key: cord-309970-jkmjiika
authors: Liu, Qin; Xu, Kaiyuan; Wang, Xiang; Wang, Wenmei
title: From SARS to COVID-19: What lessons have we learned?
date: 2020-08-21
journal: J Infect Public Health
DOI: 10.1016/j.jiph.2020.08.001
sha: 
doc_id: 309970
cord_uid: jkmjiika

Abstract After the outbreak of severe acute respiratory syndrome (SARS) in November 2002, coronaviruses (CoVs) received worldwide attention. On December 1, 2019, the first case of coronavirus disease 2019 (COVID-19), caused by a novel coronavirus (SARS-CoV-2), was reported in Wuhan, China, and CoVs returned to public view. On December 30, 2019, the World Health Organization (WHO) declared that the COVID-19 epidemic is a public health emergency of international concern (PHEIC), and on March 11, 2020, the WHO classified COVID-19 as a pandemic disease. As of July 31, 2020, COVID-19 has affected 216 countries and regions, with 17,064,064 confirmed cases and 668,073 deaths, and the number of new cases has been increasing daily. Additionally, on March 19, 2020, there were no new confirmed cases in China, providing hope and valuable experience for the international community. In this review, we systematically compare COVID-19 and SARS in terms of epidemiology, pathogenesis and clinical characteristics and discuss the current treatment approaches, scientific advancements and Chinese experience in fighting the epidemic to combat the novel coronavirus pandemic. We also discuss the lessons that we have learned from COVID-19 and SARS.

December 1, 2019 [2] , pneumonia caused by a new coronavirus began spreading rapidly in China, with a similar trend globally. As the virus continued to spread, on March 11, 2020 , the WHO declared that COVID-19 is a pandemic disease, making this the first time that a coronavirus infection has been regarded as a global pandemic, in contrast to SARS in 2002, which did not reach this level. As of July 31, 2020, 216 countries have been affected, with a global total of 17,064,064confirmed cases and 668,073 deaths (WHO real-time statistics). The main timeline of the COVID-19 pandemic is shown in Figure 1 . The outbreak has caused widespread fear and concern and threatens global health security. The virus that causes COVID-19 named SARS-COV-2 [3] , SARS-CoV-2 and SARS-CoV have highly similar gene sequences and behavior patterns. This paper summarizes the differences in the epidemiology, clinical manifestations, and treatment of SARS and COVID-19 during the two outbreaks, summarizes the lessons learned, and provides a comprehensive reference for the global epidemic prevention and treatment of reported in China and resulted in a large number of infections. However, the COVID-19 has been more widespread and has spread faster than SARS, affecting populations around the globe [4] .

There has been considerable discussion on the origin of the causative virus SARS-CoV-2 after the first reports of COVID-19 in Wuhan [5, 6] . Rapid sequencing of the nearly 30,000-nucleotide SARS-CoV-2 genome was accomplished and announced worldwide on January 10, 2020, by Zhang's group and several others in China. CoV is an enveloped RNA virus that primarily causes respiratory and gastrointestinal infections [7] . Studies have shown that the nucleotide sequences of the SARS-CoV-2 and SARS-CoV genes are less than 80% identical [5] . However, the amino acid sequences of the seven conserved replicase domains in ORF1ab that are used for CoV species classification are 94.4% identical between SARS-CoV-2 and SARS-CoV, suggesting that the two viruses belong to the same species. Notably, studies have confirmed that SARS-CoV-2 uses the same cell entry receptor-angiotensin converting enzyme II (ACE2) -as SARS-CoV [4, 8] . Wrapp et al. found that the binding affinity of SARS-CoV-2 to ACE2 was approximately [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] times that of SARS-CoV [9] , which can provide one explanation for why SARS-CoV-2 has more human-to-human transmission than SARS-CoV. However, there is no clear evidence suggesting that SARS-CoV-2 has evolved from SARS-CoV.

