Current status of application of convalescent plasma in acute viral infectious diseases and its prospect in therapy of COVID-19

Objective: To investigate the etiology distribution and laboratory diagnosis of acute respiratory infectious diseases. Methods: By searching, collecting and summarizing the etiology distribution and laboratory diagnosis of respiratory infectious diseases, the latest research progress of acute respiratory infectious diseases was studied in order to provide reference for clinical prevention and treatment. Results: In the relevant literature collected, it is considered that acute respiratory infectious diseases refer to infectious diseases caused by pathogens invading human body from the nasal cavity, throat, trachea and bronchus. The main acute respiratory infectious diseases are SARS (acute severe respiratory syndrome), MERS (Middle East respiratory syndrome), 2019-ncov infection (new coronavirus pneumonia), pulmonary plague, influenza, measles, diphtheria, pertussis, rubella, meningitis, mumps, tuberculosis, etc. Different types of infection have different diagnostic methods, and different treatments are given according to different diseases. Conclusion: The etiology distribution and laboratory diagnosis of acute respiratory tract infectious diseases are understood through reference, which can provide better reference for clinical practice. Acute respiratory infectious disease is the most common clinical disease, which seriously endangers people’s health.

Urogenital System Damaging Manifestations of 3 Human Infected Coronaviruses.

KEY IDEAS Case series studying convalescent plasma use in the treatment of COVID‐19 have been promising, but additional, high‐quality studies are needed to determine the efficacy of the treatment when applied for prophylaxis, for early phases of illness, and for severe illness.Previous studies of convalescent plasma in treating other viral diseases have identified factors to consider when designing treatment protocols, including timing of administration relative to onset of illness, timing of donation relative to resolution of symptoms, severity of illness of the donor, pretransfusion serology of the recipient, and antibody titers of the donor.There are many clinical trials studying treatment of, and prophylaxis against, COVID‐19 using convalescent plasma. In addition to clinical trials, the FDA also allows treatment through two other pathways: the “Expanded Access to Convalescent Plasma for the Treatment of Patients with COVID‐19” protocol, and emergency investigational new drug applications. The FDA also provides criteria for donation of convalescent plasma.

Emergence of institutional antithrombotic protocols for coronavirus 2019

In December 2019, a novel coronavirus was identified in Wuhan City, Hubei Province, China and later the disease was named coronavirus disease 2019 (COVID-19). On March 11, 2020, the World Health Organization (WHO) officially announced that COVID-19 had reached global pandemic status. This article summarized the understanding of the etiology, pathogenesis, epidemiology, clinical characteristics, diagnosis, treatment, rehabilitation, and prevention and control measures of COVID-19 based on the available data and anti-epidemic experience in China.

COVID-19, SARS and MERS: are they closely related?

