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1.
IUBMB Life ; 74(1): 62-73, 2022 01.
Article in English | MEDLINE | ID: covidwho-1850068

ABSTRACT

Airborne pollution has become a leading cause of global death in industrialized cities and the exposure to environmental pollutants has been demonstrated to have adverse effects on human health. Among the pollutants, particulate matter (PM) is one of the most toxic and although its exposure has been more commonly correlated with respiratory diseases, gastrointestinal (GI) complications have also been reported as a consequence to PM exposure. Due to its composition, PM is able to exert on intestinal mucosa both direct damaging effects, (by reaching it either via direct ingestion of contaminated food and water or indirect inhalation and consequent macrophagic mucociliary clearance) and indirect ones via generation of systemic inflammation. The relationship between respiratory and GI conditions is well described by the lung-gut axis and more recently, has become even clearer during coronavirus disease 2019 (COVID-19) pandemic, when respiratory symptoms were associated with gastrointestinal conditions. This review aims at pointing out the mechanisms and the models used to evaluate PM induced GI tract damage.


Subject(s)
COVID-19/etiology , Gastrointestinal Tract/injuries , Particulate Matter/toxicity , SARS-CoV-2 , Administration, Inhalation , Administration, Oral , COVID-19/physiopathology , COVID-19/prevention & control , Gastrointestinal Tract/physiopathology , Humans , Intestinal Mucosa/injuries , Intestinal Mucosa/physiopathology , Masks , Microplastics/toxicity , Models, Biological , Mucociliary Clearance/physiology , Nutrition Policy , Pandemics/prevention & control , Particulate Matter/administration & dosage , Respiratory System/injuries , Respiratory System/physiopathology
2.
PLoS One ; 16(11): e0257549, 2021.
Article in English | MEDLINE | ID: covidwho-1793615

ABSTRACT

Particulate generation occurs during exercise-induced exhalation, and research on this topic is scarce. Moreover, infection-control measures are inadequately implemented to avoid particulate generation. A laminar airflow ventilation system (LFVS) was developed to remove respiratory droplets released during treadmill exercise. This study aimed to investigate the relationship between the number of aerosols during training on a treadmill and exercise intensity and to elucidate the effect of the LFVS on aerosol removal during anaerobic exercise. In this single-center observational study, the exercise tests were performed on a treadmill at Running Science Lab in Japan on 20 healthy subjects (age: 29±12 years, men: 80%). The subjects had a broad spectrum of aerobic capacities and fitness levels, including athletes, and had no comorbidities. All of them received no medication. The exercise intensity was increased by 1-km/h increments until the heart rate reached 85% of the expected maximum rate and then maintained for 10 min. The first 10 subjects were analyzed to examine whether exercise increased the concentration of airborne particulates in the exhaled air. For the remaining 10 subjects, the LFVS was activated during constant-load exercise to compare the number of respiratory droplets before and after LFVS use. During exercise, a steady amount of particulates before the lactate threshold (LT) was followed by a significant and gradual increase in respiratory droplets after the LT, particularly during anaerobic exercise. Furthermore, respiratory droplets ≥0.3 µm significantly decreased after using LFVS (2120800±759700 vs. 560 ± 170, p<0.001). The amount of respiratory droplets significantly increased after LT. The LFVS enabled a significant decrease in respiratory droplets during anaerobic exercise in healthy subjects. This study's findings will aid in exercising safely during this pandemic.


Subject(s)
Air Conditioning/methods , COVID-19/prevention & control , Exercise/physiology , Particulate Matter/chemistry , Adult , Aerosols/chemistry , Air Filters , Anaerobic Threshold/physiology , COVID-19/metabolism , Exercise Test/methods , Exhalation/physiology , Female , Heart Rate/physiology , Humans , Japan , Lactic Acid/metabolism , Male , Oxygen Consumption/physiology , Respiration , Respiratory System/physiopathology , Running/physiology , SARS-CoV-2/pathogenicity , Ventilation/methods
4.
Viruses ; 13(12)2021 11 25.
Article in English | MEDLINE | ID: covidwho-1542796