To date, there is no evidence showing that SARS-CoV-2 originated in the seafood market. Recently, an article published in Nature Medicine on March 17 J o u r n a l P r e -p r o o f clearly showed that SARS-CoV-2 is not a laboratory construct or a purposefully manipulated virus. Several studies have shown that bats may be a potential reservoir for SARS-CoV-2 [10] . Sequencing of the viral genome showed 96.2% consistency across the whole genome sequences of bat CoV from Rhinolophus affinis and human SARS-CoV-2 [5] , indicating that they may belong to the same ancestor; however, no bats were sold in the Wuhan seafood market [6] . In addition, protein sequence alignment and phylogenetic analysis showed that similar receptor residues were found in many species, which provided more possibilities for alternative intermediate hosts,

such as pangolins or mink [11] .

According to the research by the team of academician Zhong Nanshan, the incubation period of COVID-19 ranges from 0 to 24 days, with a median incubation period of 3 days. The population is generally susceptible to infection or infectious during the incubation period [12] . COVID-19 is highly contagious among humans, and older individuals and people with underlying diseases are especially affected.

Based on the published data, the median patient age was 47-59 years in COVID-19 (similar to SARS and MERS), and 54.3-58.1% of patients were male in COVID-19

(the male-to-female ratio of 1:1.25 in SARS, and 1.82:1 in MERS) [1, 8, 12, 13] . Some studies have reported that 1.2-2% of COVID-19 patients were children (6% in SARS and 2% in MERS) [13] [14] [15] [16] . According to the available data, children appear to be at lower risk for COVID-19 than adults and children are less symptomatic with less fatality, which is concordant to earlier epidemic outbreaks of SARS-CoV respectively J o u r n a l P r e -p r o o f [14, 15] . On March 4, 2020, the national health commission issued the diagnosis and treatment program of COVID-19 pneumonia (trial seventh edition) [15] , which indicated that transmission through respiratory droplets and close contact was the main transmission route of SARS-CoV-2. The virus can be spread by aerosol when an individual is exposed to a high concentration of aerosolized virus for a long time in a relatively closed environment. Since SARS-CoV-2 can be isolated from feces and urine, attention should be paid to aerosol or contact transmission from feces, urine or environmental pollution; other avenues of spread are not entirely clear [17] . A paper published in the Lancet argues that transmission through the conjunctiva of the eye cannot be ignored [18] . Other studies have suggested that there may be mother-to-child transmission (vertical transmission) [19] . In summary, to date, the transmission route of SARS-CoV-2 has not been completely clarified, and relevant protective measures and attention should not be reduced [20] . Regardless of the exact mechanisms by which SARS-CoV-2 was naturally selected, the ongoing surveillance of pneumonia in humans and other animals is clearly of utmost importance.

According to a report published in Nature on March 20, 2020, 30%-60% of newly infected people have no symptoms or mild symptoms; however, their ability to spread the virus is not low, and covert coronavirus infections could be seeding new outbreaks.

There is growing evidence that some infected people are highly contagious when their symptoms are mild or asymptomatic [21] . Understanding the proportion of cases of asymptomatic or mild illness is important for us to understand the cause of this J o u r n a l P r e -p r o o f particular pandemic, as indicated by Michael Osterholm, director of the center for infectious disease research and policy at the University of Minnesota [22] .

SARS patients mainly present with fever and chills, accompanied by systemic and respiratory symptoms including mild fever and muscle pain. Severe respiratory failure and other organ dysfunction can occur during the incubation period from 1 to 16 days, commonly from 3 to 5 days. The onset is rapid, and the infectivity is strong, with fever as the first symptom. The course of the disease is 1-2 weeks. The prognosis of patients with headache, muscle soreness, general fatigue and diarrhea is related to the characteristics of the host (including age and sex) [23] . During hospitalization, the mean time from onset to severe respiratory distress was 9.8 to 3.0 days in 90.8% of SARS patients. Chest computed tomography (CT) shows ground-glass opacities with smooth interlobular septal thickening, sometimes with consolidation in a subpleural location [24, 25] .

