Lower Respiratory Tract Disease Research Articles

Are any specific respiratory viruses more severe than others in recipients of allogeneic stem cell transplantation? A focus on lower respiratory tract disease.

In the general population, influenza virus, respiratory syncytial virus, and SARS-CoV-2 are considered the most severe community-acquired respiratory viruses (CARVs). However, allogeneic stem cell transplant (allo-SCT) recipients may also face severe courses from other CARVs. This retrospective study compared outcomes of various CARV lower respiratory tract diseases (LRTD) in 235 adult allo-SCT recipients, excluding co-infection episodes. We included 235 adults allo-SCT recipients experiencing 353 CARV LRTD consecutive episodes (130 rhinovirus, 63 respiratory syncytial virus, 43 influenza, 43 human parainfluenza virus, 23 human metapneumovirus, 19 Omicron SARS-CoV-2, 17 common coronavirus, 10 adenovirus and 5 human bocavirus) between December 2013 and June 2023. Day 100 overall survival ranged from 78% to 90% without significant differences among CARV types. Multivariable analysis of day 100 all-cause mortality identified corticosteroid use of >1 to <30 mg/d [Hazard ratio (HR) 2.45, p = 0.02) and ≥30 mg/d (HR 2.20, p = 0.015) along with absolute lymphocyte count <0.2 × 109/L (HR 5.82, p < 0.001) and number of CARV episodes as a continuous variable per one episode increase (HR 0.48, p = 0.001) as independent risk factors for all-cause mortality. Degree of immunosuppression, rather than intrinsic CARV virulence, has the most significant impact on mortality in allo-SCT recipients with CARV-LRTD.

COVID-19 disease in children and adolescents following allogeneic hematopoietic stem cell transplantation: A report from the Turkish pediatric bone marrow transplantation study group.

Data on the risk factors and outcomes for pediatric patients with SARS-CoV-2 infection (COVID-19) following hematopoietic stem cell transplantation (HSCT) are limited. The study aimed to analyze the clinical signs, risk factors, and outcomes for ICU admission and mortality in a large pediatric cohort who underwent allogeneic HSCT prior to COVID-19 infection. In this nationwide study, we retrospectively reviewed the data of 184 pediatric HSCT recipients who had COVID-19 between March 2020 and August 2022. The median time from HSCT to COVID-19 infection was 209.0 days (IQR, 111.7-340.8; range, 0-3845 days). The most common clinical manifestation was fever (58.7%). While most patients (78.8%) had asymptomatic/mild disease, the disease severity was moderate in 9.2% and severe and critical in 4.4% and 7.6%, respectively. The overall mortality was 10.9% (n: 20). Deaths were attributable to COVID-19 in nine (4.9%) patients. Multivariate analysis revealed that lower respiratory tract disease (LRTD) (OR, 23.20, p: .001) and lymphopenia at diagnosis (OR, 5.21, p: .006) were risk factors for ICU admission and that HSCT from a mismatched donor (OR, 54.04, p: .028), multisystem inflammatory syndrome in children (MIS-C) (OR, 31.07, p: .003), and LRTD (OR, 10.11, p: .035) were associated with a higher risk for COVID-19-related mortality. While COVID-19 is mostly asymptomatic or mild in pediatric transplant recipients, it can cause ICU admission in those with LRTD or lymphopenia at diagnosis and may be more fatal in those who are transplanted from a mismatched donor and those who develop MIS-C or LRTD.

Outcome of Human Parainfluenza Virus infection in allogeneic stem cell transplantation recipients: possible impact of ribavirin therapy.

