Characteristics, Management, and Outcomes of Community-Acquired Pneumonia Due to Human Rhinovirus—A Retrospective Study

Introduction. Human rhinovirus (HRV) can lead to a variety of respiratory illnesses; it is also an uncommon cause of community-acquired pneumonia (CAP). We described the characteristics and outcomes of patients hospitalized for CAP due to HRV. Methods. We retrospectively studied consecutive adult patients admitted to King Abdulaziz Medical City-Riyadh with CAP due to HRV between 2016 and 2019. The diagnosis was made by respiratory multiplex PCR within 48 hours of hospitalization. We compared patients requiring ICU admission to those who did not. Results. One-hundred-and-six patients were studied (peak hospitalization between November and January, median age 71.5 years, hypertension 59%, diabetes 50%, and chronic respiratory disease 44.3%); 16 (15.1%) patients required ICU admission. The median pneumonia severity index score (PSI) was 107, with no significant difference between ICU and nonICU patients. ICU patients had a higher prevalence of tachypnea (62.5% vs. 26.7%, p=0.005), hemoptysis (12.5% vs 0%, p=0.001), and lymphopenia (71.4% vs 26.3%, p=0.01). Chest X-ray on presentation showed bilateral infiltrates in 47/101 (46.5%) patients and unilateral infiltrates in 26/101 (25.7%) patients. Systemic corticosteroids were used in 54.7% of patients (the median initial dose was 120 mg of prednisone equivalent and was higher in nonICU patients). Most (69.2%) ICU patients received mechanical ventilation (median duration of 8 days). Bacterial coinfection (6.6%) and superinfection (3.8%) were rare. The overall hospital mortality was 9.4% (higher for ICU patients: 37.5% vs. 4.4%, p<0.001). Conclusions. Most patients with CAP due to HRV were elderly and had significant comorbidities. ICU admission was required in almost one in six patients and was associated with higher mortality

Safety and immunogenicity of ChAdOx1 MERS Vaccine Candidate in Healthy Middle Eastern Adults: a dose-escalation, open-label, non-randomised, phase 1b trial

Background: ChAdOx1-vectored vaccine candidates against several pathogens have been developed and tested in clinical trials and ChAdOx1 nCoV-19 has now been licensed for emergency use for COVID-19. We assessed the safety and immunogenicity of the ChAdOx1 MERS vaccine in a phase 1b trial in healthy Middle Eastern adults. Method: MERS002 is an open-label, non-randomised, dose-escalation, phase 1b trial. Healthy Middle Eastern adults aged 18–50 years were included in the study. ChAdOx1 MERS was administered as a single intramuscular injection into the deltoid muscle of the non-dominant arm at three different dose groups: 5·0 × 109 viral particles in a low-dose group, 2·5 × 1010 viral particles in an intermediate-dose group, and 5·0 × 1010 viral particles in a high-dose group. The primary objective was to assess the safety and tolerability of ChAdOx1 MERS, measured by the occurrence of solicited and unsolicited adverse events after vaccination for up to 28 days and occurrence of serious adverse events up to 6 months. The study is registered with ClinicalTrials.gov, NCT04170829. Findings: Between Dec 17, 2019, and June 1, 2020, 24 participants were enrolled (six to the low-dose, nine to the intermediate-dose, and nine to the high-dose group) and received a dose; 23 were available for follow-up at 6 months. The one dose of ChAdOx1 MERS vaccine was well tolerated with no serious adverse event reported during the 6 months of follow-up. Most adverse events were mild (67, 74%) and moderate (17, 19%). Six (7%) severe adverse events were reported by two participants in the intermediate-dose group (two feverish, two headache, one joint pain, and one muscle pain). Pain at the injection site was the most common local and overall adverse event, reported by 15 (63%) of the 24 participants. The most common systemic adverse event was headache, reported by 14 (58%), followed by muscle pain reported by 13 (54%). The vaccine induced both antibody and T cell immune responses in all volunteers; antibodies peaked at day 28 and T cell responses peaked at day 14; and continued until the end of follow-up at 6 months. Interpretation: The acceptable safety and immunogenicity data from this phase 1b trial of ChAdOx1 MERS vaccine candidate in Healthy Middle Eastern adults, combined with previous safety and immunogenicity data from a trial in the UK, support selecting the ChAdOx1 MERS vaccine for advancement into phase 2 clinical evaluation.</p

Characteristics, Management, and Outcomes of Community-Acquired Pneumonia due to Respiratory Syncytial Virus: A Retrospective Study

Background. Respiratory syncytial virus (RSV), a well-known cause of bronchiolitis in children, can cause community-acquired pneumonia (CAP) in adults, but this condition is not well studied. Hence, we described the characteristics and outcomes of patients hospitalized for CAP due to RSV. Methods. This was a retrospective study of patients admitted to a tertiary-care hospital between 2016 and 2019 with CAP due to RSV diagnosed by a respiratory multiplex PCR within 48 hours of admission. We compared patients who required ICU admission to those who did not. Results. Eighty adult patients were hospitalized with CAP due to RSV (median age 69.0 years, hypertension 65.0%, diabetes 58.8%, chronic respiratory disease 52.5%, and immunosuppression 17.5%); 19 (23.8%) patients required ICU admission. The median pneumonia severity index score was 120.5 (140.0 for ICU and 102.0 for non-ICU patients; p=0.09). Bacterial coinfection was rare (10.0%). Patients who required ICU admission had more hypotension (systolic blood pressure<90 mmHg) and a higher prevalence of bilateral infiltrates on chest X-ray (CXR) (89.5% versus 32.7%; p<0.001). Systemic corticosteroids were used in 57.3% of patients (median initial dose was 40 mg of prednisone equivalent) with ICU patients receiving a higher dose compared to non-ICU patients (p=0.02). Most (68.4%) ICU patients received mechanical ventilation (median duration of 4 days). The overall hospital mortality was 8.8% (higher for ICU patients: 31.6% versus 1.6%, p<0.001). Conclusions. Most patients with CAP due to RSV were elderly and had significant comorbidities. ICU admission was required in almost one in four patients and was associated with higher mortality