In December 2019, a new pneumonic disease began to appear in Wuhan, Hubei Province, China. It seemed highly infectious and resistant to therapy, causing considerable concern amongst physicians. Within a month, 41 patients had been admitted to a single hospital and one had died. The initial cases were strongly associated with the Huanan seafood market, in which exotic animals were sold for food. The market was closed, but it was several weeks before public health officials were able to introduce strong public health quarantine measures in the local area. Within weeks of the first cases, a series of papers were released detailing the epidemiology of the disease (now termed COVID-19) [1-3]. By early January 2020 the virus was identified and the sequence determined. The virus (termed SARS-CoV-2) shares 88% sequence identity to two coronaviruses found in bats, bat-SLCoVZC45 and bat-SL-CoVZXC21, 79% identity with the Severe Acute Respiratory Syndrome (SARS) coronavirus and 50% identity with Middle Eastern Respiratory Syndrome (MERS) coronavirus [4]. From the first cohort of patients, 8 complete genomes were 99.9% identical in sequence. Given that the typical RNA coronavirus evolves at a rate of 104 nucleotide substitutions per year, this suggests a recent single source emergence in early December or late November 2019 [4]. SARS-CoV-2 is thought to be transmitted via contaminated hands, surfaces and aerosolised droplets; extensive human-to-human transmission is evident, with clusters of infected families and medical staff [5]. The number of confirmed cases has increased rapidly, at a rate that far outstripped the rate of rise of cases of SARS in 2002/3, raising serious global health concerns. By the 21st January, COVID-19 cases were widespread across mainland China, soon spreading beyond the Chinese borders. On the 30th January 2020 the International Health Regulations Emergency Committee of the World Health Organization (WHO) declared a public health emergency of international concern. As of the 24th February 2020, there were 79,331 lab confirmed cases and 2,618 deaths worldwide [6]. The majority of these are in China with 77,262 cases and 2,595 deaths [6]. Clearly, many are still suffering from COVID-19 and may or may not recover. This is only a small fraction of the total population of China (1,428 million), and strenuous efforts continue to limit spread. However, SARS-CoV-2 has now spread to 29 countries, the Republic of Korea having the 2nd highest number of cases (893 cases with 8 deaths) [6]. In the UK there have been 13 confirmed cases, 8 of whom have recovered and been discharged home. As of 25th of February 2020, 276 cases and 7 deaths have been identified in 7 EU/EEA countries. The majority of these cases have been from a spike in locally acquired cases in Italy resulting in 6 deaths. Iran has also had a recent increase in cases with 61 cases and 12 deaths [7, 8]. From the first 41 reported cases, the mortality rate was thought to be as high as 15%. The general fatality rate is currently uncertain but could be as high as 1–2% of all infections; however, as more cases are found with mild or unapparent disease this rate is expected to fall. The average incubation period is around 5 days, but also appears quite variable and may be as long as two weeks [3]. With around 60,000 active cases awaiting a final outcome, the case fatality amongst those with COVID-19 is difficult to determine at the present time. One case in Egypt is the first detected in Africa, while many developing, low resource, countries have had no cases. This apparently low transmission rate to such countries might be a consequence of public health measures enforced to limit spread of SARS-CoV-2 in China, or could reflect the limited diagnostic capacity in low resource settings. SARS-CoV-2 seems to have a predilection for the elderly male population and for patients with co-morbidities. The most common symptoms include fever (83%), cough (82%) and breathlessness (31%) [1, 2]. The majority (75%) of patients had bilateral pneumonic changes on CT imaging [2]. In a recent update by the Chinese Centre for Disease Control, 81% of infections were considered mild and only 1.2% asymptomatic [9]. The first report to detail infection in children found only 9 cases of COVID-19 in children; 7 were female and none required intensive care support, potentially indicating that children may be less susceptible to infection and/or symptomatic disease [10]. Lower respiratory tract infections are the most deadly communicable diseases globally, causing 3 million deaths per year and are the 4th commonest cause of death worldwide, including endemic, epidemic and pandemic viruses. In 2009 the influenza (H1N1) pandemic spread to 214 countries and caused an estimated 500,000 deaths with a case fatality rate of around 0.2% [11]. There are numerous other coronaviruses that are pathogenic to humans but present with mild clinical symptoms. However, SARS-CoV-2 is the 3rd highly pathogenic coronavirus to emerge in the past 2 decades. The first outbreak was SARS, in 2002 in the Guangdong province of China in 'wet markets' (like the Huanan market where SARS-Cov-2 is thought to have first emerged). In total, there were 8,422 cases of SARS with 916 deaths across 29 countries. The estimated case fatality for SARS was 11% [12]. Middle Eastern Respiratory Syndrome (MERS) coronavirus was responsible for the severe respiratory disease outbreak in 2012 in the Middle East. There were 2,494 confirmed cases with 858 fatalities; 38 deaths were reported in South Korea, with a total of 27 countries reporting cases of MERS (Table 1) [13]. Like SARS-CoV-2, SARS and MERS coronaviruses are thought to have originated from bats and transmitted to humans from an intermediate host, civets and dromedary camels respectively. For SARS-CoV-2, the zoonotic source and intermediate host is yet to be confirmed but with recent advances in whole genome sequencing, detailed phylogenetic analysis can be rapidly performed and used to establish detailed evolutionary links. The improved ability to identify and diagnose novel pathogens has enabled a rapid global response to minimise the impact and co-coordinate international resources; however, the effect that this will have on the global impact of COVID-19 remains unknown. One of the first measures taken by the local authorities was alerting the WHO within 4 weeks from the first patient being identified. This is in stark contrast to the SARS outbreak when it took 4 months. The identification of a novel coronavirus in the SARS-CoV-2 outbreak was quickly followed by the closure of the Huanan market, with the aim of preventing any further zoonotic transmission. During the SARS outbreak there was a delay in identifying the civet as a reservoir for the disease and civets continued to be sold on food markets. Steps such as closing the market has encouraged identification and reduction of transmission from potential animal sources and the WHO has advised that caution should be taken to avoid unprotected contact with farm or wild animals [6]. For now, the reported case numbers of COVID-19 continues to mount, but more slowly. However, with such widespread distribution both within and outside China, it seems likely that subsequent outbreaks will continue to be seen. Crucially there are substantial gaps in our knowledge regarding the epidemiology of disease, the major predisposing risks, transmission rates, clinical manifestations and phenotypes and treatment options. However, we have learnt much from the SARS and MERS outbreaks, which influenced the local and global response to the current outbreak. Our ability to rapidly identify novel pathogens using whole genome sequencing and to develop PCR based diagnostic tests from this data has expedited our ability to identify cases and understand the epidemiology of disease much earlier in the epidemic. This has informed the current strategy of reducing human to human transmissions, especially to healthcare professionals. Another key strategy to reduce transmission is to correctly triage and identify patients with severe acute respiratory infections at first point of contact to minimise exposure to others. The epidemiological and clinical criteria must be met to be classified as a possible case. Currently anyone with severe respiratory infection requiring hospital admission with no alternative diagnosis and a travel history to an affected country during the 14 days before the onset of symptoms, or anyone with any acute respiratory illness and contact with a confirmed or probable case of COVID-19 (including in a health care facility) falls under a suspected case definition [14]. These case definitions vary slightly in different countries and Public Health England (PHE) include clinical or radiological evidence of pneumonia, specific symptoms of breathlessness or cough, or anyone with a fever who has a history of travel to the listed countries [15]. For the public, general precautions should be taken to avoid contact with patients suffering from acute respiratory infections. In health care settings, precautions such as using good hand hygiene, and the use of personal protection equipment (PPE) to avoid direct contact with patient's secretions or bodily fluids should be followed. Specimens should be tested for routine bacterial and viral infections, as well as using both upper and lower respiratory tract samples to test for SARS-CoV-2. This should be performed using real time polymerase chain reaction testing (RT-PCR). Serological tests are in development but should only be used if RT-PCR is not available [16]. A key part of infection control is detailed contact tracing. Early supportive measures should be taken, including supportive oxygen therapy for respiratory distress and hypoxia, more invasive respiratory support if required, intravenous fluids, antimicrobials and anti-viral medications. The current published data indicates a long mild incubation period followed by rapid progression of disease with 8 days being the median time from initial symptoms to the onset of breathlessness, 9 days to acute respiratory distress syndrome (ARDS) and 10.5 days to admission to intensive care [1]. In one study of 99 cases, 17% developed ARDS, 13% required non-invasive respiratory support, 4% needed invasive ventilation and 3% needed extracorporeal membrane oxygenation (ECMO) [2]. Tools such as the MuLBSTA Score, which incorporates risk factors and comorbidities such as smoking, hypertension, age, bacterial co-infections, lymphopenia and areas of the lung involved, may be useful to predict mortality in patients with viral pneumonia [2, 17]. The SARS and MERS epidemics, and our treatment of other endemic and epidemic respiratory viruses, can provide some guidance on treatment strategies that may benefit patients with COVID-19. There are currently no specific anti-COVID-19 therapies but over 80 clinical treatment trials have been initiated to tackle COVID-19 [18]. These trials include the HIV drug combination of lopinavir and ritonavir (protease inhibitors that have been reported to reduce SARS and MERS replication), and also remdesivir (an approved reverse transcriptase inhibitor that similarly has demonstrated in vitro activity against SARS-CoV-2 [19]). It may also be possible to enhance the protective host immune response to infection, or inhibit immunopathogenesis (which is thought to contribute to disease severity for some respiratory pathogens). In particular, 'cytokine storms' are thought to be major contributors to the severity of many lower respiratory tract infections, such as influenza [20] and SARS [21]. Host-targeted therapies might therefore be aimed at either enhancement of innate immune clearance of SARS-CoV-2 or inhibition of inflammatory damage to the airway and the development of secondary bacterial pneumonias. In the first 41 cases, 22% were given systemic corticosteroids, with the aim of suppressing inflammation induced lung injury [1]; however, current WHO guidelines do not recommend their use and data from SARS and MERS showed that corticosteroids did not reduce mortality and potentially delayed viral clearance [22-24]. Alternative strategies under investigation include immunomodulation with chloroquine (which might also have anti-viral function [19]), monoclonal antibodies and immunoglobulins. These interventional studies, in addition to observational studies, will develop our understanding of severe COVID-19 infections, particularly the relative contribution of viral load and sequence (though current data indicate little strain variation amongst cases so far), bacterial co-infections, host genetics, environmental factors and immunopathogenesis (Figure 1). The SARS and MERS epidemics have put us in a better position to respond to COVID-19. The transparency demonstrated in the rapid sharing of the SARS-CoV-2 genetic information has been critical in mediating a global approach to minimise the spread of disease. This has enabled the rapid development of diagnostic tests and their global implementation. In turn these diagnostic tests have facilitated the management of cases in those areas most affected, and the identification of cases in other countries, all of which has aided in limiting the global spread of SARS-CoV-2. However, current evidence indicates that these public health measures alone may be insufficient to eliminate COVID-19. New treatments are urgently needed and the time that public health measures have bought us must be used productively. Ongoing clinical trials of existing drugs may provide further breakthroughs in limiting morbidity and mortality, but vaccines and prophylactics may be needed to prevent the spread of infections. In a little over two months SARS-CoV-2 has spread to 29 countries and caused far greater morbidity and mortality than either SARS or MERS, despite rapid identification and robust public health measures. The outlook is uncertain, but continued global spread seems likely and we must be prepared to face this threat. While continuing to delay the spread of disease we must rapidly initiate studies of potential therapeutics and develop our understanding of COVID-19 pathogenesis. All numbers in this article are correct as of 24 February 2020. As the situation regarding COVD-19 is changing daily, readers are recommended to refer to the websites listed in the references for the most up-to-date information.

