“Scuola Sicura”: a school screening program to prevent the spread of COVID-19 among students in Piedmont, Italy (preprint)

Objectives: Aims of “Scuola Sicura” (SS) were to monitor the rate of COVID-19 and to contain its spread within the school population through early case isolation. We report the initial process and outcome evaluation results. Design: Descriptive study of an experimental screening testing program in children in Piedmont in the period January-March 2021. We used data from the COVID-19 platform and the Local Health Units, the archives of birth certificates (CedAP) and hospital discharge files (SDO). Setting: and participants The screening program targeted second and third grade students in first level secondary schools. Participants were subdivided into four groups; one group each week underwent screening, yielding one test per student per month. Main outcome measures We calculated:1. number of positive cases detected vs. total number of students tested in the SS program;2. number of positive cases detected outside the SS program vs. total number of students in the target population.We detected the number of quarantines due to SS and no-SS case identification. To investigate the spread of COVID-19 in households, the mother-child pairs were identified through record linkage between the CedAP and SDO archives, and positive mothers were identified. Results: Sixty-nine percent of schools and 19.5% of the students participated in the program. SS detected 114 positives cases for SARS-CoV-2. On 08.03.2021, the target classes started distance learning: 69 of the 114 positive students were identified before that date, leading to the activation of 67 quarantine measures. We were able to identify the mothers of 61 out of 69 of those students (88%); 46 mothers had performed a swab test after the positivity of their child with a positive result in 11 cases. Asymptomatic cases identified at screening during in-class learning period accounted for 26.5% of the total number of cases occurred in the participating classes. Conclusions: This is one of the few studies (and the first in Italy) to describe the functioning and predictive capacity of school screening testing for SARS-CoV-2 in a real-world situation. Our findings provide data-driven suggestions for government agencies when planning large-scale school screening testing programs.

COVID-19-like symptoms and their relation to SARS-CoV-2 epidemic in children and adults of an Italian birth cohort (preprint)

Background A number of cases positive for SARS-CoV-2 escape surveillance systems, especially in the first epidemic waves and/or when the number of cases becomes too large to allow complete diagnostic coverage.  Methods During the first SARS-CoV-2 epidemic wave hitting Italy in the spring 2020, mothers participating in an Italian NINFEA birth cohort were invited to complete an online questionnaire on COVID-19-like symptoms in the household. We estimated the population prevalence of COVID-19-like symptoms in children and adults, assessed their geographical correlation with the cumulative number of COVID-19 cases by province, analysed their clustering within families, and estimated their sensitivity, positive predictive value (PPV) and negative predictive value (NPV) for COVID-19 diagnosis in individuals tested for SARS-CoV-2.Results Information was collected on 3184 households, 6133 adults, and 5751 children. In the period March-April 2020, 55.4% of the NINFEA families had at least one member with at least one COVID-19-like symptom. There was a strong geographical correlation between the population cumulative incidence of COVID-19 and the prevalence of muscle pain, fatigue, low-grade fever, and breathing difficulties in adults (Spearman’s rho ≥0.70). Having at least one family member with a COVID-19 diagnosis, compared with none tested for SARS-CoV-2, was associated with an increased prevalence ratio (PR) of almost all COVID-19-like symptoms in adults, and only of low-grade fever (37-37.5°C; PR 5.27; 95% confidence intervals: 2.37 to 11.74) and anosmia/dysgeusia in children. Among adults with COVID-19 diagnosis, fatigue, muscle pain, and fever had a sensitivity ≥70%. In individuals tested for SARS-CoV-2, with a 16.6% prevalence of COVID-19, breathing difficulties and nausea/vomiting had the highest PPVs, with point estimates close to 60%, and with NPVs close to 90%.Conclusions The geographical prevalence of COVID-19-like symptoms in adults may inform on local disease clusters, while certain symptoms in family members of confirmed COVID-19 cases could help identify the intra-familial spread of the virus and its further propagation in the community. Low-grade fever is frequent in children with at least one household member with COVID-19 and possibly indicates child infection. 

Is death from Covid-19 a multistep process? (preprint)

Covid-19 death has a different relationship with age than is the case for other severe respiratory pathogens. The Covid-19 death rate increases exponentially with age, and the main risk factors are age itself, as well as having underlying conditions such as hypertension, diabetes, cardiovascular disease, severe chronic respiratory disease and cancer. Furthermore, the almost complete lack of deaths in children suggests that infection alone is not sufficient to cause death; rather, one must have gone through a number of changes, either as a result of undefined aspects of aging, or as a result of chronic disease. These characteristics of Covid-19 death are consistent with the multistep model of disease, a model which has primarily been used for cancer, and more recently for amyotrophic lateral sclerosis (ALS). We applied the multi-step model to data on Covid-19 case fatality rates (CFRs) from China, South Korea, Italy, Spain and Japan. In all countries we found that a plot of ln (CFR) against ln (age) was approximately linear with a slope of about 5. As a comparison, we also conducted similar analyses for selected other respiratory diseases. SARS showed a similar log-log age-pattern to that of Covid-19, albeit with a lower slope, whereas seasonal and pandemic influenza showed quite different age-patterns. Thus, death from Covid-19 and SARS appears to follow a distinct age-pattern, consistent with a multistep model of disease that in the case of Covid-19 is probably defined by comorbidities and age producing immune-related susceptibility. Identification of these steps would be potentially important for prevention and therapy for SARS-COV-2 infection.