This retrospective study focused on analyzing community-acquired respiratory virus (CARV) infections, in particular human parainfluenza virus (hPIV) after allogeneic stem cell transplant (allo-SCT) in adults recipients. It aimed to assess the impact of ribavirin treatment, clinical characteristics, and risk factors associated with lower respiratory tract disease (LRTD) progression and all-cause mortality. The study included 230 allo-SCT recipients diagnosed with hPIV between December 2013 and June 2023. Risk factors for the development of LRTD, disease severity, and mortality were analyzed. Ribavirin treatment was administered at physician discretion in 61 out of 230 cases (27%). Risk factors for LRTD progression in multivariate analysis were corticosteroids > 30mg/day (Odds ratio (OR) 3.5, 95% Confidence Interval (C.I.) 1.3-9.4, p = 0.013), fever at the time of hPIV detection (OR 3.89, 95% C.I. 1.84-8.2, p < 0.001), and absolute lymphocyte count (ALC) < 0.2 × 109/L (OR 4.1, 95% C.I. 1.42-11.9, p = 0.009). In addition, the study found that ribavirin therapy significantly reduced progression to LRTD [OR 0.19, 95% C.I. 0.05-0.75, p = 0.018]. Co-infections (OR 5.7, 95% C.I. 1.4-23.5, p = 0.015) and ALC < 0.2 × 109/L (OR 17.7, 95% C.I. 3.6-87.1, p < 0.001) were independently associated with higher day + 100 after hPIV detection all-cause mortality. There were no significant differences in all-cause mortality and infectious mortality at day + 100 between the treated and untreated groups. ALC, corticosteroids, and fever increased the risk for progression to LRTD while ribavirin decreased the risk. However, mortality was associated with ALC and co-infections. This study supports further research of ribavirin therapy for hPIV in the allo-HSCT setting.

Vaccines for Respiratory Syncytial Virus Prevention in Older Adults.

This review evaluates the efficacy and safety of novel respiratory syncytial virus (RSV) vaccines approved for adults aged 60 years and older. A literature search through February 27, 2024 was conducted using search terms, such as RSV, viral respiratory illness, vaccine, RSVpreF, RSVpreF3, Prefusion F, Abrysvo, and Arexvy. Data from primary literature and vaccine prescribing information were reviewed, encompassing evaluations of clinical pharmacology, efficacy, safety, adverse events, warnings, and precautions. The literature review process resulted in 10 articles included within this article's scope, including the results of 2 major phase III trials presented in detail. Two RSV vaccines, Respiratory Syncytial Virus Vaccine (recombinant [adjuvanted]; RSVpreF3-ASO1E, Arexvy) and Respiratory Syncytial Virus Vaccine (recombinant; RSVpreF, Abrysvo), approved for preventing RSV-associated lower respiratory tract disease (LRTD) in adults aged 60 years or older in the United States are discussed. Results from Phase III trials have demonstrated the efficacy of 1 dose of these vaccines in preventing RSV-associated LRTD across 2 RSV seasons. The Advisory Committee on Immunization Practices currently recommends use of these vaccines under shared clinical decision-making for adults aged 60 years or older. Most common adverse effects include injection site reactions (eg, site pain, redness, and swelling). Administration requires a single intramuscular injection of 0.5 mL, reconstituted prior to administration. The RSVpreF3-ASO1E and RSVpreF vaccines effectively prevent RSV-associated LRTD in adults aged 60 years and older.

The potential public health impact of the respiratory syncytial virus prefusion F protein vaccine in people aged ≥60 years in Japan: results of a Markov model analysis

ABSTRACT Background Respiratory syncytial virus (RSV), a common respiratory pathogen, can lead to severe symptoms, especially in older adults (OA). A recently developed RSV prefusion F protein (RSVPreF3 OA) vaccine confers high protection against RSV lower respiratory tract disease (LRTD) over two full RSV seasons. The aim of this study was to assess the potential public health impact of RSVPreF3 OA vaccination in the Japanese OA population. Research design and methods A static Markov model was used to estimate the number of symptomatic RSV cases, hospitalizations and deaths in the Japanese population aged ≥ 60 years over a 3-year time horizon. Japan-specific RSV epidemiology and healthcare resource use parameters were used; vaccine efficacy was derived from a phase 3 randomized study (AReSVi-006, NCT04886596). Vaccination coverage was set to 50%. Results Without vaccination, >5 million RSV acute respiratory illness (ARI) would occur (2.5 million LRTD and 2.8 million upper respiratory tract infections) leading to ~ 3.5 million outpatient visits, >534,000 hospitalizations and ~ 25,500 RSV-related deaths over 3 years. Vaccination could prevent > 1 million RSV-ARI cases, 728,000 outpatient visits, 143,000 hospitalizations and 6,840 RSV-related deaths. Conclusions RSVPreF3 OA vaccination is projected to have a substantial public health impact by reducing RSV-related morbidity and mortality in the OA population.

