key: cord-0689089-az6g94sa
authors: Perrella, A.; BIsogno, M.; D'Argenzio, A.; Trama, U.; Coscioni, E.; Orlando, V.
title: SARS-CoV-2 Infection Breakthrough among the non-vaccinated and vaccinated: a Real World Evidence study based on Big Data
date: 2022-02-24
journal: nan
DOI: 10.1101/2022.02.22.21266830
sha: 64b406ca275aa6e59b6fb7bbcae48cacd100c524
doc_id: 689089
cord_uid: az6g94sa

ABSTRACT Background: SARS-CoV-2 infection after vaccination can occur because COVID-19 vaccines do not offer 100% protection. The aim of this study was to assess vaccination coverage among people nasopharyngeal swabs, disease symptoms and type of hospitalisation (Intensive Care Unit) between the non-vaccinated and the effective dose vaccinated and to evaluate vaccination trend over time. Methods: A retrospective cohort study was carried out among people tested positive for COVID-19 in Campania Region using collected information from Health Information System of Campania Region (Sinfonia). The status of vaccination was assess according to the following timetable: non-vaccinated; Ineffective dose vaccination; Effective dose vaccination. Univariate and multivariate logistic regression models were conducted to evaluate the association between Intensive Care Unit (ICU) to COVID-19 and gender, age groups and vaccine. To determine vaccine coverage in subjects who received an effective dose, trend changes over time were investigated using segmented linear regression models and breakpoints estimations. Vaccination coverage was assessed by analysing the trend in the percentage of covid 19 positive subjects in the 9 months after vaccination with an effective dose stratified by age group and type of vaccine. Statistical analyses were performed using R platform Results: A significant association with the risk of hospitalisation in Intensive Care Unit was the vaccination status of the subjects: subjects with ineffective dose (adjusted OR: 3.68) and subjects no-vaccination (adjusted OR: 7.14) were at three- and seven-times higher risk of hospitalisation in Intensive Care Unit, respectively, than subjects with an effective dose. Regarding subjects with an effective dose of vaccine, the vaccine's ability to protect against infection in the months following vaccination decreased. The first breakpoints is evident five months after vaccination ({beta} =1.441, p<0.001). This increase was most evident after the seventh month after vaccination ({beta} =3.110, p<0.001). Conclusions: COVID19 vaccines protect from symptomatic infection by significantly reducing the risk of ICU hospitalization for severe disease. However, it seems they have trend to decrease their fully protection against SARS-COV-2 after five months regardless age, sex or type of vaccine. Therefore it seems clear that those not undergoing vaccine had higher risk to develop clinically significant disease and being at risk of ICU stay. Thus, considering highest percentage of asymptomatic patients and that few data about their capacity to transmit SARS-CoV-2, third dose vaccination should be introduced as soon as possible, Finally, a surveillance approach based on the use of integrated BIG Data system to match all clinical conditions too, offer a precise and real analysis with low incidence of errors in the categorization of subjects.

Since WHO declared the emergence of coronavirus disease 2019 (COVID-19) pandemic on March 77 11, 2020, over 5 million people have died worldwide, including over 130,000 people in Italy. 1 78 Due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection impact on health 79 system of all countries, some countries or pharmaceutical companies have promoted research 80 protocol to find a cure or to develop a vaccine against the SARS-CoV-2. 2 Despite recent studies 6-8 there is still a lack of studies on vaccine efficacy based on real world data. 90

The aim of this study was to assess vaccination coverage among people nasopharyngeal swabs, 91 disease symptoms and type of hospitalisation (Intensive Care Unit) between the non-vaccinated and 92 the effective dose vaccinated and to evaluate vaccination trend over time. 93 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted February 24, 2022. ;

Sinfonia includes records on patient demographics and for ~ 6 million residents, comprising a well-96 defined population in Italy (~ 10% of the population of Italy). 97

Sinfonia collects information, encrypted and anonymized from Local Health Unit (LHU) whose are 98 legal owner of the original data, in accordance with the privacy laws. All analyses on the data are 99 therefore carried out on encrypted and anonymized data using transparent data encryption protocols. 100

It is complete and involves data management system that has been validated in previous studies. 9-12 101

During the pandemic emergency, the Regional Health Information System of Campania Region 102 (Sinfonia) was implemented with all records related to COVID-19 in order to create a tool to 103 support health governance in managing the COVID-19 emergency. 104

The aims of Sinfonia tool, based on previous experiences too 13 , were: 105 1) Applying data science methods to big data in order to assess pandemic trends 106 2) Creation of predictive algorithms through AI methods 107

3) ML analysis, performed according to the python scripting model (Spyder IDE 64bit ver), to 108 perform predictive analysis on contagiousness. 109

The characteristics of Sinfonia are described in Supplementary Material 1 110

A retrospective cohort study was carried out among people tested positive for COVID-19 in 112

Campania Region since March 8, 2021, until 31 October 2021 using collected information from 113