SARS-CoV-2 infections generally exhibit milder symptoms than SARS-related infections. Zhong Nanshan's team and a number of studies [26, 27] have shown that the main symptoms of COVID-19 patients are fever, cough and fatigue, and the infrequency of symptoms of the upper respiratory and gastrointestinal tracts suggests that the viral tropism of SARS-CoV-2 is different from that of SARS-CoV [28] . A study published in the New England Journal of Medicine (NEJM) on March 19 found J o u r n a l P r e -p r o o f that among COVID-19 patients, children have milder symptoms than adults, and it is not uncommon to see asymptomatic children [29] . The disease can be classified as mild, moderate, severe or critical according to whether there are clinical symptoms, whether there is pneumonia, the severity of the pneumonia, the presence of respiratory failure or shock, and whether there is other organ failure. The

Beijing Center for Disease Control and Prevention suggests that the typical COVID-19 case exhibits a progressive disease course, and current clinical data show that most deaths occur among older patients. However, severe cases have been documented among young people with specific factors, especially those with chronic diseases, such as hypertension, diabetes, and cardiovascular disease; additionally, young people who have been using hormones or immunosuppressants for a long time and whose immune function is impaired are likely to have severe disease.

Laboratory examination showed that the white blood cell count in peripheral blood was normal or decreased, that the lymphocyte count was decreased, and that the degree of lymphocyte decline was correlated with disease severity [6] . In most patients, CRP and blood sedimentation were increased, and in some patients, liver enzymes, myoglobin, LDH, and D-dimer were increased. SARS-CoV-2 nucleic acids can be detected in a variety of specimens, including pharyngeal swabs, sputum, lower respiratory tract secretions, blood and feces [12] . RT-PCR and/or NGS methods have been used to detect SARS-CoV-2 nucleic acids in lower respiratory tract specimens (sputum or airway extracts) more accurately. By serological monitoring, positivity for J o u r n a l P r e -p r o o f the new coronavirus-specific IgM antibody is evident in most cases from 3-5 days after onset, and the titer of IgG antibody in the recovery stage is 4 times higher than that in the acute stage. Regarding pathological changes, the mucus and mucus accumulation in the airway are mainly caused by damage to the lungs and immune system. Other organs show mostly secondary damage due to different underlying diseases. Data from Zhong Nanshan's team showed that on admission, a ground-glass shadow was the most common radiological manifestation on chest CT (56.4%).

Lymphocytopenia at admission affected for 83.2% of cases [12] . Radiological diagnostic sensitivity is limited, so findings should be verified by combining clinical symptoms and viral RNA detection. The first autopsy report of the COVID-19 in China indicated that the gross view of the lung had large amounts of airway viscous secretions, mainly caused by distal alveolar injury. Findings from a local histological study of COVID-19 cadaver biopsy samples published in Lancet Respiratory Medicine showed that the pathological features of COVID-19 were similar to those of SARS and MERS [30] . More systematic autopsy data and histopathological verification are needed for further study.

At present, effective antiviral drugs against the pathogen are lacking, and the main treatments are isolation and symptomatic supportive treatment.

J o u r n a l P r e -p r o o f In general, the following strategies should be applied: bedrest and intense supportive treatment to ensure adequate heat; attention to water/electrolyte balance and maintenance of stability of the internal environment; and close monitoring of vital signs, namely, oxygen saturation. For patients with anoxic dyspnea in the acute phase, oxygen therapy should be given in time, and noninvasive or invasive ventilator support, which can best restore the patient's lung function, should be given when necessary.

On the basis of symptomatic treatment, we should also actively prevent and treat complications, treat basic diseases, prevent secondary infection and provide timely organ function support for severe and critical cases. Regarding circulation support, on the basis of full fluid resuscitation, we should also improve microcirculation, use vasoactive drugs, and perform hemodynamic monitoring if necessary.

In addition, intravenous infusion of gamma globulin may be considered for severe and critical pediatric cases. Severe or critical pregnancy cases should undergo termination of pregnancy, and cesarean section is the preferred delivery method.

Patients often have anxiety and fear and should therefore undergo psychological counseling.

