountered in real-time forecasting of time series. Six different deep learning methods are examined on the data adopted from the WHO website. Three methods are LSTM, Convolutional LSTM, and GRU. The bidirectional extension is then considered for each method to forecast the rate of new cases and new deaths in Australia and Iran countries. This study is novel as it carries out a comprehensive evaluation of the aforementioned three deep learning methods and their bidirectional extensions to perform prediction on COVID-19 new cases and new death rate time series. To the best of our knowledge, this is the first time that Bi-GRU and Bi-Conv-LSTM models are used for prediction on COVID-19 new cases and new deaths time series. The evaluation of the methods is presented in the form of graphs and Friedman statistical test. The results show that the bidirectional models have lower errors than other models. A several error evaluation metrics are presented to compare all models, and finally, the superiority of bidirectional methods is determined. This research could be useful for organisations working against COVID-19 and determining their long-term plans.