The rapid expansion of the novel SARS-CoV-2 virus has raised serious public health concerns due to the possibility of misdiagnosis in regions where arboviral diseases are endemic. We performed the first study in northern Peru to describe the detection of SARS-CoV-2 IgM antibodies in febrile patients with a suspected diagnosis of dengue and chikungunya fever.A consecutive cross-sectional study was performed in febrile patients attending primary healthcare centers from April 2020 through March 2021. Patients enrolled underwent serum sample collection for the molecular and serological detection of DENV and CHIKV. Also, serological detection of IgM antibodies against SARS-CoV-2 was performed.464 patients were included during the study period, of which (40.51%) were positive for one pathogen, meanwhile (6.90%) presented co-infections between 2 or more pathogens. The majority of patients with monoinfections were positive for SARS-CoV-2 IgM with (73.40%), followed by DENV 18.09% and CHIKV (8.51%). The most frequent co-infection was DENV + SARS-CoV-2 with (65.63%), followed by DENV + CHIKV and DENV + CHIKV + SARS-CoV-2, both with (12.50%). The presence of polyarthralgias in hands  and feet  were more frequently reported in patients with CHIKV monoinfection. Also, conjunctivitis was more common in patients positive for SARS-CoV-2 IgM . The rest of the symptoms were similar among all the study groups.SARS-CoV-2 IgM antibodies were frequently detected in acute sera from febrile patients with a clinical suspicion of arboviral disease. The presence of polyarthralgias in hands and feet may be suggestive of CHIKV infection. These results reaffirm the need to consider SARS-CoV-2 infection as a main differential diagnosis of acute febrile illness in arboviruses endemic areas, as well as to consider co-infections between these pathogens. In December 2019, several cases of pneumonia of unknown etiology emerged in Wuhan, China. The causative agent was identified as SARS-CoV-2 (Severe acute respiratory syndrome Coronavirus 2) .The rapid expansion of the novel COVID-19 disease has raised serious public health concerns due to the possibility of misdiagnosis and overlapping diseases in regions where arboviral diseases are endemic , given tSeveral reasons have made it difficult to distinguish between COVID-19 and arboviral diseases, as both can be included in the differential diagnosis of undifferentiated acute febrile illness (AFI) . FirstlyFew studies have evaluated the impact of the COVID-19 pandemic and arboviral diseases in countries like Brazil and Singapore ,9. HowevThe study was carried out in the province of Jaen located in the department of Cajamarca, Peru. This region is located in northern Peru, sharing boundaries to the north with Ecuador. The province of Jaen has approximately 185 432 inhabitants, with 52% living in urban areas and 48% in rural areas, according to the last national census. This area is endemic for many pathogens responsible for AFI including arboviruses such as dengue virus, chikungunya virus, zika virus and bacterial pathogens such as leptospirosis, rickettsiosis and bartonellosis . On the Across-sectional study was performed in patients attending primary healthcare centers in Jaen from April 2020 through March 2021. The study design and research methods are summed up and represented in a flowchart, as shown in This study was approved by the ethics and investigation committee of the Regional Hospital of Cajamarca, Peru. The samples were obtained to answer the questions of the present study in the context of the epidemiological / syndromic surveillance program according to the health guidelines of the National Center for Epidemiology, Disease Control and Prevention of the Ministry of Health of Peru. The signing of an informed consent was not required since the study was carried out in a state of emergency by public health mandate in the context of epidemiological surveillance of SARS-CoV-2 and arboviruses.Patients enrolled underwent serum sample collection for the molecular and serological detection of DENV and CHIKV. Also, serological detection of IgM antibodies against SARS-CoV-2 was performed, given that nasopharyngeal swabs were not available for molecular identification of this virus. One serum sample was obtained for each patient and collected by using Vacuette TUBE Serum Separator Clot Activator . After collection, all the samples were stored at -80°C. All samples were transported to Lima (Peru) under standardized frozen conditions to perform the assays.RNA extraction of the samples was performed to carry out molecular detection by RT-PCR for DENV and CHIKV. A total of 200 μL of the serum samples was used for RNA extraction with the High Pure RNA Isolation Kit , according to the manufacturer’s instructions. Viral RNA obtained after extraction was eluted in 100 μl of nuclease-free water and then processed or stored at -20°C until use.Amplification by RT-PCR assay for the detection of CHIKV and DENV were carried out using the primers described by Leparc-Goffart et al. , and theThe presence of DENV NS1 antigen was detected by Euroimmun ELISA . DENV IgM antibodies were also detected using Euroimmun ELISA .The presence of CHIKV IgM antibodies were also detected using Euroimmun ELISA .The presence of SARS-CoV-2 IgM antibodies were also detected using Immunodiagnostic; ImmunoDiagnostics Limited Hong Kong Science Park, Sha Tin, Hong Kong. Recombinant nucleocapsid protein (NP) of SARS-CoV-2 is specifically recognized by anti-NP antibodies with a sensitivity and specificity of 88.2% and 92% respectively .In all serological tests, each serum sample was run in duplicate, in accordance with the manufacturer’s instructions.Cases were defined according to the Peruvian national guidelines for the epidemiological surveillance and diagnosis of arbovirosis . PatientAll data were recorded in a database in the Microsoft Excel program. The analysis were performed using the IBM Statistical Package for the Social Sciences (SPSS) version 21.0 software . Categorical variables were reported as frequencies and percentages. Differences between clinical symptoms and pathogens were evaluated using the Chi-square test. A value of p <0.05 was considered statistically significant. All graphs were made using the GraphPad Prism 9.0.0 program .A total of 464 patients with AFI were enrolled. The results of the most frequent pathogens in monoinfections are shown in The monthly distribution of infections by a single and co-infections is shown in We enrolled 464 febrile patients in an endemic region of Peru for DENV and CHIKV, in the context of the COVID-19 pandemic. This is the first Peruvian study evaluating the presence of SARS-CoV-2 IgM antibodies in febrile patients from an endemic region of dengue and chikungunya. Despite several advances in diagnostic techniques, the diagnosis of AFI is still challenging in resource-limited countries such as Peru and the etiology cannot always be achieved in these settings . Over thFor the detection of DENV and CHIKV, we used molecular and serological techniques according to the case definition. Meanwhile, for the detection of SARS-CoV-2 only serological tests were used. Molecular identification of SARS-CoV-2 could not be carried out by RT-PCR since the patients included were classified as dengue or chikungunya by the treating physicians and under this criterion, nasopharyngeal swab was not obtained.We identified that a high proportion of patients were positive for IgM antibodies against SARS-CoV-2. These were more frequent than the DENV and CHIKV cases. This finding is consistent with the results of other studies indicating that in arbovirus endemic regions, SARS-CoV-2 infection should always be considered as an important differential diagnosis in febrile patients. For example, Stringari et al. reported that covert cases of SARS-CoV-2 by identification of IgG antibodies were detected in 2.85% of the total patients in an endemic region for DENV and CHIKV . AnotherAn evaluation of the most frequent symptoms according to the pathogens identified, we could highlight that the most common symptoms among all groups were headaches (82.9%), myalgias 67.03%) and malaise 62.50%). Our results indicate that polyarthralgia in hands and feet were significantly more common in patients with CHIKV and cojunctivitis in patients with positive serology for SARS-CoV-2. These findings could be considered to distinguish between different pathogens. No significant differences in the other symptoms were observed among the different pathogens, which is in agreement with previous studies that report that differentiation between arboviruses is difficult by clinical picture alone , 20. Mor0%. Our r7.03% andRegarding the severity of the disease, it has been described that arbovirus and SARS-CoV-2 coinfections do not present with more severe symptoms compared to monoinfections. Therefore, patients have a favorable clinical course during the duration of the disease , 25. NorWhen evaluating the seasonal pattern of each pathogen, we could observe that the majority of AFI cases occurred during the last months of 2020; however, concurrent outbreaks were not identified. It was observed that most cases of CHIKV were identified during July, 2020; on the other hand, DENV cases occurred during November, 2020 and January, 2021. The identification of SARS-CoV-2 cases was constant through the 2020 year, with a peak in December. It has been reported that dual outbreaks between SARS-CoV-2 and DENV have occurred in other regions, with cases of both pathogens coinciding in a specific time lapse , similarWe used accurate diagnostic tests for the identification of the pathogens studied and performed and evaluation of their performance according to the day since disease onset. In the case of diagnostic methods for DENV we could observe that NS1 detection and RT-PCR performed better during the initial days of disease, which may be correlated to the early viremia observed in this disease . On the There are four major types of serological diagnostic tests . In the The most important limitation of this study is that molecular detection of SARS-CoV-2 could not be performed, and diagnosis was based on serological assays. The possibility of cross-reaction in serological tests for Dengue and SARS-CoV-2 has also been described by Lustig et al. ;however,In conclusion we found a large prevalence of SARS-CoV-2 IgM antibodies in acute sera from febrile patients with a clinical suspicion of arboviral disease. Co-infection between DENV and SARS-CoV-2 were also frequent. Symptoms among the different study groups were similar, however, the presence of polyarthralgias in hands and feet may be suggestive of CHIKV infection. These results reaffirm the need to consider SARS-CoV-2 infection as a main differential diagnosis of acute febrile illness in arboviruses endemic areas, as well as to consider co-infections between these pathogens Accurate and timely diagnostic assays, in combination with suggestive clinical symptoms are required to correctly distinguish these pathogens.


