SARS-CoV-2 detection in the lower respiratory tract of invasively ventilated ARDS patients

Niccolò Buetti, Paul-Henri Wicky, Quentin Le Hingrat, Stéphane Ruckly, Timothy Mazzuchelli, Ambre Loiodice, Pierpaolo Trimboli, Valentina Forni Ogna, Etienne de Montmollin, Enos Bernasconi, Benoit Visseaux, Jean-François Timsit, Niccolò Buetti, Paul-Henri Wicky, Quentin Le Hingrat, Stéphane Ruckly, Timothy Mazzuchelli, Ambre Loiodice, Pierpaolo Trimboli, Valentina Forni Ogna, Etienne de Montmollin, Enos Bernasconi, Benoit Visseaux, Jean-François Timsit

Abstract

Background: Data on SARS-CoV-2 load in lower respiratory tract (LRT) are scarce. Our objectives were to describe the viral shedding and the viral load in LRT and to determine their association with mortality in critically ill COVID-19 patients.

Methods: We conducted a binational study merging prospectively collected data from two COVID-19 reference centers in France and Switzerland. First, we described the viral shedding duration (i.e., time to negativity) in LRT samples. Second, we analyzed viral load in LRT samples. Third, we assessed the association between viral presence in LRT and mortality using mixed-effect logistic models for clustered data adjusting for the time between symptoms' onset and date of sampling.

Results: From March to May 2020, 267 LRT samples were performed in 90 patients from both centers. The median time to negativity was 29 (IQR 23; 34) days. Prolonged viral shedding was not associated with age, gender, cardiac comorbidities, diabetes, immunosuppression, corticosteroids use, or antiviral therapy. The LRT viral load tended to be higher in non-survivors. This difference was statistically significant after adjusting for the time interval between onset of symptoms and date of sampling (OR 3.78, 95% CI 1.13-12.64, p = 0.03).

Conclusions: The viral shedding in LRT lasted almost 30 days in median in critically ill patients, and the viral load in the LRT was associated with the 6-week mortality.

Trial registration: ClinicalTrials.gov NCT04262921.

Keywords: COVID-19; ICU; Lower respiratory tract; Mortality; SARS-CoV-2; Viral load; Viral shedding.

Conflict of interest statement

The authors have disclosed that they do not have conflict of interest. JFT received fees for lectures to 3M, MSD, Pfizer, and Biomerieux. JFT received research grants from Astellas, 3M, MSD, and Pfizer. JFT participated to advisory boards of 3M, MSD, Bayer Pharma, Nabriva, and Pfizer. BV reports grants, personal fees for lectures, and travel accommodations from Qiagen. BV received personal fees for lecture and travel accommodation support from BioMérieux. BV received personal fees for lectures from Hologic and Gilead.

Figures

Fig. 1
Fig. 1
Viral shedding in lower respiratory tract for the different patient populations, according to patients’ characteristics and to treatments received. For this descriptive analysis, we performed a log rank test for the different subgroups
Fig. 2
Fig. 2
Viral load among survivors and non-survivors at 6 weeks, stratified by the time between symptoms’ onset and date of sampling. For this descriptive analysis, we performed a Wilcoxon test between survivors and non-survivors. N, number of lower respiratory tract samples performed

