Prime-boost immunization with inactivated human adenovirus type 55 combined with an adjuvant enhances neutralizing antibody responses in mice.

BACKGROUND: Human adenovirus type 55 (hAd55) infection can lead to acute respiratory diseases that often present with severe symptoms. Despite its persistent prevalence in military camps and communities, there are no commercially available vaccines or vaccine candidates undergoing clinical evaluation; therefore, there is an urgent need to address this. In this study, we evaluated the immunogenicity of inactivated hAd55 isolates and investigated the effects of adjuvants and various immunization intervals. METHODS AND RESULTS: To select a vaccine candidate, four hAd55 strains (6-9, 6-15 (AFMRI 41014), 28-48 (AFMRI 41013), and 12-164 (AFMRI 41012)) were isolated from infected patients in military camps. Sequence analysis revealed no variation in the coding regions of structural proteins, including pentons, hexons, and fibers. Immunization with inactivated hAd55 isolates elicited robust hAd55-specific binding and neutralizing antibody responses in mice, with adjuvants, particularly alum hydroxide (AH), enhancing antibody titers. Co-immunization with AH also induced hAd14-specific neutralizing antibody responses but did not induce hAd11-specific neutralizing antibody responses. Notably, booster immunization administered at a four-week interval resulted in superior immune responses compared with shorter immunization intervals. CONCLUSIONS: Prime-boost immunization with the inactivated hAd55 isolate and an AH adjuvant shows promise as a potential approach for preventing hAd55-induced respiratory disease. Further research is needed to evaluate the efficacy and safety of these vaccine candidates in preventing hAd55-associated respiratory illnesses.

Outcomes following additional drainage during veno-venous extracorporeal membrane oxygenation: A single-center retrospective study.

Refractory hypoxemia during veno-venous (V-V) extracorporeal membrane oxygenation (ECMO) may require an additional cannula (VV-V ECMO) to improve oxygenation. This intervention includes risk of recirculation and other various adverse events (AEs) such as injury to the lung, cannula malpositioning, bleeding, circuit or cannula thrombosis requiring intervention (i.e., clot), or cerebral injury. During the study period, 23 of 142 V-V ECMO patients were converted to VV-V utilizing two separate cannulas for bi-caval drainage with an additional upper extremity cannula placed for return. Of those, 21 had COVID-19. In the first 24 h after conversion, ECMO flow rates were higher (5.96 vs 5.24 L/min, p = .002) with no significant change in pump speed (3764 vs 3630 revolutions per minute [RPMs], p = .42). Arterial oxygenation (PaO2) increased (87 vs 64 mmHg, p < .0001) with comparable pre-oxygenator venous saturation (61 vs 53.3, p = .12). By day 5, flows were similar to pre-conversion values at lower pump speed but with improved PaO2. Unadjusted survival was similar in those converted to VV-V ECMO compared to V-V ECMO alone (70% [16/23] vs 66.4% [79/119], p = .77). In a mixed effect regression model, any incidence of AEs, demonstrated a negative impact on PaO2 in the first 48 h but not at day 5. VV-V ECMO improved oxygenation with increasing flows without a significant difference in AEs or pump speed. AEs transiently impacted oxygenation. VV-V ECMO is effective and feasible strategy for refractory hypoxemia on VV-ECMO allowing for higher flow rate and unchanged pump speed.

Clustered cases of human adenovirus types 4, 7, and 14 infections in US Department of Defense Beneficiaries during the 2018-2019 season.

Human adenoviruses (HAdV) are genetically diverse and can infect a number of tissues with severities varied from mild to fatal. HAdV types 3, 4, 7, 11, 14, 21, and 55 were associated with acute respiratory illnesses outbreaks in the United States and in other countries. The risk of outbreaks can be effectively controlled by HAdV vaccination or mitigated by screening and preventive measures. During the influenza season 2018-2019, the DoD Global Respiratory Pathogen Surveillance Program (DoDGRS) received 24 300 respiratory specimens. HAdV samples that produced positive cytopathic effects in viral cultivation were subjected to next-generation sequencing for genome sequence assembly, genome typing, whole genome phylogeny, and sequence comparative analyses. A variety of HAdV types were identified in this study, including HAdV types 1-7, 14, 55, and 56. HAdV types 4, 7, and 14 were found in clustered cases in Colorado, Florida, New York, and South Carolina. Comparative sequence analyses of these isolates revealed the emergence of novel genetic mutations despite the stability of adenovirus genomes. Genomic surveillance of HAdV suggested possible undetected outbreaks and shed light on prevalence, genetic divergence, and viral evolution of HAdV. Continued surveillance will inform risk assessment and countermeasures.

