COVID-19 Disease: Myth and Reality - Dragan Primorac
At the time of writing this document (3/28/2020), according to data of the Johns Hopkins Hospital, there are 679,977 confirmed cases of COVID-19 worldwide, caused by the SARS-CoV-2 virus. So far, the total number of deaths is 31,734, while 145,625 people have fully recovered and are considered healthy. In Croatia, the number of confirmed COVID-19 cases is 657, 5 died while 45 patients have fully recovered and were discharged from the health care institutions where they were treated and are now in-home isolation (1).
Having read the excellent book “SARS: How a global epidemic was stopped”, published immediately after the SARS (Severe Acute Respiratory Syndrome) epidemic was defeated in 2003, it became clear to me that history is repeating itself with the coronavirus, though this time in an even more complex and unpredictable way. The epidemic that started on 11/16/2002 lasted for the entirety of 2003 and it was not until late 2004 that there were no new cases registered; it was caused by the SARS-CoV virus and was the first epidemic to occur during the period of globalization. However, this disease of the 21st century was not defeated by the sophisticated medicine of the time, but by measures that had already been implemented as far back as the 19th century - primarily by keeping records, by monitoring both patients and all those who were in contact with them and through isolation and quarantine measures. These measures forcefully halted the spread of the infection, and ultimately the epidemic was overcome (2). However, there are two enormous differences between the epidemic caused by the SARS-CoV virus at the time and today's COVID-19 caused by the SARS-CoV-2 virus. To our knowledge, the SARS-CoV virus was not transmitted by asymptomatic infected persons, which, it seems, is not the case with how the SARS-CoV-2 virus is spread (2). The second difference is related to transmission pathways. The transmission pathways of the SARS-CoV-2 virus are not yet fully understood but the assumption is that it is mainly transmitted via droplets generated by sneezing and coughing, as well as indirectly through contaminated hands or the secretions of affected persons since the virus can survive on various surfaces for several hours (3, 4). On the other hand, the SARS-CoV virus is transmitted primarily from person to person through direct contact (mainly droplet transmission), and the most intense period of transmission is, as expected, during the second week when there is a peak of virus excretion in various secretions (2). The main lessons learned from the SARS epidemic can be summed up in a few sentences: transparency is the key to success, countries with strong public health systems are far better at coping with the epidemics, the introduction of drastic measures to combat the spread of the infection is a necessity, the media (particularly electronic media at the time) played a key role in informing the public in a timely and accurate manner, without international cooperation the epidemic cannot be stopped or slowed, prevention of the spread of infections in hospitals is the key to success in curbing the epidemic.
It was Singapore that paid the great price in the aftermath of the SARS epidemic during 2002 and 2003, and it learned a major lesson. According to data published by the Journal of Travel Medicine just before the release of this text, from 5 February to 18 February 2020, along with China, Singapore was the country with the highest number of COVID-19 patients (5). But then everything changed. Singapore's National Center for Infectious Diseases launched the so-called unified concept, which contained an epidemiological, laboratory and clinical approach to combating infections, and the entire Government was involved in combating infections. The model involved the identification of all individuals suspected of having contracted COVID-19, and facilities doing tests were expanded from 2 laboratories doing the RT-PCR protocol (molecular diagnostics of SARS-CoV-2 viruses) to a number of other hospitals, reaching a record speed of 2,200 tests per day. The same model was taken over by South Korea, which has performed 200,000 tests to date, timely including asymptomatic persons infected with the SARS-CoV-2 virus, something that has not even been discussed in Europe until recently. This led to the isolation and hospitalization of more than 4,000 people who were in close contact with those infected, whereby the complete data on their movement, as well as a list of all persons with whom they had contact, were collected 14 days prior to the infection. At border crossings, all passengers had their body temperature checked and were subjected to a basic medical examination, with all those suspected of having been infected hospitalized immediately. Immediately after that, all travelers from China, South Korea, Italy and Iran were forbidden to enter the country. Preventive measures were constantly promoted in the media and at no point did Singapore close its schools so as not to disrupt the state's system of functioning.