Association of clinical respiratory disease signs and lower respiratory tract bacterial pathogens with systemic inflammatory response in pre-weaned dairy calves

This study investigated the potential associations between 3 acute phase proteins (APPs) haptoglobin, serum amyloid A, and fibrinogen, clinical signs of respiratory disease, and the presence of bacterial pathogens in the lower respiratory tract (LRT) of pre-weaned dairy calves. This cross-sectional study included 150 pre-weaned calves (2-86 d old) from 15 large dairy herds in Estonia. Tracheobronchial lavage, blood, and fecal samples were collected from 5 calves showing clinical signs indicative of LRT disease, and samples from 5 calves without clinical signs of LRT disease per herd. All samples collected from these calves were analyzed for concentrations of systemic APPs, LRT bacteria, and intestinal pathogens. Heifer blood and bulk tank milk samples were collected for the detection of disease-specific antibodies against bovine herpesvirus 1, bovine viral diarrhea virus, bovine respiratory syncytial virus, and Mycoplasma bovis. Mixed-effects linear regression models were used to analyze the associations of clinical respiratory disease signs and LRT bacteria with APPs. Increased plasma fibrinogen concentrations in calves were associated with higher rectal temperature (>39.5°C), increased respiratory rate (>50 breaths/min), and coughing. Increased serum amyloid A concentrations were associated with higher rectal temperature (>39.5°C) and respiratory rate between 40 and 50 breaths/min. Calves with the presence of fecal Cryptosporidium spp. and rectal temperature of 39°C and above had increased serum haptoglobin concentrations. Increased fibrinogen concentrations were associated with the presence of Pasteurella multocida in the calf LRT, whereas increased concentrations of fibrinogen and serum amyloid A were associated with the presence of Trueperella pyogenes. In conclusion, APPs showed variable associations with clinical signs of respiratory disease and LRT bacteria. Plasma fibrinogen concentration could be used as a complementary calf-side test to assess systemic inflammation caused by LRT bacteria such as P. multocida and T. pyogenes in pre-weaned dairy calves.

Association of KIR Genes with Middle East Respiratory Syndrome Coronavirus Infection in South Koreans.

Middle East respiratory syndrome (MERS) is a lower respiratory tract disease caused by a beta coronavirus (CoV) called MERS-CoV, characterized by a high mortality rate. We aimed to evaluate the association between genetic variation in killer cell immunoglobulin-like receptors (KIRs) and the risk of MERS in South Koreans. KIR genes were genotyped by multiplex polymerase chain reaction with sequence-specific primers (PCR-SSP). A case-control study was performed to identify the odds ratios (OR) of KIR genes for MERS and the association of KIR genes and their ligands, human leukocyte antigens (HLA) genes. KIR2DS4D and KIR3DP1F showed higher frequencies in the group of all patients infected with MERS-CoV than in the control group (p = 0.023, OR = 2.4; p = 0.039, OR = 2.7). KIR2DL1, KIR2DP1, and KIR3DP1D were significantly associated with moderate/mild (Mo/Mi) cases. KIR2DL2, KIR2DS1, and KIR3DP1F were affected in severe cases. When we investigated the association between KIR genes and their ligands in MERS patient and control groups, KIR3DL1+/Bw4(80I)+, KIR3DL1+/Bw6+, KIR3DL1+/Bw6-, KIR2DS1+/C2+, and KIR3DS+/Bw4(80I)+ were associated with MERS. KIR3DL1+/Bw6- was found in Mo/Mi cases. KIR2DS1+/C2+ and KIR2DS2+/C1+ were found in severe cases. Further investigations are needed to prove the various immune responses of MERS-CoV-infected cells according to variations in the KIR gene and ligand gene. A treatment strategy based on current research on the KIR gene and MERS-CoV will suggest potential treatment targets.

Burden and outcome of respiratory morbidities among children and adolescents with sickle cell disease-A retrospective review of emergency presentations in some Nigerian tertiary institutions.

