Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 68
Filter
1.
Environ Chem Lett ; 19(1): 17-24, 2021.
Article in English | MEDLINE | ID: covidwho-1906117

ABSTRACT

The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 14 million people globally. Recently, airborne transmission has been postulated to be a major contributor to the spread of the novel coronavirus, especially in enclosed public spaces. While many studies have demonstrated positive correlations between atmospheric pollutants and SARS-CoV-2 infection, the impact of indoor air pollutants on airborne transmission has been largely overlooked. In particular, laser printers are a primary source of particle emission that increases the concentrations of particulate matter in indoor atmosphere by releasing substantial quantities of electrostatic fine particles, at rates comparable with tobacco smoking and incense burning. We hypothesized that particles emitted from laser printers present a potential risk factor for the transmission of SARS-CoV-2 in offices and other indoor environments with high user occupancy. To test this hypothesis, we reviewed recent knowledge on the characteristics of particles emitted by laser printing, including their emission rates and accumulation in indoor air, electrostatic charges, localized emission and subsequent particle diffusion in relation to the human breathing zone. We then discuss the potential impact on the transmission of SAR-CoV-2 in indoor spaces. We found that emission rates from laser printers ranged from 108 to 1012 particles min-1, and these fine particles typically remain suspended for prolonged periods in indoor air. Electrostatic charges carried by these particles can reach 260-379 e per particle, thus enhancing their surface adsorption and deposition in human airways. Localized emission by laser printers and subsequent diffusion highly increase particle concentrations near the human breathing zone.

2.
Clin Infect Dis ; 74(3): 479-489, 2022 02 11.
Article in English | MEDLINE | ID: covidwho-1684541

ABSTRACT

BACKGROUND: Increased inflammation has been well defined in coronavirus disease 2019 (COVID-19), while definitive pathways driving severe forms of this disease remain uncertain. Neutrophils are known to contribute to immunopathology in infections, inflammatory diseases, and acute respiratory distress syndrome, a primary cause of morbidity and mortality in COVID-19. Changes in neutrophil function in COVID-19 may give insight into disease pathogenesis and identify therapeutic targets. METHODS: Blood was obtained serially from critically ill COVID-19 patients for 11 days. Neutrophil extracellular trap formation (NETosis), oxidative burst, phagocytosis, and cytokine levels were assessed. Lung tissue was obtained immediately postmortem for immunostaining. PubMed searches for neutrophils, lung, and COVID-19 yielded 10 peer-reviewed research articles in English. RESULTS: Elevations in neutrophil-associated cytokines interleukin 8 (IL-8) and interleukin 6, and general inflammatory cytokines IFN-inducible protien-19, granulocyte macrophage colony-stimulating factor (GM-CSF), interleukin 1ß, interleukin 10, and tumor necrosis factor, were identified both at first measurement and across hospitalization (P < .0001). COVID-19 neutrophils had exaggerated oxidative burst (P < .0001), NETosis (P < .0001), and phagocytosis (P < .0001) relative to controls. Increased NETosis correlated with leukocytosis and neutrophilia, and neutrophils and NETs were identified within airways and alveoli in lung parenchyma of 40% of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected lungs available for examination (2 of 5). While elevations in IL-8 and absolute neutrophil count correlated with disease severity, plasma IL-8 levels alone correlated with death. CONCLUSIONS: Literature to date demonstrates compelling evidence of increased neutrophils in the circulation and lungs of COVID-19 patients. Importantly, neutrophil quantity and activation correlates with severity of disease. Similarly, our data show that circulating neutrophils in COVID-19 exhibit an activated phenotype with enhanced NETosis and oxidative burst.


Subject(s)
COVID-19 , Extracellular Traps , Critical Illness , Humans , Neutrophil Activation , Neutrophils , Phenotype , SARS-CoV-2
3.
J Virol ; 95(15): e0053021, 2021 07 12.
Article in English | MEDLINE | ID: covidwho-1486507