The coronavirus disease 2019 (COVID-19) pandemic is caused by a novel betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), similar to SARS-CoV and Middle East respiratory syndrome (MERS-CoV), which cause acute respiratory distress syndrome and case fatalities. COVID-19 disease severity is worse in older obese patients with comorbidities such as diabetes, hypertension, cardiovascular disease, and chronic lung disease. Cell binding and entry of betacoronaviruses is via their surface spike glycoprotein; SARS-CoV binds to the metalloprotease angiotensin-converting enzyme 2 (ACE2), MERS-CoV utilizes dipeptidyl peptidase 4 (DPP4), and recent modeling of the structure of SARS-CoV-2 spike glycoprotein predicts that it can interact with human DPP4 in addition to ACE2. DPP4 is a ubiquitous membrane-bound aminopeptidase that circulates in plasma; it is multifunctional with roles in nutrition, metabolism, and immune and endocrine systems. DPP4 activity differentially regulates glucose homeostasis and inflammation via its enzymatic activity and nonenzymatic immunomodulatory effects. The importance of DPP4 for the medical community has been highlighted by the approval of DPP4 inhibitors, or gliptins, for the treatment of type 2 diabetes mellitus. This review discusses the dysregulation of DPP4 in COVID-19 comorbid conditions; DPP4 activity is higher in older individuals and increased plasma DPP4 is a predictor of the onset of metabolic syndrome. DPP4 upregulation may be a determinant of COVID-19 disease severity, which creates interest regarding the use of gliptins in management of COVID-19. Also, knowledge of the chemistry and biology of DPP4 could be utilized to develop novel therapies to block viral entry of some betacoronaviruses, potentially including SARS-CoV-2.