Doubts and concerns about COVID-19 uncertainties on imaging data, clinical score, and outcomes.

BACKGROUND: COVID-19 is a pandemic disease affecting predominantly the respiratory apparatus with clinical manifestations ranging from asymptomatic to respiratory failure. Chest CT is a crucial tool in diagnosing and evaluating the severity of pulmonary involvement through dedicated scoring systems. Nonetheless, many questions regarding the relationship of radiologic and clinical features of the disease have emerged in multidisciplinary meetings. The aim of this retrospective study was to explore such relationship throughout an innovative and alternative approach. MATERIALS AND METHODS: This study included 550 patients (range 25-98 years; 354 males, mean age 66.1; 196 females, mean age 70.9) hospitalized for COVID-19 with available radiological and clinical data between 1 March 2021 and 30 April 2022. Radiological data included CO-RADS, chest CT score, dominant pattern, and typical/atypical findings detected on CT examinations. Clinical data included clinical score and outcome. The relationship between such features was investigated through the development of the main four frequently asked questions summarizing the many issues arisen in multidisciplinary meetings, as follows 1) CO-RADS, chest CT score, clinical score, and outcomes; 2) the involvement of a specific lung lobe and outcomes; 3) dominant pattern/distribution and severity score for the same chest CT score; 4) additional factors and outcomes. RESULTS: 1) If CT was suggestive for COVID, a strong correlation between CT/clinical score and prognosis was found; 2) Middle lobe CT involvement was an unfavorable prognostic criterion; 3) If CT score < 50%, the pattern was not influential, whereas if CT score > 50%, crazy paving as dominant pattern leaded to a 15% increased death rate, stacked up against other patterns, thus almost doubling it; 4) Additional factors usually did not matter, but lymph-nodes and pleural effusion worsened prognosis. CONCLUSIONS: This study outlined those radiological features of COVID-19 most relevant towards disease severity and outcome with an innovative approach.

Comparison of COVID-19 Pandemic Waves in 10 Countries in Southern Africa, 2020-2021.

We used publicly available data to describe epidemiology, genomic surveillance, and public health and social measures from the first 3 COVID-19 pandemic waves in southern Africa during April 6, 2020-September 19, 2021. South Africa detected regional waves on average 7.2 weeks before other countries. Average testing volume 244 tests/million/day) increased across waves and was highest in upper-middle-income countries. Across the 3 waves, average reported regional incidence increased (17.4, 51.9, 123.3 cases/1 million population/day), as did positivity of diagnostic tests (8.8%, 12.2%, 14.5%); mortality (0.3, 1.5, 2.7 deaths/1 million populaiton/day); and case-fatality ratios (1.9%, 2.1%, 2.5%). Beta variant (B.1.351) drove the second wave and Delta (B.1.617.2) the third. Stringent implementation of safety measures declined across waves. As of September 19, 2021, completed vaccination coverage remained low (8.1% of total population). Our findings highlight opportunities for strengthening surveillance, health systems, and access to realistically available therapeutics, and scaling up risk-based vaccination.

An outbreak of acute respiratory disease caused by HAdV-55 in Beijing, China, 2020.