ABSTRACT

Elicitation of lung tissue-resident memory CD8 T cells (TRMs) is a goal of T cell-based vaccines against respiratory viral pathogens, such as influenza A virus (IAV). C-C chemokine receptor type 2 (CCR2)-dependent monocyte trafficking plays an essential role in the establishment of CD8 TRMs in lungs of IAV-infected mice. Here, we used a combination adjuvant-based subunit vaccine strategy that evokes multifaceted (TC1/TC17/TH1/TH17) IAV nucleoprotein-specific lung TRMs to determine whether CCR2 and monocyte infiltration are essential for vaccine-induced TRM development and protective immunity to IAV in lungs. Following intranasal vaccination, neutrophils, monocytes, conventional dendritic cells (DCs), and monocyte-derived dendritic cells internalized and processed vaccine antigen in lungs. We found that basic leucine zipper ATF-like transcription factor 3 (BATF3)-dependent DCs were essential for eliciting T cell responses, but CCR2 deficiency enhanced the differentiation of CD127hi, KLRG-1lo, OX40+ve CD62L+ve, and mucosally imprinted CD69+ve CD103+ve effector and memory CD8 T cells in lungs and airways of vaccinated mice. Mechanistically, increased development of lung TRMs induced by CCR2 deficiency was linked to dampened expression of T-bet but not altered TCF-1 levels or T cell receptor signaling in CD8 T cells. T1/T17 functional programming, parenchymal localization of CD8/CD4 effector and memory T cells, recall T cell responses, and protective immunity to a lethal IAV infection were unaffected in CCR2-deficient mice. Taken together, we identified a negative regulatory role for CCR2 and monocyte trafficking in mucosal imprinting and differentiation of vaccine-induced TRMs. Mechanistic insights from this study may aid the development of T-cell-based vaccines against respiratory viral pathogens, including IAV and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). IMPORTANCE While antibody-based immunity to influenza A virus (IAV) is type and subtype specific, lung- and airway-resident memory T cells that recognize conserved epitopes in the internal viral proteins are known to provide heterosubtypic immunity. Hence, broadly protective IAV vaccines need to elicit robust T cell memory in the respiratory tract. We have developed a combination adjuvant-based IAV nucleoprotein vaccine that elicits strong CD4 and CD8 T cell memory in lungs and protects against H1N1 and H5N1 strains of IAV. In this study, we examined the mechanisms that control vaccine-induced protective memory T cells in the respiratory tract. We found that trafficking of monocytes into lungs might limit the development of antiviral lung-resident memory T cells following intranasal vaccination. These findings suggest that strategies that limit monocyte infiltration can potentiate vaccine-induced frontline T-cell immunity to respiratory viruses, such as IAV and SARS-CoV-2.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , Immunity, Mucosal , Immunologic Memory , Influenza A virus/immunology , Influenza Vaccines/immunology , Orthomyxoviridae Infections/immunology , Receptors, CCR2/immunology , T-Lymphocytes, Helper-Inducer/immunology , Animals , Influenza A virus/genetics , Influenza Vaccines/genetics , Influenza Vaccines/pharmacology , Lung/immunology , Mice , Mice, Knockout , Orthomyxoviridae Infections/genetics , Orthomyxoviridae Infections/prevention & control , Receptors, CCR2/genetics
4.
Mol Cell Proteomics ; 20: 100113, 2021.
Article in English | MEDLINE | ID: covidwho-1275575

ABSTRACT

Severe coronavirus disease 2019 (COVID-19) can result in pneumonia and acute respiratory failure. Accumulation of mucus in the airways is a hallmark of the disease and can result in hypoxemia. Here, we show that quantitative proteome analysis of the sputum from severe patients with COVID-19 reveal high levels of neutrophil extracellular trap (NET) components, which was confirmed by microscopy. Extracellular DNA from excessive NET formation can increase sputum viscosity and lead to acute respiratory distress syndrome. Recombinant human DNase (Pulmozyme; Roche) has been shown to be beneficial in reducing sputum viscosity and improve lung function. We treated five patients pwith COVID-19 resenting acute symptoms with clinically approved aerosolized Pulmozyme. No adverse reactions to the drug were seen, and improved oxygen saturation and recovery in all severely ill patients with COVID-19 was observed after therapy. Immunofluorescence and proteome analysis of sputum and blood plasma samples after treatment revealed a marked reduction of NETs and a set of statistically significant proteome changes that indicate reduction of hemorrhage, plasma leakage and inflammation in the airways, and reduced systemic inflammatory state in the blood plasma of patients. Taken together, the results indicate that NETs contribute to acute respiratory failure in COVID-19 and that degrading NETs may reduce dependency on external high-flow oxygen therapy in patients. Targeting NETs using recombinant human DNase may have significant therapeutic implications in COVID-19 disease and warrants further studies.


Subject(s)
COVID-19/drug therapy , Deoxyribonuclease I/pharmacology , Extracellular Traps/metabolism , Proteome/analysis , Aged , Blood Proteins/analysis , COVID-19/metabolism , COVID-19/therapy , Female , Fluorescent Antibody Technique , Humans , Male , Middle Aged , Recombinant Proteins/pharmacology , Severity of Illness Index , Sputum/drug effects , Sputum/metabolism , Sputum/virology , Systemic Inflammatory Response Syndrome/drug therapy , Systemic Inflammatory Response Syndrome/metabolism , Systemic Inflammatory Response Syndrome/virology
5.
Mycoses ; 64(9): 980-988, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1273123

ABSTRACT

It is now well known that patients with SARS-CoV-2 infection admitted in ICU and mechanically ventilated are at risk of developing invasive pulmonary aspergillosis (IPA). Nevertheless, symptomatology of IPA is often atypical in mechanically ventilated patients, and radiological aspects in SARS-CoV-2 pneumonia and IPA are difficult to differentiate. In this context, the significance of the presence of Aspergillus in airway specimens (detected by culture, galactomannan antigen or specific PCR) remains to be fully understood. To decipher the relevance of the detection of Aspergillus, we performed a comprehensive review of all published cases of respiratory Aspergillus colonisation and IPA in COVID-19 patients. The comparison of patients receiving or not antifungal treatment allowed us to highlight the most important criteria for the decision to treat. The comparison of surviving and non-surviving patients made it possible to unveil criteria associated with mortality that should be taken into account in the treatment decision.


