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1.
BMC Pulm Med ; 20(1): 317, 2020 Dec 07.
Article in English | MEDLINE | ID: covidwho-1331939

ABSTRACT

BACKGROUND: The COVID-19 pandemic reached Europe in early 2020. Convalescent plasma is used without a consistent evidence of efficacy. Our hypothesis is that passive immunization with plasma collected from patients having contracted COVID-19 and developed specific neutralizing antibodies may alleviate symptoms and reduce mortality in patients treated with mechanical ventilation for severe respiratory failure during the evolution of SARS-CoV-2 pneumonia. METHODS: We plan to include 500 adult patients, hospitalized in 16 Belgian intensive care units between September 2020 and 2022, diagnosed with SARS-CoV-2 pneumonia, under mechanical ventilation for less than 5 days and a clinical frailty scale less than 6. The study treatment will be compared to standard of care and allocated by randomization in a 1 to 1 ratio without blinding. The main endpoint will be mortality at day 28. We will perform an intention to treat analysis. The number of patients to include is based on an expected mortality rate at day 28 of 40 percent and an expected relative reduction with study intervention of 30 percent with α risk of 5 percent and ß risk of 20 percent. DISCUSSION: This study will assess the efficacy of plasma in the population of mechanically ventilated patients. A stratification on the delay from mechanical ventilation and inclusion will allow to approach the optimal time use. Selecting convalescent plasmas with a high titer of neutralizing antibodies against SARS-CoV-2 will allow a homogeneous study treatment. The inclusion in the study is based on the consent of the patient or his/her legal representative, and the approval of the Investigational Review Board of the University hospital of Liège, Belgium. A data safety monitoring board (DSMB) has been implemented. Interim analyses have been planned at 100, 2002, 300 and 400 inclusions in order to decide whether the trail should be discontinued prematurely for ethical issues. We plan to publish our results in a peer-reviewed journal and to present them at national and international conferences. FUNDING AND REGISTRATION: The trial is funded by the Belgian Health Care Knowledge Center KCE # COV201004 TRIAL REGISTRATION: Clinicaltrials.gov registration number NCT04558476. Registered 14 September 2020-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04558476.


Subject(s)
COVID-19/therapy , Respiration, Artificial , Severe Acute Respiratory Syndrome/therapy , Adult , Antibodies, Viral/blood , Antibodies, Viral/immunology , Belgium , COVID-19/mortality , Clinical Trials, Phase II as Topic , Humans , Immunization, Passive , Intensive Care Units , Multicenter Studies as Topic , Randomized Controlled Trials as Topic , Severe Acute Respiratory Syndrome/mortality , Time Factors , Treatment Outcome
2.
Rev. Bras. Saúde Mater. Infant. (Online) ; 21(supl.2): 461-469, 2021. tab, graf
Article in English | WHO COVID, LILACS (Americas) | ID: covidwho-1328004

ABSTRACT

Abstract Objectives: to evaluate the morbidity and mortality profile and factors associated with death due to severe acute respiratory syndrome (SARS) by COVID-19 in pregnant and postpartum women. Methods: this is a quantitative and retrospective research that analyzed the SIVEP-gripe Database (Influenza Epidemiological Surveillance Information System), from 01/01/2020 to 04/01/2021. All pregnant women and postpartum women diagnosed with SARS caused by COVID-19 in the State of Minas Gerais were included. After the descriptive analysis of the hospitalizations profile, the association between different exposure variables and the occurrence of death was evaluated. Results: of the 227 records obtained, 94.3% required hospitalization. Among hospitalizations in the Intensive Care Unit, 29.8% used invasive ventilatory support. Fifteen deaths were recorded. The most frequent clinical manifestations were: cough and fever; the predominant comorbidities were cardiovascular disease and diabetes mellitus. The variables "ICU stay", "use of ventilatory support" and "heart disease" were associated with the occurrence of deaths. Conclusions: hospitalization was necessary for most pregnant women with SARS and the presence of previous heart disease increased the risk of death. Knowing the SARS morbidity and mortality profile is important in the definition of public health strategies aimed at reducing the impacts of COVID-19 during pregnancy and the puerperium.


Resumo Objetivos: avaliar o perfil de morbimortalidade e fatores associados ao óbito pela Síndrome Respiratória Aguda Grave (SRAG) por COVID-19 em gestantes e puérperas. Métodos: tratase de urna pesquisa quantitativa e retrospectiva que analisou o Banco de Dados SIVEP-gripe (Sistema de Informação de Vigilância Epidemiológica da Gripe), no período de 01/01/2020 a 04/01/2021. Foram incluídas todas as gestantes e puérperas com diagnóstico de SRAG causada por COVID-19 no Estado de Minas Gerais. Após a análise descritiva do perfil das internações, avaliou-se a associação entre diferentes variáveis de exposição e a ocurrência de óbito. Resultados: dos 227 registros obtidos, 94,3% necessitaram de hospitalização. Dentre as internações em Unidade de Terapia Intensiva, 29,8%fizeram uso de suporte ventilatório invasivo. Quinze óbitos foram registrados. As manifestações clínicas mais frequentes foram: tosse e febre; já as comorbidades predominantes foram doença cardiovascular e diabetes mellitus. As variáveis "internação em UTI", "uso de suporte ventilatório" e "cardiopatia" apresentaram associação com ao corrência de óbitos. Conclusão: a hospitalização foi necessária para a maioria das gestantes com SRAG e a presença de cardiopatia prévia aumentou o risco de óbito. Conhecer o perfil de morbimortalidade por SRAG é importante na definição de estratégias de saúde pública que visem à redução dos impactos da COVID-19 na gestação e puerpério.


