No antiviral treatment for coronavirus infection has been proven to be effective. Previous studies showed the combination of lopinavir and ritonavir may be beneficial for SARS-CoV and MERS-CoV infected patients [31, 32]. Treatment with intravenous remdesivir (a novel nucleotide analogue prodrug in development) showed significant improvement for the first case in US. A trial has been initiated quickly to assess the efficacy and safety of remdesivir in patients hospitalized with 2019-nCoV infection. Recently, a potent binding of 2019-nCoV spike protein by a SARS-CoV specific human monoclonal antibody were under investigation.

As the cytokine storm was observed in severe 2019-nCoV infection patients, low dose corticosteroids has been used to treat the patients for possible benefit by reducing inflammatory-induced lung injury. However, corticosteroids did not reduce the mortality for SARS-CoV and MERS-CoV infection by WHO interim guidance [34, 35].

Treatment regiments were classified into three categories depends on the severity of the disease: (1) For mild to moderate disease, the major treatment is supportive therapy; (2) for severe disease, oxygen inhalation through mask, high nasal oxygen flow inhalation, or non-invasive ventilation is needed. Careful and dynamic evaluation of patients oximeter and Chest imaging as well as laboratory examination is important; (3) for very severe disease, protective mechanical ventilation after tracheal intubation is required, and prone position ventilation followed if P/F ratio not improved, and eventually extracorporeal membrane oxygenation (ECMO) might be implemented if prone position plus mechanical ventilation did not work. Notably, the anxiety and depression of patients need to be consideration. We should not only pay attention to disease treatment, but also the mental issues of patients.

In addition, some traditional Chinese medicine (TCM), such as Snow Lotus (Saussuea involucrata), LianHuaQingWen, LiuShenWan might be beneficial for coronavirus infection treatment through immunity enhancement. Further evidence is needed to assess the effect of TCM treatment for patients infected with 2019-nCoV.

Infection control aspects of MERS have to do with preventing MERS exposures and minimizing person-to-person spread. Patients particularly from countries near the Arabian Peninsula who have an influenza-like illness should avoid travel until they are well. The following are based on CDC recommendations. If any patient has been exposed to a potential or known MERS case travel should be avoided. Household or family members exposed to potential or actual MERS cases should use masks. Such household and family members, while ill, if a family household member develops an ILI they should avoid public transportation, school, and work while ill. The individuals who are at increased risk for MERS include recent travelers from the Arabian Peninsula, particularly if such travelers develop fever and an ILI, including cough and shortness of breath, within 14 d after traveling from countries in or near the Arabian Peninsula. Those that have had close contact with someone that has recently traveled with respiratory symptoms and fever from countries in or near the Arabian Peninsula should be observed for 14 d starting from the day the patient was last exposed to the person.20 Those with increased risk for MERS also include those with close contact with a probable or confirmed case of MERS. Care should be taken with the exposed individual to monitor fever, cough, shortness of breath, and other symptoms, i.e., chills, myalgias, sore throat, nausea, vomiting, or diarrhea for 14 d counting from the last day of exposure to the ill contact. Healthcare personnel not utilizing proper infection control precautions are at increased risk for MERS.23,24 Close contact may be defined as any person that provides care for a patient, including healthcare workers, family members, or someone who had similarly close physical contact or any person who stayed at the same place, lived with, or visited the patient when the patient was ill.21-23 Infection control contact, and airborne precautions should be used while in close contact with symptomatic individuals or patients with MERS in the differential diagnosis.25 Infection control precautions should be observed when obtaining or conducting respiratory specimen testing for MERS. To prevent transmission to household members, masks should be worn in the house. Since person-to-person transmission has been demonstrated with MERS the use of masks and handwashing are important interventions to reduce transmission.

It has been shown that healthcare workers in contact with or taking care of MERS patients are at particularly high risk for developing MERS.23,26,27 Contact and airborne precautions should be used with appropriate personal protective devices to minimize the exposure of healthcare workers to suspected or known hospitalized MERS cases.26 Since it is not known how long MERS-CoV is present in respiratory secretions, it seems prudent that MERS patients remain on contact and airborne precautions until discharged.

