Assessment of Broadly Reactive Responses in Patients With MERS-CoV Infection and SARS-CoV-2 Vaccination

Importance: In the ongoing COVID-19 pandemic, there remain unanswered questions regarding the nature and importance of the humoral immune response against other coronaviruses. Although coinfection of the Middle East respiratory syndrome coronavirus (MERS-CoV) with the SARS-CoV-2 has not been documented yet, several patients previously infected with MERS-CoV received the COVID-19 vaccine; data describing how preexisting MERS-CoV immunity may shape the response to SARS-CoV-2 following infection or vaccination are lacking. Objective: To characterize the cross-reactive and protective humoral responses in patients exposed to both MERS-CoV infection and SARS-CoV-2 vaccination. Design, Setting, and Participants: This cohort study involved a total of 18 sera samples collected from 14 patients with MERS-CoV infection before (n = 12) and after (n = 6) vaccination with 2 doses of COVID-19 mRNA vaccine (BNT162b2 or mRNA-1273). Of those patients, 4 had prevaccination and postvaccination samples. Antibody responses to SARS-CoV-2 and MERS-CoV were assessed as well as cross-reactive responses to other human coronaviruses. Main Outcomes and Measures: The main outcomes measured were binding antibody responses, neutralizing antibodies, and antibody-dependent cellular cytotoxicity (ADCC) activity. Binding antibodies targeting SARS-CoV-2 main antigens (spike [S], nucleocapsid, and receptor-binding domain) were detected using automated immunoassays. Cross-reactive antibodies with the S1 protein of SARS-CoV, MERS-CoV, and common human coronaviruses were analyzed using a bead-based assay. Neutralizing antibodies (NAbs) against MERS-CoV and SARS-CoV-2 as well as ADCC activity against SARS-CoV-2 were assessed. Results: A total of 18 samples were collected from 14 male patients with MERS-CoV infection (mean [SD] age, 43.8 [14.6] years). Median (IQR) duration between primary COVID-19 vaccination and sample collection was 146 (47-189) days. Prevaccination samples had high levels of anti-MERS S1 immunoglobin M (IgM) and IgG (reactivity index ranging from 0.80 to 54.7 for IgM and from 0.85 to 176.3 for IgG). Cross-reactive antibodies with SARS-CoV and SARS-CoV-2 were also detected in these samples. However, cross-reactivity against other coronaviruses was not detected by the microarray assay. Postvaccination samples showed significantly higher levels of total antibodies, IgG, and IgA targeting SARS-CoV-2 S protein compared with prevaccination samples (eg, mean total antibodies: 8955.0 AU/mL; 95% CI, -5025.0 to 22936.0 arbitrary units/mL; P =.002). In addition, significantly higher anti-SARS S1 IgG levels were detected following vaccination (mean reactivity index, 55.4; 95% CI, -9.1 to 120.0; P =.001), suggesting potential cross-reactivity with these coronaviruses. Also, anti-S NAbs were significantly boosted against SARS-CoV-2 (50.5% neutralization; 95% CI, 17.6% to 83.2% neutralization; P <.001) after vaccination. Furthermore, there was no significant increase in antibody-dependent cellular cytotoxicity against SARS-CoV-2 S protein postvaccination. Conclusions and Relevance: This cohort study found a significant boost in cross-reactive NAbs in some patients exposed to MERS-CoV and SARS-CoV-2 antigens. These findings suggest that isolation of broadly reactive antibodies from these patients may help guide the development of a pancoronavirus vaccine by targeting cross-reactive epitopes between distinct strains of human coronaviruses..This work was supported by internal funds from the Biomedical Research Center of Qatar University. Dr Nasrallah received funding from The WHO Eastern Mediterranean Regional Office (WHO-EMRO) Special Grant for COVID-19 Research

Effectiveness of the neutralizing antibody sotrovimab among high-risk patients with mild-to-moderate SARS-CoV-2 in Qatar

