Infectious Diseases

ObjectiveTo evaluate the performance of two available rapid immunological tests for identification of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) antibodies and their subsequent application to a regional screening of health care workers (HCW) in Tuscany (Italy). Designmeasures of accuracy and HCW serological surveillance Setting6 major health facilities in Tuscany, Italy. Participants17,098 HCW of the Tuscany Region. Measures of accuracy were estimated to assess sensitivity in 176 hospitalized Covid-19 clinical subjects at least 14 days after a diagnostic PCR-positive assay result. Specificity was assessed in 295 sera biobanked in the pre-Covid-19 era in winter or summer 2013-14 Main outcome measuresSensitivity and specificity, and 95% confidence intervals, were measured using two serological tests, named T-1 and T-2. Positive and Negative predictive values were estimated at different levels of prevalence. HCW of the health centers were tested using the serological tests, with a follow-up nasopharyngeal PCR-test swab in positive tested cases. ResultsSensitivity was estimated as 99% (95%CI: 95%-100%) and 97% (95% CI: 90%-100%), whereas specificity was the 95% and 92%, for Test T-1 and T-2 respectively. In the historical samples IgM cross-reactions were detected in sera collected during the winter period, probably linked to other human coronaviruses. Out of the 17,098 tested, 3.1% have shown the presence of SARS-CoV-2 IgG antibodies, among them 6.8% were positive at PCR follow-up test on nasopharyngeal swabs. ConclusionBased on the low prevalence estimate observed in this survey, the use of serological test as a stand-alone test is not justified to assess the individual immunity status. Serological tests showed good performance and might be useful in an integrated surveillance, for identification of infected subjects and their contacts as required by the policy of contact tracing, with the aim to reduce the risk of dissemination, especially in health service facilities.

BackgroundQuantitative CT (QCT) analysis is an invaluable diagnostic tool to assess lung injury and predict prognosis of patients affected by COVID-19 pneumonia. PTX3 was recently described as one of the most reliable serological predictors of clinical deterioration and short-term mortality. The present study was designed to evaluate a correlation between serological biomarkers of inflammation and lung injury measured by QCT. MethodsThis retrospective monocentric study analysed a cohort of patients diagnosed with COVID-19 and admitted because of respiratory failure, or significant radiological involvement on chest CT scan. All patients, males and non-pregnant females older than 18 years, underwent chest CT scan and laboratory testing at admission. Exclusion criteria were defined by concurrent acute pathological processes and ongoing specific treatments which could interfere with immune activity. The cohort was stratified based on severity in mild and severe forms. Compromised lung at QCT was then correlated to serological biomarkers representative of SARS-CoV-2. We further developed a multivariable logistic model to predict CT data and clinical deterioration based on a specific molecular signature. Internal cross-validation led to evaluate discrimination, calibration, and clinical utility of the tool that was provided by a score to simplify its application. Findings592 patients were recruited between March 19th and December 1st, 2020. Applying exclusion criteria which consider confounders, the cohort resulted in 366 individuals characterized by 177 mild and 189 severe forms. In our predictive model, blood levels of PTX3, CRP and LDH were found to correlate with QCT values in mild COVID-19 disease. A signature of these three biomarkers had a high predictive accuracy in detecting compromised lungs as assessed by QCT. The score was elaborated and resulted representative of lung CT damage leading to clinical deterioration and oxygen need in mild disease. InterpretationThe LDH, PTX3, CRP blood signature can serve as a strong correlate of compromised lung in COVID-19, possibly integrating cellular damage, systemic inflammation, myeloid and endothelial cell activation. FundingThis work was supported by a philanthropic donation by Dolce & Gabbana fashion house (to A.M., C.G.) and by a grant from Italian Ministry of Health for COVID-19 (to A.M. and C.G.). Research in contextO_ST_ABSEvidence before this studyC_ST_ABSBesides nasopharyngeal swab and serological test, chest CT scan represents one of the most useful tools to confirm COVID-19 diagnosis; moreover, QCT has been demonstrated to foresee oxygen need as well as deterioration of health status. Several clinical and serological parameters have been studied alone or combined in scores to be applied as prognostic tools of SARS-CoV-2 pneumonia; however, no one has yet reached the everyday practice. Recently, our group has investigated the expression and clinical significance of PTX3 in COVID-19 demonstrating the correlation with short-term mortality independently of confounders. The result was confirmed by other studies in different settings increasing evidence of PTX3 as a strong biomarker of severity; noteworthy, a recent report analysed proteomic data with a machine learning approach identifying age with PTX3 or SARS-CoV-2 RNAemia as the best binary signatures associated to 28-days mortality. Added value of this studyThe present study was designed to investigate associations between markers of damage and the CT extension of SARS-CoV-2 pneumonia in order to provide a biological footprint of radiological results in paucisymptomatic patients. QCT data were considered in a binary form identifying a threshold relevant for clinical deterioration, as already proved by literature. Our findings demonstrate a significant correlation with three peripheral blood proteins (PTX3, LDH and CRP) which result representative of COVID-19 severity. The study presents a predictive model of radiological lung involvement which performs with a high level of accuracy (cvAUC of 0{middle dot}794{+/-}0{middle dot}107; CI 95%: 0{middle dot}74-0{middle dot}87) and a simple score was provided to simplify the interpretation of the three biomarkers. Besides additional finding on PTX3 role in SARS-CoV2 pathology, its prognostic value was confirmed by data on clinical deterioration; indeed, paucisymptomatic subjects showed a 11{middle dot}9% deaths. The model offers the possibility to quickly assess patients resulted positive for SARS-CoV-2 and estimate people at risk of deterioration despite normal clinical and blood gases analysis, with potential to identify those who need better clinical monitoring and interventions. Implications of all the available evidencePredicting the extension, severity, and clinical deterioration in COVID-19 patients its pivotal to allocate enough resources in emergency and to avoid health system burden. Despite the urgent clinical need of biomarkers, SARS-CoV-2 pneumonia still lacks something able to provide an easy measure of its severity. Some multiparametric scores have been proposed for severe COVID-19 and rely on deep assessment of patients status (clinical, serological, and radiological data). Our model represents an unprecedented effort to provide a tool which could predict CT pneumonia extension, oxygen requirement and clinical deterioration in mild COVID-19. Based on the measurement of three proteins on peripheral blood, this score could improve early assessment of asymptomatic patients tested positive by SARS-CoV2 specifically in first level hospitals as well in developing countries.

