)Ministry of Education and Scientific Research)

)Al-Muthanna University College of Medicine)

Data: 2020/4/

Student Name : Hussein Haider Ahmayed.

Stage: 4th

Subject : Justification of differences

in Mortality rates due to COVID-19 in(Italy, China and

Germany).

Supervise by : Dr. Aamir Sabr Oudah & dr. suha.

COVID-19
Coronavirus disease 2019 (COVID-19) is an emerging respiratory
infectious disease caused by the severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2), which was first detected in early December
2019 in Wuhan, China. As of April 6, 2020, COVID-19 had quickly spread
to the majority of countries worldwide, affected more than 1.1 million
individuals, and caused nearly 63 000 deaths. Although studies have
described the clinical characteristics of patients with COVID-19,2 and a
previous study has reported the early transmission dynamics of the first 425
confirmed cases in Wuhan, more recent data are required to illustrate the
full spectrum of the epidemiological characteristics of the outbreak in the
epicenter.
Several modeling studies have used the international cases exported from
Wuhan to extrapolate the severity of the epidemic, estimating that the
Wuhan travel ban delayed the epidemic progression by 3 to 5 days in
mainland China, while reducing case importations to other countries by
nearly 80% through mid-February. However, to our knowledge, no study
has yet comprehensively evaluated the association of various public health
interventions implemented by the Chinese government (including but not
limited to intensive intracity and intercity traffic restriction, social
distancing measures, home isolation and centralized quarantine, and
improvement of medical resources; Figure 1 with outbreak control within
Wuhan city.
In this study, the epidemiological characteristics of patients with COVID-
19 in Wuhan through March 8, 2020, were described, and the rate of
confirmed cases and effective reproduction number in different periods
according to key events and interventions were compared to evaluate the
temporal associations of multiple public health interventions with control
of the COVID-19 outbreak in Wuhan.
Figure 1. The Epidemic Curve, Key Events and Features, and Public Health Interventions Across the 5 Periods
During the COVID-19 Outbreak in Wuhan, China

Source of Data in china

Characteristics of patients with COVID-19 from December 2019 through March 8,

2020, were extracted on March 9 from the municipal Notifiable Disease Report
System, including birth date, sex, occupation, residential district, date of symptom
onset (the self-reported date of symptoms such as fever, cough, or other respiratory
symptoms), and date of confirmed diagnosis (the laboratory confirmation date of
SARS-CoV-2 infection in the biosamples). A case was recorded as a health care
worker if the patient reported working in a hospital or clinic. Waiver of informed
consent for collection of epidemiological data from patients with COVID-19 was
granted by the National Health Commission of China as part of the infectious
disease outbreak investigation. All identifiable personal information was removed
for privacy protection.
 Real estimates of mortality following COVID-19 infection

As of March 1, 2020, 79 968 patients in China and 7169 outside of China had tested
positive for coronavirus disease 2019 (COVID-19).

Among Chinese patients, 2873 deaths had occurred, equivalent to a mortality rate
of 3·6% (95% CI 3·5–3·7), while 104 deaths from COVID-19 had been reported
outside of China (1·5% [1·2–1·7]). However, these mortality rate estimates are
based on the number of deaths relative to the number of confirmed cases of
infection, which is not representative of the actual death rate; patients who die on
any given day were infected much earlier, and thus the denominator of the
mortality rate should be the total number of patients infected at the same time as
those who died. Notably, the full denominator remains unknown because
asymptomatic cases or patients with very mild symptoms might not be tested and
will not be identified. Such cases therefore cannot be included in the estimation of
actual mortality rates, since actual estimates pertain to clinically apparent COVID-
19 cases.

The maximum incubation period is assumed to be up to 14 days, whereas the

median time from onset of symptoms to intensive care unit (ICU) admission is
around 10 days. Recently, WHO reported that the time between symptom onset
and death ranged from about 2 weeks to 8 weeks.

We re-estimated mortality rates by dividing the number of deaths on a given day by

the number of patients with confirmed COVID-19 infection 14 days before. On this
basis, using WHO data on the cumulative number of deaths to March 1, 2020,
mortality rates would be 5·6% (95% CI 5·4–5·8) for China and 15·2% (12·5–17·9)
outside of China. Global mortality rates over time using a 14-day delay estimate are
shown in the figure, with a curve that levels off to a rate of 5·7% (5·5–5·9),
converging with the current WHO estimates. Estimates will increase if a longer
delay between onset of illness and death is considered. A recent time-delay
adjusted estimation indicates that mortality rate of COVID-19 could be as high as
20% in Wuhan, the epicentre of the outbreak.