ObjectivesTo estimate the real-world effectiveness of sotrovimab against severe, critical, or fatal COVID-19 in Qatar at a time in which most SARS-CoV-2 incidences occurred due to the BA.2 Omicron subvariant. MethodsWe conducted a matched case-control study among all individuals eligible for sotrovimab treatment per United States Food and Drug Administration guidelines in the resident population of Qatar. The odds of progression to severe forms of COVID-19 were compared in cases (treatment group) versus controls (eligible patients who opted not to receive the treatment). Subgroup analyses were conducted. ResultsA total of 3364 individuals were eligible for sotrovimab treatment during the study period, of whom 519 individuals received the treatment, whereas the remaining 2845 constituted the controls. The adjusted odds ratio of disease progression to severe, critical, or fatal COVID-19 comparing the treatment group to the control group was 2.67 (95% confidence interval 0.60-11.91). In the analysis including only the subgroup of patients at higher risk of severe forms of COVID-19, the adjusted odds ratio was 0.65 (95% confidence interval 0.17-2.48). ConclusionThere was no evidence for a protective effect of sotrovimab in reducing COVID-19 severity in a setting dominated by the BA.2 subvariant

Coronavirus Disease 2019 Disease Severity in Children Infected With the Omicron Variant

SHORT SUMMARY: Severe acute respiratory syndrome coronavirus 2 infection from the Omicron variant in children/adolescents is less severe than infection from the Delta variant. Those 6 to <18 years also have less severe disease than those <6 years old. BACKGROUND: There are limited data assessing coronavirus 2019 (COVID-19) disease severity in children/adolescents infected with the Omicron variant. METHODS: We identified children and adolescents <18 years of age with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with Delta and propensity score-matched controls with Omicron variant infection from the National COVID-19 Database in Qatar. Primary outcome was disease severity, determined by hospital admission, admission to the intensive care unit (ICU), or mechanical ventilation within 14 days of diagnosis, or death within 28 days. RESULTS: Among 1735 cases with Delta variant infection between 1 June and 6 November 2021, and 32 635 cases with Omicron variant infection between 1 January and 15 January 2022, who did not have prior infection and were not vaccinated, we identified 985 propensity score-matched pairs. Among those who were Delta infected, 84.2% had mild, 15.7% had moderate, and 0.1% had severe/critical disease. Among those who were Omicron infected, 97.8% had mild, 2.2% had moderate, and none had severe/critical disease (P < .001). Omicron variant infection (vs Delta) was associated with significantly lower odds of moderate or severe/critical disease (adjusted odds ratio [AOR], 0.12; 95% confidence interval [CI], .07-.18). Those aged 6-11 and 12 to <18 years had lower odds of developing moderate or severe/critical disease compared with those younger than age 6 years (aOR, 0.47; 95% CI, .33-.66 for 6-11 year olds; aOR, 0.45; 95% CI, .21-.94 for 12 to <18 year olds). CONCLUSIONS: Omicron variant infection in children/adolescents is associated with less severe disease than Delta variant infection as measured by hospitalization rates and need for ICU care or mechanical ventilation. Those 6 to <18 years of age also have less severe disease than those <6 years old

Beware of covert enemies: Candida orthopsilosis malignant otitis externa with base of the skull osteomyelitis, a case report and review of literature

Background: Malignant otitis externa (MOE) is a serious infection of the external auditory canal that is frequently associated with skull base osteomyelitis (SBO) as well as secondary neurological sequelae. Patients with poorly controlled diabetes mellitus or immunosuppression are at increased risk of developing such critical infection for multiple local and systemic factors. While most cases are secondary to bacterial infections particularlyPseudomonas aeruginosa, fungal infections are also occasionally encountered, often associated with delayed diagnosis and high morbidity and mortality. Case report: We report a case of a 63 years old man with uncontrolled diabetes mellitus who presented with symptoms and signs of MOE, supported by radiological assessments. The patient was treated presumptively with a prolonged course of antibiotics without clinical improvement, coupled with progression of radiological findings and significant disease extension. Reassessment with biopsies and tissue cultures from external auditory meatus, tempo-mandibular bone, as well as base of the skull grew Candida orthopsilosis. The patient received induction treatment with high dose liposomal amphotericin followed by fluconazole to control disease progression and complications. Conclusion: Candida MOE with secondary skull base osteomyelitis is rare and difficult to diagnose with no clear guidance on assessment and management. Clinicians should be aware of the unusual presentations where microbiological and histopathological evaluations are essential for proper management

