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1.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-320908

ABSTRACT

In the wake of the COVID-19 pandemic many countries implemented containment measures to reduce disease transmission. Studies using digital data sources show that the mobility of individuals was effectively reduced in multiple countries. However, it remains unclear whether these reductions caused deeper structural changes in mobility networks, and how such changes may affect dynamic processes on the network. Here we use movement data of mobile phone users to show that mobility in Germany has not only been reduced considerably: Lockdown measures caused substantial and long-lasting structural changes in the mobility network. We find that long-distance travel was reduced disproportionately strongly. The trimming of long-range network connectivity leads to a more local, clustered network and a moderation of the "small-world" effect. We demonstrate that these structural changes have a considerable effect on epidemic spreading processes by "flattening" the epidemic curve and delaying the spread to geographically distant regions.

2.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-316208

ABSTRACT

Vaccination against COVID-19 with the recently approved mRNA vaccines BNT162b2 (BioNTech/Pfizer) and mRNA-1273 (Moderna) is currently underway in a large number of countries. However, high incidence rates and rapidly spreading SARS-CoV-2 variants are concerning. In combination with acute supply deficits in Europe in early 2021, the question arises of whether stretching the vaccine, for instance by delaying the second dose, can make a significant contribution to preventing deaths, despite associated risks such as lower vaccine efficacy, the potential emergence of escape mutants, enhancement, waning immunity, reduced social acceptance of off-label vaccination, and liability shifts. A quantitative epidemiological assessment of risks and benefits of non-standard vaccination protocols remains elusive. To clarify the situation and to provide a quantitative epidemiological foundation we develop a stochastic epidemiological model that integrates specific vaccine rollout protocols into a risk-group structured infectious disease dynamical model. Using the situation and conditions in Germany as a reference system, we show that delaying the second vaccine dose is expected to prevent deaths in the four to five digit range, should the incidence resurge. We show that this considerable public health benefit relies on the fact that both mRNA vaccines provide substantial protection against severe COVID-19 and death beginning 12 to 14 days after the first dose. The benefits of protocol change are attenuated should vaccine compliance decrease substantially. To quantify the impact of protocol change on vaccination adherence we performed a large-scale online survey. We find that, in Germany, changing vaccination protocols may lead to small reductions in vaccination intention. In sum, we therefore expect the benefits of a strategy change to remain substantial and stable.

3.
J Thromb Haemost ; 20(4): 919-928, 2022 04.
Article in English | MEDLINE | ID: covidwho-1626880

ABSTRACT

BACKGROUND: Resistance to fibrinolysis, levels of procoagulant/antifibrinolytic neutrophil extracellular traps (NETs), and the severity of acute ischemic stroke (AIS) are increased by COVID-19. Whether NETs are components of AIS thrombi from COVID-19 patients and whether COVID-19 impacts the susceptibility of these thrombi to thrombolytic treatments remain unknown, however. OBJECTIVES: We aimed to characterize AIS thrombi from COVID-19 patients by immunohistology and to compare their response to thrombolysis to that of AIS thrombi from non-COVID-19 patients. PATIENTS/METHODS: For this monocentric cohort study, 14 thrombi from COVID-19 AIS patients and 16 thrombi from non-COVID-19 patients, all recovered by endovascular therapy, were analyzed by immunohistology or subjected to ex vivo thrombolysis by tissue-type plasminogen (tPA)/plasminogen. RESULTS: COVID-19 AIS thrombi were rich in neutrophils and contained NETs, but not spike protein. Thrombolysis assays revealed a mean resistance profile to tPA/plasminogen of COVID-19 AIS thrombi similar to that of non-COVID-19 AIS thrombi. The addition of DNase 1 successfully improved thrombolysis by potentiating fibrinolysis irrespective of COVID-19 status. Levels of neutrophil, NETs, and platelet markers in lysis supernatants were comparable between AIS thrombi from non-COVID-19 and COVID-19 patients. CONCLUSIONS: These results show that COVID-19 does not impact NETs content or worsen fibrinolysis resistance of AIS thrombi, a therapeutic hurdle that could be overcome by DNase 1 even in the context of SARS-CoV-2 infection.


