key: cord-1045763-evk2xpx1
authors: Liu, Jie; Xie, Wanli; Wang, Yanting; Xiong, Yue; Chen, Shiqiang; Han, Jingjing; Wu, Qingping
title: A comparative overview of COVID-19, MERS and SARS: Review article
date: 2020-07-26
journal: Int J Surg
DOI: 10.1016/j.ijsu.2020.07.032
sha: 8c5bd07f19b79a13a5239bc4b4767fddf8f7a228
doc_id: 1045763
cord_uid: evk2xpx1

Following the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV), a third, highly pathogenic coronavirus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) appearing at end of 2019 led to a pandemic, increased panic and attracted global attention. This review analyzes the epidemiology, etiology, clinical characteristics, treatment and sequelae of the severe acute respiratory syndrome (SARS), the Middle East respiratory syndrome (MERS) and the 2019 novel coronavirus disease (COVID-19) to help provide direction for further studies that can help understand COVID-19.

Coronaviruses are enveloped, positive-stranded RNA viruses that negatively influence the respiratory, intestinal, liver and nervous systems of animals and humans [1, 2] . Before the discovery of SARS-CoV-2, there were only six human coronaviruses identified. Among these, HCOV-229E, HCOV-NL63, HCOV-OC43 and HCOV-HKU1 mainly led to self-limited, respiratory infections that became serious in infants, immunosuppressed patients and elderly individuals. SARS and MERS belong to the B and C subclasses of β -coronavirus respectively and both can lead to fatal respiratory diseases [3] . SARS-CoV-2, SARS-CoV and MERS-CoV are zoonotic viruses that are highly pathogenic. Diseases caused by these viruses including COVID-19, SARS and MERS significantly impact infected individuals as well as the economies of infected countries. This article presents the epidemiology, etiology, clinical features, laboratory tests, imaging, treatment and sequelae of SARS-CoV-2, SRAS-CoV and MERS-CoV to provide reference for the development of treatment plans and infection-control measures that can be used for COVID-19.

SARS-CoV is the coronavirus causing first-century pandemic that originated in an animal market in Guangdong Province, China in November 2002 and eventually spread to over 30 countries in about 8 months (https://www.who.int/csr/sars/country/table2004_04_21/en/ ). Ten years later, a second coronavirus, MERS-CoV, originating in the Middle East infected over 2000 of individuals world-wide, with the highest number of cases in Saudi Arabia. Almost all MERS-CoV infected cases reported outside of the Middle East were related to travel in the Arabian Peninsula or closely related to already infected cases (http ://www.who.int/emergencies/mers-CoV/en/). At the end of 2019, pneumonia caused by a novel, highly pathogenic human coronavirus, SARS-CoV-2, was discovered in a seafood market in Wuhan, Hubei, China. Subsequently, infection quickly spread to China and around the world. By the 20 th of May 2020, COVID-19 infected 499, 3470 of individuals and caused 32, 7738 world-wide (https://www.who.int/docs/ default-source/coronaviruse/situation-reports/20200522-CoVid-19-sitr ep-123.pdf?sfvrsn¼5ad1bc3_4).

