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Coronavirus . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. |
The copyright holder for this preprint this version posted May 11, 2021. ; https://doi.org/10.1101/2021.05.11.21257037 doi: medRxiv preprint |
Since the identification of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as the cause of COVID-19 1 in December 2019 and the beginning of the SARS-CoV-2 pandemic in Germany in March 2020 nearly 490.000 cases in children and adolescents have been reported by the Robert-Koch-Institute (RKI) 2 . In con... |
While multiple studies and registers have provided reliable data on epidemiology, clinical presentation, disease course and treatment options on PIMS [7] [8] [9] to date no comparable data exists for Long-COVID19 in children and adolescents. A cross-sectional study from Italy 10 in 123 children diagnosed with a SARS-Co... |
These numbers are concerning and require attention; however, currently they merely show a temporal connection and not a causal relationship. In order to better understand the epidemiology and clinical manifestations of Long-COVID19 in children and adolescents and differentiate infectionassociated symptoms from pandemic... |
Since May 2020 students grade 8-12 in fourteen secondary schools in Eastern Saxony are enrolled in the SchoolCoviDD19study. Two of these 14 schools are vocational schools. Seroprevalence is assessed via serial SARS-CoV-2 antibody assessment in all participants. During the March/April 2021 study visit all participants w... |
. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) |
The copyright holder for this preprint this version posted May 11, 2021. ; https://doi.org/10.1101/2021.05.11.21257037 doi: medRxiv preprint |
The Survey included besides sociodemographic variables (i.e., age, sex) twelve questions on the occurrence and frequency of relevant neurocognitive, pain and mood symptoms, namely difficulties concentrating, memory loss, listlessness, headache, abdominal pain, myalgia/arthralgia, fatigue, insomnia and mood (sadness, an... |
The questions were taken from the Symptom Checklist-90-R (SCL-90-R) 12 , the Somatic Symptom Scale (SSS-8) 13 and a questionnaire about stress and stress management in children and adolescents (SS KJ 3-8 R) 14 . All questionnaires are validated in adolescents. |
Answers were coded on a categorical scale -"never", "once", "multiple times" for insomnia and all mood questions; "not at all", "a little bit", "quite", "severe" and "very severe" for the remaining questions. |
In addition, a self-generated item was used to assess the overall level of mental distress on a scale from 0 ("not at all") to 10 ("total"). |
We assessed anti-SARS-CoV-2 IgG antibodies in all samples using a commercially available chemiluminescence immunoassay (CLIA) technology for the quantitative determination of anti-S1 and anti-S2 specific IgG antibodies to SARS-CoV-2 (Diasorin LIAISON® SARS-CoV-2 S1/S2 IgG Assay). |
Antibody levels > 15·0 AU/ml were considered positive and levels between 12·0 and 15·0 AU/ml were considered equivocal. |
All samples with a positive or equivocal LIAISON® test result, as well as all samples from participants with a reported personal or household history of a SARS-CoV-2 infection, were re-tested with two additional serological tests. These were a chemiluminescent microparticle immunoassay (CMIA) intended for the qualitati... |
Participants whose positive or equivocal LIAISON® test result could be confirmed by a positive test result in at least one additional serological test were considered seropositive. Participants with a negative LIAISON® test result, but positive results in both additional serological tests were also considered positive. |
. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) |
The copyright holder for this preprint this version posted May 11, 2021. ; https://doi.org/10.1101/2021.05.11.21257037 doi: medRxiv preprint |
Results for continuous variables are presented as medians with interquartile ranges (IQR) and categorical variables as numbers with percentages, unless stated otherwise. |
Fisher's exact test was used to determine categorical variables for the statistical analysis. Thereby, the answers to the items assessing neurocognitive, pain and mood symptoms, were dummy-coded, enabling a comparison of the answer category "none" (coded 0) against the answer categories "a little bit"/ "quite"/ "severe... |
Furthermore, data distributions of the neurocognitive, pain and mood symptoms were tested for normality using the Kolmogorov-Smirnov (K-S) test. Data with distributions significantly different (p< 0·05) from normal were either transformed to ranks to allow parametric statistics or analyzed using non-parametric statisti... |
In order to examine associations between sociodemographic variables (i.e., age, sex) and the neurocognitive and pain symptoms, bivariate correlation analyses were conducted. |
In a second step, partial correlation analyses were conducted between serostatus and the neurocognitive and pain symptoms, adjusting for age and sex. |