M = 21.7 years) reported on their personality traits including their facets with the BFI-2, COVID-19-related stressors, and their perceived stress during the last month (using the PSS). Findings indicated that neuroticism was associated with higher perceived stress regardless of the COVID-19-related stressors experienced. Facet level analysis revealed differences for anxiety, depression, and volatility. Importantly, trait extraversion was unassociated with stress experiences, whereas specifically the facet of sociability was associated with higher perceived stress. Also, the facets of assertiveness and energy both moderated the relationship between COVID-19-related stressors and perceived stress. In line with the transactional theory of stress, our findings indicate that perceptions of stress were best understood by looking at the interaction of environmental stressors and personality differences. Furthermore, the study substantiates that facets of personality traits offer unique information beyond broad traits in specific contexts.Although long postulated, it has been scarcely researched how personality traits play out differently in distinct situations. We examined if Neuroticism and Extraversion, personality traits known to moderate stress processes, function differently in highly stressful situations requiring reduced social contact, that is, the COVID-19 pandemic. Based on past findings, we expected neuroticism to be associated with exacerbated perceptions of stress. In contrast to past findings, we expected extraversion, which usually ameliorates stress, to be associated with intensified perceptions of stress, especially in regard to the sociability facet. During the third wave of the COVID-19 pandemic in Germany, one-hundred-thirty adults (age  During stressful events and severe crises, most people turn to others for support, connection, and belongingness  Individuals high in neuroticism will perceive greater stress and experience more negative outcomes when COVID-19 stressors are high than those low in neuroticism.(H2) Individuals high in extraversion will perceive greater stress and experience more negative outcomes when COVID-19 stressors are high than those low in extraversion.(H3) Individuals high in sociability will perceive greater stress and experience more negative outcomes when COVID-19 stressors are high than those high in assertiveness and/or in energy.1In the current study, we sought to understand how the experience of COVID-19-related stressors interacted with personality to predict stress appraisals during the third wave of the COVID-19 pandemic in Germany in a sample of young adults. We preregistered the following hypotheses:M = 21.73, SD = 3.57; 22% men) who agreed to participate in an online survey in exchange for either a gift card raffle or partial course credit. Inclusion criteria included being at least 18 years of age as well as speaking German. Exclusion criteria included incorrectly answering at least two of three attention check questions and taking less than two minutes to complete the survey. Twenty-three additional participants completed at least part of the survey but were not included in these analyses: four were excluded for failing at least two of these three attention checks, nine were excluded for spending less than two minutes on the survey, and ten were excluded for not providing responses to the variables of interest in this study. Sample size was determined by an a priori power analysis for linear multiple regression specifying a power of .80 to detect a small (f2 = .15) effect at alpha < .05 with 11 predictors using G*Power .disagree strongly to agree strongly (coded as 1 to 5). Participants received a mean score for each trait and facet.Personality was assessed using the German version of the Big Five Inventory-2  to 3 (severe change) scale. We added four similarly-worded items to assess change related to concern for others, interactions with colleagues, workload, and important life events. A mean score was created for each participant.COVID-19-related stressors were assessed with the first 8-items of the Coronavirus Impact Scale , and averaged to create the scale mean.Participants were asked to indicate how stressful they perceived the last month of the pandemic to be using the 10-item German translation of the Perceived Stress Scale  COVID-19-related stressors, (2) personality trait(s) or facet(s), and (3) the interaction between the variables specified in steps one and two. In this way we were able to examine the additional variance in stressors appraisals explained by personality. We analyzed each trait separately. The three facets of each trait were modeled together. Results of the hypotheses-based analyses for Extraversion and Neuroticism are reported in the main text; results of exploratory analyses for the other three traits are reported in the supplementary materials.p < .001, R2 = .24).Descriptive statistics are presented in Table At the trait level, higher neuroticism was associated with greater perceived stress regardless of the COVID-19-related stressors experienced  stress perceptions. In considering these findings, it should be noted that the facets were analyzed simultaneously, thus people’s standing on the other facets is controlled in these analyses.For anxiety, individuals high in this facet do not appear to show additional reactivity to COVID-19-related stressors. One possibility is that these individuals expect the world to be an anxious, tense place, and thus the COVID-19 pandemic conditions align with their pre-existing expectations (Spielberger & Reheiser, Regarding volatility, this facet directly assesses individual’s tendency to be reactive to negative and stressful circumstances, thus it follows that these individuals would be more reactive to high levels of COVID-19 related stressors. Limited past research indicates that the facets of neuroticism may function differently in some stressful situations (e.g., workplace harassment; McCord, Although extraversion has previously been viewed as an asset for ameliorating the stress process (Leger et al., We had hypothesized that the sociability facet would be more likely to exacerbate the stress process than assertiveness or energy. Individuals high in this facet tend to be outgoing and enjoy interacting with others, which has become more difficult in the context of COVID-19 pandemic contact restrictions and physical distancing guidelines (Götz et al., On the other hand, the assertiveness facet of extraversion was associated with lower stress perceptions, and buffered stress perceptions when COVID-19-related stressors were high. Individuals high in assertiveness behave more dominantly and prefer to take charge of situations. These attributes could assist them in adopting active coping techniques that allow them to better navigate the COVID-19 pandemic (Agbaria & Mokh, The third extraversion facet, energy, did not have a main effect on perceptions of stress, but moderated perceptions depending on the level of COVID-19-related stressors experienced (cf. Schmiedeberg & Thönnissen, The COVID-19 pandemic has been a uniquely stressful situation across the globe (Kowal et al., Future research could consider how these findings manifest for more distal outcomes of the stress process, for example, life-satisfaction and mental health (Orsolini et al., In conclusion, our findings complement and extend the current research on the role of personality for the stress process during the COVID-19 pandemic. Most importantly, by adopting a facet level approach, we were able to offer insight into the functioning of neuroticism and clarify the mixed findings regarding extraversion during the COVID-19 pandemic. In particular, we demonstrated that some facets of personality function in counter-typical fashion during the pandemic: sociability no longer buffered, but enhanced stress perceptions whereas anxiety no longer augmented, but ameliorated them. One implication of this pattern is that those who are typically most at risk for negative clinical outcomes may not be those who suffer most from the pandemic. Furthermore, the findings indicate the potential for negative mental, not just physical, health outcomes as a result of the COVID-19 pandemic and measures to reduce its impact.Our findings support the importance of simultaneously considering environmental and personal differences for understanding the stress process (Caspi & Moffitt,


The primary goal of this manuscript is to develop a computer assisted diagnostic (CAD) system to assess pulmonary function and risk of mortality in patients with coronavirus disease 2019 (COVID-19). The CAD system processes chest X-ray data and provides accurate, objective imaging markers to assist in the determination of patients with a higher risk of death and thus are more likely to require mechanical ventilation and/or more intensive clinical care.To obtain an accurate stochastic model that has the ability to detect the severity of lung infection, we develop a second-order Markov-Gibbs random field (MGRF) invariant under rigid transformation (translation or rotation of the image) as well as scale . The parameters of the MGRF model are learned automatically, given a training set of X-ray images with affected lung regions labeled. An X-ray input to the system undergoes pre-processing to correct for non-uniformity of illumination and to delimit the boundary of the lung, using either a fully-automated segmentation routine or manual delineation provided by the radiologist, prior to the diagnosis. The steps of the proposed methodology are: (i) estimate the Gibbs energy at several different radii to describe the inhomogeneity in lung infection; (ii) compute the cumulative distribution function (CDF) as a new representation to describe the local inhomogeneity in the infected region of lung; and (iii) input the CDFs to a new neural network-based fusion system to determine whether the severity of lung infection is low or high. This approach is tested on 200 clinical X-rays from 200 COVID-19 positive patients, 100 of whom died and 100 who recovered using multiple training/testing processes including leave-one-subject-out (LOSO), tenfold, fourfold, and twofold cross-validation tests. The Gibbs energy for lung pathology was estimated at three concentric rings of increasing radii. The accuracy and Dice similarity coefficient (DSC) of the system steadily improved as the radius increased. The overall CAD system combined the estimated Gibbs energy information from all radii and achieved a sensitivity, specificity, accuracy, and DSC of 100%, 97% ± 3%, 98% ± 2%, and 98% ± 2%, respectively, by twofold cross validation. Alternative classification algorithms, including support vector machine, random forest, naive Bayes classifier, K-nearest neighbors, and decision trees all produced inferior results compared to the proposed neural network used in this CAD system. The experiments demonstrate the feasibility of the proposed system as a novel tool to objectively assess disease severity and predict mortality in COVID-19 patients. The proposed tool can assist physicians to determine which patients might require more intensive clinical care, such a mechanical respiratory support. Coronaviridae is a family of