ABSTRACT

Children with COVID-19 develop moderate symptoms in most cases. Thus, a proportion of children requires hospital admission. The study aimed to assess the history, clinical and laboratory parameters in children with COVID-19 concerning the severity of respiratory symptoms. The study included 332 children (median age 57 months) with COVID-19. History data, clinical findings, laboratory parameters, treatment, and outcome, were evaluated. Children were compared in the groups that varied in the severity of symptoms of respiratory tract involvement. Children who required oxygen therapy represented 8.73%, and intensive care 1.5% of the whole cohort. Comorbidities were present in 126 patients (37.95%). Factors increasing the risk of oxygen therapy included comorbidities (odds ratio (OR) = 92.39; 95% confidence interval (95% CI) = (4.19; 2036.90); p < 0.00001), dyspnea (OR = 45.81; 95% CI (4.05; 518.21); p < 0.00001), auscultation abnormalities (OR = 34.33; 95% CI (2.59; 454.64); p < 0.00001). Lactate dehydrogenase (LDH) > 280 IU/L and creatinine kinase > 192 IU/L were parameters with a good area under the curve (0.804-LDH) and a positive predictive value (42.9%-CK). The clinical course of COVID-19 was mild to moderate in most patients. Children with comorbidities, dyspnea, or abnormalities on auscultation are at risk of oxygen therapy. Laboratory parameters potentially useful in patients evaluated for the severe course are LDH > 200 IU/L and CK > 192 IU/L.


Subject(s)
COVID-19/physiopathology , Respiratory System/physiopathology , Adolescent , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/therapy , Child , Child, Preschool , Comorbidity , Female , Hospitalization , Humans , Infant , Male , Respiration, Artificial , Respiratory System/diagnostic imaging , Risk Factors , SARS-CoV-2 , Severity of Illness Index
6.
Elife ; 102021 08 20.
Article in English | MEDLINE | ID: covidwho-1368024

ABSTRACT

Background: Previously, we conducted a systematic review and analyzed the respiratory kinetics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (Chen et al., 2021). How age, sex, and coronavirus disease 2019 (COVID-19) severity interplay to influence the shedding dynamics of SARS-CoV-2, however, remains poorly understood. Methods: We updated our systematic dataset, collected individual case characteristics, and conducted stratified analyses of SARS-CoV-2 shedding dynamics in the upper (URT) and lower respiratory tract (LRT) across COVID-19 severity, sex, and age groups (aged 0-17 years, 18-59 years, and 60 years or older). Results: The systematic dataset included 1266 adults and 136 children with COVID-19. Our analyses indicated that high, persistent LRT shedding of SARS-CoV-2 characterized severe COVID-19 in adults. Severe cases tended to show slightly higher URT shedding post-symptom onset, but similar rates of viral clearance, when compared to nonsevere infections. After stratifying for disease severity, sex and age (including child vs. adult) were not predictive of respiratory shedding. The estimated accuracy for using LRT shedding as a prognostic indicator for COVID-19 severity was up to 81%, whereas it was up to 65% for URT shedding. Conclusions: Virological factors, especially in the LRT, facilitate the pathogenesis of severe COVID-19. Disease severity, rather than sex or age, predicts SARS-CoV-2 kinetics. LRT viral load may prognosticate COVID-19 severity in patients before the timing of deterioration and should do so more accurately than URT viral load. Funding: Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant, NSERC Senior Industrial Research Chair, and the Toronto COVID-19 Action Fund.


Subject(s)
COVID-19/physiopathology , Respiratory System/physiopathology , SARS-CoV-2/physiology , Virus Shedding , Adult , COVID-19/diagnosis , COVID-19/virology , Child , Female , Humans , Male , Prognosis , Respiratory System/virology , Severity of Illness Index , Viral Load
7.
Annu Rev Biomed Eng ; 23: 547-577, 2021 07 13.
Article in English | MEDLINE | ID: covidwho-1307981

ABSTRACT

The host-to-host transmission of respiratory infectious diseases is fundamentally enabled by the interaction of pathogens with a variety of fluids (gas or liquid) that shape pathogen encapsulation and emission, transport and persistence in the environment, and new host invasion and infection. Deciphering the mechanisms and fluid properties that govern and promote these steps of pathogen transmission will enable better risk assessment and infection control strategies, and may reveal previously underappreciated ways in which the pathogens might actually adapt to or manipulate the physical and chemical characteristics of these carrier fluids to benefit their own transmission. In this article, I review our current understanding of the mechanisms shaping the fluid dynamics of respiratory infectious diseases.