Analyses were performed using IBM SPSS 27.0 or Microsoft Excel 2010. All statistical tests were conducted with α < 0.05. |
The SchoolCoviDD19 study was approved by the Ethics Committee of the Technische Universität (TU) Dresden (BO-EK-156042020) and has been assigned clinical trial number DRKS00022455. |
The funder of the study had no role in the study design, data collection, data analysis, data interpretation, or writing of the report and in the decision to submit the paper for publication. |
1560 students with a median age of 15 years participated at the study visit in March/April 2021 and had their serostatus analyzed. Seven already vaccinated students were excluded from the analysis, . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a licen... |
The copyright holder for this preprint this version posted May 11, 2021. ; https://doi.org/10.1101/2021.05.11.21257037 doi: medRxiv preprint 1365 (88%) were seronegative and 188 (12%) were seropositive. Median age, sex and household size did not differ significantly between seropositive and seronegative participants (t... |
Long-COVID19 survey was answered by at least 1504 (96·8%) of the participants. Each symptom, regardless of the expression, was present in at least 35% of the students within the last seven days before the survey, most commonly happiness (98·7%) followed by tenseness (86·4%), listlessness (80·7%) and difficulties concen... |
Fisher's exact test did not reveal any significant differences between seropositive and seronegative students regarding the prevalence of any of the neurocognitive and pain symptoms reported ( figure 1 ). |
To avoid underestimation of seropositive individuals due to our relatively strict definitions of seropositivity, we also analyzed the data if only the LIAISON® test result was taken into consideration for the decision on seropositivity. This resulted in 204 (13%) LIAISON®-seropositive and 1342 (86%)seronegative student... |
Spearman correlation analyses revealed that age was positive correlate with nearly all neurocognitive and pain symptoms, except for insomnia, sad mood and angry mood (table 3) . In addition, females reported a consistently higher prevalence of neurocognitive and pain symptoms compared to men, except for Myalgia Arthral... |
Partial correlation analyses, which were performed to test for age and sex independent effects of the analysed serostatus on rank-transformed neurocognitive and pain symptoms revealed differences only with respect to sadness; with being seronegative was associated with an increased prevalence of sadness (table 4) . |
104 out 188 seropositive students (55%) had previously been tested positive for SARS-CoV-2 and/ or reported a confirmed SARS-CoV-2 positive household member and were therefore considered as known SARS-CoV2 infections. Compared to those with an unknown infection (84/188 (45%)) Fisher's exact test did not reveal any sign... |
The median score of self-reported mental distress was 4 and did not differ between seropositive and seronegative participants. |
. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. |
The copyright holder for this preprint this version posted May 11, 2021. ; https://doi.org/10.1101/2021.05.11.21257037 doi: medRxiv preprint |
The data presented in our study clearly shows a high rate of neurocognitive, pain and mood symptoms in the surveyed group of adolescents, with every item being present in at least one third of the students within the last seven days before responding to the survey. This is consistent with previous studies and surveys o... |
The differentiation between infection-associated and pandemic-associated symptoms is important because the approach to mediate these symptoms will be different. While strict lock-down measures including school closures will prevent SARS-CoV-2 transmissions in this age group and thereby prevent long-term infection relat... |
The equal prevalence of neurocognitive, pain and mood symptoms in seronegative and seropositive adolescents in our study does not negate the existence of Long-COVID19 symptoms in general or in the pediatric population. However, it does suggest that they occur less frequently than previously assumed -at least in childre... |
Furthermore, it confirms the negative effects of lockdown measures on mental health and well-being of children and adolescents 16 . These effects -affecting this whole age group -need to be balanced with the risk of Long-COVID19 in infected individuals. This balancing act will be a difficult task for public health offi... |
While self-reported symptoms cannot be equated with the diagnosis of an illness, a prevalence of at least 35% for each symptom is a concerning screening result that requires further investigation. In addition, validated, reliable tests are needed to evaluate symptom severity in affected individuals. |
The fact that self-reported overall mental distress did not differ significantly between seropositive . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. |
The copyright holder for this preprint this version posted May 11, 2021. ; https://doi.org/10.1101/2021.05.11.21257037 doi: medRxiv preprint and seronegative individuals does not suggest though that infection-associated symptoms are necessarily more severe than pandemic associated symptoms. The interpretation of the ne... |