Despite the huge burden of sickle cell disease (SCD) among Nigerian children, the burden and outcome of respiratory illnesses remain undocumented. Thus, we aimed to describe the spectrum and outcome of respiratory illnesses among SCD childrenand adolescentadmissions in ten Nigerian tertiary hospitals. A retrospective review of the SCD admission records of children and adolescents with a confirmed diagnosis of respiratory illnesses from 2012 to 2021 in ten tertiary health facilities across five geopolitical zones in Nigeria was conducted. The data, collectedbetween March and June 2023, included the age, sex, diagnosis, complications, duration and outcome of hospitalization. Of the 72,333 paediatric admissions, 7,256 (10.0%) had SCD; the proportion of SCD from the total admission ranged from 2.1 to 16.3% in the facilities. Of the 7,256 children and adolescents with SCD, 1,213 (16.7%) had respiratory morbidities. Lower respiratory disease was the most common (70.0%) respiratory entity and the majority were pneumonia (40.1.0%), followed by acute chest syndrome (26.7%). Seventeen (1.4%) patients died; all had lower respiratory diseases [(acute chest syndrome ACS (11, 64.7%), pneumonia; 5, 29.4%, and asthma (1, 5.9%). Based on the proportion of deaths among overall SCD, the 17 death cases contributed 9.4% (95% CI 5.9 to 14.5). Factors associated with deaths included duration of hospitalization less than 72 hours and lower respiratory tract diseases. Sickle cell disease is a major contributor to hospitalization among Nigerian children and adolescents, with high respiratory morbidity and mortality. Pneumonia and acute chest syndrome were associated with mortality, andthe highest risk of death within the first 72 hours.

Arexvy: A Comprehensive Review of the Respiratory Syncytial Virus Vaccine for Revolutionary Protection.

The respiratory syncytial virus (RSV) is a major cause of acute lower respiratory tract infection in children and poses a significant risk to older adults. Developing a vaccine against RSV has been a priority, and the recently approved Arexvy vaccine has shown promise in preventing lower respiratory tract disease (LRTD) caused by RSV in individuals aged 60 years and older. This comprehensive review discusses the history of RSV, challenges in vaccine development, and the mechanism of action of Arexvy. The efficacy and safety of the vaccine are explored based on phase 3 clinical trial, demonstrating its effectiveness in preventing RSV-associated LRTD. The most common adverse reactions reported include injection site pain, fatigue, myalgia, headache, and arthralgia. Ongoing research focuses on the long-term effectiveness of Arexvy, including the need for booster doses and its impact on reducing RSV-associated hospitalizations. The potential of Arexvy to lessen the burden of RSV-related illnesses, particularly in vulnerable populations, is highlighted, emphasizing the importance of widespread immunization efforts and accessibility to this groundbreaking vaccine.

Diagnostic Accuracy of the World Health Organization Pediatric Emergency Triage, Assessment and Treatment Tool Plus Among Patients Seeking Care in Nairobi, Kenya: A Cross-sectional Study.

The World Health Organization developed Emergency Triage Assessment and Treatment Plus (ETAT+) guidelines to facilitate pediatric care in resource-limited settings. ETAT+ triages patients as nonurgent, priority, or emergency cases, but there is limited research on the performance of ETAT+ regarding patient-oriented outcomes. This study assessed the diagnostic accuracy of ETAT+ in predicting the need for hospital admission in a pediatric emergency unit at Kenyatta National Hospital in Nairobi, Kenya. This was a secondary analysis of a cross-sectional study of pediatric emergency unit patients enrolled over a 4-week period using fixed random sampling. Diagnostic accuracy of ETAT+ was evaluated using receiver operating curves (ROCs) and respective 95% confidence intervals (CIs) with associated sensitivity and specificity (reference category: nonurgent). The ROC analysis was performed for the overall population and stratified by age group. A total of 323 patients were studied. The most common reasons for presentation were upper respiratory tract disease (32.8%), gastrointestinal disease (15.5%), and lower respiratory tract disease (12.4%). Two hundred twelve participants were triaged as nonurgent (65.6%), 60 as priority (18.6%), and 51 as emergency (15.8%). In the overall study population, the area under the ROC curve was 0.97 (95% CI, 0.95-0.99). The ETAT+ sensitivity was 93.8% (95% CI, 87.0%-99.0%), and the specificity was 82.0% (95% CI, 77.0%-87.0%) for admission of priority group patients. The sensitivity and specificity for the emergency patients were 66.0% (95% CI, 55.0%-77.0%) and 98.0% (95% CI, 97.0%-100.0%), respectively. ETAT+ demonstrated diagnostic accuracy for predicting patient need for hospital admission. This finding supports the utility of ETAT+ to inform emergency care practice. Further research on ETAT+ performance in larger populations and additional patient-oriented outcomes would enhance its generalizability and application in resource-limited settings.

