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John McAteer, Inci Yildirim, Ann Chahroudi, for the Society for Pediatric Research Advocacy Committee, The VACCINES Act: Deciphering Vaccine Hesitancy in the Time of COVID-19, Clinical Infectious Diseases, Volume 71, Issue 15, 1 August 2020, Pages 703–705, https://doi.org/10.1093/cid/ciaa433

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Abstract

Vaccine hesitancy has vexed the practice of immunization ever since cowpox was used as a vaccine for smallpox by Edward Jenner in 1796 [ 1]. Skepticism about vaccines is a timeworn concept with shifting ideologies that reflect historical events and individual belief systems reflective of different societal periods. Although the term "antivax" is ascribed to contemporary vaccine skeptics, "hesitant" is often a better descriptor for the majority of parents who contemplate or request delaying vaccines for their children or deviating from the recommended immunization schedule. The term hesitant avoids polarization into "pro" versus "anti" vaccination factions. Hesitancy implies, however, that minds can be swayed toward acceptance, and as pediatricians armed with the latest data, we are frustrated that these facts and figures do not always convince parents in our exam rooms and those we encounter on social media that vaccination is right for their children. How and why does this hesitancy shift from physician-guided acceptance of vaccines to their refusal?

Vaccine hesitancy is a complex issue. One important consideration is that vaccine hesitancy has evolved in response to the complicated but ultimately successful history of vaccine science. Vaccines are a victim of their own success, turning once devastating diseases into distant memories. Hesitant parents, as a result, have shifted their focus to the perceived risks of vaccination as fewer people witness the consequences of forgoing vaccines in developed countries. However, some vaccine-preventable diseases are now making a comeback, which is putting our nation's children at risk.

Outbreaks of vaccine-preventable diseases are occurring at an alarming rate across the country, especially in geographic pockets with poor immunization rates [ 2]. In 2019 alone there were 1282 confirmed cases of measles in the United States, the greatest number reported in this country since 1992 [ 3]. These outbreaks led to the possibility that the United States would lose measles elimination status, initially awarded almost 20 years ago. Despite remarkable advances in vaccine science, vaccine hesitancy has now become a recognized public health threat with potentially disastrous complications. Anti-immunization sentiment is at an all-time high, and the medical community has recognized the need to address it as a public health emergency, with research, action, and advocacy.

The nature of hesitancy directly confronts our fundamental belief system as pediatric scientists, which is based on disease prevention and anticipatory guidance. Vaccine hesitancy is one of the most challenging controversies we have faced in our history. This problem is personal to all of us. Pediatricians and vaccinologists have been disbelieved and attacked. Vaccine hesitancy has the potential to harm physician-patient relationships. It is difficult to comprehend that some of the greatest triumphs of medical science are being eroded by misinformation and distrust. To address vaccine hesitancy, we need to reframe our approach and focus on understanding the root causes of this complicated problem.

On the surface, the idea of hesitancy is perplexing given the overwhelming scientific evidence for the safety and efficacy of vaccines. Vaccine hesitancy is not a superficial issue with a universal solution, however. Rather, it is a multifaceted, deeply complex construct that may be rooted in the moral composition that guides our daily decision making. Research has shown that several distinct values are associated with vaccine hesitancy-particularly purity, liberty, and anti-authority [ 4]. Combined with the historical amnesia of the consequences of vaccine-preventable diseases, vaccine hesitancy becomes easier to understand as a belief system grounded in certain moral values. By considering these values, rather than relying solely on vaccine safety and efficacy data, some researchers believe we may be able to more effectively address vaccine hesitancy.

