Long-term outcomes for epidemic viral pneumonia survivors after discharge from the intensive care unit: a systematic review

ABSTRACT Objective To review the long-term outcomes (functional status and psychological sequelae) of survivors of critical illnesses due to epidemic viral pneumonia before the COVID-19 pandemic and to establish a benchmark for comparison of the COVID-19 long-term outcomes. Methods This systematic review of clinical studies reported the long-term outcomes in adults admitted to intensive care units who were diagnosed with viral epidemic pneumonia. An electronic search was performed using databases: MEDLINE®, Web of Science™, LILACS/IBECS, and EMBASE. Additionally, complementary searches were conducted on the reference lists of eligible studies. The quality of the studies was assessed using the Newcastle-Ottawa Scale. The results were grouped into tables and textual descriptions. Results The final analysis included 15 studies from a total of 243 studies. This review included 771 patients with Influenza A, Middle East Respiratory Syndrome, and Severe Acute Respiratory Syndrome. It analyzed the quality of life, functionality, lung function, mortality, rate of return to work, rehospitalization, and psychiatric symptoms. The follow-up periods ranged from 1 to 144 months. We found that the quality of life, functional capacity, and pulmonary function were below expected standards. Conclusion This review revealed great heterogeneity between studies attributed to different scales, follow-up time points, and methodologies. However, this systematic review identified negative long-term effects on patient outcomes. Given the possibility of future pandemics, it is essential to identify the long-term effects of viral pneumonia outbreaks. This review was not funded. Prospero database registration: (www.crd.york.ac.uk/prospero) under registration ID CRD42021190296.

Overview of the Management of COVID-19 Efficacy and Doubts

Coronavirus disease 2019 (COVID-19) is defined as an illness caused by a novel coronavirus now called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2. It was first identified during an outbreak of respiratory illness cases in Wuhan City, Hubei Province, China.Management of COVID-19 is still unspecific as there are no vaccine orspecific antiviral drugs areavailable for its treatment. This paper reviewsthemanagement efficacy and doubt of COVID-19.Methods: A comprehensive search from relevant literatures, World Health Organization (W.H.O), Centre for Disease Control and prevention (CDC) official websites and announcements was performed between 1 March2020 to 10:30 am 22 April 2020 (Nigerian time). A latest summary of 2019-nCoV and the current outbreak was drawn.Conclusion: The covid-19 pandemic is spreading rapidly and several researchers are making efforts to discover drugs for its treatment. Chloroquine phosphate, vaccines and other forms of management strategies have been employed. However, preventive measureslike social distancing, washing of handswith soap and water, wearing of face masks and psychosocial treatment should be adopted while waiting for pharmacological treatments.

COVID-19: The outbreak caused by a new coronavirus / COVID-19: la epidemia causada por un nuevo coronavirus

Abstract Before the severe acute respiratory syndrome outbreak in 2003, coronaviruses (CoVs) were not considered to be highly pathogenic to humans. However, it was this epidemic that highlighted this group of viruses and included them among the causative agents of emerging epidemic diseases. In addition, in 2012, another new CoV responsible for the Middle East respiratory syndrome was identified. Both infections were considered a threat to global health security. At present, the third epidemic caused by a CoV is being faced. This new CoV, called 2019-nCoV, was originated in the city of Wuhan, China, and has been linked to severe respiratory infections in humans. Thanks to the collaboration of experts worldwide, more information about this virus and its infection is reported each day, which allows modifying the recommendations for its prevention and treatment, without forgetting that the ultimate goal is to control this epidemic. In this review, the important aspects of this new coronavirus, 2019-nCoV, and its disease, COVID-19, have been summarized with the information available up to February 2020.