Subject(s)
Antifungal Agents/therapeutic use , Bronchoalveolar Lavage Fluid/microbiology , COVID-19/microbiology , Cause of Death , Invasive Pulmonary Aspergillosis/diagnosis , Invasive Pulmonary Aspergillosis/drug therapy , Invasive Pulmonary Aspergillosis/mortality , Adult , Aged , Aged, 80 and over , Female , Humans , Intensive Care Units , Male , Middle Aged , SARS-CoV-2
6.
Rev Environ Health ; 37(2): 229-246, 2022 Jun 27.
Article in English | MEDLINE | ID: covidwho-1238797

ABSTRACT

Nitrogen (N) is a critical component of food security, economy and planetary health. Human production of reactive nitrogen (Nr) via Haber-Bosch process and cultivation-induced biological N2 fixation (BNF) has doubled global N cycling over the last century. The most important beneficial effect of Nr is augmenting global food supplies due to increased crop yields. However, increased circulation of Nr in the environment is responsible for serious human health effects such as methemoglobinemia ("blue baby syndrome") and eutrophication of coastal and inland waters. Furthermore, ammonia (NH3) emission mainly from farming and animal husbandary impacts not only human health causing chronic lung disease, inflammation of human airways and irritation of eyes, sinuses and skin but is also involved in the formation of secondary particulate matter (PM) that plays a critical role in environment and human health. Nr also affects human health via global warming, depletion of stratospheric ozone layer resulting in greater intensity of ultra violet B rays (UVB) on the Earth's surface, and creation of ground-level ozone (through reaction of NO2 with O2). The consequential indirect human health effects of Nr include the spread of vector-borne pathogens, increased incidence of skin cancer, development of cataracts, and serious respiratory diseases, besides land degradation. Evidently, the strategies to reduce Nr and mitigate adverse environmental and human health impacts include plugging pathways of nitrogen transport and loss through runoff, leaching and emissions of NH3, nitrogen oxides (NO x ), and other N compounds; improving fertilizer N use efficiency; reducing regional disparity in access to N fertilizers; enhancing BNF to decrease dependence on chemical fertilizers; replacing animal-based proteins with plant-based proteins; adopting improved methods of livestock raising and manure management; reducing air pollution and secondary PM formation; and subjecting industrial and vehicular NO x emission to pollution control laws. Strategic implementation of all these presents a major challenge across the fields of agriculture, ecology and public health. Recent observations on the reduction of air pollution in the COVID-19 lockdown period in several world regions provide an insight into the achievability of long-term air quality improvement. In this review, we focus on complex relationships between Nr and human health, highlighting a wide range of beneficial and detrimental effects.


Subject(s)
COVID-19 , Fertilizers , Agriculture/methods , Animals , Communicable Disease Control , Humans , Nitrogen , Nitrogen Compounds
7.
Clin Infect Dis ; 74(3): 479-489, 2022 02 11.
Article in English | MEDLINE | ID: covidwho-1228461

ABSTRACT

BACKGROUND: Increased inflammation has been well defined in coronavirus disease 2019 (COVID-19), while definitive pathways driving severe forms of this disease remain uncertain. Neutrophils are known to contribute to immunopathology in infections, inflammatory diseases, and acute respiratory distress syndrome, a primary cause of morbidity and mortality in COVID-19. Changes in neutrophil function in COVID-19 may give insight into disease pathogenesis and identify therapeutic targets. METHODS: Blood was obtained serially from critically ill COVID-19 patients for 11 days. Neutrophil extracellular trap formation (NETosis), oxidative burst, phagocytosis, and cytokine levels were assessed. Lung tissue was obtained immediately postmortem for immunostaining. PubMed searches for neutrophils, lung, and COVID-19 yielded 10 peer-reviewed research articles in English. RESULTS: Elevations in neutrophil-associated cytokines interleukin 8 (IL-8) and interleukin 6, and general inflammatory cytokines IFN-inducible protien-19, granulocyte macrophage colony-stimulating factor (GM-CSF), interleukin 1ß, interleukin 10, and tumor necrosis factor, were identified both at first measurement and across hospitalization (P < .0001). COVID-19 neutrophils had exaggerated oxidative burst (P < .0001), NETosis (P < .0001), and phagocytosis (P < .0001) relative to controls. Increased NETosis correlated with leukocytosis and neutrophilia, and neutrophils and NETs were identified within airways and alveoli in lung parenchyma of 40% of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected lungs available for examination (2 of 5). While elevations in IL-8 and absolute neutrophil count correlated with disease severity, plasma IL-8 levels alone correlated with death. CONCLUSIONS: Literature to date demonstrates compelling evidence of increased neutrophils in the circulation and lungs of COVID-19 patients. Importantly, neutrophil quantity and activation correlates with severity of disease. Similarly, our data show that circulating neutrophils in COVID-19 exhibit an activated phenotype with enhanced NETosis and oxidative burst.


