International Journal of

Environmental Research
and Public Health

Review
The Epidemiological Characteristics of the COVID-19 Pandemic
in Europe: Focus on Italy
Giovanni Gabutti 1, *, Erica d’Anchera 2 , Francesco De Motoli 2 , Marta Savio 2 and Armando Stefanati 1

1 Department of Medical Sciences, University of Ferrara, via Fossato di Mortara 64/B, 44121 Ferrara, Italy;
[email protected]
2 Department of Medical Sciences, Postgraduate School of Hygiene and Preventive Medicine, University of Ferrara,
44121 Ferrara, Italy; [email protected] (E.d.); [email protected] (F.D.M.); [email protected] (M.S.)
* Correspondence: [email protected]

Abstract: Starting from December 2019, SARS-CoV-2 has forcefully entered our lives and profoundly
changed all the habits of the world population. The COVID-19 pandemic has violently impacted
the European continent, first involving only some European countries, Italy in particular, and then
spreading to all member states, albeit in different ways and times. The ways SARS-CoV-2 spreads are
still partly unknown; to quantify and adequately respond to the pandemic, various parameters and
reporting systems have been introduced at national and European levels to promptly recognize the
most alarming epidemiological situations and therefore limit the impact of the virus on the health of
the population. The relevant key points to implement adequate measures to face the epidemic include
identifying the population groups most involved in terms of morbidity and mortality, identifying the
events mostly related to the spreading of the virus and recognizing the various viral mutations. The
main objective of this work is to summarize the epidemiological situation of the COVID-19 pandemic





 in Europe and Italy almost a year after the first reported case in our continent. The secondary
Citation: Gabutti, G.; d’Anchera, E.; objectives include the definition of the epidemiological parameters used to monitor the epidemic,
De Motoli, F.; Savio, M.; Stefanati, A. the explanation of superspreading events and the description of how the epidemic has impacted on
The Epidemiological Characteristics health and social structures, with a particular focus on Italy.
of the COVID-19 Pandemic in Europe:
Focus on Italy. Int. J. Environ. Res. Keywords: COVID-19; SARS-CoV-2; epidemiology; preventive measures; public health; nursing
Public Health 2021, 18, 2942. https:// homes; intensive care unit; mortality; lethality; R0
doi.org/10.3390/ijerph18062942

Academic Editor: Paul B. Tchounwou

1. Introduction
Received: 27 January 2021
Accepted: 11 March 2021
The COVID-19 epidemic, after the initial spread starting from the city of Wuhan in the
Published: 13 March 2021
province of Hubei in China, has begun to spread to other continents, first Europe, violently
hitting member states and putting a strain on all health systems. [1]. Even before the
Publisher’s Note: MDPI stays neutral
pandemic was declared by the World Health Organization (WHO), the cases of COVID-19
with regard to jurisdictional claims in
were already beginning to significantly increase in some European states and then ended
published maps and institutional affil- up involving the continent as a whole. As of 12 January 2021, 84,532,824 confirmed cases
iations. were recorded in the world; in the European Union and the European Economic Area
(EU/EEA) 15,857,298 cases and 1,845,597 deaths were recorded [2].
The main objective of this work is to summarize the epidemiological situation of
COVID-19 pandemic in Europe and Italy almost a year after the first reported case in
our continent. The secondary objectives include the definition of the epidemiological
Copyright: © 2021 by the authors.
Licensee MDPI, Basel, Switzerland.
parameters used to monitor the epidemic, the explanation of superspreading events and
This article is an open access article
the description of how the epidemic has impacted on health and social structures, with a
distributed under the terms and particular focus on Italy.
conditions of the Creative Commons
Attribution (CC BY) license (https://
2. Epidemiological Parameters and Superspreading Events
creativecommons.org/licenses/by/ Several parameters can be used to appropriately describe the spreading dynamics of
4.0/). an infectious disease; among these, the fundamental one is the basic reproduction number

Int. J. Environ. Res. Public Health 2021, 18, 2942. https://doi.org/10.3390/ijerph18062942 https://www.mdpi.com/journal/ijerph
Int. J. Environ. Res. Public Health 2021, 18, 2942 2 of 14

(R0), which represents the average number of secondary infections produced from each
infected individual in a completely susceptible population. A value of R0 >1 assumes that
the pathogen is spreading and a value <1 indicates an epidemic potentially capable of
being contained. R0 is a value to be considered as a function of the number of contacts of
an infected person and the duration of the infectivity. This indicator alone is not enough to
adequately describe the spreading of the disease. Another factor, called Rt, helps make this
description; its definition is equivalent to that of R0 with the difference that Rt is calculated
over time. Rt allows, for example, to monitor the effectiveness of interventions adopted
during an epidemic. R0 and Rt can be calculated from daily case incidence. R0 and Rt differ
from each other; they are complementary and not contradictory. In Italy, R0 and Rt are used
to monitor the epidemiological trend of COVID-19. The Italian National Health Agency
(Istituto Superiore di Sanità, ISS) underlines that the two indicators are calculated on
slightly different data: Rt is calculated on the subgroup of non-imported cases and refers to
when these symptoms developed (considered by date of early symptoms). The ISS decided
to consider for the calculation of both R0 and Rt only symptomatic cases. The statistical
method of calculating Rt is defined as robust if it is calculated on a number of infections
identified according to sufficiently stable criteria in time. Criteria adopted in all Italian
regions to identify symptomatic cases or hospitalize most serious cases are almost the same,
and the number of this type of patients can be closely linked to the transmissibility of the
virus. On the other hand, the identification of asymptomatic infections depends a lot on
the ability of public health departments to perform screening tests and, unfortunately, this
can vary a lot over time, especially in the case of overloading of the health system [3,4].
Another particularly effective indicator in the epidemiological description of the
COVID-19 pandemic is the secondary attack rate (SAR), which defines the ability to become
infected in groups of susceptible individuals linked by close contacts, such as families
or in overcrowded spaces. Some studies during the COVID-19 pandemic have assumed
that the secondary attack rate can be as high as 35% if secondary cases originating from a
known index case in a restricted setting, such as a restaurant dinner or a family lunch, are
considered. In such situations, it is therefore of primary importance to promptly trace the
close contacts of the participants in these events to effectively reduce the transmission of
the virus [4,5].
These indicators can be supported by a further index, called factor K (coefficient of
dispersion K), useful for quantifying the individual differences of a single infected subject
to be able to transmit the infection to a susceptible contact. In practice, some subjects are
able to infect a large number of people while others have a lower ability to spread the
virus; a factor of K < 1 is indicated if the variation between the different subjects is large,
while K > 1 if it is not [4]. The factor K is of crucial importance for the correct framing
of the so-called super spreader events (SSEs) relatively common in infectious diseases’
epidemiology. Outbreaks sustained by an infectious subject infecting several contacts has
been described not only for COVID-19 but also for other infections such as tuberculosis
and measles. SSEs happen and are documented in coffee shops, restaurants, churches and
ships, as well as in health and social settings. In these cases, R0 is not useful to justify the
total number of infections [4,6].
Regarding the COVID-19 pandemic, several SSEs have been reported, highlighting
how many factors have a role in the spread of SARS-CoV-2. Taking into account the direct,
person-to-person, diffusion of the virus, there are individual factors that contribute to the
spread of viral particles such as speech characterized by a greater production of saliva
and therefore of droplets, the viral load, the site of greatest concentration of the virus (for
example, upper airways) and the availability of an infecting viral dose. Other ways of viral
spreading imply environmental factors such as staying in closed unventilated spaces, the
persistence of the virus on surfaces, the population density, the non-compliance rather than
the compliance with preventive regulations such as social distancing, hand hygiene and the
use of personal protective equipment. Finally, some social parameters must be considered,
such as the type of work (health workers in close contact with several people) and the
Int. J. Environ. Res. Public Health 2021, 18, 2942 3 of 14