Subject(s)
Humans , Female , Pregnancy , Comorbidity , Indicators of Morbidity and Mortality , Severe Acute Respiratory Syndrome/mortality , Pregnant Women , Postpartum Period , COVID-19/mortality , Pregnancy Complications, Infectious , Brazil/epidemiology , Risk Factors , COVID-19/epidemiology , Heart Diseases , Intensive Care Units
3.
Rev. Bras. Saúde Mater. Infant. (Online) ; 21(supl.2): 461-469, 2021. tab, graf
Article in English | WHO COVID, LILACS (Americas) | ID: covidwho-1328003

ABSTRACT

Abstract Objectives: to evaluate the morbidity and mortality profile and factors associated with death due to severe acute respiratory syndrome (SARS) by COVID-19 in pregnant and postpartum women. Methods: this is a quantitative and retrospective research that analyzed the SIVEP-gripe Database (Influenza Epidemiological Surveillance Information System), from 01/01/2020 to 04/01/2021. All pregnant women and postpartum women diagnosed with SARS caused by COVID-19 in the State of Minas Gerais were included. After the descriptive analysis of the hospitalizations profile, the association between different exposure variables and the occurrence of death was evaluated. Results: of the 227 records obtained, 94.3% required hospitalization. Among hospitalizations in the Intensive Care Unit, 29.8% used invasive ventilatory support. Fifteen deaths were recorded. The most frequent clinical manifestations were: cough and fever; the predominant comorbidities were cardiovascular disease and diabetes mellitus. The variables "ICU stay", "use of ventilatory support" and "heart disease" were associated with the occurrence of deaths. Conclusions: hospitalization was necessary for most pregnant women with SARS and the presence of previous heart disease increased the risk of death. Knowing the SARS morbidity and mortality profile is important in the definition of public health strategies aimed at reducing the impacts of COVID-19 during pregnancy and the puerperium.


Resumo Objetivos: avaliar o perfil de morbimortalidade e fatores associados ao óbito pela Síndrome Respiratória Aguda Grave (SRAG) por COVID-19 em gestantes e puérperas. Métodos: tratase de urna pesquisa quantitativa e retrospectiva que analisou o Banco de Dados SIVEP-gripe (Sistema de Informação de Vigilância Epidemiológica da Gripe), no período de 01/01/2020 a 04/01/2021. Foram incluídas todas as gestantes e puérperas com diagnóstico de SRAG causada por COVID-19 no Estado de Minas Gerais. Após a análise descritiva do perfil das internações, avaliou-se a associação entre diferentes variáveis de exposição e a ocurrência de óbito. Resultados: dos 227 registros obtidos, 94,3% necessitaram de hospitalização. Dentre as internações em Unidade de Terapia Intensiva, 29,8%fizeram uso de suporte ventilatório invasivo. Quinze óbitos foram registrados. As manifestações clínicas mais frequentes foram: tosse e febre; já as comorbidades predominantes foram doença cardiovascular e diabetes mellitus. As variáveis "internação em UTI", "uso de suporte ventilatório" e "cardiopatia" apresentaram associação com ao corrência de óbitos. Conclusão: a hospitalização foi necessária para a maioria das gestantes com SRAG e a presença de cardiopatia prévia aumentou o risco de óbito. Conhecer o perfil de morbimortalidade por SRAG é importante na definição de estratégias de saúde pública que visem à redução dos impactos da COVID-19 na gestação e puerpério.


Subject(s)
Humans , Female , Pregnancy , Comorbidity , Indicators of Morbidity and Mortality , Severe Acute Respiratory Syndrome/mortality , Pregnant Women , Postpartum Period , COVID-19/mortality , Pregnancy Complications, Infectious , Brazil/epidemiology , Risk Factors , COVID-19/epidemiology , Heart Diseases , Intensive Care Units
4.
IUBMB Life ; 73(8): 1005-1015, 2021 08.
Article in English | MEDLINE | ID: covidwho-1291220

ABSTRACT

The kidney is one of the main targets attacked by viruses in patients with a coronavirus infection. Until now, SARS-CoV-2 has been identified as the seventh member of the coronavirus family capable of infecting humans. In the past two decades, humankind has experienced outbreaks triggered by two other extremely infective members of the coronavirus family; the MERS-CoV and the SARS-CoV. According to several investigations, SARS-CoV causes proteinuria and renal impairment or failure. The SARS-CoV was identified in the distal convoluted tubules of the kidney of infected patients. Also, renal dysfunction was observed in numerous cases of MERS-CoV infection. And recently, during the 2019-nCoV pandemic, it was found that the novel coronavirus not only induces acute respiratory distress syndrome (ARDS) but also can induce damages in various organs including the liver, heart, and kidney. The kidney tissue and its cells are targeted massively by the coronaviruses due to the abundant presence of ACE2 and Dpp4 receptors on kidney cells. These receptors are characterized as the main route of coronavirus entry to the victim cells. Renal failure due to massive viral invasion can lead to undesirable complications and enhanced mortality rate, thus more attention should be paid to the pathology of coronaviruses in the kidney. Here, we have provided the most recent knowledge on the coronaviruses (SARS, MERS, and COVID19) pathology and the mechanisms of their impact on the kidney tissue and functions.


Subject(s)
COVID-19/mortality , Coronavirus Infections/mortality , Middle East Respiratory Syndrome Coronavirus/pathogenicity , SARS Virus/pathogenicity , SARS-CoV-2/pathogenicity , Severe Acute Respiratory Syndrome/mortality , Viral Tropism/genetics , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/genetics , COVID-19/pathology , COVID-19/virology , Coronavirus Infections/genetics , Coronavirus Infections/pathology , Coronavirus Infections/virology , Dipeptidyl Peptidase 4/genetics , Dipeptidyl Peptidase 4/metabolism , Gene Expression Regulation , Humans , Kidney/metabolism , Kidney/pathology , Kidney/virology , Middle East Respiratory Syndrome Coronavirus/genetics , Middle East Respiratory Syndrome Coronavirus/metabolism , Protein Binding , Receptors, Virus/genetics , Receptors, Virus/metabolism , SARS Virus/genetics , SARS Virus/metabolism , SARS-CoV-2/genetics , SARS-CoV-2/metabolism , Severe Acute Respiratory Syndrome/genetics , Severe Acute Respiratory Syndrome/pathology , Severe Acute Respiratory Syndrome/virology , Severity of Illness Index , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism , Survival Analysis
5.
Eur J Pharmacol ; 906: 174248, 2021 Sep 05.
Article in English | MEDLINE | ID: covidwho-1267662