The coronavirus is one of the major pathogens responsible for respiratory infections. There are six known coronaviruses that cause disease in humans. The SARS-CoV and MERS-CoV viruses cause the so-called severe acute respiratory syndrome (SARS), while four other coronaviruses that cause human diseases (HCoV-OC43, HCoV-229E, HCoV-NL63 and HCoV-HKU1) lead to mild upper respiratory tract infections, against which most adults have antibodies (4, 6). Earlier studies have found that serum antibodies begin to grow one week after contracting a coronavirus infection, reaching a peak after two weeks, and persisting for a long time and protecting individuals from reinfection from more severe forms of the disease (7).
The majority of known coronaviruses circulate among animals. It is still unclear why some types of coronaviruses switch to infecting humans, and many theories have been suggested. One of them warns that in some places, such as the very specific markets in Asia, contact occurs between animal species that do not normally interact in nature. Such conditions create the potential for interactions between individual bacteria or viruses from different animal species, as well as for possible genetic recombination between them. This could lead to individual viruses assuming different behavioral patterns, regardless of the species involved. The recently published results on the structure of the SARS-CoV-2 genome also support this, showing that some parts of it, such as the S glycoprotein ("Spike glycoprotein") and the membrane protein (M-protein), contain major changes caused by numerous mutations. It is particularly interesting that the S-protein, for instance, contains a sequence of 39 nucleotides that is similar to the genome of the fish Myripristis murdjan, which inhabits the Indo-Pacific. All of the above points to changes in the genetic material (recombination) that have occurred in nature or otherwise (8), which we still do not have a clear understanding of.
The SARS-CoV-2 Virus
The results to date suggest that the new coronavirus that appeared in 2019 (SARS-CoV-2) is closer to the two bat-borne coronaviruses (bat-SL-CoVZC45 and bat-SL-CoVZXC21) than to the coronaviruses that infect humans, including SARS-CoV, the virus that affected more than 8,000 people between 2002 and 2003 and spread to about thirty countries (9).
The genome of the SARS-CoV-2 virus is composed of a single-stranded (positive-sense) ribonucleic acid (RNA) molecule and contains 29,903 nucleotides (10). Using a special spike-like glycoprotein on its surface, the SARS-CoV-2 virus binds itself to cells, mainly in the respiratory system, where it successfully uses the cell structures to produce a new generation of viruses. In the meantime, a number of scientists have shown that it is the so-called ACE2 (angiotensin-converting enzyme) receptors that are the key for virus entry into the cell (11). Following the onset of the first patients in Wuhan, the scientific journal The Lancet published the results of a genome analysis of the viruses extracted from the first 9 patients analyzed, which found that the sequences of the SARS-CoV-2 viruses of the different patients matched at a percentage exceeding 99.98%, suggesting that the virus had only recently infiltrated the human population, most likely from a single location (9).
SARS-CoV-2 and the Infection Spread Rate
At the same time, since SARS-CoV-2 is a new virus and the population has not been in contact with it before, the organism cannot produce antibodies and neutralize the virus. In the absence of rigorous measures, the virus will spread exponentially. Statistical data is unrelenting - each person infected with SARS-CoV-2 will infect two new people, and every 6 days the number of those infected will double (4, 12).