Resumen Previo al brote del síndrome respiratorio agudo grave de 2003, los coronavirus (CoV) no eran considerados como agentes altamente patogénicos para los humanos. Sin embargo, fue dicha epidemia la que destacó este grupo de virus y lo incluyó entre los agentes causantes de enfermedades epidémicas emergentes. Adicionalmente, en 2012 se identificó un nuevo CoV causante del síndrome respiratorio de Oriente Medio. Ambas infecciones fueron consideradas una amenaza para la seguridad sanitaria mundial. Hoy en día se presenta la tercera epidemia causada por un CoV. Este nuevo CoV, llamado 2019-nCoV, se originó en la ciudad de Wuhan, China, y ha sido relacionado con infecciones respiratorias graves en humanos. Gracias a la colaboración de expertos en todo el mundo, cada día se logra obtener más información sobre este virus y la infección que causa, lo cual permite modificar las recomendaciones para su prevención y tratamiento sin olvidar que el fin último es lograr el control de la epidemia. En esta revisión se resumen los aspectos más importantes acerca del nuevo 2019-nCoV y la enfermedad COVID-19, con la información disponible hasta febrero de 2020.

Bat-related coronavirus / 第二军医大学学报

The outbreak of coronavirus disease 2019 (COVID-19) in Dec. 2019 sounded another alarm for humanbeing, with the first being the outbreak of severe acute respiratory syndrome (SARS) in 2003. Researchers found that the natural host of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen of COVID-19, may be the Rhinolophus sinicus. There have been four outbreaks of coronaviruses (severe acute respiratory syndrome coronavirus [SARS-CoV], Middle East respiratory syndrome coronavirus [MERS-CoV], swine acute diarrhea syndrome coronavirus [SADS-CoV] and SARS-CoV-2) worldwide since the beginning of 21st century, and they have caused huge threats and losses to human health, public health, economic development, and social stability. A large amount of evidence suggests that the natural host of all these four coronaviruses may be bats. This article reviews the species and global geographic distribution of bat-related coronaviruses, and the above-metioned four coronaviruses causing severe outbreaks.

Diagnosis, treatment, control and prevention of SARS-CoV-2 and coronavirus disease 2019: back to the future / 生物工程学报

The ongoing outbreak of the coronavirus disease 2019 (COVID-19) as named by the World Health Organization has millions of confirmed cases around the world and has claimed hundreds of thousands of lives. The virus was named SARS-CoV-2 in February by International Committee on Taxonomy of Viruses. COVID-19 presents as fever, dry cough, dyspnea, headache and pneumonia. In a small subset of severe cases, the disease quickly progresses to respiratory failure and even death. Since the 21st century, there have been three major outbreaks caused by human coronaviruses, including the severe acute respiratory syndrome (SARS) that broke out in 2003, the Middle East respiratory syndrome (MERS) in 2012, and the recent pandemic of COVID-19. Since 2003, significant progress has been made in the study of SARS-CoV and MERS-CoV concerning their natural origins, pathogenesis, antiviral development and vaccine design. Since SARS-CoV-2 and SARS-CoV are closely related, previous findings on SARS-CoV are highly relevant to a better understanding as well as diagnosis, treatment, prevention and control of SARS-CoV-2. In this review, we highlight recent progresses in the field; compare the biological characteristics of SARS-CoV and SARS-CoV-2; summarize the urgently-needed diagnostic, treatment, prevention and control options; and provide future perspectives for the outcome of the outbreak and research questions to be answered, including some of the difficulties in vaccine development. Hopefully, our comments and suggestions would prove useful for the control of the SARS-CoV-2 epidemic in China and the world.

Absence of neutralizing activity in serum 1 year after successful treatment with antivirals and recovery from MERS in South Korea

We evaluated the neutralizing activity in serum from three patients >1 year after recovery from Middle East respiratory syndrome (MERS) associated with mild pneumonia treated with antivirals during the MERS outbreak in South Korea at 2015. The neutralizing activity in serum was measured by pseudovirus inhibition assays. Three-fold diluted serum of subjects showed only 9.7%, 10.3%, and 2.2% reductions in relative light units. So, significant neutralizing activity was not demonstrated in any sera of three patients with mild pneumonia >1 year after being successfully treated with antiviral agents and recovering from MERS coronavirus infection.