ABSTRACT

Concern regarding coronavirus (CoV) outbreaks has stayed relevant to global health in the last decades. Emerging COVID-19 infection, caused by the novel SARS-CoV2, is now a pandemic, bringing a substantial burden to human health. Interferon (IFN), combined with other antivirals and various treatments, has been used to treat and prevent MERS-CoV, SARS-CoV, and SARS-CoV2 infections. We aimed to assess the clinical efficacy of IFN-based treatments and combinational therapy with antivirals, corticosteroids, traditional medicine, and other treatments. Major healthcare databases and grey literature were investigated. A three-stage screening was utilized, and included studies were checked against the protocol eligibility criteria. Risk of bias assessment and data extraction were performed, followed by narrative data synthesis. Fifty-five distinct studies of SARS-CoV2, MERS-CoV, and SARS-CoV were spotted. Our narrative synthesis showed a possible benefit in the use of IFN. A good quality cohort showed lower CRP levels in Arbidol (ARB) + IFN group vs. IFN only group. Another study reported a significantly shorter chest X-ray (CXR) resolution in IFN-Alfacon-1 + corticosteroid group compared with the corticosteroid only group in SARS-CoV patients. In a COVID-19 trial, total adverse drug events (ADEs) were much lower in the Favipiravir (FPV) + IFN-α group compared with the LPV/RTV arm (P = 0.001). Also, nausea in patients receiving FPV + IFN-α regimen was significantly lower (P = 0.03). Quantitative analysis of mortality did not show a conclusive effect for IFN/RBV treatment in six moderately heterogeneous MERS-CoV studies (log OR = -0.05, 95% CI: (-0.71,0.62), I2 = 44.71%). A meta-analysis of three COVID-19 studies did not show a conclusive nor meaningful relation between receiving IFN and COVID-19 severity (log OR = -0.44, 95% CI: (-1.13,0.25), I2 = 31.42%). A lack of high-quality cohorts and controlled trials was observed. Evidence suggests the potential efficacy of several combination IFN therapies such as lower ADEs, quicker resolution of CXR, or a decrease in inflammatory cytokines; Still, these options must possibly be further explored before being recommended in public guidelines. For all major CoVs, our results may indicate a lack of a definitive effect of IFN treatment on mortality. We recommend such therapeutics be administered with extreme caution until further investigation uncovers high-quality evidence in favor of IFN or combination therapy with IFN.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , Coronavirus Infections/drug therapy , Interferons/therapeutic use , Severe Acute Respiratory Syndrome/drug therapy , Antiviral Agents/adverse effects , COVID-19/diagnostic imaging , COVID-19/mortality , Coronavirus Infections/diagnostic imaging , Coronavirus Infections/mortality , Humans , Interferons/adverse effects , Severe Acute Respiratory Syndrome/diagnostic imaging , Severe Acute Respiratory Syndrome/mortality
6.
Mol Cells ; 44(6): 384-391, 2021 Jun 30.
Article in English | MEDLINE | ID: covidwho-1259762

ABSTRACT

The recent appearance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected millions of people around the world and caused a global pandemic of coronavirus disease 2019 (COVID-19). It has been suggested that uncontrolled, exaggerated inflammation contributes to the adverse outcomes of COVID-19. In this review, we summarize our current understanding of the innate immune response elicited by SARS-CoV-2 infection and the hyperinflammation that contributes to disease severity and death. We also discuss the immunological determinants behind COVID-19 severity and propose a rationale for the underlying mechanisms.


Subject(s)
COVID-19/immunology , Cytokine Release Syndrome/immunology , Host-Pathogen Interactions/immunology , SARS-CoV-2/pathogenicity , Severe Acute Respiratory Syndrome/immunology , Anti-Inflammatory Agents/therapeutic use , COVID-19/drug therapy , COVID-19/mortality , COVID-19/virology , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/mortality , Cytokine Release Syndrome/virology , Dexamethasone/therapeutic use , Gene Expression Regulation , Host-Pathogen Interactions/genetics , Humans , Immunity, Innate/drug effects , Inflammation , Interferon Type I/genetics , Interferon Type I/immunology , Interleukins/genetics , Interleukins/immunology , SARS-CoV-2/immunology , Severe Acute Respiratory Syndrome/drug therapy , Severe Acute Respiratory Syndrome/mortality , Severe Acute Respiratory Syndrome/virology , Severity of Illness Index , Signal Transduction , Survival Analysis
7.
Int Rev Immunol ; 40(1-2): 5-53, 2021.
Article in English | MEDLINE | ID: covidwho-1236148

ABSTRACT

Coronavirus infections are responsible for mild, moderate, and severe infections in birds and mammals. These were first isolated in humans as causal microorganisms responsible for common cold. The 2002-2003 SARS epidemic caused by SARS-CoV and 2012 MERS epidemic (64 countries affected) caused by MERS-CoV showed their acute and fatal side. These two CoV infections killed thousands of patients infected worldwide. However, WHO has still reported the MERS case in December 2019 in middle-eastern country (Saudi Arabia), indicating the MERS epidemic has not ended completely yet. Although we have not yet understood completely these two CoV epidemics, a third most dangerous and severe CoV infection has been originated in the Wuhan city, Hubei district of China in December 2019. This CoV infection called COVID-19 or SARS-CoV2 infection has now spread to 210 countries and territories around the world. COVID-19 has now been declared a pandemic by the World Health Organization (WHO). It has infected more than 16.69 million people with more than 663,540 deaths across the world. Thus the current manuscript aims to describe all three (SARS, MERS, and COVID-19) in terms of their causal organisms (SARS-CoV, MERS-CoV, and SARS-CoV2), similarities and differences in their clinical symptoms, outcomes, immunology, and immunopathogenesis, and possible future therapeutic approaches.