BackgroundThe aim of this study was to investigate the presence of mediastinal lymphadenopathy in hospitalized Covid-19 patients in a tertiary care hospital in the metropolitan city of Lahore, Pakistan from September 2020 till July 2021. MethodsWe retrospectively collected data of Covid-19 patients hospitalized from September 2020 till July 2021. Only those patients who tested PCR positive through a nasopharyngeal swab, were enrolled in the study. Patients whose data were missing were excluded from this study. Our exclusion criteria included patients who tested negative on Covid-19 PCR, patients with comorbidities that may cause enlarged mediastinal lymphadenopathies such as haemophagocytic lymphohistiocytosis, neoplasia, tuberculosis, sarcoidosis or a systemic disease. The extent of lung involvement in Covid-19 patients was quantified by using a 25-point visual quantitative assessment called the Chest Computed Tomography Score. This score was then correlated with the presence of mediastinal lymphadenopathy. FindingsOf the 210 hospitalized patients included in the study, 131 (62.4%) had mediastinal lymphadenopathy. The mean and median Severity Score of Covid-19 patients with mediastinal lymphadenopathy (mean: 17.1, SD:5.7; median: 17, IQR: 13-23) were higher as compared to those without mediastinal lymphadenopathy (mean: 12.3, SD:5.4; median: 12, IQR:9-16) InterpretationOur study documents a high prevalence of mediastinal lymphadenopathy in hospitalized patients with Covid-19 with the severity score being higher in its presence representing a more severe course of disease.

IntroductionAntiandrogens are candidates against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) due to host cell entry inhibition by the suppression of TMPRSS2. Proxalutamide is a nonsteroidal anti-androgen (NSAA) with strong antagonism on androgen receptor (AR) and angiotensin-converting enzyme 2 (ACE2). Efficacy of proxalutamide was previously demonstrated for early COVID-19 outpatients, and also reduction of deaths in hospitalized COVID-19 patients. Whether radiological changes would follow the improvement in clinical outcomes with proxalutamide is not established. The present post-hoc analysis aims to evaluate whether proxalutamide improves lung injury observed through chest computerized tomography (CT) scans. MethodsThis is a post-hoc analysis of the radiological findings of The Proxa-Rescue AndroCoV Trial with all enrolled patients from the three participating institutions of the city of Manaus, Brazil, that had at least two chest CT scans during hospitalization. The quantification of lung parenchyma involvement was performed by blinded radiologists with expertise in analysis of COVID-19 images. A first chest CT scan was performed upon randomization and a second CT scan was performed approximately five days later, whenever feasible. Improvement rate was the first endpoint, and relative and absolute changes between the first and second CT scans were the second endpoints. ResultsOf the 395 patients initially evaluated, 77 and 169 patients from the proxalutamide and placebo arms, respectively, were included (n=246). Baseline characteristics and percentage of lung parenchyma affected in the baseline chest CT scan were similar between groups. In the second chest CT scan, the percentage of lungs affected (Median - IQR) was 35.0% (25.0-57.5%) in the proxalutamide group versus 67.5% (50.0-80.0%) in the placebo group (p < 0.001). The absolute and relative change between the second and first chest CT scans (Median - IQR) were -15.0 percent points (p.p.) (-30.0 - 0.0p.p.) and -25.0% (-50.0 - 0.0%) in the proxalutamide group, respectively, and +15.0p.p. (0.0 - +30.0p.p.) and +32.7% (0.0 - +80.0%) in the placebo group, respectively (p < 0.001 for both absolute and relative changes). The improvement rate, i.e., the percentage of subjects that had improvement from the first to the second CT scan, was 72.3% in the proxalutamide group and 23.1% in the placebo group (p < 0.0001), with an improvement rate ratio (95%CI) of 3.15 (2.32 - 4.28). ConclusionProxalutamide improves lung opacities in hospitalized COVID-19 patients when compared to placebo. (NCT04728802)