nonsegmented, enveloped, positive-sense, single-stranded ribonucleic acid viruses. Six species of coronavirus had previously been identified as pathogenic in humans: four of these cause mild respiratory illnesses, whereas the other two species, severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), have led to epidemics with significant rates of mortality5.Coronavirus disease 2019 (COVID-19) was initially detected in Wuhan, China and is caused by a novel RNA virus belonging to the Coronaviridae family. It is believed to have been transmitted to humans from bats via an intermediate mammalian host before achieving human to human transmission. Such zoonotic origin is consistent with similar coronavirus outbreaks8. The disease may be classified as (i) mild type: moderate clinical symptoms with normal chest X-ray; (ii) typical type: fever, respiratory, and other clinical findings indicating signs of pneumonia; (iii) severe type: respiratory distress signs , fatigue (45%), muscle aches (45%), difficulty breathing (55%), and acute respiratory distress syndrome (ARDS) (20%). Severe cases may progress to multiorgan dysfunction and even death (2.5%)15. The current reference standard for this purpose is real-time reverse transcription polymerase chain reaction (PCR) of viral RNA. The PCR test, according to current guidelines, is run on samples from nasopharyngeal and/or throat swabs. While PCR is the gold standard in diagnosing patients with COVID-19 infection, the sensitivity of a single PCR is suboptimal and depends on the timing of the test, sampling sites and sampling techniques12.Due to the wide variations in clinical presentation and progression rate for COVID-19, laboratory confirmation of SARS-CoV-2 infection is essential to initiate appropriate early treatment and to prevent further spread of the disease17.Chest radiography is helpful for first-line evaluation of patients with a high pre-test probability of overt COVID-19 pneumonia, clinical follow up, and for the evaluation of potential complications. Chest radiography can detect areas of ground glass density, also observed on chest computed tomography (CT), which may often have a correlation with the severity of the disease, and may be intermixed with reticular patternBased on the recent clinical research, COVID-19 radiological forms are variable in severity using plain radiography or CT, ranging from a normal chest , to patchy involvement of one or both lungs in mild or moderate cases, to diffuse infiltration (white lung) in severe cases. This is an important issue as mild or moderate cases can be managed by medical treatment or non-invasive ventilation, while severe cases with bilateral lung infection urgently need mechanical ventilation to support respiration as patients develop ARDS. Given the paucity of mechanical ventilation units, patient selection for ventilation plays a crucial role in saving lives. We propose a methodology that utilizes the current state of machine learning and artificial intelligence (AI) to assist physicians by providing an objective metric that can differentiate severe cases from mild/moderate cases and potentially even predict mortality.25.There are few preliminary studies and case reports discussing the role of AI on plain radiography and CT for early diagnosis of patients with COVID-19. AI can be used in conjunction with radiologists to improve the results of detection of COVID-19. AI can be a powerful aid in delineating and quantifying lesions in X-ray images and in tracking longitudinal changes between exams, which is crucial for precision medicine. In essence, AI is another means of analyzing data that clinicians can draw on to inform their judgment in issues of triage, diagnosis , prognosis, and selection between therapeutic alternatives in patients exhibiting COVID-19 symptoms. Plain radiography involves a low radiation dose compared to CT and is better suited for routine monitoring and follow up compared to a CT scan. AI may be capable of detecting subtle changes visible on either chest X-ray or CT in the lung, and can improve efficiency by decreasing the amount of time to return test results. This is necessary for screening the general population during the current COVID-19 pandemic and in the epicenters of any future outbreaks. Computer assisted detection alleviates the burden on radiologists and clinicians and facilitates rapid triage. Also, AI can be used for the differentiation of previous lung injury unrelated to COVID-19 from advanced lung dysfunction due to COVID-19, and assist in patient selection for ventilation26 developed an approach using deep transfer learning to detect signs of COVID-19-related pneumonia in chest X-ray images. Hassanien et al.27 developed an automatic segmentation method for lung areas affected by COVID-19 that employed an Otsu-derived algorithm for multi-level thresholding of X-ray images and a support vector machine for the prediction task. Apostolopoulos et al.28 studied the efficacy of deep learning convolutional neural networks (CNN) for deriving characteristic COVID-19 biomarkers from chest X-rays. Wang et al.29 presented a novel CNN, named COVID-Net, tailored to the detection of COVID-19-related changes in chest X-rays. The deep learning network of Hammoudi et al.30, on the other hand, was designed to automatically detect if a chest X-ray image indicates healthy lungs or evidence of pneumonia . Combined with prior information regarding the likelihood the patient has been exposed to the virus, an automatic diagnosis of viral pneumonia has a high true positive rate for detection of COVID-19.CAD systems for assessing lung function in COVID-19 are limited in the literature. Sun et al.Currently, the primary challenge is to apply different AI-based approaches to determine the severity of chest infection in COVID-19 patients given that X-ray images vary enormously in image quality due to the wide range of X-ray machines in use across the world. To overcome this challenge, we develop a new CAD system that operates on extracted X-ray image markers that are invariant under rotation, scaling, and translation.31, data from COVID-19 open research dataset challenge (CORD-19)32, and data from the University of Louisville, USA and Mansoura University, Egypt. The research protocol was approved by the institutional review board (IRB) at the University of Louisville and Mansoura university as well as all methods were performed in accordance with the relevant guidelines and regulations and the patients informed consent was obtained. For the patients who passed away, an informed consent was obtained from legal guardian/Next of kin for the dead patients. These databases include 200 subjects tested as COVID-19 positive, 100 from patients who eventually died from the infection and 100 patients who ultimately recovered. These databases comprise a heterogeneous collection of digital X-ray images, which was the primary motivation to develop rotation, scale, and translation invariant MGRF model from which we extract the proposed imaging markers to grade the severity of lung infection in COVID-19 patients. We did our experiments using the merged datasets from all three databases to overcome the issue of data balance as the number of subjects for the two classes, (high and low severity cases), in each database was different. The dead cases had been confirmed based on the following radiology protocol33: (i) Bilateral and predominantly peripheral opacifications and/or consolidations were rated as typical for a COVID-19 infection. (ii) A distribution pattern with opacifications and/or consolidations limited to one pulmonary lobe consistent with lobar pneumonia was rated as non-typical for a COVID-19 infection. All changes that could not be classified as non-typical or typical were rated as indeterminate. In a subgroup of these patients with indeterminate findings, soft criteria for a possible COVID-19 infection were defined as the unilateral presence of predominantly peripheral.The proposed approach is tested and validated on data from a publicly available archive of COVID-19 positive casesThe proposed CAD system to detect the severity of lung infection is shown in Fig. 34. Proper analysis of the type of noise present in the chest X-ray image may help to select proper denoising methods, which preserve the important texture information while reducing the noise36. The RDHE approach divides the image into blocks x rows high by y columns wide. Then, dynamic histogram equalization is applied within each block to adaptively enhance the contrast. Therefore, the image histogram is remapped by block, and pixel values are adjusted relative to the other pixels in their To improve the accuracy of the proposed approach, we manually segmented the lung region from the original X-ray image, Fig. entclass1pt{minima37 that considers both the spatial interaction between nearby image pixels and the intensity distribution of those pixels within the lung region of interest. We follow the conventional description of the MGRF model in terms of independent signals (images) and interdependent region labels (segmentations); yet we focus on more accurate model identification37. Each image segment corresponds to a single dominant mode of the empirical distribution (i.e. histogram) of gray levels. To identify the dominant modes, each image histogram is considered to be sampled from a linear combination of discrete Gaussians (LCDG) distribution37. We fit an initial LCDG model to the empirical distribution using a modified expectation-maximization (EM) algorithm37. Free parameters of the LCDG to be optimized are the number of discrete Gaussian components and their respective weights (positive and negative), shape, and scale parameters. Then, the initial LCDG-based segmentation is iteratively refined using the MGRF model with its analytically estimated potentials37. Figure 37.The third preprocessing step is to identify and mask off the healthy lung tissues from the infected tissues. This step narrows the search space to focus only on the abnormal tissues and serves to increase the diagnostic accuracy of the CAD system. To achieve this step, we use our previously published methodologyx, y) comprises all pixels Q is the range of pixel gray levels, e.g. We constructed the proposed MGRF model in order that the image need not be aligned with any particular frame of reference in order to use it to grade the severity of lung infection (low vs. high). To construct the appearance of the infected lung regions, we consider the X-ray images as samples from a piecewise stationary MGRF with a central-symmetric system of pixel-pixel interactions. Let S, For a given image/label map pair Finally let The joint probability of object pixels in image S: S are statistically independent , the expression for joint probability of object pixels may be likewise simplified38:Assuming lungs having the same pathology exhibit similar morphology in X-ray images, then we may approximate the previous expressions by their averages over the training set Here, mentclass2pt{minim38 suggests using The Bayesian quadratic loss estimate suggests using the offset 38, the Gibbs potential functions are approximated using the centered, training-set average, normalized histograms and co-occurrence matrices:Using