Dr. Wissam S.A. Al-Janabi, Physician in the department of Acute Medical Unit (AMU) Walsall Manor Hospital,
Dr. Ahmed Abras, Clinical Director of Geriatric Medicine Walsall Manor Hospital
Editor: Abdalla H. Sadoon
How to cite this article: Al-Janabi WSA, Abras A. Worldwide Crude Death Rate, Case Fatality Rate, and Attack Rate from COVID-19: with up to date Comprehensive Review. USAJMR 2020;1 doi: 10.35456/USAJMR001001004.
Conflicts of Interests: The authors decalre there are no competing interests
Objective: This article sheds light on the up to date details of COVID-19 and why it began in Wuhan. Further, it discusses the available treatment options and their effects on patients with COVID-19, and which drugs patients and clinicians should avoid. It elucidates the common signs and symptoms and the stages of the severity of patients' condition with COVID-19, including its definition, according to the World Health Organization (WHO). It shows possible ways to break up the transmission mechanism by giving a simple table with a clear and concise caption for each point.
Moreover, it announces three ways to diagnose COVID-19, including the latest five-minutes test that was approved by the US Food Drug Administration (FDA) on March 28, 2020. It also elaborates on the main features that can be found on the Chest Computed Tomography Scan (CT-scan) and its four stages. This article will show the difference between previous similar virus attacks like Severe Acute Respiratory Syndrome (SARS) and Middle Eastern Respiratory Syndrome (MERS). It talks briefly about children and pregnant women with COVID. It shows the latest toll of death from COVID-19 and the number of new cases for several countries.
Keywords: COVID-19, WHO, NHS, hydroxychloroquine, SARS.
Abstract: The apocalyptic event of the COVID-19 outbreak led to global disasters in all aspects of human life. On January 30, 2020, the WHO declared a global health emergency. On average, over 50,000 cases is the incidence rate per day worldwide. High profile personnel like the UK prime minister and Prince Charles contracted the virus on March 28, 2020. the limiting number of Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) pushed pharmaceutical companies such as Abbott to find a five-minute test to diagnose COVID-19 with a handheld machine. Conjunctivitis is a critical feature of COVID-19 that caused death in one ophthalmologist because of the close contact. Patients on hydroxychloroquine phosphate have shown auspicious results and fast improvement when compared to the placebo groups in many clinical trials. Meanwhile, the United States of America is testing a novel vaccine against the COVID-19 on healthy people.
1 | Introduction:
Five agents from the coronavirus family, including Middle East Respiratory Syndrome (MERS), are zoonotic viruses, and this explains why the first cluster of cases was near the South China Seafood Market.  Even though scientists found approximately 80% genetic similarities between SARS and COVID-19, the epidemiological characteristics for COVID-19 are quite different. COVID-19 has a shorter replication time and incubation period than SARS. [1,2] COVID-19 causes four distinct clinical patterns: Minor upper respiratory tract (URI) symptoms, Mild pneumonia, severe pneumonia with Acute Respiratory Distress Syndrome (ARDS), or septic shock that puts the patient in the Intensive Therapeutic Unit (ITU) and ventilator.  The swift increase in the number of affected people with COVID-19 and over 3% case fatality rate as of now put a gloomy picture on how this outbreak will end.  Because of the rising pressure on the laboratories, most countries, including the United Kingdom (UK), decided to test only those who are hospitalized with symptoms suggesting COVID-19.  Currently, in the UK, all elective surgeries and non-urgent appointments put on hiatus.  The death toll is highest in China, South Korea, Italy, and Iran.  The lack of prior knowledge of the world about the COVID-19 may end up with over 50% of the entire population infected with COVID-19.  Fang et al.  have found in a retrospective study of the sample comprised 51 patients who confirmed to have COVID-19 that the sensitivity of chest CT-scan is 98% compared to 70.5% for Polymerase Chain Reaction (PCR). A five-minutes test was invented by the Abbott company and approved by the Food Drug Administration (FDA)in the United States.  In March 2020, on Diamond and Grand princess cruise ships, over 800 cases and ten deaths were confirmed following their voyages that carried about 5,000 passengers and crew members.  over 30 million people transport via cruise ships each year.  On March 13, 2020, the WHO has published on its website an interim guidance document to aid clinicians in providing safe management to the confirmed cases of COVID-19 based on the severity of the condition.  Around 5% of the cases develop Acute Respiratory Distress Syndrome (ARDS), sepsis, septic shock along with multiorgan failures like kidney or heart.  D-dimer > 1 μg/L has been associated with higher mortality.  Co-infection with another pathogen is not uncommon with COVID-19. 