Subject(s)
COVID-19 , Extracellular Traps , Critical Illness , Humans , Neutrophil Activation , Neutrophils , Phenotype , SARS-CoV-2
8.
mBio ; 12(3)2021 05 11.
Article in English | MEDLINE | ID: covidwho-1225698

ABSTRACT

The spike (S) polypeptide of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) consists of the S1 and S2 subunits and is processed by cellular proteases at the S1/S2 boundary that contains a furin cleavage site (FCS), 682RRAR↓S686 Various deletions surrounding the FCS have been identified in patients. When SARS-CoV-2 propagated in Vero cells, it acquired deletions surrounding the FCS. We studied the viral transcriptome in Vero cell-derived SARS-CoV-2-infected primary human airway epithelia (HAE) cultured at an air-liquid interface (ALI) with an emphasis on the viral genome stability of the FCS. While we found overall the viral transcriptome is similar to that generated from infected Vero cells, we identified a high percentage of mutated viral genome and transcripts in HAE-ALI. Two highly frequent deletions were found at the FCS region: a 12 amino acid deletion (678TNSPRRAR↓SVAS689) that contains the underlined FCS and a 5 amino acid deletion (675QTQTN679) that is two amino acids upstream of the FCS. Further studies on the dynamics of the FCS deletions in apically released virions from 11 infected HAE-ALI cultures of both healthy and lung disease donors revealed that the selective pressure for the FCS maintains the FCS stably in 9 HAE-ALI cultures but with 2 exceptions, in which the FCS deletions are retained at a high rate of >40% after infection of ≥13 days. Our study presents evidence for the role of unique properties of human airway epithelia in the dynamics of the FCS region during infection of human airways, which is likely donor dependent.IMPORTANCE Polarized human airway epithelia at an air-liquid interface (HAE-ALI) are an in vitro model that supports efficient infection of SARS-CoV-2. The spike (S) protein of SARS-CoV-2 contains a furin cleavage site (FCS) at the boundary of the S1 and S2 domains which distinguishes it from SARS-CoV. However, FCS deletion mutants have been identified in patients and in vitro cell cultures, and how the airway epithelial cells maintain the unique FCS remains unknown. We found that HAE-ALI cultures were capable of suppressing two prevalent FCS deletion mutants (Δ678TNSPRRAR↓SVAS689 and Δ675QTQTN679) that were selected during propagation in Vero cells. While such suppression was observed in 9 out of 11 of the tested HAE-ALI cultures derived from independent donors, 2 exceptions that retained a high rate of FCS deletions were also found. Our results present evidence of the donor-dependent properties of human airway epithelia in the evolution of the FCS during infection.


Subject(s)
Bronchi/virology , Furin/metabolism , Respiratory Mucosa/virology , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/genetics , Transcriptome , Animals , Bronchi/cytology , Cells, Cultured , Chlorocebus aethiops , Epithelial Cells/virology , Humans , RNA-Seq , Respiratory Mucosa/cytology , Sequence Deletion , Spike Glycoprotein, Coronavirus/metabolism , Vero Cells
9.
J Virol ; 95(15): e0053021, 2021 07 12.
Article in English | MEDLINE | ID: covidwho-1218208

