Virological and serological kinetics of SARS-CoV-2 Delta variant vaccine-breakthrough infections: a multi-center cohort study

ObjectivesHighly effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed but variants of concerns (VOCs) with mutations in the spike protein are worrisome, especially B.1.617.2 (Delta) which has rapidly spread across the world. We aim to study if vaccination alters virological and serological kinetics in breakthrough infections. MethodsWe conducted a multi-centre retrospective cohort study of patients in Singapore who had received a licensed mRNA vaccine and been admitted to hospital with B.1.617.2 SARS-CoV-2 infection. We compared the clinical features, virological and serological kinetics (anti-nucleocapsid, anti-spike and surrogate virus neutralization titres) between fully vaccinated and unvaccinated individuals. ResultsOf 218 individuals with B.1.617.2 infection, 84 had received a mRNA vaccine of which 71 were fully vaccinated, 130 were unvaccinated and 4 received a non-mRNA. Despite significantly older age in the vaccine breakthrough group, the odds of severe COVID-19 requiring oxygen supplementation was significantly lower following vaccination (adjusted odds ratio 0.07 95%CI: 0.015-0.335, p=0.001). PCR cycle threshold (Ct) values were similar between both vaccinated and unvaccinated groups at diagnosis, but viral loads decreased faster in vaccinated individuals. Early, robust boosting of anti-spike protein antibodies was observed in vaccinated patients, however, these titers were significantly lower against B.1.617.2 as compared with the wildtype vaccine strain. ConclusionThe mRNA vaccines are highly effective at preventing symptomatic and severe COVID-19 associated with B.1.617.2 infection. Vaccination is associated with faster decline in viral RNA load and a robust serological response. Vaccination remains a key strategy for control of COVID-19 pandemic.

Data-driven analysis of COVID-19 reveals specific severity patterns distinct from the temporal immune response

Key immune signatures of SARS-CoV-2 infection may associate with either adverse immune reactions (severity) or simply an ongoing anti-viral response (temporality); how immune signatures contribute to severe manifestations and/or temporal progression of disease and whether longer disease duration correlates with severity remain unknown. Patient blood was comprehensively immunophenotyped via mass cytometry and multiplex cytokine arrays, leading to the identification of 327 basic subsets that were further stratified into more than 5000 immunotypes and correlated with 28 plasma cytokines. Low-density neutrophil abundance was closely correlated with hepatocyte growth factor levels, which in turn correlated with disease severity. Deep analysis also revealed additional players, namely conventional type 2 dendritic cells, natural killer T cells, plasmablasts and CD16+ monocytes, that can influence COVID-19 severity independent of temporal progression. Herein, we provide interactive network analysis and data visualization tools to facilitate data mining and hypothesis generation for elucidating COVID-19 pathogenesis.

Radiographic features of COVID-19 based on an initial cohort of 96 patients in Singapore

INTRODUCTION@#Chest radiographs (CXRs) are widely used for the screening and management of COVID-19. This article describes the radiographic features of COVID-19 based on an initial national cohort of patients.@*METHODS@#This is a retrospective review of swab-positive patients with COVID-19 who were admitted to four different hospitals in Singapore between 22 January and 9 March 2020. Initial and follow-up CXRs were reviewed by three experienced radiologists to identify the predominant pattern and distribution of lung parenchymal abnormalities.@*RESULTS@#In total, 347 CXRs of 96 patients were reviewed. Initial CXRs were abnormal in 41 (42.7%) out of 96 patients. The mean time from onset of symptoms to CXR abnormality was 5.3 ± 4.7 days. The predominant pattern of lung abnormality was ground-glass opacity on initial CXRs (51.2%) and consolidation on follow-up CXRs (51.0%). Multifocal bilateral abnormalities in mixed central and peripheral distribution were observed in 63.4% and 59.2% of abnormal initial and follow-up CXRs, respectively. The lower zones were involved in 90.2% of initial CXRs and 93.9% of follow-up CXRs.@*CONCLUSION@#In a cohort of swab-positive patients, including those identified from contact tracing, we found a lower incidence of CXR abnormalities than was previously reported. The most common pattern was ground-glass opacity or consolidation, but mixed central and peripheral involvement was more common than peripheral involvement alone.

