新型冠状病毒肺炎疫情对慢性非传染性疾病防控的影响.pdf
新型冠状病毒肺炎疫情对慢性非传染性疾病防控的影响.pdf
Characteristics of SARS-CoV-2 patients dying in Italy Report based on available data on January 27th, 2021 1. Sample The present report describes the characteristics of 85,418 SARS-CoV-2 patients dying in Italy*, as reported by the Integrated Covid-19 Surveillance System coordinated by the National Institute of Health-ISS. Geographic distribution across the 19 regions and 2 autonomous provinces of Trento and Bozen is presented in Table 1. Absolute number and percentage of deaths are reported according to the 3 phases that characterized the pandemic from the beginning in 2020 to the 27th of January 2021: the first wave (March-May 2020), the low incidence phase (June-September 2020), and the second wave (October 2020 – January 2021), the latter is still ongoing. The surveillance data on deaths are constantly updated and consolidated and both activities require time to be carried out. Each Region has its own organization for updating data and related execution times. Therefore, when reading the data by Region, it is necessary to take into account that the timing of notification, control, verification and updating of data varies from Region to Region and from period to period; this may involve variations (increasing and/or decreasing) and differences both with the data already published in the previous reports, and with the data published by the Civil Protection. It should also be considered that the regional differences in the percentage of deaths reported in the table should not be interpreted in terms of risk. In fact, case fatality depends on the number of infections occurring in each region over a period of time compatible with the possible observation of the fatal event. In this regard, it should also be taken into account that the difference between the number of infections and the notified cases may vary regionally and over time as a function of different test access strategies adopted during the epidemic, thus distorting the comparison of regional case fatality. Table 1. Geographic distribution of deceased patients SARS-CoV-2 positive by period March-May 2020 REGION Lombardia Emilia-Romagna Veneto Piemonte Lazio Toscana Campania Sicilia Liguria Puglia Friuli-Venezia Giulia Marche Abruzzo Trento Sardegna June-Sept. 2020 Oct. 202027th Jan. 2021 Total N % N % N % N % 16,362 4,313 1,949 3,992 840 1,046 477 300 1,516 524 347 978 446 402 131 47.7 12.6 5.7 11.6 2.5 3.1 1.4 0.9 4.4 1.5 1.0 2.9 1.3 1.2 0.4 608 173 247 123 144 96 59 58 138 76 21 7 37 4 24 33.1 9.4 13.4 6.7 7.8 5.2 3.2 3.2 7.5 4.1 1.1 0.4 2.0 0.2 1.3 9,704 4,782 6,528 3,923 3,747 2,870 3,234 2,932 1,558 2,492 1,695 991 956 733 790 19.7 9.7 13.2 8.0 7.6 5.8 6.6 6.0 3.2 5.1 3.4 2.0 1.9 1.5 1.6 26,674 9,268 8,724 8,038 4,731 4,012 3,770 3,290 3,212 3,092 2,063 1,976 1,439 1,139 945 31.2 10.9 10.2 9.4 5.5 4.7 4.4 3.9 3.8 3.6 2.4 2.3 1.7 1.3 1.1 Bolzano Umbria Calabria Valle d'Aosta Molise Basilicata 290 75 96 143 22 29 0.8 0.2 0.3 0.4 0.1 0.1 2 9 4 3 2 2 0.1 0.5 0.2 0.2 0.1 0.1 586 653 375 257 238 230 1.2 1.3 0.8 0.5 0.5 0.5 878 737 475 403 262 261 1.0 0.9 0.6 0.5 0.3 0.3 Total 34,278 100.0 1,837 100.0 49,274 100.0 85,389 100.0 Note: For 29 deceased persons, period was not possible to be evaluated; the number of deaths, relating to the period October 2020-January 2021, is in the consolidation phase due to the delay in notification. * SARS-CoV-2 related deaths presented in this report are those occurring in patients who test positive for SARS-CoV-2RT by PCR, independently from pre-existing diseases. 