the same analytical approach as in Ref.Using the above estimated potentials, we can calculate the Gibbs energy of the infected lung region Here, Read all infected regions from the training data having class “severe” lung infection.Calculate the co-occurrence of the image signal at various radii ; the number of neurons per hidden layer is 50, 20, and 2 for NN 1, NN 2, and Fusion NN, respectively (searching from 1 to 200); and finally, the sigmoid activation function has been selected after also considering the tangent and softmax activation functions.To highlight the innovation in our approach, we demonstrate the Gibbs energy calculated at three radii as a color map fused over the X-ray images. One example for which it holds, it is clear from Fig. To highlight the contribution of each Gibbs energy at each radius, we construct an NN-based classifier using the estimated Gibbs energy at each radius. As is clear from Table entclass1pt{minima42. Post hoc comparison of our proposed NN-based classifier with the alternatives was done using Wilcoxon signed rank tests with Bonferroni correction to the estimated Statistical significance of the choice of feature set or classifier architecture on diagnostic performance was assessed using Friedman rank sum testsmentclass2pt{minim9. ARDS occurred in 20% of hospitalized patients and 61% of ICU patients in Zhongnan Hospital in Wuhan4. ARDS occurs when capillaries in the lung leak fluid into the alveoli, thereby impairing gas exchange in the lung and reducing oxygen uptake into the systemic arterial circulation. The consequent decrease in blood oxygen levels can be directly life-threatening, leading to multi-organ failure. Respiratory support of COVID-19 may use invasive or non-invasive methods to force oxygen into the airways under pressure. Invasive ventilation uses an endotracheal tube to feed oxygen directly into the lungs. Non-invasive methods employ such devices as continuous positive airway pressure (CPAP) and oxygen hoods; there is no use of an internal tube, and they are used in the management of less severe cases.ARDS is the most common and severe pulmonary complication in COVID-19 patients. It is an acute hypoxemic respiratory failure that requires oxygen and ventilation therapy including intubation and invasive ventilation. Clinically patients may have dyspnea, tachypnea . Even non-invasive ventilation carries some risk, as stress and strain associated with high tidal volumes may cause patient self-induced lung injury (P-SILI). The additional inflammation due to VILI or P-SILI may lead to aggravation of pulmonary edema and worsening of the very respiratory distress that ventilation was intended to treat. There is also the risk of heart failure, hypervolemia, and multi organ dysfunction, alone or in combination53. AI can increase the utility of chest X-ray imaging beyond first-line diagnostic imaging and into the areas of risk stratification, monitoring of clinical course, and selection between management approaches, such as invasive vs. non-invasive ventilation, for COVID-19 patients. Multimodal data, be they clinical, epidemiological, or potentially molecular data, can by fused with imaging data in an AI framework to build systems to detect and treat COVID-19 patients and potentially to contain its spread54. Moreover, we plan to work on X-ray scans/data that are collected at different time points to evaluate the progressing of the infection/pneumonia with the treatment course.Accurate and rapid diagnosis of COVID-19 pneumonia severity is very challenging for radiologists as the disease has rapidly spread across the globe. Based on the results demonstrated in this study, AI systems, especially those based on deep learning, are promising tools to assist initial screening by radiologists. It could decrease workload, improve diagnostic accuracy, and enable appropriate treatments and ventilation management of COVID-19 patients. In the case of a pandemic as we now face, medical resources are seriously strained and must be used as efficiently as possible. Rapid diagnosis and accurate prognosis are essential. The AI-based method shows great potential to quantify disease severity and could be used to inform treatment decision-making in patients with COVID-19. AI in concert with thoracic imaging and other clinical information  can effectively improve clinical outcomesIn conclusion, the results herein demonstrate the feasibility of using AI with chest X-ray imaging data to determine the severity of lung involvement in cases of COVID-19. Severity of pneumonia on chest X-ray correlated highly with mortality in this study, and thus this CAD system can potentially also be used to predict mortality in COVD-19 patients.


We report on a 72-year-old female patient who was sent to our clinic for evaluation of a biventricular intracardiac defibrillator (BIV-ICD). The patient was diagnosed with ischemic cardiomyopathy and showed a persistently low ejection fraction in the range of 20%–25% with New York Heart Association class III heart failure symptoms despite being on guideline-directed medical therapy, including a β-blocker and a combination of sacubitril and valsartan, for >3 months. In addition, the patient had underlying right bundle branch block (RBBB) with a QRS duration of 160 ms. The device was programmed with a Sync-AV algorithm on with nominal settings (delta of −50 ms). The thresholds and lead impedances were acceptable. Electrocardiography was performed in the postoperative period, showing persistent RBBB similar to the baseline electrocardiogram without much QRS narrowing. In this report, we discuss the mechanism and troubleshooting of this problem. In view of her persistent cardiomyopathy and QRSd of >150 ms, it was decided to implant a BIV-ICD. The left ventricular (LV) lead was implanted in the mid-lateral branch. The device was programmed with a Sync-AV algorithm  on with nominal settings (delta of −50 ms). The thresholds and lead impedances were acceptable. An electrocardiogram (ECG) was performed in the postoperative period, which showed persistent RBBB  similar to the baseline electrocardiogram (ECG) without much QRS narrowing. The device interrogation was repeated, and all the lead parameters were stable with acceptable thresholds. What is the reason for persistent wide QRS and lack of desired QRS narrowing in this patient with baseline RBBB?A 72-year-old woman was sent to our clinic for the evaluation of biventricular-intracardiac defibrillator (BIV-ICD). The patient was diagnosed with ischemic cardiomyopathy and was having persistently low ejection fraction in the range of 20%–25% with New York Heart Association class III heart failure symptoms despite being on guidelines-directed medical therapy, including a β-blocker and sacubitril–valsartan combination, for >3 months. In addition, the patient had underlying right bundle branch block (RBBB) with a QRS duration (QRSd) of 160 ms 1 However, not all patients respond to this therapy, and such patients are labeled as non-responders. Almost one-third of patients with advanced heart failure who undergo CRT implantation are non-responders.2 Furthermore, response to CRT is a continuum rather than a binary outcome.3 Hence, there is a lot of interest in the optimization of CRT post-implant in non-responders as well as maximizing outcomes in those who are considered responders. Further, multiple studies have shown that paced ECG QRSd can be used as a surrogate for the effectiveness of resynchronization therapy as well as patient outcomes.4 A variety of post-implant issues besides patient selection may contribute to suboptimal responses. The most common reasons are non-left bundle branch block (LBBB), suboptimal lead location, and a narrower QRS complex. Post-implant device optimization predominantly focuses on the modification of atrioventricular (AV) and interventricular timing delays either manually or with the use of proprietary algorithms. The aim of optimizing these delays is to obtain a narrower paced QRS complex as a metric of electrical resynchronization. One of the proprietary algorithms for optimizing the AV delays (AVDs) is the Sync-AV algorithm (Abbott) that dynamically adjusts AVD to synchronize ventricular pacing with each beat’s intrinsic AV conduction.Cardiac resynchronization therapy (CRT) is an established evidence-based therapy in patients with systolic heart failure and wide QRS.Briefly, Sync-AV functions as follows. Every 256 beats, the algorithm automatically extends the paced and sensed AVD for 3 beats, during which it measures the intrinsic AV interval. With the default Sync-AV offset, 50 ms is subtracted from the measured intrinsic AV interval, and the result is applied as the paced AV interval for the following 255 beats . The cycle repeats every 256 beats, thus permitting dynamic adjustment of the paced AV interval. The offset value may be reprogrammed across a wide range of offsets (10–120 ms).5 examined the effect of Sync-AV on paced QRSd in 73 patients and showed that, in already well-selected patients with LBBB and optimized LV lead position, patient-tailored BIV pacing adjusted to intrinsic AV timing using Sync-AV resulted in the narrowest QRSd. Further studies showed an improvement in acute hemodynamic measures and reverse remodeling on echocardiography.7 Also, Sync-AV fusion pacing provided the greatest improvement in electrical synchrony compared to conventional CRT and multipoint pacing as well as having a synergistic effect when superimposed on the latter.8 However, these studies were almost exclusively performed in patients with LBBB. Hence, current recommendations for using the Sync-AV algorithm include patients with (1) intact AV conduction PR, (2) PR <300 ms; (c) LBBB, (d) minimal ventricular ectopy, and (e) low atrial tachycardia/atrial fibrillation burden. It is intuitive to think that similar programming cannot lead to optimal electrical synchrony in both RBBB and LBBB patients as the activation patterns are different.The initial study of Sync-AV1 In patients who receive CRT devices, post-implant optimization is routinely performed with an aim to achieve a narrower QRSd. One post-implant optimization analysis showed that suboptimal programming of AV timings was found to be contributory in as high as 47% of patients with a poor response to CRT.9 Early trials showed significant changes in acute hemodynamics (LVdp/dt max) with different AVDs, and AVD optimization using echo parameters showed a small benefit in clinical outcome.11 However, larger prospective studies did not replicate these results.12 This was thought to be due to the dynamic nature of the intrinsic AV intervals, dependent on heart rate, autonomic tone, and other factors, where “best” AVDs may vary significantly over time. This led to a search for automated algorithms to assess intrinsic AV times, and thus several proprietary algorithms for programming AVDs were developed. Several CRT studies demonstrated a link between acute QRS narrowing and long-term clinical response.13 Consequently, many studies have been done to optimize device programming post-implant by modification of the AVDs aimed at achieving a narrower QRSd.Although the American College of Cardiology/Heart Rhythm Society/European Society of Cardiology recommend CRT in