Although each family is unique, there are likely common drivers for vaccine hesitancy, and these, we submit, are being inadequately addressed. Hesitant families frequently express concern about vaccine safety, but even this issue has multiple layers, including fears regarding potential links to autism (now thoroughly refuted [ 5]), learning difficulties, and chronic illnesses, as well as a perceived lack of safety testing prior to approval for use [ 6]. A famous quote from Bernard Shaw applies here: "The greatest problem in communication is the illusion that it has been accomplished." Properly identifying and completely responding to fears regarding vaccines within the confines of a 15-minute wellness visit is next to impossible. Furthermore, how we discuss and communicate about vaccines, as much as the evidence-based facts provided, may be very important. We need a systematic assessment of factors affecting vaccine uptake on a continuing basis to develop the most effective and efficient communication strategies. As a medical community, we must investigate the determinants of vaccine hesitancy and the continuously evolving challenges that it entails in order to tailor evidence-based strategies to overcome the problem with sustainable interventions.

In a step forward in the fight against vaccine misinformation, Facebook announced on 4 September 2019 that user searches for vaccine-related content will be directed to either the US Centers for Disease Control and Prevention (CDC) or the World Health Organization (WHO) websites for accurate information regarding vaccines. In his statement of support [ 7], the WHO Director-General Dr Tedros Ghebreyesus asserted that "These online efforts must be matched by tangible steps by governments and the health sector to promote trust in vaccination and respond to the needs and concerns of parents." In order to adequately respond to these needs and concerns, which differ depending on the cultural, societal, and personal beliefs of a particular region, the WHO recommends that each country take steps to develop an understanding of vaccine hesitancy at a local level on an ongoing basis [ 8]. Unfortunately, such a surveillance program in the United States (and in many other countries, for that matter) does not exist. As such, much of the information we have about vaccine hesitancy is retrospective and anecdotal.

The absence of federal investment in understanding vaccine hesitancy was clear during the 2019 measles outbreaks. As cases increased nationally, CDC officials tracked cases and exposures across state lines. However, insight into the vulnerability of exposed communities was varied and depended solely on the quality and attention state governments paid to evaluating measles, mumps, rubella (MMR) immunization rates in those communities. New York State, for example, quickly realized reluctance to immunize was centered in specific Orthodox Jewish communities in Brooklyn and Rockland counties and was rooted in concerns about potential pork products in vaccines. With local governments, the state created public awareness campaigns led by rabbis urging vaccination. Other areas, absent this granular understanding, could simply react to burgeoning cases and missed opportunities that may have prevented the spread of cases to 31 states.

In recognition of these missed opportunities and in response to declining immunization rates and increasing national skepticism on the safety of vaccines, Congress has introduced bipartisan legislation to expand research into vaccine hesitancy. Spearheaded by Congresswoman and pediatrician Dr Kim Schrier, the Vaccine Awareness Campaign to Champion Immunization Nationally and Enhance Safety (VACCINES) Act (H.R. 2862) would provide federal funding for vaccine hesitancy surveillance and authorization of a public awareness campaign to increase public confidence in vaccines [ 9]. The bipartisan bill introduced in May 2019 will amend the Public Health Service Act of 1944 to support a rigorous scientific approach to learn more about the factors that drive vaccine hesitancy and will fund national surveillance of hesitant regions. Although commendable, it should be noted that the requested resources in the current version of the VACCINES Act are inadequate to fund serious communications campaigns, given that some of the areas with the highest hesitancy also have the most expensive media markets. The bill does include a vital provision to support awareness campaigns tailored to specific communities that could prove to be an essential tool in the fight to protect children from vaccine-preventable diseases. Signing this bill into law will provide a framework to better understand and respond to vaccine hesitancy in the United States.

Current research suggests that the drivers of vaccine hesitancy depend heavily on personal experiences and belief systems [ 4, 8]. Having an adequately federally funded surveillance program will permit analysis of contextual influences that promote and perpetuate reluctance at the local level. High-risk populations can be identified and specifically targeted based on their societal and cultural belief systems. Awareness campaigns can be tailored to specific locales to address identified concerns regarding vaccines. Studying all these factors will expand our armamentarium in preventing the rise of vaccine-preventable diseases. The VACCINES Act is currently in the first stage of the legislative process. It has been assigned to the House Energy and Commerce Committee where the chairs will determine if the bill will pass to the House Floor [ 9]. The odds of any bill becoming law at this stage are collectively low (around 3% since 2015) and even worse without strong public support [ 10]. It is thus of paramount importance for the scientific community to come together in support of this legislation.