Subject(s)
Communicable Diseases/physiopathology , Communicable Diseases/transmission , Hydrodynamics , Respiration Disorders/physiopathology , Aerosols , COVID-19/transmission , History, 19th Century , History, 20th Century , History, 21st Century , Humans , Infectious Disease Medicine/history , Physical Distancing , Respiratory System/physiopathology , Respiratory System/virology , Rheology , SARS-CoV-2 , Saliva , Ventilation
8.
Ann N Y Acad Sci ; 1486(1): 15-38, 2021 02.
Article in English | MEDLINE | ID: covidwho-1263857

ABSTRACT

Exposure to air pollutants has been previously associated with respiratory viral infections, including influenza, measles, mumps, rhinovirus, and respiratory syncytial virus. Epidemiological studies have also suggested that air pollution exposure is associated with increased cases of SARS-CoV-2 infection and COVID-19-associated mortality, although the molecular mechanisms by which pollutant exposure affects viral infection and pathogenesis of COVID-19 remain unknown. In this review, we suggest potential molecular mechanisms that could account for this association. We have focused on the potential effect of exposure to nitrogen dioxide (NO2 ), ozone (O3 ), and particulate matter (PM) since there are studies investigating how exposure to these pollutants affects the life cycle of other viruses. We have concluded that pollutant exposure may affect different stages of the viral life cycle, including inhibition of mucociliary clearance, alteration of viral receptors and proteases required for entry, changes to antiviral interferon production and viral replication, changes in viral assembly mediated by autophagy, prevention of uptake by macrophages, and promotion of viral spread by increasing epithelial permeability. We believe that exposure to pollutants skews adaptive immune responses toward bacterial/allergic immune responses, as opposed to antiviral responses. Exposure to air pollutants could also predispose exposed populations toward developing COIVD-19-associated immunopathology, enhancing virus-induced tissue inflammation and damage.


Subject(s)
Air Pollution/adverse effects , COVID-19/etiology , Pandemics , SARS-CoV-2 , Adaptive Immunity , Air Pollutants/adverse effects , COVID-19/immunology , COVID-19/virology , Host Microbial Interactions , Humans , Immunity, Innate , Models, Biological , Particulate Matter/adverse effects , Receptors, Virus/physiology , Respiratory System/physiopathology , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , SARS-CoV-2/physiology , Toll-Like Receptors/physiology , Virus Internalization , Virus Replication
10.
J Transl Med ; 19(1): 128, 2021 03 29.
Article in English | MEDLINE | ID: covidwho-1158209

ABSTRACT

BACKGROUND: Omega-3 polyunsaturated fatty acids (n3-PUFAs) may exert beneficial effects on the immune system of patients with viral infections. This paper aimed to examine the effect of n3-PUFA supplementation on inflammatory and biochemical markers in critically ill patients with COVID-19. METHODS: A double-blind, randomized clinical trial study was conducted on 128 critically ill patients infected with COVID-19 who were randomly assigned to the intervention (fortified formula with n3-PUFA) (n = 42) and control (n = 86) groups. Data on 1 month survival rate, blood glucose, sodium (Na), potassium (K), blood urea nitrogen (BUN), creatinine (Cr), albumin, hematocrit (HCT), calcium (Ca), phosphorus (P), mean arterial pressure (MAP), O2 saturation (O2sat), arterial pH, partial pressure of oxygen (PO2), partial pressure of carbon dioxide (PCO2), bicarbonate (HCO3), base excess (Be), white blood cells (WBCs), Glasgow Coma Scale (GCS), hemoglobin (Hb), platelet (Plt), and the partial thromboplastin time (PTT) were collected at baseline and after 14 days of the intervention. RESULTS: The intervention group had significantly higher 1-month survival rate and higher levels of arterial pH, HCO3, and Be and lower levels of BUN, Cr, and K compared with the control group after intervention (all P < 0.05). There were no significant differences between blood glucose, Na, HCT, Ca, P, MAP, O2sat, PO2, PCO2, WBCs, GCS, Hb, Plt, PTT, and albumin between two groups. CONCLUSION: Omega-3 supplementation improved the levels of several parameters of respiratory and renal function in critically ill patients with COVID-19. Further clinical studies are warranted. Trial registry Name of the registry: This study was registered in the Iranian Registry of Clinical Trials (IRCT); Trial registration number: IRCT20151226025699N3; Date of registration: 2020.5.20; URL of trial registry record: https://en.irct.ir/trial/48213.