Subject(s)
COVID-19/pathology , Coronaviridae/ultrastructure , Middle East Respiratory Syndrome Coronavirus/immunology , SARS Virus/immunology , SARS-CoV-2/immunology , Severe Acute Respiratory Syndrome/pathology , Animals , COVID-19/diagnosis , COVID-19/mortality , Camelus/virology , Chiroptera/virology , Coronaviridae/classification , Disease Reservoirs/virology , Disease Susceptibility/virology , Humans , Middle East Respiratory Syndrome Coronavirus/pathogenicity , SARS Virus/pathogenicity , SARS-CoV-2/pathogenicity , Severe Acute Respiratory Syndrome/diagnosis , Severe Acute Respiratory Syndrome/mortality , Virus Replication/physiology
9.
Eur Rev Med Pharmacol Sci ; 25(3): 1743-1751, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-1102761

ABSTRACT

OBJECTIVE: This study evaluated the ability of mid-regional proadrenomedullin (MR-proADM) to identify disease severity in Coronavirus disease 2019 (COVID-19) patients in comparison to conventional inflammatory biomarkers and clinical scores. PATIENTS AND METHODS: In an observational trial, COVID-19 acute respiratory distress syndrome (ARDS) patients were enrolled. MR-proADM, C-reactive protein (CRP), procalcitonin (PCT) and lactic acid (LA) were measured in all patients at admission (T0), at 24 hours (T1) and in the third (T3) and fifth day (T5) of hospitalization. The aims of this study were to determine the role of MR-proADM to detect patients with high risk of mortality and compare the prognostic value of MR-proADM with commonly used clinical scores (Sequential Organ Failure Assessment score - SOFA score, Acute Physiologic Assessment and Chronic Health Evaluation II score - APACHE II score, and Simplified Acute Physiological score II - SAPS II score). RESULTS: Twenty-one COVID-19 ARDS patients admitted to the Intermediate Care Unit (IMCU) were enrolled. The median MR-proADM values were 2.28, 2.41, 1.96 and 1.89 nmol/L at T0, T1, T3 and T5, respectively. The 30-day all-cause mortality rate was 52.4%. Mean MR-proADM T0 value was significantly higher in non-survivors compared with survivors (3.5 vs. 1.1 nmol/L, p < 0.05). No significant differences were found for the other inflammatory biomarkers. In terms of the area under the receiver-operating characteristic curve (AUC), MR-proADM showed a similar discriminatory power compared with APACHE II, SOFA and SAPS II score (0.81, 0.91, 0.70 and 0.78, respectively). The optimal MR-proADM cut-point cut-off point was 1.07 nmol/L, which corresponds to a sensitivity of 91% and a specificity of 71%. CONCLUSIONS: MR-proADM, in addition to the clinical scores, could be useful to predict outcome in COVID-19 ARDS patients.


Subject(s)
Adrenomedullin/blood , COVID-19/blood , Protein Precursors/blood , SARS-CoV-2 , Severe Acute Respiratory Syndrome/blood , APACHE , Biomarkers/blood , C-Reactive Protein/analysis , COVID-19/mortality , Humans , Italy , Organ Dysfunction Scores , Prognosis , ROC Curve , Severe Acute Respiratory Syndrome/mortality , Severe Acute Respiratory Syndrome/virology
10.
Rev Med Virol ; 31(6): e2225, 2021 11.
Article in English | MEDLINE | ID: covidwho-1095682

ABSTRACT

Convalescent plasma therapy (CPT) has been investigated as a treatment for COVID-19. This review evaluates CPT in COVID-19 and other viral respiratory diseases, including severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and influenza. PubMed and Google scholar databases were used to collect eligible publications until 8 December 2020. Meta-analysis used Mantel-Haenszel risk ratio (RR) with 95% confidence interval (CI) and pooled analysis for individual patient data with inverse variance weighted average. The study is registered at PROSPERO with the number of CRD4200270579. Forty-four studies with 36,716 participants were included in the pooled analysis and 20 studies in the meta-analysis. Meta-analysis showed reduction of mortality (RR 0.57, 95% CI [0.43, 0.76], z = 3.86 [p < 0.001], I2  = 44% [p = 0.03]) and higher number of discharged patients (RR 2.53, 95% CI [1.72, 3.72], z = 4.70 [p < 0.001], I2  = 3% [p = 0.39]) in patients receiving CPT compared to standard care alone. A possible mechanism of action is prompt reduction in viral titre. Serious transfusion-related adverse events were reported to be less than 1% of cases, suggesting the overall safety of CPT; nevertheless, the number of patients participating in the studies was still limited. It is also important to notice that in all the studies, the majority of patients were also given other medications, such as antivirals, antibiotics and corticosteroid; furthermore, randomized controlled studies involving more patients and in combination with other treatment modalities are urgently needed.


Subject(s)
COVID-19/therapy , Coronavirus Infections/therapy , Influenza, Human/therapy , Severe Acute Respiratory Syndrome/therapy , Adrenal Cortex Hormones/therapeutic use , Anti-Bacterial Agents/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/immunology , COVID-19/mortality , COVID-19/virology , Combined Modality Therapy/methods , Coronavirus Infections/immunology , Coronavirus Infections/mortality , Coronavirus Infections/virology , Humans , Immunization, Passive , Influenza A Virus, H1N1 Subtype/genetics , Influenza A Virus, H1N1 Subtype/immunology , Influenza, Human/immunology , Influenza, Human/mortality , Influenza, Human/virology , Middle East Respiratory Syndrome Coronavirus/drug effects , Middle East Respiratory Syndrome Coronavirus/immunology , Middle East Respiratory Syndrome Coronavirus/pathogenicity , RNA, Viral/antagonists & inhibitors , RNA, Viral/genetics , RNA, Viral/immunology , SARS Virus/drug effects , SARS Virus/immunology , SARS Virus/pathogenicity , SARS-CoV-2/drug effects , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , Severe Acute Respiratory Syndrome/immunology , Severe Acute Respiratory Syndrome/mortality , Severe Acute Respiratory Syndrome/virology , Survival Analysis , Treatment Outcome
11.
Biomed J ; 44(1): 86-93, 2021 03.
Article in English | MEDLINE | ID: covidwho-1091932