1Since its discovery, more than 37 million people have been infected by SARS-CoV-2 with deaths around 1 million worldwide. The prevalence is not known because infected individuals may be asymptomatic. In addition, the use of specific diagnostic tests is not always conclusive, raising doubts about the etiology of the disease. The best diagnostic method and the ideal time of collection remains the subject of study. The gold standard for diagnosing COVID 19 is the RT PCR molecular test, usually using an oropharynx and nasopharynx swab. Its sensitivity is 70% and drops significantly after the second week of symptoms. Serological tests, in turn, have increased sensitivity after 14 days, and can contribute to the diagnosis when SARS-CoV-2 infection is suspected, even with negative RT PCR. Our study showed sensitivity and specificity of 100% of the serological test (ELISA method) for cases of viral pneumonia caused by the new coronavirus, suggesting that this test could assist in the diagnosis of pulmonary interstitial changes that have not yet been etiologically clarified. We found a greater immune response in men, regardless of the severity of symptoms. The greater the severity, the higher the levels of IgA and IgG, mainly found in patients with multilobar impairment and in need for oxygen. We concluded that the serological test collected around 30 days after the onset of symptoms is the best diagnostic tool in the convalescence phase, not only for epidemiological purposes, but also for the etiological clarification of pulmonary changes that have not yet been diagnosed.

Tuberculosis (TB) screening often relies on cross-sectional symptom assessment. To determine the added value of longitudinal symptom monitoring, we conducted a prospective cohort study among 2,282 incarcerated men in Brazil. Every four months, participants were assessed for symptoms and incident TB (Xpert or culture positive). Compared to remaining asymptomatic, developing symptoms was associated with higher TB risk (aRR 2.31; 95% CI 1.55-3.43), strongest among those with prior radiographic abnormalities (aRR 2.49; 95% CI 1.56-3.97), while remaining symptomatic was not associated (aRR 1.27; 95% CI 0.72-2.24). Longitudinal symptom monitoring may enhance TB screening in high-risk settings, particularly in complement with radiography. GENERAL SUMMARYIn an active case-finding program for TB, developing new symptoms was associated with over double the TB risk, while persistent symptoms were not. Monitoring symptom changes longitudinally, especially combined with chest radiography, may improve TB case detection in high-risk settings.

BackgroundSpinal tuberculosis is the most common osteoarticular tuberculosis. Many published isolated reports indicated that many patients with spinal tuberculosis have lung abnormalities. In this study, we aimed to prospectively evaluate the prevalence and spectrum of lung abnormalities. MethodsWe enrolled consecutive newly diagnosed patients with spinal tuberculosis. They were subjected to spinal magnetic resonance imaging and computed tomography (CT) of the chest. They were followed for 6 months. The outcome was assessed by using the modified Rankin scale. ResultsOut of 66 patients, 22 (33.3%) patients had CT thorax abnormalities. The most frequent finding was lung fibrosis (13 patients). Six patients had consolidation. Miliary tuberculosis was demonstrated in one patient. Cavitation, atelectasis, emphysema, and traction bronchiectasis were noted in one patient each. Nine patients had pleural effusion. Pleural thickening and empyema were noted in two patients each. Empyema was noted in 2 patients. Hydropneumothorax was seen in one patient. One patient had endobronchial tuberculosis. Hilar and Mediastinal lymphadenopathy was noted in 6 patients. At inclusion, 59 (89.4%) patients had modified Rankin scale scores[&ge;]3. After 6 months, 58 (87.9%) patients showed improvement and achieved a score <3. In 4 patients, spinal surgery was needed. The remaining three patients disability statuses remained unaltered. CT chest abnormalities were not associated with improvement in disability. ConclusionOne-third of patients with spinal tuberculosis had tuberculous CT thorax abnormalities. The most frequent CT thorax finding was lung fibrosis. CT abnormalities did not affect the outcome.

The clinical course of COVID-19 in patients undergoing chronic immunosuppressive therapy is yet poorly known. We performed a monocentric cross-sectional study describing the clinical course of COVID-19 in a cohort of patients from northern Italy treated with calcineurin-inhibitors for organ transplantation or rheumatic diseases. Data were collected by phone call and clinical chart review between March 27th- 31st 2020. COVID-19 related symptoms, rynopharingeal swab, therapeutic changes and outcome were assessed in 384 consecutive patients (57% males; median age 61 years, IQR 48-69). 331 patients (86%) received solid organ transplantation (kidney n=140, 36%, heart n=100, 26%, lung n=91, 24%) and 53 (14%) had a rheumatic disease. Calcineurin inhibitors were the only immunosuppressant administered in 46 patients (12%). 14 patients developed a "confirmed COVID-19" (swab positivity) and 14 a "clinical COVID-19" (only typical symptoms). Fever (75%) and diarrhoea (50%) were the most common symptoms. Fourteen patients were hospitalized and 11 have already been dismissed. No patient required start/changes of the O2 therapy or developed superinfection. Only one patient, with metastatic lung cancer, died. In conclusion, COVID-19 showed a mild course in our cohort, with low mortality. Calcineurin inhibitor-based immunosuppressive regimens appear safe in this context and should not be discontinued.