Subject(s)
COVID-19/diet therapy , COVID-19/diagnosis , Critical Illness/therapy , Fatty Acids, Omega-3/pharmacology , Adult , Aged , Aged, 80 and over , Biomarkers/analysis , Biomarkers/blood , Blood Gas Analysis , Blood Glucose/drug effects , Blood Glucose/metabolism , COVID-19/mortality , COVID-19/physiopathology , Critical Illness/mortality , Dietary Supplements , Double-Blind Method , Fatty Acids, Omega-3/administration & dosage , Female , Hematocrit , Humans , Inflammation Mediators/analysis , Inflammation Mediators/blood , Iran/epidemiology , Kidney/drug effects , Kidney/physiopathology , Kidney/virology , Male , Middle Aged , Mortality , Prognosis , Respiratory System/drug effects , Respiratory System/physiopathology , Respiratory System/virology , SARS-CoV-2/drug effects , Survival Analysis , Treatment Outcome
11.
Nutrients ; 13(3)2021 Mar 20.
Article in English | MEDLINE | ID: covidwho-1143547

ABSTRACT

Severe obesity is associated with an increased risk of admission to intensive care units and need for invasive mechanical ventilation in patients with COVID-19. The association of obesity and COVID-19 prognosis may be related to many different factors, such as chronic systemic inflammation, the predisposition to severe respiratory conditions and viral infections. The ketogenic diet is an approach that can be extremely effective in reducing body weight and visceral fat in the short term, preserving the lean mass and reducing systemic inflammation. Therefore, it is a precious preventive measure for severely obese people and may be considered as an adjuvant therapy for patients with respiratory compromise.


Subject(s)
COVID-19/diet therapy , Diet, Ketogenic/methods , COVID-19/etiology , COVID-19/prevention & control , Humans , Inflammation/prevention & control , Obesity/complications , Respiratory System/physiopathology , Respiratory System/virology
12.
J Investig Allergol Clin Immunol ; 31(1): 17-35, 2021 Feb 17.
Article in English | MEDLINE | ID: covidwho-1102728

ABSTRACT

Airway examination procedures can potentially transmit infectious diseases to patients and to the health care professionals who perform them via various mechanisms. The COVID-19 pandemic has halted most of the activity of the clinics and laboratories involved in assessment of lung and nasal function, and clear recommendations in this regard have been made. Today, we still do not know for sure what its consequences will be in the short or long term, since important gaps remain in our knowledge of aspects as fundamental as virus transmission mechanisms, pathophysiology, immune response, and diagnosis. In this review, we study the examination techniques used to assess patients with respiratory allergy, asthma, and associated diseases during this period and highlight their possible advantages and disadvantages. Therefore, we focus on exploring the entire upper and lower airways, from the perspective of the safety of both health professionals and patients and their specific characteristics. We also analyze the intrinsic value of these interventions in terms of diagnosis and patient management. The changing situation of COVID-19 may mean that some of the assertions presented in this review will have to be modified in the future. While we seek to ensure a consistently broad approach, some differences in operational details may apply owing to local regulations.