Human adenoviruses (HAdVs) can cause acute respiratory diseases (ARDs) worldwide, and HAdV-55 is a reemergent pathogen in recent years. In the study, we investigated an outbreak of ARD at a school due to HAdV-55 in Beijing, China, during the early outbreak of coronavirus disease 2019 (COVID-19). The epidemic prevention team was dispatched to the school to collect epidemiologic data and nasopharyngeal samples. Then, real-time reverse transcription polymerase chain reaction (PCR) and multiplex PCR assays were used to detect severe acute respiratory syndrome coronavirus 2 and other respiratory pathogens, respectively. One representative HAdV-55 isolate was selected and submitted for whole-genome sequencing using a MiSeq system and the whole-genome phylogenetic tree was conducted based on the maximum likelihood method. The outbreak lasted from January 27 to February 6, 2020, and 108 students developed fever, among whom 60 (55.56%) cases were diagnosed with HAdV-55 infection in the laboratory using real-time PCR and 56 cases were hospitalized. All the confirmed cases had a fever and 11 cases (18.33%) presented with a fever above 39°C. Other main clinical symptoms included sore throat (43.33%) and headache (43.33%). We obtained and assembled the full genome of one isolate, BJ-446, with 34 761 nucleotides in length. HAdV-55 isolate BJ-446 was 99.85% identical to strain QS-DLL, which was the first HAdV-55 strain in China isolated from an ARD outbreak in Shanxi in 2006. One and four amino acid mutations were observed in the hexon gene and the coding region of L2 pV 40.1 kDa protein, respectively. We identified the first HAdV-55 infection associated with the ARD outbreak in Beijing since the emergence of COVID-19. The study suggests that improved surveillance of HAdV is needed, although COVID-19 is still prevalent in the world.

Bioprospecting of microalgae metabolites against cytokine storm syndrome during COVID-19.

In viral respiratory infections, disrupted pathophysiological outcomes have been attributed to hyper-activated and unresolved inflammation responses of the immune system. Integration between available drugs and natural therapeutics have reported benefits in relieving inflammation-related physiological outcomes and microalgae may be a feasible source from which to draw from against future coronavirus-infections. Microalgae represent a large and diverse source of chemically functional compounds such as carotenoids and lipids that possess various bioactivities, including anti-inflammatory properties. Therefore in this paper, some implicated pathways causing inflammation in viral respiratory infections are discussed and juxtaposed along with available research done on several microalgal metabolites. Additionally, the therapeutic properties of some known anti-inflammatory, antioxidant and immunomodulating compounds sourced from microalgae are reported for added clarity.

Completed absorption of coronavirus disease 2019 (COVID-19) pneumonia lesions: a preliminary study.

Background: Complete absorption of coronavirus disease 2019 (COVID-19) pneumonia in a short term was not detailedly reported. We aimed to investigate the clinical and imaging characteristics of COVID-19 patients with complete absorption of pulmonary lesions. Methods: Retrospectively collected the clinical and chest CT data of 224 patients with COVID-19 in one regional medical center. Currently, pulmonary lesions in 37 patients were completely absorbed. The clinical manifestations, laboratory examinations, and CT findings of lesions for these patients were summarized. Results: Among the 37 patients (age, 39.0 ± 12.4 [14-63] years, 20 males), disease in 36 (97.3%) was mild and in 1 (2.7%) was from severe to mild. The most common symptoms were cough (24/37, 64.9%) and fever (23/37, 62.2%). Their laboratory indicators at admission were usually normal, while the white blood cell and neutrophil count significantly increased at discharge (p = 0.004, p = 0.006). On initial CT images, all patients had various pulmonary lesions (mean involved lobes: 2.8 ± 1.5, range: 1-5; mean involved segments: 6.6 ± 4.3, range: 1-16), which mainly manifested as multiple patchy and or spherical ground glass opacities (GGOs) (30/37, 81.1%) with fibrous strips (19/30, 63.3%) or consolidation (11/30, 36.7%). After treatment, lesions in most (33/37, 89.2%) patients were continuously absorbed. At discharge, previous lesions were mostly absorbed in 11 patients (11/37, 29.7%), the main residues were GGOs (24/37, 64.9%), followed by fibrous strips (13/37, 35.1%). On the latest CT, all the pulmonary lesions were completely absorbed, the duration of lesions was 31.6 ± 11.4 days (range: 5-50 days). Conclusion: The pulmonary lesions in some mild COVID-19 patients (generally with normal laboratory indicators at admission, GGOs as the main manifestation on initial CT, and representation of continuous absorption after treatment) could be completely absorbed with a mean duration of 31.6 days.

Is leukopenia and lymphopenia a characteristic feature of COVID-19 in children?