SARS-CoV-2 and its Transmission
Since 2003, we have been affected by three major coronavirus outbreaks, so our knowledge of the potential routes of transmission (aerosol, touch, transmission via contaminated surfaces, etc.) is mainly related to our experiences with other members of the coronavirus family. Although it is indicated that animals (bats, snakes, crustaceans) are a possible reservoir of the SARS-CoV-2 virus, still no one can say with certainty which animal was its source (13, 14). An article published in The Lancet that points out that eight out of the nine first original patients in China had visited the Huanan seafood market in Wuhan, but that the ninth patient had never been to the market, which suggests that the transmission of the virus was carried out in a way unknown to us or that the source of the infection was a place other than the Huanan Market, as was originally claimed (9). When, ten days ago, one of the world's leading authorities in the field of virology, Prof. Anthony Fauci, director of the American National Institute of Allergy and Infectious Diseases, said that the virus could be transmitted by asymptomatic persons, he came under criticism (15). However, today the realization that an asymptomatic person can spread the infection has become crucial in preventing the further spread of the epidemic (16, 17).
A study published in the scientific journal Annals of Internal Medicine analyzed 181 SARS-CoV-2 virus patients and found that the majority of subjects (95%) showed their first symptoms on the fifth day after infection, though it should be noted that the incubation period lasts 1 to 14 days on average, and in some patients an incubation period of almost one month has been reported (4, 18). In any case, the results undoubtedly support the introduction of a 14-day quarantine for anyone suspected of having been in contact with the SARS-CoV-19 virus or infected persons. However, the US Center for Disease Control and Prevention (CDC) warns that the possibility of spreading the virus is far faster with those who have shown symptoms of the disease than with asymptomatic persons (19).
Diagnosis guidelines for COVID-19 change on a day-to-day basis. The guidelines encompass: clinical criteria (symptoms, laboratory findings, CT of the thorax), epidemiological patient history and molecular diagnosis (RT-PCR SARS-CoV-2 detection in samples of sputum, pharyngeal swab, lower respiratory tract aspirate, blood and urine. The alternative molecular diagnosis is gene sequencing of SARS-CoV-2). The details of diagnostics have just been made available in a paper by Bischof et al. (20)
SARS-CoV-2 and Disease Course
The clinical presentation of patients infected with the SARS-COV-2 virus is diverse and the symptoms that may occur include: fever, fatigue, dry cough, muscle pain and dyspnea (difficulty breathing), while the less common symptoms include: diarrhea and nausea, headache, hemoptysis (coughing up blood), productive cough and chest pain (4, 21–23). However, most of those infected with the SARS-COV-2 virus (about 80%) recover quickly from the disease, showing minimal signs of inflammation, mostly similar to the common cold. The COVID-19 mortality rate remains between 3% and 4% and varies daily, ranging from about 1.0% in South Korea to 7.9% in Italy (1). The mortality rate of the SARS-CoV virus that affected more than 8,000 patients in 2002-2003 was around 10%, while the mortality rate of the MERS-CoV virus, which spread from China to the Middle East in 2012, was above 35% (4).
SARS-CoV-2 and Particularly Vulnerable Groups
According to the available data, the morbidity and mortality rates are particularly high in the 70-79 age group (a mortality rate of 8.0%), while in patients over the age of 80 the mortality rate is about 14.8% (24). The Chinese Center for Disease Control indicates, based on its own results, that persons with a previous chronic illness have a far greater chance of contracting COVID-19 and a far higher mortality rate than the average total mortality rate, reaching 2.3%. For instance, in COVID-19 patients suffering from cancer the mortality rate is 5.6%, in patients suffering from hypertension 6.0%, in patients suffering from diabetes 7.3%, while the highest mortality rate is found in patients suffering from cardiovascular disease - 10.5% (24).
Similar results were published in an article in the JAMA journal, analyzing 138 COVID-19 patients who were hospitalized with pneumonia (21). The article points out that 46.4% of these patients had one chronic disease such as hypertension (31.2%), diabetes (10.1%), cardiovascular disease (14.5%) or cancer 7.2%. In addition, it was found that a large percentage of patients requiring intensive care treatment had a chronic disease. 58.3% had hypertension, 22.2% diabetes, 25% cardiovascular disease and 16.7% cerebrovascular disease. Almost all patients (98.6%) had fever, 69.6% felt fatigue, 59.4% had a dry cough, 34.8% felt muscle pain, and 31.2% had difficulty breathing. Of the total number of patients, 10.1% had diarrhea and nausea 1-2 days before the onset of the fever and difficulties with breathing (21). A decreased lymphocyte count (lymphocytopenia) was observed in 70.3% of patients, while lung CTs of all the treated patients showed bilateral shadowing. Of the 138 COVID-19 patients hospitalized with pneumonia, 26.1% ended up in intensive care, primarily due to acute respiratory syndrome, arrhythmia and shock (21).