Establishment and evaluation of receptor binding domain (RBD)-based ELISA for Middle East respiratory syndrome coronavirus (MERS-CoV) antibody detection / 中华微生物学和免疫学杂志

Objective@#To establish an indirect enzyme-linked immunosorbent assay (ELISA)and to compare the efficiency of receptor binding domain (RBD) proteins in different forms for Middle East respiratory syndrome coronavirus (MERS-CoV) antibody detection.@*Methods@#The monomeric and trimeric forms of MERS-CoV RBD were expressed in Bac-insect cells, 293T cells and ExpiCHO-S™ expression system and then purified. The purified RBD proteins were identified with native gel electrophoresis and Western blot. Then, an equal amount of each RBD protein was used as coating antigen to establish an ELISA for detecting MERS-CoV IgG titer. For comparison, the newly developed ELISA and the commercial MERS-CoV IgG antibody detection kit (Euroimmune with S1 as the coating antigen) were used to measure the MERS-CoV antibody reference panel supplied by World Health Organization (WHO).@*Results@#The purified monomeric and trimeric MERS-CoV RBD were successfully prepared using 293T cells and ExpiCHO-S™ system. RBD antigens of different forms and from different systems could recognize MERS-CoV specific antibody without having any cross reaction with the sera from healthy adults. The in-house RBD-based ELISA had good detection consistency with the Euroimmune commercial kit. The positive samples showed higher and more concentrated values based on the RBD trimer than the monomer.@*Conclusions@#Novel indirect ELISA methods based on the monomeric and trimeric forms of RBD protein were established. The trimetric form-based ELISA achieved higher detection efficiency than the one using the monomer antigen, suggesting that it could be uses as a competent alternative to the commercial kit.

Establishment and evaluation of receptor binding domain (RBD)-based ELISA for Middle East re-spiratory syndrome coronavirus (MERS-CoV) antibody detection / 中华微生物学和免疫学杂志

Objective To establish an indirect enzyme-linked immunosorbent assay (ELISA)and to compare the efficiency of receptor binding domain (RBD) proteins in different forms for Middle East re-spiratory syndrome coronavirus (MERS-CoV) antibody detection. Methods The monomeric and trimeric forms of MERS-CoV RBD were expressed in Bac-insect cells, 293T cells and ExpiCHO-STM expression sys-tem and then purified. The purified RBD proteins were identified with native gel electrophoresis and Western blot. Then, an equal amount of each RBD protein was used as coating antigen to establish an ELISA for de-tecting MERS-CoV IgG titer. For comparison, the newly developed ELISA and the commercial MERS-CoV IgG antibody detection kit (Euroimmune with S1 as the coating antigen) were used to measure the MERS-CoV antibody reference panel supplied by World Health Organization (WHO). Results The purified mon-omeric and trimeric MERS-CoV RBD were successfully prepared using 293T cells and ExpiCHO-STM system. RBD antigens of different forms and from different systems could recognize MERS-CoV specific antibody without having any cross reaction with the sera from healthy adults. The in-house RBD-based ELISA had good detection consistency with the Euroimmune commercial kit. The positive samples showed higher and more concentrated values based on the RBD trimer than the monomer. Conclusions Novel indirect ELISA methods based on the monomeric and trimeric forms of RBD protein were established. The trimetric form-based ELISA achieved higher detection efficiency than the one using the monomer antigen, suggesting that it could be uses as a competent alternative to the commercial kit.

Rapid establishment of a mouse model of MERS-CoV pseudovirus infection based on DPP4 transduction / 中华微生物学和免疫学杂志

Objective To rapidly establish a mouse model for optical imaging of the dynamical process of pseudotyped Middle East respiratory syndrome coronavirus (MERS-CoV) infection. Methods In vitro expression in HeLa cells and functions of hDPP4 encoded by recombinant adenovirus Ad5 and pseudo-typed MERS-CoV were verified. The recombinant adenovirus expressing hDPP4 (Ad5-hDPP4) was injected into BALB/ c mice, which were then injected with pseudotyped MERS-CoV expressing firefly luciferase at a titer of 3×107 TCID50(50％ tissue culture infective dose) via intrathoracic (I. T. ) or intraperitoneal (I. P. ) injection. MERS-CoV infection and tissue distribution were observed using optical imaging techniques. Re-sults hDPP4 and firefly luciferase were efficiently expressed in HeLa cells. In BALB/ c mice injected with Ad5-hDPP4 via I. P. , firefly luciferase expression were detected in abdomen between 48-96 h after pseudo-typed MERS-CoV infection. The expression of firely luciferase was also detected in chests of BALB/ c mice injected with Ad5-hDPP4 via I. T. around 48 h after pseudotyped MERS-CoV infection. Conclusions This study reported a simple and rapid method for establishing a mouse model for conveniently and dynamically monitoring pseudotyped MERS-CoV infection, which might provide an effective means for in vivo evaluation of neutralizing antibodies or entry inhibitors by visualization with optical imaging techniques.