Subject(s)
COVID-19 , Occupational Health , Patient Safety , Respiratory Hypersensitivity/physiopathology , Respiratory System/physiopathology , SARS-CoV-2 , COVID-19/diagnosis , COVID-19/transmission , Health Personnel , Humans , Mass Screening , Respiratory Function Tests , Ventilation
13.
Am J Gastroenterol ; 116(1): 202-205, 2021 01 01.
Article in English | MEDLINE | ID: covidwho-1068052

ABSTRACT

INTRODUCTION: During the coronavirus disease 2019 pandemic, whether endoscopy generates aerosols needs to be determined. METHODS: In patients undergoing upper gastrointestinal endoscopy with an enclosure covering their heads, 0.3-10-µm aerosols were measured for 60 seconds before, during, and after endoscopy by an optical counter. Whether aerosols increased in the situation with and without endoscopy was examined. RESULTS: The analysis included 103 consecutive patients undergoing endoscopy and 90 control patients. Aerosols increased significantly during endoscopy compared with the control group. Body mass index and burping were significant factors related to increased aerosols during endoscopy. DISCUSSION: Upper gastrointestinal endoscopy was an aerosol-generating procedure.


Subject(s)
Aerosols/analysis , COVID-19 , Disease Transmission, Infectious/prevention & control , Endoscopy, Gastrointestinal , Gastrointestinal Diseases/diagnosis , Infection Control , Respiratory Protective Devices/virology , Respiratory System , COVID-19/epidemiology , COVID-19/prevention & control , Endoscopy, Gastrointestinal/adverse effects , Endoscopy, Gastrointestinal/methods , Female , Humans , Infection Control/instrumentation , Infection Control/methods , Japan/epidemiology , Male , Materials Testing , Middle Aged , Outcome Assessment, Health Care , Respiratory System/physiopathology , Respiratory System/virology , SARS-CoV-2
14.
J Nepal Health Res Counc ; 18(3): 351-359, 2020 Nov 13.
Article in English | MEDLINE | ID: covidwho-934733

ABSTRACT

Coronavirus disease 2019 has emerged as a global pandemic, affecting millions of people across the globe. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters the human cell after binding to the Angiotensin-Converting Enzyme 2 receptors, that are present in various organs. The involvement of the respiratory system is common and may progress to acute respiratory distress syndrome. Besides the involvement of respiratory system other systems like cardiovascular, renal, gastrointestinal and central nervous are not uncommon. In-depth understanding of the pathophysiological basis of organs and systems involvement and disease progression aids in the safe and effective management of the COVID-19 patients. It also helps to guide future well-designed clinical trials, which is the need of time. This review aims to explore the current understanding of pathophysiological basis of various organ system involvement in patients with COVID-19, that can have relevance for patient management and future research. We reviewed the articles in various databases to assemble the current evidences. Keywords: Coronavirus disease 2019; COVID-19; pathophysiology; severe acute respiratory syndrome coronavirus 2.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , COVID-19/physiopathology , Biomarkers , Cardiovascular System/physiopathology , Cytokines/metabolism , Gastrointestinal Tract/physiopathology , Humans , Kidney/physiopathology , Nervous System/physiopathology , Respiratory System/physiopathology , SARS-CoV-2
15.
Salud Publica Mex ; 62(5): 582-589, 2020.
Article in Spanish | MEDLINE | ID: covidwho-841637

ABSTRACT

OBJECTIVE: To analyze the evidence on the relationship between air pollution and an increased risk of morbidity and mortality from Covid-19. MATERIALS AND METHODS: An adaptation of the Cochrane rapid review methodology was used. The search was performed in PubMed and MedRxiv and was limited until April 28 and 26, respectively. The titles and abstracts were reviewed by five researchers who, in turn, reviewed the full texts of the final selection. RESULTS: 450 manuscripts were found, 15 met the inclusion criteria. The evidence reports that the incidence and risk of morbidity and mortality from Covid-19 increase with chronic and acute exposure to air pollution, particularly to particulate matter (PM2.5, P M10) and nitrogen dioxide. CONCLUSIONS: More studies are required especially in Latin American cities. It is necessary to strengthen the recommendations in cities with higher levels of pollutants and to reduce their emissions.


