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1.
eClinicalMedicine ; 47:101409, 2022.
Article in English | ScienceDirect | ID: covidwho-1800090

ABSTRACT

Summary Background In COVACTA, a randomised, placebo-controlled trial in patients hospitalised with coronavirus disease-19 (COVID-19), tocilizumab did not improve 28-day mortality, but shortened hospital and intensive care unit stay. Longer-term effects of tocilizumab in patients with COVID-19 are unknown. Therefore, the efficacy and safety of tocilizumab in COVID-19 beyond day 28 and its impact on Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) clearance and antibody response in COVACTA were investigated. Methods Adults in Europe and North America hospitalised with COVID-19 (N = 452) between April 3, 2020 and May 28, 2020 were randomly assigned (2:1) to double-blind intravenous tocilizumab or placebo and assessed for efficacy and safety through day 60. Assessments included mortality, time to hospital discharge, SARS-CoV-2 viral load in nasopharyngeal swab and serum samples, and neutralising anti-SARS-CoV-2 antibodies in serum. ClinicalTrials.gov registration: NCT04320615. Findings By day 60, 24·5% (72/294) of patients in the tocilizumab arm and 25·0% (36/144) in the placebo arm died (weighted difference –0·5% [95% CI –9·1 to 8·0]), and 67·0% (197/294) in the tocilizumab arm and 63·9% (92/144) in the placebo arm were discharged from the hospital. Serious infections occurred in 24·1% (71/295) of patients in the tocilizumab arm and 29·4% (42/143) in the placebo arm. Median time to negative reverse transcriptase–quantitative polymerase chain reaction result in nasopharyngeal/oropharyngeal samples was 15·0 days (95% CI 14·0 to 21·0) in the tocilizumab arm and 21·0 days (95% CI 14·0 to 28·0) in the placebo arm. All tested patients had positive test results for neutralising anti–SARS-CoV-2 antibodies at day 60. Interpretation There was no mortality benefit with tocilizumab through day 60. Tocilizumab did not impair viral clearance or host immune response, and no new safety signals were observed. Future investigations may explore potential biomarkers to optimize patient selection for tocilizumab treatment and combination therapy with other treatments. Funding F. Hoffmann-La Roche Ltd and the US Department of Health and Human Services, Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority, under OT number HHSO100201800036C.

3.
Aust N Z J Obstet Gynaecol ; 2022 Apr 08.
Article in English | MEDLINE | ID: covidwho-1784575

ABSTRACT

We evaluated the impact of the COVID-19 pandemic and Melbourne's multiple community lockdowns (between 2020-21) on total live birth rates and preterm births in a large health network. Analysis revealed a decrease in total live birth rates following easing of initial lockdowns, and a sharp increase in births at one stage in between lockdowns. The proportion and number of preterm births (<37 weeks gestation) decreased at the start of initial lockdowns with the strongest decrease after the end of the second lockdown period. Births <34 weeks gestation also decreased during lockdowns, but no significant change was identified for births <28 weeks gestation.

4.
J Appl Physiol (1985) ; 132(4): 1104-1113, 2022 Apr 01.
Article in English | MEDLINE | ID: covidwho-1759485

ABSTRACT

The common pulmonary consequence of SARS-CoV-2 infection is pneumonia, but vascular clot may also contribute to COVID pathogenesis. Imaging and hemodynamic approaches to identifying diffuse pulmonary vascular obstruction (PVO) in COVID (or acute lung injury generally) are problematic particularly when pneumonia is widespread throughout the lung and hemodynamic consequences are buffered by pulmonary vascular recruitment and distention. Although stimulated by COVID-19, we propose a generally applicable bedside gas exchange approach to identifying PVO occurring alone or in combination with pneumonia, addressing both its theoretical and practical aspects. It is based on knowing that poorly (or non) ventilated regions, as occur in pneumonia, affect O2 more than CO2, whereas poorly (or non) perfused regions, as seen in PVO, affect CO2 more than O2. Exhaled O2 and CO2 concentrations at the mouth are measured over several ambient-air breaths, to determine mean alveolar Po2 and Pco2. A single arterial blood sample is taken over several of these breaths for arterial Po2 and Pco2. The resulting alveolar-arterial Po2 and Pco2 differences (AaPo2, aAPco2) are converted to corresponding physiological shunt and deadspace values using the Riley and Cournand 3-compartment model. For example, a 30% shunt (from pneumonia) with no alveolar deadspace produces an AaPO2 of almost 50 torr, but an aAPco2 of only 3 torr. In contrast, a 30% alveolar deadspace (from PVO) without shunt leads to an AaPO2 of only 12 torr, but an aAPco2 of 9 torr. This approach can identify and quantify physiological shunt and deadspace when present singly or in combination.NEW & NOTEWORTHY Identifying pulmonary vascular obstruction in the presence of pneumonia (e.g., in COVID-19) is difficult. We present here conversion of bedside measurements of arterial and alveolar Po2 and Pco2 into values for shunt and deadspace-when both coexist-using Riley and Cournand's 3-compartment gas exchange model. Deadspace values higher than expected from shunt alone indicate high ventilation/perfusion ratio areas likely reflecting (micro)vascular obstruction.