lifestyle of the subject, who may be more or less prone to close contacts with different
people. For preventive purposes, it is absolutely relevant the early identification of cases
during these events and to quickly carry out a contact tracing, including a retrospective
investigation also of all contacts occurred before the index event in order to effectively slow
down the spread of SARS-CoV-2 [5–7].

3. European and Italian Surveillance Systems

The European Center for Disease Prevention and Control (ECDC) has established
community surveillance objectives for COVID-19 that can reconcile both the extreme
usefulness of having updated data, useful to modify the strategies for containing the
pandemic, and not to overload already overwhelmed health systems [8] (Table 1).

Table 1. ECDC targets of COVID-19 surveillance (modified from [8]).

Targets Actions
Monitor intensity, geographical to estimate the impact of the
spreading and disease’s severity disease on population
to address research for tailored
Identify new variants of the virus
therapies
European Level
Evaluate the impact
to optimize resource allocation
on health services
Evaluate the impact to evaluate timeline
of preventive measures and strength of interventions
Identify and control outbreaks to protect healthcare workers
in the healthcare setting and patients
National Level
Identify and control outbreaks in to protect groups at most risk
families and closed communities and with the possible worst outcome

The ECDC recognizes the real difficulty that European countries have in daily updat-
ing data and asks for at least a weekly report with aggregated data on the total number
of cases, a reduced dataset (case-based) on the most severe cases in at risk groups and a
weekly update on viral sequences. It also indicates, in order of relevance, the list of groups
to be tested as a priority in the case of limited resources, identifying health workers and the
elderly as priority groups, followed by hospitalized patients with respiratory symptoms
and finally all cases with even mild symptoms [8].
In Italy, national surveillance was arranged starting from 22 January 2020 and the
first criteria and reporting methods to the ISS Department of Infectious Diseases were
defined, identifying supervisors at regional level and in each autonomous province. The
ISS designed a dedicated computer platform where data had to be sent, collected and
analyzed at national level. Unfortunately, notification to ISS is available only 2–3 weeks
after the onset of the disease. In almost all cases, the swab for diagnosis is carried out after
the onset of first symptoms. This excludes the evaluation of the incubation period and
only in some cases a positive swab for SARS-CoV-2 is obtained from close contacts of a
patient. In addition, the speed of swab execution largely depends on local organization,
significantly different throughout the Italian territory due to demand and the availability
of medical staff as well as of laboratories [9].

4. Epidemiological Characteristics of SARS-CoV-2 Infection in Europe

Europe was the first continent heavily hit by SARS-CoV-2 pandemic after Asia. As of
6 December 2020, total cases in the European continent were 20,296,503 and deaths 449,793.
Of these, 56% were men and 89% were >65 years of age. In addition, 96% of people who
died from COVID-19 suffered from at least one other pathological condition. In particular,
82% of deceased subjects had a cardiovascular disease. The eight countries with the highest
number of cases are, in decreasing order: Russia, France, Italy, the United Kingdom, Spain,
Germany and Poland, with 12%, 11%, 8%, 8%, 8%, 6% and 5% of cases, respectively. As
Int. J. Environ. Res. Public Health 2021, 18, 2942 4 of 14