Bed rest, strengthen supportive treatment, ensure sufficient energy; pay attention to water-electrolytes balance and maintain the stability of the internal environment; closely monitor vital signs and finger oxygen saturation, and so on.Monitor the blood routine, urine routine, C-reactive protein (CRP) and health indications (liver enzyme, myocardial enzyme, renal function, etc.), coagulation function, arterial blood gas analysis if necessary, and recheck chest imaging.According to the change of oxygen saturation, give effective oxygen therapy in time, including oxygen given by nasal catheter or mask. If necessary, apply high flow oxygen therapy via the nose, noninvasive or invasive mechanical ventilation, and so on.Antiviral treatment: no effective antiviral drug at present. Treat with IFN-α aerosol inhalation (five million U per time for adults, two times per day), and/or Lopinavir/Ritonavir oral administration (two tablets per time, two times per day).Antibiotic treatment: avoid blind and improper use of antibiotics, especially the combination use of broad-spectrum antibiotics. Strengthen bacteriological monitoring. Antibiotics should be used in time in secondary bacterial infection.

Initially, interferons-α nebulization, broad-spectrum antibiotics, and anti-viral drugs were used to reduce the viral load,,, however, only remdesivir has shown promising impact against the virus. Remdesivir only and in combination with chloroquine or interferon beta significantly blocked the SARS-CoV-2 replication and patients were declared as clinically recovered,,. Various other anti-virals are currently being evaluated against infection. Nafamostat, Nitazoxanide, Ribavirin, Penciclovir, Favipiravir, Ritonavir, AAK1, Baricitinib, and Arbidol exhibited moderate results when tested against infection in patients and in-vitro clinical isolates,,,. Several other combinations, such as combining the antiviral or antibiotics with traditional Chinese medicines were also evaluated against SARS-CoV-2 induced infection in humans and mice. Recently in Shanghai, doctors isolated the blood plasma from clinically recovered patients of COVID-19 and injected it in the infected patients who showed positive results with rapid recovery. In a recent study, it was identified that monoclonal antibody (CR3022) binds with the spike RBD of SARS-CoV-2. This is likely due to the antibody’s epitope not overlapping with the divergent ACE2 receptor-binding motif. CR3022 has the potential to be developed as a therapeutic candidate, alone or in combination with other neutralizing antibodies for the prevention and treatment of COVID-19 infection.

Treatment principle: based on symptomatic treatment, actively prevent and treat complications, treat basic diseases, prevent secondary infection, and timely apply organ function support.Respiratory support: apply noninvasive mechanical ventilation for two hours, if the condition is not improved, or the patient is intolerable to noninvasive ventilation, accompanied with increased airway secretions, severe coughing, or unstable hemodynamics, the patient should be transferred to invasive mechanical ventilation in time. The “lung-protective ventilation strategy” with low tidal volume should be adopted in invasive mechanical ventilation to reduce ventilator-associated lung injury. If necessary, ventilation in the prone position, recruitment maneuver, or extracorporeal membrane oxygenation (ECMO) can be used.Circulation support: improve microcirculation based on full fluid resuscitation, use vasoactive drugs, and apply hemodynamic monitoring if necessary.Others: according to the degree of dyspnea and the progress of chest imaging, use glucocorticoids appropriately for a short time (3–5 days) with the recommended dose no more than what is equivalent to methylprednisolone 1–2 mg/kg·day.

Ideally, infected patients should be treated with a customized treatment plan. However, currently, no specific antiviral therapies are available for 2019-nCoV. The National Health Commission recommends the following treatment for infected individuals.8

The evidence study about efficacy of GCs provided significant reduction in levels of markers of systemic inflammation and duration of mechanical ventilation, ICU stay, and decrease mortality. GCs also have a wide range in diminishing the release of cytokines, such as those on plasma interleukin-6 levels, neutrophil counts, CRP levels in serum, and BAL.

Even though there were not enough lines evidence suggesting that GCs can be considered as adjunctive treatment due to its harmful effect and still unknown clinical outcome, we should consider that whether the respond to GCs is ineffective, effective, or harmful is influenced by drug dosage and duration of administration. We summarized that low to moderate dosage of GCs provides beneficial outcome. The potential benefit effect during GCs administration may be diminished if discontinuation of treatment is not preceded by slow tapering and may lead to rebound inflammation noticed by increasing CRP value. A better understanding of the interaction between systemic GCs and immune response is necessary before recommending their use in the treatment of severe pneumonia.

Until the results of new studies that are already in progress are published, it seems reasonable to think that some patients could benefit from the use of GCs, such as patients with severe pneumonia of certain etiologies, those with adrenal insufficiency, and those who develop septic shock with a poor response to the resuscitation maneuvers with liquids and perfusion of pressor amines. We suggested for future studies to pay attention to enroll a standardized treatment regimen, including timing, dosage, formulation, duration, and length of tapering.