Convalescent COVID-19 patients are susceptible to endothelial dysfunction due to persistent immune activation

The rapid rise of coronavirus disease 2019 patients who suffer from vascular events after their initial recovery is expected to lead to a worldwide shift in disease burden. We aim to investigate the impact of COVID-19 on the pathophysiological state of blood vessels in convalescent patients. Here, convalescent COVID-19 patients with or without preexisting conditions (i.e. hypertension, diabetes, hyperlipidemia) were compared to non-COVID-19 patients with matched cardiovascular risk factors or healthy participants. Convalescent patients had elevated circulating endothelial cells (CECs), and those with underlying cardiovascular risk had more pronounced endothelial activation hallmarks (ICAM1, P-selectin or CX3CL1) expressed by CECs. Multiplex microbead-based immunoassays revealed some levels of cytokine production sustained from acute infection to recovery phase. Several proinflammatory and activated T lymphocyte-associated cytokines correlated positively with CEC measures, implicating cytokine-driven endothelial dysfunction. Finally, the activation markers detected on CECs mapped to the counter receptors (i.e. ITGAL, SELPLG, and CX3CR1) found primarily on CD8+ T cells and natural killer cells, suggesting that activated endothelial cells could be targeted by cytotoxic effector cells. Clinical trials in preventive therapy for post-COVID-19 vascular complications may be needed. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=69 SRC="FIGDIR/small/20232835v1_ufig1.gif" ALT="Figure 1"> View larger version (19K): org.highwire.dtl.DTLVardef@d34a61org.highwire.dtl.DTLVardef@1b82feeorg.highwire.dtl.DTLVardef@152ea88org.highwire.dtl.DTLVardef@a3b382_HPS_FORMAT_FIGEXP M_FIG C_FIG

Neutralizing antibodies from early cases of SARS-CoV-2 infection offer cross-protection against the SARS-CoV-2 D614G variant.

The emergence of a SARS-CoV-2 variant with a point mutation in the spike (S) protein, D614G, has taken precedence over the original Wuhan isolate by May 2020. With an increased infection and transmission rate, it is imperative to determine whether antibodies induced against the D614 isolate may cross-neutralize against the G614 variant. In this report, profiling of the anti-SARS-CoV-2 humoral immunity reveals similar neutralization profiles against both S protein variants, albeit waning neutralizing antibody capacity at the later phase of infection. These findings provide further insights towards the validity of current immune-based interventions. IMPORTANCERandom mutations in the viral genome is a naturally occurring event that may lead to enhanced viral fitness and immunological resistance, while heavily impacting the validity of licensed therapeutics. A single point mutation from aspartic acid (D) to glycine (G) at position 614 of the SARS-CoV-2 spike (S) protein, termed D614G, has garnered global attention due to the observed increase in transmissibility and infection rate. Given that a majority of the developing antibody-mediated therapies and serological assays are based on the S antigen of the original Wuhan reference sequence, it is crucial to determine if humoral immunity acquired from the original SARS-CoV-2 isolate is able to induce cross-detection and cross-protection against the novel prevailing D614G variant.

The Accuracy of Healthcare Worker versus Self Collected (2-in-1) Oropharyngeal and Bilateral Mid-Turbinate (OPMT) Swabs and Saliva Samples for SARS-CoV-2