Recently, based on the experiences of China and other countries worldwide in the fight against COVID-19, the WHO summarized and launched the four most promising COVID-19 treatment regimens: (1) remdesivir (2) chloroquine phosphate and hydroxychloroquine (3) lopinavir + ritonavir (4) lopinavir + ritonavir + interferon.

The four treatment regimens will be widely and randomly tested in a number of countries and regions, and we hope to find an effective and safe treatment for COVID-19 as soon as possible.

COVID-19 is highly infectious and belongs to the category of traditional Chinese medicine (TCM) "epidemic" diseases, and "dampness, poison, stasis, closure and deficiency" are the characteristics of its pathogenesis [31] . TCM formulates treatment based on a symptom-based diagnosis, an approach that is increasingly emphasized in other disciplines [32] . According to the latest research by Zhong Nanshan's team, LH significantly inhibits SARS-CoV-2 replication, affects viral morphology and has anti-inflammatory activity in vitro [33] . These findings indicate that LH protects against viral attack, J o u r n a l P r e -p r o o f making LH treatment a novel strategy for controlling COVID-19.

The differences and similarities between SARS and COVID-19 are summarized in Table 1 .

On March 11, the WHO declared the outbreak of COVID-19 to be a "pandemic" and on July 31, 2020, the global epidemic had spread to 216 countries and regions.

Among these countries, the United States has confirmed a total of 4,388,566 cases, both Brazil and India had more than 1,600,000 confirmed patients and the epidemic is in a period of rapid growth. Additionally, on March 19, the Chinese mainland, including Hubei Province, reported zero new confirmed or suspected cases, and the new confirmed cases was lower than 10 everyday now. During the outbreak, China acted quickly; an epidemiological investigation was carried out on December 29. On January 1, the South China seafood market in Wuhan was closed. On January 23, the Wuhan lockdown was implemented. On January 25, the CPC central committee set up a leading group to address the epidemic. Digital media was used to monitor and report the epidemic situation in real time [34] . The government formulated epidemic prevention policies (strict restrictions on travel and public gatherings; closure of public places; implementation of strict temperature monitoring across the country; correct use of masks; suspension of work and school; personal monitoring at home, etc.), and people throughout the country actively cooperated.

In an interview on March 18, the WHO representative in China, Dr. Colliers, said that China has shown the world that the trajectory of the epidemic can be changed. Typically, an epidemic grows exponentially, peaks, and then gradually begins to decline after all susceptible people have been infected or become ill. But that has not occurred in China. The epidemiological curve in China is irregular, the epidemic has been snuffed out in its growth phase, and the transmission of the virus has been blocked, as is clearly shown by both the collected data and the observed social reality. The national emergency response appears to have delayed the growth and limited the size of the COVID-19 epidemic in China, averting hundreds of thousands of cases by 19 February (day 50) [35] . Chinese experience shows that not all infectious diseases need to manifest as large outbreaks that overwhelm health systems. Every country can learn from this experience and apply the obtained knowledge on its own terms.

(1) Early detection: Viral detection reagents play an important role in this process.

Early in the outbreak, a community in the heart of the Italian epidemic conducted an experiment in controlling the epidemic and was able to stop the rise in cases (all residents were tested repeatedly for the virus, regardless of whether they had symptoms). After the infection is confirmed, strict quarantine measures are imposed on contacts. This highlights the importance of detecting and isolating carriers of the virus. Various measures should be taken to strengthen the effective control of the source of infection.

(2) Early diagnosis: Integrated medical thinking is required because viruses involve the respiratory system, oral cavity, digestive tract, eyes, skin, genital tract, and central nervous system.

(3) Early quarantine: The population is generally susceptible, regardless of race, with slightly more males than females affected, with more older patients and fewer pediatric cases. 

The authors declare no conflicts of interest.

The authors declare no conflicts of interest. 

We declare no competing interests. J o u r n a l P r e -p r o o f Shaping a protocol to use a batch of effective TCM formulas.

There is no FDA-approved vaccine for SARS. Accelerating the development of vaccines. 

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This work was supported by the National Natural Scientific Foundation of China