Middle East respiratory syndrome coronavirus in pediatrics: a report of seven cases from Saudi Arabia / 医学前沿

Infection with Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012 as an important respiratory disease with high fatality rates of 40%-60%. Despite the increased number of cases over subsequent years, the number of pediatric cases remained low. A review of studies conducted from June 2012 to April 19, 2016 reported 31 pediatric MERS-CoV cases. In this paper, we present the clinical and laboratory features of seven patients with pediatric MERS. Five patients had no underlying medical illnesses, and three patients were asymptomatic. Of the seven cases, four (57%) patients sought medical advice within 1-7 days from the onset of symptoms. The three other patients (43%) were asymptomatic and were in contact with patients with confirmed diagnosis of MERS-CoV. The most common presenting symptoms were fever (57%), cough (14%), shortness of breath (14%), vomiting (28%), and diarrhea (28%). Two (28.6%) patients had platelet counts of < 150 × 10/L, and one patient had an underlying end-stage renal disease. The remaining patients presented with normal blood count, liver function, and urea and creatinine levels. The documented MERS-CoV Ct values were 32-38 for four of the seven cases. Two patients (28.6%) had abnormal chest radiographic findings of bilateral infiltration. One patient (14.3%) required ventilator support, and two patients (28.6%) required oxygen supplementation. All the seven patients were discharged without complications.

Evolutionary relationship analysis of Middle East respiratory syndrome coronavirus 4a and 4b protein coding sequences

The 4a and 4b proteins of the Middle East respiratory syndrome coronavirus (MERS-CoV) have been described for their antagonism on host innate immunity. However, unlike clustering patterns of the complete gene sequences of human and camel MERS-CoVs, the 4a and 4b protein coding regions did not constitute species-specific phylogenetic groups. Moreover, given the estimated evolutionary rates of the complete, 4a, and 4b gene sequences, the 4a and 4b proteins might be less affected by species-specific innate immune pressures. These results suggest that the 4a and 4b proteins of MERS-CoV may function against host innate immunity in a manner independent of host species and/or evolutionary clustering patterns.

Asymptomatic Middle East Respiratory Syndrome coronavirus infection using a serologic survey in Korea / 한국역학회지

OBJECTIVES: The rates of asymptomatic infection with Middle East Respiratory Syndrome (MERS) coronavirus vary. A serologic study was conducted to determine the asymptomatic MERS infection rate in healthcare workers and non-healthcare workers by exposure status. METHODS: Study participants were selected from contacts of MERS patients based on a priority system in 4 regions strongly affected by the 2015 MERS outbreak. A sero-epidemiological survey was performed in 1,610 contacts (average duration from exposure to test, 4.8 months), and the collected sera were tested using an enzyme-linked immunespecific assay (ELISA), immunofluorescence assay (IFA), and plaque reduction neutralization antibody test (PRNT). Among the 1,610 contacts, there were 7 ELISA-positive cases, of which 1 exhibited positive IFA and PRNT results. RESULTS: The asymptomatic infection rate was 0.060% (95% confidence interval, 0.002 to 0.346). The asymptomatic MERS case was a patient who had been hospitalized with patient zero on the same floor of the hospital at the same time. The case was quarantined at home for 2 weeks after discharge, and had underlying diseases, including hypertension, angina, and degenerative arthritis. CONCLUSIONS: The asymptomatic infection was acquired via healthcare-associated transmission. Thus, it is necessary to extend serologic studies to include inpatient contacts who have no symptoms.

Middle East respiratory syndrome: what we learned from the 2015 outbreak in the Republic of Korea

Middle East Respiratory Syndrome coronavirus (MERS-CoV) was first isolated from a patient with severe pneumonia in 2012. The 2015 Korea outbreak of MERSCoV involved 186 cases, including 38 fatalities. A total of 83% of transmission events were due to five superspreaders, and 44% of the 186 MERS cases were the patients who had been exposed in nosocomial transmission at 16 hospitals. The epidemic lasted for 2 months and the government quarantined 16,993 individuals for 14 days to control the outbreak. This outbreak provides a unique opportunity to fill the gap in our knowledge of MERS-CoV infection. Therefore, in this paper, we review the literature on epidemiology, virology, clinical features, and prevention of MERS-CoV, which were acquired from the 2015 Korea outbreak of MERS-CoV.