regards the total number of deaths, the United Kingdom ranks first (14% of total deaths),
followed by Italy, France, Spain and Russia with 13%, 12%, 10% and 10%, respectively [10].
In the EU/EEA region, the first cases of COVID-19 were identified at the end of January
2020. In France and Finland, cases were imported while in Germany a local transmission
occurred with an indirect epidemiological connection with Wuhan [11]. Following these
first notifications, Italy began to record a significant increase in COVID-19 cases due to
the clusters identified in the Veneto and Lombardy regions at the end of February [12].
Despite an initial and heavy involvement of Italy alone (February and March), SARS-CoV-2
considerably spread in other countries of the old continent. During the first week of March,
62% of cases in Europe were notified by Italy; within one month, in the first week of April,
Spain reported 21%, Italy 20%, Germany 15% and France 11% of cases in Europe and
then the whole continent was involved [13,14]. Since mid-March 2020, the number of new
diagnosed cases in the EU/EEA region considerably started to rise, accounting for an
increasing rate of non-Chinese cases; European countries begun to move rapidly towards
a sustained community transmission framework [15]. With the widespread presence of
SARS-CoV-2 at the community level, it was necessary to implement several preventive
measures, both collective (restrictive “stay at home” policies recommended or mandatory)
and individual (hand hygiene, respiratory hygiene and social distancing). Restrictive
measures adopted have not been univocal and concurrent in all European countries; in any
case, they led to a stabilization of the incidence. In fact, at the end of April 2020, the initial
transmission wave had exceeded its peak in twenty EU/EEA countries and a decreasing
incidence was reported (Figure 1) [16].
After a partial relief in summer, a resumption of incidence was observed during
the first week of July; however, there was not a unique explanation for this resurgence
of cases in different countries [17]. From the end of August, a further and increasingly
substantial rise in COVID-19 cases was observed throughout the EU/EEA region, initially
in young people and later also in adults and elderly. The continuous growth of positivity
index highlighted how this increase was no longer related only to the higher number of
tests performed or to the modified case definition but to a real increased transmission of
SARS-CoV-2 (Figure 1) [18]. Noteworthy, during spring, the most affected age group was
that of the >65-year-olds while from July 2020 the notification rates significantly increased
in the younger age classes (15–24 years and 25–49 years) [19].
The excess mortality related to COVID-19 during the first wave was particularly
relevant in Belgium, Italy, France, Ireland, Spain, the Netherlands, Sweden, Switzerland and
the United Kingdom. During the second wave, an excess of mortality was seen in Slovenia
and confirmed for the above-mentioned countries except for Sweden, Ireland and the
United Kingdom; the highest excesses mortality was found in ≥75-year-old subjects [19].
Despite the strong impact that COVID-19 had on population, in terms of both cases
and deaths (Figure 1), the level of herd immunity in most European nations at the end
of October was <15%, highlighting how the risk for the population was already high
before the winter season [18]. Since the end of October many European countries have
begun to implement and gradually re-establish the restrictive measures, previously already
adopted during the first months of the pandemic. Despite this, there has been a constant
and relevant increase in the transmission of SARS-CoV-2 as well as in COVID-19 cases,
particularly noteworthy in respect to levels reached during the first part of summer [20].
The difficulty of facing again a situation comparable to the first months of the pan-
demic has not only put a strain on health systems of all countries but also on the willingness
and ability to face a worsening emergency of the whole European population. This phe-
nomenon, characterized by the difficulty of accepting, again and positively, the restrictive
containment measures, is identified as “pandemic fatigue” [20]. Besides, the recent discov-
ery of several variants of SARS-CoV-2 has raised new concerns in the scientific community.
The presence of viral variants was expected, and there are currently several thousand
of them, most of which have not created any further threat to humans. Unfortunately,
there are also some concerning variants; the most worrying are the Danish (in mink),
Int. J. Environ. Res. Public Health 2021, 18, 2942 5 of 14

English, South African and Brazilian variants [21,22]. The role of an intermediate animal
in the spread of SARS-CoV-2 is widely discussed and the infection has been defined as a
zoonosis [23]. Although the initial stages of the pandemic were traced back to a Wuhan
wet market and several tests carried out on the cages and on the surfaces of the market
benches were SARS-CoV-2 positive, no tests carried out on animals were positive [24].
Nevertheless, SARS-CoV-2 transmission between different animal species is considered a
possible event. An example is the epidemic detected in mink starting from April 2020 in
Denmark. In this case, transmission can be bi-directional, from human to mink and from
mink to human [25]. It is currently believed that mink-related viral variants do not have
greater transmissibility or a more severe clinical course [25].The only fearsome variant is
the so-called “Cluster 5”, as it seems to have a lower antigenicity, and thus a lower chance
to be identified by diagnostic tests. It has been postulated that the presence of these new
variants could be related to transmission of SARS-CoV-2 by humans to mink, followed
by viral mutations and subsequently transmission back to humans [25]. In general, the
SARS-CoV-2 ability to infect animals depends on several factors, unfortunately not yet
fully understood. Among these, the compatibility between the viral protein S and the host
ACE-2 receptor is included [25]. Concerning the English variant (Variant of Concern, VOC
202012/01), the hypothesis of human–animal–human spreading seems very unlikely. The
hypothesis that SARS-CoV-2 was able to progressively accumulate mutations is not widely
accepted; in fact, the variant has an unusually high number of mutations of the spike
protein and has new genomic properties, compared to the scheme of random mutations
forecasted by models. A possible hypothesis concerns the genesis of the variant from a
single individual with “long-lasting” infection and compromised immune system. This
fact would have allowed SARS-CoV-2 to accumulate favorable mutations with the aim of
evading the immune system [22]. The greater transmissibility of this variant is of concern;
it has been estimated that R0 for the English variant has increased by 0.4% or more with
an increase in transmissibility equal to 70% [26]. The first cases caused by this variant
were recorded in September 2020, but a significant and sudden increase in cases in the
southern region of England was registered in November. Most cases involve <60-year-old
subjects [26] and at the end of December an increase in the severity of the clinical course
has not yet been found [22]. Unfortunately, cases due to this variant are not limited to the
United Kingdom but have also been found in other European (Belgium, Denmark, Fin-
land, France, Germany, Iceland, Ireland, Italy, The Netherlands, Norway, Portugal, Spain
and Sweden) and not European countries (Australia, Canada, Hong Kong, India, Israel,
Japan, Jordan, Lebanon, South Korea, Switzerland and Singapore) [22]. In addition, a third
variant of SARS-CoV-2, the South African variant (501.V2), has been circulating since last
August, and it is worrisome due to its greater transmissibility [22]. Finally, a fourth variant
needs to be monitored: the Brazilian (P.1). To date, it has only been identified in Brazil
and in travelers from Brazil. The risk for a spread in Europe of the variants mentioned
above is currently considered very high [21,22]. Besides, in almost all EU/EEA countries,
except Denmark, the ability to track and identify the spread of SARS-CoV-2 variants is very
limited [22]. As a matter of fact, since September 2020, only Denmark and Norway have
sequenced and published more than 1% of cases and only eight countries have sequenced
and published 0.1% of cases related to these new variants [22]. The SARS-CoV-2 positivity
of some gorillas has also recently been reported in the San Diego Zoo in the United States.
It has been speculated that animals became infected due to the presence of some positive
zoo operators; if so, this would be the first confirmed SARS-CoV-2 transmission between
primates [27].
The start of vaccination campaigns across Europe at the end of December certainly
brought a glimmer of hope; the epidemiological trend should positively reflect the rate of
vaccinated people which increases every day. As of 14 February 2021, 21,944,944 doses
have been administered in the EU/EEA countries [28]. However, several doubts are arising
on the management of vaccinated subjects in case of contact with a positive case. The
American Center for Disease Control recommends in a recently published document not to
 The start of vaccination campaigns across Europe at the end of December certainly
brought a glimmer of hope; the epidemiological trend should positively reflect the rate of
vaccinated people which increases every day. As of 14 February 2021, 21,944,944 doses
have been administered in the EU/EEA countries [28]. However, several doubts are aris-
Int. J. Environ. Res. Public Health 2021, 18, 2942 6 of 14
ing on the management of vaccinated subjects in case of contact with a positive case. The
American Center for Disease Control recommends in a recently published document not
to quarantine these subjects as long as they have completed the vaccination course (with
quarantine
the m-RNA these within
vaccine) subjectsno
as more
long as theythree
than havemonths
completed
andthe vaccination
have course [29].
no symptoms (withThere
the
m-RNA vaccine) within no more than three months and have no symptoms [29].
is currently no such recommendation in Europe, but it is certainly an issue that must soon There is
currently no such recommendation in Europe, but it is certainly an issue that must soon
be addressed and clarified. Unfortunately, the lack of data on the ability of vaccinees to
be addressed and clarified. Unfortunately, the lack of data on the ability of vaccinees to
transmit the virus makes it difficult to provide complete indications.
transmit the virus makes it difficult to provide complete indications.