5.
Critical care explorations ; 4(2), 2022.
Article in English | EuropePMC | ID: covidwho-1696151

ABSTRACT

OBJECTIVES: Although proning is beneficial to acute respiratory distress syndrome, impressions vary about its efficacy. Some providers believe that paralysis is required to facilitate proning. We studied impact of paralysis on prone-induced gas exchange improvements and provider attitudes regarding paralytics. DESIGN: Observational. SETTING: University of California San Diego. PATIENTS: Intubated COVID acute respiratory distress syndrome patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: 1) Changes in Pao2:Fio2 and Spo2:Fio2 ratios before and after proning with and without paralytics, 2) adverse events during proning with and without paralytics, and 3) nurse and physician attitudes about efficacy/safety of proning with and without paralytics. Gas-exchange improvement with proning was similar with and without paralytics (with no serious adverse events). Survey results showed similar attitudes between nurses and physicians about proning efficacy but differing attitudes about the need for paralytics with proning. CONCLUSIONS: Findings support use of proning and may help in design of randomized trials to assess paralytics in acute respiratory distress syndrome management.

6.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-316601

ABSTRACT

Background: Increased inflammation is a hallmark of COVID-19, with pulmonary and systemic inflammation identified in multiple cohorts of patients. Definitive cellular and molecular pathways driving severe forms of this disease remain uncertain. Neutrophils, the most numerous leukocytes in blood circulation, can contribute to immunopathology in infections, inflammatory diseases and acute respiratory distress syndrome (ARDS), a primary cause of morbidity and mortality in COVID-19. Neutrophilia, elevated neutrophil:lymphocyte ratios, and elevated neutrophil-associated cytokines are present in COVID-19, but changes in neutrophil functions have not been characterized. Here we analyzed the functional state of circulating neutrophils in COVID-19.Methods: Blood was obtained from critically ill COVID-19 patients over two weeks and healthy controls across multiple timepoints. Plasma cytokine profiles were assessed by bead array. Neutrophils were isolated and tested ex vivo for oxidative burst, neutrophil extracellular trap formation (NETosis) and phagocytosis. Lung tissue was obtained immediately post-mortem from COVID-19 patients for immunostaining.Results: Elevations in neutrophil-associated cytokines IL-8 and IL-6 were identified in COVID-19 plasma both at the first measurement and across their hospitalization (p < 0.0001). Elevations in cytokines IP-10, GM-CSF, IL-1b, IL-10 and TNF were also present at the first measurement and across hospital stays. Functionally, circulating neutrophils from COVID-19 patients had exaggerated oxidative burst (p < 0.0001), NETosis (p < 0.0001) and phagocytosis (p < 0.0001) relative to controls. Increased NETosis was found to be correlated with both leukocytosis and neutrophilia in COVID-19 patients. Neutrophils and NETs were identified within airways and alveoli in lung parenchyma. While elevations in IL-8 and ANC correlated to COVID-19 disease severity, plasma IL-8 levels alone correlated with death.Conclusions: Circulating neutrophils in COVID-19 exhibit an activated phenotype with increased oxidative burst, NETosis and phagocytosis. Readily accessible and dynamic, plasma IL-8 and circulating neutrophil function can be explored as potential COVID-19 disease biomarkers.Funding Statement: This work was supported by the Department of Veterans Affairs (salary support and VA Merit Award, PI Crotty Alexander) and NIH NHLBI (PI Crotty Alexander).Declaration of Interests: The authors report no conflicts of interest.Ethics Approval Statement: The research protocol was approved by the UCSD, VASDHS and Rady Children’s Hospital institutional review boards (IRBs) and all participants or designated family member gave written informed consent.

