Infectious Diseases

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).

The fast spread of the novel coronavirus (SARS-CoV-2) has become a global threat hitting the worldwide fragile health care system. In Italy, there is a continued COVID-19 growth of cases and deaths that requires control measures for the correct management of the epidemiological emergency. To contribute to increasing the overall knowledge of COVID-19, systematic tests in the general population are required. Here, we describe the first Italian survey performed in 727 employees belonging to a Mother-Child Research hospital tested for both viral (nasopharyngeal and oropharyngeal swabs) and antibody presence. Individuals were divided into three risk categories (high, medium and low) according to their job activity. Only one subject was positive at the swab test while 17.2% of the cohort was positive for the presence of antibodies. Results highlighted that the presence of Positive antibodies is significantly associated with high and medium risk exposure occupation (p-value=0.026) as well as cold and conjunctivitis symptoms (p-value=0.016 and 0.042 respectively). Moreover, among healthcare professionals, the category of medical doctors showed a significant association with the presence of antibodies against SARS-CoV-2 (p-value=0.0127). Finally, we detected a rapid decrease in antibody intensity between two assessments performed within a very short period (p-value=0.009). Overall, the present study increases our knowledge of the epidemiological data of COVID-19 infection in Italy, suggesting a high prevalence of immune individuals (i.e. at least among at-risk categories) and the efficacy of the combined diagnostic protocol to monitor the possible outbreak.

Although the emerging SARS-CoV-2 variants of concern (VOC) have shown increasing transmissibility, their role for causing severe disease has not been fully clarified. Here, we studied changes in rates of hospitalisation and severe illness (subjection to high-flow nasal oxygen or admission to an intensive care unit during hospital stay) among all (n=685 891) unvaccinated SARS-CoV-2 positive adults without risk factors in Sweden from November 2020 to September 2021. After adjustment for age, sex, and socio-economic factors, and with November 2020 (non-VOC period) as reference, the odds ratios (OR) for hospitalisation were 1.6-1.7 in March-May 2021 (Alpha VOC dominance) and 2.4-3.0 in June-September 2021 (Delta VOC dominance), and the ORs for severe illness were 1.8-2.1 in March-May 2021 and 3.1-4.7 in June-September 2021. This study shows that unvaccinated adults without risk factors, have had a gradually increased risk for hospital admission and severe illness when infected with the Alpha and Delta VOCs, respectively.

ObjectivesThe Milan metropolitan area in Northern Italy was among the most severely hit by the SARS-CoV-2 outbreak. The epidemiological trends of mild COVID-19 are however still unknown. The aim of this study was to examine the seroprevalence of SARS-CoV-2 infection in healthy asymptomatic adults, the risk factors, and laboratory correlates. DesignWe conducted a cross-sectional study during the outbreak. Presence of anti-SARS-CoV-2 IgM/IgG antibodies against the Nucleocapsid protein was assessed by a lateral flow immunoassay. SettingBlood center at a leading academic hospital serving as COVID-19 referral center. ParticipantsWe considered a random sample of blood donors since the start of the outbreak (February 24th to April 8th 2020, n=789). Main outcome measuresThe main outcome was the prevalence of IgG/IgM anti-SARS-CoV-2 antibodies. ResultsThe test had a 98.3% specificity and 100% sensitivity, and for IgG+ was validated in a subset by an independent ELISA against the Spike protein (N=34, P<0.001). At the start of the outbreak, the overall seroprevalence of SARS-CoV-2 was 4.6% (2.3 to 7.9; P<0.0001 vs. 120 historical controls). During the study period characterized by a gradual implementation of social distancing measures, there was a progressive increase in seroprevalence to 7.1% (4.4 to 10.8), due to a rise in IgG+ to 5% (2.8 to 8.2; P=0.004 for trend, adjusted weekly increase 2.7{+/-}1.3%), but not of IgM+ (P=NS). At multivariate logistic regression analysis, seroconversion to IgG+ was more frequent in younger (P=0.043), while recent infections (IgM+) in older individuals (P=0.002). IgM+ was independently associated with higher triglycerides, eosinophils, and lymphocytes (P<0.05). ConclusionsSARS-CoV-2 infection was already circulating in Milan at the outbreak start. Social distancing may have been more effective in younger individuals, and by the end of April 4.4-10.8% of healthy adults had evidence of seroconversion. Asymptomatic infection may affect lipid profile and blood count. SUMMARY BOXO_ST_ABSWhat is already know on this topicC_ST_ABSO_LISARS-CoV-2 causes COVID-19, associated with a high mortality rate, but may be asymptomatic in a still undefined fraction of individuals. C_LIO_LICOVID-19 is associated with altered hematological, inflammatory and biochemical parameters, but the laboratory correlates of non-severe infection are unknown. C_LIO_LIA severe COVID-19 outbreak severely hit Milan at the end of February 2020, but the number of infected individuals and risk factors remain unclear. C_LI What this study addsO_LISARS-CoV-2 was already circulating in Milan at the COVID-19 outbreak start on February 2020, with only 1 in 20 infected individuals being symptomatic and diagnosed. C_LIO_LISocial distancing may have been more effective in reducing new infections in younger individuals, and by the end of April 4.4-10.8% of healthy asymptomatic adults had evidence of seroconversion. C_LIO_LIAsymptomatic infection may affect lipid profile and be associated with higher circulating lymphocytes and eosinophils. C_LI

