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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">At the time when WHO reports that Italy is currently the fifth country in the world for number of cases of Severe Acute Respiratory Syndrome Coronavirus-2 &#40;SARS-CoV-2&#41; infection &#40;225&#44;886 confirmed positive cases to 19<span class="elsevierStyleSup">th</span> May 2020&#41;&#44; and the third country for number of related deaths &#40;32&#44;007 fatal cases&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a> it is important to underline that the distribution of affected subjects in our country is very inhomogeneous&#46; 85&#37; of total fatal cases have been registered&#44; in fact&#44; in the Northern Italy &#40;in particular 37&#46;8&#37; in the Lombardia region&#41;&#44; with an abrupt decrease from north to south<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; This geographic difference is still difficult to understand and many factors may account for it&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0010" class="elsevierStylePara elsevierViewall">&#945;1-Antitrypsin &#40;AAT&#41; is a serine protease inhibitor whose primary function is to counterbalance the proteolytic action of human neutrophil elastase in the lungs&#46; An autosomal codominant disorder&#44; AAT deficiency &#40;AATD&#41; is characterized by reduced serum level or abnormal function of AAT&#44; that increases the risk of developing a variety of diseases&#44; including pulmonary emphysema and liver cirrhosis&#46; The most common hereditary disorder in adults&#44; AATD was found to have the highest prevalence rates in northern regions of Italy and to decrease very fast from north to south&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a> Recent data from the Italian Registry for AATD&#44; showed a geographic distribution of confirmed cases very similar to the one reported for SARS-CoV-2 infection&#44; with 47&#37; of the total amount registered in the Lombardia region &#40;237 out of 508&#41;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">4</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Although population size is much smaller than the SARS-CoV-2 patient population&#44; it is noteworthy that AATD is largely under-recognized in our country&#44; with a relation between diagnosed and expected cases of 1&#8211;460&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Cell entry of coronaviruses depends on binding of the viral spike &#40;S&#41; proteins to cellular receptors and on S protein priming by host cell proteases&#46; A recent study demonstrated that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a> Moreover&#44; the Authors reported that a TMPRSS2 inhibitor approved for clinical use blocked viral entry&#46; Based on these results&#44; we argue that a protease-antiprotease imbalance could play a central role in the pathogenicity and virulence of SARS-CoV-2 and we hypothesize that the high prevalence of AATD could have contributed to the devastating impact of coronavirus infection in the Northern Italy&#46; Could causality and not casualness explain geographical overlap between AATD and COVID-19 infection in our country&#63; A detailed analysis of data from the Italian Registry will give us an answer&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Funding</span><p id="par0020" class="elsevierStylePara elsevierViewall">This work was not funded by any organization&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Conflict of interest</span><p id="par0025" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span></span>"
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Scientific Letter
Geographical Overlap Between Alpha-1 Antitrypsin Deficiency and COVID-19 Infection in Italy: Casual or Causal?
Superposición geográfica entre la deficiencia de alfa-1 antitripsina y la infección por COVID-19 en Italia: casual o causal?
Andrea Vianello
Corresponding author
andrea.vianello@aopd.veneto.it

Corresponding author.
, Fausto Braccioni
Respiratory Pathophysiology Division, Department of Cardio-Thoracic and Vascular Sciences, University of Padova, Padova, Italy
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Distribution of confirmed cases of Alpha-1 antitrypsin deficiency and Severe Acute Respiratory Syndrome Coronavirus-2 infection in Italy to 18th April 2020 &#40;AATD<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>alpha-1 antitrypsin deficiency&#59; SARS-CoV-2<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>Severe Acute Respiratory Syndrome Coronavirus-2&#41;&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">At the time when WHO reports that Italy is currently the fifth country in the world for number of cases of Severe Acute Respiratory Syndrome Coronavirus-2 &#40;SARS-CoV-2&#41; infection &#40;225&#44;886 confirmed positive cases to 19<span class="elsevierStyleSup">th</span> May 2020&#41;&#44; and the third country for number of related deaths &#40;32&#44;007 fatal cases&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a> it is important to underline that the distribution of affected subjects in our country is very inhomogeneous&#46; 85&#37; of total fatal cases have been registered&#44; in fact&#44; in the Northern Italy &#40;in particular 37&#46;8&#37; in the Lombardia region&#41;&#44; with an abrupt decrease from north to south<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; This geographic difference is still difficult to understand and many factors may account for it&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0010" class="elsevierStylePara elsevierViewall">&#945;1-Antitrypsin &#40;AAT&#41; is a serine protease inhibitor whose primary function is to counterbalance the proteolytic action of human neutrophil elastase in the lungs&#46; An autosomal codominant disorder&#44; AAT deficiency &#40;AATD&#41; is characterized by reduced serum level or abnormal function of AAT&#44; that increases the risk of developing a variety of diseases&#44; including pulmonary emphysema and liver cirrhosis&#46; The most common hereditary disorder in adults&#44; AATD was found to have the highest prevalence rates in northern regions of Italy and to decrease very fast from north to south&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a> Recent data from the Italian Registry for AATD&#44; showed a geographic distribution of confirmed cases very similar to the one reported for SARS-CoV-2 infection&#44; with 47&#37; of the total amount registered in the Lombardia region &#40;237 out of 508&#41;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">4</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Although population size is much smaller than the SARS-CoV-2 patient population&#44; it is noteworthy that AATD is largely under-recognized in our country&#44; with a relation between diagnosed and expected cases of 1&#8211;460&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Cell entry of coronaviruses depends on binding of the viral spike &#40;S&#41; proteins to cellular receptors and on S protein priming by host cell proteases&#46; A recent study demonstrated that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a> Moreover&#44; the Authors reported that a TMPRSS2 inhibitor approved for clinical use blocked viral entry&#46; Based on these results&#44; we argue that a protease-antiprotease imbalance could play a central role in the pathogenicity and virulence of SARS-CoV-2 and we hypothesize that the high prevalence of AATD could have contributed to the devastating impact of coronavirus infection in the Northern Italy&#46; Could causality and not casualness explain geographical overlap between AATD and COVID-19 infection in our country&#63; A detailed analysis of data from the Italian Registry will give us an answer&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Funding</span><p id="par0020" class="elsevierStylePara elsevierViewall">This work was not funded by any organization&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Conflict of interest</span><p id="par0025" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span></span>"
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ISSN: 03002896
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