7.
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
10.
Int J Environ Res Public Health ; 18(24)2021 12 15.
Article in English | MEDLINE | ID: covidwho-1572482

ABSTRACT

The COVID-19 pandemic generated large amounts of stress across the globe. While acute stress negatively impacts health, defining exact consequences and behavioral interventions can be difficult. We hypothesized that a generalized increase in stress and anxiety caused by continuation of the global pandemic would negatively impact sleep quality and that ever users of e-cigarettes and conventional tobacco would have more profound alterations over time. Participants were recruited via social media to complete an online survey in April 2020 (n = 554). Inhalant use was assessed through the UCSD Inhalant Questionnaire and sleep quality was gauged through the Pittsburgh Sleep Quality Index (PSQI). A set of participants (n = 217) retook the survey in June 2020. Inhalant users-historical or current e-cigarette vapers, conventional tobacco smokers, and dual users-had higher PSQI scores than never smoker/never vapers, demonstrating worse sleep quality in inhalant users. Non-smoking/non-vaping subjects who retook the survey in June 2020 had improvement in their PSQI scores by paired t test, indicating better sleep quality as the pandemic continued, while inhalant users of all types had persistently high PSQI scores (poor sleep quality). These data suggest that ever users of tobacco products may be susceptible to overall diminished sleep quality in the setting of stressful life circumstances. These data also suggest that pandemic-initiated lifestyle changes may have led to improvements in sleep quality. Finally, these findings raise concerns for correlations between either past or active e-cigarette use on sleep, and thus overall health.


Subject(s)
COVID-19 , Electronic Nicotine Delivery Systems , Vaping , Cross-Sectional Studies , Humans , Pandemics , SARS-CoV-2 , Vaping/adverse effects
11.
Children (Basel) ; 8(12)2021 Dec 10.
Article in English | MEDLINE | ID: covidwho-1572380

ABSTRACT

Background Community lockdowns during the coronavirus disease 2019 (COVID-19) pandemic may influence preterm birth rates, but mechanisms are unclear. Methods We compared neonatal outcomes of preterm infants born to mothers exposed to community lockdowns in 2020 (exposed group) to those born in 2019 (control group). Main outcome studied was composite of significant neonatal morbidity or death. Results Median gestational age was 35 + 4 weeks (295 infants, exposed group) vs. 35 + 0 weeks (347 infants, control group) (p = 0.108). The main outcome occurred in 36/295 (12.2%) infants in exposed group vs. 46/347 (13.3%) in control group (p = 0.69). Continuous positive airway pressure (CPAP) use, jaundice requiring phototherapy, hypoglycaemia requiring treatment, early neonatal white cell and neutrophil counts were significantly reduced in the exposed group. Conclusions COVID-19 community lockdowns did not alter composite neonatal outcomes in preterm infants, but reduced rates of some common outcomes as well as early neonatal inflammatory markers.

13.
J Thorac Dis ; 13(11): 6214-6216, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1518878
14.
Curr Opin Crit Care ; 27(5): 462-467, 2021 10 01.
Article in English | MEDLINE | ID: covidwho-1462552

ABSTRACT

PURPOSE OF REVIEW: Currently, there is no cure for SARS-CoV-2 infection, yet hospital mortality rates for COVID-19 have improved over the course of the pandemic and may be due in part to improved supportive care in the ICU. This review highlights the evidence for and against various ICU supportive therapies for the treatment of critically ill patients with COVID-19. RECENT FINDINGS: Early in the pandemic, there was great interest in novel ICU supportive care, both for the benefit of the patient, and the safety of clinicians. With a few exceptions (e.g. prone ventilation of nonintubated patients), clinicians abandoned most of these approaches (e.g. early intubation, avoidance of high flow or noninvasive ventilation). Standard critical care measures, especially for the treatment of severe viral respiratory infection including acute respiratory distress syndrome (ARDS) were applied to patients with COVID-19 with apparent success. SUMMARY: In general, the COVID-19 pandemic reaffirmed the benefits of standard supportive care for respiratory failure and in particular, recent advances in ARDS treatment. Prone ventilation of nonintubated patients, an approach that was adopted early in the pandemic, is associated with improvement in oxygenation, but its impact on clinical outcome remains unclear. Otherwise, prone mechanical ventilation and avoidance of excessive tidal volumes, conservative fluid management, antibiotic stewardship and early evaluation for extracorporeal membrane oxygenation (ECMO) -- basic tenants of severe respiratory infections and ARDS care -- remain at the core of management of patients with severe COVID-19.