patients with a QRSd of >150 ms, there is a paucity of data on the utility of CRT in patients with RBBB. Despite recommendations of CRT in patients with a QRSd of >150 ms, there are no clear-cut guidelines regarding the utility of CRT in patients with RBBB.. The patient was discharged home in a stable condition.In our case, Sync-AV fusion pacing stimulation resulted in a wider QRS than CRT with a nominal fixed AVD. After confirming that the thresholds were stable, the Sync-AV algorithm was turned off and manual optimization was performed with an AVD of 130–150 ms with an LV offset of 0 ms. This programming resulted in significant narrowing of QRS and disappearance of RBBB Figure 4. As demonstrated in the figure, it would take a large Sync-AV delta and a short LV offset timing to achieve proper fusion pacing in patients with RBBB. Also, in the St. Jude devices, the sensing is performed by a right ventricular (RV) lead only. Thus, it is also possible that, with a longer AVD, the impulse reached the RV at the same time as the RV pacing artifact was delivered (pseudo-fusion). This could also lead to the functional loss of captures from the LV lead and, thus, no change in the QRS was noted post-implant with Sync-AV on.The mechanism behind this phenomenon may be the inability to achieve triple wave-front fusion in RBBB with Sync-AV on. Using programming parameters originally tested for patients with LBBB may lead to pseudo-fusion between biventricular pacing and intrinsic beat in RBBB or pseudo-fusion with little contribution from the pacing stimulation. This has been depicted in 14 the performance of Sync-AV was evaluated with multiple LV pacing sites in a broader cohort of 99 patients of RBBB, and nonspecific intraventricular conduction delay was observed in 5% and 32% of patients, respectively. The authors reported that the reduction in QRSd was not significantly influenced by the presence or absence of LBBB. In another study,15 8 consecutive patients with RBBB at a single tertiary care center, who were implanted with a CRT device capable of biventricular fusion pacing using Sync-AV programming, were assessed and compared to a historical cohort of CRT patients without RBBB. With programming optimization, they could demonstrate that the reduction in QRSd with optimized Sync-AV observed in those with RBBB approached the level of that seen in patients with LBBB. In those with LBBB, the optimal Sync-AV offset was 30–50 ms in around 66%–80% of patients, and the majority of the remaining patients had an optimal offset of <30 ms. In contrast, it was found that in patients with RBBB, the optimal offset was around 90 ms in the vast majority of patients. This finding is key in considering the optimal negative AV hysteresis offset required to achieve fusion; given that the AVD is measured by the device using the RV lead, the presence of RBBB results in the delayed detection of ventricular activation (relative to surface ECG) and the need to program a more negative AV offset to achieve fusion. These considerations are similar to those depicted in Figure 3. However, the degree to which fusion can be achieved with fixed AVD adjustment in RBBB patients without a dynamic fusion pacing algorithm was not evaluated in this study. In our case a fixed nominal AVD led to better electrical synchrony with a narrower QRS on the ECG . One of the limitations of this case is that, although the QRSd decreased with manual optimization, its long-term effects on patient outcomes are unknown.Studies evaluating the utility of Sync-AV fusion pacing in patients with RBBB are sparse. In 1 study,This case highlights that Sync-AV fusion pacing may not be ideal for patients with RBBB in achieving electrical synchrony. Larger comparative studies are needed to address the nuances of CRT programming and device-based optimization in patients with RBBB and other non-LBBB intraventricular conduction delays.


The use of coronavirus disease 2019 RNA vaccines in pregnant women led to reports on the first cases of newborns with antibodies to sudden acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a phenomenon that was unknown when using immunizations with inactivated viruses. Thus, this study aimed to report a case of passive anti-SARS-CoV-2 immunity in a newborn through immunoprophylaxis of a pregnant woman who received the CoronaVac® vaccine in the third trimester of pregnancy. Twenty-four hours after delivery, samples were collected from the newborn and screened by enzyme immunoassays, which revealed antibodies to SARS-CoV-2. Pregnancy alters various functions of the human body, leaving women more vulnerable to infectious diseases, including SARS-CoV-2 and its vertical transmission to the fetus; the latter has not yet been ruled out,SARS-CoV-2 infections present a very heterogeneous clinical scenario that may depend on the viral load and vulnerability of an infected person. Symptoms may include cough, runny nose, fever, sore throat, and dyspnea that can vary from asymptomatic to severe respiratory failureThere are limited data regarding the safety of vaccines against COVID-19 during pregnancy. Clinical trials on their efficacy and safety did not include pregnant women; therefore, the decision to vaccinate pregnant women against COVID-19 is based on a risk-benefit ratio. In Brazil, pregnant healthcare professionals working on the frontline of the COVID-19 outbreak were immunized with CoronaVac® because this vaccine uses a known and safe technology for pregnancy as long as its use is recommended by a woman’s obstetricianThis study aimed to report a case of passive transmission of anti-SARS-CoV-2 antibodies through immunoprophylaxis in pregnant women during the third trimester of pregnancy.T.M.I, a 33-year-old physician, was multiparous. On February 23, 2021, at 34 weeks of gestation, she received the first 0.5 mL dose of the CoronaVac® vaccine  containing 600 SU of the inactivated virus antigen to SARS-CoV-2. A second dose of equal volume and composition was administered on March 15, 2021, when she was at 37 weeks of gestation. No complications were detected during prenatal care. She attended 10 antenatal consultations without any symptoms of SARS-CoV-2 infection. There was a weight gain of 14 kg, and she ended the pregnancy at a weight of 110 kg and height of 166 cm.The delivery took place at 39 weeks of gestation by cesarean section on April 9, 2021. The newborn was male, weighed 3.44 kg, was 48 cm long, and had a head circumference of 33 cm. He was breastfed, and a comprehensive physical assessment revealed that he was healthy. The Apgar scores at 1 and 5 minutes were 9 and 10, respectively.Blood specimens were collected by peripheral venipuncture 24 h after birth to detect neutralizing antibodies against SARS-CoV-2/COVID-19. The serological test, carried out by enzymatic immunoassay , showed a result of 22%, which was considered positive based on the cutoff value of 20%. The cPass™ SARS-CoV-2 Neutralization Antibody Detection Kit is a blocking enzyme-linked immunosorbent assay (ELISA) intended for the qualitative direct detection of total neutralizing antibodies to SARS-CoV-2 in human serum and K2-EDTA plasma as a detection tool. Using purified receptor binding domain, protein from the viral spike (S) protein, and the host cell receptor ACE2, this test is designed to mimic the virus-host interaction by a direct protein-protein interaction in a test tube or a well of an ELISA plate. This highly specific interaction can then be neutralized in the same manner as in a conventional virus neutralization test. This study was approved by the Research Ethics Committee of the University of Southern Santa Catarina (opinion no. 4.728.687) on May 24, 2021. Informed consent was obtained from the mother of the child prior to the data collection. The inactivated SARS-CoV-2 vaccine with aluminum hydroxide developed by Sinovac Life Sciences Co. Ltd., known as CoronaVac®, has been shown to be safe and effective for inducing neutralizing specific antibodiesThe Butantan Institute (Brazil) conducted a study of 9,823 participants who received two doses of CoronaVac between July and December 2020. The primary efficacy rate was 50.7%  against symptomatic COVID-19, while the secondary efficacy was 83.7%  against moderate cases requiring assistance and 100%  against severe cases,In this case report, the CoronaVac vaccine was administered to a pregnant woman and assumed to be safe according to the literature because inactivated vaccines consist of dead antigens and are safe for this specific group without any major adverse effects or damage to the fetus. Studies have revealed that the vaccination of pregnant women against influenza, hepatitis A, and tetanus, for example, is common practice,Studies comparing the behavior of COVID-19 between pregnant and non-pregnant women have been conducted to enhance antenatal care and find safe alternatives to immunization during pregnancy. These studies showed that pregnant women who acquired SARS-CoV-2 and developed infectious symptoms were at great risk of hospital admission; the development of severe conditions requiring intensive care unit admission; progression to respiratory failure requiring invasive ventilation ; and, consequently, a high mortality risk. From an obstetric point of view, high rates of preterm births and the prevalence of operative deliveries have been observed as well,,In this case report, passive immunity may have occurred via the transplacental route measured by total antibodies after exposure to inactivated antigens of the vaccine administered in the third gestational trimester. Immunoglobulin G transfer from the mother to the fetus begins at the end of the first trimester of gestation and increases throughout pregnancy, ranging from 10% of maternal concentration in weeks 17-22 to 50% in weeks 28-32. The concentration continues to increase in the third trimester, allowing fetal antibody concentrations to exceed maternal levels by 20-30%Therefore, immunization during pregnancy can increase maternal immune protection and provoke the production and transfer of antibodies across the placenta to provide early infant protection. Recent studies have shown that this strategy is a safe and efficient means for protecting mothers and infants from vaccine-preventable infectionsVaccination during pregnancy is a strategy to improve the health of mothers, fetuses, and newborns. Understanding the characteristics of antibody transfer is crucial to the development of a vaccine to help protect newbornsIn this case report, passive immunity to the fetus was observed through maternal vaccination. The mother was exposed to inactive virus, a technology used in the CoronaVac® immunizer. The two doses administered at 31 and 34 weeks of gestation provided an increase in the mother’s total antibodies and, consequently, provided immunity to the fetus as assessed by the total antibody response.To the best of our knowledge, this is the first case of newborn immunization after vaccination of the mother during the third trimester of pregnancy with the CoronaVac® vaccine. The monitoring of this and similar cases is essential to estimating the duration of circulating antibodies in the child and the role of breastfeeding in maintaining immunity against SARS-CoV-2.