The most likely natural hosts of SARS-CoV, MERS-CoV and SARS-CoV-2 are bats. Chinese horseshoe bats coronaviruses are closely related to SARS-CoV. Among these, RsSHC014 and Rs3367 from Yunnan horseshoe bats have 95% homology with SARS-CoV [4] . The ORF8 protein SARSr-Rf-BatCoV YNLF_31C and YNLF_34C from greater horseshoe bats has over 80% homology to human SARS-CoV [5] . MERS-CoV has high homology with bat coronavirus HKU4 or HKU5 and its polymerase gene (RdRp) has 90-92% amino acid homology with the bat coronavirus HKU4 or HKU5 [1] . The genomes of SARS-CoV-2 and SARS-CoV are similar and have 79.6% identity. The SARS-CoV-2 and bat coronavirus RaTG13 has 96% identity in genome sequence. Given the high homology between SARS-CoV-2 and bats coronaviruses, bats may be the original host of SARS-CoV-2 [6, 7] . Intermediate hosts between the three coronaviruses differ. SARS-CoV was isolated from civets, cats, raccoons and ferret badgers in live animal market, suggesting that these animals may serve as intermediate hosts [8] . MERS-CoV was isolated secretions obtained from the nose of a camel and those who were infected with this virus were in close contact with camels, suggesting that camels served as an intermediate host for the transmission of MERS-CoV [9] . Studies on COVID-19 have shown that the pangolin is an intermediate host for promoting the transfer of SARS-CoV-2 to humans [10] . Furthermore, in an animal model of SARS-CoV-2, animals vulnerable to the virus were ferrets and cats, which may also act as intermediate hosts for transmission to humans. The number and array of intermediate hosts for this virus are still uncertain [11] . The transmission of zoonotic coronaviruses to humans through an intermediate host may be related to human consumption of intermediate hosts via their meat, serum or milk or direct contact with these host animals. For example, a patient diagnosed with MERS-CoV infection experienced frequent contact with camels and consumed unpasteurized camel milk before diagnosis [12] . Active markets may provide ideal conditions for the amplification, recombination and transmission of the human coronaviruses to human hosts. During the process of epidemic prevention, public health surveillance in active markets is very important.

The spread of SARS and MERS between individuals is dominated by transmission through health care settings. A study on SARS in Hong Kong showed that 49.3% of infected individuals were related to clinics, hospitals or nursing homes, and health care workers accounted for 23% of infected individuals [13] . In the Toronto study, out of 144 patients diagnosed with SARS, 77% were associated with hospital exposure [14] . The incidence of MERS in health care settings may be high, reaching 100%. Nosocomial outbreaks of SARS and MERS are characterized by highly heterogeneous transmission and marked by super-spreading events. However, the prevalence rate of health-care workers with SARS is higher than MERS [15] [16] [17] . Among the first 138 cases of COVID-19, 41% of infections may be hospital-related transmissions [18] . Some secondary transmission cases for the three viruses were through community or family clusters. Among these, the famous Amoy Gardens SARS outbreak was associated to the sewage system failure after fecal pollution in the index case [13] . In the MERS family cluster study, close contact with patients and direct patient-care activities, such as resting in the room of target patients, contact with patient respiration secretions or the removal of human excreta were risk factors for family transmission of MERS [19] . There is a good number of asymptomatic patients with SARS, MERS and COVID-19. In a retrospective study, serological tests revealed asymptomatic SARS patients that composed a small number of cases [20] . There is a larger number of infected MERS and COVID-19 patients that appear to be asymptomatic [21, 22] . Some asymptomatic COVID-19 patients continued to test negative through CT [23] . Asymptomatic patients contained high viral loads and long virus shedding times, indicating that transmission potential existed in asymptomatic patients [22, 24] . Therefore, asymptomatic patients cannot be ignored in the process of epidemic prevention.

R0 indicates the average number of additional infections among fully susceptible people. In the absence of intervention and control measures, the R0 of SARS was about 3. Without effective public health intervention, the epidemic spread continuously and widely [25] . The R0 of COVID-19 is also large. Designating cases on the Japanese cruise ship Diamond Princess as a group, the R0 value was about 2.28 at the beginning of the outbreak. Another analysis of over 400 cases confirmed in Wuhan estimated that the R0 value was 2.2. Like SARS, COVID-19 has an R0 greater than 1 and is highly contagious [26, 27] . The study on the ability of interhuman transmissibility of MERS showed that in most pessimistic scenario, the R0 of MERS in secondary cases was about 0.69 [28] , A similar study estimated that without control, the range of R0 values for MERS was 0.8-1.3 [29] . R0 values for MERS was much lower than the epidemic threshold and did not show a trend of a continuous epidemic. However, during hospital outbreaks in Saudi Arabia and South Korea, the R0 of MERS was estimated to be 2-5, possibly since nosocomial infection could be transmitted not only by contact but also by aerosol contrary to community-acquired infection [30] . The above-mentioned R0 is mainly used for human-to-human transmission and R0 varies when used in host-to-human transmission.