OBJECTIVES: To analyze whether leucopenia and lymphopenia a characteristic feature of children with COVID-19 and to find out its association with the disease severity. METHODS: This was a descriptive cross-sectional study conducted at The Children's Hospital Lahore from March 2020 to October 2020. All confirmed cases of COVID-19 infection and post-COVID MIS-C/Kawasaki Disease diagnosed on the basis of RT-PCR and Antibody test respectively were included. Complete blood and differential counts were performed on the day of admission. RESULTS: Out of a total of 83 patients 60 (72%) were diagnosed as COVID-19 and 23 (28%) as post-COVID MIS-C/KD. The mean age of children was 7.0±4.3 years (95%CI: 6.07 - 8.75) with a male preponderance 51 (61%). Twenty (24%) children had an underlying comorbidity and 7 (8%) were surgical cases. Our case fatality rate was 5 (6%) and all children who died had an underlying comorbid condition. In both, COVID and MIS-C/KD the mean leukocyte count was (14.0 ± 12.5 vs 13.6 ± 6.9 x109/L), respectively (p=0.888). The mean lymphocyte count in children with COVID was (39.1 ± 21.4%). Patients with MIS-C/KD showed significantly higher levels of neutrophil count (76.5 ± 15.0%) as compared to children with COVID (52.0 ± 22.1%), absolute lymphocyte count was (5.02±4.81 vs 2.13±0.95 x109/L) in COVID and MIS-C respectively (p=<0.001). In 60 COVID-19 patients, the mean neutrophil lymphocyte ratio (NLR) in mild-moderate and severe-critical group was 2.00 and 5.08 respectively (p=0.009). CONCLUSION: The blood picture of COVID-19 in children does not show leukopenia. NLR was a prognostic factor to assess the severity in COVID-19 patients. The presence of an underlying comorbid conditions is significant a risk factor for poor outcome.

Human Adenovirus Type 55 Distribution, Regional Persistence, and Genetic Variability.

Human adenovirus type 55 (HAdV-55) causes acute respiratory disease of variable severity and has become an emergent threat in both civilian and military populations. HAdV-55 infection is endemic to China and South Korea, but data from other regions and time periods are needed for comprehensive assessment of HAdV-55 prevalence from a global perspective. In this study, we subjected HAdV-55 isolates from various countries collected during 1969-2018 to whole-genome sequencing, genomic and proteomic comparison, and phylogenetic analyses. The results show worldwide distribution of HAdV-55; recent strains share a high degree of genomic homogeneity. Distinct strains circulated regionally for several years, suggesting persistent local transmission. Several cases of sporadic introduction of certain strains to other countries were documented. Among the identified amino acid mutations distinguishing HAdV-55 strains, some have potential impact on essential viral functions and may affect infectivity and transmission.

18F-FDG PET/CT findings of COVID-19: a series of four highly suspected cases.

PURPOSE: The aim of this case series is to illustrate the 18F-FDG PET/CT findings of patients with acute respiratory disease caused by COVID-19 in Wuhan, Hubei province of China. METHODS: We describe the 18F-FDG PET/CT results from four patients who were admitted to the hospital with respiratory symptoms and fever between January 13 and January 20, 2020, when the COVID-19 outbreak was still unrecognized and the virus infectivity was unknown. A retrospective review of the patients' medical history, clinical and laboratory data, as well as imaging findings strongly suggested a diagnosis of COVID-19. RESULTS: All patients had peripheral ground-glass opacities and/or lung consolidations in more than two pulmonary lobes. Lung lesions were characterized by a high 18F-FDG uptake and there was evidence of lymph node involvement. Conversely, disseminated disease was absent, a finding suggesting that COVID-19 has pulmonary tropism. CONCLUSIONS: Although 18F-FDG PET/CT cannot be routinely used in an emergency setting and is generally not recommended for infectious diseases, our pilot data shed light on the potential clinical utility of this imaging technique in the differential diagnosis of complex cases.

Household Transmission of Human Adenovirus Type 55 in Case of Fatal Acute Respiratory Disease.

We identified a case of fatal acute respiratory disease from household transmission of human adenovirus type 55 (HAdV-55) in Anhui Province, China. Computed tomography showed severe pneumonia. Comparative genomic analysis of HAdV-55 indicated the virus possibly originated in Shanxi Province, China. More attention should be paid to highly contagious HAdV-55.

Identification of a Critical and Conformational Neutralizing Epitope in Human Adenovirus Type 4 Hexon.