Vaccine hesitancy remains a persistent global threat and is a concept we are only beginning to understand. We have been lagging in our response, in part because the epidemic of vaccine hesitancy has personally challenged our motivations and values as doctors, scientists, advocates, and often, family members and friends. Although we wonder if the COVID-19 pandemic will begin to change minds regarding the overwhelming value of immunization, we fear that as time elapses and memories fade, a SARS-CoV-2 vaccine may join the ranks of MMR in eliciting hesitancy from some groups. The bipartisan VACCINES Act is an important step in supporting evidence-based research into vaccine hesitancy. It is a call for the scientific community to shift our focus toward understanding the underlying causes of this epidemic. As this bill goes through the legislative process, we strongly urge the scientific and medical communities to contact their representatives to voice support for a fully resourced VACCINES Act. We believe that all children and their families deserve it.

Note

Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest.

References

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VACCINES Act: Deciphering Vaccine Hesitancy in the Time of COVID-19

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Vaccine hesitancy has vexed the practice of immunization ever since cowpox was used as a vaccine for smallpox by Edward Jenner in 1796 [ 1]. Skepticism about vaccines is a timeworn concept with shifting ideologies that reflect historical events and individual belief systems reflective of different societal periods.

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Dorit R Reiss, Arthur L Caplan, Considerations in mandating a new Covid-19 vaccine in the USA for children and adults, Journal of Law and the Biosciences, Volume 7, Issue 1, January-June 2020, lsaa025, https://doi.org/10.1093/jlb/lsaa025

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Considerations in mandating a new Covid-19 vaccine in the USA for children and adults

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As cases of coronavirus disease 2019 (COVID-19) spread globally and across the USA, reaching over 140,000 US cases by March 30, 2020 (a number that is almost ce

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Jingwei Li, Jun Shao, Chengdi Wang, Weimin Li Author Notes

Precision Clinical Medicine, Volume 3, Issue 2, June 2020, Pages 71–84, https://doi.org/10.1093/pcmedi/pbaa017

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Abstract

An outbreak of coronavirus disease 2019 (COVID-19), a disease caused by a novel pneumonia virus, has affected over 200 countries and regions worldwide. With the increasing number of patients and deaths, WHO have declared it as a global pandemic currently, indicating a third large-scale epidemic coronavirus has appeared since the emergence of severe acute respiratory syndrome coronavirus (SARS) and Middle-East respiratory syndrome (MERS) in the twenty-first century. Considering the great harm it has caused, researchers throughout the world have been chasing to exploit the pathophysiology, characteristics, and potential remedies for COVID-19 to better battle the outbreak. Therefore, the current study revisits advances of the virology, epidemiology, clinical features, therapeutic options, and prevention of COVID-19. The features of asymptomatic carriers are also been explored.

Introduction

At the end of 2019, a sudden outbreak of pneumonia occurred in Wuhan, China, which was later confirmed to be caused by a coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Soon after, the virus spread rapidly around the world and affected human health as well as causing huge economic losses to society. On 12 February 2020, this novel disease was named coronavirus disease 2019 (COVID-19) by WHO. Since then, medical experts around the world have been trying to find the control measures and treatment for it.

Because COVID-19 is highly contagious, the number of patients has increased rapidly. Thus, realizing its basic characteristics and finding appropriate methods to detect and cure COVID-19 is necessary for outbreak control. The detection and rehabilitation judgment of COVID-19 are mainly through reverse transcription-polymerase chain reaction (RT-PCR), but experts have pointed out the low sensitivity will lead to missed diagnosis. So a combination of RT-PCR and other clinical features of COVID-19 is important for diagnosis. The treatments for COVID-19 are still unclear and mainly contain administration of oxygen, drug therapy, and emergency treatments such as ECMO., As we know, few studies have summarized and classified therapies for COVID-19 systematically.