Initial public health response and interim clinical guidance for the 2019 novel coronavirus outbreak - United States, December 31, 2019-February 4, 2020.

Data sharing and outbreaks: best practice exemplified

Coronavirus Disease 2019: Coronaviruses and Kidney Injury.

Aim . The aim of this review is a comprehensive analysis of current literature data on coronaviruses identified in bats. Discussion . Coronaviruses ( Coronaviridae ) constitute the most extensive family of viruses of the order Nidovirales. Coronaviruses have a wide range of hosts, including mammals ( Alphacoronavirus, Betacoronavirus, Deltacoronavirus, Gammacoronavirus ) and birds ( Deltacoronavirus, Gammacoronavirus ), amphibians ( Alphaletovirus ) and are pathogens of respiratory, intestinal, cardiovascular. Until the beginning of this century, only etiological agents of mild and moderate respiratory diseases were known among pathogenic coronaviruses for humans. In the 21st century, new highly pathogenic coronaviruses were discovered that caused outbreaks of severe pneumonia with high mortality: the severe acute respiratory syndrome coronavirus (Severe acute respiratory syndrome ‐ related coronavirus, SARS ‐ CoV; 2002 ‐ 2003, southern provinces of China), the Middle East respiratory coronavirus Syndrome (Middle East respiratory syndrome ‐ related coronavirus, MERS ‐ CoV; 2012, western part of Saudi Arabia) and type 2 acute respiratory syndrome coronavirus (Severe acute respiratory syndrome ‐ related coronavirus 2, SARS ‐ CoV ‐ 2; 2019 ‐ ..., the eastern part of central China). The natural reservoirs of SARS ‐ CoV, SARS ‐ CoV ‐ 2 and MERS ‐ CoV are bats ( Chiroptera ). Coronaviruses circulating in bat populations are not only phylogenetically close to the currently known especially dangerous human viruses but probably have epidemic potential that can be realized in the future. Conclusion . This review presents current data on coronaviruses of bats: taxonomic status, spectrum of potential hosts, distribution. The ecological features of coronaviruses of bats are considered in the context of their epidemiological significance. The origin of pathogenic human coronaviruses is discussed.

