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1.
Res Sq ; 2022 Jan 14.
Article in English | MEDLINE | ID: covidwho-1766249

ABSTRACT

SARS-CoV-2 infection fatality rate (IFR) doubles with every five years of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-ß are found in ~20% of deceased patients across age groups. In the general population, they are found in ~1% of individuals aged 20-70 years and in >4% of those >70 years old. With a sample of 1,261 deceased patients and 34,159 uninfected individuals, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to non-carriers. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRD was 17.0[95% CI:11.7-24.7] for individuals under 70 years old and 5.8[4.5-7.4] for individuals aged 70 and over, whereas, for autoantibodies neutralizing both molecules, the RRD was 188.3[44.8-774.4] and 7.2[5.0-10.3], respectively. IFRs increased with age, from 0.17%[0.12-0.31] for individuals <40 years old to 26.7%[20.3-35.2] for those ≥80 years old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84%[0.31-8.28] to 40.5%[27.82-61.20] for the same two age groups, for autoantibodies neutralizing both molecules. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, particularly those neutralizing both IFN-α2 and -ω. Remarkably, IFR increases with age, whereas RRD decreases with age. Autoimmunity to type I IFNs appears to be second only to age among common predictors of COVID-19 death.

2.
Chest ; 160(1): 175-186, 2021 07.
Article in English | MEDLINE | ID: covidwho-1525725

ABSTRACT

BACKGROUND: SARS-CoV-2 aerosolization during noninvasive positive-pressure ventilation may endanger health care professionals. Various circuit setups have been described to reduce virus aerosolization. However, these setups may alter ventilator performance. RESEARCH QUESTION: What are the consequences of the various suggested circuit setups on ventilator efficacy during CPAP and noninvasive ventilation (NIV)? STUDY DESIGN AND METHODS: Eight circuit setups were evaluated on a bench test model that consisted of a three-dimensional printed head and an artificial lung. Setups included a dual-limb circuit with an oronasal mask, a dual-limb circuit with a helmet interface, a single-limb circuit with a passive exhalation valve, three single-limb circuits with custom-made additional leaks, and two single-limb circuits with active exhalation valves. All setups were evaluated during NIV and CPAP. The following variables were recorded: the inspiratory flow preceding triggering of the ventilator, the inspiratory effort required to trigger the ventilator, the triggering delay, the maximal inspiratory pressure delivered by the ventilator, the tidal volume generated to the artificial lung, the total work of breathing, and the pressure-time product needed to trigger the ventilator. RESULTS: With NIV, the type of circuit setup had a significant impact on inspiratory flow preceding triggering of the ventilator (P < .0001), the inspiratory effort required to trigger the ventilator (P < .0001), the triggering delay (P < .0001), the maximal inspiratory pressure (P < .0001), the tidal volume (P = .0008), the work of breathing (P < .0001), and the pressure-time product needed to trigger the ventilator (P < .0001). Similar differences and consequences were seen with CPAP as well as with the addition of bacterial filters. Best performance was achieved with a dual-limb circuit with an oronasal mask. Worst performance was achieved with a dual-limb circuit with a helmet interface. INTERPRETATION: Ventilator performance is significantly impacted by the circuit setup. A dual-limb circuit with oronasal mask should be used preferentially.


Subject(s)
COVID-19 , Continuous Positive Airway Pressure , Disease Transmission, Infectious/prevention & control , Noninvasive Ventilation , Air Filters , Benchmarking/methods , COVID-19/therapy , COVID-19/transmission , Continuous Positive Airway Pressure/adverse effects , Continuous Positive Airway Pressure/instrumentation , Continuous Positive Airway Pressure/methods , Critical Pathways/standards , Critical Pathways/trends , Humans , Infectious Disease Transmission, Patient-to-Professional/prevention & control , Noninvasive Ventilation/adverse effects , Noninvasive Ventilation/instrumentation , Noninvasive Ventilation/methods , Research Design , Respiratory Function Tests/methods , SARS-CoV-2 , Treatment Outcome , Ventilators, Mechanical
3.
Sci Immunol ; 6(62)2021 08 19.
Article in English | MEDLINE | ID: covidwho-1434876