BackgroundIn France, cervical cancer screening for females aged 30 to 65 primarily targets high-risk human papillomavirus (HPV) infections using DNA tests ( HR HPV test). AimThe primary goal was to map the prevalence of cervical infections caused by HPV16 and/or 18, or by any of 12 other carcinogenic genotypes (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68). The secondary goal was to compare prevalence estimates obtained from tests conducted after spontaneous medical visits ( opportunistic screening) or as part of the national screening programme ( organised screening). MethodsThe analytic sample contained 362,963 results of HR HPV tests collected, between 2020 and 2023, in metropolitan France. A full hierarchical Bayesian model was used to compute spatially resolved prevalence maps at the postcode level. ResultsAmong samples from organised and opportunistic screening, 2.9% and 3.8% were positive for HPV16 and/or 18, respectively. For other genotypes, these percentages were 6.9% and 9.4%, respectively. During the last week of the study period, among females aged 30, opportunistic screening was associated with a greater HPV infection prevalence for HPV16 and/or 18 (other genotypes) in 97.2 [72.9,100.0]% (99.9 [99.3,100.0]%) of postcodes. The probability of this percentage being lower among females aged 66 was below 95% for both genotype groups. After correcting for this effect, a pronounced northwest/southeast gradient in HR HPV infection prevalence was found across France, for both genotype groups, with some hotspots located at the border with Spain and Italy and Switzerland. ConclusionOpportunistic screening is associated with systematic inflation in HR HPV infection prevalence.

Human papillomaviruses (HPVs) are the most oncogenic viruses known to humans, with 12 high-risk (HR) genotypes causing nearly all cervical cancers. Cytology is commonly used to screen for cervical lesions but is currently being replaced by testing for high-risk HPV (HR HPV). Although HR HPV screening has a higher sensitivity, its specificity is limited, and it is currently advised to repeat the first screening 4 to 6 months later. To increase the sensitivity of the screening triage, other biomarkers have been suggested, including HPV viral load. Indeed, since 1999, several independent studies have found an association between HR HPV viral load in cervical samples and the severity of cervical disease. Here, we further explore the determinants of variations in HPV viral load in genital infections in young adult women. We analysed samples collected in the PAPCLEAR clinical cohort for participants who were infected by HPV genotypes for which we quantified virus load using qPCR targeting 13 genotypes. We developed a Bayesian statistical model estimating the effect of covariates of interest on the HPV viral load. To analyse precisely the viral load difference between HPV genotypes, phylogenetic distances between HPVs were also integrated in the Bayesian model. Our results fail to identify an effect of anti-HPV vaccination, co-infections by multiple HPVs or tobacco smoking on the detected viral load. On the opposite, swabs contained significantly more viral copies than cervical smears. Our results also highlight that most of the viral load variance could be explained at the genotype level (80%) rather than at the individual level (20%). Our model reveals important differences in viral load detected between the different genotypes tested, with HPV16 being the highest and HPV18 the lowest. The impact of phylogenetic signal on viral load was also estimated to be low, except for a cluster comprised of HPV53, HPV66 and HPV56. These results contribute to identifying the main drivers of HPV viral load detected and could help design needed future screening policies.

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.