Fatal Coronavirus Disease 2019-associated Pulmonary Aspergillosis; A Report of Two Cases and Review of the Literature

Coronavirus Disease 2019 (COVID-19)-associated pulmonary aspergillosis is an emerging entity. We report two fatal cases of putative COVID-19-associated pulmonary aspergillosis. Both cases were diagnosed on the basis of respiratory tract cultures yielding Aspergillus species and otherwise unexplained clinical and radiological deterioration. Existing published literature on COVID-19-associated pulmonary aspergillosis indicate poor outcomes and high mortality. CAPA should be considered in patients with critical COVID-19 who have unexplained progressive respiratory failure despite optimized supportive care. Diagnostic work-up should be initiated as early as possible and should ideally include fungal cultures, galactomannan detection and Aspergillus PCR on tracheal aspirates or broncho-alveolar lavage fluid. Empiric systemic antifungal therapy may be justified in selected cases, pending diagnostic work up results. Large, multi-center studies are required to further understand the pathogenesis of invasive aspergillosis in COVID-19, and the optimal diagnostic and treatment strategies

Candida auris Blood stream infection- a descriptive study from Qatar

Abstract Background Candida auris is an emerging yeast pathogen that can cause invasive infections, particularly candidemia, in healthcare settings. Candida auris is characterized by resistance to multiple classes of antifungal drugs and high mortality. Objective To describe the risk factors, clinical characteristics, antifungal susceptibility pattern and outcomes of Candida auris blood stream infection. Methods We conducted a retrospective review of electronic medical records of C. auris fungemia cases in the facilities under Hamad Medical corporation, Qatar from 1/11/2018 to 31/7/2021. Demographic data, risk factors, antibiogram and 30-day outcome are described. Results We identified 36 patients with C. auris fungemia. Most of the patients were in intensive care unit following severe COVID-19 pneumonia and had received steroids and broad-spectrum antibiotics. Most cases were central line related. Over 90% of isolates were non-susceptible to fluconazole, while amphotericin B resistance reached 85%. Factors associated with high mortality included initial SOFA score of 9 or above and absence of source control. Conclusion Our study reveals a concerning 41.6% mortality rate within 30 days of C. auris candidemia. Furthermore, the prevalence of amphotericin B resistance in Qatar exceeds what has been reported in the literature necessitating further exploration. Echinocandins retains nearly 100% susceptibility and should be prioritized as the treatment of choice. These findings emphasize the need for vigilant monitoring and appropriate management strategies to combat C. auris infections and improve patient outcomes

Antibody-Dependent Enhancement (ADE) and the role of complement system in disease pathogenesis

Antibody-dependent enhancement (ADE) has been associated with severe disease outcomes in several viral infections, including respiratory infections. In vitro and in vivo studies showed that antibody-response to SARS-CoV and MERS-CoV could exacerbate infection via ADE. Recently in SARS CoV-2, the in vitro studies and structural analysis shows a risk of disease severity via ADE. This phenomenon is partially attributed to non-neutralizing antibodies or antibodies at sub-neutralizing levels. These antibodies result in antigen-antibody complexes' deposition and propagation of a chronic inflammatory process that destroys affected tissues. Further, antigen-antibody complexes may enhance the internalization of the virus into cells through the Fc gamma receptor (FcγR) and lead to further virus replication. Thus, ADE occur via two mechanisms; 1. Antibody mediated replication and 2. Enhanced immune activation. Antibody-mediated effector functions are mainly driven by complement activation, and the first complement in the cascade is complement 1q (C1q) which binds to the virus-antibody complex. Reports say that deficiency in circulating plasma levels of C1q, an independent predictor of mortality in high-risk patients, including diabetes, is associated with severe viral infections. Complement mediated ADE is reported in several viral infections such as dengue, West Nile virus, measles, RSV, Human immunodeficiency virus (HIV), and Ebola virus. This review discusses ADE in viral infections and the in vitro evidence of ADE in coronaviruses. We outline the mechanisms of ADE, emphasizing the role of complements, especially C1q in the outcome of the enhanced disease.Qatar National LibraryOpen access funding is provided by the Qatar National Library.Scopu

