Dynamics of SARS-CoV-2 shedding in the respiratory tract depends on the severity of disease in COVID-19 patients

Munker, Dieter; Osterman, Andreas; Stubbe, Hans; Muenchhoff, Maximilian; Veit, Tobias; Weinberger, Tobias; Barnikel, Michaela; Mumm, Jan‐Niclas; Milger, Katrin; Khatamzas, Elham; Klauss, Sarah; Scherer, Clemens; Hellmuth, Johannes C.; Gießen-Jung, Clemens; Zöller, Michael; Herold, Tobias; Stecher, Stephanie Susanne; Toni, Enrico N. De; Schulz, Christian; Kneidinger, Nikolaus; Keppler, Oliver T.; Behr, Jürgen; Mayerle, Julia; Munker, Stefan

doi:10.1183/13993003.02724-2020

Cited by 45 publications

(47 citation statements)

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“…Therefore, repeated analysis of plasma ACE2 may provide increased predictive value. This is in line with a recent study showing increasing SARS-CoV-2 viral load during hospitalization and prolonged viral shedding in more severe COVID-19 disease [ 44 ]. Further, it is interesting that the association between plasma ACE2 and maximal acuity within 28 days in COVID-19 patients was statistically significant also after correction for age, BMI, pre-existing medical conditions, and the laboratory tests CRP, absolute neutrophil count and D-dimer.…”

Section: Discussionsupporting

confidence: 92%

Plasma ACE2 predicts outcome of COVID-19 in hospitalized patients

et al. 2021

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Aims Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to angiotensin converting enzyme 2 (ACE2) enabling entrance of the virus into cells and causing the infection termed coronavirus disease of 2019 (COVID-19). Here, we investigate associations between plasma ACE2 and outcome of COVID-19. Methods and results This analysis used data from a large longitudinal study of 306 COVID-19 positive patients and 78 COVID-19 negative patients (MGH Emergency Department COVID-19 Cohort). Comprehensive clinical data were collected on this cohort, including 28-day outcomes. The samples were run on the Olink® Explore 1536 platform which includes measurement of the ACE2 protein. High admission plasma ACE2 in COVID-19 patients was associated with increased maximal illness severity within 28 days with OR = 1.8, 95%-CI: 1.4–2.3 (P < 0.0001). Plasma ACE2 was significantly higher in COVID-19 patients with hypertension compared with patients without hypertension (P = 0.0045). Circulating ACE2 was also significantly higher in COVID-19 patients with pre-existing heart conditions and kidney disease compared with patients without these pre-existing conditions (P = 0.0363 and P = 0.0303, respectively). Conclusion This study suggests that measuring plasma ACE2 is potentially valuable in predicting COVID-19 outcomes. Further, ACE2 could be a link between COVID-19 illness severity and its established risk factors hypertension, pre-existing heart disease and pre-existing kidney disease.

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Section: Discussionsupporting

confidence: 92%

Plasma ACE2 predicts outcome of COVID-19 in hospitalized patients

et al. 2021

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“…Patients with immunocompromising conditions and those hospitalized for their initial infection also had higher rates of suspected reinfection. While we cannot rule out continued viral shedding in some cases, prolonged viral shedding for ≥90 days is uncommon [ 11 , 12 ]; Munker et al. found no viral shedding beyond 60 days even in severe disease [ 11 ].…”

Section: Discussionmentioning

confidence: 99%

Rate and severity of suspected SARS-Cov-2 reinfection in a cohort of PCR-positive COVID-19 patients