There is no available vaccine against COVID-19, while previous vaccines or strategies used to develop a vaccine against SARS-CoV can be effective. Recombinant protein from the Urbani (AY278741) strain of SARS-CoV was administered to mice and hamsters, resulted in the production of neutralizing antibodies and protection against SARS-CoV,. The DNA fragment, inactivated whole virus or live-vectored strain of SARS-CoV (AY278741), significantly reduced the viral infection in various animal models,,,,,. Different other strains of SARS-CoV were also used to produce inactivated or live-vectored vaccines which efficiently reduced the viral load in animal models. These strains include, Tor2 (AY274119),, Utah (AY714217), FRA (AY310120), HKU-39849 (AY278491),, BJ01 (AY278488),, NS1 (AY508724), ZJ01 (AY297028), GD01 (AY278489) and GZ50 (AY304495). However, there are few vaccines in the pipeline against SARS-CoV-2. The mRNA based vaccine prepared by the US National Institute of Allergy and Infectious Diseases against SARS-CoV-2 is under phase 1 trial. INO-4800-DNA based vaccine will be soon available for human testing. Chinese Centre for Disease Control and Prevention (CDC) working on the development of an inactivated virus vaccine,. Soon mRNA based vaccine’s sample (prepared by Stermirna Therapeutics) will be available. GeoVax-BravoVax is working to develop a Modified Vaccina Ankara (MVA) based vaccine. While Clover Biopharmaceuticals is developing a recombinant 2019-nCoV S protein subunit-trimer based vaccine.

Although research teams all over the world are working to investigate the key features, pathogenesis and treatment options, it is deemed necessary to focus on competitive therapeutic options and cross-resistance of other vaccines. For instance, there is a possibility that vaccines for other diseases such as rubella or measles can create cross-resistance for SARS-CoV-2. This statement of cross-resistance is based on the observations that children in china were found less vulnerable to infection as compared to the elder population, while children are being largely vaccinated for measles in China.

As the case count and death toll of the epidemic continue to increase, it becomes imperative to identify therapeutic options for COVID-19. Once in vitro and in vivo systems have been established, these tests can proceed. Drug repurposing may prove to be the best strategy for quick development of novel therapeutic options. A novel therapeutic being tested is remdesivir (19, 20), which in combination with chloroquine has been found to inhibit SARS-CoV-2 growth in vitro (21). It was recently announced by the NIH that remdesivir would be entering phase 3 clinical trials in humans. Chloroquine has also been reported to be effective in patients in China (22). A combination of lopinavir and ritonavir is also under investigation in human cases of COVID-19 in China. Many more people will need to be treated with these drugs to determine true efficacy, but they are promising leads.

Since the outbreak in 2003, a respiratory disease, caused by coronavirus or well known as SARS, quickly spread around parts of the world; many studies have demonstrated empirical GCs therapy to treat SARS. At that time, because the urgency of the international outbreak did not allow time for efficacy studies, physicians in Canada and Hong Kong treated the earliest patients with intravenous ribavirin, broad-spectrum antiviral activity, and then followed by empirical GCs therapy and other treatment [75, 76].

Hien et al. confirmed that early hydrocortisone administration was initiated in <7 days of illness associated with significantly higher subsequent plasma viral load in second and third weeks; duration of viraemia may also be prolonged. Ho et al. recommended that initial use of pulse methylprednisolone (≥500 mg/day) has more efficacious benefit such as reducing ICU admission, improving mechanical ventilation and mortality rate; it is also equally shown to be safer compared with low dosage. Thus, low-dosage GCs also provided better prognosis in SARS patient's symptom and improved lung function [78–80]. In studies of SARS patients in Guangzhou, 121 of 152 critical patients (79.6%) received GCs at a mean daily dose of 133.5 ± 102.3 mg, which showed beneficial effect of GCs on mortality and shorter hospitalization days.

In October 2003, WHO established an International SARS Treatment Study Group in managing SARS and demonstrated optimal treatment options to deal with SARS. This systematic review reported summary effects of ribavirin, lopinavir, ritonavir (LPV/r), GCs, type I IFN, intravenous immunoglobulin (IVIG), or convalescent plasma in relation to (1) SARS-CoV replication inhibition in vitro, (2) mortality or morbidity in SARS patients, and (3) effects on ARDS in adult patients.