The initial impact of a national BNT162b2 mRNA COVID-19 vaccine rollout

Objective: This study examined the initial impact of a national BNT162b2 vaccine rollout on SARS-CoV-2 infections in Qatar. Methods: All individuals who had completed ≥14 days of follow-up by 16 March 2021 after receiving the BNT162b2 vaccine were included. This study calculated incidence rates (IR) and their 95% confidence intervals (CI) during days 1–7, 8–14, 15–21, 22–28, and >28 days post-vaccination. Poisson regression was used to calculate incidence rate ratios (IRR) relative to the first 7-day post-vaccination period. Results: A total of 199,219 individuals with 6,521,124 person-days of follow-up were included. SARS-CoV-2 infection was confirmed in 1877 (0.9%), of which 489 (26.1%) were asymptomatic and 123 (6.6%) required oxygen support. The median time from first vaccination to SARS-CoV-2 confirmation was 11.9 days (IQR 7.7–18.2). Compared with the first 7-day post-vaccination period, SARS-CoV-2 infections were lower by 65.8–84.7% during 15–21, 22–28, and >28 days (P < 0.001 for each). For severe COVID-19, the incidence rates were 75.7–93.3% lower during the corresponding time periods (P < 0.001 for each). Conclusion: The results were consistent with an early protective effect of BNT162b2 vaccine against all degrees of SARS-CoV-2 severity

Acinetobacter Infections among Adult Patients in Qatar: A 2-Year Hospital-Based Study

This retrospective study was conducted at Hamad General Hospital, Qatar, to describe the demographic data, clinical features underlying diseases, antimicrobial susceptibility, and outcome of A. baumannii infection. It involved all adult patients 15 years of age or older who were managed at Hamad General Hospital for A. baumannii infection from January 1, 2012, to December 31, 2013. We identified a total of 239 patients with A. baumannii infection, of which 182 (76.2%) were males. The mean age was 49.10±19.57 years. The majority of the episodes (25.1%) occurred in elderly patients (≥65 years) and the most commonly identified site of A. baumannii infection was the respiratory tract, 117 (48.9%). Most episodes of infection, 231 (96.7%), were hospital-acquired and high rate of nosocomial infections occurred in the medical intensive care unit, 66 (28.6%). All patients had underlying medical conditions. Maximum resistance was seen to cefotaxime, 147 (58.3%), and minimum resistance was seen to colistin, 2 (1.4%). Of the 239 isolates, 102 (42.7%) were susceptible and 137 (57.3%) were multidrug-resistant. The in-hospital mortality in our study was 31%. Male gender, multidrug resistance, and septic shock were found to be independent mortality predictors

Phylogenetic diversity of human pathogenic Fusarium and emergence of uncommon virulent species

OBJECTIVES: Fusarium species cause a broad spectrum of infections. However, little is known about the etiological agents to the species level. We identified Fusarium species isolated from clinical specimens including those of high risk patients to better understand the species involved in the pathogenesis. METHODS: A set of 44 Fusarium isolates were identified by two-locus sequence typing using partial sequences of the second largest subunit of RNA polymerase (RPB2) and translation elongation factor 1 alpha (TEF-1α). RESULTS: The identified species belonged to four species complexes (SC); the most common SC was Fusarium solani (FSSC) (75%), followed by Fusarium oxysporum (FOSC) (4.5%), Fusarium fujikuroi (FFSC) (13.6%), and Fusarium dimerum (FDSC) (6.8%). Sites of infections were nails (n = 19, 43.2%), skin (n = 7, 15.9%), cornea (n = 6, 13.6%), blood (n = 3, 9%), wound (n = 4, 6.8%), burn (n = 2, 4.5%), tissue (n = 2, 4.5%), and urine (n = 1, 2.27%). Fusarium acutatum was rare and seem restricted to the Middle East. Comorbidities associated with invasive infections were hematological malignancy and autoimmune disorders. CONCLUSIONS: Members of the FSSC predominantly caused cornea, nail and bloodstream infections. Less frequently encountered were the FOSC, FFSC and FDSC. More accurate molecular identification of Fusarium species is important to predict therapeutic outcome and the emergence of these species