Subject(s)
COVID-19 , Respiratory Insufficiency , Humans , Intensive Care Units , Pandemics , Respiration, Artificial , Respiratory Insufficiency/therapy , SARS-CoV-2 , Treatment Outcome
15.
Health Policy Open ; 2: 100051, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1454155

ABSTRACT

BACKGROUND: UC San Diego Health System (UCSDHS) is the largest academic medical center and integrated care network in US-Mexico border area of California contiguous to the Northern Baja region of Mexico. The COVID-19 pandemic compelled several UCSDHS and local communities to create awareness around best methods to promote regional health in this economically, socially, and politically important border area. PURPOSE: To improve understanding of optimal strategies to execute critical care collaborative programs between academic and community health centers facing public health emergencies during the COVID-19 pandemic, based on the experience of UCSDHS and several community hospitals (one US, two Mexican) in the US-Mexico border region. METHODS: After taking several preparatory steps, we developed a two-phase program that included 1) in-person activities to perform needs assessments, hands-on training and education, and morale building and 2) creation of a telemedicine-based (Tele-ICU) service for direct patient management and/or educational coaching experiences.Findings.A clinical and educational program between academic and community border hospitals was feasible, effective, and well received. CONCLUSION: We offer several policy-oriented recommendations steps for academic and community healthcare programs to build educational, collaborative partnerships to address COVID-19 and other cross-cultural, international public health emergencies.

16.
Endocrinol Diabetes Metab ; 5(1): e00301, 2022 01.
Article in English | MEDLINE | ID: covidwho-1441962

ABSTRACT

AIMS: Type 2 diabetes mellitus (T2DM) is a strong risk factor for complications of coronavirus disease 2019 (COVID-19). The effect of T2DM medications on COVID-19 outcomes remains unclear. In a retrospective analysis of a cohort of 131 patients with T2DM hospitalized for COVID-19 in Wuhan, we have previously found that metformin use prior to hospitalization is associated with reduced mortality. The current study aims to investigate the effects of inpatient use of T2DM medications, including metformin, acarbose, insulin and sulfonylureas, on the mortality of COVID-19 patients with T2DM during hospitalization. METHODS: We continue to carry out a retrospective analysis of a cohort of 131 patients with T2DM hospitalized for COVID-19 and treated with different combinations of diabetes medications. RESULTS: We found that patients using metformin (p = .02) and acarbose (p = .04), alone or both together (p = .03), after admission were significantly more likely to survive than those who did not use either metformin or acarbose. 37 patients continued to take metformin after admission and 35 (94.6%) survived. Among the 57 patients who used acarbose after admission, 52 survived (91.2%). A total of 20 patients used both metformin and acarbose, while 57 used neither. Of the 20 dual-use patients, 19 (95.0%) survived. CONCLUSION: Our analyses suggest that inpatient use of metformin and acarbose together or alone during hospitalization should be studied in randomized trials.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , Metformin , Acarbose/therapeutic use , Diabetes Mellitus, Type 2/drug therapy , Humans , Hypoglycemic Agents/therapeutic use , Inpatients , Metformin/therapeutic use , Retrospective Studies , SARS-CoV-2
18.
Crit Care Explor ; 3(6): e0471, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1276252