Different host selectivity and tissue toxicity of coronaviruses may depend on differences in spike (S) protein. The spike (S) protein of coronavirus is a type I membrane glycoprotein with multiple functional domains. It binds to the specific cell receptor through its S1 subunit and then mediates the fusion of the virus and the cell membrane through its S2 subunit [2] . SARS-CoV and SARS-CoV-2 enter the target cell through the ACE2 receptor and initiates S protein infection based on the host cell protease TMPRSS2 [31] [32] [33] [34] . Compared to SARS-CoV, the RBD of SARS-CoV-2 binds to angiotensin converting enzyme II (ACE2) more closely and RBD residue changes make binding between the virus and receptor more stable [32] . A ten-year structure study based on SARS-CoV shows that the efficiency of SARS-CoV-2 using human ACE2 may be lower than human SARS-CoV (2002) but higher than human SARS-CoV (2003), indicating that COVID-19 has acquired some transmission power between individuals [35] . ACE2 is highly expressed in the lung, gastrointestinal tract, kidney, testis and cardiovascular system, especially in type II alveolar cells and intestinal epithelial cells, which is consistent with symptoms observed in SARS and COVID-19 cases [36, 37] . ACE2 plays a role in a variety of biological functions such as regulating blood pressure, heart and kidney function [38, 39] . ACE2 can reduce acute lung injury and shows protective effects in the lung [40, 41] . CD209L (a transmembrane glycoprotein) is another receptor involved in SARS-CoV infection. However, the efficiency of mediating infection is much lower than that of ACE2 [42] .

The MERS-CoV receptor is an exopeptidase dipeptidyl peptidase-IV (DPP IV; also known as CD26), which is a multifunctional type II transmembrane glycoprotein. DPP IV is highly expressed in the liver, kidney, intestinal epithelial cells and prostate. DPP IV also has a wide range of effects such as reducing intestinal insulin degradation. It also plays a role in lymphocyte immune functions and tumor transformation [43] .

The cellular susceptibility of the three coronaviruses differs. In 9 different cell tests, SARS-CoV-2 and SARS-CoV showed similar tissue tendency and replicated stably in the lung cells, intestinal cells, hepatocytes and kidney cells. The replication ability of SARS-CoV-2 in the lung and intestine was opposite to what was observed for SARS-CoV. Moreover, SARS-CoV-2 had the ability to replicate in neuronal cells [44] . In a sensitivity study including 28 cell lines, MERS had the ability to effectively replicate in 17 cell types. In addition to respiratory tract infection, the viral load of MERS in the kidney, intestine, hepatocytes, tissue cells, neurons, monocytes and T lymphocytes increased significantly, showing a greater tissue tendency than SARS [45] .

The peak viral load of SARS appeared on the 10th day and the peak viral load of MERS appeared during the second week of the disease [46, 47] . Compared to SARS and MERS, the viral peak of COVID-19 appeared earlier, and the salivary viral load was the highest in the first week after symptom onset [48, 49] . The viral load of the three viruses in severe cases was higher than that in mild groups [46, 47, 50] . In severe MERS-CoV infections, the time for virus shedding in respiratory secretions was also significantly longer than in mild patients [51] . Some studies had shown that there was a positive correlation between age and peak viral load in both SARS and COVID-19 cases [49, 52] . Also, the initial viral load of people infected with SARS-CoV was independently correlated with poor prognosis [50] .

