Dear Editor
The paper by Buetti et al. [1] regarding the prolonged SARS-CoV-2 viral shedding in lower respiratory tract samples of critically ill patients presented a fascinating finding. In this Swiss cohort, the presence of diabetes mellitus (DM) in critically ill patients proved to be a risk factor for prolonged SARS-CoV-2 RNA. In a recent work, we assessed clinical and demographic risk factors for prolonged viral RNA shedding and time to achieve the cessation of viral RNA shedding (CVS) in 251 patients with COVID-19 based on nasopharyngeal samples only [2].
We identified 34 (14%) patients with DM (Table 1). These patients were older (60 years [IQR 15.5] vs. 50 years [IQR 28]; p < 0.001) and had a higher frequency of comorbidities such as obesity, coronary artery disease, chronic obstructive pulmonary disease, and heart failure (p < 0.01) when compared to patients without DM. Patients with DM were more frequently hospitalized (61.8 vs. 18.9%; p < 0.001) than patients without DM. Dyspnea, diarrhea, and dizziness were more frequently seen in patients with DM (p < 0.01) at the time of diagnosis. Despite these differences, there was no difference in time to achieve CVS when compared to patients with and without DM (24 days (IQR 11.8) vs. 23 days (IQR 12); p = 0.591). This is best observed in Fig. 1. Interestingly, dizziness was more commonly reported at the time of CVS in patients with DM. DM was not associated with prolonged viral RNA shedding in a univariate regression model (p = 0.49).
Table 1.
Clinical characteristics, timing of PCR test, symptoms at diagnosis, and symptoms after cessation of viral shedding of COVID-19 patients with and without diabetes mellitus
Clinical characteristics | Diabetes mellitus (N = 34) | No diabetes mellitus (N = 217) | Total (N = 251) | p value |
---|---|---|---|---|
Demographics | ||||
Age, years | 60 (15.5) | 50 (28) | 53 (27) | <0.001a |
Male | 20 (58.8%) | 128 (59%) | 148 (59%) | 0.986b |
Hospitalized | 21 (61.8%) | 41 (18.9%) | 62 (24.7%) | <0.001b |
Comorbidities | ||||
Coronary artery disease | 25 (73.5%) | 45 (20.7%) | 70 (27.9%) | <0.001b |
Obesity | 19 (55.9%) | 56 (25.8%) | 75 (29.9%) | <0.001b |
Chronic obstructive pulmonary disease | 9 (26.5%) | 13 (6.0%) | 22 (8.8%) | <0.001b |
Chronic kidney disease | 5 (14.7%) | 15 (6.9%) | 20 (8.0%) | 0.119b |
Heart failure | 4 (11.8%) | 5 (2.3%) | 9 (3.6%) | 0.006b |
Asthma | 3 (8.8%) | 43 (19.8%) | 46 (18.3%) | 0.123b |
Use of anti-neoplastic chemotherapy, immunomodulators, or immunosuppressive drugs | 3 (8.8%) | 13 (6.0%) | 16 (6.4%) | 0.53b |
Initial symptoms | ||||
Cough | 30 (88.2%) | 181 (83.4%) | 211 (84.1%) | 0.475b |
Dyspnea | 26 (76.5%) | 107 (49.3%) | 133 (53.0%) | 0.003b |
Fever (T > 38.5 °C) | 16 (47.1%) | 110 (50.7%) | 126 (50.2%) | 0.694b |
Subjective fever | 8 (23.5%) | 43 (19.8%) | 51 (20.3%) | 0.617b |
Chills | 19 (55.9%) | 104 (47.9%) | 123 (49.0%) | 0.388b |
Shivering | 0 (0.0%) | 1 (0.5%) | 1 (0.4%) | 0.692b |
Muscle pain | 27 (79.4%) | 139 (64.1%) | 166 (66.1%) | 0.079b |
Diarrhea | 17 (50.0%) | 55 (25.3%) | 72 (28.7%) | 0.003b |