Given the lack of effective antiviral therapy against COVID-19, current treatments mainly focused on symptomatic and respiratory support according to the Diagnosis and Treatment of Pneumonia Caused by COVID-19 (updated to version 6) issued by National Health Commission of the People’s Republic of China. Nearly all patients accepted oxygen therapy, and WHO recommended extracorporeal membrane oxygenation (ECMO) to patients with refractory hypoxemia. Rescue treatment with convalescent plasma and immunoglobulin G are delivered to some critical cases according to their conditions.

Based on the experience of fighting the epidemic SARS-CoV and MERS-CoV previously, we may learn some lessons for some treatment strategies against coronavirus. Antiviral drugs and systemic corticosteroid treatment commonly used in clinical practice previously, including neuraminidase inhibitors (oseltamivir, peramivir, zanamivir, etc), ganciclovir, acyclovir, and ribavirin, as well as methylprednisolone [46, 75] for influenza virus, are invalid for COVID-19 and not recommended. Remdesivir (GS-5734) is a 1′-cyano-substituted adenosine nucleotide analog prodrug and shows broad-spectrum antiviral activity against several RNA viruses. Based on the data collected from in vitro cell line and mouse model, remdesivir could interfere with the NSP12 polymerase even in the setting of intact ExoN proofreading activity. Remdesivir has been reported to treat the first US case of COVID-19 successfully. Chloroquine is a repurposed drug with great potential to treat COVID-19. Chloroquine has been used to treat malaria for many years, with a mechanism that is not well understood against some viral infections. Several possible mechanisms are investigated: Chloroquine can inhibit pH-dependent steps of the replication of several viruses, with a potent effect on SARS-CoV infection and spread. Moreover, chloroquine has immunomodulatory effects, suppressing the production/release of TNF-α and IL-6. It also works as a novel class of autophagy inhibitor, which may interfere with viral infection and replication. Several studies have found that chloroquine interfered with the glycosylation of cellular receptors of SARS-CoV and functioned at both entry and at post-entry stages of the COVID-19 infection in Vero E6 cells. A combination of remdesivir and chloroquine was proven to effectively inhibit the recently emerged SARS-CoV-2 in vitro.

Scientists previously confirmed that the protease inhibitors lopinavir and ritonavir, used to treat infection with human immunodeficiency virus (HIV), could improve the outcome of MERS-CoV and SARS-CoV patients. It has reported that β-coronavirus viral loads of a COVID-19 patient in Korea significantly decreased after lopinavir/ritonavir (Kaletra®, AbbVie, North Chicago, IL, USA) treatment. Additionally, clinicians combined Chinese and Western medicine treatment including lopinavir/ritonavir (Kaletra®), arbidol, and Shufeng Jiedu Capsule (SFJDC, a traditional Chinese medicine) and gained significant improvement in pneumonia associated symptoms in Shanghai Public Health Clinical Center, China.The other antiviral drugs include nitazoxanide, favipiravir, nafamostat, and so on (See Table 1 for details).

After an initial push to look for therapeutic and vaccine options to help treat and prevent COVID-19, it will be important to better understand the host response to infection and the pathology of disease. A prerequisite step will of course be the development of appropriate animal models. Better understanding of how SARS-CoV-2 causes pathology and the way in which the host responds may help direct further therapeutic avenues. Understanding how comorbidities such as diabetes impact the host response to infection will also be important to better understand COVID-19.

Early diagnosis and strict implementation of the current WHO guidelines for preventing infection and control during the care of probable or confirmed cases of MERS-CoV are crucial for preventing spread.59 General supportive care continues to be the keystone for managing patients who have an acute respiratory failure and a septic shock as a consequence of severe infection.2 Patients with suspected MERS-CoV infections were initially treated empirically with broadspectrum antibacterial drugs that are effective against other agents that cause typical and atypical acute community-acquired pneumonia to exclude these diagnoses. 2,60,61