Subject(s)
Brain Ischemia , COVID-19 , Ischemic Stroke , Stroke , Thrombosis , Brain Ischemia/drug therapy , COVID-19/drug therapy , Cohort Studies , Fibrinolysis , Humans , SARS-CoV-2 , Stroke/drug therapy , Stroke/metabolism , Thrombolytic Therapy , Thrombosis/metabolism , Tissue Plasminogen Activator/therapeutic use
4.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-293021

ABSTRACT

Vaccines are the most powerful pharmaceutical tool to combat the COVID-19 pandemic. While the majority (about 65%) of the German population were fully vaccinated, incidence started growing exponentially in October 2021 with about 41% of recorded new cases aged twelve or above being symptomatic breakthrough infections, presumably also contributing to the dynamics. At the time, it (i) remains elusive how significant this contribution is and (ii) whether targeted non-pharmaceutical interventions (NPIs) may stop the amplification of the ongoing crisis. Here, we estimate that about 67%-76% of all new infections are caused by unvaccinated individuals, implying that only 24%-33% are caused by the vaccinated. Furthermore, we estimate 38%-51% of new infections to be caused by unvaccinated individuals infecting other unvaccinated individuals. In total, unvaccinated individuals are expected to be involved in 8-9 of 10 new infections. We further show that decreasing the transmissibility of the unvaccinated by, e.g. targeted NPIs, causes a steeper decrease in the effective reproduction number R than decreasing the transmissibility of vaccinated individuals, potentially leading to temporary epidemic control. Furthermore, reducing contacts between vaccinated and unvaccinated individuals serves to decrease R in a similar manner as increasing vaccine uptake. Taken together, our results contribute to the public discourse regarding policy changes in pandemic response and highlight the importance of combined measures, such as vaccination campaigns and contact reduction, to achieve epidemic control and preventing an overload of public health

5.
Proc Natl Acad Sci U S A ; 117(52): 32883-32890, 2020 12 29.
Article in English | MEDLINE | ID: covidwho-960372

ABSTRACT

In the wake of the COVID-19 pandemic many countries implemented containment measures to reduce disease transmission. Studies using digital data sources show that the mobility of individuals was effectively reduced in multiple countries. However, it remains unclear whether these reductions caused deeper structural changes in mobility networks and how such changes may affect dynamic processes on the network. Here we use movement data of mobile phone users to show that mobility in Germany has not only been reduced considerably: Lockdown measures caused substantial and long-lasting structural changes in the mobility network. We find that long-distance travel was reduced disproportionately strongly. The trimming of long-range network connectivity leads to a more local, clustered network and a moderation of the "small-world" effect. We demonstrate that these structural changes have a considerable effect on epidemic spreading processes by "flattening" the epidemic curve and delaying the spread to geographically distant regions.


Subject(s)
COVID-19/prevention & control , Pandemics , Quarantine , Spatial Analysis , Travel/statistics & numerical data , Cell Phone , Germany , Humans
6.
Stroke ; 52(1): 31-39, 2021 01.
Article in English | MEDLINE | ID: covidwho-939945

ABSTRACT

BACKGROUND AND PURPOSE: Acute ischemic stroke and large vessel occlusion can be concurrent with the coronavirus disease 2019 (COVID-19) infection. Outcomes after mechanical thrombectomy (MT) for large vessel occlusion in patients with COVID-19 are substantially unknown. Our aim was to study early outcomes after MT in patients with COVID-19. METHODS: Multicenter, European, cohort study involving 34 stroke centers in France, Italy, Spain, and Belgium. Data were collected between March 1, 2020 and May 5, 2020. Consecutive laboratory-confirmed COVID-19 cases with large vessel occlusion, who were treated with MT, were included. Primary investigated outcome: 30-day mortality. SECONDARY OUTCOMES: early neurological improvement (National Institutes of Health Stroke Scale improvement ≥8 points or 24 hours National Institutes of Health Stroke Scale 0-1), successful reperfusion (modified Thrombolysis in Cerebral Infarction grade ≥2b), and symptomatic intracranial hemorrhage. RESULTS: We evaluated 93 patients with COVID-19 with large vessel occlusion who underwent MT (median age, 71 years [interquartile range, 59-79]; 63 men [67.7%]). Median pretreatment National Institutes of Health Stroke Scale and Alberta Stroke Program Early CT Score were 17 (interquartile range, 11-21) and 8 (interquartile range, 7-9), respectively. Anterior circulation acute ischemic stroke represented 93.5% of cases. The rate modified Thrombolysis in Cerebral Infarction 2b to 3 was 79.6% (74 patients [95% CI, 71.3-87.8]). Thirty-day mortality was 29% (27 patients [95% CI, 20-39.4]). Early neurological improvement was 19.5% (17 patients [95% CI, 11.8-29.5]), and symptomatic intracranial hemorrhage was 5.4% (5 patients [95% CI, 1.7-12.1]). Patients who died at 30 days exhibited significantly lower lymphocyte count, higher levels of aspartate, and LDH (lactate dehydrogenase). After adjustment for age, initial National Institutes of Health Stroke Scale, Alberta Stroke Program Early CT Score, and successful reperfusion, these biological markers remained associated with increased odds of 30-day mortality (adjusted odds ratio of 2.70 [95% CI, 1.21-5.98] per SD-log decrease in lymphocyte count, 2.66 [95% CI, 1.22-5.77] per SD-log increase in aspartate, and 4.30 [95% CI, 1.43-12.91] per SD-log increase in LDH). CONCLUSIONS: The 29% rate of 30-day mortality after MT among patients with COVID-19 is not negligible. Abnormalities of lymphocyte count, LDH and aspartate may depict a patient's profiles with poorer outcomes after MT. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT04406090.