ABSTRACT

Elicitation of lung tissue-resident memory CD8 T cells (TRMs) is a goal of T cell-based vaccines against respiratory viral pathogens, such as influenza A virus (IAV). C-C chemokine receptor type 2 (CCR2)-dependent monocyte trafficking plays an essential role in the establishment of CD8 TRMs in lungs of IAV-infected mice. Here, we used a combination adjuvant-based subunit vaccine strategy that evokes multifaceted (TC1/TC17/TH1/TH17) IAV nucleoprotein-specific lung TRMs to determine whether CCR2 and monocyte infiltration are essential for vaccine-induced TRM development and protective immunity to IAV in lungs. Following intranasal vaccination, neutrophils, monocytes, conventional dendritic cells (DCs), and monocyte-derived dendritic cells internalized and processed vaccine antigen in lungs. We found that basic leucine zipper ATF-like transcription factor 3 (BATF3)-dependent DCs were essential for eliciting T cell responses, but CCR2 deficiency enhanced the differentiation of CD127hi, KLRG-1lo, OX40+ve CD62L+ve, and mucosally imprinted CD69+ve CD103+ve effector and memory CD8 T cells in lungs and airways of vaccinated mice. Mechanistically, increased development of lung TRMs induced by CCR2 deficiency was linked to dampened expression of T-bet but not altered TCF-1 levels or T cell receptor signaling in CD8 T cells. T1/T17 functional programming, parenchymal localization of CD8/CD4 effector and memory T cells, recall T cell responses, and protective immunity to a lethal IAV infection were unaffected in CCR2-deficient mice. Taken together, we identified a negative regulatory role for CCR2 and monocyte trafficking in mucosal imprinting and differentiation of vaccine-induced TRMs. Mechanistic insights from this study may aid the development of T-cell-based vaccines against respiratory viral pathogens, including IAV and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). IMPORTANCE While antibody-based immunity to influenza A virus (IAV) is type and subtype specific, lung- and airway-resident memory T cells that recognize conserved epitopes in the internal viral proteins are known to provide heterosubtypic immunity. Hence, broadly protective IAV vaccines need to elicit robust T cell memory in the respiratory tract. We have developed a combination adjuvant-based IAV nucleoprotein vaccine that elicits strong CD4 and CD8 T cell memory in lungs and protects against H1N1 and H5N1 strains of IAV. In this study, we examined the mechanisms that control vaccine-induced protective memory T cells in the respiratory tract. We found that trafficking of monocytes into lungs might limit the development of antiviral lung-resident memory T cells following intranasal vaccination. These findings suggest that strategies that limit monocyte infiltration can potentiate vaccine-induced frontline T-cell immunity to respiratory viruses, such as IAV and SARS-CoV-2.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , Immunity, Mucosal , Immunologic Memory , Influenza A virus/immunology , Influenza Vaccines/immunology , Orthomyxoviridae Infections/immunology , Receptors, CCR2/immunology , T-Lymphocytes, Helper-Inducer/immunology , Animals , Influenza A virus/genetics , Influenza Vaccines/genetics , Influenza Vaccines/pharmacology , Lung/immunology , Mice , Mice, Knockout , Orthomyxoviridae Infections/genetics , Orthomyxoviridae Infections/prevention & control , Receptors, CCR2/genetics
10.
PLoS Pathog ; 17(4): e1009500, 2021 04.
Article in English | MEDLINE | ID: covidwho-1197396

ABSTRACT

The high transmissibility of SARS-CoV-2 is related to abundant replication in the upper airways, which is not observed for the other highly pathogenic coronaviruses SARS-CoV and MERS-CoV. We here reveal features of the coronavirus spike (S) protein, which optimize the virus towards the human respiratory tract. First, the S proteins exhibit an intrinsic temperature preference, corresponding with the temperature of the upper or lower airways. Pseudoviruses bearing the SARS-CoV-2 spike (SARS-2-S) were more infectious when produced at 33°C instead of 37°C, a property shared with the S protein of HCoV-229E, a common cold coronavirus. In contrast, the S proteins of SARS-CoV and MERS-CoV favored 37°C, in accordance with virus preference for the lower airways. Next, SARS-2-S-driven entry was efficiently activated by not only TMPRSS2, but also the TMPRSS13 protease, thus broadening the cell tropism of SARS-CoV-2. Both proteases proved relevant in the context of authentic virus replication. TMPRSS13 appeared an effective spike activator for the virulent coronaviruses but not the low pathogenic HCoV-229E virus. Activation of SARS-2-S by these surface proteases requires processing of the S1/S2 cleavage loop, in which both the furin recognition motif and extended loop length proved critical. Conversely, entry of loop deletion mutants is significantly increased in cathepsin-rich cells. Finally, we demonstrate that the D614G mutation increases SARS-CoV-2 stability, particularly at 37°C, and, enhances its use of the cathepsin L pathway. This indicates a link between S protein stability and usage of this alternative route for virus entry. Since these spike properties may promote virus spread, they potentially explain why the spike-G614 variant has replaced the early D614 variant to become globally predominant. Collectively, our findings reveal adaptive mechanisms whereby the coronavirus spike protein is adjusted to match the temperature and protease conditions of the airways, to enhance virus transmission and pathology.


Subject(s)
COVID-19/metabolism , Respiratory System/metabolism , Respiratory System/virology , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/metabolism , COVID-19/transmission , Coronavirus 229E, Human/metabolism , Furin/metabolism , Humans , Membrane Proteins/metabolism , Middle East Respiratory Syndrome Coronavirus/metabolism , Peptide Hydrolases/metabolism , Serine Endopeptidases/metabolism , Spike Glycoprotein, Coronavirus/genetics , Temperature , Virus Internalization , Virus Replication/physiology
11.
Perioper Care Oper Room Manag ; 23: 100168, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1193441