We found that 99.5% of the HCWs who received the two doses of the BNT162b2 vaccine developed protective antibodies that were maintained at detectable levels for as long as 250 days after the second dose of the vaccine. Multivariate analysis was performed on anti-S-RBD titers in a subgroup of participants (n = 173) that were evaluated twice during this period. The results of this analysis reveal that the antibody titer observed at the second time point was significantly related to the magnitude of the primary response, the time that had elapsed between the first and the second evaluation, and a previous history of SARS-CoV-2 infection. Of importance is the finding that despite waning antibody titers following vaccination, none of the study participants contracted severe COVID-19 during the observational period.The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has had a tremendous impact on health services; hundreds of thousands of healthcare workers (HCWs) have died from coronavirus disease 2019 (COVID-19). The introduction of the BNT162b2 mRNA vaccine in Italy provided recipients with significant protection against COVID-19 within one to two weeks after the administration of the second of the two recommended doses. While the vaccine induces a robust T cell response, the protective role of factors and pathways other than those related to memory B cell responses to specific SARS-CoV-2 antigens remains unclear. This retrospective study aimed to evaluate the determinants of serological protection in a group of vaccinated HCWs ( Health services are recognized as critical components in the overall response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. According to the World Health Organization (WHO), between 80,000 and 180,000 healthcare workers (HCWs) died after developing coronavirus disease 2019 (COVID-19) between January 2020 and May 2021 [®) [On 21 December 2020, four COVID-19 vaccines were authorized for use in Italy by the Italian Medicines Agency (AIFA). Among the first of this group was the BNT162b2 mRNA vaccine developed by BioNTech SE and Pfizer, Inc., New York & Mainz, Germany (tradename Comirnaty®) . The BNT®) . The rec®) . Several®) ,8.Full protection against SARS-CoV-2 infection can be achieved within one to two weeks after the administration of the second of the two 30 μg doses of BNT162b2. Results from several reports revealed that a detectable level of protection might also develop in subjects who received a single dose of the vaccine ,10,11. TWhile both convalescent and vaccinated subjects show evidence of immunological memory in the form of specific B and T cell responses, clear laboratory correlates for protective immunity have not yet been defined . To dateThe strong immunological response initially elicited by vaccination appears to wane over time in association with diminished circulating antibody titers and reductions in the number of memory T and B cells. However, it is not yet clear whether the vaccine-mediated protection against infection, severe disease, and death also wanes over time in association with diminished titers of anti-S IgG and reductions in serum neutralizing capacity. Results from a recent survey revealed that the decrease in vaccine effectiveness against SARS-CoV-2 infections over time could be attributed to waning immunity rather than the development of a viral escape mutant  .At this time, we have only a limited understanding of the duration of vaccine-induced protection against COVID-19. These findings may be crucial for the ongoing assessment of the risk of breakthrough infection among vaccinated HCWs who are routinely exposed to SARS-CoV-2 and for evaluation of the need for vaccine booster doses. Thus, this study aimed to evaluate the determinants of serological protection in a group of immunized HCWs via an exploration of the levels of circulating anti-S-RBD antibodies during a nine-month period following vaccination.We performed a retrospective evaluation of data that are collected routinely at our hospital facility. The study was approved by the Ethics Committee of Polyclinic Rome “Tor Vergata” (184/2021). Our study enrolled 793 HCWs who were actively employed at the Polyclinic “Tor Vergata” and who received the complete vaccination series, including two doses of 0.3 mL of the BNT162b2 mRNA vaccine by 15 March 2021, after providing informed consent.n = 435), were identified as night shift workers (NSWs). Participants who did not work any night shifts (n = 358) were identified as daytime workers (DWs). The number of days that elapsed between completed vaccination and serological evaluation was calculated for each participant.Demographic data and confirmation of SARS-CoV-2 infection (either before or after vaccination) were collected from the Occupational Medicine Service of the University of Tor Vergata. The following data were collected for each study participant: age, sex, job task, night shift status, date of the second vaccine shot, serum level of anti-S-RBD antibodies, date of serological evaluations, and the number of serological evaluations. Participants who worked a 12 h shift on four to seven nights per month, followed by two days off  underwent two serological evaluations during the study period. We recorded the date of the first and second evaluations and calculated the changes in anti-S-RBD antibody titers detected over the intervening time period.A subset of participants (® SPSS® Statistics (version 26), with a level of significance set at p < 0.05.Quantitative data are presented as means ± standard deviations (SDs). Categorical variables are presented as the number (percentage) of study participants. We calculated the mean antibody titer against viral S-RBD in the group of HCWs who completed the full two-dose vaccination cycle. We also calculated the changes in anti-S-RBD titers exhibited by participants who underwent two serological evaluations during the study period. Linear regression analysis was performed to identify any associations linking the observed decrease in antibody titers in this latter group with night shift status, previous natural viral infection, first antibody titer, age, and gender. However, because age and male gender did not contribute to the risk of the primary outcome, our multivariable models were limited to the other aforementioned variables. All analyses were performed using IBMWe enrolled 793 HCWs (mean age 43.9 ± 11.3 years) who worked in various areas of the hospital. Of this cohort, 262 of the participants were physicians (33.0%), 269 were nurses (33.9%), and 262 (33%) were identified as other healthcare professionals. All participants received two doses of the BNT162b2 mRNA vaccine; a total of 25 (3.5%) had been previously diagnosed with COVID-19. Of them, 22 had COVID-19 with mild to moderate symptoms, while 3 had an asymptomatic disease.Circulating anti-spike S-RBD antibodies were detected in 99.75% of the study population . Six hundred and twenty of the participants underwent a single serological evaluation during the study period, while one hundred and seventy-three participants were evaluated twice.The interval between the final vaccination and the serological evaluation ranged from 13 and 253 days (mean 122.9 days). The serological evaluation was performed at >90 days and >150 days after the second dose of the vaccine in 403 (50.8%) and 164 (20.7%) of the participants, respectively. Twenty-five of the study participants had been diagnosed with COVID-19 before vaccination, while thirteen were diagnosed with COVID-19 after completion of the two recommended doses. Interestingly, none of the study participants were diagnosed with COVID-19 during the interval between the two doses.p < 0.001, p < 0.01). Overall, female participants exhibited higher antibody titers than their male counterparts .Our findings document an overall reduction in the mean antibody titer over time , the number of days between the two serology assessments (p < 0.01), night shift status (p < 0.05), and the magnitude of the first set of serological results (p < 0.01). Interestingly, these decreases did not correlate with age or sex. Of note, we excluded the four subjects who contracted COVID-19 between the two serological evaluations because the acute infection may have had a natural booster effect.In the 173 participants who underwent two serological evaluations, the sampling time ranged from 11 to 183 days (mean 92 ± 42). To avoid the possibility of confounding interactions between the study variables, we performed a multiple regression analysis. Our model included the factors identified in the univariate analysis that were significantly associated with diminished antibody titers. The results of the multiple regression analysis reveal that diminished antibody titers observed in the second serological evaluation were significantly associated with the magnitude of the results of the first evaluation, the time that elapsed between the first and the second evaluation, and a previous diagnosis of COVID-19. By contrast, diminished antibody titers were not associated with night shift status .Although they were first introduced twelve months ago, the duration of protection afforded by COVID-19 vaccines as well as the need for and timing of booster doses remains unclear. These concerns continue to be major public health issues largely because a feasible, working correlate of protection against COVID-19 remains to be established. While the BNT162b2 mRNA vaccine clearly elicits strong memory and effector T cell responses , the rolPersistence of protection after vaccination is currently a critical healthcare issue, as is the need to evaluate the efficacy of a booster dose for subjects at high risk of COVID-19 complications and those at high risk of exposure, including HCWs. The results of our study clearly demonstrate detectable levels of anti-S-RBD in nearly all participants; these levels remain in the detectable range for up to nine months after vaccination. We also found that circulating antibody titers wane at rates that were directly related to the magnitude of the first serological response evaluated as well as the time elapsed between repeated serological evaluations. This latter result indicates that the humoral response to SARS-CoV-2 tended to wane over time. Several studies focused on long-term immune responses demonstrated that, after an initial exponential decay, antibody half-lives typically stabilize to ≥10 years. Depending on when this transition occurs, vaccinated subjects with waning neutralizing antibody titers may become susceptible to mild infection while remaining protected against severe disease ,21,22,23In our univariate analysis of these data, night shift work was associated with a reduced rate of decrease in the anti-SARS-CoV-2 antibody titer, and thus a higher level of protection among these HCWs. This finding was somewhat unexpected, given that a high risk of infection has been widely reported among NSWs compared to DWs . HoweverParticipants who were previously diagnosed with COVID-19 showed both stronger immunological responses and diminished loss of protective antibody levels over time compared to control (unaffected) subjects . This finding was identified as independent of all other relevant factors. This finding provides the research community with the opportunity to explore anamnestic responses to previous SARS-CoV-2 exposure among high-risk HCWs and may be particularly important given the high rate of both symptomatic and asymptomatic infections reported among these subjects ,21. Moren = 255) [n = 33), serum antibody levels elicited by the mRNA vaccine were higher among younger participants, although this difference did not achieve statistical significance [Our findings also reveal that antibody production in response to vaccination was significantly influenced by participant age and sex. Compared to the participants who were both younger and female, the older male participants maintained significantly lower levels of antibody titers, albeit with similar rates of waning over time. Interestingly, recent results have revealed that while the duration of the antibody response after natural virus infection was somewhat variable, even in younger participants , there wn = 255) . In anotificance .Our work has several limitations. First, our study mainly used a retrospective approach and had an exploratory nature, and no prospective analysis has been performed to date. Another limitation of this study was the relatively low number of participants who underwent multiple serological evaluations. This presents the possibility of selection bias as this activity might be undertaken more frequently by participants who developed comparatively low antibody titers immediately after vaccination. However, in our dataset, we found that the initial antibody titers measured in participants who underwent multiple evaluations were not significantly lower than the levels reported in those who underwent only one determination. Another limitation was that we did not address the presence and the magnitude of specific memory B and T cell responses. Robust adaptative responses were previously reported following the administration of the COVID-19 mRNA vaccine, although the relationship between these findings and the serological response remains unclear. Moreover, we did not determine the absence or presence of serum neutralizing capacity; thus, we are unable to determine whether serum concentrations of anti-S-RBD antibodies correlate directly with this capacity. We do note that other published studies have documented that serum neutralizing activity correlates directly with circulating titers of anti-spike or anti-RBD IgG . FinallyBy contrast, one strength of our study is that we evaluated the IgG titer in a large sample of HCWs at different times following vaccination. This approach permitted us to perform a quantitative evaluation of both the trend and the main determinants of the diminished antibody response over time.This work contributes to the existing knowledge that focuses on the kinetics of the anti-SARS-CoV-2 antibody decline by providing a long-term evaluation of the anti-S-RBD IgG in vaccinated HCWs. Further studies will be needed to explore the neutralizing potential of all anti-SARS-CoV-2 antibodies and their role in promoting long-term protection from COVID-19 infection in real-life settings, as well as the need for booster doses among fully vaccinated subjects.Our results reveal detectable levels of circulating protective anti-S-RBD antibodies in 99.5% of the participants in our study that persist for up to 250 days after the second dose of the BNT162b2 vaccine. While antibody levels waned over time, we found that the rate of decrease in repeated evaluations was directly related to the source of the response, the time elapsed, and a previous diagnosis of COVID-19. Interestingly, although antibody titers clearly waned over time following vaccination, no cases of severe COVID-19 were diagnosed among the HCWs enrolled in our study. Collectively, these data underscore the importance of achieving high levels of vaccine coverage among HCWs. The need for booster doses, specifically for those at high risk of occupational exposure, should also be carefully addressed.