Subject(s)
COVID-19/complications , Endovascular Procedures , Ischemic Stroke/complications , Ischemic Stroke/surgery , Thrombectomy , Aged , Aged, 80 and over , COVID-19/epidemiology , Cohort Studies , Endovascular Procedures/mortality , Europe , Female , Humans , Ischemic Stroke/mortality , Male , Middle Aged , Registries , Risk Factors , SARS-CoV-2 , Thrombectomy/mortality , Treatment Outcome
7.
Stroke ; 51(11): 3366-3370, 2020 11.
Article in English | MEDLINE | ID: covidwho-722391

ABSTRACT

BACKGROUND AND PURPOSE: Reports are emerging regarding the association of acute ischemic strokes with large vessel occlusion and coronavirus disease 2019 (COVID-19). While a higher severity of these patients could be expected from the addition of both respiratory and neurological injury, COVID-19 patients with strokes can present with mild or none respiratory symptoms. We aimed to compare anterior circulation large vessel occlusion strokes severity between patients with and without COVID-19. METHODS: We performed a comparative cohort study between patients with COVID-19 who had anterior circulation large vessel occlusion and early brain imaging within 3 hours from onset, in our institution during the 6 first weeks of the COVID-19 outbreak and a control group admitted during the same calendar period in 2019. RESULTS: Twelve COVID-19 patients with anterior circulation large vessel occlusion and early brain imaging were included during the study period and compared with 34 control patients with anterior circulation large vessel occlusion and early brain imaging in 2019. Patients in the COVID-19 group were younger (P=0.032) and had a history of diabetes mellitus more frequently (P=0.039). Patients did not significantly differ on initial National Institutes of Health Stroke Scale nor time from onset to imaging (P=0.18 and P=0.6, respectively). Patients with COVID-19 had more severe strokes than patients without COVID-19, with a significantly lower clot burden score (median: 6.5 versus 8, P=0.016), higher rate of multivessel occlusion (50% versus 8.8%, P=0.005), lower DWI-ASPECTS (Diffusion-Weighted Imaging-Alberta Stroke Program Early CT Scores; median: 5 versus 8, P=0.006), and higher infarct core volume (median: 58 versus 6 mL, P=0.004). Successful recanalization rate was similar in both groups (P=0.767). In-hospital mortality was higher in the COVID-19 patients' group (41.7% versus 11.8%, P=0.025). CONCLUSIONS: Early brain imaging showed higher severity large vessel occlusion strokes in patients with COVID-19. Given the massive number of infected patients, concerns should be raised about the coming neurovascular impact of the pandemic worldwide.


Subject(s)
Coronavirus Infections/complications , Pneumonia, Viral/complications , Stroke/diagnostic imaging , Aged , Aged, 80 and over , Betacoronavirus , COVID-19 , Case-Control Studies , Cerebral Angiography , Computed Tomography Angiography , Diffusion Magnetic Resonance Imaging , Female , Hospital Mortality , Humans , Infarction, Anterior Cerebral Artery/complications , Infarction, Anterior Cerebral Artery/diagnostic imaging , Infarction, Anterior Cerebral Artery/physiopathology , Infarction, Anterior Cerebral Artery/therapy , Infarction, Middle Cerebral Artery/complications , Infarction, Middle Cerebral Artery/diagnostic imaging , Infarction, Middle Cerebral Artery/physiopathology , Infarction, Middle Cerebral Artery/therapy , Infarction, Posterior Cerebral Artery/complications , Infarction, Posterior Cerebral Artery/diagnostic imaging , Infarction, Posterior Cerebral Artery/physiopathology , Infarction, Posterior Cerebral Artery/therapy , Magnetic Resonance Angiography , Male , Middle Aged , Pandemics , SARS-CoV-2 , Severity of Illness Index , Stroke/complications , Stroke/physiopathology , Stroke/therapy , Thrombectomy , Thrombolytic Therapy
8.
Stroke ; 51(8): 2540-2543, 2020 08.
Article in English | MEDLINE | ID: covidwho-418810