A study published in the New England Journal of Medicine included 1,099 patients and once again confirmed the extremely significant role a pre-existing chronic disease plays in COVID-19 patients. Specifically, 173 patients had severe clinical features and of these, 23.7% had pre-existing hypertension, 16.2% diabetes, 5.8% coronary heart disease, and 2.3% cerebrovascular disease (22).
Another (retrospective) article, published in The Lancet, covered 99 COVID-19 patients who developed pneumonia, with an average age of 55.5 years (23). Half of the patients had contact with the Huanan seafood market. This study also points out that at least one chronic disease was present in 50% of the COVID-19 patients. The authors point out that 83% of the patients had a fever, 82% experienced coughing, 31% shortness of breath, 11% muscle pain, 9% showed signs of confusion, 8% suffered from a headache, 5% had a sore throat, 4% had a runny nose, 2% experienced chest pain, 2% had diarrhea, and 1% of the patients experienced nausea and vomiting. Still, most of the patients, more than 90%, experienced multiple symptoms at the same time. Radiological examinations confirmed that 75% of the patients had bilateral pneumonia, 14% showed multiple mottling and ground-glass opacity, while 1% had pneumothorax - penetration of air into the pleural cavity (between the two pleural layers that separate the lungs from the chest wall). The authors point out that 17 patients developed severe acute respiratory syndrome and 11 of them developed multi-organ failure in a short period of time leading to a fatal outcome (23).
SARS-CoV-2 is a Multi-Organ Disease
In addition to respiratory symptoms, COVID-19 patients were also diagnosed with multiple-organ involvement, including a deficiency of cellular immunity, coagulation activation and myocardial damage, as well as liver and kidney damage (4, 21, 25).
Treatment of COVID-19 Patients who Develop Pneumonia
A paper published by Chen et al. in The Lancet points out that oxygen therapy was required in 76% of cases and non-invasive mechanical ventilation using a mask in 13% of cases, while invasive mechanical ventilation was required in 4% of cases. On the other hand, continuous renal replacement therapy (CRRT), which involves substituting impaired renal function with a 24-hour extracorporeal circulation system, was required in 9% of patients, and extracorporeal membrane oxygenation (ECMO) was required in 3% of cases. In a total of 71% of patients, additional antibiotic therapy was introduced due to bacterial superinfection, in 15% an additional antimycotic therapy and in 75% an antiviral therapy was introduced. Glucocorticoids were introduced in 19% of cases, while intravenous immunoglobulins were administered in 27% of cases (23).
Laboratory Findings in COVID-19 Patients
The most commonly reported laboratory findings in COVID-19 patients are: leukopenia, lymphocytopenia, elevated CRP levels, and elevated LDH levels. Less common laboratory findings include an increase in AST and ALT levels, and an increase in D-dimer and creatine kinase (4, 22, 23)
According to Chen et al., among COVID-19 patients who also developed pneumonia, 85% showed increased sedimentation, 63% increased serum ferritin and 86% increased C-reactive protein levels. Other blood tests were diverse, ranging from decreased leukocyte levels (9% of patients), elevated leukocyte levels (24% of patients), 38% patients had elevated neutrophil levels, and a number of patients showed signs of liver damage with elevated typical liver enzyme levels (23). Constant findings, however, suggest that in patients with a severe form of the disease, lymphocytes are lower than in patients with milder clinical features. Elevated troponin levels, suggesting myocardial damage, are significantly higher in patients with a severe form of the disease, and a significant increase in CRP has been observed in these patients as well, suggesting acute inflammation. In the conclusion to the paper, in which the authors analyzed 41 COVID-19 patients, it is noted that elevated troponin values, rapid heart rate (tachycardia) and low epicardial fat density (as measured by CT) were observed in COVID-19 patients with severe clinical features or who are in critical condition (26).