Headache | 12 (35.3%) | 82 (37.8%) | 94 (37.5%) | 0.78b |
Sore throat | 15 (44.1%) | 94 (43.3%) | 109 (43.4%) | 0.93b |
Ageusia | 7 (20.6%) | 44 (20.3%) | 51 (20.3%) | 0.966b |
Anosmia | 7 (20.6%) | 48 (22.1%) | 55 (21.9%) | 0.841b |
Dizziness | 14 (41.2%) | 43 (19.8%) | 57 (22.7%) | 0.006b |
Timing to PCR tests | ||||
Days from symptoms to positive PCR (IQR) | 2 (5.5) | 3 (6) | 3 (6) | 0.509a |
Days from symptoms to negative PCR (IQR) | 24 (11.8) | 23 (12) | 23 (12) | 0.591a |
Symptoms at time of negative PCR | ||||
Cough | 7 (20.6%) | 55 (25.3%) | 62 (24.7%) | 0.55b |
Dyspnea | 0 (0.0%) | 2 (0.9%) | 2 (0.8%) | 0.574b |
Chills | 0 (0.0%) | 1 (0.5%) | 1 (0.4%) | 0.692b |
Muscle pain | 11 (32.4%) | 65 (30.0%) | 76 (30.3%) | 0.777b |
Diarrhea | 1 (2.9%) | 1 (0.5%) | 2 (0.8%) | 0.13b |
Headache | 1 (2.9%) | 13 (6.0%) | 14 (5.6%) | 0.471b |
Sore throat | 7 (20.6%) | 42 (19.4%) | 49 (19.5%) | 0.866b |
Ageusia | 6 (17.6%) | 41 (18.9%) | 47 (18.7%) | 0.862b |
Anosmia | 6 (17.6%) | 45 (20.7%) | 51 (20.3%) | 0.677b |
None | 9 (26.5%) | 56 (25.8%) | 65 (25.9%) | 0.934b |
Unknown | 1 (2.9%) | 10 (4.6%) | 11 (4.4%) | 0.659b |
Dizziness | 6 (17.6%) | 12 (5.5%) | 18 (7.2%) | 0.011b |
aKruskal–Wallis rank sum test
bPearson’s Chi-squared test
Bold values indicate statistical significance
Fig. 1.
Time to cessation of SARS-CoV-2 viral RNA shedding in people with and without diabetes mellitus
In contrast to Buetti et al., our findings suggest that patients with DM do not show prolonged RNA viral shedding based on nasopharyngeal sampling despite older age and a higher frequency of comorbidities. DM has been described by Wang et al. [3] as a risk factor for viral RNA detection in both nasopharyngeal and sputum samples. Nevertheless, the presence of DM was not associated with prolonged shedding in their sample either. The determination of whether prolonged viral RNA shedding in lower respiratory samples represents a particular phenomenon of patients with DM or other immunocompromising states requires additional research and collaboration that combines different types of samples, timelines, and clinical characteristics.
Compliance with ethical standards
Conflict of interest
J.C.O. has provided consulting services for Elsevier, Inc and Bates College.
Footnotes
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
References
- 1.N. Buetti, P. Trimboli, T. Mazzuchelli, 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). 10.1007/s12020-020-02465-4 [DOI] [PMC free article] [PubMed]
- 2.Campioli CC, Cevallos EC, Assi M, Patel R, Binnicker MJ, O’Horo JC. Clinical predictors and timing of cessation of viral RNA shedding in patients with COVID-19. J. Clin. Virol. 2020;130:104577. doi: 10.1016/j.jcv.2020.104577. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.K. Wang, X. Zhang, J. Sun, et al. Differences of severe acute respiratory syndrome coronavirus 2 shedding duration in sputum and nasopharyngeal swab specimens among adult inpatients with coronavirus disease 2019. Chest (2020). 10.1016/j.chest.2020.06.015 [DOI] [PMC free article] [PubMed]