ABSTRACT

BACKGROUND AND PURPOSE: Higher rates of strokes have been observed in patients with coronavirus disease 2019 (COVID-19), but data regarding the outcomes of COVID-19 patients suffering from acute ischemic stroke due to large vessel occlusion (LVO) are lacking. We report our initial experience in the treatment of acute ischemic stroke with LVO in patients with COVID-19. METHODS: All consecutive patients with COVID-19 with acute ischemic stroke due to LVO treated in our institution during the 6 first weeks of the COVID-19 outbreak were included. Baseline clinical and radiological findings, treatment, and short-term outcomes are reported. RESULTS: We identified 10 patients with confirmed COVID-19 treated for an acute ischemic stroke due to LVO. Eight were men, with a median age of 59.5 years. Seven had none or mild symptoms of COVID-19 at stroke onset. Median time from COVID-19 symptoms to stroke onset was 6 days. All patients had brain imaging within 3 hours from symptoms onset. Five patients had multi-territory LVO. Five received intravenous alteplase. All patients had mechanical thrombectomy. Nine patients achieved successful recanalization (mTICI2B-3), none experienced early neurological improvement, 4 had early cerebral reocclusion, and a total of 6 patients (60%) died in the hospital. CONCLUSIONS: Best medical care including early intravenous thrombolysis, and successful and prompt recanalization achieved with mechanical thrombectomy, resulted in poor outcomes in patients with COVID-19. Although our results require further confirmation, a different pharmacological approach (antiplatelet or other) should be investigated to take in account inflammatory and coagulation disorders associated with COVID-19.


Subject(s)
Arterial Occlusive Diseases/complications , Brain Ischemia/etiology , Brain Ischemia/therapy , Coronavirus Infections/complications , Pneumonia, Viral/complications , Stroke/etiology , Stroke/therapy , Aged , Arterial Occlusive Diseases/diagnostic imaging , Blood Coagulation Disorders/etiology , Brain/diagnostic imaging , Brain Ischemia/diagnostic imaging , COVID-19 , Cerebral Arteries , Cerebral Veins , Female , Hospital Mortality , Humans , Male , Middle Aged , Pandemics , Plasminogen Activators/therapeutic use , Stroke/diagnostic imaging , Thrombectomy , Thrombolytic Therapy , Time-to-Treatment , Tissue Plasminogen Activator/therapeutic use , Treatment Outcome
9.
Science ; 368(6492): 742-746, 2020 05 15.
Article in English | MEDLINE | ID: covidwho-46625

ABSTRACT

The recent outbreak of coronavirus disease 2019 (COVID-19) in mainland China was characterized by a distinctive subexponential increase of confirmed cases during the early phase of the epidemic, contrasting with an initial exponential growth expected for an unconstrained outbreak. We show that this effect can be explained as a direct consequence of containment policies that effectively deplete the susceptible population. To this end, we introduce a parsimonious model that captures both quarantine of symptomatic infected individuals, as well as population-wide isolation practices in response to containment policies or behavioral changes, and show that the model captures the observed growth behavior accurately. The insights provided here may aid the careful implementation of containment strategies for ongoing secondary outbreaks of COVID-19 or similar future outbreaks of other emergent infectious diseases.


Subject(s)
Betacoronavirus , Coronavirus Infections/epidemiology , Coronavirus Infections/prevention & control , Disease Outbreaks/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/epidemiology , Pneumonia, Viral/prevention & control , Basic Reproduction Number , Behavior , COVID-19 , China/epidemiology , Communicable Disease Control , Contact Tracing , Coronavirus Infections/transmission , Disease Susceptibility , Humans , Models, Statistical , Pneumonia, Viral/transmission , Quarantine , SARS-CoV-2
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