ABSTRACT

Coronavirus disease 2019 (COVID-19) outbreak is proving to be an unprecedented disaster that lays its dark shadow on global health, economics and personal freedom. Severe acute respiratory syndrome (SARS) and middle east respiratory syndrome (MERS) epidemics provide scientific data that is useful in better understanding and resolution of COVID-19. Similarities among SARS-CoV, MERS-CoV and SARS-CoV-2 have been investigated in the light of available data. SARS-CoV, MERS-CoV and SARS-CoV-2 evolved in bats and have positive-sense RNA genomes of 27.9 kb, 30.1 kb and 29.9 kb, respectively. Molecular and serological tools used for diagnosis of SARS and MERS patients resemble COVID-19 diagnostic tools. Stability and longevity data of SARS and MERS epidemics contribute in the current pandemic precaution policies. Trials to produce vaccines for SARS-CoV and MERS-CoV failed, therefore different strategies were employed for SARS-CoV2 vaccines production and during the past period antiviral agents, Convalescent plasma and monoclonal antibodies provide potential treatments for sever patients. The mortality rate caused by the SARS-CoV and MERS-CoV reached 15% and 37%, respectively. The first declarations about mortality rate of SARS-CoV-2 was around 2-4% but now this rate differed globally and reached more than 13% in some countries. A realistic COVID-19 outbreak scenario suggest that the pandemic might last for three years with fluctuation in the number of infected cases, unless vaccination process goes faster and/or antiviral drug is discovered.


Subject(s)
COVID-19/epidemiology , Coronavirus Infections/epidemiology , SARS-CoV-2 , Severe Acute Respiratory Syndrome/epidemiology , Adult , Age Factors , Aged , COVID-19/mortality , COVID-19/therapy , Comorbidity , Coronavirus Infections/mortality , Coronavirus Infections/therapy , Female , Humans , Male , Middle Aged , Severe Acute Respiratory Syndrome/mortality , Severe Acute Respiratory Syndrome/therapy , Sex Characteristics
12.
J Immunol ; 206(7): 1569-1575, 2021 04 01.
Article in English | MEDLINE | ID: covidwho-1067833

ABSTRACT

The IL-1 receptor antagonist, anakinra, may represent a therapeutic option for acute respiratory distress syndrome (ARDS) associated with coronavirus disease 2019 (COVID-19). In this study, COVID-19 ARDS patients admitted to the Azienda Socio Sanitaria Territoriale of Lecco, Italy, between March 5th to April 15th, 2020, and who had received anakinra off-label were retrospectively evaluated and compared with a cohort of matched controls who did not receive immunomodulatory treatment. The primary end point was survival at day 28. The population consisted of 112 patients (56 treated with anakinra and 56 controls). Survival at day 28 was obtained in 69 patients (61.6%) and was significantly higher in anakinra-treated patients than in the controls (75.0 versus 48.2%, p = 0.007). When stratified by continuous positive airway pressure support at baseline, anakinra-treated patients' survival was also significant compared with the controls (p = 0.008). Univariate analysis identified anakinra usage (odds ratio, 3.2; 95% confidence interval, 1.47-7.17) as a significant survival predictor. This was not supported by multivariate modeling. The rate of infectious-related adverse events was similar between groups. In conclusion, anakinra improved overall survival and invasive ventilation-free survival and was well tolerated in patients with ARDS associated with COVID-19.


Subject(s)
COVID-19 , Interleukin 1 Receptor Antagonist Protein/administration & dosage , Respiration, Artificial , SARS-CoV-2/immunology , Severe Acute Respiratory Syndrome , Aged , COVID-19/immunology , COVID-19/mortality , COVID-19/therapy , Disease-Free Survival , Female , Humans , Interleukin 1 Receptor Antagonist Protein/antagonists & inhibitors , Interleukin 1 Receptor Antagonist Protein/immunology , Male , Middle Aged , Retrospective Studies , Severe Acute Respiratory Syndrome/immunology , Severe Acute Respiratory Syndrome/mortality , Severe Acute Respiratory Syndrome/therapy , Severe Acute Respiratory Syndrome/virology , Survival Rate
13.
Am J Surg Pathol ; 45(5): 587-603, 2021 05 01.
Article in English | MEDLINE | ID: covidwho-1044003

ABSTRACT

Coronavirus Disease 2019 (COVID-19), caused by the novel Severe Acute Respiratory Syndrome-associated Coronavirus 2 (SARS-CoV-2), has become a global threat to public health. COVID-19 is more pathogenic and infectious than the prior 2002 pandemic caused by SARS-CoV-1. The pathogenesis of certain disease manifestations in COVID-19 such as diffuse alveolar damage (DAD) are thought to be similar to SARS-CoV-1. However, the exact pathogenesis of COVID-19 related deaths remains poorly understood. The aim of this article was to systematically summarize the rapidly emerging literature regarding COVID-19 autopsies. A meta-analysis was also conducted based on data accrued from preprint and published articles on COVID-19 (n=241 patients) and the results compared with postmortem findings associated with SARS-CoV-1 deaths (n=91 patients). Both autopsy groups included mostly adults of median age 70 years with COVID-19 and 50 years with SARS-CoV-1. Overall, prevalence of DAD was more common in SARS-CoV-1 (100.0%) than COVID-19 (80.9%) autopsies (P=0.001). Extrapulmonary findings among both groups were not statistically significant except for hepatic necrosis (P <0.001), splenic necrosis (P<0.006) and white pulp depletion (P <0.001) that were more common with SARS-CoV-1. Remarkable postmortem findings in association with COVID-19 apart from DAD include pulmonary hemorrhage, viral cytopathic effect within pneumocytes, thromboembolism, brain infarction, endotheliitis, acute renal tubular damage, white pulp depletion of the spleen, cardiac myocyte necrosis, megakaryocyte recruitment, and hemophagocytosis.


