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We conducted a retrospective cohort study at Montichiari Hospital (Brescia, Italy) to better understand the determinants of outcome in two different COVID-19 outbreaks. A total of 634 unvaccinated patients admitted from local emergency room to the Internal Medicine ward with a confirmed diagnosis of SARS-CoV-2 infection and a moderate-to-severe COVID-19 were included in the study. A group of 260 consecutive patients during SARS-CoV-2 first wave (from February to May 2020) and 374 consecutive patients during SARS-CoV-2 2nd\/3rd wave (from October 2020 to May 2021) were considered. Demographic data were not significantly different between waves, except a lower prevalence of female sex during first wave. Mortality was significantly higher during the 1<jats:sup>st<\/jats:sup> wave than in the following periods (24.2% vs. 11%; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). Time from symptoms onset to hospital admission was longer during first wave (8\u2009\u00b1\u20096 vs. 6\u2009\u00b1\u20094\u00a0days; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001), while in-hospital staying was significantly shorter (10\u2009\u00b1\u200914 vs. 15\u2009\u00b1\u200911\u00a0days; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). Other significant differences were a larger use of corticosteroids and low-molecular weight heparin as well less antibiotic prescription during the second wave. Respiratory, bio-humoral and X-ray scores were significantly poorer at the time of admission in first-wave patients. After a multivariate regression analysis, C-reactive protein and procalcitonin values, % fraction of inspired oxygen on admission to the Internal Medicine ward and length of hospital stay and duration of symptoms were the strongest predictors of outcome. Concomitant anti-hypertensive treatment (including ACE-inhibitors and angiotensin-receptor blockers) did not affect the outcome. In conclusion, our data suggest that earlier diagnosis, timely hospital admission and rational use of the therapeutic options reduced the systemic inflammatory response and were associated to a better outcome during the 2nd\/3rd wave.<\/jats:p>","DOI":"10.1007\/s11739-022-03034-5","type":"journal-article","created":{"date-parts":[[2022,7,9]],"date-time":"2022-07-09T11:02:48Z","timestamp":1657364568000},"page":"1941-1949","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Comparison of the characteristics, morbidity and mortality of COVID-19 between first and second\/third wave in a hospital setting in Lombardy: a retrospective cohort study"],"prefix":"10.1007","volume":"17","author":[{"given":"Francesca","family":"Leidi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca Edoardo Mario","family":"Boari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ottavio","family":"Scarano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedetta","family":"Mangili","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Gorla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Corbani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrice","family":"Accordini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Napoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Ghidelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Archenti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Turini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Saottini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vittoria","family":"Guarinoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Ferrari-Toninelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Manzoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Bonetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Chiarini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Malerba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Braglia-Orlandini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca","family":"Bianco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Faustini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Agabiti-Rosei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"De Ciuceis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1253-0186","authenticated-orcid":false,"given":"Damiano","family":"Rizzoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,7,9]]},"reference":[{"key":"3034_CR1","unstructured":"WHO (2020) Clinical Care Severe Acute Respiratory Infection. 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