SARS-CoV-2 is a novel virus currently causing a major pandemic. Recent studies have shown that SARS-CoV-2 has an affinity to ACE2 receptors which are present in the olfactory epithelium as well as the pulmonary and gastrointestinal (GI) systems. It is stipulated that these receptors are responsible for the entry of the virus into cells explaining the respiratory and GI symptoms of this infection. The anosmia related to COVID-19 is likely due to an aberrant immune response to the virus rather than direct damage to the olfactory epithelium. Similarly, achalasia is also believed to result from an aberrant immune response through which there is degeneration of inhibitory neurons in the myenteric plexus. In this case report, we present the first case of achalasia thought to be linked to a SARS-CoV-2 infection in contemporary literature.We hypothesize that SARS-CoV-2 caused an aberrant immune response in our patient, leading him to develop achalasia. We hope to expose clinicians to this potential complication of COVID-19, allowing them to consider it sooner in their differential.The patient’s file was reviewed to extract the relevant information. A second gastroenterologist’s opinion was obtained on the manometry to confirm the diagnosis of type III achalasia.A 61-year-old man with a medical history of myasthenia gravis, chronic obstructive pulmonary disease, hypothyroidism, and chronic renal failure was treated in our establishment for a SARS-CoV-2 pneumonia. He experienced new severe dysphagic symptoms, regurgitations, and lost 10 pounds during his hospitalization. He also developed anosmia and diarrhea. A CT-scan of his neck and thorax showed no extrinsic compression of his esophagus. No neoplasm was found on his gastroscopy. A barium study was then conducted showing a stagnation of contrast in the distal third of his esophagus. No relaxation of the inferior gastroesophageal sphincter was noted. A manometry was then performed and confirmed a type III achalasia. The mean lower esophageal sphincter residual pressure was elevated at 43.7 mmHg. A calculated 69% of wet swallows were premature contractions with a distal latency value less than 4.5 seconds. The mean distal contractile integral was 13613 mmHg. This corroborates the spastic nature of type III achalasia.Considering that our patient developed anosmia and knowing its pathogenesis in the context of COVID-19, an inappropriate immune response to SARS-CoV-2 could have equally taken place in the esophagus. This inflammatory response might have caused the degeneration of the inhibitory neurons in the myenteric plexus responsible for the achalasia. Furthermore, given the fact that our patient had diarrhea, this suggests that the virus has a GI tropism supporting our hypothesis. We therefore believe that achalasia may be a potential complication of COVID-19.High resolution esophageal motility study showing a type III achalasia pattern.None


Survivors in motor vehicle accident (MVA) may have posttraumatic stress disorder (PTSD). Yoga is a complementary approach for PTSD therapy.This randomized controlled trial explored whether yoga intervention has effects on reducing the symptoms of PTSD in women survived in MVA. Participants (n = 94) were recruited and randomized into control group or yoga group. Participants attended 6 45-minuite yoga sessions in 12 weeks. Depression Anxiety Stress Scales (DASS) and Impact of Events Scale-Revised (IES-R) were used to assess psychological distress.Post-intervention IES-R total score of yoga group was significantly lower than that of control group (p = 0.01). At both post-intervention and 3-months post intervention, the DASS-21 total scores of yoga group were both significantly lower than those of control group . Yoga group showed lower anxiety and depression level compared to control group at both post-intervention  and post-follow-up . Yoga group had lower levels of intrusion and avoidance compared to control group after intervention .Results illustrate that yoga intervention may alleviate anxiety and depression and improve the symptoms of PTSD in women with PTSD following MVA. Having the experience of motor vehicle accident (MVA) will trigger the generation of psychosocial impacts and psychological disorders . The psyTo reduce the risk of psychological distress caused by MVA, interventions are performed and proved to be effective. Cognitive behavior therapy which enhances the adaptive psychological, social, and behavioral skills of survivors is effective in the improvement of psychological symptoms after MVA .As a non-pharmacologic strategy, yoga combines the practice of meditation, physical postures, and breathing . RecentlSince yoga is able to ameliorate psychological and physical conditions of PTSD patients, this randomized controlled trial aimed to evaluate the effect of yoga on reducing symptoms of PTSD in women after MVA.This study was approved by the Ethics Committee of Qingdao Mental Health Center. Eligible participants were adult women diagnosed with MVA-related PTSD that happened at least 3 months ago. PTSD was diagnosed by meeting Diagnostic and Statistical Manual of Mental Disorders 4th Edition (DSM-IV) PTSD criterion A1 for a traumatic event. The exclusion criteria were: (1) Having organic mental disorder, symptomatic bipolar disorder, psychotic disorder, or schizophrenia; (2) Having brain surgery history, brain damage, or neurological problems; (3) Having substance abuse or currently suicidal.Figure Participants in yoga group were provided 12-week yoga sessions developed by the research team, 1 session in every 2 weeks. Yoga sessions were held in a specific meeting room and performed under the instruction of a yoga instructor. The style of yoga in this trail was Kripalu. This kind of yoga focuses on compassionate self‐observation, building connections between mind and body on the present moment. The yoga sessions were designed to adapt for all body types and be noncompetitive. The contents of yoga sessions were shown in Table In this trail, psychometric assessments included the Impact of Events Scale-Revised (IES-R) and the Depression, Anxiety and Stress Scale (DASS-21). All the measures were collected at baseline, post-intervention, and 3-month follow-up.IES-R was employed to evaluate PTSD symptoms. This self-report measure consists of 22 items. The score of each item is from 0 to 4 . There are three subscales, avoidance, intrusion, and hyperarousal. The total score is the sum of the three subscales scores, ranges from 0 to 88. Higher IES-R score indicates worse symptom.DASS-21 was employed to assess the severity of psychological distress. This self-report scale has 21 items to evaluate anxiety, depression, and stress. The score of each item is from 0 to 3 and the sum of the scores of items is total score. Higher score shows stronger symptom of anxiety, depression, and stress.In this research, statistical analyses were performed by SPSS version 17.0 software. Data were presented as mean ± standard deviation (SD) or proportion (%). Differences in continuous variables between different groups were compared by ANOVA test. *p < 0.05, **p < 0.01, ***p < 0.001, ns: no significance.Table IES-R total scores of participants in these two groups were shown in Fig. DASS-21 total scores were shown in Fig. The scores of subscales in DASS-21 and IES-R were presented in Table This randomized controlled trail examined a 12-week yoga intervention’s effect on psychological distress in women with PTSD following MVA. The preliminary results demonstrated that both yoga group and control group showed trends for the improvement of psychological distress, while the intervention of yoga promoted the recovery of psychological disorders in women with PTSD following MVA. There were significant reductions in depression, anxiety, and intrusion in yoga group as compared to control group after 12-week intervention and 3-month follow-up. Additionally, the intervention of yoga had no notable influence on stress and hyperarousal in women with PTSD following MVA.PTSD refers to a series of clinical symptoms shown by the patient's psychological and physical excessive stress response after personally experiencing a serious traumatic event that causes or may lead to death or physical injury . With thIn recent years, yoga has been considered as complementary and alternative medicine . Yoga isMeditation and yoga are promising complementary approaches in the treatment of PTSD among adults . A studyIn this trail, participants in yoga group were provided 12-week Kripalu-based yoga sessions. Sessions were held once every 2 weeks. Kripalu-based yoga emphasizes the connections between mind and body. Kripalu yoga is often described as "dynamic meditation", focusing less on the physical details of the yoga postures and more on the emotional and psychological feelings they bring to the person, thus requiring the student to maintain a gentle, compassionate and introspective attitude. This kind of yoga believes that the body has its own wisdom and sends out messages to prompt the individual to practice the yoga postures in a fluid and natural way. Each yoga pose is held for a long period of time in order to uncover or release repressed emotions. Kripalu yoga may have potential as a PTSD therapy in a veteran or military population .In 47 participants of yoga group, only 6 dropped out during 12-week intervention. Thus, most of participants were satisfied with the intervention. Time, mood, and stress might be the major reason for not completing the study. When examined