As a positive takeaway the fact that happiness is by far the most common response in our survey is reassuring und clearly points to the resilience of this age group. |
There are several limitations to our study. The sample size of around 180 infected individuals is not large enough to detect rare symptoms and a screening questionnaire cannot reliably compare the severity of symptoms in affected individuals. Furthermore, our questionnaire concentrated on neurocognitive, general pain a... |
However, our survey covers a variety of symptoms reported in the context of Long-COVID19 and having a control group of age-matched peers who never had a SARS-CoV-2 infection adds valuable information to the Long-COVID19 discussion that is urgently needed. |
In our cohort of adolescents more than one third reported the presence of at least one neurocognitive, pain or mood symptom with tenseness, listlessness and difficulties concentrating being reported most commonly. However, there was no statistical difference comparing the reported symptoms between seropositive students... |
We searched PubMed for articles published between January 1, 2020, and May 1, 2021, using the search terms ("Long-Covid19") AND ("adolescent") AND ("children"). We identified 1 relevant cross . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to ... |
The copyright holder for this preprint this version posted May 11, 2021. ; https://doi.org/10.1101/2021.05.11.21257037 doi: medRxiv preprint sectional study and 1 case series. Persisting symptoms up to 120 days after the SARS-CoV-2 infection were reported in at least 50% of children and adolescents. |
By adding a control group this study documents that there is no significant difference in the prevalence of neurocognitive, pain and mood symptoms in seropositive compared to seronegative adolescents. This suggests that pandemic-and lockdown-associated factors affect the mental health of adolescents more than infection... |
These findings add relevant new data that will help to inform scientists, public health authorities and policy makers in regard to future policy measures in an ongoing pandemic. |
We thank the Federal State of Saxony for supporting this study by a financial grant. |
We thank J. Schneider for her support and excellent organization of the study visit March/ April 2021. |
We thank J. Herrmann and K. Jackisch for their great support in collecting all samples. All corresponding authors had full access to all the data in the study and had final responsibility for the decision to submit for publication. |
. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. |
The copyright holder for this preprint this version posted May 11, 2021. Deidentified individual participant data will be made available, in addition to study protocols, the statistical analysis plan, and the informed consent form. The data will be made available upon publication to researchers who provide a methodolog... |
The copyright holder for this preprint this version posted May 11, 2021. ; https://doi.org/10.1101/2021.05.11.21257037 doi: medRxiv preprint Table 3 ) Spearman-Rho bivariate correlations between age, sex, and the reported neurocognitive, pain and mood symptoms (n = 1553, * significant at level 0·05, ** significant at ... |
·23** ·25** (4) Concentration ·08** ·14** ·35** (5) Memory ·10** ·07** ·24** ·47** (6) Listlessness ·17** ·08** ·36** ·52** ·32** (7) Headache ·10** ·27** ·30** ·30** ·23** ·27** (8) Abdominal Pain ·05* ·21** ·26** ·21** ·20** ·23** ·28** (9) Myalgia Arthralgia -·07* ·05 ·15** ·24** ·21** ·20** ·21** ·26** (10) Fatigue... |
The copyright holder for this preprint this version posted May 11, 2021. ; https://doi.org/10.1101/2021.05.11.21257037 doi: medRxiv preprint . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. . CC-BY-NC-ND 4... |
The copyright holder for this preprint this version posted May 11, 2021. ; https://doi.org/10.1101/2021.05.11.21257037 doi: medRxiv preprint |
Droplet-laden, turbulent sprays are complex multiphase flows where a dispersed liquid phase is transported by a turbulent gaseous one. The distinguished phases mutually interact exchanging mass, momentum and energy in the turbulent regime. These complex flows play an important role in many industrial applications as we... |
A phenomenological description of the overall evolution of a turbulent spray can be found in the review of Jenny et al. [23] . The whole process starts with the jet breakup, or atomization, as a high-velocity liquid flow is injected from a duct into a gaseous atmosphere. During the so-called primary atomization, Kelvin... |
In order to gain an insight into the fundamental physics of turbulent sprays, various theoretical and numerical studies, which complement traditional experimental techniques, have been conducted with a rapid growth of their applications. One of the former attempts to describe the vaporization process of spherical dropl... |