Therefore, we review basic characteristics such as virology and epidemiology of COVID-19 and classified explore antiviral therapy, symptomatic treatment, and traditional Chinese medicines for curing COVID-19. Considering no licensed vaccine exists for COVID-19, we also summarize the research and development of its vaccine. Notice that the recent emergence of asymptomatic carriers has brought great difficulties for prevention and control of this disease, we highlight the characteristics of asymptomatic carriers and how to reduce their impact on the development of the COVID-19 pandemic.

Virology

In January 2020, after the outbreak of COVID-19, scientists identified its pathogen and immediately confirmed it to be a novel coronavirus, which is found to be a β coronavirus of group 2B and was named 2019-nCoV by WHO initially. Because 70% of its genetic sequences are similar to the SARS-CoV, it was later renamed SARS-CoV-2. The origin of SARS-CoV-2 is unclear and is thought to be related to bat coronaviruses. Zhou et al. compared gene sequence of SARS-CoV-2 with RaTG13, a bat coronavirus, and found the whole-genome sequence of SARS-CoV-2 is 96.2% similar to RaTG13, indicating that SARS-CoV-2 may originate from a bat coronavirus. At the same time, Wu and colleagues reported that the genome sequence of SARS-CoV-2 was closely linked with SL-CoVZC45, another bat coronavirus, with 82.3% similarity. However, despite the high similarity of SARS-CoV-2 to the virus from bats, the genetic differences will take at least a few decades of evolution to make up. Thus, bats are unlikely to be the definitive hosts of it, and there may exist other intermediate hosts which brought the virus into humans. The relative synonymous codon usage analysis of viruses found SARS-CoV-2 used the translation machinery of several snakes effectively. Therefore, snakes are a potential reservoir of the novel virus. Apart from this, pangolins are thought to be the potential intermediate host of SARS-CoV-2 due to the sequence similarity of their spike receptor binding domains. Furthermore, Liu et al. declared that turtles were another possible host of SARS-CoV-2. Thus, more studies are necessary for confirming the intermediate host of SARS-CoV-2.

Epidemiology

Up until now, the largest case series data of China has shown that 86.6% of COVID-19 patients were aged 30-79 years, 1% were aged under 1 year old, 1% aged 10-19 years, and 3% were aged above 80 years. Among all patients, males account for 51%, and females account for 49%. Furthermore, 4% of them are medical workers. In the United States, the elderly (aged over 65) account for 31% of total COVID-19 cases, 45% of inpatients, 53% of ICU patients, and 80% of death cases.

Clinical features and diagnosis (Table 1)

Typical clinical features of COVID-19

Like most respiratory illnesses, COVID-19 has many typical respiratory clinical symptoms. Data from 1099 confirmed COVID-19 patients have shown that 88.7% had a fever, 67.8% developed a cough, and 2.3% received invasive mechanical ventilation, which is consistent with other studies. For some severe patients, acute respiratory distress syndrome (ARDS), shock, and arrhythmia are common complications. Apart from these symptoms, COVID-19 patients sometimes have other non-respiratory symptoms such as fatigue, myalgia, headache, and digestive tract symptoms. Moreover, the main changes in laboratory results of COVID-19 are decreases in lymphocytes and eosinophils as well as increases in D-dimer, C-reactive protein, prothrombin time, and procalcitonin.

Computed tomography (CT) is one of the most efficient techniques for evaluating severity and differential diagnosis of pulmonary diseases, thus the CT characteristics (Fig. 1) of COVID-19 are another important clinical feature. This clinical evidence indicates that ground glass opacity (GGO), consolidation, and interlobular septal thickening are the most common CT characteristics of COVID-19, which occurs mainly in the posterior lung area and middle and lower lung regions. Compared to patients with mild symptoms, signs such as consolidation, thickened bronchial wall, linear opacities, extrapulmonary lesions, and higher CT scores are marked CT features of critically ill patients. Therefore, CT is potentially used to diagnose and predict the prognosis of COVID-19 patients.