A review of published reports by the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC)61 suggested that the use of convalescent sera from recovered patients, although untested, is likely to be the best therapy because of its likely efficacy in the treatment of subjects with SARS-related pneumonia. Viral kinetic data for MERS-CoV are currently lacking, and knowledge in this area will facilitate planning of infection control and clinical management. The administration of convalescent plasma for SARS-CoV within 14 days of the onset of illness was associated with a higher discharge rate on day 22 of illness than for those who received convalescent plasma late or not at all.61,62 Although convalescent plasma may provide a useful treatment modality for severe MERS-CoVco disease; however, the use should be accompanied by an appropriately planned evaluation of effectiveness. Peg IFN was 50 to 100 times more effective for MERS-CoV than SARS-CoV.63 Recent published data suggests this is the most active agent in vitro of various compounds screened. Type I and III IFN efficiently reduced MERS-CoV replication in HAE cultures. MERS-CoV appears to be 50 to 100 times more sensitive to IFN-α than is SARS-CoV.63,64 A 16-hr subcutaneous administration with ribavirin in MERS-CoV–infected macaques led to improvements in clinical signs, radiographic changes, and viral load. The combination appeared to have no clinical benefit when given to patients infected with MERS-CoV.42 There is limited, inconsistent evidence that Lopinavir/ritonavir (Kaletra) has in vitro anti-SARS-CoV effect and possible clinical benefit in patients, though the scientific rationale for these effects is unclear.65 Ongoing in vitro studies with MERS-CoV are not yet conclusive, and there is no evidence that administration would be beneficial for patients with MERS-CoV.62 Early in vitro evidence suggests cyclosporin A—a potential pan-CoV inhibitor—demonstrates some in vitro effect against MERS-CoV, although no clinical or animal studies exist.63 The use of cyclosporine A is not recommended outside of an appropriately planned evaluation of effectiveness. The ISARIC recommends that neither ribavirin nor corticosteroids be used outside of a randomized clinical trial (unless for some other clinical indication) because of their potential severe adverse side effects.

Due to the absence of a specific antiviral therapeutics and vaccine, main treatment strategy for COVID-19 is supportive care, which is supplemented by the combination of broad-spectrum antibiotics, antivirals, corticosteroids and convalescent plasma 16 (Table 1). HIV protease inhibitors ritonavir and lopinavir have been used, typically in combination with appropriate antibiotics or with IFNα-2b, in the treatment of SARS-CoV-2 infected patients 7, 17. Nucleoside analogs such as ribavirin 12 may be potentially beneficial for the treatment of COVID-19, since ribavirin was approved for treating respiratory syncytial virus (RSV) infection 18 and used extensively during the SARS and MERS outbreak 10. However, ribavirin had severe side effects such as anemia 18 and whether it had sufficient antiviral activity against SARS-CoV-2 is unclear. Nucleoside analogs favipiravir (T-705) can effectively inhibit the activity of RNA polymerase of RNA viruses such as influenza 19. A recent in vitro study found that it had the anti-SARS-CoV-2 activity 20, but the in vivo effect remains elusive. Remdesivir may be the most promising antiviral drug for treating COVID-19. It has in vitro and in vivo antiviral activity against a wide array of RNA viruses including SARS and MERS 21, and could decrease viral loads and pathology of lungs in animal models 22. A study showed remdesivir markedly inhibited the infection of SARS-CoV-2 in Vero E6 cells 20, and most symptoms of the first US patient infected with SARS-CoV-2 had resolved swiftly after intravenous administration with remdesivir 23. Currently, it is under clinical trial to evaluate the safety and efficacy of intravenous remdesivir for patients with SARS-CoV-2 infection 24. Oral oseltamivir has been used for the treatment of the cases with SARS-CoV-2 7, while its efficacy currently remains uncertain.

Host-targeted small molecules approved for other human diseases may modulate the virus-host interactions of SARS-CoV-2. Chloroquine, a potential broad-spectrum antiviral drug 25, 26, was shown by a recent study had anti-SARS-CoV-2 activity 20. Its clinical efficacy is under study in an open-label trial (ChiCTR2000029609) 12. IFNα (5 million U) atomization inhalation was recommended as antiviral therapy to treat SARS-CoV-2 16. A trial testing IFNα-2b combination of the approved anti-HCV inhibitors has been initiated 17, however, whether it could act synergistically against SARS-CoV-2 is unclear.

Corticosteroids were frequently used to suppress the elevated cytokine levels in patients with SARS-CoV 27, 28 and MERS-CoV 29, 30. However, there are no evidence showing that the mortality of SARS and MERS patients was reduced by the treatment with corticosteroids, while the clearance of viral was delayed by such treatment 31-33. Consequently, corticosteroids are not suggested to systemically use in SARS-CoV-2 infected patients 34, 35.

Previously, it was shown that, either in severe influenza or SARS-CoV infection, convalescent plasma treatment could significantly decrease viral load and reduce the mortality 31, 36. Convalescent plasma has been used for severe SARS-CoV-2 infection in China 22, although promising, the efficacy and safety need to be carefully further evaluated.

Consistent with previous analysis, WHO also concluded "to date, there is no specific medicine recommended to prevent or treat SARS-CoV-2" 37. TCM has been used in control of infectious diseases for thousands of years. There is a clear room for the intervention of TCM as a complementary therapy for COVID-19 patients. It is reported that the patients with SARS-CoV infection have benefited from TCM treatment 38, including amelioration of side effect of conventional therapeutics 39, 40. Based on these factors, there is a general expectation that TCM would be a valuable weapon in the armory against SARS-CoV-2.