Radiological Signs in COVID-19 Patients
According to a study published by Xu et al., the most common radiological signs, shown in CT scans in a sample of 90 patients infected with SARS-CoV-2, are multifocal bilateral pulmonary lesions with a peripheral distribution in more than half of the patients, ground-glass opacity in 72% of patients, interlobular thickening in 37% of patients, consolidation in 13%, pleural thickening in 56% and linear shadowing in 61% of patients. In the sample covered by the study, atypical findings included: pulmonary or pericardial effusion and lymphadenopathy (27).
In COVID-19 Patients, Particular Attention should be Given to Signs of Heart Damage
A recently published multi-center study analyzing the causes of death of 68 COVID-19 patients found that 53% of the patients died on account of pulmonary failure, 7% on account of heart muscle failure, and 33% on account of a combination of the two (25). The authors emphasize that a number of patients have died of fulminant myocarditis and a "cytokine storm" as a result of the body's immune system flaring out of control (25). At the same time, another study that analyzed 41 COVID-19 patients, particularly monitoring the status of epicardial adipose tissue via computed tomography, found that cardiac troponin levels (an intracellular protein essential for regulating muscle contraction) and heart rate clearly indicates that heart damage is very rare in COVID-19 patients with mild and moderate clinical symptoms, while it is very common in patients with severe clinical features, which is why it is extremely important to place special emphasis on the treatment of cardiac complications in these patients (26).
Unfortunately, there is yet no specific drug or vaccine that would be effective in treating patients infected with COVID-19. At the time of writing this text there is more than 100 registered clinical trials that explore COVID-19 treatment options, including: corticosteroid treatment, antivirals such as ribavirin, lopinavir/ritonavir, chloroquine, hydroxychloroquine, interferon, etc. In a recently published paper 600 mg hydroxychloroquine in combination with azithromycin taken orally were identified as a possible treatment option for COVID-19 (28).
Discussions on possible (new) treatment approaches
Angiotensin-converting enzyme 2 (ACE2) as a cellular receptor is important for virus entry into the cell via the S protein. The role of the ACE2 is to deactivate angiotensin II into angiotensin 1-7, which has a vasodilatory effect, unlike the angiotensin-converting enzyme (ACE) whose role is to convert angiotensin I into angiotensin II, which has a vasoconstrictive effect. Angiotensin receptor 1 (AT1R) blockers or antagonists (Losartan and Olmesartan), often prescribed for the purpose of lowering blood pressure, have previously been shown to increase ACE2 expression, even threefold after 28 days of treatment. Despite the fact that administering AT1R receptor antagonists would lead to an increase in the number of ACE2 receptors, which seems counterproductive when it comes to preventing virus entry into the cell, earlier studies monitoring the spread of the SARS-CoV virus in 2002 showed that binding the coronavirus via the S protein to ACE2 leads to a decrease in ACE2, which in turn leads to an increase in the production of angiotensin via a similar ACE enzyme, which has far more detrimental effects on lung tissue (11). The idea is, therefore, that increasing the expression of ACE2 receptors via the AT1R antagonists would paradoxically protect the lung tissue from major damage. It was this revelation that led to the publication of an article in Drug Dev Res suggesting that, in the meantime (until a vaccine is developed), angiotensin receptor 1 (AT1R) antagonists such as Losartan may play an important role in preventing major lung tissue damage (11). It should be pointed out that the European Society of Cardiology does not recommend therapy involving angiotensin-converting enzyme inhibitors or angiotensin receptor blockers to either physicians or patients, as there are no clinical studies to prove this effect (29). Discoveries regarding the receptor site for virus entry and associated potential therapy should remain in the domain of tertiary health care facilities.