Prevalence of SARS-CoV-2 antibodies is an essential indicator to guide measures. Few population-based estimates are available in Germany. We determine seroprevalence allowing comparison between regions, time points, socio-demographic and health-related factors. MuSPAD is a sequential multi-local seroprevalence study. We randomly recruited adults in five counties with differing cumulative SARS-CoV-2 incidence July 2020 -February 2021. Serostatus was determined using Spike S1-specific IgG ELISA. We determined county-wise proportions of seropositivity. We assessed underestimation of infections, county and age specific infection fatality risks, and association of seropositivity with demographic, socioeconomic and health factors. We found seroprevalence of 2.4 % (95%CI: 1.8-3.1%) for Reutlingen in June 2020 (stage 1) which increased to 2.9% (95%CI: 2.1-3.8%) in October (stage 2), Freiburg stage 1 1.5% (95% CI: 1.1-2.1%) vs. 2.5% (95%CI: 1.8-3.4%), Aachen stage 1 2.3% (95% CI: 1.7-3.1%) vs. 5.4% (95%CI: 4.4-6.6%), Osnabruck 1.3% (95% CI: 1.0-1.9%) and Magdeburg in Nov/Dec 2020. 2.4% (95%CI 1.9-3.1%). Number needed to quarantine to prevent one infection was 8.2. The surveillance detection ratio (SDR) between number of infections based on our results and number reported to health authorities ranged from 2.5-4.5. Participants aged 80+ had lower SDR. Infection fatality estimates ranged from 0.2-2.4%. Lower education was associated with higher, smoking with lower seropositivity. Seroprevalence remained low until December 2020 with high underdetection. The second wave from November 2020 to February 2021 resulted in additional 2-5% of the population being infected. Detected age specific differences of SDR should be taken into account in modelling and forecasting COVID-19 morbidity. FundingThe Helmholtz Association, European Unions Horizon 2020 research and innovation programme [grant number 101003480] and intramural funds of the Helmholtz Centre for infection (HZI). HighlightsO_ST_ABSEvidence before this studyC_ST_ABSSeroepidemiological surveys on SARS-CoV-2 are a useful tool to track the transmission during the epidemic. We searched PubMed/the pre-print server medRxiv and included web-based reports from German health organizations using the keywords "seroprevalence", "SARS-CoV-2", "Germany" and similar other English and German terms in the period from January 1st, 2020 until March 2021. We identified 30 published studies in Germany which mostly report low SARS-CoV-2 seroprevalence (<5%). Most of these surveys were so-called hotspot studies which assessed seroprevalence after localized outbreaks or examined seroprevalence of specific population groups such as e.g. medical staff. Few studies are either population-based or blood donor-based, but do not allow comparisons between regions. To date, we only consider the Corona sub-study of the Rhineland study similar to MuSPAD. It reports a low SARS-CoV-2 seroprevalence (46/4755; 0.97%; 95% CI: 0.72-1.30). Based on this, almost the entire German population remained susceptible to a SARS-CoV-2 infection by the end of 2020. Added value of this studyWe provide the first comprehensive, high-precision multi-region population-based SARS-CoV-2 seroprevalence study with representative sampling following the WHO protocol in Germany. By measuring SARS-CoV-2 IgG, we explore immunity at regional and national level over time. We also assess risk factors and sample each region twice, which permits to monitor seroprevalence progression throughout the epidemic in different exemplary German regions. Implications of all the available evidenceOur results show low seroprevalence (<3%) until Mid-December 2020 in all regions. While estimates in Reutlingen, Aachen, Freiburg and Osnabruck reflect low seroprevalence mostly after the first wave, the survey in Magdeburg cumulatively already represents the beginning of the second wave. The number needed to quarantine to prevent one infection was 8.2 in our study. We also show that for the first wave reported infections reflected overall around 25% of those actually infected rising to 40-50% in the second wave. A slightly raised infection risk could be shown for persons with lower education.

ObjectiveTo assess the characteristics of computed tomography (CT) features and changes in CT monitoring in patients with novel coronavirus pneumonia (NCP). MethodsIn this retrospective, two-center study, we reviewed the medical records of 57 patients with NCP in CT from January 21 to February 12, 2020. Cases were confirmed by the results of nucleic acid test positive, and were analyzed for demographic, clinical, and CT features. ResultsOf the 57 patients, 31cases were male, and 45.6% were female. The average age was 46.5 {+/-} 15.8 years. Patients had fever (84.2%), cough (49.1%), weak (31.6%), muscle ache (17.5%), shortness of breath (12.3%). The distribution of abnormality was a subpleural lesions in 51 cases, with 96.5% ground-glass opacity (GGO) and 68.4% consolidation. Another observation reveals 45.6% fibrosis, 33.3% lymph node enlargement, 21.1% pleural thickening, 17.5% small nodule, 7.0% white lung, 5.3% emphysema, and 3.5% bronchiectasis. Importantly, the group of men had more septal thickening and air trapping than the female group (p<0.05); Compared with the younger, the elderly had higher of subpleural lesion, interlobular septal thickening and pleural thickening (p<0.05). In the first monitoring, there were 37.3% improvement, 60.8% progress. In the second monitoring, there were 55% improvement, 35% progress. The improvement rate during the third follow-up visit was 100%. ConclusionsCT features and CT dynamic observation play a vital role in the diagnosis and treatment with NCP. It is conducive to early diagnosis, deepen the knowledge of NCP and accumulate experience. Key pointsBilateral and subpleural regions on CT are common in patients with novel coronavirus pneumonia (NCP), which were more extensive GGOs than consolidation. At CT, NCP shows GGOs without or with consolidation, which most of the patients appear interlobular interstitium thickening, vascular bundle thickening, air bronchogram, and fibrosis. In patients with fever in close contact with eruption areas of 2019-nCoV, familiarity with the CT findings may help with early diagnosis, early isolation, and management.