2. Demographics Mean age of patients dying for SARS-CoV-2 infection was 81 years (median 83, range 0-109, IQR 75-88). Women were 37,295 (43.7%). Figure 1 shows that median age of patients dying for SARS-CoV-2 infection was more than 30 years higher as compared with the national sample diagnosed with SARS-CoV-2 infection (median age 48 years). Figure 2 shows the absolute number of deaths by age group. Women dying for SARS-CoV-2 infection had an older age than men (median age women, 86 years - median age men, 80 years). Figure 1. Median age of patients with SARS-CoV-2 infection and SARS-CoV-2 positive deceased patients SARS-CoV-2 Diagnosed SARS-CoV-2 Deaths Min 0 20 40 60 80 Median age (years) 100 120 Max Figure 2. Absolute number of deaths by age group 40000 35508 Women Men All 35000 30000 25000 20795 20000 14277 15000 16166 17344 11498 8056 6518 5986 10000 5000 0 19342 5 4 9 4 5 9 18 27 45 2774 2070 2040 69 102171 213494707 734 <=9 10-19 20-29 30-39 40-49 Age-groups 50-59 60-69 70-79 5846 80-89 90+ Figure 3 shows the trend in the average age of SARS-CoV-2 positive deceased patients per calendar week, starting from the 3rd week of February 2020 (the date of the first death dates back to 21st February 2020). The average age of weekly deceased persons has substantially increased up to 85 years (1st week of July) and then dropped slightly. Figure 3. Mean age of SARS-CoV-2 positive deceased patients by week of death 90 88 86 84 82 80 78 76 74 72 70 68 Weekly deaths mean age Total mean age 3. Deaths under the age of 50 years As of January 27th 2021, 941 out of the 85,418 (1,1%), positive SARS-CoV-2 patients under the age of 50 died. In particular, 234 of these were less than 40 years (138 men and 96 women), age range between 0 and 39 years. For 52 patients under the age of 40 years no clinical information is available; out of the remaining ones, 147 had serious pre-existing pathologies (cardiovascular, renal, psychiatric pathologies, diabetes, obesity) and 35 had no major pathologies. 4. Pre-existing conditions Table 2 presents most common comorbidities diagnosed before SARS-CoV-2 infection in a sample of SARSCoV-2 positive deceased patients. Data on diseases were based on chart review and was available on 6,381 patients dying in-hospital for whom it was possible to analyse clinic charts. The medical records are sent to the ISS by the hospitals at different times, compatibly with the priorities of the activities carried out in the hospitals themselves. Therefore, the sample is opportunistic; it represents deaths in subjects who needed hospitalization only, and the regions are represented trying to maintain a proportionality with respect to the number of deaths. Mean number of diseases was 3.6 (median 3, SD 2.1). Overall, 3.1% of the sample presented with a no comorbidities, 12.1% with a single comorbidity, 18.6% with 2, and 66.3% with 3 or more. Before hospitalization, 21% of SARS-CoV-2 positive deceased patients followed ACE-inhibitor therapy and 13% angiotensin receptor blockers-ARBs therapy. This information can be underestimated because data on drug treatment before admission were not always described in the chart. Table 2. Most common comorbidities observed in SARS-CoV-2 positive deceased patients Diseases N % Ischemic heart disease 1,790 28.1 Atrial Fibrillation 1,547 24.2 Heart failure 1,028 16.1 Stroke 733 11.5 Hypertension 4,200 65.8 Type 2-Diabetes 1,868 29.3 Dementia 1,501 23.5 COPD (Chronic Obstructive Pulmonary Disease) 1,112 17.4 Active cancer in the past 5 years 1,065 16.7 Chronic liver disease 309 4.8 Chronic renal failure 1,339 21.0 Dialysis 137 2.1 Respiratory failure 425 6.7 HIV Infection 16 0.3 Autoimmune diseases 267 4.2 Obesity 688 10.8 Number of comorbidities 0 comorbidities 1 comorbidity 2 comorbidities 3 comorbidities and over 196 772 1,185 4,228 3.1 12.1 18.6 66.3 Table 3 presents the most common pre-existing chronic pathologies in patients who died, separately in men (n = 3,835) and women (n = 2,546). The average number of pathologies observed in women is 3.8 (median 4, Standard Deviation 2.0). In men the average number of pathologies observed is 3.5 (median 3, Standard Deviation 2.1). Table 3. Most common comorbidities observed in SARS-CoV-2 positive deceased patients by gender Women Diseases Men N % N % Ischemic heart disease Atrial Fibrillation Heart Failure Stroke Hypertension Type 2-Diabetes Dementia COPD (Chronic Obstructive Pulmonary