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) airway response teams concentrate equipment and expertise while minimizing the number of providers exposed to aerosol generating procedures. These airway teams were implemented in various hospitals around the world to respond to the acute increase of critical ill patients requiring ventilatory support. We created a financial model to estimate the costs for staffing and maintaining a dedicated COVID-19 airway response team based on the experience at an urban academic hospital in the Northeastern United States between March and June of 2020. METHODS: The institutional review board at Brigham and Women's Hospital approved this protocol and the requirement for informed consent was waived. The average reimbursement for 125 COVID-19 airway consultations was measured. Our team estimated the costs of consumable items for each airway based on previously published recommendations for equipment and personal protective equipment. A sensitivity analyses was performed for variable numbers of monthly airway consults and different staffing patterns based on a literature review of available COVID-19 airway team structures. RESULTS: Based on the average reimbursements and estimates of the consumable costs, each airway procedure represented a net loss of $34 to the institution. The overall estimated cost of staffing a dedicated airway team was between $109,472 and $204,575 per month. CONCLUSIONS: Development and implementation of a dedicated COVID-19 airway response teams represents a significant institutional expense. Institutions should establish necessary cost sharing, consider volume and team structure, and identify reimbursement opportunities that mitigate the necessary expense associated with airway response programs.

12.
Thorax ; 76(10): 1010-1019, 2021 10.
Article in English | MEDLINE | ID: covidwho-1180971

ABSTRACT

BACKGROUND: Knowledge of the pathophysiology of COVID-19 is almost exclusively derived from studies that examined the immune response in blood. We here aimed to analyse the pulmonary immune response during severe COVID-19 and to compare this with blood responses. METHODS: This was an observational study in patients with COVID-19 admitted to the intensive care unit (ICU). Mononuclear cells were purified from bronchoalveolar lavage fluid (BALF) and blood, and analysed by spectral flow cytometry; inflammatory mediators were measured in BALF and plasma. FINDINGS: Paired blood and BALF samples were obtained from 17 patients, four of whom died in the ICU. Macrophages and T cells were the most abundant cells in BALF, with a high percentage of T cells expressing the ƴδ T cell receptor. In the lungs, both CD4 and CD8 T cells were predominantly effector memory cells (87·3% and 83·8%, respectively), and these cells expressed higher levels of the exhaustion marker programmad death-1 than in peripheral blood. Prolonged ICU stay (>14 days) was associated with a reduced proportion of activated T cells in peripheral blood and even more so in BALF. T cell activation in blood, but not in BALF, was higher in fatal COVID-19 cases. Increased levels of inflammatory mediators were more pronounced in BALF than in plasma. INTERPRETATION: The bronchoalveolar immune response in COVID-19 has a unique local profile that strongly differs from the immune profile in peripheral blood. Fully elucidating COVID-19 pathophysiology will require investigation of the pulmonary immune response.


Subject(s)
COVID-19/immunology , Immunity, Cellular/physiology , Inflammation Mediators/metabolism , Aged , Bronchoalveolar Lavage Fluid/chemistry , Bronchoalveolar Lavage Fluid/cytology , COVID-19/blood , COVID-19/pathology , Critical Care , Critical Illness , Female , Flow Cytometry , Humans , Macrophages/physiology , Male , Middle Aged , T-Lymphocytes/physiology
13.
Microorganisms ; 9(4)2021 Apr 10.
Article in English | MEDLINE | ID: covidwho-1178362

ABSTRACT

The aim of this study was to investigate the persistence of SARS-CoV-2 in post-mortem swabs of subjects who died from SARS-CoV-2 infection. The presence of the virus was evaluated post-mortem from airways of 27 SARS-CoV-2 positive patients at three different time points (T1 2 h; T2 12 h; T3 24 h) by real-time PCR. Detection of antibodies to SARS-CoV-2 was performed by Maglumi 2019-nCoV IgM/IgG chemiluminescence assay. SARS-CoV-2 viral RNA was still detectable in 70.3% of cases within 2 h after death and in 66,6% of cases up to 24 h after death. Our data showed an increase of the viral load in 78,6% of positive individuals 24 h post-mortem (T3) in comparison to that evaluated 2 h after death (T1). Noteworthy, we detected a positive T3 post-mortem swab (24 h after death) from 4 subjects who were negative at T1 (2 h after death). The results of our study may have an important value in the management of deceased subjects not only with a suspected or confirmed diagnosis of SARS-CoV-2, but also for unspecified causes and in the absence of clinical documentation or medical assistance.

14.
ERJ Open Res ; 7(2)2021 Apr.
Article in English | MEDLINE | ID: covidwho-1172825

ABSTRACT

Severe COVID-19 patient airways plugged by MUC5AC-containing mucus exhibit hyperplasia of goblet cells, and hypoplasia of multiciliated cells and club cells, as well as significantly reduced CC16 and MUC5B levels, and increased IL-13 levels https://bit.ly/2M2NcdO.