BackgroundThe outbreak of coronavirus disease 2019 (COVID-19) has caused a public catastrophe and global concern. The main symptoms of COVID-19 are fever, cough, myalgia, fatigue and lower respiratory tract infection signs. Almost all populations are susceptible to the virus, and the basic reproduction number (R0) is 2.8–3.9. The fight against COVID-19 should have two aspects: one is the treatment of infected patients, and the other is the mobilization of the society to avoid the spread of the virus. The treatment of patients includes supportive treatment, antiviral treatment, and oxygen therapy. For patients with severe acute respiratory distress syndrome (ARDS), extracorporeal membrane oxygenation (ECMO) and circulatory support are recommended. Plasma therapy and traditional Chinese medicine have also achieved good outcomes. This review is intended to summarize the research on this new coronavirus, to analyze the similarities and differences between COVID-19 and previous outbreaks of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) and to provide guidance regarding new methods of prevention, diagnosis and clinical treatment based on autodock simulations.MethodsThis review compares the multifaceted characteristics of the three coronaviruses including COVID-19, SARS and MERS. Our researchers take the COVID-19, SARS, and MERS as key words and search literatures in the Pubmed database. We compare them horizontally and vertically which respectively means concluding the individual characteristics of each coronavirus and comparing the similarities and differences between the three coronaviruses.ResultsWe searched for studies on each outbreak and their solutions and found that the main biological differences among SARS-CoV-2, SARS-CoV and MERS-CoV are in ORF1a and the sequence of gene spike coding protein-S. We also found that the types and severity of clinical symptoms vary, which means that the diagnosis and nursing measures also require differentiation. In addition to the common route of transmission including airborne transmission, these three viruses have their own unique routes of transmission such as fecal-oral route of transmission COVID-19.ConclusionsIn evolutionary history, these three coronaviruses have some similar biological features as well as some different mutational characteristics. Their receptors and routes of transmission are not all the same, which makes them different in clinical features and treatments. We discovered through the autodock simulations that Met124 plays a key role in the efficiency of drugs targeting ACE2, such as remdesivir, chloroquine, ciclesonide and niclosamide, and may be a potential target in COVID-19.

Objective: to provide reliable evidence of evidence-based medicine for the treatment and prevention of the 2019 novel coronavirus (2019-nCoV) by analyzing all the published studies on the clinical characteristics of patients with 2019-nCoV. Methods: PubMed,Cochrane Library, Embase and other databases were searched. Some studies on the clinical characteristics of 2019-nCoV infection were collected for Meta-analysis. Results: 8 studies were included in Meta-analysis, including a total of 5732 patients with 2019-nCoV infection.According to Meta-analysis, among the clinical characteristics of patients with 2019-nCoV infection, the incidence of fever is 90.9%, the incidence of cough is 70.8%, and the incidence of muscle soreness or fatigue is 41%. The incidence of acute respiratory distress syndrome (ARDS) was 14.8%, the incidence of abnormal chest CT was 95.6%, the proportion of severe cases in all infected cases was 24.3%, and the mortality rate of patients with 2019-nCoV infection was 6.4%. Conclusion: Fever and cough are the most common symptoms in patients with 2019-nCoV infection, and most of them have abnormal chest CT examination.Some people have muscle soreness or fatigue, ARDS. Diarrhea, hemoptysis, headache, sore throat, shock and other symptoms only occur in a small number of patients.The mortality rate of patients with 2019-nCoV infection was lower than that of Severe Acute Respiratory Syndrome (SRAS) and Middle East Respiratory Syndrome (MERS). Funding Statement: There is no funding for our research. Declaration of Interests: The authors have declared that there is no conflict of interest in this study. Ethics Approval Statement: This study utilized PRISMA.

Host-pathogen interaction in COVID-19: Pathogenesis, potential therapeutics and vaccination strategies