Subject(s)
COVID-19/pathology , Lung/pathology , Severe Acute Respiratory Syndrome/pathology , Autopsy , Brain/pathology , COVID-19/mortality , Case-Control Studies , Global Health , Humans , Kidney/pathology , Myocardium/pathology , Severe Acute Respiratory Syndrome/mortality , Spleen/pathology
14.
Clin Microbiol Rev ; 34(1)2020 10 14.
Article in English | MEDLINE | ID: covidwho-1029783

ABSTRACT

The outbreak of coronavirus disease 2019 (COVID-19) in December 2019 in Wuhan, China, introduced the third highly pathogenic coronavirus into humans in the 21st century. Scientific advance after the severe acute respiratory syndrome coronavirus (SARS-CoV) epidemic and Middle East respiratory syndrome coronavirus (MERS-CoV) emergence enabled clinicians to understand the epidemiology and pathophysiology of SARS-CoV-2. In this review, we summarize and discuss the epidemiology, clinical features, and virology of and host immune responses to SARS-CoV, MERS-CoV, and SARS-CoV-2 and the pathogenesis of coronavirus-induced acute respiratory distress syndrome (ARDS). We especially highlight that highly pathogenic coronaviruses might cause infection-associated hemophagocytic lymphohistiocytosis, which is involved in the immunopathogenesis of human coronavirus-induced ARDS, and also discuss the potential implication of hemophagocytic lymphohistiocytosis therapeutics for combating severe coronavirus infection.


Subject(s)
Coronavirus Infections/epidemiology , Cytokine Release Syndrome/epidemiology , Lymphohistiocytosis, Hemophagocytic/epidemiology , Pandemics , Pneumonia, Viral/epidemiology , Severe Acute Respiratory Syndrome/epidemiology , Betacoronavirus/genetics , Betacoronavirus/immunology , Betacoronavirus/pathogenicity , COVID-19 , Coronavirus Infections/immunology , Coronavirus Infections/mortality , Coronavirus Infections/physiopathology , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/mortality , Cytokine Release Syndrome/physiopathology , Host-Pathogen Interactions , Humans , Infectious Disease Incubation Period , Lung/immunology , Lung/physiopathology , Lung/virology , Lymphohistiocytosis, Hemophagocytic/immunology , Lymphohistiocytosis, Hemophagocytic/mortality , Lymphohistiocytosis, Hemophagocytic/physiopathology , Middle East Respiratory Syndrome Coronavirus/genetics , Middle East Respiratory Syndrome Coronavirus/immunology , Middle East Respiratory Syndrome Coronavirus/pathogenicity , Phylogeny , Pneumonia, Viral/immunology , Pneumonia, Viral/mortality , Pneumonia, Viral/physiopathology , SARS Virus/genetics , SARS Virus/immunology , SARS Virus/pathogenicity , SARS-CoV-2 , Severe Acute Respiratory Syndrome/immunology , Severe Acute Respiratory Syndrome/mortality , Severe Acute Respiratory Syndrome/physiopathology , Severity of Illness Index , Survival Analysis
15.
Epidemiol. serv. saúde ; 29(5): e2020644, 2020. tab
Article in English, Portuguese | WHO COVID, LILACS (Americas) | ID: covidwho-1015986

ABSTRACT

Objetivo: Descrever o perfil dos óbitos e a letalidade de síndrome respiratória aguda grave (SRAG) por COVID-19 em crianças e adolescentes hospitalizados no Brasil. Métodos: Estudo transversal, realizado com dados das fichas de notificação de SRAG de crianças e adolescentes (0 a 19 anos) com confirmação laboratorial para COVID-19. Foram incluídas as notificações com evolução completa de SRAG por COVID-19 até a 38ᵃ Semana Epidemiológica de 2020. Resultados: Foram investigadas 6.989 hospitalizações, das quais 661 evoluíram a óbito, perfazendo uma letalidade hospitalar de 9,5%. Observou-se maior letalidade entre menores de 1 ano de idade (14,2%), crianças e adolescentes do sexo feminino (9,7%), indígenas (23,0%) e residentes em zonas rurais (18,1%), como também nas regiões Nordeste (15,4%) e Norte (9,7%) do país. Conclusão: Foram observadas diferenças na letalidade hospitalar, conforme as características sociodemográficas e marcantes desigualdades regionais.


Objetivo: Describir el perfil de muertes y letalidad del Síndrome Respiratorio Agudo Severo (SRAS) por COVID-19 en niños y adolescentes hospitalizados en Brasil. Métodos: Estudio transversal realizado con datos de los formularios de notificación de SRAS de niños y adolescentes (0 a 19 años) confirmados en laboratorio para COVID-19. Se incluyeron notificaciones con evolución completa del SRAS por COVID-19, hasta la 38ª Semana Epidemiológica de 2020. Resultados: Se incluyeron 6.989 hospitalizaciones, 661 fallecidas, resultando en letalidad hospitalaria del 9,5%. Se observaron mayores tasas de letalidad entre los niños menores de un año (14,2%), niñas y adolescentes (9,7%), indígenas (23,0%) y residentes en zonas rurales (18,1%), así como en las regiones Nordeste (15,4%) y Norte (9,7%). Conclusión: Se observaron diferencias en la mortalidad hospitalaria según las características sociodemográficas y marcadas desigualdades regionales.


Objective: To describe the profile of deaths and the lethality of Severe Acute Respiratory Syndrome (SARS) due to COVID-19 in hospitalized children and adolescents in Brazil. Methods: This was a cross-sectional study conducted with data from the SARS notification forms of children and adolescents (0 to 19 years old) with laboratory-confirmed COVID-19. Notifications with complete progression of SARS due to COVID-19 were included, up to the 38th Epidemiological Week of 2020. Results: 6,989 hospitalizations were investigated, 661 died, resulting in 9.5% hospital lethality. Higher lethality rates were observed among children under 1 year of age (14.2%), female children and adolescents (9.7%), the indigenous (23.0%), and those living in rural areas (18.1 %), as well as in the Northeast (15.4%) and North (9.7%) regions of Brazil. Conclusion: Differences in hospital mortality were found according to sociodemographic characteristics and marked regional inequalities.