Clinical diagnosis of COVID-19

Clinical symptoms are often used as indicators of clinically suspected cases. Thus, when it comes to the clinical features above, it is easy to think about clinical diagnosis of COVID-19 (Table 2 and Fig. 2). According to the Diagnosis and Treatment Program of Novel Coronavirus Pneumonia, only a suspected case has one of the pieces of evidence of etiology or serology, such as positive nucleic acid, confirmation of gene sequencing, and virus specific antibody, to be confirmed to be COVID-19 patient, and the suspected cases were identified by a comprehensive analysis of epidemiological history and clinical manifestations. However, there are also many problems with this program. The most obvious problem is that RT-PCR is the most common method for nucleic acid testing, but its sensitivity is not as high as expected, thus it possibly causes misdiagnosis of COVID-19. Furthermore, although viral gene sequencing is an accurate diagnostic method and used on a small scale, its complex operation and time-consuming process make it difficult for wider clinical use. SARS-CoV-2 specific antibody detection is a simple detection method with higher sensitivity than RT-PCR, but its high sensitivity is only reflected after 5.5 days of symptom onset, so it is just a supplementary means to RT-PCR. Luckily, the fast and convenient method, CT, was found to have a higher diagnostic sensitivity for COVID-19 than other diagnostic methods such as RT-PCR and can predict the prognosis of patients, thus it is meaningful for the initial screening. Zhang et al. developed a deep learning system for image recognition of COVID-19 patients. They collected CT images from 4154 patients for validation and found this system precisely identified the COVID-19 and other forms of pneumonia, and it also divided these patients into high- and low-risk groups correctly, so rational use of artificial intelligence such as this may be better able to screen COVID-19 patients and give them timely interventions to ensure a better prognosis. In addition, a CRISPR-Cas12-based technique was confirmed to be a faster test for COVID-19 with higher sensitivity, thus it is possibly a replacement for the RT-PCR assay.

Remedies

The therapeutic schedule issued by the General Office of National Health Committee of China on 3 March has shown that therapy of COVID-19 should be combined with etiological treatment and symptomatic treatment, and symptomatic treatment is especially important for severe and critical patients. Furthermore, traditional Chinese medicine can be also used for the whole treatment cycle of COVID-19 patients. In the processes of COVID-19 therapy, drugs and bioproducts play important roles (Table 3). Here, we summarize the main treatments of novel pneumonia.

Etiological treatment for COVID-19

The etiological treatment for COVID-19 means antiviral therapy for it, which depends on antiviral drugs and bioproducts. The processes of virus infection could be described as attachment, penetration, uncoating, biosynthesis, assembly, and release. After that, the virus complete its proliferation and causes damage to host cells. Similarly, the mechanism of antiviral therapy is through disturbing these processes. Thus, the medicines for antiviral treatment of COVID-19 are divided into penetration and uncoating inhibitors, biosynthesis inhibitors, and assembly inhibitors.

Antiviral medicines for COVID-19

Antiviral biological products for COVID-19

The most common antiviral products are IFNs, which induce cells to synthesize antiviral proteins and thus inhibit all processes of the viral replication cycle. Furthermore, it could also enhance immunity of patients, so it is widely used for therapy for multiple viruses such as MERS-CoV. In this outbreak, IFNs combined with antiviral drugs were recommended to treat COVID-19, which has achieved good clinical therapeutic effect. Xu et al. reported that the combination of IFNs and arbidol or lopinavir/ritonavir cured 62 COVID-19 patients in the Zhejiang province. In addition, a combination use of IFN beta-1b, ribavirin, and lopinavir-ritonavir was found to be more effective than pure lopinavir-ritonavir. These therapies have been initiated into multiple clinical trials.