The development of an effective vaccine is a lengthy process, best demonstrated by the fact that even 17 years after the onset of SARS and MERS, no vaccine has been produced. However, the fact is that never before has the world been as united in creating an effective vaccine as it is now, and the US National Institute of Allergy and Infectious Diseases has announced that the vaccine will be developed in just over a year.
Meanwhile, scientists have already begun using bioinformatic methods to analyze certain regions of the SARS-CoV virus that have a similar sequence to the SARS-CoV-2 virus, with the aim of finding the so-called epitopes that will stimulate cellular and humoral immunity (30). Based on such efforts, the spike structure of the glycoproteins with the involved glycans was published a few days ago (31).
At this point, about 80 clinical studies are recruiting patients to determine the effect of antiretroviral therapy and vaccines related to COVID-19 infection. At present, intense efforts are underway to develop mRNA vaccines, which have shown a strong immune-stimulating effect in other cases (32). The idea of this type of vaccine is to introduce individual segments (sequences) of the so-called messenger RNA or mRNA of the virus into the body to stimulate the body's immune system to start producing antibodies to the virus, although it was never really exposed to the virus itself. Based on previous research into the MERS-CoV vaccine, another group of scientists is working intensively on the production of the so-called monoclonal antibodies, which would bind specifically to the virus - more specifically to the virus's S protein - which it requires for cell binding (33). Immediately after the discovery of the genetic structure of the 2019-nCoV, it was suggested that the ideal therapy would use an artificially created mRNA strand that would bind to the viral mRNA molecules, thereby completely inhibiting the role of the viral mRNA.
COVID-19 Recovery Criteria
Guidelines have been issued by various countries and expert groups to determine the recovery criteria for patients infected by SARS-CoV-2. According to the guidelines of the Chinese Center for Disease Control and Prevention, a patient is considered to have recovered if he or she meets the following criteria: absence of fever for at least 3 consecutive days, significantly improved respiratory function in patients who developed respiratory failure, CT signs of a decrease in the inflammatory infiltrate and two consecutive negative results of the PCR SARS-CoV-2 laboratory tests taken over a 2-day interval (34). After discharge, it is suggested that patients remain in home isolation for 14 days with as little contact as possible with others (34).
Preventing the Spread of the SARS-CoV-19 Virus
The only known ways of preventing the spread of the SARS-CoV-19 virus are related to hygiene measures, which include thorough washing of hands, avoiding touching one's mouth, eyes and nose with unwashed hands, avoiding contact with persons suffering from respiratory infections, minimizing handshaking, avoiding travel, particularly to areas that are epicenters of the epidemics, avoiding public gatherings, etc. (4). It is especially important that all persons with signs of respiratory infection avoid contact with other persons, which should be customary conduct in any case. Everyone instructed to do so by the epidemiological services staying in home isolation has proven an extremely effective measure (4).