Disease) 587 648 464 315 1,733 684 824 23.1 25.5 17.8 12.4 68.1 26.9 32.4 1,203 899 564 418 2,467 1,184 677 31.4 23.4 14.5 10.9 64.3 30.9 17.7 355 13.9 757 19.7 Active cancer in the past 5 years Chronic liver disease Chronic renal failure Dialysis Respiratory failure HIV Infection Autoimmune diseases Obesity Number of comorbidities 0 comorbidities 1 comorbidity 2 comorbidities 3 comorbidities and over 386 110 492 42 176 2 149 275 15.2 4.3 19.3 1.6 6.9 0.1 5.9 10.8 679 199 847 95 249 14 118 413 17.7 5.2 22.1 2.5 6.5 0.4 3.1 10.8 50 272 447 1,777 2.0 10.7 17.6 69.8 146 500 738 2,451 3.8 13.0 19.2 63.9 Table 4 presents the most common pre-existing chronic diseases in deceased patients divided into 4 age groups (16-59, 60-69, 70-79, 80+ years). The prevalence of ischemic heart disease, atrial fibrillation, heart failure, stroke, arterial hypertension, dementia, chronic renal failure, respiratory failure increase with age. On the other hand, prevalence of chronic liver disease, diseases for which dialysis is required, HIV infection, and obesity decrease with age increasing; for diabetes, COPD, and cancer prevalence decreases only in the last age group in contrast to the growth with age; for autoimmune diseases, on the contrary, prevalence increases only in the last age group, in contrast to the decreasing with age. As for the number of pathologies, the prevalence of those with 3 or more pathologies increases with age, while the prevalence of those with less than 3 pathologies decreases with age. For all the considered pathologies, the trend is statistically significant Table 4. Most common comorbidities observed in SARS-CoV-2 positive deceased patients by age-groups Age-groups 16-59 (n=445) 60-69 (n=652) 70-79 (n=1,597) 80+ (n=3,683) Total (n=6,377) Diseases Ischemic heart disease Atrial Fibrillation Heart Failure Stroke N 32 12 22 14 % 7.2 2.7 4.9 3.1 N 138 69 67 60 % 21.2 10.6 10.3 9.2 N 468 305 216 167 % 29.3 19.1 13.5 10.5 N 1,152 1,161 722 492 % 31.3 31.5 19.6 13.4 N 1,790 1,547 1,027 733 % 28.1 24.3 16.1 11.5 Hypertension 164 36.9 390 59.8 1,083 67.8 2,563 69.6 4,200 65.9 Type 2-Diabetes Dementia COPD (Chronic Obstructive Pulmonary Disease) Active cancer in the past 5 years Chronic liver disease Chronic renal failure Dialysis Respiratory failure HIV Infection Autoimmune diseases Obesity Number of comorbidities 0 comorbidities 1 comorbidity 2 comorbidities 3 comorbidities and over 104 13 23.4 2.9 220 40 33.7 6.1 567 181 35.5 11.3 977 1,267 26.5 34.4 1,868 1,501 29.3 23.5 34 7.6 83 12.7 313 19.6 682 18.5 1,112 17.4 74 16.6 125 19.2 330 20.7 535 14.5 1,064 16.7 33 49 19 20 10 30 130 7.4 11.0 4.3 4.5 2.2 6.7 29.2 40 96 18 27 2 35 142 6.1 14.7 2.8 4.1 0.3 5.4 21.8 97 310 45 96 3 55 206 6.1 19.4 2.8 6.0 0.2 3.4 12.9 139 884 55 282 1 147 210 3.8 24.0 1.5 7.7 0.0 4.0 5.7 309 1,339 137 425 16 267 688 4.8 21.0 2.1 6.7 0.3 4.2 10.8 46 115 103 181 10.3 25.8 23.1 40.7 41 121 150 340 6.3 18.6 23.0 52.1 50 217 321 1,009 3.1 13.6 20.1 63.2 59 318 610 2,696 1.6 8.6 16.6 73.2 196 771 1,184 4,226 3.1 12.1 18.6 66.3 5. Diagnosis of hospitalization In 90.7% of hospitalized persons who died and whose medical records were analysed (N=6,381), conditions (e.g. pneumonia, respiratory failure) or symptoms (e.g. fever, dyspnoea, cough) compatible with SARS-CoV2 were mentioned. In 554 cases (9.3% of cases) the diagnosis of hospitalization was not related to the infection. In 77 cases the diagnosis of hospitalization concerned exclusively neoplastic pathologies, in 184 cases cardiovascular pathologies (for example Acute Myocardial Infarction-AMI, heart failure, stroke), in 74 cases gastrointestinal pathologies (for example cholecystitis, perforation of the intestine, intestinal obstruction, cirrhosis), in 219 cases other pathologies. 