Convalescent plasma therapy (CPT) is based on the principle of using a certain titer of viral-specific antibodies in the recovered plasma to obtain passive immunity, neutralize specific pathogens, and eventually clear the pathogens in blood circulation, thus achieving the treatment expectation. Luckily, key indicators of laboratory testing, clinical signs, and symptoms of several COVID-19 patients were confirmed to improve significantly after CPT, so CPT is recommended for COVID-19 treatment. Currently, clinical trials are under way to further evaluate the efficiency and safety of CPT to COVID-19. The monoclonal antibody is a highly uniform antibody that is produced by a single B cell and specific to target the antigen epitopes, which have been confirmed to suppress viruses entering host cells extracellularly for many coronaviruses including SARS-CoV-2., Tian et al. reported that monoclonal antibody CR3022 bound stably to receptor-binding domain of SARS-CoV-2 (KD of 6.3 nM), thus it potentially cures COVID-19. Nevertheless, the development of monoclonal antibodies takes a certain period of time. For new pathogens, monoclonal antibodies are a research direction, but it is difficult to achieve clinical application in a short time.

Complications treatment of COVID-19

Like most diseases, the main treatments of the complications of COVID-19 are to strengthen supportive treatment, ensure adequate energy, and pay attention to water and electrolyte balance to maintain internal environment homeostasis. For COVID-19, hypoxia is a typical clinical symptom of COVID-19, thus oxygen inhalation is the essential treatment for both mild and severe patients.,

Furthermore, patients with underlying diseases such as hypertension, diabetes, and cardiovascular disease have a potential bad prognosis, ⁻ so care should be taken to cure these basic diseases during treatment. COVID-19 patients with low immunity are susceptible to hospital-acquired bacterial infections, therefore, antibiotics such as amoxicillin are another symptomatic treatment medicine for COVID-19.

Traditional Chinese medicine for treatment of COVID-19

Traditional Chinese medicine has been confirmed to play a vital role in treating many respiratory viruses such as SARS-CoV. Furthermore, the General Office of National Health Committee pointed out that Chinese medicines such as qingfei paidu decoction, qingfei touxie fuzheng recipe, and sheganmahuang decoction could be used for the whole therapeutic process of COVID-19, thus they are widely used for COVID-19 treatment currently. The present clinical evidence has shown that a combination of western and Chinese medicines apparently improved curative effect. For example, Wan et al. treated 124 patients with multiple traditional Chinese medicines such as Suhuang Zhike capsule and Xuebijing, and found their respiratory symptoms were significantly improved in a shorter time. Furthermore, four cases treated with antiviral drugs and Shufeng Jiedu Capsule had an obvious improvement both in symptoms and blood biochemical indexes. However, lack of a control group means these results are not reliable enough.

Although treatment based on syndrome differentiation and lack of scientific evidence on mechanisms are typical characteristics of traditional Chinese medicines, many of them are gradually found to have antiviral potential for SARS-CoV-2. Theaflavin is conventional ingredient of Chinese medicine, which was found to have hydrogen bonds to RNA-dependent RNA polymerase with a binding energy of −8.8 kcal/mol, thus it possibly inhibits the proliferation of SARS-CoV-2. Lianhuaqingwen was also confirmed to significantly inhibit the replication of SARS-CoV-2 and suppress the inflammatory factors TNF-α, IL-6, CCL-2/MCP-1, and CXCL-10/IP-10 in Vero E6 cells, so it is potentially a specific medicine for COVID-19 both etiologically and symptomatically.

Prevention and control of COVID-19

The prevention and control of COVID-19 can be divided into controlling the source of infection, cutting off the transmission route, and protecting susceptible people. Controlling the source of infection in this outbreak mainly refers to timely isolation of suspected and confirmed cases, which greatly depends on wireless communication data. Isolation of convalescent patients is also necessary, because some of them have a positive RT-PCR test even after 13 days of recovery. Cutting off the transmission route includes sterilizing and wearing suitable masks such as N95, KN95, and medical surgical masks. Protecting susceptible people means self-segregation, improving constitution, and prophylactic vaccination.