The initial symptoms of MERS, SARS or COVID-19 infection are nonspecific. Fever and cough are the most familiar and dry cough is the main symptom. Other communal symptoms include myalgia, shortness of breath or dyspnea, chills and gastrointestinal symptoms. Gastrointestinal symptoms (diarrhea, nausea and vomiting) are the first symptoms observed in some patients and most patients show potential complications. Severe cases will progress from no hypoxemia to acute respiratory distress syndrome, multiple organ failure or even death [13] [14] [15] 18, 19, 24, 46, [53] [54] [55] [56] [57] [58] [59] [60] [61] [62] [63] [64] [65] [66] [67] . A corresponding summary is presented in Table 1 .

Factors related to the progression of SARS and COVID-19 differ. Age and chronic hepatitis B virus infection were shown to be important independent risk factors for the progression of SARS to ARDS. Immunity of patients diagnosed with hepatitis B infection may not be able to resist coronavirus infection. Advanced age was a predictor of adverse outcomes for SARS [46] . Besides age, neutropenia, organ and coagulation dysfunctions also are associated with the progression of COVID-19 to ARDS and even the progression of ARDS to death. Among COVID-19 patients, patients with high fever are more likely to develop ARDS but have a lower risk of death [62] .

Severe coronavirus cases show characteristics of advanced age, diabetes, hypertension, chronic heart disease and other chronic complications and greater APACHE-II and SOFA scores at admission. The main reason for entering the ICU may be that mechanical ventilation treatment is needed for ARDS [13, 14, 55, 59, [68] [69] [70] [71] . It is possible that patients with these complications are more likely to trigger the release of a large number of cytokines during coronavirus infection. In SARS cases, tachycardia and elevated creatine kinase were associated with poor prognosis. Bilateral X-ray pulmonary infiltration was more common in patients who subsequently needed ICU care [55] . Central tachycardia is the score content of APACHE II in critically ill patients. Severe MERS patients required more renal replacement therapy than SARS and COVID-19 and showed extrapulmonary organ dysfunction [64, 68, 72] . Critically ill MERS patients were more likely to be treated with vasopressors. The need for vasopressors was an independent risk factor for death in MERS patients [69] . The use of vasopressor may indicate tissue perfusion disorders. Severe COVID-19 cases were also more likely to develop a sore throat, dyspnea, dizziness, abdominal pain and anorexia [70] .

The most common laboratory tests for COVID-19, MERS and SARS measure lymphocytopenia, elevated lactate dehydrogenase and elevated liver transaminase. Thrombocytopenia and elevated creatine kinase can also be analyzed in some patients [13] [14] [15] 18, 19, 24, 46, [53] [54] [55] [56] [57] [58] [59] [60] [61] [62] [63] [64] [65] [66] [67] . Elevated lactate dehydrogenase levels are associated with tissue injury. High or peak LDH levels were associated with ICU or death in SARS and COVID-19 patients [13, 53, 62] . This could predict pulmonary fibrosis in patients with MERS and SARS after discharged from the hospital [73, 74] . In some SARS and COVID-19 cases, coagulation disorders were observed such as increased levels of D-dimer, prolonged prothrombin time or activated partial thromboplastin time [53, 60] . In hospitalized COVID-19 patients, D-dimer levels greater than 1 μg/mL were associated with increased mortality [60] . In addition, hypoproteinemia was an independent risk factor for severe MERS infections [24] .

The abnormal rate of chest X-rays for coronaviruses is over 70% and the abnormal rate of chest X-ray in MERS and COVID-19 is greater than SARS [13] [14] [15] 18, 19, 24, 46, [53] [54] [55] [56] [57] [58] [59] [60] [61] [62] [63] [64] [65] [66] [67] . Air-space opacity is an abnormality observed in SARS chest radiographs. After an initial, normal chest radiograph, it may develop into focal consolidation or bilateral, multifocal consolidation, primarily in the middle and lower regions of the lung and surrounding tissues without pleural effusion, cavitation or hilar lymph node enlargement [53, [75] [76] [77] . A chest computed tomography (CT) is more sensitive to the changes of disease than a chest radiograph. Thin sliced CT for SARS was often manifested as ground glass opacity or ground glass opacity combined with consolidation. Interlobular septal thickening, interlobular interstitial thickening, the crazy-paving mode and bronchiectasis were also identified [78] .