Persistence of Anti-SARS-CoV-2 Spike IgG Antibodies Following COVID-19 Vaccines

Purpose: This study was conducted to investigate antibody immune responses induced by BNT162b2 and AZD1222 human COVID-19 vaccines in Riyadh city, Saudi Arabia. Patients and methods: ELISA was used to evaluate antibodies, against the SARS-CoV-2 spike S1 protein, in serum samples from 432 vaccinated individuals at six time points: pre-vaccination (baseline), post-prime, post-boost, 6-months, and 1 year post-vaccination, and 3 weeks post a third dose. Virus microneutralization assay was used to confirm antibody responses in a subset of samples. Results: Anti-SARS-CoV-2 spike IgG were detected in most subjects post-prime, reached a peak level post-boost, and remained at high level at the 6-month follow-up. At 1 year post-vaccine, the antibody levels were low but increased to a significant level higher than the peak following a third dose. The third dose was given at an average of 250 days after the second dose. The virus microneutralization assay confirmed the neutralization activity of the induced SARS-CoV-2 IgG antibodies. The vaccines induced higher IgG titres at post-prime (p=0.0001) and 6 months (p=0.006) in previously infected individuals. An increased interval between prime and boost, more than recommended time, appeared to enhance the IgG levels (p=0004). Moreover, the vaccines induced higher IgG levels in younger subjects (p=0.01). Conclusion: These data provide insights and build on the current understanding of immune responses induced by these two vaccines; and support a third boosting dose for these COVID-19 vaccines

Outcomes of single dose COVID-19 vaccines: Eight month follow-up of a large cohort in Saudi Arabia

Background: Two vaccines for COVID-19 have been approved and administered in the Kingdom of Saudi Arabia (KSA); Pfizer-BioNtech BNT162b2 and AstraZeneca-Oxford AZD1222 vaccines. The purpose of this study was to describe the real-world data on the outcome of single dose of these COVID-19 vaccines in a large cohort in KSA and to analyse demographics and co-morbidities as risk factors for infection post one-dose vaccination. Methods: In this prospective cohort study, a total of 18,543 subjects received one dose of either of the vaccines at a vaccination centre in KSA, and were followed up for three to eight months. Data were collected from three sources; clinical data from medical records, adverse events (AEs) from a self-reporting system, and COVID-19 infection data from the national databases. The study was conducted during the pandemic restrictions on travel, mobility, and social interactions. Results: The median age of participants was 33 years with an average body mass index of 27.3. The majority were males (60.1%). Results showed that 92.17% of the subjects had no COVID-19 infection post-vaccination as infection post-vaccination was documented for 1452 (7.83%). Diabetes mellitus 03), organ transplantation (p = 0.02), and obesity (p < 0.01) were associated with infection post-vaccination. Unlike vaccine type, being Saudi, male, or obese was associated with the occurrence breakthrough infections more than other parameters. AEs included injection site pain, fatigue, fever, myalgia, headache and was reported by 5.8% of the subjects. Conclusion: Single dose COVID-19 vaccines showed a protection rate of 92.17% up to eight months follow-up in this cohort. This rate in AZD1222 was higher than what have been previously reported in effectiveness studies and clinical trials. Obese, male, and Saudi were at higher risk of contracting the infection post-vaccination, Saudi and male might have more social interaction with the public when mobility and social interactions were limited during the pandemic. Side effects and AEs were within what has been reported in clinical trials

Immunogenicity of High-Dose MVA-Based MERS Vaccine Candidate in Mice and Camels

The Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic pathogen that can transmit from dromedary camels to humans, causing severe pneumonia, with a 35% mortality rate. Vaccine candidates have been developed and tested in mice, camels, and humans. Previously, we developed a vaccine based on the modified vaccinia virus Ankara (MVA) viral vector, encoding a full-length spike protein of MERS-CoV, MVA-MERS. Here, we report the immunogenicity of high-dose MVA-MERS in prime–boost vaccinations in mice and camels. Methods: Three groups of mice were immunised with MVA wild-type (MVA-wt) and MVA-MERS (MVA-wt/MVA-MERS), MVA-MERS/MVA-wt, or MVA-MERS/MVA-MERS. Camels were immunised with two doses of PBS, MVA-wt, or MVA-MERS. Antibody (Ab) responses were evaluated using ELISA and MERS pseudovirus neutralisation assays. Results: Two high doses of MVA-MERS induced strong Ab responses in both mice and camels, including neutralising antibodies. Anti-MVA Ab responses did not affect the immune responses to the vaccine antigen (MERS-CoV spike). Conclusions: MVA-MERS vaccine, administered in a homologous prime–boost regimen, induced high levels of neutralising anti-MERS-CoV antibodies in mice and camels. This could be considered for further development and evaluation as a dromedary vaccine to reduce MERS-CoV transmission to humans