Total cases reported weekly New cases reported weekly

25,000,000 2,000,000

1,800,000

20,000,000 1,600,000

1,400,000

15,000,000 1,200,000

1,000,000

10,000,000 800,000

600,000

5,000,000 400,000

200,000

0 0

Total deaths reported weekly New deaths reported weekly

600,000 40,000

35,000
500,000
30,000
400,000
25,000

300,000 20,000

15,000
200,000
10,000
100,000
5,000

0 0

Figure 1. Trend of COVID-19 cases and deaths in EU/EEA region, 2 March 2020–13 December 2020
Figure 1. Trend of COVID-19 cases and deaths in EU/EEA region, 2 March 2020–13 December 2020
(modified from [13,14,30–38]).
(modified from [13,14,30–38]).
5. Epidemiological Characteristics of SARS-CoV-2 Infection and COVID-19 in Italy
5. Epidemiological Characteristics of SARS-CoV-2 Infection and COVID-19 in Italy
5.1. General Epidemiology in Italy
5.1. General
In Epidemiology
Italy, accordingintoItaly
the latest update of the ISS of 22 December 2020, the SARS-CoV-2
epidemic
In recorded atototal
Italy, according number
the latest of cases
update equal
of the ISStoof1,963,023
22 December(Figure 2) [39,40]
2020, out of a
the SARS-CoV-
total population of 60,244,269 as reported by the ISTAT statistical yearbook
2 epidemic recorded a total number of cases equal to 1,963,023 (Figure 2) [39,40] out of published in a
total population of 60,244,269 as reported by the ISTAT statistical yearbook publishedain
2020 [41]. The impact of the second wave in terms of total diagnosed cases and, albeit to
2020 lesser extent,
[41]. The also of
impact of total symptomatic
the second wave incases,
termsis clearly
of totalhigher than that
diagnosed of the
cases and,first wave,
albeit to a
mainly due to the greater number of swabs performed, although from mid-November
lesser extent, also of total symptomatic cases, is clearly higher than that of the first wave,
a decline has been observed. The median age of those affected by the virus is equal to
mainly due to the greater number of swabs performed, although from mid-November a
48 years (range 0–109 years), a downward trend compared to the one recorded during the
decline
firsthas
twobeen observed.
months The median
of the epidemic age The
(60 years). of those
lowestaffected
value wasbyregistered
the virusinismid-August
equal to 48
yearswith
(range 0–109age
a median years), a downward
of about trend
30 years. From thecompared
month of May,to the
thereone recorded
was a decreaseduring
in casesthe
in all age groups, more markedly in subjects >50 years of age, which however showed a
new increase from mid-August. Since the end of September, cases considerably increased,
especially in the age groups 0–18 and 19–50 years, while from mid-November there was
again a decrease in all age groups. Females are the mostly affected gender (52.5%), while
males were mostly involved in the initial phase of the epidemic. Looking at the total
number of reported cases, the date of appearance of the first symptoms is available for
 first two months of the epidemic (60 years). The lowest value was registered in mid-Au-
gust with a median age of about 30 years. From the month of May, there was a decrease
in cases in all age groups, more markedly in subjects >50 years of age, which however
showed a new increase from mid-August. Since the end of September, cases considerably
increased, especially in the age groups 0–18 and 19–50 years, while from mid-November
Int. J. Environ. Res. Public Health 2021, 18, 2942 7 of 14
there was again a decrease in all age groups. Females are the mostly affected gender
(52.5%), while males were mostly involved in the initial phase of the epidemic. Looking
at the total number of reported cases, the date of appearance of the first symptoms is avail-
able for 1,037,226
1,037,226 out of 1,963,023
out of 1,963,023 subjects. subjects.
This gapThis gap is
is linked linked
both both
to the facttothat
the many
fact that many
subjects
subjects
were were asymptomatic
asymptomatic and to theand to the consolidation
consolidation of data
of data after someafter
time.someThetime.
timeThe time
elapsed
between diagnosis
elapsed between and the and
diagnosis datethe
of onset
date ofofonset
symptoms is available
of symptoms for 1,036,238
is available cases;
for 1,036,238
from
cases;the beginning
from of theofepidemic,
the beginning this ranged
the epidemic, 4–5 days
this ranged 4–5 daysuntiluntil
mid-June,
mid-June,andand then it
then
decreased to two days, although the decline was not regular over the months
it decreased to two days, although the decline was not regular over the months [39]. In [39]. In Italy,
notifications duringduring
Italy, notifications the first
thewave reached
first wave a peakain
reached March
peak with 113,011
in March diagnoses;
with 113,011 then,
diagnoses;
athen,
progressive decline
a progressive in April
decline (94,257)
in April and May
(94,257) was registered,
and May mainly
was registered, as a result
mainly of the
as a result of
national lockdown
the national announced
lockdown on 11
announced onMarch 20202020
11 March [42].[42].