Respiratory Syncytial Virus Prefusion F Subunit Vaccine: First Approval of a Maternal Vaccine to Protect Infants.

Pfizer is developing a bivalent respiratory syncytial virus (RSV) prefusion F subunit vaccine (RSVpreF; ABRYSVO™) for preventing RSV illness in infants and individuals aged ≥ 60 years. RSVpreF received approval for vaccination of pregnant individuals to help protect infants against RSV illness on 21 August 2023 in the USA. RSVpreF is also approved in the USA (31 May 2023) for active immunization of individuals aged ≥ 60 years for the prevention of lower respiratory tract disease (LRTD) caused by RSV. In the EU, RSVpreF has received approval for both indications, and it has been submitted for regulatory approval in Canada (both indications) and in Japan (maternal immunization to protect infants). This article summarizes the milestones in the development of RSVpreF leading to the approval for use in pregnant individuals to prevent LRTD in infants.

Two vaccines (Arexvy and Abrysvo) for prevention of RSV disease.

Two recombinant vaccines, Arexvy (GSK) and Abrysvo (Pfizer), have been approved by the FDA for prevention of lower respiratory tract disease (LRTD) caused by respiratory syncytial virus (RSV) in adults ≥60 years old.

The effect of biologics in lung function and quality of life of patients with united airways disease: A systematic review

Increasing evidence supports the united airway disease concept for the management of upper and lower respiratory tract diseases, particularly in patients with asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). However, evidence for a combined approach in asthma and CRSwNP is scarce. In this systematic review, we focused on the role of biologics in the lung function and quality of life in patients with severe asthma and CRSwNP. We conducted a systematic search of 3 electronic databases using 2 search strategies to identify studies published from January 2010 to March 2022. Quality assessment was performed with the Critical Appraisal Skills Programme. Of 1030 studies identified, 48 original studies reporting data of benralizumab (12), dupilumab (14), mepolizumab (10), omalizumab (13), and reslizumab (2) were analyzed. Primary diagnosis was mostly asthma or CRSwNP, with only 15 studies, mainly observational, performed in populations with united airway disease. In total, 18 studies reported data on quality of life (mostly 22-item Sino-Nasal Outcome Test score), 8 on lung function (mostly FEV1), and 22 on both outcomes. Significant FEV1 and 22-item Sino-Nasal Outcome Test score improvements were consistently observed after 24-week treatment, and thereafter, mostly in real-world studies that included variable proportions of patients with asthma/CRSwNP. The use of biologics in patients with severe asthma and CRSwNP was overall associated with significant improvements in lung function and quality of life. However, we observed a high heterogeneity of populations and outcome measurements across studies. Notwithstanding the need of larger studies, our results reinforce the joint management of asthma and CRSwNP as united airway disease in clinical practice.

Nirsevimab (Beyfortus) for prevention of severe RSV disease in young children.

The FDA has approved nirsevimab-alip (Beyfortus – AstraZeneca/Sanofi), a long-acting monoclonal antibody, for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease in neonates and infants born during or entering their first RSV season, and in children ≤24 months old who are at increased risk for severe RSV disease through their second RSV season. Nirsevimab is the first drug to be approved for protection of all infants during their first RSV season.

Licochalcone A plays dual antiviral roles by inhibiting RSV and protecting against host damage.

Respiratory syncytial virus (RSV) causes lower respiratory tract diseases and bronchiolitis in children and elderly individuals. There are no effective drugs currently available to treat RSV infection. In this study, we report that Licochalcone A (LCA) can inhibit RSV replication and mitigate RSV-induced cell damage in vitro, and that LCA exerts a protective effect by reducing the viral titer and inflammation in the lungs of infected mice in vivo. We suggest that the mechanism of action occurs through pathways of antioxidant stress and inflammation. Further mechanistic results demonstrate that LCA can induce nuclear factor erythroid 2-related factor 2 (Nrf2) translocation into the nucleus, activate heme oxygenase 1 (HO-1), and inhibit reactive oxygen species-induced oxidative stress. LCA also works to reverse the decrease in I-kappa-B-alpha (IкBα) levels caused by RSV, which in turn inhibits inflammation through the associated nuclear factor kappa B and tumor necrosis factor-α signaling pathways. The combined action of the two cross-talking pathways protects hosts from RSV-induced damage. To conclude, our study is the first of its kind to establish evidence of LCA as a viable treatment for RSV infection.