BackgroundReliable identification of early predictors of adverse outcomes was essential during the pre-vaccination phase of the COVID-19 pandemic. Few studies have comprehensively integrated clinical presentation, laboratory parameters including arterial blood gas analysis, and chest computed tomography (CT) findings within a single well-characterized cohort, particularly in underrepresented regions of Brazil. MethodsThis retrospective cohort study included 482 consecutive adults (median age 61 years [IQR 49-73]; 64.3% men) with RT-PCR-confirmed SARS-CoV-2 infection hospitalized at a tertiary cardiac center in Central-West Brazil between March 2020 and January 2021. Demographic, clinical, laboratory (including arterial blood gas analysis), and chest CT data obtained within 48 hours of admission were analyzed. Univariable logistic regression was performed for 76 variables. Multivariable models were constructed using an a priori variable selection strategy based on clinical relevance, representation of distinct pathophysiological domains, and adherence to events-per-variable principles. Complete-case analyses were performed without imputation. ResultsIn-hospital mortality was 9.3% (45/482). Invasive mechanical ventilation was required in 74 patients (15.4%), with a mortality rate of 58.1% among those ventilated. In univariable analysis, 42 variables were associated with mortality (p < 0.05). In multivariable analysis (n = 438), five independent predictors of death were identified: age (adjusted OR 1.66 per 10 years; 95% CI 1.19-2.32; p = 0.003), arterial pH (adjusted OR 0.47 per 0.1-unit increase; 95% CI 0.25-0.89; p = 0.021), neutrophil-to-lymphocyte ratio (adjusted OR 1.30; 95% CI 1.18-1.44; p < 0.001), number of comorbidities (adjusted OR 1.59; 95% CI 1.25-2.02; p < 0.001), and serum creatinine (adjusted OR 1.37; 95% CI 1.05-1.77; p = 0.019). The model demonstrated good calibration (Hosmer-Lemeshow p > 0.05) and moderate-to-high explanatory power (Nagelkerke R{superscript 2} = 0.43). For the composite outcome of death or invasive mechanical ventilation (74 events; 15.4%), four predictors remained independently associated; serum creatinine showed a non-significant trend (p = 0.069). On chest CT (n = 424), analyzed descriptively and in univariable models only, pulmonary involvement > 50% was associated with increased odds of death (OR 2.87; 95% CI 1.42-5.79; p = 0.003). ConclusionsFive admission variables representing distinct pathophysiological domains--age, arterial pH, neutrophil-to-lymphocyte ratio, comorbidity burden, and serum creatinine--were independently associated with in-hospital mortality in this pre-vaccination cohort. Arterial pH provided independent prognostic information beyond inflammatory and renal markers. These findings support early risk stratification using routinely available clinical data.

We investigated the SARS-CoV-2 specific antibody titers in 133 asymptomatic healthcare providers working at the Department of Laboratory Medicine of our tertiary center. A commercial chemiluminescence immunoassay, validated according to the ISO15189 standard requirements, was used. All the enrolled healthcare professionals underwent, simultaneously to the blood sampling, a nasopharyngeal swab for molecular testing with quantitative reverse-transcriptase-based polymerase chain reaction (RT-PCR). An overall positiveness of 5.25% was found. We strongly promote a wide use of validated serologic assays in asymptomatic, healthy individuals, as a crucial information for epidemiological surveillance.

BackgroundComplex surgical resection and reconstruction for rare thoracic cancers (RTCs) represent a major challenge, given their very low frequency, extreme variability of presentation, multi-modality treatment options and inadequate outcome prediction. We reported the experience of a tertiary referral centre on a consecutive series of RTC patients, to predict outcome by disease and complexity of surgical procedures. MethodsFrom Jan 2003 to Dec 2018, 1122 surgical procedures were performed with curative intent on 952 RTC patients. Study endpoints were: post-operative hospital stay (Pod), 30-day and 90-day mortality, 5-year and 10-year survival (OS). The follow-up was closed at June 2020. ResultsMedian Pod was 8 days, with a 2% 30-day and 3.9% 90-day mortality. Overall survival (OS) was 85.7% at 1 year, 61.7% at 5 years and 50.7% at 10 years. Ten-year OS was 64.8% in low, 58.8% in intermediate, and 42.4% in high complexity score (Log-rank tests p<0.0001); 64.4% in patients with 1 or 2 reconstructions and 32.8% in patients with 3 or more reconstructions; 44.5% with vascular and 48% with chest wall reconstruction; 71.8% in germ cell tumors and 0% in mesothelioma. ConclusionComplex surgical resection and reconstruction was associated with acceptable 90-day mortality and good 10-year survival in all RTCs but mesothelioma. A predictive score based on surgical complexity and cancer type can help the clinical decision making.