ABSTRACT

Autosomal inborn errors of type I IFN immunity and autoantibodies against these cytokines underlie at least 10% of critical COVID-19 pneumonia cases. We report very rare, biochemically deleterious X-linked TLR7 variants in 16 unrelated male individuals aged 7 to 71 years (mean: 36.7 years) from a cohort of 1,202 male patients aged 0.5 to 99 years (mean: 52.9 years) with unexplained critical COVID-19 pneumonia. None of the 331 asymptomatically or mildly infected male individuals aged 1.3 to 102 years (mean: 38.7 years) tested carry such TLR7 variants (p = 3.5 × 10-5). The phenotypes of five hemizygous relatives of index cases infected with SARS-CoV-2 include asymptomatic or mild infection (n=2, 5 and 38 years), or moderate (n=1, 5 years), severe (n=1, 27 years), or critical (n=1, 29 years) pneumonia. Two boys (aged 7 and 12 years) from a cohort of 262 male patients with severe COVID-19 pneumonia (mean: 51.0 years) are hemizygous for a deleterious TLR7 variant. The cumulative allele frequency for deleterious TLR7 variants in the male general population is < 6.5x10-4 We also show that blood B cell lines and myeloid cell subsets from the patients do not respond to TLR7 stimulation, a phenotype rescued by wild-type TLR7 The patients' blood plasmacytoid dendritic cells (pDCs) produce low levels of type I IFNs in response to SARS-CoV-2. Overall, X-linked recessive TLR7 deficiency is a highly penetrant genetic etiology of critical COVID-19 pneumonia, in about 1.8% of male patients below the age of 60 years. Human TLR7 and pDCs are essential for protective type I IFN immunity against SARS-CoV-2 in the respiratory tract.


Subject(s)
COVID-19/complications , Genetic Diseases, X-Linked/complications , Immune System Diseases/complications , Toll-Like Receptor 7/deficiency , Adolescent , Adult , Aged , Aged, 80 and over , Alleles , Child , Child, Preschool , Humans , Infant , Male , Middle Aged , Pedigree , Penetrance , Toll-Like Receptor 7/genetics , Young Adult
4.
Sci Immunol ; 6(62)2021 08 19.
Article in English | MEDLINE | ID: covidwho-1434875

ABSTRACT

Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/mL, in plasma diluted 1 to 10) of IFN-α and/or -ω are found in about 10% of patients with critical COVID-19 pneumonia, but not in subjects with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-α and/or -ω (100 pg/mL, in 1/10 dilutions of plasma) in 13.6% of 3,595 patients with critical COVID-19, including 21% of 374 patients > 80 years, and 6.5% of 522 patients with severe COVID-19. These antibodies are also detected in 18% of the 1,124 deceased patients (aged 20 days-99 years; mean: 70 years). Moreover, another 1.3% of patients with critical COVID-19 and 0.9% of the deceased patients have auto-Abs neutralizing high concentrations of IFN-ß. We also show, in a sample of 34,159 uninfected subjects from the general population, that auto-Abs neutralizing high concentrations of IFN-α and/or -ω are present in 0.18% of individuals between 18 and 69 years, 1.1% between 70 and 79 years, and 3.4% >80 years. Moreover, the proportion of subjects carrying auto-Abs neutralizing lower concentrations is greater in a subsample of 10,778 uninfected individuals: 1% of individuals <70 years, 2.3% between 70 and 80 years, and 6.3% >80 years. By contrast, auto-Abs neutralizing IFN-ß do not become more frequent with age. Auto-Abs neutralizing type I IFNs predate SARS-CoV-2 infection and sharply increase in prevalence after the age of 70 years. They account for about 20% of both critical COVID-19 cases in the over-80s, and total fatal COVID-19 cases.


Subject(s)
Autoantibodies/immunology , COVID-19/immunology , Interferon Type I/immunology , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Autoantibodies/blood , COVID-19/mortality , Case-Control Studies , Child , Child, Preschool , Critical Illness , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Infant , Infant, Newborn , Interferon-alpha/immunology , Middle Aged , Young Adult
7.
BMJ Open ; 11(8): e048187, 2021 08 18.
Article in English | MEDLINE | ID: covidwho-1376500