Immunogenicity and protective efficacy of an RSV G S177Q central conserved domain nanoparticle vaccine.

Respiratory syncytial virus (RSV) can cause lower respiratory tract disease in infants and elderly populations. Despite decades of research, there remains no safe and approved RSV vaccine. Previously, we showed that an RSV G glycoprotein subunit vaccine candidate with a single point mutation within the central conserved domain (CCD), i.e. S177Q, considerably improved immunogenicity. Here, we examine the development of nanoparticle (NP) vaccines having either an RSV G protein CCD with wild-type sequence (NPWT) or an S177Q mutation (NP-S177Q). The NP vaccine immunogens were adjuvanted with monophosphoryl lipid A (MPLA), a TLR4 agonist to improve Th1- type responses. BALB/c mice were primed with 10 μg of NP-WT vaccine, NPS177Q, or vehicle, rested, and then boosted with a high (25 μg) or low (10 μg) dose of the NP-WT or NP-S177Q homologous candidate and subsequently challenged with RSV A2. The results showed that mice boosted with NP-S177Q developed superior immunogenicity and neutralizing antibodies compared to NP-WT boosting. IgG from either NP-S177Q or NP-WT vaccinated mice did not interfere with fractalkine (CX3CL1) binding to CX3CR1 and effectively blocked G protein CX3C-CX3CR1 binding. Both NP-WT and NP-S177Q vaccination induced similar neutralizing antibodies to RSV in challenged mice compared to vehicle control. NP-S177Q boosting improved correlates of protection including reduced BAL cell infiltration following RSV challenge. However, the NP vaccine platform will require improvement due to the poor solubility and the unexpectedly weaker Th1-type IgG2a response. The results from this study support further NP-S177Q vaccine candidate development.

Outcome of SARS-CoV2 infection in hematopoietic stem cell transplant recipients for autoimmune diseases

Hematopoietic stem cell transplant (HSCT) recipients may be at high risk of mortality from coronavirus disease 2019 (COVID-19). However, specific data on COVID-19 after treatment with HSCT in patients affected by autoimmune diseases (ADs) are still lacking.In this multicenter observational study of the European Society for Blood and Marrow Transplantation (EBMT), clinical data on COVID-19 in 11 patients affected by severe ADs treated with HSCT (n = 3 allogeneic transplant; n = 8 autologous transplant) are reported. All patients were symptomatic during the initial phase of the SARS-CoV-2 infection. At screening, 5 patients reported upper respiratory symptoms, 3 patients had cough without oxygen requirement, and 6 patients exhibited extra-pulmonary symptoms. Four cases developed a lower respiratory tract disease (LRTD). Hospitalization was required in 6 cases, without necessity of intensive care unit (ICU) admission and/or ventilation/supplemental oxygen. Different interventions were adopted: remdesivir (n = 1), nirmatrelvir/ritonavir (n = 1), sotrovimab (n = 1), immunoglobulins (n = 1). At last follow-up, all patients are alive and had resolution of the infection.The current analysis describing the mild-moderate course of COVID-19 in transplant recipients affected by ADs, similar to the course observed in ADs under standard treatments, provides useful information to support the delivery of HSCT programs in this field. Vaccination and new treatments available for SARS-CoV-2 may be useful to further minimize the risk of infection.

A Review on Strategies for COVID-19 Vaccine Development and Regulatory Requirements

Scientists first identified Human Coronavirus in the year 1965. Then, a study was performed on different human and animal viruses, which were named based on their crown-like appearance. Human coronaviruses are responsible for many children's upper respiratory tract infections. At least five new human coronaviruses have been identified since 2003, including the severe acute respiratory syndrome (SARS) coronavirus, which caused significant morbidity and mortality.1 Per NL and the New Haven, the virus associated with upper and lower respiratory tract disease and likely common human pathogens are identified as the Group-I coronaviruses (SARS- CoV-I). The novel coronavirus (SARS-CoV-II), which appeared in Wuhan, China, in December 2019, is responsible for Coronavirus disease 2019 (COVID-19) and causes respiratory symptoms that can feel like a cold, flu, or pneumonia. Geographical transmission of the virus and the sudden increase in cases are much faster than SARS and Middle East respiratory syndrome (MERS). COVID-19 is the first global pandemic caused by a coronavirus causing outbreaks in 211 countries. The vaccine against COVID-19 is an effective prophylactic strategy for controlling and preventing the virus. The vaccine is being developed in about 90 institutions worldwide. This research paper focuses on COVID-19 vaccine development strategies implemented by various institutions and pharmaceutical companies worldwide and regulatory requirements for vaccine approval.&#x0D; Keywords: Human Coronavirus, Severe Acute Respiratory Syndrome (SARS), COVID-19 vaccine development strategies