MERS chest radiographs showed that common changes included surrounding ground glass followed by consolidation, patchy consolidation, confluence or a round nodular shadow. In the late stage of the disease, more patients exhibited pleural effusion and pneumothorax. Pleural effusion and higher chest X-ray or chest CT scores were associated with poor prognosis and short-term mortality [69, 79, 80] . The chest CT of COVID-19 is very similar to the other two viruses. Most of the lesions involve bilateral lungs, showing multiple patchy ground glass opacity or consolidation, distributed in the surrounding tissues and some patients exhibited nodular lesions [66, 67] . In early stages, multifocal incidence was greater than what was observed in the other two viruses. COVID-19 and MERS were more visible than SARS in pleural effusion and the pneumothorax [67,77,79]. 

At present, there is no effective prevention or targeted treatment for the three coronaviruses but symptomatic support is available. Frequently used drugs to treat symptoms include antibiotics, antiviral drugs (ribavirin, oseltamivir, lopinavir/ritonavir, interferon) and steroids. Empirical antibiotic therapy is widely used since patients may have bacterial infections or complications cannot be ruled out.

Ribavirin is a ribonucleoside analog that shows antiviral activity against a variety of DNA and RNA viruses. Its antiviral effect is directly related to its mutagenic activity in the treatment of poliomyelitis [81] . Even though ribavirin has widely been used in the treatment of coronaviruses, its efficacy has been controversial. In a retrospective cohort study investigating MERS, ribavirin combined with interferon-alpha significantly improved the 14-day survival rate of patients [82] . Another retrospective study investigating critically ill patients with MERS suggested that ribavirin/interferon may not lead to quicker RNA clearance of MERS-CoV and was associated with higher 90-day mortality in critically ill patients [83] . Ribavirin and glucocorticoids were widely used as a first-line treatment in critically ill SARS patients, but treatment outcomes suggested that the combination of ribavirin and glucocorticoids did not significantly benefit SARS [84] . Ribavirin shows obvious signs of toxicity and the use of high doses of ribavirin in critically ill patients can lead to progressive hemolytic anemia, bradycardia and hypomagnesemia [85] . The exact effects of ribavirin are unknown due to the mixed-use of multiple drugs. In the treatment of COVID-19, there have been many clinical trials for ribavirin, but the exact results are unknown.

Remdesivir shows broad-spectrum, anti-coronavirus activity and can inhibit the replication of SARS-CoV and MERS-CoV in human epithelial cells, improve lung function and reduce viral load [86] . Remdesivir was effective in controlling SARS-CoV-2 infection in vitro [87] . However, evidence is needed through a large number of clinical trials to validate the role of Remdesivir in COVID-19.

Corticosteroids have anti-inflammatory effects and can improve lung injury and reduce mortality in ARDS [88] . The three coronaviruses can cause patients to develop ARDS and the body produced a large number of inflammatory factors. Thus, immune regulation of corticosteroids may be suitable for the treatment of these viruses, but this is controversial [61, 89, 90] . Corticosteroids may be effective in relieving symptoms of SARS and the use of glucocorticoids was recommended [91] . In ARDS patients diagnosed with COVID-19, methylprednisolone treatment reduced risk of death [62] . However, in a trial evaluating the efficacy and safety of corticosteroids for ARDS treatment, methylprednisolone was found to increase risk of death after use of corticosteroids, although the cardiopulmonary function of patients improved [92] . Corticosteroid treatment could significantly delay the clearance of MERS-CoV RNA in respiratory secretions or SARS-CoV in the blood, probably through immunosuppressive effects [93, 94] .