2 | Statistical comparison between COVID-19 and SARS:
SARS in 2003 caused about 8000 cases and around 800 deaths. [10,11] Whereas, COVID-19 caused over 375,498 confirmed cases and 16,362 deaths in 196 countries up to March 25 of 2020.  Although both viruses emerged from China and share some genetic similarities, COVID-19 is more severe than SARS when comparing transmissibility, clinical severity, and velocity of community spread. [11-13]
3 | Three ways to diagnose COVID-19:
A five-minutes test was discovered by Abbott pharmaceutical company and approved by the US FDA on March 28, 2020.  This quick handheld machine may change the world's perspective towards COVID-19. 
Although the standard tool for definitive diagnosis is the RT-PCR, non-contrast chest CT-scan during end inspiration with a good history taking, have comparable sensitivity to RT-PCR test. [14,15,19,20] Nasal swab or throat are the most abundant areas of viral collection and replication; nonetheless, sputum, aspiration, bronchoalveolar lavage, stool, eye tears samples have been used to provide the diagnosis and show the presence of the virus. 
Wang et al.  in his study on the first 138 cases that occurred in Wuhan, China shows that elevated White Blood Cell count (WBC), Neutrophil count, Blood Urea Nitrogen (BUN) level, and decline in the lymphocyte count associated with sinister prognosis. Nonetheless, laboratory findings in other reported cases such as leukopenia, lymphopenia, and elevation in prothrombin time (PT), D-dimer, Aspartate Aminotransferase, and Troponin-I have been reported in some cases with severe illness and subsequently admitted to the ITU. [1,15-16,21]
Bernheim and colleagues , in their study on 121 patients' chest CT-scans, show that 56% of patients in the early stage of COVID (0-2 days) may have normal findings on CT-scan.
4 | The incubation period of COVID-19, signs & symptoms of its patients:
The incubation period ranges between 9-18 days with 95% Confidence Interval of 12.5 days and a median period of 5 days. [1,14]
The most common reposted signs and symptoms are fever, dry cough, sinus congestion, myalgia, fatigue, chest tightness, shortness of breath (SOB), headache, vomiting, abdominal pain, loss of appetite, especially among pregnant women. [1,14-16,18-20,25] In addition, conjunctivitis is an important distinguishing feature of COVID-19 when compared to SARS or MERS. 
4.1 | In some patients, COVID-19 may lead to one of the followings:
4.1.1 | Severe pneumonia: Is defined according to the WHO as Fever plus one of the following: Respiratory Rate (RR) > 30/minutes, severe respiratory distress, or SPO2< 93% on room air. [9,13]
4.1.2 | Acute Respiratory Distress Syndrome (ARDS): Is defined either PaO2/FiO2 < 300 mmHg or SPO2/FiO2< 315 mmHg. [9,13]
4.1.3 | Septic shock: Is defined as persistent hypotension despite the volume resuscitation and needs for vasopressors to keep the Mean Arterial Pressure (MAP) > 65 mmHg plus serum Lactate > 2mmol/L. [9,13]
5 | The salient features on non-contrast chest CT-scan:
Bilateral ground-glass opacities, and subsegmental areas of consolidation with a predilection to the posterior segments of the lower lobes. [1,18,19] Noteworthy, within two weeks from the clinical improvement in patients with COVID-19, the ground glass appearance fades away on chest CT-scan.  Absence of radiological evidence of lymphadenopathy or pleural effusion in confirmed cases with COVID-19. [18,19]
5.1 | Four stages can be identified on non-contrast chest CT-scan: early-stage (0-4 days) characterized by subpleural ground-glass opacities(GGO); progressive stage (5-8 days) the GGO grows gradually with crazy-paving patterns; peak stage (10-13 days) lung involvement increases with consolidation; finally, the resolution stage (> 14 days) absorption of GGO and consolidation are seen obviously on the chest CT-scan. 
6 | Proposed treatment options and its efficacy according to the results of ongoing clinical trials:
6.1 | Anti-viral drugs:
Remdesivir is a novel drug that was developed to treat MERS-CoV has shown a promising effect when used in the United States for a patient who was diagnosed with COVID-19, and no randomized clinical trial has begun to investigate its effect against COVID-19.  Ribavirin is inefficient in treating a patient with COVID-19 and may cause hemolytic anemia. [1,25] No sufficient evidence on the effectiveness of the combination of Lopinavir 400 mg and Ritonavair 100 mg twelve hourly. [1,16,25]
6.2 | Anti-malarial drugs:
Many ongoing Chinese clinical studies have shown a promising response from patients who take hydroxychloroquine phosphate when compared to the control groups. [22-26] Besides, it has a dual anti-malarial and anti-viral effect.  Over 100 patients who are on hydroxychloroquine showed shorter duration of the viral course, less severity of pneumonia, and rapid radiological resolution; however, careful consideration of the dose is warranted to avoid serious side effects of chloroquine like vision impairment. [22-26] The most recent recommendation is to use hydroxychloroquine instead of chloroquine for five days, starting with a loading dose on the first day of 400 mg twice daily, then 200 mg twice daily for four days. 