separately for the two groups, the IES-R total scores and DASS-21 total scores both decreased for both groups after 12-week intervention and 3-month follow-up. IES-R total scores in yoga group was significantly lower than in control group postintervention. DASS-21 total scores also had significant differences between groups postintervention and post-follow-up. Thus, the 12-week intervention of yoga enhanced the improvement of psychological distress in women with PTSD following MVA. Decreased scores of IES-R and DASS-21 indicated that clinical improvement in the PTSD symptoms of women also happened in control group. It was possible that the exchanging of daily life experiences and playing board games enhanced the communication between patients and contributed to the improvement of psychological distress. Alternatively, other unmeasured variables may also account for the improvement in control group. When compared with control group, there were significant reduction in anxiety and depression symptoms at post-intervention and follow-up, but not in stress. The intervention of yoga might have no significant effect on alleviating stress caused by PTSD in woman survived from MVA. Results also demonstrated the short-term effects of yoga on intrusion and avoidance symptoms and the long-term effect on intrusion in women with PTSD following MVA. These findings provided preliminary evidence to suggest that yoga may reduce psychological distress and improve PTSD symptoms among women with PTSD following MVA.Several limitations of the research should be noted. First, the limitation of time and funding caused a relatively small sample size. Limited sample size might influence the detection of differences both between and within groups and limit the generalizability of conclusion. Second, we only evaluated the influence of the Kripalu-based yoga intervention on the participants. Since many different styles of yoga exist, different types might have diverse effects on physical and mental health and PTSD symptom reduction. Kripalu-based yoga might not be the most beneficial type. Although Kripalu-based yoga reduced psychological distress and improve PTSD symptoms, which specific aspect of the yoga practice in this trail was most effective was not evaluated. Third, in this trail, we utilized self-report data. Data might be influenced by the expectancy effects of patients and the results were subject to biases that are inevitable with this type of data.In conclusion, the intervention of a 12-week yoga practice may be an effective and feasible strategy to reduce psychological distress in women with PTSD following MVA. The results of this study suggest that alleviating PTSD after a car accident through yoga is very feasible and can be sustained in daily life. PTSD from car accidents remains a noteworthy social problem that requires effective and feasible programs to alleviate PTSD in order to prevent negative health effects. The results of this study support the use of Kripalu yoga to improve the mental health of women with PTSD who have experienced a major car accident.


Since nucleoside-modified mRNA vaccines strongly activate T follicular helper cells, it is important to explore the possible impact of approved SARS-CoV-2 mRNA vaccines on neoplasms affecting this cell type. Herein, we report and discuss unexpected rapid progression of lymphomatous lesions after administration of a BNT162b2 mRNA vaccine booster in a man recently diagnosed with AITL. The remarkable efficiency of nucleoside-modified SARS-CoV-2 mRNA vaccines has been related to their ability to induce a potent stimulation of T follicular helper (TFH) cells, resulting in persistent germinal center B cell responses , 2. ClinA 66-year-old man with no significant medical history except for hypertension, hypercholesterolemia and type 2 diabetes presented on September 1, 2021 with cervical lymphadenopathies that became recently apparent during a flu-like syndrome. The two doses of BNT162b2 mRNA vaccine had been administered, respectively, 5 and 6 months earlier in the left deltoid. Besides moderate asthenia, he did not report any constitutional symptom. Blood examination indicated a mild inflammatory syndrome, without anemia or white blood cell changes; Lymphocytes immunophenotyping was unremarkable. Protein electrophoresis and immunoglobulin levels were normal and Coombs test was negative.A 18F-FDG PET/CT revealed multiple voluminous hypermetabolic lymphadenopathies above and below the diaphragm as well as several extra-nodal hypermetabolic lesions . These fFourteen days after the PET/CT, a booster dose of the BNT162b2 mRNA vaccine was administered in the right deltoid in preparation of the first cycle of chemotherapy. Within a few days following the vaccine booster, the patient reported noticeable swelling of right cervical lymph nodes. In order to get a baseline close to the initiation of the therapy, a second 18F-FDG PET/CT was performed 8 days after the vaccine booster administration, i.e. 22 days after the first one.It demonstrated a clear increase in number, size and metabolic activity of pre-existing lymphadenopathies at the supra- and sub-diaphragmatic level. Furthermore, new hypermetabolic lymphadenopathies and new hypermetabolic sites had developed since the first examination, in several different locations . As compMethylprednisolone administration was initiated immediately after the 2nd PET/CT, followed by a first course of brentuximab vendotin combined with cyclophosphamide, doxorubicin (BV-CHP) according to a recently published protocol . At the Soon after the initiation of the anti-SARS-CoV-2 vaccination campaigns, it appeared that the injection of mRNA vaccines may induce swelling of lymph nodes draining the injection site. Although considered as benign, this vaccine reaction sometimes complicated the interpretation of 18F-FDG PET/CT imaging for suspicion of a neoplastic process affecting lymph nodes . When a Published studies on hypermetabolic lymphadenopathy after SARS-CoV-2 vaccination were recently reviewed and the subject of a meta-analysis , 12. MosConsidering oncologic patients, the most informative study was conducted in a series of 728 patients having received the BNT162b2 mRNA vaccine . PET/CT To the best of our knowledge, this is the first observation suggesting that administration of a SARS-CoV-2 vaccine might induce AITL progression. Several arguments support this possibility. First, the dramatic speed and magnitude of the progression manifested on two 18F-FDG PET-CT performed 22 days apart. Such a rapid evolution would be highly unexpected in the natural course in the disease. Since mRNA vaccination is known to induce enlargement and hypermetabolic activity of draining lymph nodes, it is reasonable to postulate that it was the trigger of the changes observed. Indeed, the increase in size and metabolic activity was higher in axillary lymph nodes draining the site of vaccine injection as compared to their contralateral counterparts. However, pre-existing lymphomatous nodes were also clearly enhanced as compared to the first test. Moreover, new hypermetabolic lesions most likely of lymphomatous nature clearly appeared at distance of the injection site.In fact, the supposed enhancing action of the vaccine on AITL neoplastic cells is fully consistent with previous observations identifying TFH cells within germinal centers as key targets of nucleoside-modified mRNA vaccines both in animals and in man , 2. MaliOur case first raises the question of the COVID-19 prevention strategy to be used in this patient which is currently poorly protected against COVID-19. On the short term, the only option is to recommend strict masking and social distancing, and to offer him anti-SARS-CoV-2 antibody therapy in case of high-risk contact . On the At this time, extrapolation of the findings of this case to other patients with AITL or other peripheral T cell lymphoma involving TFH cells is premature. AITL patients are rare and their mutation profile is heterogeneous. Furthermore, their immune reactions might be affected by their treatment. It is therefore unlikely that existing pharmacovigilance systems will be efficient to identify extremely rare cases like ours. Prospective studies involving systematic PET/CT imaging after SARS-CoV-2 vaccination in AITL patients with specified mutation profiles might eventually be needed. Whatever the result of such studies, it should not affect the overall favorable benefit-risk ratio of these much-needed vaccines.This observation, which has been posted as a pre-print on the SSRN platform , suggestThe patient is the corresponding author of this case report. He hopes that this report will incentivize investigations to clarify the possible impact of anti-SARS-CoV-2 mRNA vaccination on the course of AITL. He remains convinced that mRNA vaccines represent very efficient products with a favorable benefit-risk ratio.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.Ethical approval was not provided for this study on human participants because the retrospective analysis of the PET/CT data has been approved by the Ethics Committee of the Hôpital Erasme (ref. P2017/020). Being one of the authors, the patient consented to the publication. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.The department of nuclear medicine of Hôpital Erasme is financially supported by the Fonds Erasme and the Association Vinçotte Nuclear (Belgium).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. 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