Human adenovirus type 4 (HAdV-4) is an epidemic virus that contributes to serious acute respiratory disease (ARD) in both pediatric and adult patients. However, no licensed drug or vaccine is currently available to the civilian population. The identification of neutralizing epitopes of HAdV-4 should allow the development of a novel antiviral vaccine and a novel gene transfer vector, and an effective neutralizing monoclonal antibody (MAb) will be useful in developing appropriate antiviral drugs. In this study, we report that MAb MN4b shows strong neutralizing activity against HAdV-4. MN4b recognizes a conformational epitope (418AGSEK422) within hypervariable region 7 (HVR7). Mutations within this site permitted HAdV-4 mutants to escape neutralization by MN4b and to resist neutralization by animal and human anti-HAdV-4 sera. A recombinant virus, rAd3-A4R7-1, containing the identified neutralizing epitope in the HVR7 region of HAdV-3 hexon, successfully induced antiserum that inhibited HAdV-4 infection. These results indicate that a small surface loop of HAdV-4 hexon is a critical neutralization epitope for this virus. The generation of MN4b and the identification of this neutralizing epitope may be useful in developing therapeutic treatment, a subunit vaccine, and a novel vector that can escape preexisting neutralization for HAdV-4.IMPORTANCE Neutralizing antibodies are considered good tools for the prevention of human adenovirus type 4 (HAdV-4) infections. The identification of the epitopes recognized by such neutralizing antibodies is important for the generation of recombinant antiviral vaccines. However, until now, no neutralizing epitope has been reported for HAdV-4. Here, we developed a serotype-specific neutralizing MAb directed against HAdV-4, MN4b. We provide evidence that MN4b recognizes a conformational epitope within HVR7 of HAdV-4 hexon. Antisera generated to this conformational epitope displayed on HAdV-3 hexon inhibited infection of AD293 cells by HAdV-4. Our findings are very important for the development of therapeutic treatment, a subunit vaccine, and a novel vector for HAdV-4.

Adenovirus Type 4 Respiratory Infections among Civilian Adults, Northeastern United States, 2011-20151.

Human adenovirus type 4 (HAdV-4) is most commonly isolated in military settings. We conducted detailed molecular characterization on 36 HAdV-4 isolates recovered from civilian adults with acute respiratory disease (ARD) in the northeastern United States during 2011-2015. Specimens came from college students, residents of long-term care facilities or nursing homes, a cancer patient, and young adults without co-morbidities. HAdV-4 genome types 4a1 and 4a2, the variants most frequently detected among US military recruits in basic training before the restoration of vaccination protocols, were isolated in most cases. Two novel a-like variants were recovered from students enrolled at a college in Tompkins County, New York, USA, and a prototype-like variant distinguishable from the vaccine strain was isolated from an 18-year-old woman visiting a physician's office in Ulster County, New York, USA, with symptoms of influenza-like illness. Our data suggest that HAdV-4 might be an underestimated causative agent of ARD among civilian adults.

Acute Respiratory Disease in US Army Trainees 3 Years after Reintroduction of Adenovirus Vaccine 1.

The 1999 cessation of vaccination against adenovirus types 4 and 7 among US Army trainees resulted in reemergence of acute respiratory disease (ARD) outbreaks. The 2011 implementation of a replacement vaccine led to dramatic and sustained decreases in ARD cases, supporting continuation of vaccination in this population at high risk for ARD.

COVID-19 Australia: Epidemiology Report 84: Reporting period ending 11 February 2024.

Abstract: This is the eighty-fourth epidemiological report for coronavirus disease 2019 (COVID-19), reported in Australia as at 23:59 Australian Eastern Daylight Time [AEST] 11 February 2024. It includes data on COVID-19 cases diagnosed in Australia.

COVID-19 Australia: Epidemiology Report 85: Reporting period ending 10 March 2024.

Abstract: This is the eighty-fifth and final epidemiological report for coronavirus disease 2019 (COVID-19), reported in Australia as at 23:59 Australian Eastern Daylight Time [AEST] 10 March 2024. It includes data on COVID-19 cases diagnosed in Australia.

COVID-19 Australia: Epidemiology Report 83: Reporting period ending 14 January 2024.

Abstract: This is the eighty-third epidemiological report for coronavirus disease 2019 (COVID-19), reported in Australia as at 23:59 Australian Eastern Daylight Time [AEST] 14 January 2024. It includes data on COVID-19 cases diagnosed in Australia.