116. Potential Clinical Impact of Respiratory Syncytial Virus (RSV) Vaccination in Older Adults in the United States

Abstract Background RSV causes acute respiratory disease (ARD), including severe lower respiratory tract disease (LRTD) in older adults, which can lead to hospitalization and death. Currently, there are no vaccines approved to prevent RSV disease. This study estimated the potential clinical impact of a hypothetical RSV vaccine over a 1-year time horizon in older adults aged ≥ 60 years. Methods A decision-analytic model was developed (Figure 1). A strategy was used where the entire US population aged ≥ 60 years was given a single dose vaccine with an assumed efficacy of 75% against ARD, LRTD, and LRTD-hospitalizations and compared to a population who did not receive a vaccine. Given the uncertainty around RSV hospitalization rates, 2 base-case scenarios were created: (1) hospitalization rates that used RSV-specific claim codes and (2) hospitalization rates increased by 49% to account for underreporting in claims; Table 1 shows key inputs. One-way sensitivity analyses were used to assess the impact of specific parameter estimates. Results The vaccine would prevent 1.8 million and 0.6 million upper respiratory disease and LRTD cases, respectively; Figure 2 shows additional results for both base-case scenarios. The number needed to vaccinate (NNV) to prevent 1 LRTD case is 119; the NNV to prevent 1 LRTD hospitalization or death ranges from 792 to 1180 and 10,452 to 15,574, respectively. Sensitivity analyses indicate that results mainly depend on vaccine efficacy, and incidence of ARD and LRTD. Conclusion There is substantial US public health benefit associated with utilization of an effective RSV vaccine in individuals ≥ 60 years of age to reduce RSV-associated morbidity and mortality; however, the magnitude of impact depends on RSV epidemiology, which is still being defined for older adults. Several model parameters were based on assumptions, and robust evidence generation is needed including the efficacy of an RSV vaccine, which is an important consideration in assessing the impact of vaccination in this age group. Disclosures Kelly Fust, MS, Quadrant Health Economics Inc: Contractor at Quadrant Health Economics Inc who was funded by Moderna to perform this study Michele Kohli, PhD, Quadrant Health Economics Inc: Shareholder at Quadrant Health Economics Inc who was funded by Moderna to perform this study|Quadrant Health Economics Inc: Stocks/Bonds Catherine A. Panozzo, PhD, Moderna, Inc.: Salary|Moderna, Inc.: Stocks/Bonds Philip Buck, PhD, MPH, Moderna, Inc.: Salary|Moderna, Inc.: Stocks/Bonds Parinaz Ghaswalla, PhD, Moderna, Inc.: Salary|Moderna, Inc.: Stocks/Bonds.

2094. A prospective multicenter study of HHV-6B genomic DNA and gene transcription in paired bronchoalveolar lavage fluid and blood from HCT recipients