These findings show that the current figures might underestimate the potential
threat of COVID-19 in symptomatic patients.
Figure Global COVID-19 mortality rates (Feb 11 to March 1, 2020)
Current WHO mortality estimates (total deaths divided by total confirmed cases), and mortality rates calculated by dividing
the total number of deaths by the total number of confirmed cases 14 days previously.

 The epidemic curve of onset of symptoms peaked around January 23rd to 26th,
then began to decline up to February 11th. Most cases were aged 30 to 79 years
of age (87%), 1% aged ≤ 9 years, 1% aged 10 to 19 years, and 3% 80 years or
older.
Age (deaths/cases) CFR (95% CI)
≤ 9 years (0/416) 0%
10 to 19 years (1/549) 0.18% (0.03 to 1.02%)
20 to 49 years (63/19790) 0.32% (0.25% to 0.41%)

50 to 59 years (130/10,008) 1.3% (1.1% to 1.5%)

60 to 69 years (309/8583) 3.6% (3.2% to 4.0%)

70 to 79 years (312/3918) 8.0% (7.2% to 8.9%)
≥80 years (208/1408) 14.8% (13.0% to 16.7%)

Patients with comorbid conditions had much higher CFR rates. Those with no
comorbidites had a CFR of 0.9%. Critical cases had a CFR of 49%, no deaths
occurred among those with mild or even severe symptoms.

 Critical cases: respiratory failure, septic shock, and/or multiple organ

dysfunction/failure.
 Severe: dyspnea, respiratory rate ≥30/min, oxygen sats ≤93%, PaO2/FiO2 ratio
<300, lung infiltrates >50% within 24–48 hrs
Limitation: some variables (i.e., comorbid condition and case severity) are not
required fields in the Chinese CDC Infectious Disease Information System, some
records have missing data.

Why is cardiovascular disease (CVD) so

prevalent in those who died with COVID-19?
Most acute viral infections have three short-term effects on the CVD system: the
inflammatory response can increase the risk of an acute coronary syndrome;
depression of the myocardium can worsen heart failure, and inflammation can
unmask heart arrhythmias. Seasonal influenza infections can increase CVD deaths
significantly, and community-level rises in Influenza-like illness (ILI) lead to rises in
CVD mortality:

Nature Medicine: Estimating the clinical severity of COVID-19 from the

transmission dynamics in Wuhan, China~:

 Those with coronavirus symptoms in Wuhan, China, had a 1.4% (95% CI,
0.9% to 23.1%) chance of dying,
 29th February, the crude CFR case risk, outside Hubei was 0.85%,
 Risk of symptomatic infection increased with age, maybe preferential
ascertainment of older and more severe cases. *

*Because Wuhan prioritized the admission of more severe cases, the sCFR will be
substantially lower than the HFR. *sCFR (s for symptomatic) defines a case as
someone who is infected and shows certain symptoms; HFR (hospitalized) defines a
case as someone who is infected and hospitalized.
Estimates of basic reproductive number, mean serial interval, initial doubling time, intervention effectiveness,
ascertainment rate and the mean time from onset to death, assuming Psym is 0.50 (red), 0.75 (green) and 0.95 (blue). The
markers show the posterior means and the bars show 95% CrIs.

CASE-FATALITY RATE AND CHARACTERISTICS OF PATIENTS DYING IN RELATION TO

COVID-19 IN ITALY
Another cluster of patients with COVID-19 was simultaneously identified in Veneto,
which borders Lombardy. Since then, the number of cases identified in Italy has
rapidly increased, mainly in northern Italy, but all regions of the country have
reported having patients with COVID-19. After China, Italy now has the second
largest number of COVID-19 cases and also has a very high case-fatality rate. This
Viewpoint reviews the Italian experience with COVID-19 with an emphasis on
fatalities.
Surveillance System and Overall Fatality Rate:

At the outset of the COVID-19 outbreak, the Italian National Institute of Health
(Istituto Superiore di Sanità [ISS]) launched a surveillance system to collect
information on all people with COVID-19 throughout the country. Data on all
COVID-19 cases were obtained from all 19 Italian regions and the 2 autonomous
provinces of Trento and Bozen. COVID-19 cases were identified by reverse
transcriptase–polymerase chain reaction (RT-PCR) testing for the severe acute
respiratory syndrome coronavirus 2 (SARS-CoV-2). The fatality rate was defined as
number of deaths in persons who tested positive for SARS-CoV-2 divided by
number of SARS-CoV-2 cases. The overall fatality rate of persons with confirmed
COVID-19 in the Italian population, based on data up to March 17, was 7.2% (1625
deaths/22 512 cases). This rate is higher than that observed in other countries and
may be related to 3 factors.

Fatality Rate and Population Age:

The demographic characteristics of the Italian population differ from other countries.
In 2019, approximately 23% of the Italian population was aged 65 years or older.
COVID-19 is more lethal in older patients, so the older age distribution in Italy may
explain, in part, Italy’s higher case-fatality rate compared with that of other
countries. The Table shows the age-specific fatality rate in Italy compared with that
of China.
Definition of COVID-19–Related Deaths:
A second possible explanation for the high Italian case-fatality rate may be how
COVID-19–related deaths are identified in Italy. Case-fatality statistics in Italy are
based on defining COVID-19–related deaths as those occurring in patients who test
positive for SARS-CoV-2 via RT-PCR, independently from preexisting diseases that
may have caused death. This method was selected because clear criteria for the
definition of COVID-19–related deaths is not available.

Electing to define death from COVID-19 in this way may have resulted in an
overestimation of the case-fatality rate. A subsample of 355 patients with COVID-19
who died in Italy underwent detailed chart review. Among these patients, the mean
age was 79.5 years (SD, 8.1) and 601 (30.0%) were women. In this sample, 117
patients (30%) had ischemic heart disease, 126 (35.5%) had diabetes, 72 (20.3%)
had active cancer, 87 (24.5%) had atrial fibrillation, 24 (6.8%) had dementia, and 34
(9.6%) had a history of stroke. The mean number of preexisting diseases was 2.7
(SD, 1.6). Overall, only 3 patients (0.8%) had no diseases, 89 (25.1%) had a single
disease, 91 (25.6%) had 2 diseases, and 172 (48.5%) had 3 or more underlying
diseases. The presence of these comorbidities might have increased the risk of
mortality independent of COVID-19 infection.

COVID-19–related deaths are not clearly defined in the international reports

available so far, and differences in definitions of what is or is not a COVID-19–
related death might explain variation in case-fatality rates among different countries.
To better understand the actual causes of death, the ISS is now reviewing the
complete medical records of all patients with positive RT-PCR results who have died
in Italy.
The risk ratios give the ratio of case-fatality rate in one age-band with the case-fatality rate in the reference age-
band (here set to age 60-69).

Category Risk ratio 95% CI

Age 30-39 0.06 0.038 to 0.10
Age 40-49 0.14 0.11 to 0.17
Age 50-59 0.31 0.27 to 0.35
Age 60-69 (Reference) 1.00 –
Age 70-79 2.95 2.7 to 3.2
Age 80-89 4.47 4.1 to 4.8
Age 90+ 4.83 4.4 to 5.3
Female 1.00 –
Male 1.66 1.58 to 1.74
Rate ratio estimates (95% CI) for CFR under independence model
 Germany has the third highest number of coronavirus cases in
Europe, but deaths are relatively few when compared with
neighbouring countries. Ned Stafford explains why

As the covid-19 pandemic continues to grow in severity, one of the most closely
watched statistics has been Germany’s number of deaths from the virus, which has
been remarkably low in comparison with other nations, especially neighbouring
European countries.

As of 2 April official statistics showed that 872 deaths from covid-19 had been
recorded in Germany from 73 522 confirmed cases, translating to a fatality rate of
1.2%. This compares with fatality rates of 11.9% in Italy, 9% in Spain, 8.6% in the
Netherlands, 8% in the UK, and 7.1% in France.

Christian Drosten, director of the Institute of Virology at the Charité hospital in

Berlin, believes that Germany’s relatively low covid-19 fatality rate can be attributed
partly to the nation’s early and high level of testing among a wide sample of the
German population. While other countries were conducting a limited number of tests
of older patients with severe cases of the virus, Germany was conducting many more
tests that included milder cases in younger people.