Figure 2.
Figure 2. Diagnosed
Diagnosedand asymptomatic
and cases,
asymptomatic 29 January
cases, 2020–22
29 January December
2020–22 2020 (modified
December from
2020 (modified
[40]).
from [40]).

5.2.
5.2. Cases Stratified
Stratified by
by Regions
Regions
During
During thethe early
early stages
stages of
of epidemic,
epidemic, the geographic spread spread was very heterogeneous;
heterogeneous;
for
for this
this reason,
reason, the
the Italian
Italian provinces
provinces were
were divided
divided into
into three
three groups
groups accordingly
accordingly to to the
the
distribution
distribution of of standardized
standardized incidence
incidence rates
rates (“low”,
(“low”, “medium”
“medium” and and “high”
“high” spread).
spread). TheThe
low
low prevalence
prevalence provinces (34, mainly
provinces (34, mainly those
those ofof the
theSouth
SouthandandthetheIslands)
Islands)arearethose
thosewith
witha
arate
rate<60
<60cases
casesper
per100,000
100,000residents;
residents;thethe medium-spread
medium-spread provinces
provinces (32, (32, mostly those of
mostly those of
Central
Central Italy) have a rate between 60 and 150 cases per 100,000 residents; and
Italy) have a rate between 60 and 150 cases per 100,000 residents; and the
the high
high
circulation
circulation group
group includes
includes those
those provinces
provinces (41,(41, especially
especially in
in Northern
Northern Italy)
Italy) with
with aa rate
rate
>150
>150 cases
cases per
per 100,000
100,000 residents. [42]
residents.[42]
As
As of
of 22
22 December
December 2020,2020, the
the regions
regions that
that reported
reported the
the highest
highest number
number of of cases
cases were
were
Lombardy,
Lombardy, Veneto and Piedmont with 469,991 (23.9%), 222,868 (11.4%) and 186,045cases
Veneto and Piedmont with 469,991 (23.9%), 222,868 (11.4%) and 186,045 cases
(9.5%),
(9.5%), respectively.
respectively. On Onthethecontrary,
contrary,the theregions
regionswith
withthethe lowest
lowest number
number of of subjects
subjects af-
affected
fected by the virus were Molise, Aosta Valley and Basilicata with 6139 (0.3%), 7096 (0.4%)
by the virus were Molise, Aosta Valley and Basilicata with 6139 (0.3%), 7096 (0.4%)
and
and 9864
9864cases
cases(0.5%),
(0.5%),respectively.
respectively.ItItshould
shouldbebenoted
notedthat the
that Aosta
the Aosta Valley,
Valley,while
whilereporting
report-
a not particularly high number of cases, has a cumulative incidence per 100,000 inhabitants
ing a not particularly high number of cases, has a cumulative incidence per 100,000 inhab-
even higher than that of Lombardy (5654.14 vs. 4651.55 per 100,000). In addition, the
itants even higher than that of Lombardy (5654.14 vs. 4651.55 per 100,000). In addition,
autonomous province of Bolzano, with a cumulative incidence of 5183.99 per 100,000
the autonomous province of Bolzano, with a cumulative incidence of 5183.99 per 100,000
inhabitants and a total of 27,583 diagnosed cases, precedes Lombardy (Table 2). Most
inhabitants and a total of 27,583 diagnosed cases, precedes Lombardy (Table 2). Most
(87.1%) cases were diagnosed in 10 regions: Lombardy, Veneto, Piedmont, Campania,
(87.1%) cases were diagnosed in 10 regions: Lombardy, Veneto, Piedmont, Campania,
Emilia-Romagna, Lazio, Tuscany, Sicily, Puglia and Liguria [39].
Emilia-Romagna, Lazio, Tuscany, Sicily, Puglia and Liguria [39].
There are several possible causes at the basis of a faster and greater spread of the virus
in the regions of Northern Italy (more central geographical location, greater migratory
flows from abroad, less time, resources and the absence of protocols to better face the
emergency in the early stages). A detailed discussion of this is beyond the scope of this
manuscript; however, all of this cannot be reduced to a simple difference in terms of
population density, as shown in Table 2 [41].
 virus in the regions of Northern Italy (more central geographical location, greater migra-
tory flows from abroad, less time, resources and the absence of protocols to better face the
emergency in the early stages). A detailed discussion of this is beyond the scope of this
manuscript; however, all of this cannot be reduced to a simple difference in terms of pop-
Int. J. Environ. Res. Public Health 2021,ulation
18, 2942 density, as shown in Table 2 [41]. 8 of 14

Table 2. Regions with higher and lower cumulative incidence per 100,000 inhabitants (modified
from [39,41]).
Table 2. Regions with higher and lower cumulative incidence per 100,000 inhabitants (modified
Region/ Population Density Cumulative Incidence
from [39,41]).
Autonomous Province (Inhabitants/km2) per 100,000
Aosta Valley
Region/Autonomous 38 Density
Population 5654.14
Cumulative
Province (Inhabitants/km2) Incidence per 100,000
AP Bolzano 72 5183.99
Higher incidence Aosta Valley
Lombardy 42338 5654.14
4651.55
AP
VenetoBolzano 26872 5183.99
4541.19
Higher incidence Lombardy 423 4651.55
Piedmont
Veneto 171268 4285.39
4541.19
Molise
Piedmont 68171 2031.00
4285.39
Basilicata
Molise 5568 1771.13
2031.00
Lower incidence Sicily
Basilicata 19255 1707.49
1771.13
Lower incidence Sicily
Sardinia 68192 1707.49
1529.49
Sardinia 68 1529.49
Calabria
Calabria 126126 1155.61
1155.61