Abstract Background We previously demonstrated frequent detection of HHV-6B DNA in bronchoalveolar lavage fluid (BALF) and its positive association with mortality in HCT recipients from 1992-2015 with lower respiratory tract disease (LRTD). Whether these findings remain pertinent in contemporary patients, the additive value of testing for viral gene transcription, and the correlation of HHV-6 detection in blood and BALF, are unknown. Methods We conducted a prospective study of allogeneic HCT recipients undergoing BAL for LRTD within 120 days of HCT at three cancer centers from 2015-2019. We collected and tested paired blood and BALF for HHV-6B DNA by qPCR and HHV-6B mRNA (U38 and U90 gene transcripts) among DNA positive samples using RT-qPCR. We described the detection of HHV-6B DNA and mRNA in blood and BALF, generated receiver operating characteristic (ROC) curves to determine the ability of BALF HHV-6B DNA detection to predict HHV-6B mRNA detection, and analyzed the association of HHV-6B DNA detection with mortality. Results We enrolled 116 allogeneic HCT recipients who underwent 125 BALs. HHV-6B DNA was detected in 45 of 122 BALF (37%) compared to 19 of 124 (15%) plasma samples. Among the 45 BALF samples with HHV-6B DNA detected, either HHV-6B mRNA transcript was detected in 22 (49%) (Figure 1). BALF HHV-6B DNA ≥ 218 copies/ml had an area under the curve of 0.93 for predicting detection of BALF viral mRNA (Figure 2). In turn, patients with BALF HHV-6B DNA ≥ 218 copies/mL had increased risk for mortality and death due to LRTD within 60 days after the BAL (Figure 3). This association remained after adjustment for age, oxygen use, and steroid use at the time of BAL in a multivariable Cox model (Figure 3). Conclusion HHV-6B was detected more frequently in BALF than plasma, suggesting compartment-specific reactivation. BALF HHV-6B DNA ≥ 218 copies/mL had high sensitivity and specificity for detection of viral gene transcription in BALF and was associated with increased mortality; this viral load is strikingly similar to the BALF viral load threshold of 251 copies/mL associated with mortality in our prior retrospective study. Together, these data suggest transcriptionally active HHV-6B is a clinically impactful pulmonary pathogen in contemporary HCT recipients. Disclosures Joshua A. Hill, MD, Allovir: Advisor/Consultant|Allovir: Grant/Research Support|Covance/CSL: Advisor/Consultant|CRISPR: Advisor/Consultant|Deverra: Grant/Research Support|Gilead: Grant/Research Support|Karius: Advisor/Consultant|Karius: Grant/Research Support|Merck: Grant/Research Support|Octapharma: Advisor/Consultant|OptumHealth: Advisor/Consultant|Oxford Immunotec: Grant/Research Support|Pfizer: Advisor/Consultant|Symbio: Advisor/Consultant|Takeda: Advisor/Consultant Alpana waghmare, MD, Allovir: Grant/Research Support|Ansun BioPharma: Grant/Research Support|Kyorin Pharmaceutical: Advisor/Consultant|Pfizer: Grant/Research Support|Vir/GSK: Grant/Research Support Geoffrey Hill, M.D., FRACP, FRCPA, Applied Molecular Transport: Grant/Research Support|Compass Therapeutics: Grant/Research Support|Generon Corporation: Advisor/Consultant|Heat Biologics: Grant/Research Support|iTeos Therapeutics: Advisor/Consultant|iTeos Therapeutics: Grant/Research Support|Laevoroc Oncology: Grant/Research Support|NapaJen Pharma: Advisor/Consultant|Neoleukin Therapeutics: Advisor/Consultant|Serplus Technology: Grant/Research Support|Syndax Pharmaceuticals: Grant/Research Support Danielle M. Zerr, MD MPH, AlloVir: Advisor/Consultant Sanjeet S. Dadwal, MD, FACP, FIDSA, AlloVir: Advisor/Consultant|AlloVir: Grant/Research Support|Ansun Biopharma: Grant/Research Support|Aseptiscope: Advisor/Consultant|Aseptiscope: Stocks/Bonds|Astellas: Speaker's Bureau|Cidara: Advisor/Consultant|Gilead: Grant/Research Support|Karius: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support|Merck: Speaker's Bureau|Takeda: Speaker's Bureau Michael J. Boeckh, MD PhD, Allovir: Advisor/Consultant|Amazon: Grant/Research Support|Ansun Biopharma: Grant/Research Support|EvrysBio: Advisor/Consultant|Gates Ventures: Grant/Research Support|Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|GlaxoSmithKline: Advisor/Consultant|GlaxoSmithKline: Grant/Research Support|Helocyte: Advisor/Consultant|Janssen: Advisor/Consultant|Janssen: Grant/Research Support|Kyorin Pharmaceuticals: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Moderna: Advisor/Consultant|Moderna: Grant/Research Support|Regeneron: Grant/Research Support|ReViral: Advisor/Consultant|Symbio: Advisor/Consultant|Takeda: Grant/Research Support|Vir Biotechnology: Advisor/Consultant|Vir Biotechnology: Grant/Research Support.