Transmission of 2019-nCoV probably occurs through spreading airborne and contact. Aerosol and fecal–oral transmission remain unclear. Public health measures, including quarantining in the community as well as timely diagnosis and strict adherence to universal precautions in health care settings, were critical in reducing the transmission of 2019-nCoV.

For healthcare personnel, to minimize the chance of exposures to 2019-nCoV needs to follow the standard of contact and airborne precautions, personal protection including gloves, gowns, respiratory protection, eye protection, and hand hygiene. Some procedures performed on 2019-nCoV infected patients could generate infectious aerosols, e.g., nasopharyngeal specimen collection, sputum induction, and open suctioning of airways should be performed cautiously. If performed, these procedures should take place in an airborne infection isolation room, and personnel should use respiratory and eye protection, and hand hygiene. In addition, management of environmental infection control including laundry, food service utensils, and medical waste should also be performed. Artificial Intelligence (AI), alternative selection to reducing infection for medical personnel, should be explored (Joint developed by Respiratory Research Institution of Zhongshan Hospital, Fudan University and RealMax Ltd Co), which will be benefit for remote guidance of practices.

During the hospitalization, six patients (21.4%) required oxygen supplement therapy: four with nasal cannula and two with face mask. No one required mechanical ventilator or ECMO therapy. Nineteen patients (67.9%) received lopinavir/ritonavir for antiviral therapy. Ultimately, pneumonia was present in 22 patients (78.5%) and the proportion of pneumonia was 91.3% (21/23) among the patients who received a CT scan (Table 2). Seventeen patients (60.7%) developed fever and became afebrile during the hospitalization and the median day of defervescence was 9 days (range, 3–18) after symptom onset (Supplementary Fig. 1). By February 17, 10 patients were off isolation or discharged, and the median day of off-isolation/discharge was 18.5 days after symptom onset (range, 11–27).

Standard nosocomial preventive control measures are in urgent need to block further spreading of the disease. The in-hospital preventive control measures should vary among patients, close contacts, and health care workers in precision medicine approach.

The triage of patients by disease severity is the priority; patients should be triaged as soon as possible when they come to the clinic or hospital, depending on disease severity.

The infection is defined as severe when a patient meets any of the criteria established by the Diagnosis and Treatment Scheme issued by the National Health Commission4:

(i) A respiration rate greater than 30 breaths per minute, dyspnea;(ii) A blood oxygen saturation of <93% in resting state;(iii) A PaO2:FiO2 ratio (the ratio of arterial oxygen partial pressure to fractional inspired oxygen) of <300 mm Hg;(iv) Radiologic evidence of foci in multiple lobes or more than a 50% progression of lung inflammation.

The infection is defined as critical when any one of following is met:

(i) Respiratory failure and the need for mechanical ventilation;(ii) Shock;(iii) Multiple organ failure and admission to the intensive care unit.

According to the Diagnosis and Treatment Scheme, timely isolation of suspected cases is essential.4 Patients suspected of infection with 2019-nCoV should be examined only in an isolated area where health workers are protected by protective clothing with adequate protection level.

Once the virus is detected, patients should be admitted to a negative-pressure isolation ward or to private rooms. Several researchers have found that confinement to an isolation ward can prevent the airborne spread of pathogens.15 Patients with mild symptoms can be observed in separate isolation wards or during home quarantine if hospital beds are unavailable. However, all critically ill patients should be immediately admitted to isolation wards with environmental negative pressure equipment and medical protection.

Health care workers should be given appropriate equipment, including respirators (NIOSH-certified N95, EU FFP2, or higher-level protection), eye protection (goggles or a face shield), and clean, long-sleeved gown and gloves.12 Equipment should be thoroughly disinfected between patients, and health workers should wash their hands for at least 20 seconds after patient contact. Occupational exposures in workplace should be immediately reported to the infection control unit at the hospital, and the exposed doctor or nurse should be quarantined in the hospital.

People in close contact with patients or with those suspected of 2019-nCoV infection should be examined immediately if they experience respiratory symptoms, such as fever, or related symptoms. Even if their test result is negative, they should be temporarily isolated at home for 14 days after the last contact with confirmed patients—since 14 days is the disease maximum incubation period.16 The National Health Commission also recommends that members of the public should wash their hands with soap and water for at least 20 seconds and, when going outside, wear a medical face mask and cover their nose and mouth with a tissue, arm, or hand when coughing or sneezing.