6. Symptoms Figure 4 shows symptoms most commonly observed at hospital admission of hospitalized persons who died and whose medical records were analysed (N=6,381). Fever, dyspnoea and cough were the most commonly observed symptoms, while diarrhoea and haemoptysis were less commonly observed. Overall, 8.1% of patients did not present any symptoms at hospital admission. Figure 4. Most common symptoms observed in SARS-CoV-2 positive deceased patients 69 73 Fever Dyspnoea 33 Cough Diarrhea 6 Hemoptysis 1 0 20 40 60 80 100 (%) 7. Acute conditions Between patients whose medical records were analysed, Acute Respiratory Distress syndrome was observed in the majority of patients (94.0% of cases), followed by acute renal failure (24.4%). Superinfection was observed in 19.6% and acute cardiac injury in 10.8% of cases. 8. Treatments Antibiotics were used by 85.9% of patients during hospital stay, while less used were corticosteroids (53.3%) and antivirals (46.4%). Concomitant use of these 3 treatments was observed in 23.1% of cases. Out of SARS-CoV-2 positive deceased patients, 4.0% were treated with Tocilizumab during hospitalization. 9. Time-line Figure 5 shows, for SARS-CoV-2 positive deceased patients whose medical records were analysed (N=6,381), the median times, in days, from the onset of symptoms to death (12 days), from the onset of symptoms to hospitalization (5 days) and from hospitalization to death (7 days). The time from hospitalization to death was 6 days longer in those who were transferred to intensive care than those who were not transferred (12 days vs. 6 days). Figure 5. Median hospitalization times (in days) in SARS-CoV-2 positive deceased patients 12 Onset of symptoms --> Hospitalization 5 Hospitalization --> Death 7 Hospitalization --> Death (NO ICU) 6 12 0 5 Onset of symptoms --> Death 10 Hospitalization --> Death (YES ICU) 15 Median number of days 10. Comparison of death characteristics in the 3 quarters March-May 2020, June- September 2020, and October 2020 – January 2021 Table 5 summarizes the main characteristics of deaths with COVID-19 that occurred in 3 periods of time from the beginning of the pandemic in 2020: the initial quarter, March-May 2020, the second quarter, June-September 2020, and the third period October 2020 – January 2021. Overall, the sample represents 7.6% of all deaths from the beginning of the pandemic; in particular, the 13.5% of those who died between March and May 2020, 28.5% of those who died between June and September 2020, and 2.8% of those who died between October 2020 and January 2021. Deaths of people with 3 or more pre-existing pathologies increase and those of persons with fewer pathologies or none decrease: this seems to indicate that in the second and third periods deaths concern older people and persons with a pre-existing health condition worse than those dying in the first quarter (table 5). The use of drugs is also extremely different in the three periods, with a clear reduction in the use of antivirals and an increase in the use of steroids in the second and third periods. Table 5. Mean age, prevalence of women, number of pre-existing diseases, complications and treatments in deaths with COVID-19 in the 3 periods March-May 2020, June-September 2020, and October 2020– January 2021 All (n=6,381) March-May 2020 (n=4,532) June-Sept. 2020 (n=518) Oct. 2020 – January 2021 (n=1,331) pvalue* 79.1 78.5 81.1 80.7 <0.001 n (%) n (%) n (%) n (%) 2,546 (39.9) 1,743 (38.5) 267 (51.5) 536 (40.3) 0 196 (3.1) 169 (3.7) 8 (1.5) 19 (1.4) 1 772 (12.1) 608 (13.4) 44 (8.5) 120 (9.0) 2 1,185 (18.6) 915 (20.2) 70 (13.5) 200 (15.0) 3 or more 4,228 (66.3) 2,840 (62.7) 369 (76.4) 992 (74.5) 5,852 (94.0) 4,159 (95.1) 425 (83.3) 1,268 (94.2) <0.001 1,517 (24.4) 1,003 (22.9) 140 (27.5) 374 (27.8) <0.001 Acute cardiac injury 671 (10.8) 472 (10.8) 51 (10.0) 148 (11.0) 0.823 Superinfection 1,218 (19.6) 728 (16.7) 215 (42.2) 275 (20.4) <0.001 Antibiotics 5,378 (82.5) 3,830 (86.7) 438 (86.2) 1,110 (82.9) 0.002 Antivirals 2,903 (46.4) 2,606 (59.0) 162 (31.9) 135 (10.1) <0.001 Steroids 3,341 (53.3) 1,911 (43.3) 333 (65.6) 1,097 (81.9) <0.001 Tocilizumab 229 (4.0) 172 (4.4) 29 (5.9) 28 (2.2) <0.001 Sample of the evaluated clinical charts Mean age (years) Women <0.001 N of comorbidities Complications during hospitalization Acute Respiratory Distress Syndrome Acute renal failure <0.001 Treatments * p-value for difference between the 3 periods The distribution of the main pre-existing diseases in the different periods is presented in figure 6. The prevalence of atrial fibrillation, stroke, dementia, COPD, cancer, renal insufficiency, and obesity varies significantly in the three periods. These pathologies are more frequently diagnosed in the deceased in the second and third period than in the first (Figure 6). Figure 6. Pre-existing pathologies in deaths with COVID-19 in the 3 periods Comorbidities in deaths with COVID-19 according to the 3 periods of death % 70.0 60.0 50.0 40.0 30.0 20.0 10.0 0.0 * * * * * March-May 2020 * * June-September 2020 October 2020-January 2021 * p-value <0.05 Table 6 shows the durations, as median times (in days), from the symptoms onset to death, SARS-CoV-2 testing, and hospitalization, and from the hospitalization to death, in the 3 periods considered. Between the first and second period doubles the time that passes from the onset of symptoms to death, while it returns to the initial levels in the third period; the time from the onset of symptoms to the swab for the detection of SARS-CoV-2 infection decreases in the second period and remain stable in the third, as well as the time between the onset of symptoms and hospitalization; the median duration in days from hospitalization to death doubles between the first and second period; it decreases again in the third period. These results seem to suggest a greater reactivity of the Health System evidenced by the greater speed in carrying out diagnostic tests and hospitalization. Table 6. Median times (in days) between symptoms onset, PCR test, hospitalization and death in the 3 periods All (n=6,381) Times(in days) March-May 2020 (n=4,532) Median IQR Median IQR 12 7-20 12 4 2-8 4 7 From symptoms onset to death From symptoms onset to SARS-CoV-2 testing From symptoms onset to hospitalization From hospitalization to death June-Sept. 2020 (n=518) Oct. 2020 – January 2021 (n=1,331) Median IQR pvalue* Median IQR 7-19 23 10-57 12 7-19 <0.001 5 2-9 3 0-7 3 0-6 <0.001 2-7 4 2-7 3 1-7 3 1-7 <0.001 3-14 7 3-13 15 6-45 7 3-13 <0.001 * p-value for difference between the 3 periods IQR = Inter-Quartile Range The data here presented can be explained by a greater knowledge about the infection and a greater ability and timeliness of treatment in the period June-August in comparison to the previous quarter. In addition, it is likely that in the months of March and April SARS-CoV-2 infection was under-diagnosed in many frail elderly who died (such as those living in RSA). This may have led to an underestimation of the burden of the diseases in persons dying in that period This report was produced by SARS-CoV-2 Surveillance Group Members of the SARS-CoV-2 Surveillance Group Luigi Palmieri, Elvira Agazio, Xanthi Andrianou, Pierfrancesco Barbariol, Antonino Bella, Eva Benelli, Luigi Bertinato, Matilde Bocci, Stefano Boros, Giovanni Calcagnini, Marco Canevelli, Federica Censi, Alessandra Ciervo, Elisa Colaizzo, Martina Del Manso, Corrado Di Benedetto, Chiara Donfrancesco, Massimo Fabiani, Francesco Facchiano, Marco Floridia, Fabio Galati, Marina Giuliano, Tiziana Grisetti, Cecilia Guastadisegni, Yllka Kodra, Ilaria Lega, Cinzia Lo Noce, Pietro Maiozzi, Valerio Manno, Margherita Martini, Alberto Mateo Urdiales, Eugenio Mattei, Claudia Meduri, Paola Meli, Giada Minelli, Lorenza Nisticò, Graziano Onder, Lucia Palmisano, Daniele Petrone, Patrizio Pezzotti, Flavia Pricci, Ornella Punzo, Vincenzo Puro, Federica Quarata, Valeria Raparelli, Flavia Riccardo, Simone Rocchetto, Paolo Salerno, Giulia Sarti, Debora Serra, Matteo Spuri, Paola Stefanelli, Marco Tallon, Manuela Tamburo De Bella, Dorina Tiple, Marco Toccaceli Blasi, Federica Trentin, Brigid Unim, Luana Vaianella, Nicola Vanacore, Maria Fenicia Vescio, Emanuele Rocco Villani, Silvio Brusaferro.