Diabetes mellitus is a risk factor for prolonged SARS-CoV-2 viral shedding in lower respiratory tract samples of critically ill patients

Abstract

Purpose The length of time a critically ill coronavirus disease 2019 (COVID-19) patient remains infectious and should therefore be isolated remains unknown. This prospective study was undertaken in critically ill patients to evaluate the reliability of single negative real-time polymerase chain reaction (RT-PCR) in lower tracheal aspirates (LTA) in predicting a second negative test and to analyze clinical factors potentially influencing the viral shedding. Methods From April 9, 2020 onwards, intubated COVID-19 patients treated in the intensive care unit were systematically evaluated for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by RT-PCR of nasopharyngeal swabs and LTA. The time to negativity was defined as the time between the onset of symptoms and the viral clearance in LTA. In order to identify risk factors for prolonged viral shedding, we used univariate and multivariate Cox proportional hazards models. Results Forty-eight intubated SARS-CoV-2 patients were enrolled. Overall, we observed that the association of the first negative RT-PCR with a second negative result was 96.7%. Median viral shedding was 25 (IQR: 21.5-28) days since symptoms' onset. In the univariate Cox model analysis, type 2 diabetes mellitus was associated with a prolonged viral RNA shedding (hazard ratio [HR]: 0.41, 95% CI: 0.06-3.11, p = 0.04). In the multivariate Cox model analysis, type 2 diabetes was associated with a prolonged viral RNA shedding (HR: 0.31, 95% CI: 0.11-0.89, p = 0.029). Conclusion Intubated patients with type 2 diabetes mellitus may have prolonged SARS-CoV-2 shedding. In critically ill COVID-19 patients, one negative LTA should be sufficient to assess and exclude infectivity.

SARS-CoV-2 viral shedding among diabetic patients: from upper to lower respiratory tract

“…The recently published letter by Cano et al suggested that patients with diabetes mellitus (DM) did not show prolonged RNA viral shedding based on nasopharyngeal sampling [2]. At first glance, these data seem to be in contrast to our study showing a prolonged viral shedding in lower respiratory tract of critically ill patients [1]. However, we respectfully would underline that this discrepancy could depend on differences in demographic feature and methodological/ statistical approaches.…”

“…However, we respectfully would underline that this discrepancy could depend on differences in demographic feature and methodological/ statistical approaches. Then, the following two issues have to be considered when comparing our results [1] with that from Cano et al [2]:…”

“…We would like to thank Cano et al for their interest in our manuscript "Diabetes mellitus is a risk factor for prolonged SARS-CoV-2 viral shedding in lower respiratory tract samples of critically ill patients" [1]. Data on SARS-CoV-2 viral shedding in COVID-19 patients are conflicting and this topic achieves high interest.…”

“…We performed a biweekly screening on lower respiratory tract samples in all patients, which is probably a different sample collection strategy compared to the patients included by Cano and colleagues. In addition, to evaluate risk factors for prolonged viral shedding, we used the survival Cox models [1], which are different to univariate regression models used by Cano et al [2]. Moreover, both studies included a limited number of patients and the statistical analyses should be interpreted with caution: It is conceivable that a larger samples size would allow to define more correctly risk factors for prolonged viral shedding.…”

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

“…The primary objective was the description of viral shedding duration (i.e., time to negativity) in LRTS and was defined as the time between onset of symptoms and viral clearance process (i.e., first negative detection of viral RNA in LRT). Of note, we previously showed that the association of the first negative RT-PCR with a second negative result was very high (i.e., 97%) in LRTS [11]. Secondary objectives were (1) the analysis of RT-PCR viral load in LRTS and (2) the assessment of 6-week mortality.…”