Vaccine

Considering the strong infectivity of COVID-19, the secondary outbreak of COVID-19 can be prevented only if the public has immunity to SARS-CoV-2, thus vaccine is the key area among all prevention measures. Therefore, scientists all over the world are working on the vaccine for SARS-CoV-2, aiming to completely control the outbreak. After a long period of effort, the vaccine targets of the virus had been found and shared with the world., Soon afterward, medical institutions around the world adapted joint research and identified five development approaches, including a live attenuated vaccine, inactivated whole-virus vaccine, nucleic acid vaccine, protein vaccine, and viral vector-based vaccine (Table 4), and most of them used the S protein of SARS-CoV-2 as the main inducer of neutralizing antibodies directly, or inducing the expression of the whole S protein or receptor-binding domain of the S protein indirectly. By interaction of the S protein and ACE2 of host cells, uncoating and penetration of SARS-CoV-2 are induced. Thus, S-protein-based vaccines potentially inhibit the uncoating and penetration of the virus.

Live attenuated vaccine and inactivated whole-virus vaccine

Whole-virus vaccines are conventional strategies to develop a vaccine for most viruses. By injecting artificially attenuated or inactivated viruses, pathogens trigger the body's immune response without causing disease. Compared to other vaccines, these keep the inherent immunogenicity of SARS-CoV-2 and stimulate the body's innate immunity such as releasing toll-like receptors. However, live viruses have the potential to cause disease. Furthermore, it has been reported that patients were more easily infected by SARS-CoV after immunization with a live attenuated vaccine or inactivated whole-virus vaccine. Thus, sufficient experiments are necessary to verify their safety. Currently, three inactivated novel coronavirus pneumonia vaccines have entered the phase I/II clinical trials. ⁻

Nucleic acid vaccine

Nucleic acid vaccines, including DNA vaccines and mRNA vaccines, are to directly deliver foreign genes encoding antigenic proteins into host cells and synthesize the antigenic proteins by host cells to induce the immunity of hosts. Nucleic acid vaccines of COVID-19 mainly aim to induce the whole S protein or receptor-binding domain of S protein expression, and several of them have entered clinical trials. For example, researchers of Inovio Pharmaceuticals are conducting the clinical trial of a DNA vaccine. In the meantime, the National Institute of Allergy and Infectious Diseases have developed a mRNA vaccine, mRNA-1273, which uses lipid nanoparticles to encapsulate the mRNA encoding S protein of SARS-CoV-2. Interestingly, Symvivo Corporation have developed an oral DNA vaccine to avoid invasive injection. It consists of live Bifidobacterium longum, which contain the synthetic DNA encoding S protein.

Protein vaccine

The protein vaccines of SARS-CoV-2 mainly include the whole S protein, recombinant S protein, and receptor-binding domain of the S protein, aiming to stimulate the body to produce corresponding neutralizing antibodies directly. Up to now, several subunit vaccines have been developed. For instance, Vaxart developed an oral recombinant protein vaccine to stimulate the mucosal immune responses for COVID-19. Up to now, some protein vaccines have entered clinical trials.

Viral vector-based vaccine

Viral vector-based vaccine is a kind of carrier vaccine that induces an immune response by inserting an exogenous antigen gene into the viral genome to obtain a recombinant virus, and then express the corresponding target protein after vaccination. The viral vector-based vaccines of COVID-19 are engineered with the insertion of genes encoding the full length S protein or S protein receptor-binding domain, which include the lentiviral vector vaccine and adenovirus vector vaccine. ⁻ Shenzhen Geno-Immune Medical Institute developed a lentiviral vector system (NHP/TYF) for expression of the S protein in human body to activate T cells., Furthermore, Adenovirus vector vaccine (Adenovirus Type 5 Vector) sponsored by Insitute of Biotechnology, Academy of Military Medical Sciences, PLA of China, has entered phase II clinical trials.