5.3.
5.3. Severity
Severityofofthe
theClinical
ClinicalCourse
Course
One
One of the main differences observed
of the main differences observed between
between the the first
first weeks
weeks after
after the
the onset
onset of
of the
the
epidemic and the following months concerns the course and the severity
epidemic and the following months concerns the course and the severity of the infection. of the infection.
In
In fact, while initially
fact, while initiallythere
therewaswasa ahigher
higherraterate
of of severe
severe cases
cases andand deaths
deaths already
already at theattime
the
time of diagnosis
of diagnosis (swabs(swabs carried
carried out post-mortem),
out post-mortem), subsequently
subsequently an increase
an increase in asympto-
in asymptomatic
matic or pauci-symptomatic cases was observed as well as a
or pauci-symptomatic cases was observed as well as a marked reduction of severemarked reduction of severe
cases
cases and deaths
and deaths [39]. [39].
Figure
Figure 33 shows
shows thethetrend
trendofofhospitalizations
hospitalizations duedue to COVID-19
to COVID-19 in period
in the the period 20 Feb-
20 February–
ruary–22
22 DecemberDecember
2020. 2020. The distribution
The distribution is biphasic
is biphasic withwith
the the
firstfirst
peak peak in the
in the early
early stages
stages of
of epidemic
epidemic (March),while
(March), whilethethesecond
secondisisininNovember.
November.ItItisisworth
worth noting
noting that
that data
data for
for the
the
month
month of of December
December may may still
still be
be incomplete
incomplete duedue toto an
an update
update delay
delay [40].
[40].

Figure3.
Figure Trend of
3. Trend of hospitalizations
hospitalizationsdue
dueto
toCOVID-19,
COVID-19,20
20February
February20–22
20–22December
December2020
2020(modified
(modified
from [40]).
from [40]).
5.4. Mortality and Lethality
5.4. Mortality and Lethality
Deaths updated to 22 December 2020 account for 67,540 [39]. The distribution of
COVID-19 mortality presented a double peak over the year: the first in the period March–
May and the second between October and December. A sharp decline was observed during
the summer season (Figure 4) [40]. Based on the ISS report on deceased patients updated
to 16 December 2020, the region with the highest number of deaths was Lombardy with
24,070 cases (37.9%), followed by Emilia-Romagna (6718, 10.6%) and Piedmont (5543, 8.7%).
Calabria, Basilicata and Molise were the regions with the lowest number of deaths, 325
(0.5%), 174 (0.3%) and 170 (0.3%), respectively. The average age of deceased subjects was
80 years (median 82); 42.4% of deaths involved women (25,185). The median age was
 325 (0.5%), 174 (0.3%) and 170 (0.3%), respectively. The average age of deceased subjects
was 80 years (median 82); 42.4% of deaths involved women (25,185). The median age was
equal to 85 and 80 years in women and men, respectively. Data concerning the age dif-
fered considerably from that concerning the above-mentioned median age of diagnosis;
the total number of deceased subjects <50 and <40 years of age was 737 and 190, respec-
Int. J. Environ. Res. Public Health 2021, 18, 2942 9 of 14
tively. Data on pre-existing pathologies were available from 5962 deceased patients after
hospitalization; the mean number of diseases observed in this population was 3.6. Hyper-
tension was the most frequent condition found in both genders (68.7% in females vs. 64.2%
in males).
equal to 85Women with dementia
and 80 years in womenand andtype
men,IIrespectively.
diabetes mellitus
Data rank secondthe
concerning andagethird place
differed
(32.1% and 26.7%),
considerably from that followed
concerning by the
atrial fibrillation (25.6%)
above-mentioned medianandageischemic heartthe
of diagnosis; disease
total
number
(23.4%). of Indeceased
men, typesubjects <50 mellitus
II diabetes and <40 and
yearsischemic
of age was 737disease
heart and 190, respectively.
showed Data
overlapping
on pre-existing
rates (30.7% andpathologies were available
30.8%), followed from
by atrial 5962 deceased
fibrillation patients
(23.4%) after hospitalization;
and chronic renal failure
the mean
(22.2%) [43]. number of diseases observed in this population was 3.6. Hypertension was the
most Thefrequent condition
lethality found showed
of the disease in both agenders
relevant(68.7%
increasein according
females vs. 64.2%
to age, in males).
reaching the
Women
maximum with
in dementia andage
the ≥90 years type II diabetes
class (36.0% inmellitus
males andrank20.4%
second and thirdTotal
in females). placelethality
(32.1%
and
was 26.7%),
4.1% in followed
men and 2.9%by atrial fibrillation
in females. (25.6%)
Lethality was and ischemic
also heart
higher in malesdisease (23.4%).
of all age In
groups;
men, type II diabetes
the lethality value was mellitus
close and
to 0 ischemic heart disease
in both genders in theshowed overlapping
0–29 years age group.ratesAs(30.7%
of 22
and 30.8%),2020,
December followed by atrial
the healed fibrillation
subjects were (23.4%)
1,151,639 and chronic renal failure (22.2%) [43].
[39].

Figure 4.
Figure 4. Daily
Daily deaths
deaths due
due to
to SARS-CoV-2,
SARS-CoV-2,21
21February–22
February–22December
December2020
2020(modified
(modifiedfrom
from[40]).
[40]).