Along with the previously reported models for droplet dynamics in turbulent gaseous flows, various numerical techniques have been proposed and many are currently in use to tackle the simulation of dilute sprays laden with dispersed droplets. The hybrid Eulerian-Lagrangian numerical approaches based on the Reynolds aver... |
Although different numerical studies, in conjunction with theoretical exploitation, have been already conducted, it is still premature to draw a conclusion that a satisfying comprehension of turbulent spray dynamics has been achieved. The capabilities of existing models of reproducing the involved phenomena are not tho... |
The numerical results reported in this paper have been computed employing a MPI-parallel code that has been previously used in other numerical studies and has undergone an extensive validation and testing campaign [44, 38, 14, 12] . The numerical algorithm is based on a hybrid Eulerian-Lagrangian approach and the point... |
The Eulerian fields , , and are the density, velocity, temperature and hydrodynamic pressure of the carrier phase, respectively. In the frame of the low-Mach number asymptotic expansion considered in this paper, the thermodynamic pressure, referred to as 0 , results to be spatially uniform and constant in time, due to ... |
The Lagrangian variables , , , , and are the position, velocity, mass and temperature of the droplets, respectively, whereas the parameter is the specific heat of the liquid phase. The summations are taken over the whole droplet population located within the domain (index ). The delta function, ( − ), accounts for the ... |
As mentioned above, the point-droplet approximation is adopted to describe the dispersed phase: the droplets are treated as rigid evaporating spheres and the liquid properties (e.g. temperature) are assumed to be uniform inside each droplet. Since the focus of this paper is on the spray dynamics restricted to dilute co... |
where the parameter is the density of the liquid phase, , is the heat capacity at constant pressure of the gaseous component of the carrier mixture and the latent heat of vaporization of the liquid phase evaluated at the droplet temperature. The variable is the droplet relaxation time, = 2 2 ∕(9 ), with = 2 ‖ − , ‖ ∕ i... |
ℎ 0 = 2 + 0.552 |
A correction is then applied to 0 and ℎ 0 to account for the effect of Stefan flow Abramzon and Sirignano [1] : |
where , is the specific heat capacity of the pure vapor at constant pressure, is the vapor mass fraction evaluated at the droplet position, whereas , is the vapor mass fraction evaluated at the droplet surface. The latter corresponds to the mass fraction of the vapor, in a fully saturated vapor-gas mixture, evaluated a... |
where , is the vapor molar fraction evaluated at the droplet temperature and 0 the thermodynamic pressure. The parameter is the saturated vapor pressure evaluated at the reference temperature , whereas = ∕ is the specific constant of the vapor. The saturated vapor mass fraction is, then, |
The Eulerian computational domain is a cylinder. The droplet-laden jet-spray is injected through a circular orifice of radius located at the centre of the lower base of the domain and streams out towards the opposite one. The domain extends for 2 × 20 × 70 in the azimuthal, , radial, and axial, , directions and is disc... |
The present paper addresses the numerical simulation of liquid acetone droplets dispersed within a gaseous jet consisting of mixture of air and acetone vapor. The jet streams out from the inflow section into an open environment filled by dry air. The absolute pressure of the environment is 0 = 101300 while the temperat... |
Concerning the reliability of the simulation, additional information and validation benchmarks about the turbulent periodic pipe, single-phase jet simulations as well as evaporation model can be found in [14, 12] . Table 1 Thermodynamic and physical properties of acetone and dry air. |
In this section the outcomes from the present DNS case, = 10, 000, is shown and compared with results at = 6, 000 [14] . The essential difference between the two cases taken into consideration is the bulk Reynolds number of the injected carrier phase, all of the other parameters being the same. From physical point of v... |
In particular, the value of the initial Stokes numbers are 0 ≃ 1.04 and 0 ≃ 0.62 for the = 10, 000 and = 6, 000 cases, respectively. |
A macroscopic overview of the turbulent jets can be given visualizing coherent structures and enstrophy. Several methods have been proposed in order to identify, quantify and visualize the three-dimensional coherent structures in incompressible turbulent flows [22, 11, 24, 51] . We address the visualization of vortical... |
with |
where Ω and are the vorticity tensor and the rate-ofstrain tensor, respectively. By this approach, a vortex is defined as a spatial region where > 0, . . the Euclidean (c) Radial-axial slices of the turbulent sprays at = 10, 000 and = 6, 000. The black points represent a subset of the whole droplet population constitut... |