MERS is a viral pneumonia with rapidly progressive respiratory failure leading to ARDS. As with severe pandemic influenza (H1N1), and severe avian influenza (H7N9) death is due to hypoxemia from acute respiratory failure.14-16 Like SARS and avian influenza (H7N9), MERS has not been complicated by bacterial co-infections.5,28-30 Pandemic influenza, in contrast, which may be complicated by simultaneous bacterial co-infection, with S. aureus (MSSA or MRSA), or sequential co-infection in patients who improve ~1 wk who then may develop a secondary bacterial pneumonia due to Haemophilus influenzae or S. pneumoniae.14,15 Since any patient, including MERS or influenza patients, that receive prolonged mechanical ventilation may develop late nosocomial bacterial pneumonia.5 These are not co-infections, per se, but rather are nosocomial complications of mechanical ventilation. Like pandemic influenza, MERS mortality can be high in normal young adults, but mortality is highest in those with comorbidities.5

As an emerging virus, there is no effective drug or vaccine approved for the treatment of SARS-CoV-2 infection yet. Currently, supportive care is provided to the patients, including oxygen therapy, antibiotic treatment, and antifungal treatment, extra-corporeal membrane oxygenation (ECMO) etc. 21,22. To search for an antiviral drug effective in treating SARS-CoV-2 infection, Wang and colleagues evaluated seven drugs, namely, ribavirin, penciclovir, nitazoxanide, nafamostat, chloroquine, remdesivir (GS-5734) and favipiravir (T-750) against the infection of SARS-CoV-2 on Vero E6 cells in vitro

63. Among these seven drugs, chloroquine and remdesivir demonstrated the most powerful antiviral activities with low cytotoxicity. The effective concentration (EC50) for chloroquine and remdesivir were 0.77µM and 1.13µM respectively. Chloroquine functions at both viral entry and post-entry stages of the SARS-CoV-2 infection in Vero E6 cells whereas remdesivir does at post-entry stage only. Chloroquine is a drug used for an autoimmune disease and malarial infection with potential broad-spectrum antiviral activities 64,65. An EC90 (6.90 µM) against the SARS-CoV-2 in Vero E6 cells is clinically achievable in vivo according to a previous clinical trial 66. Remdesivir is a drug currently under the development for Ebola virus infection and is effective to a broad range of viruses including SARS-CoV and MERS-CoV 67,68. Functioning as an adenosine analogue targeting RdRp, Remdesivir can result in premature termination during the virus transcription 69,70. The EC90 of remdesivir against SARS-CoV-2 in Vero E6 cells is 1.76 µM, which is achievable in vivo based on a trial in nonhuman primate experiment 63,69. Encouragingly, in the first case of SARS-CoV-2 infection in the United States, treatment with remdesivir was provided intravenously to the patient on the day 7 without any adverse events observed. The patient's clinical condition was improved on day 8 and the previous bilateral lower-lobe rales disappeared, implying the remdesivir might be effective to the treatment of SARS-CoV-2 infection 22. This result, however, should be interpreted with caution as this is only single case study and a proper trial control was lacking. In addition, baricitinib, a Janus kinase inhibitor, was also predicted to reduce the ability of virus to infect lung cell by an analysis of BenevolentAI 71.

Currently, chloroquine and remdesivir are under phase 3 clinical trial and open-label trial for treatment of SARS-CoV-2 infection respectively (Table 2) 72. Preliminary results showed that chloroquine phosphate had apparent efficacy in treatment of COVID-19 73. However, caution must be taken during clinical use of chloroquine as its overdose is highly fatal without known antidote 74. Despite the lack of documented in vitro data supporting the antiviral efficacy on SARS-CoV-2, several antiviral chemotherapeutic agents have been registered for the clinical trials for the treatment of COVID-19 (Table 2) 72.

Nine key questions on antiviral drugs and adjuvant treatments were selected following the collection and evaluation of evidence relating to the treatment of MERS-CoV and the similar virus SARS-CoV as well as a review of overseas MERS-CoV treatment guidelines.

We performed a search of the literature relating to MERS-CoV and SARS-CoV treatment guidelines published after 2002. We searched the literature from the past 20 years for details of the doses and adverse effects of antiviral drugs including interferon, ribavirin, and lopinavir/ritonavir. Searches were performed on PubMed (www.pubmed.gov) using combinations of the following search terms: Middle East respiratory syndrome, severe acute respiratory syndrome, coronavirus, treatment, therapy, and antiviral. Because the number of original articles on MERS-CoV treatment is small, we reviewed all articles including case reports.