Health Information System of Campania Region (Sinfonia). 114 Nasopharyngeal swabs were collected by trained personnel of Regional Healthcare system and/or 115 authorized and trained territorial laboratory staff. RT-PCR testing was performed with the use of 116 standardized RT-PCR machine from Coronavirus Network Laboratory (CoroNetLab), with four 117 genes analysis RdRP, S and N genes specific to SARS-CoV-2, and the E gene with results 118 expressed as the cycle threshold (Ct). A Ct value of less than 30, which indicated an increased viral 119 load, was used to determine infectivity. 14,15 120

Were considered as fully positive only results when all 4 genes found to be amplified by while in all other case results were considered doubt and repeated. 14,15 Participant consent was 122

given for the release of all SARS-CoV-2 PCR test results before or after vaccination. All positive 123 participants were followed-up until negative PCR test. 124

For all individuals being positive at nasal swab clinical symptoms were collected according to 125

Italian National Health Institute. Typical COVID-19 symptoms were fever, cough, or change or loss 126 of taste or smell. Participants were recorded as having other symptoms if they reported any of the 127 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Outcomes 153

The primary outcome was to assess the risk of intensive care unit (ICU) admission for COVID-19 154 between the non-vaccinated and the effective dose vaccinated. 155

Secondary outcome was to evaluate vaccination coverage, over time, stratified by age group and 156 vaccine type 157

The study population baseline characteristics were analyzed using descriptive statistics. 159

Quantitative variables were described as counts and percentages. The chi-square test and t-test were 160 performed to determine the difference between non-vaccinated and vaccinated subjects who tested 161 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted February 24, 2022. Among subjects in Intensive Care Unit (ICU) the majority (90.5%) were non-vaccinated, 7.6% 205 received a non-effective dose and 1.9% received an effective dose (Table 1) . 206 <0.001) were more than thirty times and twenty-nine times, respectively, likely to the risk of 217 hospitalization in Intensive Care Unit compared to subjects aged 0-39 years. Equivalent results were 218 found for the vaccination status of the subjects: subjects with ineffective dose (adjusted OR: 3.68; 219 95% CI: 1.23 -11.02, p value <0.001) and subjects no-vaccination (adjusted OR: 7.14; 95% CI: 220 2.64 -19.27, p value <0.001) were at three-and seven-times higher risk of hospitalisation in 221

Intensive Care Unit, respectively, than subjects with an effective dose. Further it is interestingly to emphasize that they also showed a strongly significant reduction of ICU 261 hospital stay when vaccinated patients are hospitalized compared to unvaccinated subjects (Table  262 2). However, despite these findings, we found a rate of breakthrough infection of (7.3%) among 263 currently approved vaccines. Therefore, in conclusion, in this study we found that although the 300 current approved COVID19 vaccine are extremely effective in reducing hospitalization and 301 particularly ICU, breakthrough infections occur with a breakpoint between 5 th and 7 th month after 302 vaccination and they may carry a potential infectiveness. This event could represent a challenge, 303 since such infections are often asymptomatic and may pose a risk to vulnerable populations. 304

Consequently, a boost dose could be a possible strategy while awaiting the antiviral 18, 19 that could 305

give us a final weapon against SARS-CoV-2. However, considering highest percentage of 306 asymptomatic patients and that few data about their capacity to transmit SARS-CoV-2, further 307 screening, quarantine procedure and other preventing strategies should be guaranteed in all 308 vaccinated subjects. Finally, a surveillance approach based on the use of integrated BIG Data 309 system to match all clinical conditions too, offer a precise and real analysis with low incidence of 310 errors in the categorization of subjects. 311 312 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted February 24, 2022. ; CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted February 24, 2022. ; 

. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted February 24, 2022. ; https://doi.org/10.1101/2022.02.22.21266830 doi: medRxiv preprint

WHO Coronavirus (COVID-19) Dashboard

SARS-CoV-2 vaccines in development

Optimising the COVID-19 vaccination programme for maximum short-term impact

Can COVID vaccines stop transmission? Scientists race to find answers

Impatto della vaccinazione COVID-19 sul rischio di infezione da SARS-CoV-2 e successivo

Covid-19 Breakthrough Infections in Vaccinated Health Care Workers

COVID-19 vaccine -Long term immune decline and 350 breakthrough infections. Vaccine

Walker 354 AS. Effect of Delta variant on viral burden and vaccine effectiveness against new SARS-CoV-2 355 infections in the UK

Prophylaxis with Hydroxychloroquine Does Not Prevent COVID-19 nor Virus Related Venous 359 Thromboembolism. Viruses

Menditto 361 E. Drug-utilisation profiles and COVID-19. Sci Rep

Development and validation of a clinical risk score to predict the risk of 365 SARS-CoV-2 infection from administrative data: A population-based cohort study from Italy

Baseline Drug Treatments as Indicators of Increased Risk of 369 COVID-19 Mortality in Spain and ItalyInt

Sars-CoV2): a global emergency that needs new approaches?

Duration of Severe Acute Respiratory Syndrome 376

Coronavirus 2 (SARS-CoV-2) Infectivity: When Is It Safe to Discontinue Isolation?

SARS-CoV-2 in Urine May Predict a Severe Evolution of COVID-19

Antibody 387 responses to SARS-CoV-2 vaccines in 45

Molnupiravir, an Oral Antiviral Treatment for COVID-19. medRxiv 393

Treatments for COVID-19: 395 Lessons from 2020 and new therapeutic options