The more tests are performed, the more likely it is that new cases will be found, and
the higher total case numbers are relative to the proportion of cases that lead to
death. Thus, the fatality rate decreases as this ratio widens.

Drosten, corresponding author of a January 2020 paper describing a reliable method

for covid-19 testing, says that, under Germany’s public health system, testing is not
restricted to a central laboratory as in many other nations but can be conducted at
quality controlled laboratories throughout the country.

―In this situation, it was easy for us to roll out a test protocol already in January,‖ he
says. ―German labs are testing a lot. The overall capacity as of last week is likely to
have exceeded half a million RT-PCR [reverse transcription polymerase chain
reaction] tests.‖

Another possible explanation, says Drosten, is that many cases were imported into
Germany by younger people who had been on ski holidays in Italy and Austria,
although he emphasises that this is just a hypothesis. ―We have not seen a lot of
transmission in senior citizen homes or nosocomial outbreaks in hospitals,‖ he says.
―When this type of outbreak occurs, the age and fatality rate will be higher.‖
Swift action

Germany also took actions sooner than some other nations to stop the spread of
covid-19. Initial actions were taken unilaterally by Germany’s 16 states, led by
Bavaria—its largest state and the hardest hit by covid-19. By mid-March states were
closing schools and most retail businesses, as well as banning gatherings of people
and mandating isolation of people who had covid-19 or were exposed to it.

On 22 March, after consulting state leaders, Chancellor Angela Merkel announced

rules banning more than two people who lived in different households from being
outside together. People who ventured out to supermarkets, pharmacies, doctor’s
offices, and banks also had to stay 1.5 to 2 metres apart. The great majority of people
in Germany are voluntarily adhering to the contact restrictions, although there are, of
course, exceptions.

Gérard Krause, head of the Department for Epidemiology at the Helmholtz Centre
for Infection Research in Braunschweig, commented, ―I support the current approach
in Germany, which seems to be characterised more by appealing on compliance to
rules rather than on enforcing them by micromanagement laws.‖ He added, however,
that some cities and federal states were now exploring legal enforcement.

Caution urged

Concern is growing that the relatively low fatality rate may be ―the calm before the
storm,‖ as the German health minister Jens Spahn has put it. Drosten warns that the
apparent case fatality may not stay this low, while Krause says that ―we may still be
at the very beginning of the wave compared to other countries.‖

There are worrying signs of acceleration. The Robert Koch Institute’s daily covid-19
report on 26 March showed a total of 149 deaths, meaning a fatality rate of 0.5%. In
the following days the death rate edged higher, doubling from 66 deaths on 30
March to 128 the next day. The 1 April report showed 149 new deaths (a total of 732
and a 1.1% fatality rate).

Krause, whose research team is investigating whether patients who recover from
covid-19 are immune to reinfection, thinks that the question is not whether Germany
has done enough to fight covid-19 but whether it has done the right things.

He explains, ―Additional action with respect to equipment and protection of medical

staff and protection of individuals with high risk for severe disease would certainly
be a good investment. In such a situation, it is probably impossible to have done
enough.‖
 Conclusions
 A series of multifaceted public health interventions was temporally associated
with improved control of the COVID-19 outbreak in Wuhan, China. These
findings may inform public health policy in other countries and regions to
combat the global pandemic of COVID-19.
 the current data illustrate that Italy has a high proportion of older patients with
confirmed COVID-19 infection and that the older population in Italy may
partly explain differences in cases and case-fatality rates among countries.
Within Italy, COVID-19 deaths are mainly observed among older, male
patients who also have multiple comorbidities. However, these data are limited
and were derived from the first month of documented COVID-19 cases in
Italy. In addition, some patients who are currently infected may die in the near
future, which may change the mortality pattern.
 From a research perspective, the comparisons discussed highlight the need for
transparency in reporting testing policies, with clear reporting of the
denominators used to calculate case-fatality rates and the age, sex, and clinical
comorbid status of affected persons when comparing COVID-19 case and
mortality rates between different countries and regions. Finally, because the
outbreak is new, continued surveillance, with transparent and accurate
reporting of patient characteristics and testing policies, is needed from multiple
countries to better understand the global epidemiology of COVID-19.
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6- And