The lethality
Taking of the disease
into account the totalshowed
numberaofrelevant increase
deaths for according
all causes, to age, reaching
the provisional toll for
the
the maximum in the ≥90 years2020
period January–November age amounted
class (36.0%
to in malesdeaths,
664,623 and 20.4% in females).
i.e., 77,136 Total
more deaths
lethality
than thewas 4.1%registered
average in men andin2.9% in females.
the period Lethality
2015–2019. Onwas
the also higher
other hand,inconsidering
males of allonly
age
groups;
the periodthewhen
lethality value
deaths wasCOVID-19
from close to 0 are
in both genders
included in the 0–29 years age
(February–November group.
2020), the As
ex-
of 22 mortality
cess Decemberis2020,eventhehigher
healed(83,985
subjects were 1,151,639
deaths). [39]. the ratio between reported
Noteworthy,
Taking
deaths and into account
excess the total
mortality in thenumber
periodofFebruary–November
deaths for all causes,(69%)
the provisional tollinto
did not take for
the period January–November 2020 amounted to 664,623 deaths, i.e.,
account the actual impact of COVID-19 and November’s data are not yet consolidated77,136 more deaths
than
[44]. the average registered in the period 2015–2019. On the other hand, considering only
the period when deaths from COVID-19 are included (February–November 2020), the
excess mortality is even higher (83,985 deaths). Noteworthy, the ratio between reported
deaths and excess mortality in the period February–November (69%) did not take into
account the actual impact of COVID-19 and November’s data are not yet consolidated [44].

5.5. Epidemiology in Nursing Homes in Italy

Nursing homes (RSAs) are structures used to take care of elderly people affected
by multiple morbidity as well as of not self-sufficient subjects. Other factors that can
contribute to worsening the health of guests of these structures, and consequently increase
the risk of death, include detachment from affects and the loss of one’s daily life activities,
which negatively affect the patient’s mental well-being [45]. After the outbreak of the
COVID-19 epidemic in Italy, healthcare residences and post-acute hospitals were probably
the most affected care settings, due to both the positivity to the virus of patients and
healthcare personnel and the high number of deaths that occurred in a short time. What
has happened in recent months and is still happening now has caused enormous uproar
and concern in the population and triggered the launch of judicial investigations aimed at
Int. J. Environ. Res. Public Health 2021, 18, 2942 10 of 14

identifying any accountability. The high number of victims in nursing homes is probably
the result of a rapid contagion in these cohorts of fragile subjects, rather than of actual
organizational/structural deficiencies of the structures themselves. [46] A report published
by the Lombardy region concerning the analysis of deaths from COVID-19 in the RSAs of
the Metropolitan City of Milan highlighted how the mortality within these structures in
>70 years of age patients actually increased in 2020 when compared to the previous four
years (2016–2019). This increase clearly started in March 2020; peaks of at least 80 deaths
per day were registered in the first two weeks of April 2020 compared to an average of
about 20 per day in the previous four years. These data are even more significant if we
consider that at the beginning of 2020 the average of deaths in this cohort of subjects was
lower than the average registered in the 2016–2019 period. The increase in the overall risk
of death from 1 January to 30 April 2020 was therefore estimated to be two times higher
than the mortality reference value observed in the period 2016–2019. In the period from
1 March to 30 April 2020 the risk of death increased about four times [46]. In the same
region, a study analyzed the 2020 mortality data in the provinces of Mantua and Cremona
in comparison to the previous two years, evaluating deaths in the general population and
in the >75-year-old RSA residents. Although the risk of death within these structures
was already higher than that registered in the non-institutionalized population in the pre-
COVID-19 era (about 2–3 times in 2018–2019), the study showed that, during the pandemic,
the risk of death worsened becoming about seven times greater compared to that of the
general population. These estimates were done evaluating and eliminating any bias due to
demography and health state [45].
The ISS launched a survey on COVID-19 in RSAs from 24 March 2020 involving
3292 structures (96% of those present on the national territory). At the end of the survey
(5 May 2020), approximately 41% (1356) of the structures provided data. The regions that
involved more structures were Lombardy (292), Piedmont (249) and Tuscany (200), and in
total 97,521 residents were reported as of 1 February 2020 with an average of 72 residents
per evaluated facility (range 7–632). [47]
Table 3 reports the total number of RSA residents by region as of 1 February 2020, the
total deaths since this date due to any cause, the total deaths due to confirmed COVID-19
and the total number of patients who have died with no diagnosis of COVID-19 but with
flu-like symptoms. As of 1 February 2020, 9154 deaths were registered among residents,
considering all causes of death; 680 deaths were due to confirmed COVID-19 disease and
3092 due to flu-like symptoms (7.4% and 33.8% of the total deaths occurring within these
facilities, respectively) [47].
As noted above, the involvement of nursing homes was linked to not only the conta-
gion of residents but of health workers as well. At the national level, it has been highlighted
that, taking into account the survey conducted by the ISS, the regions with the higher
rates of structures with infected personnel were the autonomous provinces of Bolzano
(50.0%) and Trento (46.7%), followed by Lombardy (40.0%), Piedmont (25.0%), Marche
(23.5%), Emilia-Romagna (18.1%), Veneto (16.6%), Liguria (15.8%) Friuli Venezia Giulia
(12.8%) and Tuscany (12.4%); values <10% or equal to zero were reported for the other
regions. However, this evaluation is affected by the number of swabs performed in each
local context. The explanation for this high number of infections and deaths could be
related to what has been reported by evaluated structures. Among these, 77.2% reported
the lack of Personal Protective Equipment, 33.8% the absence of health personnel, 26.2%
the difficulty in isolating residents affected by COVID-19 and 20.9% the lack of adequate
instructions on how to cope with the infection. In addition, 12.5% of the evaluated nursing
homes had difficulty in transferring residents affected by COVID-19 to hospitals and 9.8%
reported a lack of drugs. Finally, 282 nursing homes declared the impossibility of having
swabs performed. However, as this last question was included on 8 April 2020, this last
datum refers to 52.1% of the structures taking part to the survey (541). Almost all structures
decided to block visits to residents by family members and/or caregivers. This measure
was implemented by 9 March 2020 by approximately 90% of the structures involved in the
Int. J. Environ. Res. Public Health 2021, 18, 2942 11 of 14

survey. Many facilities (68.5%) also reported having resorted to alternative forms instead
of visit, such as video calls or phone calls and e-mails [47]. Since 9 March 2020, in the
provinces of Mantua and Cremona, in addition to the access ban for visitors, recreational
activities were suspended, physical distancing measures were implemented and access
to work for staff with symptoms was banned [45]. In addition, the possibility of isolating
the patient with suspected or confirmed infection was another measure adopted, even if
differently in each structure (single rooms, dedicated structures, etc.). However, 8% of 1351
involved nursing home reported the impossibility of isolating the patient [47].