BackgroundSeveral municipalities in the Lombardy Region have been affected by the SARS-CoV-2 infection since the earliest stages of the epidemic. To date, 89442 confirmed cases have been diagnosed in Lombardy, and mortality in several municipalities has already surpassed that of the past decade. Currently, the true extent of the SARS-CoV-2 infection remains unknown as several affected subjects may have been asymptomatic or have presented mild disease, thus not resulting in the identified COVID-19 cases. MethodsThis cross-sectional study aims to define the spread of infection within the population by determining the seroprevalence of IgG antibodies directed against SARS-CoV-2 by rapid immunochromatographic testing and subsequent confirmation by serology on venous blood by liquid phase immunochemical testing, also allowing to compare the two methods. Testing will be performed on adults and minors residing, domiciled or working in several municipalities of the Lombardy Region, involved in the initial stages of the epidemic. The study will include rapid finger-prick testing and venous sampling for antibodies against SARS-CoV-2, and nasopharyngeal swabbing (NPS). Concurrent notification of test results will occur via the regional healthcare information system (SISS). DiscussionThis study was developed with the desire to understand the seroprevalence of SARS-CoV-2 infection and the epidemiological transmission characteristics of this virus. Understanding the spread and severity of the disease could help in the implementation of effective infection surveillance containment and countermeasures facilitating the identification of cases that have been exposed to the virus and the traceability of contacts. This study has been approved by the Ethics Committee of the University of Milan (35/2020).

Objective Many anecdotal reports indicate the presence of &amp;[prime]long COVID&amp;[prime] - COVID-19-related symptoms weeks to months after the acute illness. However, frequency and symptom-pattern of &amp;[prime]long COVID&amp;[prime] in relation to acute disease severity are uncertain. As part of an ongoing, prospective cohort study we therefore conducted an online survey among adults 6 months after acute COVID-19. Methods The prospective online study Life&amp;Covid is ongoing in Germany since May 2020. Participants were recruited 0 to 4 months after their SARS-CoV-2 infection und followed up by subsequent surveys. The survey 6 months after the infection was completed by 127 out of 148 individuals invited by email (86%). All grades of acute disease severity were included and 91% of the participants had been treated as outpatients during their acute illness. Results Six months after the infection, 67% of the study participants reported at least one symptom as a consequence of COVID-19. Exertional dyspnea (30% of participants), fatigue (25%) and diminished sense of taste/smell (19%) were the most common individual symptoms. At least one symptom, exertional dyspnea, and fatigue were reported more often after a severe acute illness, but diminished sense of taste/smell was unrelated to acute severity. Age group and sex did not associate with the frequency of symptoms at 6 months. Conclusions Based on this study, the prevalence of COVID-19-related symptoms 6 months after the infection is high. Some bias for overestimation may have affected this result. Nevertheless, &amp;[prime]long COVID&amp;[prime] requires attention in medical care and a better scientific understanding.

ImportanceRisk factors associated with COVID-19, the viral pneumonia originating in Wuhan, China, in Dec 2019, require clarification so that medical resources can be prioritized for those at highest risk of severe COVID-19 complications. Infection with M. tuberculosis (MTB), the pathogen that causes TB and latently infects [~]25% of the global population, may be a risk factor for SARS-CoV-2 infection and severe COVID-19 pneumonia. ObjectiveTo determine if latent or active TB increase susceptibility to SARS-COV-19 infection and disease severity, and lead to more rapid development of COVID-19 pneumonia. DesignAn observational case-control study of 36 confirmed COVID-19 cases from Shenyang, China, conducted in Feb 2020. Final date of follow-up: Feb 29, 2020. Cases were grouped according to COVID-19 pneumonia severity (mild/moderate, severe/critical), and MTB infection status compared. Comparisons were made with MTB infection data from another case-control study on bacterial/viral pneumonia at Shenyang Chest Hospital. SettingMulti-center study involving three primary care hospitals in Shenyang, China. Participants86 suspected COVID-19 cases from participating primary-care hospitals in Shenyang. All 36 SARS-CoV-2 +ve cases (based on RT-PCR assay) were included. Disease severity was assessed using the Diagnostic and Treatment Guidelines of the National Health Commission of China (v6). Mean age, 47 years (range: 25-79), gender ratio, 1:1. ExposuresConfirmed COVID-19 pneumonia. Interferon-gamma Release Assays (IGRA) were performed using peripheral blood to determine MTB infection. Main Outcome and MeasuresEpidemiological, demographic, clinical, radiological, and laboratory data were collected. Comparison of MTB infection status between patients with mild/moderate and severe/critical COVID-19 pneumonia. ResultsMean age of 36 COVID-19 patients: 47 (range: 25-79); M/F: 18/18; Wuhan/Hubei connection: 42%. Mild/moderate cases: 27 (75%); severe/critical: 9 (25%). MTB infection (IGRA+ve): 13 cases (36.11%), including 7 of 9 severe/critical cases. MTB infection rate: higher in COVID-19 (36.11%) than bacterial pneumonia (20%; p=0.0047) and viral pneumonia patients (16.13%; p=0.024). MTB infection more common than other co-morbidities (36.11% vs diabetes: 25%; hypertension: 22.2%; coronary heart disease: 8.33%; COPD: 5.56%). MTB co-infection linked with disease severity (severe/critical 78% vs mild/moderate cases 22%; p=0.0049), and rate of disease progression: infection to development of symptoms (MTB+SARS-CoV-2: 6.5{+/-}4.2 days vs SARS-COV-2: 8.9{+/-}5.2 days; p=0.073); from symptom development to diagnosed as severe (MTB+SARS-CoV-2: 3.4{+/-}2.0 days vs SARS-COV-2: 7.5{+/-}0.5 days; p=0.075). Conclusions and RelevanceMTB infection likely increases susceptibility to SARS-CoV-2, and increases COVID-19 severity, but this requires validation in a larger study. MTB infection status of COVID-19 patients should be checked routinely at hospital admission. Key PointsO_ST_ABSQuestionC_ST_ABSIs latent or active tuberculosis (TB) a risk factor for SARS-CoV-19 infection and progression to severe COVID-19 pneumonia? FindingsIn this observational case-control study of 36 COVID-19 cases from Shenyang, China, we found tuberculosis history (both of active TB and latent TB) to be an important risk factor for SARS-CoV-2 infection. Patients with active or latent TB were more susceptible to SARS-CoV-2, and COVID-19 symptom development and progression were more rapid and severe. MeaningTuberculosis status should be assessed carefully at patient admission and management and therapeutic strategies adjusted accordingly to prevent rapid development of severe COVID-19 complications.