norm of the vorticity tensor dominates that of the rate of strain [20] . In general, larger values are associated with more intensive vortexes. Figure 2a shows a comparison of the instantaneous vortical structure of the flow for the two Reynolds number cases visualized by the iso-surfaces = 1 contoured by the magnitude... |
Fluid and particle mean velocities are displayed in fig-ure 4. In the panels 4a and 4b for each case is shown the mean gas velocity in the half-left image and the mean droplet velocity in the half-right image. As apparent, the dispersed phase velocity is slightly higher than the corresponding fluid velocity, but no sig... |
In a turbulent spray, as the turbulent core spreads and slowly decays, the dry and irrotational environmental air surrounding the jet is entrained continuously diluting the vapor concentration and permitting the overall vaporization process to advance. Since the inner core fluid does not reach the outer jet dry region,... |
To compute in equation above, (21) , the Eulerian domain is discretized employing an uniform and equispaced Cartesian grid of cubic sampling cells. The edge size of the cells is set to ∕ = 0.2. The variables and ( ) 2 are the mean and the variance of the number of droplets located into each sampling cell, respectively.... |
To determine the leading mechanism driving the preferential segregation of droplets in different spray regions, we consider the droplet Stokes number evaluated at the dissipative time scale. Figure 8b provides the trend of the mean Stokes number , defined as the ratio of the droplet response time, , and the characteris... |
To quantify the importance of the droplet preferential segregation on the evaporation process, we provide a comparison between the conditional mean vapor concentration sampled by the droplets (droplet-conditional), , , and the unconditional Eulerian one, , . The latter is computed by averaging the vapor mass fraction f... |
In the core region the jet presents a nearly uniform vapor mass fraction field that nullifies the oversampling actuated by the droplets. On the other hand, in the mixing layer, the entrainment of bubble of dry air depleted of droplets causes the Eulerian, unconditional statistics to assume lower values than the conditi... |
To better analyze the mixing layer of jet spray, we remind that the inner core and the irrotational outer region are separated by a nearly-sharp fluctuating interface, which is highly convoluted over a wide range of vortical scales [13] . Different approaches can be employed to identify this interface [7, 50, 21, 25] .... |
with the Heaviside function. = 1 denotes a turbulent event at Eulerian position , while = 0 an irrotational one. The conditionally average profile of vorticity magnitude has been proven to weakly depend on the threshold value in the range ℎ ≈ 0.7 0 ∕ , with 0 the mean velocity scale of the wake and the shear layer thic... |
Turbulent fluctuations are responsible for extremely different Lagrangian histories of the evaporating droplets. The joint probability density function (JPDF) of the droplet vaporization lengths and time are reported for both cases in figure 10 . The vaporization length for a single droplet is defined as the axial dist... |
To predict the temporal evolution of the droplet dynamics, the d-square law is often adopted. In this context, a linear behavior for the square diameter of each droplet is expected, |
where, in many practical and experimental application, the constant can only be estimated based on the reference environmental state, e.g. bulk vapor concentration. We provide in Fig. 12 the joint probability density function of the droplet square diameter and flight time, 2 ( , 2 ). As expected, droplets do not follow... |
,0 ), for both Reynolds number cases. These two quantities have been directly extracted from the JPDF, 2 , as: |
Although the two quantities are strictly related, their significance is different. The mean square diameter, eq. (25), pro-(a) (b) Figure 12 : Joint probability density function of droplet square diameter and flight time, 2 ( , 2 ), for for different Reynolds numbers. The mean square droplet diameter conditioned to the... |
Then the two estimated values of appear six times lower than than those estimated at environemental conditions, , for both cases. The large discrepancies between the values of and further confirm the crucial importance of improving bulk spray dispersion models accounting for the complex dynamics arising from the strong... |
A direct numerical simulation has been conducted to investigate the motion and evaporation of inertial droplets in (a) (b) Figure 13 : Mean square droplet diameter conditioned to the flight time (triangle symbol), ⟨ 2 ∕ 2 ,0 ⟩( ∕ 0 ), and the mean droplet flight time conditioned to the square droplet diameter (square s... |
An intense droplet clustering is apparent in both cases. This originates in the mixing layer of the near field and propagates downstream. In the mixing layer, we identify two states separated by the turbulent/non-turbulent interface: the entrained dry air depleted of droplets and saturated gas clouds full of droplets c... |
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