Encouraging preliminary results of a research supported by National Key R&D Program in China and The National Science Foundation of China suggest that warmer temperatures and humidity play a key role in lowering the infectivity of SARS-CoV-2 virus. A team of Chinese scientists led by dr. Wang had measured the daily effective reproductive number (R), that represents the average number of secondary cases per infectious case in a population made up of both susceptible and non-susceptible hosts. That number is especially important in cases of emerging new viruses, such as SARS-CoV-2, when there was no prior adaptive immunity response. It is well known that the effective reproductive number varies and can depend on many factors, which include weather conditions, temperature, hygiene and all epidemiological measures like self-isolation, etc. In their paper “High temperature and High Humidity Reduce the Transmission of COVID-19” Wang et al. from the University of Beihang (BUAA) have demonstrated that the increase of temperature by 10C decreases the R value by 0.0383, while the increase of humidity by 1% decreases the R value by 0.0224 by measuring the daily R values from January 21st till January 23rd 2020 in 100 Chinese cities with over 40 infected residents. These results suggest that the arrival of summer and the rainy season in the Earth’s Northern hemisphere might significantly slow down the transmission rate of SARS-CoV-2 virus (35). These results are at hand with the previously published animal studies that demonstrated that dry air blocks the function of the mucous barrier and allows a more efficient viral transmission of respiratory viruses. Recently, Moriyama and colleagues listed tips (humidification of indoor air, ventilation of indoor air, wearing face mask to keep the nose warm and moist, vitamin D supplement, sleeping more than 7h/day, washing hands to prevent indirect contact transmission) for limiting respiratory virus (36). Mucins secreted to our body fluids represent an important protective mechanism that attenuates viral infectivity (37). However, for this barrier to stay functional it is necessary to maintain constant flow of mucins which mimic glycans on our cell surface and block infection. If exposed to dry air, glycocalyx and mucins dries out, mucosal barrier becomes non-functional and viruses and bacteria have free access to our cells. Animal experiments convincingly demonstrated that increasing relative humidity from 20% to 50% can significantly decrease mortality from both bacterial (38) and viral infections (39).
True (verified) information
The WHO-declared SARS-CoV-2 pandemic has affected the world at a time of never before seen connectedness via telecommunications networks. In addition to the mass media, information is now provided to individuals by Internet portals, social networks, fake news portals and so-called Internet trolls. Public health issues must be communicated to the general public in a timely, open and clear manner by expert services in order to reduce the potential negative public health effects of fake news and rumors about methods of disease prevention and treatment (40). In this sense, the World Health Organization declared COVID-19 an infodemic due to the record amount of information published at almost every moment. The great public interest is understandable from the perspective of people’s concern for their own health and a reasonable amount of fear certainly has a good influence on people adhering to disease prevention measures. Everyone must understand that infection is not preventable at this stage, but that it can be slowed considerably, and that this is the responsibility of all of us. Each month that the spread of the infection is slowed, is a huge gain since the exponential spread of the infection must be avoided at all costs as there is no healthcare system that could bear such an excessive burden on its medical staff and hospitals. Croatia has been mobilized at all levels. Healthcare professionals are once again demonstrating an enormous commitment and sacrifice in halting the spread of the SARS-CoV-2 virus, while those responsible are informing the public in a timely manner of any measures taken. However, due to the large amount of false information that can be found in everyday communication, it is important to highlight several addresses where one can find verified expert information on the measures to combat the spread of the disease and the state of the pandemic:
World Health Organization (WHO): technical documents for coronavirus (covid-19) outbreak: https://www.who.int/health-topics/coronavirus
European Centre for Disease Prevention and Control: latest guidance for EU/EEA: https://www.ecdc.europa.eu/en/novel-coronavirus-china
US Centers for Disease Control and Prevention: latest guidance, advice and information: https://www.cdc.gov/coronavirus/2019-ncov/index.html
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About the author:
Prof. Dragan Primorac, M.D., Ph.D., is a pediatrician, medical genetics subspecialist and forensic expert witness. He is a professor at the Penn State University and University of New Haven in the US, the Xi’an Jiaotong University in China, the College of Medicine and Forensics and the Schools of Medicine at the Universities of Split, Osijek and Rijeka. He has given over 150 keynote lectures on all continents and has published a total of about 200 scientific papers, conference papers and book chapters. He was the first person to be awarded the Global Penn State Ambassador title. Dragan Primorac is the Chair of the International Affairs Committee of the American Academy of Forensic Sciences as well as the president of the International Society for Applied Biological Sciences, one of the most renowned international scientific organizations in the field of personalized medicine, and clinical and forensic genetics. In addition, he is the President of the Board of Trustees of St. Catherine Hospital, the Croatian Society of Human Genetics, the Croatian Society of Personalized Medicine and the Croatian Competitiveness Cluster for Personalized Medicine.