BackgroundThe coronavirus disease 2019 (Covid-19) outbreak is a main concern and data are lacking concerning risk of 2019 novel coronavirus (SARS-CoV-2) environmental contamination.ObjectiveTo identify risk factors of SARS-CoV-2 environmental contamination in Covid-19 patients admitted to the intensive care unit (ICU).MethodsProspective single center 1 day study in the ICU. Four surfaces (1/ the ventilator control screen, 2/ the control buttons of syringe pump 3/ bed rails, and 4/ the computer table located at more than a meter away of the patient) were systematically swabbed at least 8 h after any cleaning process. We analysed clinical, microbiological and radiological data to identify risk factor of SARS-CoV-2 environmental contamination.ResultsForty percent of ICU patients did 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. By univariate analysis lymphopenia<0.7 G·L−1 was associated to environmental contamination.ConclusionDespite small effective, our study generate surprising results. Modality of oxygen support is not associated with risk of environmental contamination. Further studies are needed.
Background
We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases.
Methods
We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.
Results
No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5–528.7, P = 1.1 × 10−4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3–8.2], P = 2.1 × 10−4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1–2635.4], P = 3.4 × 10−3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3–8.4], P = 7.7 × 10−8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10−5).
Conclusions
Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old.
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