6.3 | Other Chinese remedies:
Chinese remedy such as the Glycyrrhizin, which is the component of liquorice roots was used before to treat SARS and may be used in an attempt to alleviate symptoms in patients with COVID-19. 
6.4 | Should we use NSAIDs with COVID-19?
The minister of health in France tweeted on his account advising patients with COVID-19 to avoid the use of ibuprofen as it reduces the immune response, and may delay the viral clearance duration, this statement was supported by professor Little, a British researcher at the Southampton University  They advise in using paracetamol as an antipyretic or to dampen the pain instead of ibuprofen or Aspirin. [9,27]
6.5 | Steroid:
Corticosteroid should be avoided unless it is used for treating other associated conditions like asthma, as it may delay the virus clearance besides other well-known side effects like diabetes, psychosis, and avascular necrosis. [1,11,28]
6.6 | Mechanical Ventilation:
Patients who require mechanical ventilation, keep tidal volume between 4-8ml/kg, and low inspiratory pressure (plateau pressure < 30 mmHg). 
6.7 | Reduce the risk of pressure & stress ulcers:
Turn the patient every two hours and give enteral feeding within 24-48 hours if a patient is unable to eat to avoid stress ulcers. 
6.8 | COVID-19 patients who develop ARDS:
Patients who develop ARDS with refractory hypoxemia should be transferred to an expert center in giving Extracorporeal Membrane Oxygenation (ECMO) that was proved to reduce the mortality rate in such patients. 
6.9 | When is the patient considered clear from COVID-19?
According to the Public Health of England (PHE), two sequential negative PCR tests and complete resolution of the symptoms are required before a patient is declared clear from COVID-19. 
7 | How does COVID-19 affect children and pregnant women?
Cases of COVID-19 in children and infants have been reported as mild illnesses with the main symptoms of dry cough and fever.  Symptoms among pregnant and non-pregnant women are the same.  No transmission has been reported from pregnant women to their babies during delivery or through breastfeeding. 
In countries with a large population like China, non-contrast chest CT-scan with clinical evaluation and history are the main tools in diagnosing the COVID-19, especially in children and pregnant populations, with similar findings on CT-scans for adult and non-pregnant women. 
8 | The crude death rate, case fatality rate, and the attack rate in the UK and Worldwide up to March 30, 2020:
Table 1 [30-32] below reflects countries with the highest number of reported and confirmed COVID-19. It also sheds light on mortality rate, crude death rate, and the attack rate for COVID-19, which were calculated based on number of cases, death, total populations information on European Center for Disease Prevention: Situation update worldwide, as of March 30, 2020
9 | Main international public health tips to reduce COVID-19 transmission:
10 | In a nutshell: Despite some genome and clinical similarities between the SARS outbreak in 2002-2003 and COVID-19, COVID-19 has a faster spread rate and causes far more mortality, which led to an unprecedented global response.  WHO declared that COVID-19 is an international public health emergency.  In the United States, there is a clinical trial to test a new vaccine that does not contain the virus on healthy volunteers.  FDA approved a five-minutes test on March 28, 2020, which may lead to a drastic change in the number of COVID-19 patients. 
Lots of worldwide sacrifices have been submitted so far, such as the rapid plummet of the global economy as a result of international public health measures from banning all types of transportations between and even within most of the countries around the globe in an attempt to end this apocalyptic event. 
Hydroxychloroquine and some antiretrovirals are showing optimistic responses in ongoing clinical trials. [22-26] NSAIDs, including ibuprofen, should be avoided in patients with COVID-19 due to their harmful effects on the immune system.  Patients and clinicians are advised to avoid steroid unless it is used for other associated condition. 
Abbreviations: World Health Organization (WHO), Center for Disease Control and Prevention (CDC), New Strain of Coronavirus family (COVID-19), Computed Tomography scan (CT-scan), Severe Acute Respiratory Syndrome (SARS).
Declaring of competing interest: We declare no competing interest, and we read and comprehended BMJ policy.
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