References

    1. Faust JS, Del Rio C. Assessment of deaths from COVID-19 and from seasonal influenza. JAMA Intern Med. 2020;180(8):1045–46. 10.1001/jamainternmed.2020.2306.
    1. Zheng S, Fan J, Yu F, Feng B, Lou B, Zou Q, et al. Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January-March 2020: retrospective cohort study. Bmj. 2020;369:m1443. doi: 10.1136/bmj.m1443.
    1. Yu F, Yan L, Wang N, Yang S, Wang L, Tang Y, et al. Quantitative detection and viral load analysis of SARS-CoV-2 in infected patients. Clin Infect Dis. 2020;71(15):793–98. 10.1093/cid/ciaa345.
    1. Fang Z, Zhang Y, Hang C, Ai J, Li S, Zhang W. Comparisons of viral shedding time of SARS-CoV-2 of different samples in ICU and non-ICU patients. J Infection. 2020;81(1):147–178.
    1. Wolfel R, Corman VM, Guggemos W, Seilmaier M, Zange S, Muller MA, et al. Virological assessment of hospitalized patients with COVID-2019. Nature. 2020;581(7809):465–469. doi: 10.1038/s41586-020-2196-x.
    1. Huang Y, Chen S, Yang Z, Guan W, Liu D, Lin Z, et al. SARS-CoV-2 viral load in clinical samples from critically ill patients. Am J Respir Crit Care Med. 2020;201(11):1435–1438. doi: 10.1164/rccm.202003-0572LE.
    1. Pujadas E, Chaudhry F, McBride R, Richter F, Zhao S, Wajnberg A, et al. SARS-CoV-2 viral load predicts COVID-19 mortality. Lancet Respir Med. 2020;8(9):e70. 10.1016/S2213-2600(20)30354-4.
    1. ECDC (2020) Guidance for discharge and ending isolation in the context of widespread community transmission of COVID-19. Availbale from: . Last Accessed 15th July 2020. 2020.
    1. Lescure FX, Bouadma L, Nguyen D, Parisey M, Wicky PH, Behillil S, et al. Clinical and virological data of the first cases of COVID-19 in Europe: a case series. Lancet Infect Dis. 2020;20(6):697–706. doi: 10.1016/S1473-3099(20)30200-0.
    1. Pan Y, Zhang D, Yang P, Poon LLM, Wang Q. Viral load of SARS-CoV-2 in clinical samples. Lancet Infect Dis. 2020;20(4):411–412. doi: 10.1016/S1473-3099(20)30113-4.
    1. Buetti N, Trimboli PP, Mazzuchelli T, Lo Priore E, Balmelli C, Trkola A, et al. Diabetes mellitus is a risk factor for prolonged SARS-CoV-2 viral shedding in lower respiratory tract samples of critically ill patients. Endocrine. 2020:1–7. 10.1007/s12020-020-02465-4.
    1. Fu Y, Han P, Zhu R, Bai T, Yi J, Zhao X, et al. Risk factors for viral RNA shedding in COVID-19 patients. Eur Respir J. 2020.
    1. Xu K, Chen Y, Yuan J, Yi P, Ding C, Wu W, et al. Factors associated with prolonged viral RNA shedding in patients with COVID-19. Clin Infect Dis. 2020;71(15):799–806. 10.1093/cid/ciaa351.
    1. Xiao AT, Tong YX, Zhang S. Profile of RT-PCR for SARS-CoV-2: a preliminary study from 56 COVID-19 patients. Clin Infectious Diseases. 2020;ciaa460. 10.1093/cid/ciaa460.
    1. Qi L, Yang Y, Jiang D, Tu C, Wan L, Chen X, et al. Factors associated with duration of viral shedding in adults with COVID-19 outside of Wuhan, China: a retrospective cohort study. Int J Infect Dis. 2020;96:531–37. 10.1016/j.ijid.2020.05.045.
    1. von Elm E, Altman DG, Egger M, Pocock SJ, Gotzsche PC, Vandenbroucke JP, et al. Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Bmj. 2007;335(7624):806–808. doi: 10.1136/.
    1. Siddiqi HK, Mehra MR. COVID-19 illness in native and immunosuppressed states: a clinical-therapeutic staging proposal. J Heart Lung Transplantation. 2020;39(5):405–407. doi: 10.1016/j.healun.2020.03.012.
    1. Toniati P, Piva S, Cattalini M, Garrafa E, Regola F, Castelli F, et al. Tocilizumab for the treatment of severe COVID-19 pneumonia with hyperinflammatory syndrome and acute respiratory failure: a single center study of 100 patients in Brescia, Italy. Autoimmunity Reviews. 2020;19(7):102568. doi: 10.1016/j.autrev.2020.102568.
    1. Yan D, Liu XY, Zhu YN, Huang L, Dan BT, Zhang GJ, et al. Factors associated with prolonged viral shedding and impact of lopinavir/ritonavir treatment in hospitalised non-critically ill patients with SARS-CoV-2 infection. Eur Respir J. 2020.

Source: PubMed

Sponsoren und Mitarbeiter

Krankheiten

Drogeninterventionen

3
Abonnieren