ObjectivesTaste or smell disorders have been reported as strongly associated with COVID-19 diagnosis. We aimed to identify subject characteristics, symptom associations, and humoral response intensity associated with taste or smell disorders. Patients and methodsWe used data from SAPRIS, a study based on a consortium of five prospective cohorts gathering 279,478 participants in the French general population. In the analysis, we selected participants who were presumably infected by SARS-CoV-2 during the first epidemic wave. ResultsThe analysis included 3,439 patients with a positive ELISA-Spike. Sex (OR = 1.28 [95% CI 1.05-1.58] for women), smoking (OR = 1.54 [95% CI 1.13-2.07]), consumption of more than 2 drinks of alcohol a day (OR = 1.37 [95% CI 1.06-1.76]) were associated with a higher probability of taste or smell disorders. The relationship between age and taste or smell disorders was non-linear. Serological titers were associated with taste or smell disorders: OR = 1.31 [95% CI 1.26-1.36], OR = 1.37 [95% CI 1.33-1.42] and OR = 1.34 [95% CI 1.29-1.39] for ELISA-Spike, ELISA-Nucleocapsid and seroneutralization, respectively. Among participants with taste or smell disorders, 90% reported a wide variety of other symptoms whereas 10% reported no other symptom or only rhinorrhea. ConclusionAmong patients with a positive ELISA-Spike test, women, smokers and people drinking more than 2 drinks a day were more likely to develop taste or smell disorders. This symptom was strongly associated with a humoral response. The overwhelming majority of patients with taste or smell disorders experienced a wide variety of symptoms.

So far, 170,000 Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) infections have been confirmed in Germany, of which more than 5,000 have been detected in the Frankfurt am Main metropolitan region. When examining 1,000 nasopharyngeal swabs and serum samples from healthy volunteers from this region, one RT-PCR-positive and five antibody-positive persons were identified. The five positive serum samples were confirmed to be specific. Four of the five positive sera cross-neutralized SARS-CoV.

Since the emergence of Omicron, reinfections with SARS-CoV-2 have been rising. We estimated the risk of SARS-CoV-2 reinfection in the widely vaccinated French population, from January to August 2022. At nine weeks post-infection, the relative risk of reinfection, primary infection with pre-Delta variants being the reference group, was estimated at 0.43 [95%CI 0.40-0.47] if the primary infection was attributed to Delta, 0.21 [95%CI 0.19-0.24] with BA.1 and 0.17 [95% CI 0.15-0.18] with BA.2, and rapidly waned overtime. After a BA.1 primary infection the protection was similar against BA.2 or BA.4/5 reinfection.

Seroprevalence studies can contribute to better assess the actual incidence of infection. Since long-term data for Germany are lacking, we determined seroprevalence of IgG-antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 3,759 regular blood donors in three German federal states between July 2020 and June 2021. The IgG seroprevalence was 5.48% (95% confidence interval (CI): 4.77-6.25) overall, ranging from 5.15% (95% CI: 3.73-6.89) in Lower Saxony to 5.62% (95% CI: 4.57-6.84) in North Rhine Westphalia.

Investigations on the concordance in monozygotic (MZ) as compared to dizygotic (DZ) twins may reveal if there is a genetic component increasing the susceptibility or resistance against an infectious disease. Here, we compared the concordance rates of SARS-CoV-2 infection in MZ versus DZ young twins who shared the same bedrooms and were equally exposed to the virus. The concordance rate was higher in the MZ group supporting a complex multifactorial inheritance responsible for SARS-Cov-2 infection.

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.

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.

IntroductionWe assessed the incidence of redetection with the same human papillomavirus (HPV) genotype, predictors of first HPV detections and redetections, and prevalence of cytological lesions during HPV redetections. MethodsThe Ludwig-McGill cohort study followed women aged 18-60 years from Sao Paulo, Brazil in 1993-1997 for up to 10 years. Women provided cervical samples for cytology testing and HPV DNA testing at each visit. A redetection was defined as a recurring genotype-specific HPV positive result after one or more intervening negative visits. Predictors of genotype-specific redetection were assessed using adjusted hazard ratios (aHR) with Cox regression modeling. Results2184 women contributed 2368 incident HPV genotype-specific first detections and 308 genotype-specific redetections over a median follow-up of 6.5 years. The cumulative incidence of redetection with the same genotype was 7% at 1 year and 15% at 5 years after the loss of positivity of the first detection. Neither age (aHR 0.90, 95%CI 0.54-1.47 for [&ge;]45y vs. <25y) nor new sexual partner acquisition (aHR 0.98, 95%CI 0.70-1.35) were statistically associated with genotype-specific redetection. High-grade squamous intraepithelial lesion prevalence was similar during first HPV detections (2.9%) and redetection (3.2%). ConclusionsOur findings suggest many HPV redetections were likely reactivations of latent recurring infections.