OBJETIVO: Analizar la evidencia sobre la relación entre la contaminación del aire y un riesgo mayor de morbimor-talidad por Covid-19. MATERIAL Y MÉTODOS: Se utilizó una adaptación de la metodología de revisiones rápidas de Cochrane. La búsqueda se realizó en PubMed y MedRxiv y se limitó hasta el 28 y 26 de abril, respectivamente. Los títu-los y resúmenes fueron revisados por cinco investigadores que, a su vez, revisaron los textos completos de la selección final. RESULTADOS: Se encontraron 450 manuscritos, 15 cumplieron los criterios de inclusión. La evidencia encon-trada reporta que la incidencia y el riesgo de morbilidad y mortalidad por Covid-19 se incrementan con la exposición crónica y aguda a la contaminación del aire, particularmente a material particulado (PM2.5, P M10) y dióxido de nitrógeno. CONCLUSIONES: Se requieren más estudios especialmente en ciudades latinoamericanas. Es necesario fortalecer las recomendaciones en las ciudades con mayores niveles de contaminantes y reducir sus emisiones.


Subject(s)
Air Pollution/adverse effects , Betacoronavirus , Coronavirus Infections/epidemiology , Pandemics , Pneumonia, Viral/epidemiology , Air Pollutants/adverse effects , COVID-19 , Cities , Coronavirus Infections/etiology , Disease Susceptibility , Environmental Exposure , Environmental Monitoring , Humans , Incidence , Latin America/epidemiology , Meteorological Concepts , Particulate Matter/adverse effects , Pneumonia, Viral/etiology , Respiratory System/physiopathology , Respiratory System/virology , SARS-CoV-2 , Severe Acute Respiratory Syndrome/etiology , Severe Acute Respiratory Syndrome/mortality , Urban Health
16.
Biomed Res Int ; 2020: 3292916, 2020.
Article in English | MEDLINE | ID: covidwho-825385

ABSTRACT

In December of 2019, there was an outbreak of a severe acute respiratory syndrome caused by the coronavirus 2 (SARS-CoV-2 or COVID-19) in China. The virus rapidly spread into the whole world causing an unprecedented pandemic and forcing governments to impose a global quarantine, entering an extreme unknown situation. The organizational consequences of quarantine/isolation are absence of organized training and competition, lack of communication among athletes and coaches, inability to move freely, lack of adequate sunlight exposure, and inappropriate training conditions. The reduction of mobility imposed to contain the advance of the SARS-Cov-2 pandemic can negatively affect the physical condition and health of individuals leading to muscle atrophy, progressive loss of muscle strength, and reductions in neuromuscular and mechanical capacities. Resistance training (RT) might be an effective tool to counteract these adverse consequences. RT is considered an essential part of an exercise program due to its numerous health and athletic benefits. However, in the face of the SARS-Cov-2 outbreak, many people might be concerned with safety issues regarding its practice, especially in indoor exercise facilities, such as gyms and fitness centers. These concerns might be associated with RT impact in the immune system, respiratory changes, and contamination due to equipment sharing and agglomeration. In this current opinion article, we provide insights to address these issues to facilitate the return of RT practices under the new logistical and health challenges. We understand that RT can be adapted to allow its performance with measures adopted to control coronavirus outbreak such that the benefits would largely overcome the potential risks. The article provides some practical information to help on its implementation.


Subject(s)
Coronavirus Infections/epidemiology , Pandemics , Pneumonia, Viral/epidemiology , Resistance Training/adverse effects , Resistance Training/methods , Betacoronavirus , COVID-19 , China/epidemiology , Coronavirus Infections/physiopathology , Coronavirus Infections/transmission , Disinfection/methods , Humans , Immune System/physiopathology , Pandemics/prevention & control , Pneumonia, Viral/physiopathology , Pneumonia, Viral/transmission , Resistance Training/instrumentation , Respiratory System/physiopathology , Risk Factors , SARS-CoV-2 , Safety
19.
Immunity ; 52(6): 905-909, 2020 06 16.
Article in English | MEDLINE | ID: covidwho-324218

ABSTRACT

Respiratory viruses affect us throughout our lives, from infancy to old age, causing illnesses ranging from a common cold to severe pneumonia. They belong to several virus families, and although many features of infection with these diverse viruses are shared, some have unique characteristics. Here we explain what happens when we are infected by respiratory viruses, including SARS-CoV-2, which causes COVID-19.