Background Self-sampling for SARS-CoV-2 would significantly raise testing capacity and reduce healthcare worker (HCW) exposure to infectious droplets personal, and protective equipment (PPE) use. Methods We conducted a diagnostic accuracy study where subjects with a confirmed diagnosis of COVID-19 (n=401) and healthy volunteers (n=100) were asked to self-swab from their oropharynx and mid-turbinate (OPMT), and self-collect saliva. The results of these samples were compared to an OPMT performed by a HCW in the same patient at the same session. Results In subjects confirmed to have COVID-19, the detection rates of the HCW-swab, self-swab, saliva, and combined self-swab plus saliva samples were 82.8%, 75.1%, 74.3% and 86.5% respectively. All samples obtained from healthy volunteers were tested negative. Compared to HCW-swab, the detection rates of a self-swab sample and saliva sample were inferior by 8.7% (95%CI: 2.4% to 15.0%, p=0.006) and 9.5% (95%CI: 3.1% to 15.8%, p=0.003) respectively. The combined detection rate of self-swab and saliva had a higher detection rate of 2.7% (95%CI: -2.6% to 8.0%, p=0.321). The sensitivity of both the self-collection methods are higher when the Ct value of the HCW swab is less than 30. The negative correctness of both the self-swab and saliva testing was 100% (95% CI 96.4% to 100%). Conclusion Our study provides evidence that detection rates of self-collected OPMT swab and saliva samples were inferior to a HCW swab, but they could still be useful testing tools in the appropriate clinical settings.

Disseminated Mucormycosis Due to Saksenaea vasiformis Complex in an Immunocompetent Adult with Sustained Response to Posaconazole Treatment.

Saksenaea vasiformis complex is an emerging cause of mucormycosis. We report a case of an immunocompetent patient presenting with a non-resolving lung mass who developed multiple skin nodules. Skin biopsy yielded Saksenaea vasiformis complex. This showcases an uncommon occurrence of disseminated Saksenaea infection without cutaneous inoculation that improved with posaconazole.

Potent neutralizing antibodies in the sera of convalescent COVID-19 patients are directed against conserved linear epitopes on the SARS-CoV-2 spike protein

The ongoing SARS-CoV-2 pandemic demands rapid identification of immunogenic targets for the design of efficient vaccines and serological detection tools. In this report, using pools of overlapping linear peptides and functional assays, we present two immunodominant regions on the spike glycoprotein that were highly recognized by neutralizing antibodies in the sera of COVID-19 convalescent patients. One is highly specific to SARS-CoV-2, and the other is a potential pan-coronavirus target.

Klebsiella Pneumoniae Visceral Organ Abscesses - Clinical Characteristics

INTRODUCTION@#In recent years, () has emerged as the predominant cause of pyogenic liver abscess in Asia. - as the causative microorganism in other visceral organ abscesses-is less described. In this study, we seeked to describe the clinical characteristics of visceral organ abscesses in our institution and evaluated the prescription practices of physicians with regard to antibiotic therapy.@*MATERIALS AND METHODS@#A retrospective analysis of patients with culture positive (blood or abscess aspirate) visceral organ abscesses from May 2014 to April 2016 requiring hospitalisation in Changi General Hospital was conducted.@*RESULTS@#A total of 140 adult patients with visceral organ abscesses were identified. The commonest site of involvement was the liver (77.9%), followed by genitourinary tract (20.7%). Diabetic patients were more likely to have liver abscesses, genitourinary abscesses, abscesses in 2 or more organs, genitourinary disease with abscess formation outside of the genitourinary tract, and endovascular infection. Patients with extended spectrum beta-lactamase producing , were more likely to have an obstructive lesion related to the site of the abscess. Overall mortality rate was 7.1%. Amongst survivors, the mean total duration of parenteral antimicrobial therapy was 2.5 weeks before switching to oral antimicrobial agents.@*CONCLUSION@#Genitourinary tract is the commonest extra-hepatic site for visceral organ abscess in infections. Parenteral to oral switch of antimicrobial agents appears to be a safe and effective treatment option.

Ischemic Stroke in an HIV Positive Patient: An Initial Presentation of Neurosyphilis.

Ischemic stroke occurring in patients with human immunodeficiency virus (HIV) needs to be approached with a vast differential diagnosis in mind. We report a case of middle-aged male patient with immune reconstituted HIV on therapy without known cardiovascular risk factors who had a right middle cerebral artery territory infarct. After a thorough evaluation, he received a final diagnosis of neurosyphilis-associated vasculitis leading to stroke. He recovered without any neurological deficits following treatment with intravenous benzylpenicillin. Neurosyphilis is an easily diagnosed and treatable cause of a stroke that can be an initial presentation of neurosyphilis but requires a high index of suspicion.