Asymptomatic patients of COVID-19

Conclusions and future perspectives

COVID-19, a disease that seriously endanger the safety of human life and properties, is caused by SARS-CoV-2, which attacks host cells through ACE2. The spread of COVID-19 mainly depends on airborne and droplet transmission. Some researchers pointed out the possibility of fecal-oral transmission and vertical transmission, but these opinions need further confirmation. An accurate diagnosis of COVID-19 is essential for containing disease, thus combnation of RT-PCR and clinical characteristics is widely used for its detection currently. The typical clinical features of COVID-19 patients include fever, cough, and dyspnea. Moreover, GGO, consolidation, and interlobular septal thickening are also typical CT signals of COVID-19. Using artificial intelligence to screen COVID-19 early on is likely to be the future diagnostic directions of it.

Good treatment is necessary to reduce mortality, and drug therapy is the main treatment of COVID-19. Thus, we summarize the chief medicines and bioproducts for its treatment. According to the current reports, combined use of the drugs and bioproducts to treat COVID-19 both etiologically and symptomatically has received great clinical effect. However, not all antiviral drugs for COVID-19 have passed the clinical trials. A few clinical trial reports demonstrated that lopinavir-ritonavir, chloroquine, and remdesivir did not work as well as expected,, , which reflects the fact that many antiviral drugs have gone through many extensive clinical trials with currently only modest effect. Instead, some bioproducts such as monoclonal antibodies and stem cells are more likely to play important roles in treatment of severely affected patients in the future. Furthermore, we should also focus on vaccine research and artificial intelligence-based studies for fighting the outbreak, both of which play vital roles in controlling the it.

Although antiviral effects of many drugs and vaccines have been obtained in vitro, it remains to be seen as to whether they have comparable activity in vivo. Therefore, establishing efficient animal models as soon as possible is important for virology research, drug, and vaccine development. Currently, rhesus macaques models have been established to study the transmission and distribution of SARS-CoV-2 as well as effects of viral infection on host prognosis,, which is meaningful for virology study. Furthermore, hACE2 transgenic mice have been found to own typical COVID-19 clinical symptoms, which could not be found in wild-type mice, indicating this model may be used for development of therapeutic drugs and vaccines. Thus, perhaps further researching effective animal models and making full use of them shows the future direction to develop drugs and vaccines with high specificity as soon as possible.

Acknowledgements

This work was supported by the National Natural Science Foundation of China (grants No. 81871890 and 91859203)and the Science and Technology Project of Chengdu for Precision Medicine Research (grant No. 2017-CY02-00030-GX).

Author contributions

J.L., J.S., and C.W. wrote the initial draft of the manuscript. J.L. and C.W. gathered important information. C.W. and W.L. provided critical revision of the manuscript.

Conflict of interests

All authors declared that they had no conflict of interest.

References

Author notes

This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

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epidemiology and therapeutic options for the COVID-19

# data[].attributes.attachment_link.description
An outbreak of coronavirus disease 2019 (COVID-19), a disease caused by a novel pneumonia virus, has affected over 200 countries and regions worldwide. With the increasing number of patients and deaths, WHO have declared it as a global pandemic currently, indicating a third large-scale epidemic coronavirus has appeared since the emergence of severe acute respiratory syndrome coronavirus (SARS) and Middle-East respiratory syndrome (MERS) in the twenty-first century.

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Sharma, Nilesh Kumar ; Sarode, Sachin C ; Sarode, Gargi ; Patil, Shankargouda

Medical hypotheses, December 2020, Vol.145

PEER REVIEWED

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Muhammad Bilal, Muhammad Shahzad Nazir, Roberto Parra-Saldivar, & Hafiz M.N. Iqbal. (2020). 2019-nCoV/COVID-19 - Approaches to Viral Vaccine Development and Preventive Measures. Journal of Pure & Applied Microbiology : An International Research Journal of Microbiology, 14(1), 25-29.