ABSTRACT

IMPORTANCE: Prone positioning improves clinical outcomes in moderate-to-severe acute respiratory distress syndrome and has been widely adopted for the treatment of patients with acute respiratory distress syndrome due to coronavirus disease 2019. Little is known about the effects of prone positioning among patients with less severe acute respiratory distress syndrome, obesity, or those treated with pulmonary vasodilators. OBJECTIVES: We characterize the change in oxygenation, respiratory system compliance, and dead-space-to-tidal-volume ratio in response to prone positioning in patients with coronavirus disease 2019 acute respiratory distress syndrome with a range of severities. A subset analysis of patients treated with inhaled nitric oxide and subsequent prone positioning explored the influence of pulmonary vasodilation on the physiology of prone positioning. DESIGN SETTING AND PARTICIPANTS: Retrospective cohort study of all consecutively admitted adult patients with acute respiratory distress syndrome due to coronavirus disease 2019 treated with mechanical ventilation and prone positioning in the ICUs of an academic hospital between March 11, 2020, and May 1, 2020. MAIN OUTCOMES AND MEASURES: Respiratory system mechanics and gas exchange during the first episode of prone positioning. RESULTS: Among 122 patients, median (interquartile range) age was 60 years (51-71 yr), median body mass index was 31.5 kg/m2 (27-35 kg/m2), and 50 patients (41%) were female. The ratio of Pao2 to Fio2 improved with prone positioning in 90% of patients. Prone positioning was associated with a significant increase in the ratio of Pao2 to Fio2 (from median 149 [123-170] to 226 [169-268], p < 0.001) but no change in dead-space-to-tidal-volume ratio or respiratory system compliance. Supine ratio of Pao2 to Fio2, respiratory system compliance, positive end-expiratory pressure, and body mass index did not correlate with absolute change in the ratio of Pao2 to Fio2 with prone positioning. However, patients with ratio of Pao2 to Fio2 less than 150 experienced a greater relative improvement in oxygenation with prone positioning than patients with ratio of Pao2 to Fio2 greater than or equal to 150 (median percent change in ratio of Pao2 to Fio2 62 [29-107] vs 30 [10-70], p = 0.002). Among 12 patients, inhaled nitric oxide prior to prone positioning was associated with a significant increase in the ratio of Pao2 to Fio2 (from median 136 [77-168] to 170 [138-213], p = 0.003) and decrease in dead-space-to-tidal-volume ratio (0.54 [0.49-0.58] to 0.46 [0.44-0.53], p = 0.001). Subsequent prone positioning in this subgroup further improved the ratio of Pao2 to Fio2 (from 145 [122-183] to 205 [150-232], p = 0.017) but did not change dead-space-to-tidal-volume ratio. CONCLUSIONS AND RELEVANCE: Prone positioning improves oxygenation across the acute respiratory distress syndrome severity spectrum, irrespective of supine respiratory system compliance, positive end-expiratory pressure, or body mass index. There was a greater relative benefit among patients with more severe disease. Prone positioning confers an additive benefit in oxygenation among patients treated with inhaled nitric oxide.

19.
Crit Care ; 25(1): 208, 2021 06 14.
Article in English | MEDLINE | ID: covidwho-1269886

ABSTRACT

BACKGROUND: Despite considerable progress, it remains unclear why some patients admitted for COVID-19 develop adverse outcomes while others recover spontaneously. Clues may lie with the predisposition to hypoxemia or unexpected absence of dyspnea ('silent hypoxemia') in some patients who later develop respiratory failure. Using a recently-validated breath-holding technique, we sought to test the hypothesis that gas exchange and ventilatory control deficits observed at admission are associated with subsequent adverse COVID-19 outcomes (composite primary outcome: non-invasive ventilatory support, intensive care admission, or death). METHODS: Patients with COVID-19 (N = 50) performed breath-holds to obtain measurements reflecting the predisposition to oxygen desaturation (mean desaturation after 20-s) and reduced chemosensitivity to hypoxic-hypercapnia (including maximal breath-hold duration). Associations with the primary composite outcome were modeled adjusting for baseline oxygen saturation, obesity, sex, age, and prior cardiovascular disease. Healthy controls (N = 23) provided a normative comparison. RESULTS: The adverse composite outcome (observed in N = 11/50) was associated with breath-holding measures at admission (likelihood ratio test, p = 0.020); specifically, greater mean desaturation (12-fold greater odds of adverse composite outcome with 4% compared with 2% desaturation, p = 0.002) and greater maximal breath-holding duration (2.7-fold greater odds per 10-s increase, p = 0.036). COVID-19 patients who did not develop the adverse composite outcome had similar mean desaturation to healthy controls. CONCLUSIONS: Breath-holding offers a novel method to identify patients with high risk of respiratory failure in COVID-19. Greater breath-hold induced desaturation (gas exchange deficit) and greater breath-holding tolerance (ventilatory control deficit) may be independent harbingers of progression to severe disease.


Subject(s)
COVID-19/physiopathology , Carbon Dioxide/analysis , Hypercapnia/physiopathology , Adult , Case-Control Studies , Humans , Hypercapnia/complications , Inspiratory Capacity , Lung Volume Measurements/methods , Male , Middle Aged
20.
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
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