15.
Hum Antibodies ; 29(1): 27-40, 2021.
Article in English | MEDLINE | ID: covidwho-1170066

ABSTRACT

A novel Coronavirus (SARS-CoV-2) causing a cluster of respiratory infections (Coronavirus Disease 2019, COVID-19) first discovered in Wuhan, China, is responsible for a new illness that has been found to affect the lungs and airways of patients with associated symptoms of fever, cough and shortness of breath. In the light of few cases recorded so far in West Africa there is tendency for complacency. The region needs to make strategic plans based on available evidence to enable them effectively deal with this rapidly evolving pandemic. At this very moment countries like China, Italy, France, Spain, Iran, UK and many others are witnessing sustained and intensive community transmission of this virus and increasing numbers of severe disease and death particularly among elderly patients with other comorbidities. The reality of the seriousness of this pandemic is alarming. Government of member states of ECOWAS need to prepare themselves by building capacity as well as implement evidenced-based steps to mitigate this rapidly evolving pandemic by testing persons presenting with symptoms (fever, cough and shortness of breath), isolating and treating those found positive, tracing and quarantining contacts, implementing social distancing as well as optimizing human and material endowment to allow healthcare workers offer safe quality clinical care for affected patients to prevent secondary infection among healthcare workers.


Subject(s)
COVID-19/epidemiology , COVID-19/prevention & control , Civil Defense/organization & administration , Pandemics , SARS-CoV-2/pathogenicity , Africa, Western/epidemiology , Age Factors , Americas/epidemiology , Asia/epidemiology , COVID-19/diagnosis , COVID-19/transmission , Europe/epidemiology , Global Health/statistics & numerical data , Humans , Incidence , Personal Protective Equipment/supply & distribution , Physical Distancing , Quarantine/methods , Quarantine/organization & administration
16.
Environ Res ; 197: 111096, 2021 06.
Article in English | MEDLINE | ID: covidwho-1163738

ABSTRACT

This study is motivated by the amplified transmission rates of the SAR-CoV-2 virus in areas with high concentrations of fine particulates (PM2.5) as reported in northern Italy and Mexico. To develop a deeper understanding of the contribution of PM2.5 in the propagation of the SAR-CoV-2 virus in the population, the deposition patterns and efficiencies (DEs) of PM2.5 laced with the virus in healthy and asthmatic airways are studied. Physiologically correct 3-D models for generations 10-12 of the human airways are applied to carry out a numerical analysis of two-phase flow for full breathing cycles. Two concentrations of PM2.5 are applied for the simulation, i.e., 30 µg⋅m-3 and 80 µg⋅m-3 for three breathing statuses, i.e., rest, light exercise, and moderate activity. All the PM2.5 injected into the control volume is assumed to be 100% contaminated with the SAR-CoV-2 virus. Skewed air-flow phenomena at the bifurcations are proportional to the Reynolds number at the inlet, and their intensity in the asthmatic airway exceeded that of the healthy one. Upon exhalation, two peak air-flow vectors from daughter branches combine to form one big vector in the parent generation. Asthmatic airway models has higher deposition efficiencies (DEs) for contaminated PM2.5 as compared to the healthy one. Higher DEs arise in the asthmatic airway model due to complex secondary flows which increase the impaction of contaminated PM2.5 on airways' walls.


Subject(s)
Asthma , Lung , Computer Simulation , Humans , Italy , Mexico , Models, Biological , Particulate Matter/toxicity
17.
Curr Opin Allergy Clin Immunol ; 21(3): 245-251, 2021 06 01.
Article in English | MEDLINE | ID: covidwho-1153254

ABSTRACT

PURPOSE OF REVIEW: Data regarding the effects of coronavirus disease 2019 (COVID-19) on host-microbiome alteration and subsequent effects on susceptibility and clinical course of COVID-19, especially in atopic patients, are currently limited. Here, we review the studies regarding the microbiome of atopic patients with other respiratory infections and discuss the potential role of probiotics as therapeutic targets for COVID-19 to decrease its susceptibility and severity of COVID-19. RECENT FINDINGS: Respiratory tract virus infection affects the gut and airway microbiome structures and host's immune function. Diverse factors in atopic diseases affect the airway and gut microbiome structures, which are expected to negatively influence host health. However, response to respiratory virus infection in atopic hosts depends on the preexisting microbiome and immune responses. This may explain the inconclusiveness of the effects of COVID-19 on the susceptibility, morbidity, and mortality of patients with atopic diseases. Beneficial probiotics may be a therapeutic adjuvant in COVID-19 infection as the beneficial microbiome can decrease the viral load in the early phase of respiratory virus infection and improve the morbidity and mortality. SUMMARY: Application of probiotics can be a potential adjuvant treatment in respiratory virus infection to improve host immune responses and disturbed microbiome structures in atopic patients. Further related studies involving COVID-19 are warranted in near future.