Lopinavir/ritonavir is a protease inhibitor and may serve as a broadspectrum anti-coronavirus inhibitor. The antiviral ability of ritonavir is weak, mainly inhibiting the metabolism of CYP3A-mediated lopinavir and increasing its serum concentration. In vitro tests show that 4 μ g/ml of lopinavir had antiviral effects on SRAS-CoV [95] . SARS patients initially treated with lopinavir/ritonavir showed reduced use of steroids, viral load, overall mortality and intubation rates [95, 96] . In an in vitro study for MERS, a low concentration of lopinavir inhibited the replication of MERS-CoV and the inhibitory effect could reach 89% at the dose of 12 μM [97] . However, for SARS-CoV-2, lopinavir/ritonavir did not lead to a relevant decrease in viral load or significant clinical improvement and was more likely to cause gastrointestinal adverse events, including anorexia and nausea [98] .

Chloroquine/hydroxychloroquine is an anti-malarial drug showing direct antiviral and immunomodulatory effects [99] . In vitro experiments revealed that chloroquine was effective in the prevention and treatment of SARS-CoV infection. The addition of chloroquine before SARS infection showed that cells were not sensitive to SRAS-CoV infection [100, 101] . Chloroquine inhibited MERS-CoV replication in a dose-dependent manner, with a 50% effective concentration of 3.0 μM [97] . The role of chloroquine in SRAS-CoV-2 is similar to SARS-CoV [87] . Another randomized trial of COVID-19 showed that hydroxychloroquine significantly shortened clinical recovery time and promoted the absorption of pneumonia [102] .

Plasma in the recovery phase contains antibodies. Passive immunotherapy can suppress viremia and neutralize pathogens [103] . In early stage SARS patients, the recovery period plasma prognosis was more optimal and the discharge rate was greater [104] . Compared to continuous use of high-dose methylprednisolone, hospital stays were shorter and the mortality rate was lower [105] . Five critically ill patients with COVID-19 given convalescent plasma resulted in decreased viral load and improved prognosis [106] . However, there are some uncertainties and limitations in the use of restored plasma, such as the lack of randomized clinical trials, the risk of transmitting the infection to transfusion service personnel and the appropriate choice of donors for high neutralizing antibody titers [103] . Therefore, considerations are needed during plasma transfusions.

Spike protein and its fragments are the key targets for developing a highly effective coronavirus vaccine, which will be a long process.

There are many vaccines under development for SARS, such as an inactivated or whole-killed virus vaccine, recombinant vector vaccines, subunit vaccines, DNA vaccines or attenuated vaccines. However, the effects of the vaccine for protecting humans from clinical symptoms and lung injury is still uncertain [107] . A study investigating the safety and efficacy of a modified vaccine based on the expression of SARS-CoV spike protein or nucleocapsid protein found that when vaccinated ferrets were exposed to SARS-CoV, liver tissue damage was significantly stronger than what was observed in the unvaccinated group [108] . Also, the candidate vaccines developed by MERS were similar to SARS. Among these, the MERS-CoV RBD-based subunit vaccine showed strong safety and effectiveness in protecting transgenic mice from MERS-CoV attack. Most vaccine studies on MERS are under preclinical development [109, 110] . Vaccines against human SARS and MERS have not yet been approved. Presently, there are many countries working towards COVID-19 vaccine development. The vaccine development platform is similar to the previous two viruses. Some vaccines have rapidly entered into the clinical trial stage and the effectiveness and safety of the vaccines need to be seriously considered [111] .

In conclusion, various drugs used for COVID-19 need to be confirmed by high-quality clinical trials.

Surgical thresholds during the SARS-CoV-2 pandemic should be higher than normal. A cohort study involving 24 countries showed that half of patients with perioperative COVID-19 patients had postoperative pulmonary complications, and were associated with high mortality [112] ; Another study in Italy estimated that the surgical complications in COVID-19 patients with cancer was 13 times higher than that in the control group [113] . During the COVID-19 pandemic, surgeons need to balance the risks of delayed emergency surgery against the increased morbidity and mortality associated with SARS-CoV-2 infection.