Asymptomatic Middle East Respiratory Syndrome coronavirus infection using a serologic survey in Korea / 한국역학회지

OBJECTIVES: The rates of asymptomatic infection with Middle East Respiratory Syndrome (MERS) coronavirus vary. A serologic study was conducted to determine the asymptomatic MERS infection rate in healthcare workers and non-healthcare workers by exposure status.METHODS: Study participants were selected from contacts of MERS patients based on a priority system in 4 regions strongly affected by the 2015 MERS outbreak. A sero-epidemiological survey was performed in 1,610 contacts (average duration from exposure to test, 4.8 months), and the collected sera were tested using an enzyme-linked immunespecific assay (ELISA), immunofluorescence assay (IFA), and plaque reduction neutralization antibody test (PRNT). Among the 1,610 contacts, there were 7 ELISA-positive cases, of which 1 exhibited positive IFA and PRNT results.RESULTS: The asymptomatic infection rate was 0.060% (95% confidence interval, 0.002 to 0.346). The asymptomatic MERS case was a patient who had been hospitalized with patient zero on the same floor of the hospital at the same time. The case was quarantined at home for 2 weeks after discharge, and had underlying diseases, including hypertension, angina, and degenerative arthritis.CONCLUSIONS: The asymptomatic infection was acquired via healthcare-associated transmission. Thus, it is necessary to extend serologic studies to include inpatient contacts who have no symptoms.

Impact of Middle East respiratory syndrome outbreak on the use of emergency medical resources in febrile patients

OBJECTIVE: Outbreaks of transmissible respiratory infection are suspected to have significant effects on the health of pediatric and geriatric patients. The objective was to assess the impact of the Middle East respiratory syndrome (MERS) outbreak on the use of emergency resources. METHODS: An ecologic analysis of emergency department (ED) records between September and December 2015, was performed. Data was obtained from the National Emergency Department Information System database for Korea. All demographic and diagnostic data from patients presenting with febrile symptoms as a main complaint were collected. The data were compared to the equivalent period in the three years preceding the MERS outbreak in Korea. RESULTS: Following the MERS outbreak, there was an increase in overall ED visits by febrile patients and the proportion of visits by febrile patients, relative to total ED attendances. This effect was more prominent in the children under five years. The duration of the chief complaint before ED arrival and the length of ED stay were significantly increased among younger pediatric patients. Decreased body temperature on arrival was observed in younger pediatric patients. CONCLUSION: MERS outbreak appears to have had a significant effects on ED use by febrile patients. The use of emergency care services by pediatric patients makes them more vulnerable to an outbreak of a transmissable disease. An effective strategy to control emergency center visits by non-urgent febrile patients and provide proper medical services is urgently needed.

Effects of Timely Control Intervention on the Spread of Middle East Respiratory Syndrome Coronavirus Infection

OBJECTIVES: The 2015 Middle East Respiratory Syndrome Coronavirus (MERS-CoV) outbreak in Korea caused major economic and social problems. The control intervention was conducted during the MERS-CoV outbreak in Korea immediately after the confirmation of the index case. This study investigates whether the early risk communication with the general public and mass media is an effective preventive strategy. METHODS: The SEIR (Susceptible, Exposed, Infectious, Recovered) model with estimated parameters for the time series data of the daily MERS-CoV incidence in Korea was considered from May to December 2015. For 10,000 stochastic simulations, the SEIR model was computed using the Gillespie algorithm. Depending on the time of control intervention on the 20th, 40th, and 60th days after the identification of the index case, the box plots of MERS-CoV incidences in Korea were computed, and the results were analyzed via ANOVA. RESULTS: The box plots showed that there was a significant difference between the non-intervention and intervention groups (the 20th day, 40th day, and 60th day groups) and seemed to show no significant difference based on the time of intervention. However, the ANOVA revealed that early intervention was a good strategy to control the disease. CONCLUSION: Appropriate risk communication can secure the confidence of the general public in the public health authorities.