Subject(s)
COVID-19 , Dysbiosis , Gastrointestinal Microbiome/immunology , Hypersensitivity , Pandemics , Probiotics/therapeutic use , SARS-CoV-2/immunology , COVID-19/epidemiology , COVID-19/immunology , COVID-19/microbiology , COVID-19/therapy , Dysbiosis/epidemiology , Dysbiosis/immunology , Dysbiosis/microbiology , Dysbiosis/therapy , Humans , Hypersensitivity/epidemiology , Hypersensitivity/immunology , Hypersensitivity/microbiology , Hypersensitivity/therapy
18.
Comput Mech ; 67(5): 1497-1513, 2021.
Article in English | MEDLINE | ID: covidwho-1141424

ABSTRACT

To respond to the ongoing pandemic of SARS-CoV-2, this contribution deals with recently highlighted COVID-19 transmission through respiratory droplets in form of aerosols. Unlike other recent studies that focused on airborne transmission routes, this work addresses aerosol transport and deposition in a human respiratory tract. The contribution therefore conducts a computational study of aerosol deposition in digital replicas of human airways, which include the oral cavity, larynx and tracheobronchial airways down to the 12th generation of branching. Breathing through the oral cavity allows the air with aerosols to directly impact the larynx and tracheobronchial airways and can be viewed as one of the worst cases in terms of inhalation rate and aerosol load. The implemented computational model is based on Lagrangian particle tracking in Reynolds-Averaged Navier-Stokes resolved turbulent flow. Within this framework, the effects of different flow rates, particle diameters and lung sizes are investigated to enable new insights into local particle deposition behavior and therefore virus loads among selected age groups. We identify a signicant increase of aerosol deposition in the upper airways and thus a strong reduction of virus load in the lower airways for younger individuals. Based on our findings, we propose a possible relation between the younger age related fluid mechanical protection of the lower lung regions due to the airway size and a reduced risk of developing a severe respiratory illness originating from COVID-19 airborne transmission.

19.
Vaccines (Basel) ; 9(3)2021 Mar 10.
Article in English | MEDLINE | ID: covidwho-1125263

ABSTRACT

Most advanced vaccines against severe acute respiratory syndrome coronavirus (SARS-CoV)-2 are designed to induce antibodies against spike (S) protein. Differently, we developed an original strategy to induce CD8+ T cytotoxic lymphocyte (CTL) immunity based on in vivo engineering of extracellular vesicles (EVs). This is a new vaccination approach based on intramuscular injection of DNA expression vectors coding for a biologically inactive HIV-1 Nef protein (Nefmut) with an unusually high efficiency of incorporation into EVs, even when foreign polypeptides are fused to its C-terminus. Nanovesicles containing Nefmut-fused antigens released by muscle cells can freely circulate into the body and are internalized by antigen-presenting cells. Therefore, EV-associated antigens can be cross-presented to prime antigen-specific CD8+ T-cells. To apply this technology to a strategy of anti-SARS-CoV-2 vaccine, we designed DNA vectors expressing the products of fusion between Nefmut and different viral antigens, namely N- and C-terminal moieties of S (referred to as S1 and S2), M, and N. We provided evidence that all fusion products are efficiently uploaded in EVs. When the respective DNA vectors were injected in mice, a strong antigen-specific CD8+ T cell immunity became detectable in spleens and, most important, in lung airways. Co-injection of DNA vectors expressing the diverse SARS-CoV-2 antigens resulted in additive immune responses in both spleen and lungs. Hence, DNA vectors expressing Nefmut-based fusion proteins can be proposed for new anti-SARS-CoV-2 vaccine strategies.

20.
Environ Res ; 197: 110975, 2021 06.
Article in English | MEDLINE | ID: covidwho-1118425

ABSTRACT

The deposition phenomenon of microparticle and SAR-CoV-2 laced bioaerosol in human airways is studied by Taguchi methods and response surface methodology (RSM). The data used herein is obtained from simulations of airflow dynamics and deposition fractions of drug particle aerosols in the downstream airways of asthma patients using computational fluid dynamics (CFD) and discrete particle motion (DPM). Three main parameters, including airflow rate, drug dose, and particle size, affecting aerosol deposition in the lungs of asthma patients are examined. The highest deposition fraction (DF) is obtained at the flow rate of 45 L min-1, the drug dose of 200 µg·puff-1, and the particle diameter of 5 µm. The optimized combination of levels for the three parameters for maximum drug deposition is performed via the Taguchi method. The importance of the influencing factors rank as particle size > drug dose > flow rate. RSM reveals that the combination of 30 L min-1, 5 µm, 200 µg·puff- has the highest deposition fraction. In part, this research also studied the deposition of bioaerosols contaminated with the SAR-CoV-2 virus, and their lowest DF is 1.15%. The low DF of bioaerosols reduces the probability of the SAR-CoV-2 virus transmission.


Subject(s)
Hydrodynamics , Lung , Administration, Inhalation , Aerosols , Computer Simulation , Humans , Models, Biological , Particle Size
SELECTION OF CITATIONS
SEARCH DETAIL