ABSTRACT

INTRODUCTION: At the time of the worrying emergence and spread of bacterial resistance, reducing the selection pressure by reducing the exposure to antibiotics in patients with community-acquired pneumonia (CAP) is a public health issue. In this context, the combined use of molecular tests and biomarkers for guiding antibiotics discontinuation is attractive. Therefore, we have designed a trial comparing an integrated approach of diagnosis and treatment of severe CAP to usual care. METHODS AND ANALYSIS: The multiplex PCR and procalcitonin to reduce duration of antibiotics exposure in patients with severe-CAP (MULTI-CAP) trial is a multicentre (n=20), parallel-group, superiority, open-label, randomised trial. Patients are included if adult admitted to intensive care unit for a CAP. Diagnosis of pneumonia is based on clinical criteria and a newly appeared parenchymal infiltrate. Immunocompromised patients are excluded. Subjects are randomised (1:1 ratio) to either the intervention arm (experimental strategy) or the control arm (usual strategy). In the intervention arm, the microbiological diagnosis combines a respiratory multiplex PCR (mPCR) and conventional microbiological investigations. An algorithm of early antibiotic de-escalation or discontinuation is recommended, based on mPCR results and the procalcitonin value. In the control arm, only conventional microbiological investigations are performed and antibiotics de-escalation remains at the clinician's discretion. The primary endpoint is the number of days alive without any antibiotic from the randomisation to day 28. Based on our hypothesis of 2 days gain in the intervention arm, we aim to enrol a total of 450 patients over a 30-month period. ETHICS AND DISSEMINATION: The MULTI-CAP trial is conducted according to the principles of the Declaration of Helsinki, is registered in Clinical Trials and has been approved by the Committee for Protection of Persons and the National French Drug Safety Agency. Written informed consents are obtained from all the patients (or representatives). The results will be disseminated through educational institutions, submitted to peer-reviewed journals for publication and presented at medical congresses. TRIAL REGISTRATION NUMBER: NCT03452826; Pre-results.


Subject(s)
COVID-19 , Pneumonia , Adult , Anti-Bacterial Agents/therapeutic use , Humans , Intensive Care Units , Multiplex Polymerase Chain Reaction , Pneumonia/drug therapy , Procalcitonin
8.
Sci Immunol ; 6(62)2021 08 19.
Article in English | MEDLINE | ID: covidwho-1367380

ABSTRACT

Autosomal inborn errors of type I IFN immunity and autoantibodies against these cytokines underlie at least 10% of critical COVID-19 pneumonia cases. We report very rare, biochemically deleterious X-linked TLR7 variants in 16 unrelated male individuals aged 7 to 71 years (mean: 36.7 years) from a cohort of 1,202 male patients aged 0.5 to 99 years (mean: 52.9 years) with unexplained critical COVID-19 pneumonia. None of the 331 asymptomatically or mildly infected male individuals aged 1.3 to 102 years (mean: 38.7 years) tested carry such TLR7 variants (p = 3.5 × 10-5). The phenotypes of five hemizygous relatives of index cases infected with SARS-CoV-2 include asymptomatic or mild infection (n=2, 5 and 38 years), or moderate (n=1, 5 years), severe (n=1, 27 years), or critical (n=1, 29 years) pneumonia. Two boys (aged 7 and 12 years) from a cohort of 262 male patients with severe COVID-19 pneumonia (mean: 51.0 years) are hemizygous for a deleterious TLR7 variant. The cumulative allele frequency for deleterious TLR7 variants in the male general population is < 6.5x10-4 We also show that blood B cell lines and myeloid cell subsets from the patients do not respond to TLR7 stimulation, a phenotype rescued by wild-type TLR7 The patients' blood plasmacytoid dendritic cells (pDCs) produce low levels of type I IFNs in response to SARS-CoV-2. Overall, X-linked recessive TLR7 deficiency is a highly penetrant genetic etiology of critical COVID-19 pneumonia, in about 1.8% of male patients below the age of 60 years. Human TLR7 and pDCs are essential for protective type I IFN immunity against SARS-CoV-2 in the respiratory tract.


Subject(s)
COVID-19/complications , Genetic Diseases, X-Linked/complications , Immune System Diseases/complications , Toll-Like Receptor 7/deficiency , Adolescent , Adult , Aged , Aged, 80 and over , Alleles , Child , Child, Preschool , Humans , Infant , Male , Middle Aged , Pedigree , Penetrance , Toll-Like Receptor 7/genetics , Young Adult
9.
Sci Immunol ; 6(62)2021 08 19.
Article in English | MEDLINE | ID: covidwho-1367379