Subject(s)
Coronavirus Infections/physiopathology , Pneumonia, Viral/physiopathology , Respiratory System/physiopathology , Adaptive Immunity , Betacoronavirus/physiology , COVID-19 , Coronavirus Infections/immunology , Coronavirus Infections/therapy , Coronavirus Infections/virology , Humans , Immunity, Innate , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/therapy , Pneumonia, Viral/virology , Respiratory System/immunology , Respiratory System/virology , SARS-CoV-2 , Virus Physiological Phenomena , Viruses/classification
20.
Lancet Respir Med ; 8(7): 687-695, 2020 07.
Article in English | MEDLINE | ID: covidwho-197584

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019, causing a respiratory disease (coronavirus disease 2019, COVID-19) of varying severity in Wuhan, China, and subsequently leading to a pandemic. The transmissibility and pathogenesis of SARS-CoV-2 remain poorly understood. We evaluate its tissue and cellular tropism in human respiratory tract, conjunctiva, and innate immune responses in comparison with other coronavirus and influenza virus to provide insights into COVID-19 pathogenesis. METHODS: We isolated SARS-CoV-2 from a patient with confirmed COVID-19, and compared virus tropism and replication competence with SARS-CoV, Middle East respiratory syndrome-associated coronavirus (MERS-CoV), and 2009 pandemic influenza H1N1 (H1N1pdm) in ex-vivo cultures of human bronchus (n=5) and lung (n=4). We assessed extrapulmonary infection using ex-vivo cultures of human conjunctiva (n=3) and in-vitro cultures of human colorectal adenocarcinoma cell lines. Innate immune responses and angiotensin-converting enzyme 2 expression were investigated in human alveolar epithelial cells and macrophages. In-vitro studies included the highly pathogenic avian influenza H5N1 virus (H5N1) and mock-infected cells as controls. FINDINGS: SARS-CoV-2 infected ciliated, mucus-secreting, and club cells of bronchial epithelium, type 1 pneumocytes in the lung, and the conjunctival mucosa. In the bronchus, SARS-CoV-2 replication competence was similar to MERS-CoV, and higher than SARS-CoV, but lower than H1N1pdm. In the lung, SARS-CoV-2 replication was similar to SARS-CoV and H1N1pdm, but was lower than MERS-CoV. In conjunctiva, SARS-CoV-2 replication was greater than SARS-CoV. SARS-CoV-2 was a less potent inducer of proinflammatory cytokines than H5N1, H1N1pdm, or MERS-CoV. INTERPRETATION: The conjunctival epithelium and conducting airways appear to be potential portals of infection for SARS-CoV-2. Both SARS-CoV and SARS-CoV-2 replicated similarly in the alveolar epithelium; SARS-CoV-2 replicated more extensively in the bronchus than SARS-CoV. These findings provide important insights into the transmissibility and pathogenesis of SARS-CoV-2 infection and differences with other respiratory pathogens. FUNDING: US National Institute of Allergy and Infectious Diseases, University Grants Committee of Hong Kong Special Administrative Region, China; Health and Medical Research Fund, Food and Health Bureau, Government of Hong Kong Special Administrative Region, China.


Subject(s)
Betacoronavirus/immunology , Conjunctiva/virology , Coronavirus Infections/immunology , Immunity, Innate/immunology , Pneumonia, Viral/immunology , Respiratory System/virology , Viral Tropism/physiology , Virus Replication/physiology , Adult , Aged , Aged, 80 and over , Betacoronavirus/physiology , COVID-19 , Conjunctiva/immunology , Conjunctiva/physiopathology , Coronavirus Infections/physiopathology , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/physiopathology , Respiratory Mucosa/immunology , Respiratory Mucosa/physiopathology , Respiratory Mucosa/virology , Respiratory System/immunology , Respiratory System/physiopathology , SARS-CoV-2
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