IntroductionOur purpose was to describe the course of Long COVID symptoms after 12-month follow-up, their impact on daily life and the factors associated with the relief of symptoms. MethodsA cross-sectional survey was conducted within an out-patient clinic for Long COVID patients. Participants, who had experienced their initial COVID-19 episode between January, 15 2020 and May 21, 2021, were contacted 12-months post onset. Their characteristics, symptom course at initial COVID-19 episode, Long COVID phase and one year follow-up along with remission status were collected through a questionnaire and a specific post COVID remission scale from complete remission to persistence of symptoms and dependence in daily life activities. ResultsAmong the 231 long COVID participants who answered the 12-month follow-up questionnaire, 63.2% had developed SARS-CoV-2 antibodies before COVID-19 vaccination. At 12-month follow-up, only 8.7% of the participants felt in complete remission while 28.6% noted a significant improvement of their symptoms. The prevalence rate of most symptoms remained high at 12 months: asthenia 83.1%, neurocognitive and neurological symptoms 91.8%, cardiothoracic symptoms 77.9%, musculoskeletal 78.8%. During Long COVID phase, 62.2% had to stop working at least once and only 32.5% resumed professional activities full time at one year follow-up. The presence of SARS-CoV-2 antibodies before COVID-19 vaccination was associated with an increased probability of significant improvement at one year (aPRR: 1.60, p=0.028) while ageusia at initial Long COVID phase was associated with a lower probability of improvement (aPRR: 0.38, p=0.007). ConclusionWhile observing a trend towards some improvement in a majority of long COVID patients at a 12-month follow-up, fatigue, musculoskeletal pain, cardiothoracic symptoms and neurocognitive impairment persisted in most of them. Having developed SARS-CoV-2 antibodies was associated with a better prognosis while persistent ageusia at long COVID phase seems to be associated with the persistence of symptoms.

In fall 2021 in Finland, the recommendation to use face masks in schools for pupils ages 12 years and above was in place nationwide. Some cities recommended face masks for younger pupils as well. Our aim was to compare COVID-19 incidence among 10-12-year-olds between cities with different recommendations on the use of face masks in schools. COVID-19 case numbers were obtained from the National Infectious Disease Registry (NIDR) of the Finnish Institute for Health and Welfare, where clinical microbiology laboratories report all positive SARS-CoV-2 tests with unique identifiers in a timely manner, including information such as date of birth, gender, and place of residence. The NIDR is linked to the population data registry, enabling calculation of incidences. We compared the differences in trends of 14-day incidences between Helsinki and Turku among 10-12-year-olds, and for comparison, also among ages 7-9 and 30-49 by using joinpoint regression. According to our analysis, no additional effect seemed to be gained from this, based on comparisons between the cities and between the age groups of the unvaccinated children (10-12 years versus 7-9 years).

On February 27th, three cases of COVID-19 were reported among Norwegians that had recently returned from Lombardy, Italy. Travellers from the region rapidly became the most common source of imported infections in the earliest stage of the Norwegian COVID-19 epidemic. The situation was exacerbated by the unfortunate temporal overlap between the Norwegian winter holidays and intense epidemic spread of COVID-19 in Northern Italy, resulting in a large number of infected travellers. Here we combined flight data on travels between Norway and Lombardy with patient-level data to determine the fraction of travellers returning to Norway that had been infected with SARS-CoV-2. Travellers returning to Norway from Lombardy contracted COVID-19 at incidence rates up to 0.02 per person-day in the period spanning February 21st and March 1st, with a clear uptick in transmission in the middle of the period. This shows an example of the infection risk in tourist destinations being several fold higher than elsewhere in the region. In Norway, this is also supported by high rates of infections among tourists returning from Austria in February and March, despite a low number of reported cases in the country at the time. The massive COVID-19 prevalence among travellers suggest that mandatory quarantine of returning travellers or suspension of non-essential international flights is essential if the aim is to control or suppress the COVID-19 pandemic.