BackgroundThe antibody response to SARS-CoV-2 does not follow the immunoglobulin isotype pattern expected in a primary response and is inconsistent with the current interpretation of COVID-19 immunopathology as the result of a primary infection. To better understand the immune response to SARS-CoV-2, it is essential to determine whether it is primary or secondary (or recall). The analysis of highly granular immunological variable trajectories of a homogeneous cohort of patients receiving standardised medical care should discern between primary and secondary responses. MethodsThis is a prospective cohort study of 191 SARS-CoV-2 infection cases and 44 healthy controls from the second wave of COVID-19 in the Barcelona area. The study stratified patients by severity and analysed the trajectories of SARS-CoV-2 antibodies and multiple immune variables for features associated with primary and recall immune responses. FindingsIsotype-specific antibody trajectories to SARS-CoV-2 proteins revealed a pattern of recall response in 94{middle dot}2% of cases. In these cases, the detailed trajectories of plasmablasts, B cells, cTfh high-resolution subsets, and cytokines were consistent with a secondary response. The transcriptomic data indicated that this cohort is strictly comparable to contemporary cohorts. ConclusionsIn most cases, the immune response to SARS-CoV-2 is a recall response. This opens the possibility that most COVID-19 cases are subjected to immune imprinting by endemic coronavirus, which, in turn, can contribute to severity by interfering with the immune response to SARS-CoV-2 and by antibody-dependent enhancement. Considering the immune responses to SARS-CoV-2 secondary provides a better perspective to interpret COVID-19 pathology. FundingGrants COV20/00416, Cov20/00654, and COV20/00388 from Instituto de Salud Carlos III (ISCIII), Madrid, Spain, co-financed by the European Regional Development Fund (ERDF).

BackgroundOn January 31st the first case of COVID-19 was detected in Spain, an imported case from Germany in Canary Islands, and thereafter on February 25th the first case was detected in Madrid. The first case of COVID-19 was confirmed at the Hospital Universitario 12 de Octubre on March 1st, a large public hospital with 1200 beds, covering an area over 400000 inhabitants in southern Madrid. During March 2020 highly active circulation of SARS-CoV-2 was experienced in Madrid with 24090 cases officially reported by March 29th. MethodsSince the beginning of the epidemics the Occupational Health and Safety Service (OHSS) organized the consulting and testing of the hospital personnel with confirmed exposure and also those presenting symptoms suggestive of viral respiratory infection. For molecular diagnosis of SARS-CoV-2 infection both nasopharyngeal and oropharyngeal swabs were obtained from suspected cases and processed at the Microbiology Laboratory by automatized specific PCR methods that was operative from February 25th as part of the preparedness. ResultsFrom a total of 6800 employees of the hospital, 2085 (30,6 %) were tested during the period 1-29 March 2020, some of them repeatedly (2286 total samples). The first HCW infected was confirmed on March 9th. A total of 791 HCW and personnel were confirmed to be infected by March 29th, representing 38% of those tested and 11,6 % of all the hospital workers. The proportion of infected individuals was estimated among the different groups of occupational exposure and the evolution of the cases during the expansive epidemic wave was compared between HCW and those patients attending at the Emergency Department (ER) during the same period and adjusted by the same age range. There were no statistically significant differences in the proportion of SARS- CoV-2 positive PCR detection between HCW from high risk areas involved in close contact with COVID-19 patients in comparison with clerical, administrative or laboratory personnel without direct contact with patients. The curves of evolution of accumulated cases between patients and HCW during March 2020 showed an almost parallel shape. DiscussionThe recommendation from our OHSS did not include testing of asymptomatic cases but was highly proactive in testing even patients with minor symptoms therefore, a high proportion of HCW and non-sanitary personnel was tested in March 2020 during the rapid period of expansion of the epidemics in Madrid, accounting for a total of 30,6 % of the hospital employees. Most of the COVID-19 cases among the hospital HCW and personnel were mild and managed at home under self-isolation measures, however 23 (3%) required hospitalization mostly due to severe bilateral interstitial pneumonia, two of those cases required mechanical ventilation at the ICU. No fatalities occurred during the study period. Although there were some cases of highly probable transmission from COVID-19 patients to HCWs, mainly at the first phase of the epidemics, there were no significant differences on the infection rates of HCW and hospital personnel that can be related to working in areas of high exposure risk. Furthermore, the evolution of cases during the same time period (March 2020) between patients attending the ER and hospital staff suggests that both groups were driven by the same dynamics. This experience is similar to the communicated from Wuhan verified by the WHO Joint Mission and also from recent experiences at hospital in the Netherlands, where most of the infections of HCW were related to household or community contacts. SignificanceSince the collective of hospital HCW are exhaustively screened in specific centers, their rate of infection for SARS-CoV-2 could be an indicator of the epidemic dynamics in the community. There appears to be a close connection between HCW infection and the driving forces of transmission in the community. Although we cannot exclude an additional risk factor of infection by SARS-CoV-2 due to the fact of the hospital environment, the similar proportions of positive cases among all the areas of the hospital and the evolutive wave of infection, as compared with the community, are clear arguments against a major factor of occupational risk. Exhaustive testing, such as the one carried out in our institution, covering over one third of all the workers, could be used as a reference of the population infected in the community. Since a significant proportion of COVID-19 cases can be asymptomatic and not all the hospital employees were actually tested, it is highly likely that this 11,6 % is a minimum estimation of the impact of SARS-CoV-2 circulation in Madrid during the first 4 weeks of the epidemics. This is in high and clear contrast with the official figures circulating at national and international levels. This has important implications to more precisely estimate the actual number of cases in the community and to develop public health policies for containment, treatment and recovery.