ABSTRACT

Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/mL, in plasma diluted 1 to 10) of IFN-α and/or -ω are found in about 10% of patients with critical COVID-19 pneumonia, but not in subjects with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-α and/or -ω (100 pg/mL, in 1/10 dilutions of plasma) in 13.6% of 3,595 patients with critical COVID-19, including 21% of 374 patients > 80 years, and 6.5% of 522 patients with severe COVID-19. These antibodies are also detected in 18% of the 1,124 deceased patients (aged 20 days-99 years; mean: 70 years). Moreover, another 1.3% of patients with critical COVID-19 and 0.9% of the deceased patients have auto-Abs neutralizing high concentrations of IFN-ß. We also show, in a sample of 34,159 uninfected subjects from the general population, that auto-Abs neutralizing high concentrations of IFN-α and/or -ω are present in 0.18% of individuals between 18 and 69 years, 1.1% between 70 and 79 years, and 3.4% >80 years. Moreover, the proportion of subjects carrying auto-Abs neutralizing lower concentrations is greater in a subsample of 10,778 uninfected individuals: 1% of individuals <70 years, 2.3% between 70 and 80 years, and 6.3% >80 years. By contrast, auto-Abs neutralizing IFN-ß do not become more frequent with age. Auto-Abs neutralizing type I IFNs predate SARS-CoV-2 infection and sharply increase in prevalence after the age of 70 years. They account for about 20% of both critical COVID-19 cases in the over-80s, and total fatal COVID-19 cases.


Subject(s)
Autoantibodies/immunology , COVID-19/immunology , Interferon Type I/immunology , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Autoantibodies/blood , COVID-19/mortality , Case-Control Studies , Child , Child, Preschool , Critical Illness , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Infant , Infant, Newborn , Interferon-alpha/immunology , Middle Aged , Young Adult
10.
Chest ; 160(1): 175-186, 2021 07.
Article in English | MEDLINE | ID: covidwho-1298651

ABSTRACT

BACKGROUND: SARS-CoV-2 aerosolization during noninvasive positive-pressure ventilation may endanger health care professionals. Various circuit setups have been described to reduce virus aerosolization. However, these setups may alter ventilator performance. RESEARCH QUESTION: What are the consequences of the various suggested circuit setups on ventilator efficacy during CPAP and noninvasive ventilation (NIV)? STUDY DESIGN AND METHODS: Eight circuit setups were evaluated on a bench test model that consisted of a three-dimensional printed head and an artificial lung. Setups included a dual-limb circuit with an oronasal mask, a dual-limb circuit with a helmet interface, a single-limb circuit with a passive exhalation valve, three single-limb circuits with custom-made additional leaks, and two single-limb circuits with active exhalation valves. All setups were evaluated during NIV and CPAP. The following variables were recorded: the inspiratory flow preceding triggering of the ventilator, the inspiratory effort required to trigger the ventilator, the triggering delay, the maximal inspiratory pressure delivered by the ventilator, the tidal volume generated to the artificial lung, the total work of breathing, and the pressure-time product needed to trigger the ventilator. RESULTS: With NIV, the type of circuit setup had a significant impact on inspiratory flow preceding triggering of the ventilator (P < .0001), the inspiratory effort required to trigger the ventilator (P < .0001), the triggering delay (P < .0001), the maximal inspiratory pressure (P < .0001), the tidal volume (P = .0008), the work of breathing (P < .0001), and the pressure-time product needed to trigger the ventilator (P < .0001). Similar differences and consequences were seen with CPAP as well as with the addition of bacterial filters. Best performance was achieved with a dual-limb circuit with an oronasal mask. Worst performance was achieved with a dual-limb circuit with a helmet interface. INTERPRETATION: Ventilator performance is significantly impacted by the circuit setup. A dual-limb circuit with oronasal mask should be used preferentially.


Subject(s)
COVID-19 , Continuous Positive Airway Pressure , Disease Transmission, Infectious/prevention & control , Noninvasive Ventilation , Air Filters , Benchmarking/methods , COVID-19/therapy , COVID-19/transmission , Continuous Positive Airway Pressure/adverse effects , Continuous Positive Airway Pressure/instrumentation , Continuous Positive Airway Pressure/methods , Critical Pathways/standards , Critical Pathways/trends , Humans , Infectious Disease Transmission, Patient-to-Professional/prevention & control , Noninvasive Ventilation/adverse effects , Noninvasive Ventilation/instrumentation , Noninvasive Ventilation/methods , Research Design , Respiratory Function Tests/methods , SARS-CoV-2 , Treatment Outcome , Ventilators, Mechanical
11.
Cell Death Dis ; 12(4): 310, 2021 03 24.
Article in English | MEDLINE | ID: covidwho-1149708