Table 3. Total of residents in nursing homes involved in the survey on 1 February 2020, total deaths due to all causes, total
deaths due to confirmed COVID-19 and total deaths in subjects with flu-like symptoms since 1 February 2020 (modified
from [47]).

Total Residents at Deaths Due to All Deaths Due to Deaths Related to Flu-Like
Region
1 February 2020 Causes (N) COVID-19 (N; % *) Symptoms (N; % *)
Abruzzo 410 47 1 (2.1) 0 (0)
Bolzano AP 418 28 3 (10.7) 10 (35.7)
Calabria 1510 75 0 (0) 1 (1.3)
Campania 626 50 6 (12) 13 (26)
Emilia-Romagna 7906 639 81 (12.7) 265 (41.5)
FVG 3491 222 6 (2.7) 41 (18.5)
Lazio 4439 158 1 (0.6) 28 (17.7)
Liguria 1515 136 20 (14.7) 34 (25)
Lombardy 26,981 3793 281 (7.4) 1807 (47.6)
Marche 1280 160 13 (8.1) 59 (36.9)
Molise 228 24 0 (0) 2 (8.3)
Piedmont 16,629 1658 161 (9.7) 410 (24.7)
Puglia 2056 111 0 (0) 4 (3.6)
Sardinia 568 67 0 (0) 17 (25.4)
Sicily 930 73 0 (0) 11 (15.1)
Tuscany 9245 640 36 (5.6) 154 (24.1)
Trento AP 1189 99 33 (33.3) 45 (45.5)
Umbria 719 38 0 (0) 11 (28.9)
Veneto 17,381 1136 38 (3.3) 180 (15.8)
TOTAL 97,521 9154 680 (7.4) 3092 (33.8)
AP, Autonomous Province; FVG, Friuli-Venezia-Giulia; * the rates reported for each region are calculated on the total of deaths due to all
causes in the region itself.

6. Conclusions
The year 2020 will certainly be remembered for the COVID-19 pandemic that endan-
gered our lives, putting a strain on the political, economic and social health balances of the
various states of the world and undermining the certainties of millions of individuals. The
current epidemiological situation is constantly evolving and remains serious.
An increase in COVID-19 cases was observed in Europe and Italy in the early months
of 2021 [48,49]. In Italy, in particular, there was an increase in the incidence of COVID-19 in
the younger age groups (0–18 years) and a significant increase in pressure on the prevention
departments which led to a delay in notification. and in updating epidemiological data. [48]
Continuing the monitoring of the indicators, also paying more attention to super-
spreader events by concentrating and intensifying tracking procedures and acting promptly
as soon as changes in the epidemiological trend are detected is also fundamental to try to
contain the spread of new variants of SARS-CoV-2. The strengths we currently have to keep
the epidemiological situation under control are certainly the vaccination campaigns started
at the end of last December, the increasing knowledge about SARS-CoV-2, the attention
that is paid to the identification of new variants and the implementation of both individual
and collective preventive measures. Unfortunately, there are also difficulties: the inability
of most European countries to sequence the minimum number of samples required by
ECDC, the continuous variation of the spreading dynamics of SARS-CoV-2 and the fatigue
Int. J. Environ. Res. Public Health 2021, 18, 2942 12 of 14

of the health systems. The main future issue certainly concerns the possible appearance of
new variants with even higher transmissibility and a worse clinical course; this issue is
directly linked to the ability of European countries to quickly implement the resources to
be dedicated to molecular biology in terms of both equipment and human resources. A sec-
ond emerging issue is that concerning the duration of immunity in vaccinated individuals.
Knowing how long an immunized person is protected from COVID-19 and whether he
can still transmit the virus or not is a fundamental step in managing the pandemic from a
public health perspective. In addition, as long as the rate of vaccinated individuals does
not grow to the target required for the development of herd immunity, it is of fundamental
relevance that European countries comply with the indications provided by the ECDC
and do their utmost to implement a flawless case surveillance. From this point of view,
the greatest difficulties certainly arise when the infections grow rapidly and suddenly, as
happened last autumn; therefore, keeping the trend of infections at a stable level or even
better to a decreasing level is to be considered a winning point in this phase. Finally, what
has emerged during the recent months of the pandemic, in Italy as in the rest of the world,
is the awareness of how important it is for a country to have a solid and efficient public
health system. This topic, which has been the subject of debate for years, will represent
an even more critical point in the near future from which to restart and on which to base
health policies at European and global level. The strengthening of health systems as well as
the centralization of key issues such as health promotion and prevention must be a priority
to avoid a recurrence of an emergency of this magnitude in the coming years.

Author Contributions: E.d., F.D.M. and M.S. equally contributed to this work with: conceptual-
ization, writing—original draft preparation and writing—review and editing, A.S. and G.G.; and
writing—review and editing, visualization, supervision and project administration. All authors have
read and agreed to the published version of the manuscript.
Funding: This research received no external funding.
Institutional Review Board Statement: Not applicable.
Informed Consent Statement: Not applicable.
Data Availability Statement: No new data were created or analyzed in this study. Data sharing is
not applicable to this article.
Conflicts of Interest: A.S., E.d., F.D.M. and M.S. declare no conflict of interest. G.G. declares that
he does not have a specific conflict of interest related to this paper; however, he reports grants
from Sanofi Pasteur MSD, GSK Biologicals SA, Pfizer, Sanofi Pasteur Italy, MSD Italy, Emergent
BioSolutions and Seqirus for taking part in advisory boards, expert meetings, acting as speaker
and/or organizer of meetings/congresses and acting as principal investigator and chief of OU
in RCTs.

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