Subject(s)
Humans , Male , Female , Infant , Child, Preschool , Child , Adolescent , Young Adult , Coronavirus Infections/complications , Coronavirus Infections/mortality , Coronavirus Infections/epidemiology , Severe Acute Respiratory Syndrome/mortality , Severe Acute Respiratory Syndrome/epidemiology , Hospitalization/statistics & numerical data , Brazil/epidemiology , Cross-Sectional Studies , Hospital Mortality , Pandemics/statistics & numerical data , Epidemiological Monitoring , Betacoronavirus/classification
16.
Cancer Cell ; 39(2): 257-275.e6, 2021 02 08.
Article in English | MEDLINE | ID: covidwho-1009339

ABSTRACT

Given the immune system's importance for cancer surveillance and treatment, we have investigated how it may be affected by SARS-CoV-2 infection of cancer patients. Across some heterogeneity in tumor type, stage, and treatment, virus-exposed solid cancer patients display a dominant impact of SARS-CoV-2, apparent from the resemblance of their immune signatures to those for COVID-19+ non-cancer patients. This is not the case for hematological malignancies, with virus-exposed patients collectively displaying heterogeneous humoral responses, an exhausted T cell phenotype and a high prevalence of prolonged virus shedding. Furthermore, while recovered solid cancer patients' immunophenotypes resemble those of non-virus-exposed cancer patients, recovered hematological cancer patients display distinct, lingering immunological legacies. Thus, while solid cancer patients, including those with advanced disease, seem no more at risk of SARS-CoV-2-associated immune dysregulation than the general population, hematological cancer patients show complex immunological consequences of SARS-CoV-2 exposure that might usefully inform their care.


Subject(s)
COVID-19/immunology , Neoplasms/immunology , Neoplasms/virology , Severe Acute Respiratory Syndrome/immunology , Adult , Aged , Aged, 80 and over , COVID-19/etiology , COVID-19/mortality , Female , Hematologic Neoplasms/immunology , Hematologic Neoplasms/mortality , Hematologic Neoplasms/therapy , Hematologic Neoplasms/virology , Humans , Immunophenotyping , Male , Middle Aged , Nasopharynx/virology , Neoplasms/mortality , Neoplasms/therapy , Severe Acute Respiratory Syndrome/etiology , Severe Acute Respiratory Syndrome/mortality , Severe Acute Respiratory Syndrome/virology , T-Lymphocytes/virology , Virus Shedding , Young Adult
17.
Front Public Health ; 8: 578645, 2020.
Article in English | MEDLINE | ID: covidwho-1004709

ABSTRACT

The COVID-19 pandemic brings to light the reality of the Brazilian health system. The underreporting of COVID-19 deaths in the state of Minas Gerais (MG), where the second largest population of the country is concentrated, reveals government unpreparedness, as there is a low capacity of testing in the population, which prevents the real understanding of the general panorama of SARS-CoV-2 dissemination. The goals of this research are to analyze the causes of deaths in different Brazilian government databases (Civil Registry Transparency Portal and InfoGripe) and to assess whether there are sub-records showing an unexpected increase in the frequency of deaths from causes clinically similar to COVID-19. A descriptive and quantitative analysis of the number of deaths by COVID-19 and similar causes was performed in different databases. Our results demonstrate that different official sources had a discrepancy of 109.45% between these data referring to the same period. There was also a 758.57% increase in SARI deaths in 2020, when compared to the average of previous years. Finally, it was shown that there was an increase in the rate of pneumonia and respiratory insufficiency (RI) by 6.34 and 6.25%, respectively. In conclusion, there is an underreporting of COVID-19 deaths in MG due to the unexplained excess of deaths caused by SARI, respiratory insufficiency, and pneumonia compared to previous years.


Subject(s)
COVID-19 , Cause of Death/trends , Severe Acute Respiratory Syndrome , Brazil/epidemiology , COVID-19/epidemiology , COVID-19/mortality , Humans , Pneumonia/epidemiology , Pneumonia/mortality , Respiratory Insufficiency/epidemiology , Respiratory Insufficiency/mortality , SARS-CoV-2 , Severe Acute Respiratory Syndrome/epidemiology , Severe Acute Respiratory Syndrome/mortality
18.
Theranostics ; 11(3): 1207-1231, 2021.
Article in English | MEDLINE | ID: covidwho-966958

ABSTRACT

Rationale: Coronavirus disease 2019 (COVID-19) has spread worldwide and poses a threat to humanity. However, no specific therapy has been established for this disease yet. We conducted a systematic review to highlight therapeutic agents that might be effective in treating COVID-19. Methods: We searched Medline, Medrxiv.org, and reference lists of relevant publications to identify articles of in vitro, in vivo, and clinical studies on treatments for severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and COVID-19 published in English until the last update on October 11, 2020. Results: We included 36 studies on SARS, 30 studies on MERS, and 10 meta-analyses on SARS and MERS in this study. Through 12,200 title and 830 full-text screenings for COVID-19, eight in vitro studies, 46 randomized controlled trials (RCTs) on 6,886 patients, and 29 meta-analyses were obtained and investigated. There was no therapeutic agent that consistently resulted in positive outcomes across SARS, MERS, and COVID-19. Remdesivir showed a therapeutic effect for COVID-19 in two RCTs involving the largest number of total participants (n = 1,461). Other therapies that showed an effect in at least two RCTs for COVID-19 were sofosbuvir/daclatasvir (n = 114), colchicine (n = 140), IFN-ß1b (n = 193), and convalescent plasma therapy (n = 126). Conclusions: This review provides information to help establish treatment and research directions for COVID-19 based on currently available evidence. Further RCTs are required.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/therapy , Coronavirus Infections/therapy , Severe Acute Respiratory Syndrome/therapy , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Alanine/analogs & derivatives , Alanine/therapeutic use , Animals , COVID-19/mortality , Carbamates/therapeutic use , Coronavirus Infections/mortality , Disease Models, Animal , Drug Combinations , Drug Evaluation, Preclinical , Drug Therapy, Combination/methods , Humans , Imidazoles/therapeutic use , Immunization, Passive/methods , Pyrrolidines/therapeutic use , Randomized Controlled Trials as Topic , Severe Acute Respiratory Syndrome/mortality , Sofosbuvir/therapeutic use , Treatment Outcome , Valine/analogs & derivatives , Valine/therapeutic use
19.
Clin Microbiol Rev ; 34(1)2020 12 16.
Article in English | MEDLINE | ID: covidwho-962931