ABSTRACT

SARS-CoV-2 is responsible for the ongoing world-wide pandemic which has already taken more than two million lives. Effective treatments are urgently needed. The enzymatic activity of the HECT-E3 ligase family members has been implicated in the cell egression phase of deadly RNA viruses such as Ebola through direct interaction of its VP40 Protein. Here we report that HECT-E3 ligase family members such as NEDD4 and WWP1 interact with and ubiquitylate the SARS-CoV-2 Spike protein. Furthermore, we find that HECT family members are overexpressed in primary samples derived from COVID-19 infected patients and COVID-19 mouse models. Importantly, rare germline activating variants in the NEDD4 and WWP1 genes are associated with severe COVID-19 cases. Critically, I3C, a natural NEDD4 and WWP1 inhibitor from Brassicaceae, displays potent antiviral effects and inhibits viral egression. In conclusion, we identify the HECT family members of E3 ligases as likely novel biomarkers for COVID-19, as well as new potential targets of therapeutic strategy easily testable in clinical trials in view of the established well-tolerated nature of the Brassicaceae natural compounds.


Subject(s)
COVID-19/drug therapy , COVID-19/enzymology , Ubiquitin-Protein Ligases/antagonists & inhibitors , Ubiquitin-Protein Ligases/metabolism , Adult , Aged , Animals , Antiviral Agents/pharmacology , COVID-19/genetics , COVID-19/metabolism , Chlorocebus aethiops , Endosomal Sorting Complexes Required for Transport/metabolism , Female , Humans , Indoles/pharmacology , Male , Mice , Mice, Inbred BALB C , Middle Aged , Nedd4 Ubiquitin Protein Ligases/genetics , Nedd4 Ubiquitin Protein Ligases/metabolism , SARS-CoV-2/isolation & purification , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/metabolism , Ubiquitin-Protein Ligases/genetics , Ubiquitination , Vero Cells
12.
ERJ Open Res ; 7(1)2021 Jan.
Article in English | MEDLINE | ID: covidwho-1133578

ABSTRACT

Pneumomediastinum in severe #COVID19 presentations could be due to a lung parenchymal retractive process generated by intense inflammation as in acute exacerbation of idiopathic pulmonary fibrosis or MDA-5 acute interstitial lung disease https://bit.ly/3qzBYMW.

13.
Ann Intensive Care ; 11(1): 37, 2021 Feb 27.
Article in English | MEDLINE | ID: covidwho-1105741

ABSTRACT

BACKGROUND: The efficacy of high flow nasal canula oxygen therapy (HFNO) to prevent invasive mechanical ventilation (IMV) is not well established in severe coronavirus disease 2019 (COVID-19). The aim of this study was to compare the risk of IMV between two strategies of oxygenation (conventional oxygenation and HFNO) in critically ill COVID 19 patients. METHODS: This was a bicenter retrospective study which took place in two intensive care units (ICU) of tertiary hospitals in the Paris region from March 11, to May 3, 2020. We enrolled consecutive patients hospitalized for COVID-19 and acute respiratory failure (ARF) who did not receive IMV at ICU admission. The primary outcome was the rate of IMV after ICU admission. Secondary outcomes were death at day 28 and day 60, length of ICU stay and ventilator-free days at day 28. Data from the HFNO group were compared with those from the standard oxygen therapy (SOT) group using weighted propensity score. RESULTS: Among 138 patients who met the inclusion criteria, 62 (45%) were treated with SOT alone, and 76 (55%) with HFNO. In HFNO group, 39/76 (51%) patients received IMV and 46/62 (74%) in SOT group (OR 0.37 [95% CI, 0.18-0.76] p = 0.007). After weighted propensity score, HFNO was still associated with a lower rate of IMV (OR 0.31 [95% CI, 0.14-0.66] p = 0.002). Length of ICU stay and mortality at day 28 and day 60 did not significantly differ between HFNO and SOT groups after weighted propensity score. Ventilator-free days at days 28 was higher in HNFO group (21 days vs 10 days, p = 0.005). In the HFNO group, predictive factors associated with IMV were SAPS2 score (OR 1.13 [95%CI, 1.06-1.20] p = 0.0002) and ROX index > 4.88 (OR 0.23 [95%CI, 0.008-0.64] p = 0.006). CONCLUSIONS: High flow nasal canula oxygen for ARF due to COVID-19 is associated with a lower rate of invasive mechanical ventilation.