For surgeons, standard personal protective equipment is absolutely necessary, specially performing operations related to aerosol generating procedures [114] . In addition, in order to minimize the risk of infection for patients and health care workers, surgeons should consider another clinical practice that limits time-in-hospital and promotes telemedicine to follow patients when needed [114, 115] .

During follow-ups for patients who have recovered from SARS and MERS, permanent damage to the lungs, commonly pulmonary fibrosis, was observed [73, 74] . In an 8-month follow-up study of SARS patients, most patients showed focal, multifocal fibrosis through chest high-resolution computed tomography (HRCT). A total of 7% showed mild restrictive lung injury and 38% showed reduced diffusivity [116] . Since COVID-19 is a new outbreak, it is worrisome that follow-up results and sequelae may be assessed at a later time.

Presently, COVID-19 has resulted in a global pandemic, posing a major threat to public health. There is no effective treatment for COVID-19. Infected individuals are asked to stay in isolation while receiving treatment for their symptoms. Since all three zoonotic coronaviruses are similar, it is important to learn from SARS and MERS to understand how these may be related to this new outbreak. To further understand the pathogenesis and therapeutic targets of COVID-19, a larger number of animal studies and clinical trials are required.

1、The National Key Research and Development Program of China (Grant No. 2018YFC2001900) .

2、The National Natural Science Foundation of China (Grant No. 81873952 ).

3、The National Natural Science Foundation of China (Grant No. 81901948 ).

Name of the registry: Unique Identifying number or registration ID: Hyperlink to your specific registration (must be publicly accessible and will be checked):

Qingping Wu.

Not commissioned, externally peer-reviewed.

Qingping Wu and Wanli Xie designed and conceived the paper. Jie Liu wrote the manuscript. Yanting Wang, Yue Xiong, Shiqiang Chen, Jingjing Han revised the manuscript. All authors read and approved the final manuscript.

The data presented in the article may be requested by consulting the correspondence author.

None.

None. 

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Corticosteroid therapy for critically ill patients with Middle East respiratory syndrome

Effects of early corticosteroid treatment on plasma SARS-associated Coronavirus RNA concentrations in adult patients

Role of lopinavir/ritonavir in the treatment of SARS: initial virological and clinical findings

Treatment of severe acute respiratory syndrome with lopinavir/ritonavir: a multicentre retrospective matched cohort study

Screening of an FDA-approved compound library identifies four small-molecule inhibitors of Middle East respiratory syndrome coronavirus replication in cell culture

A trial of lopinavirritonavir in adults hospitalized with severe covid-19

Effects of chloroquine on viral infections: an old drug against today's diseases?

Chloroquine is a potent inhibitor of SARS coronavirus infection and spread

In vitro inhibition of severe acute respiratory syndrome coronavirus by chloroquine

Efficacy of Hydroxychloroquine in Patients with COVID-19: Results of a Randomized Clinical Trial

Convalescent plasma: new evidence for an old therapeutic tool? Blood transfusion

Use of convalescent plasma therapy in SARS patients in Hong Kong

Retrospective comparison of convalescent plasma with continuing high-dose methylprednisolone treatment in SARS patients, Clinical microbiology and infection : the official publication of the

Treatment of 5 critically ill patients with COVID-19 with convalescent plasma

SARS vaccines: where are we? Expet Rev. Vaccine

Evaluation of modified vaccinia virus Ankara based recombinant SARS vaccine in ferrets

Middle East respiratory syndrome: current status and future prospects for vaccine development

Prospects for a MERS-CoV spike vaccine

The COVID-19 vaccine development landscape

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Determinants of COVID-19 disease severity in patients with cancer

Management of primary hepatic malignancies during the COVID-19 pandemic: recommendations for risk mitigation from a multidisciplinary perspective

Cancer in the time of COVID-19: expert opinion on how to adapt current practice

Eight-month prospective study of 14 patients with hospital-acquired severe acute respiratory syndrome