ABSTRACT

Patients and physicians worldwide are facing tremendous health care hazards that are caused by the ongoing severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) pandemic. Remdesivir (GS-5734) is the first approved treatment for severe coronavirus disease 2019 (COVID-19). It is a novel nucleoside analog with a broad antiviral activity spectrum among RNA viruses, including ebolavirus (EBOV) and the respiratory pathogens Middle East respiratory syndrome coronavirus (MERS-CoV), SARS-CoV, and SARS-CoV-2. First described in 2016, the drug was derived from an antiviral library of small molecules intended to target emerging pathogenic RNA viruses. In vivo, remdesivir showed therapeutic and prophylactic effects in animal models of EBOV, MERS-CoV, SARS-CoV, and SARS-CoV-2 infection. However, the substance failed in a clinical trial on ebolavirus disease (EVD), where it was inferior to investigational monoclonal antibodies in an interim analysis. As there was no placebo control in this study, no conclusions on its efficacy in EVD can be made. In contrast, data from a placebo-controlled trial show beneficial effects for patients with COVID-19. Remdesivir reduces the time to recovery of hospitalized patients who require supplemental oxygen and may have a positive impact on mortality outcomes while having a favorable safety profile. Although this is an important milestone in the fight against COVID-19, approval of this drug will not be sufficient to solve the public health issues caused by the ongoing pandemic. Further scientific efforts are needed to evaluate the full potential of nucleoside analogs as treatment or prophylaxis of viral respiratory infections and to develop effective antivirals that are orally bioavailable.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/pharmacology , Coronavirus Infections/drug therapy , Hemorrhagic Fever, Ebola/drug therapy , Pneumonia, Viral/drug therapy , Severe Acute Respiratory Syndrome/drug therapy , Adenosine Monophosphate/pharmacokinetics , Adenosine Monophosphate/pharmacology , Alanine/pharmacokinetics , Alanine/pharmacology , Antiviral Agents/pharmacokinetics , Betacoronavirus/drug effects , Betacoronavirus/growth & development , Betacoronavirus/pathogenicity , COVID-19 , Clinical Trials as Topic , Compassionate Use Trials/methods , Coronavirus Infections/mortality , Coronavirus Infections/pathology , Coronavirus Infections/virology , Drug Administration Schedule , Ebolavirus/drug effects , Ebolavirus/growth & development , Ebolavirus/pathogenicity , Hemorrhagic Fever, Ebola/mortality , Hemorrhagic Fever, Ebola/pathology , Hemorrhagic Fever, Ebola/virology , Humans , Middle East Respiratory Syndrome Coronavirus/drug effects , Middle East Respiratory Syndrome Coronavirus/growth & development , Middle East Respiratory Syndrome Coronavirus/pathogenicity , Pandemics , Patient Safety , Pneumonia, Viral/mortality , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , SARS Virus/drug effects , SARS Virus/growth & development , SARS Virus/pathogenicity , SARS-CoV-2 , Severe Acute Respiratory Syndrome/mortality , Severe Acute Respiratory Syndrome/pathology , Severe Acute Respiratory Syndrome/virology , Survival Analysis , Treatment Outcome
20.
Ren Fail ; 43(1): 1-15, 2020 Nov 09.
Article in English | MEDLINE | ID: covidwho-951457

ABSTRACT

OBJECTIVES: A meta-analysis and systematic review was conducted on kidney-related outcomes of three recent pandemics: SARS, MERS, and COVID-19, which were associated with potentially fatal acute respiratory distress syndrome (ARDS). METHODS: A search of all published studies until 16 June 2020 was performed. The incidence/prevalence and mortality risk of acute and chronic renal events were evaluated, virus prevalence, and mortality in preexisting hemodialysis patients was investigated. RESULTS: A total of 58 eligible studies involving 13452 hospitalized patients with three types of coronavirus infection were included. The reported incidence of new-onset acute kidney injury (AKI) was 12.5% (95% CI: 7.6%-18.3%). AKI significantly increased the mortality risk (OR = 5.75, 95% CI 3.75-8.77, p < 0.00001) in patients with coronavirus infection. The overall rate of urgent-start kidney replacement therapy (urgent-start KRT) use was 8.9% (95% CI: 5.0%-13.8%) and those who received urgent-start KRT had a higher risk of mortality (OR = 3.43, 95% CI 2.02-5.85, p < 0.00001). Patients with known chronic kidney disease (CKD) had a higher mortality than those without CKD (OR = 1.97, 95% CI 1.56-2.49, p < 0.00001). The incidence of coronavirus infection was 7.7% (95% CI: 4.9%-11.1%) in prevalent hemodialysis patients with an overall mortality rate of 26.2% (95% CI: 20.6%-32.6%). CONCLUSIONS: Primary kidney involvement is common with coronavirus infection and is associated with significantly increased mortality. The recognition of AKI, CKD, and urgent-start KRT as major risk factors for mortality in coronavirus-infected patients are important steps in reducing future mortality and long-term morbidity in hospitalized patients with coronavirus infection.


Subject(s)
Acute Kidney Injury , COVID-19 , Coronavirus Infections , Kidney Failure, Chronic , Severe Acute Respiratory Syndrome , Acute Kidney Injury/epidemiology , Acute Kidney Injury/therapy , Acute Kidney Injury/virology , COVID-19/mortality , COVID-19/physiopathology , Coronavirus , Coronavirus Infections/mortality , Coronavirus Infections/physiopathology , Humans , Incidence , Kidney Failure, Chronic/epidemiology , Kidney Failure, Chronic/therapy , Kidney Failure, Chronic/virology , Pandemics/statistics & numerical data , Renal Replacement Therapy/statistics & numerical data , Risk Factors , Severe Acute Respiratory Syndrome/mortality , Severe Acute Respiratory Syndrome/physiopathology
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