BackgroundThere are conflicting results about the duration of antibodies induced by SARS-CoV-2, but several studies show a rapid decay in a few months after infection. To evaluate antibody decline, we re-evaluated the presence of anti-SARS-CoV-2 antibodies among individuals found seropositive in a first population survey conducted 4 months before. MethodsAll individuals above ten years of age resident in 5 municipalities of the Autonomous Province of Trento, northern Italy, who resulted IgG positive for anti-SARS-CoV-2 nucleocapsid (NC) antibodies in a serosurvey conducted on May 2020 were retested after 4 months. Anti-SARS-CoV-2 antibodies were detected using the Abbott SARS-CoV-2 IgG assay (Abbott Diagnostics, USA) detecting anti-NC antibodies. Samples that gave a negative result were re-tested using the same test plus Liaison SARS-CoV-2 IgG assay (DiaSorin, Italy) to assess anti-spike (S) S1/S2 IgG antibodies. Seroprevalence was calculated as the proportion of positive people on the total number of tested. A neutralizing assay was performed on a subgroup of formerly positives sera using fifty-percent tissue culture infective dose (TCID50) as endpoint dilution to produce a cytopathic effect in 50% of inoculated Vero E6 cells culture. In all the analyses a p value < 0.05 were considered statistically significant. Statistical analysis was performed by STATA version 16.1 (STATA Corp., College Station, Texas, USA). FindingsOverall, 1159 out of 1402 initially anti-NC seropositive participants were enrolled in the study. Of them, 480 (41.1%) became seronegative for anti-NC IgG antibodies. When 479 negative sera were tested for anti-S IgG, 373 samples (77.9%) resulted positives. A functional neutralization assay was performed on 106 sera showing high concordance with anti-S antibodies positivity. InterpretationA decline of anti-NC IgG values was recorded 4 months after the first evaluation. Worth of note, a high proportion of anti-NC seronegative individuals were positive for anti-spike IgG antibodies, which appear to persist longer and to better correlate with neutralization activity.

Background and ObjectivesTest-to-stay concepts apply serial testing of children in daycare after exposure to SARS-CoV-2 without use of quarantine. This study aims to assess safety of a test-to-stay screening in daycare facilities. Methods714 daycare facilities and approximately 50,000 children [&le;]6 years in Cologne, Germany participated in a SARS-CoV-2 Pool-PCR screening from March 2021 to April 2022. The screening initially comprised post-exposure quarantine and was adapted to a test-to-stay approach during its course. To assess safety of the test-to-stay approach, we explored potential changes in frequencies of infections among children following the adaptation to the test-to-stay approach by applying regression discontinuity in time (RDiT) analyses. To this end, PCR-test data were linked with routinely collected data on reported infections in children and analyzed using ordinary least squares regressions. Results219,885 Pool-PCRs and 352,305 Single-PCRs were performed. 6,440 (2.93%) Pool-PCRs tested positive, and 17,208 infections in children were reported. We estimated that during a period of 30 weeks, the test-to-stay concept avoided between 7 and 20 days of quarantine per eligible daycare child. RDiT revealed a 26% reduction (Exp. Coef: 0.74, CI:0.52;1.06) in infection frequency among children and indicated no significant increase attributable to the test-to-stay approach. This result was not sensitive to adjustments for 7-day incidence, season, SARS-CoV-2 variant, and socioeconomic status. ConclusionOur analyses provide evidence that suggest safety of the test-to-stay approach compared to traditional quarantine measures. This approach offers a promising option to avoid use of quarantine after exposure to respiratory pathogens in daycare settings.