BackgroundDuring the Covid19 pandemic, school closure has been mandated in analogy to its known effect against influenza, but it is unclear whether schools are early amplifiers of Covid19 cases. MethodsWe performed a cross-sectional and prospective cohort study in Italy. We used databases from the Italian Ministry of Education containing the number of new positive SARS-CoV-2 cases per school from September 20 to November 8, 2020 to calculate incidence among students and staff. We calculated incidence across each age group using databases from the Veneto Region system of SARS-CoV-2 cases notification in the period August 26- November 24, 2020. We used a database from the Veneto Region system of SARS-CoV-2 secondary cases tracing in Verona province schools to estimate number of tests, the frequency of secondary infections at school by type of index case and the ratio positive cases/ number of tests per school institute using an adjusted multivariable generalized linear regression model. We estimated the reproduction number Rt at the regional level from the Italian Civil Protection of regional SARS-CoV-2 cases notification database in the period 6 August-2 December 2020. FindingsFrom September 12 to November 7 2020, SARS-CoV-2 incidence among students was lower than that in the general population of all but two Italian regions. Secondary infections were <1%, and clusters of >2 secondary cases per school were 5-7% in a representative November week. Incidence among teachers was greater than in the general population. However, when compared with incidence among similar age groups, the difference was not significant (P=0.23). Secondary infections among teachers were more frequent when the index case was a teacher than a student (38% vs. 11%, P=0.007). From August 28 to October 25 in Veneto where school reopened on September 14, the growth of SARS-CoV- 2 incidence was lower in school age individuals, maximal in 20-29 and 45-49 years old individuals. The delay between the different school opening dates in the different Italian regions and the increase in the regional Covid19 reproduction number Rt was not uniform. Reciprocally, school closures in two regions where they were implemented before other measures did not affect the rate of Rt decline. InterpretationOur analysis does not support a role for school opening as a driver of the second wave of SARS-CoV-2 epidemics in Italy, a large European country with high SARS-CoV-2 incidence. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSThe role of schools and at large of children as amplifiers of the Covid19 pandemics is debated. Despite biological and epidemiological evidence that children play a marginal role in Sars-CoV-2 spread, policies of school closures have been predicated, mostly based on the temporal coincidence between school reopening in certain countries and Covid19 outbreaks. Whether schools contributed to the so called "second wave" of Covid19 is uncertain. Italys regionalized calendar of school reopening and databases of positivity at school allows to estimate the impact of schools on the increase of Sars-CoV-2 that occurred in autumn 2020. Added value of this studyWe found that incidence among students is lower than in the general population and that whereas incidence among teachers appears higher than that in the general population, it is comparable to that among individuals of the same age bracket. Moreover, secondary infections at school are rare and clusters even less common. The index case of a secondary teacher case is more frequently a teacher than a student. In Veneto, during the first phase of the second wave incidence among school age individuals was low as opposed to the sustained incidence among individuals of 45-49 years. Finally, the time lag between school opening and Rt increase was not uniform across different Italian regions with different school opening dates, with lag times shorter in regions where schools opened later. Implications of the available evidenceThese findings contribute to indicate that Covid19 infections rarely occur at school and that transmission from students to teachers is very rare. Moreover, they fail to support a role for school age individuals and school openings as a driver of the Covid19 second wave. Overall, our findings could help inform policy initiatives of school openings during the current Covid19 pandemic.

The goal of this study was to estimate rates of SARS-CoV-2 carriership and viral loads in the general Antwerp population and to compare the estimated prevalences and incidences with governmental data (numbers of detected positive cases, stringency measure index) in order to evaluate the dynamics leading to the second wave. We used (pre)admission screening results from the major Antwerp hospitals for estimating community prevalences and incidences. 43.545 samples were included (April - November 2020). High SARS-CoV-2 carriership rates (mean week prevalence of 1.3%) were found in the general Antwerp population. 35.4% of positive cases carried high viral loads. Only a small proportion (15.3%) of the viral circulation was detected by the nationally implemented testing policy. In the weeks before the second Belgian wave, increasing prevalences and incidences were found, together with country-wide easing of restriction measures. In our opinion these findings have led to origin of the second viral wave.