14.
J Clin Immunol ; 41(3): 536-544, 2021 04.
Article in English | MEDLINE | ID: covidwho-1092712

ABSTRACT

PURPOSE: To report four cases of life-threatening COVID-19 pneumonia in patients with high blood concentrations of neutralizing autoantibodies against type I interferons (IFNs), who were treated with plasma exchange (PE) as a rescue therapy. METHODS: Prospective case series, which included patients, diagnosed with RT-PCR-confirmed SARS-CoV-2 infection and positive autoantibodies against type I IFNs in two French intensive care units (ICUs) between October 8 and November 14, 2020. Six critically ill COVID-19 patients with no anti-IFN antibodies were used as controls. Anti-IFN autoantibodies and IFN concentrations, together with the levels of anti-SARS-CoV-2 antibodies, were measured sequentially in serum. Viral load was determined in the upper and lower respiratory tract. Patients were followed during hospital stay. RESULTS: Three men and one woman were included. Three of the patients had four PE sessions each, while another had three PE sessions. PE decreased the concentrations of autoantibodies against type I IFN in all four patients, whereas anti-SARS-CoV-2 antibody levels remained stable. Autoantibodies against type I IFN levels were high in tracheal aspirates of one patient and decreased after three PE sessions. By contrast, anti-IFN autoantibodies were not detected in tracheal aspirates from five control patients without detectable anti-IFN autoantibodies in serum. During PE, serum IFN-α levels slightly increased in three out of four patients, and upper respiratory tract viral load decreased in all patients. All patients were alive at day 28 of ICU admission. Two patients eventually died in the ICU, while the two survivors were discharged from the ICU at days 50 and 66. CONCLUSIONS: PE efficiently removes autoantibodies against type I IFNs, including those detected in tracheal aspirates, without affecting anti-SARS-CoV-2 antibody levels, in patients with life-threatening COVID-19 pneumonia. The clinical benefit of PE in patients with autoantibodies against type I IFNs should be tested in a larger study.


Subject(s)
Autoantibodies/blood , COVID-19/therapy , Interferon Type I/immunology , Plasma Exchange , SARS-CoV-2 , Adult , Aged , Autoantibodies/isolation & purification , COVID-19/immunology , Female , Humans , Male , Prospective Studies
16.
ERJ Open Res ; 6(4)2020 Oct.
Article in English | MEDLINE | ID: covidwho-951705

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) outbreak is a primary global concern, and data are lacking concerning risk of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) environmental contamination. OBJECTIVE: To identify risk factors for SARS-CoV-2 environmental contamination in COVID-19 patients admitted to the intensive care unit (ICU). METHODS: A prospective single centre 1-day study was carried out in an ICU. Four surfaces (the ventilator control screen, the control buttons of the syringe pump, the bed rails and the computer table located >1 m away from the patient) were systematically swabbed at least 8 h after any cleaning process. We analysed clinical, microbiological and radiological data to identify risk factors for SARS-CoV-2 environmental contamination. RESULTS: 40% of ICU patients were found to contaminate their environment. No particular trend emerged regarding the type of surface contaminated. Modality of oxygen support (high-flow nasal cannula oxygenation, invasive mechanical ventilation, standard oxygen mask) was not associated with the risk of environmental contamination. Univariate analysis showed that lymphopenia <0.7×109·L-1 was associated with environmental contamination. CONCLUSION: Despite small sample size, our study generated surprising results. Modality of oxygen support is not associated with risk of environmental contamination. Further studies are needed.

17.
Science ; 370(6515)2020 10 23.
Article in English | MEDLINE | ID: covidwho-889832

ABSTRACT

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-ω (IFN-ω) (13 patients), against the 13 types of IFN-α (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men.


Subject(s)
Autoantibodies/blood , Coronavirus Infections/immunology , Interferon Type I/immunology , Interferon alpha-2/immunology , Pneumonia, Viral/immunology , Adult , Aged , Aged, 80 and over , Antibodies, Neutralizing/blood , Asymptomatic Infections , Betacoronavirus , COVID-19 , Case-Control Studies , Critical Illness , Female , Humans , Immunoglobulin G/blood , Male , Middle Aged , Pandemics , SARS-CoV-2
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