Slezak¹,

Bruxvoort²,

Fischer³

et al. 2021

Clinical Microbiology and Infection

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Objectives To estimate the burden and severity of suspected reinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods A retrospective cohort of members of Kaiser Permanente Southern California with PCR-positive SARS-CoV-2 infection between 1st March 2020 and 31st October 2020 was followed through electronic health records for subsequent positive SARS-CoV-2 tests (suspected reinfection) ≥90 days after initial infection, through 31st January 2021. Incidence of suspected reinfection was estimated using the Kaplan–Meier method. Cox proportional hazards models estimated the association of suspected reinfection with demographic and clinical characteristics, hospitalization, and date of initial infection. Results The cohort of 75 149 was predominantly Hispanic (49 648/75 149, 66.1%) and included slightly more females than males (39 736, 52.9%), with few immunocompromised patients (953, 1.3%); 315 suspected reinfections were identified, with a cumulative incidence at 270 days of 0.8% (95% confidence interval (CI) 0.7–1.0%). Hospitalization was more common at suspected reinfection (36/315, 11.4%) than initial infection (4094/75 149, 5.4%). Suspected reinfection rates were higher in females (1.0%, CI 0.8–1.2% versus 0.7%, CI 0.5–0.9%, p 0.002) and immunocompromised patients (2.1%, CI 1.0–4.2% versus 0.8%, CI 0.7–1.0%, p 0.004), and lower in children than adults (0.2%, CI 0.1–0.4% versus 0.9%, CI 0.7–1.0%, p 0.023). Patients hospitalized at initial infection were more likely to have suspected reinfection (1.2%, CI 0.6–1.7% versus 0.8%, CI 0.7–1.0%, p 0.030), as were those with initial infections later in 2020 (150-day incidence 0.4%, CI 0.2–0.5% September–October versus 0.2%, CI 0.1–0.3% March–May and 0.3%, CI 0.2–0.3% June–August, p 0.008). In an adjusted Cox proportional hazards model, being female (hazard ratio (HR) 1.44, CI 1.14–1.81), adult (age 18–39, HR 2.71, CI 1.38–5.31, age 40–59 HR 2.22, CI 1.12–4.41, age ≥60 HR 2.52, CI 1.23–5.17 versus <18 years), immunocompromised (HR 2.48, CI 1.31–4.68), hospitalized (HR 1.60, CI 1.07–2.38), and initially infected later in 2020 (HR 2.26, CI 1.38–3.71 September–October versus March–May) were significant independent predictors of suspected reinfection. Conclusions Reinfection with SARS-CoV-2 is uncommon, with suspected reinfections more likely in women, adults, immunocompromised subjects, and those previously hospitalized for coronavirus 2019 (COVID-19). This suggests a need for continued precautions and vaccination in patients with COVID-19 to prevent reinfection.

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“…We diagnosed COVID-19 in patients with matching symptoms and documented positivity for SARS-CoV-2 RNA in a reverse transcriptase-polymerase chain reaction (RT-PCR) from nasopharyngeal swabs (NPS) as described previously [ 15 ]. In case of high clinical suspicion but negativity for SARS-CoV-2 RNA in available clinical samples, e.g.…”

Section: Methodsmentioning

confidence: 99%

“…Repeated collection of either sample (NPS, sputum, and endotracheal aspirates) was performed in hospitalized patients for clinical monitoring purposes. When COVID-19 symptoms resolved and two consecutive NPS (at least with a day distance) showed a negative result, testing was stopped [ 15 ]. In this analysis, we used the term “duration of positivity for viral shedding.” It expresses the duration in days between the first and last confirmed positivity for SARS-CoV-2 in days.…”

Section: Methodsmentioning

confidence: 99%

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Pulmonary function impairment of asymptomatic and persistently symptomatic patients 4 months after COVID-19 according to disease severity

et al. 2021

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Objective Evaluation of pulmonary function impairment after COVID-19 in persistently symptomatic and asymptomatic patients of all disease severities and characterisation of risk factors. Methods Patients with confirmed SARS-CoV-2 infection underwent prospective follow-up with pulmonary function testing and blood gas analysis during steady-state cycle exercise 4 months after acute illness. Pulmonary function impairment (PFI) was defined as reduction below 80% predicted of DLCOcSB, TLC, FVC, or FEV1. Clinical data were analyzed to identify risk factors for impaired pulmonary function. Results 76 patients were included, hereof 35 outpatients with mild disease and 41 patients hospitalized due to COVID-19. Sixteen patients had critical disease requiring mechanical ventilation, 25 patients had moderate–severe disease. After 4 months, 44 patients reported persisting respiratory symptoms. Significant PFI was prevalent in 40 patients (52.6%) occurring among all disease severities. The most common cause for PFI was reduced DLCOcSB (n = 39, 51.3%), followed by reduced TLC and FVC. The severity of PFI was significantly associated with mechanical ventilation (p < 0.001). Further risk factors for DLCO impairment were COPD (p < 0.001), SARS-CoV-2 antibody-Titer (p = 0.014) and in hospitalized patients CT score. A decrease of paO2 > 3 mmHg during cycle exercise occurred in 1/5 of patients after mild disease course. Conclusion We characterized pulmonary function impairment in asymptomatic and persistently symptomatic patients of different severity groups of COVID-19 and identified further risk factors associated with persistently decreased pulmonary function. Remarkably, gas exchange abnormalities were revealed upon cycle exercise in some patients with mild disease courses and no preexisting pulmonary condition.

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Dynamics of SARS-CoV-2 shedding in the respiratory tract depends on the severity of disease in COVID-19 patients

Cited by 45 publications

References 46 publications

Plasma ACE2 predicts outcome of COVID-19 in hospitalized patients

Plasma ACE2 predicts outcome of COVID-19 in hospitalized patients

Rate and severity of suspected SARS-Cov-2 reinfection in a cohort of PCR-positive COVID-19 patients

Pulmonary function impairment of asymptomatic and persistently symptomatic patients 4 months after COVID-19 according to disease severity

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