Middle East respiratory syndrome clinical practice guideline for hemodialysis facilities

The Korean Society of Nephrology participated in the task force team consisting of government authorities and civilian experts to prevent and control the spread of Middle East respiratory syndrome (MERS) in 2015. The Korean Society of Nephrology MERS Task Force Team took an immediate action and drafted ‘the clinical recommendation for hemodialysis facilities’ to follow when the first and the only confirmed case was reported in the hemodialysis unit. Owing to the dedicated support from medical doctors, dialysis nurses, and related medical companies, we could prevent further transmission of MERS infection successfully in hemodialysis units. This special report describes the experience of infection control during MERS outbreak in 2015 and summarizes the contents of ‘the clinical practice guideline for hemodialysis facilities dealing with MERS patients’ built upon our previous experience.

The experience of endotracheal intubation in Middle East respiratory syndrome patients: A case report

After Middle East respiratory syndrome (MERS) was first confirmed in Korea on May 20, 2015, a total of 186 confirmed cases and 37 deaths occurred until the announcement of its cessation on December 23, 2015. MERS often causes severe pneumonia; accordingly, many patients require endotracheal intubation for mechanical ventilation. At our hospital, we treated 30 confirmed and 29 suspected cases and performed 9 endotracheal intubations in 8 of these patients, using conventional direct laryngoscopy (DL) and GlideScope video-laryngoscopy (GL). We faced difficulty in conducting endotracheal intubation due to the personal protective equipment and the limited bed height required for managing MERS patients. In such cases, GL improved the ease and direct confirmation of success of endotracheal intubation as compared to DL. In addition, we found that portable end-tidal CO2-monitoring devices may facilitate more precise and reliable confirmation of successful intubation.

Study on Causes of Respiratory Disease to the Middle East Respiratory Syndrome-negative Subjects

Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe cases of human respiratory disease. The current outbreak of infection with this virus in South Korea, which began on May 20, 2015, has infected 186 patients and caused 36 deaths within 2 months. In this study, to investigate the viral pathogen causing acute respiratory infections, multiplex/RT-PCR was performed on were obtained from nucleic acid of the Middle East Respiratory Syndrome-negative subjects. Viruses and atypical bacteria were detected in 39 of 337 (11.6%). Frequent viruses were human rhinovirus (n=11, 3.3%), human metapneumovirus (n=9, 2.7%), parainfluenza (n=9, 2.7%) and adenovirus (n=4, 1.2%). Mycoplasma pneumonia (M. pneumonia) was detected in 1.8 % (n=6). Out of 9 human metapneumovirus (hMPV) positive samples, 6 samples were successfully sequenced using F gene. And M. pneumoniae was sequencing of a repetitive region of the P1 gene. Phylogenetic analysis revealed that hMPV clustered into A2b lineage (n=4), B2 lineage (n=2) and M. pneumoniae clustered into two genotypes: Type 1 (n=4), Type 2a (n=2).

Study on Causes of Respiratory Disease to the Middle East Respiratory Syndrome-negative Subjects

Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe cases of human respiratory disease. The current outbreak of infection with this virus in South Korea, which began on May 20, 2015, has infected 186 patients and caused 36 deaths within 2 months. In this study, to investigate the viral pathogen causing acute respiratory infections, multiplex/RT-PCR was performed on were obtained from nucleic acid of the Middle East Respiratory Syndrome-negative subjects. Viruses and atypical bacteria were detected in 39 of 337 (11.6%). Frequent viruses were human rhinovirus (n=11, 3.3%), human metapneumovirus (n=9, 2.7%), parainfluenza (n=9, 2.7%) and adenovirus (n=4, 1.2%). Mycoplasma pneumonia (M. pneumonia) was detected in 1.8 % (n=6). Out of 9 human metapneumovirus (hMPV) positive samples, 6 samples were successfully sequenced using F gene. And M. pneumoniae was sequencing of a repetitive region of the P1 gene. Phylogenetic analysis revealed that hMPV clustered into A2b lineage (n=4), B2 lineage (n=2) and M. pneumoniae clustered into two genotypes: Type 1 (n=4), Type 2a (n=2).