The pathogenesis of hMPV infection is strongly affected by bacterial coinfections with pneumococcus. One study has shown that administration of a conjugate pneumococcal vaccine is sufficient to reduce the incidence of hMPV infection of the lower respiratory tract and the incidence of clinical pneumonia in both HIV positive and negative patients. These finding suggest that the incidence of hospitalizations in hMPV infections may be decreased by vaccination with a conjugate pneumococcal vaccine. Another case report of severe respiratory failure was found to be caused by coinfection with hMPV and Streptococcus pneumonia in a 64 year old patient. Both in vitro and in vivo studies have shown that infection with hMPV facilitates adhesion of pneumococcal bacteria, which may provide an explanation for the coinfection with pneumococcal strains and hMPV.

Viral coinfections between hMPV and RSV have been reported, but remain a contentious issue. The typical seasonal overlap of the two viruses has been suggested to promote viral coinfection. One study reported a 10-fold increase in risk of admission to an intensive care unit in pediatric patients coinfected with RSV and hMPV and associated the dual infection as capable of augmenting severe bronchiolitis. Other studies do not support this finding and further report a decreased correlation between hMPV-RSV coinfections and hospitalization and additionally lists dual infection, along with breastfeeding, as having protective effects.

Despite that respiratory infections with HCoVs can result in severe respiratory disease there are currently no effective prophylactic or therapeutic treatment options available. However, the emergence of novel coronaviruses has emphasized the need to develop effective treatment options. For example, vaccines using the spike proteins of both SARS- and MERS-CoVs have proven protective in animal models [91, 92] suggesting that a vaccine against HCoVs for human use might be achievable.

Additionally, various drugs that inhibit HCoV infection at different stages of the replication cycle have been reported and some could potentially serve as treatment options for HCoV associated severe respiratory disease. For example, patients presenting with severe respiratory disease, caused by SARS- or MERS-CoVs, are generally treated with steroids and interferon, sometimes in combination with the antiviral drug Ribavirin [93–96]. This treatment, however, is not especially effective highlighting the need for HCoV specific antivirals. Many different compounds have been determined to have anti-HCoV activity. For example, protease inhibitors which suppress HCoV entry [97–99], Cyclosporin A (CsA) treatment blocks the replication of coronaviruses from all subgroups and non-immunosuppressive derivatives of CsA represent a possible therapeutic option for both human and animal CoV infections.

HCoV infection can also be inhibited by pre-treating HAE cultures with either recombinant IFN alpha or lambda. Similar effect has also been shown for recombinant IFN alpha and beta which could inhibit MERS-CoV in ex vivo lung cultures. As previously described, IFN treatment of active HCoV infection is not particularly effective in vivo. Therefore, the use of IFN in humans might be limited to prophylactic treatment of exposed persons and/or health care workers treating infected patients.

Screenings of compound libraries have also resulted in the identification of some HCoV specific antivirals. For example, a novel small compound inhibitor (K22) has been identified, and showed to be effective against a broad spectrum of CoVs and could inhibit both HCoV-229E and MERS-CoV in HAE cultures. Additionally, HCoV-NL63 has been inhibited in HAE cultures with polymer-based compounds.

To date, most treatment and inhibitor studies have been conducted in HCoV susceptible cell lines. However, the HAE cultures represent an ideal system to test the application and efficacy of those already identified, and new, antiviral compounds against HCoVs in cells that represent the primary site of replication. Furthermore, the HAE cultures are heterogenous, containing many different cellular sub-populations, and would allow for the evaluation of compound toxicity and effect in a differentiated layer similar to human airway epithelium. Compounds already shown to inhibit HCoVs in cell lines should be applied to HAE cultures as well before any animal or human trials.

SARS-CoV-2 is an emerging pathogen, without any effective drug available for treatment at the moment. It spreads quickly and can result in death of the infected patients. Despite the current mortality rate is 2.3% 26, the emergence of large number of infected patients within short period of time could result in the collapse of health care system, and thus the mortality rate might be elevated. Effective preventive measures must be implemented to control it from global spreading. In addition, great effort should be made on the development of vaccine and antiviral drugs. Meanwhile, the intermediate host and the molecular mechanism of its cross-species spread should be further investigated. Legislation should be employed to prohibit the trade of wild animals, the potential intermediate host(s) of various viruses, to prevent the outbreak of this and other novel viruses in future.