Defining factors that influence vaccine-induced, cross-variant neutralizing antibodies for SARS-CoV-2 in Asians

The scale and duration of neutralizing antibody responses targeting SARS-CoV-2 viral variants represents a critically important serological parameter that predicts protective immunity for COVID-19. In this study, we present longitudinal data illustrating the impact of age, sex and comorbidities on the kinetics and strength of vaccine-induced neutralizing antibody responses for key variants in an Asian volunteer cohort. We demonstrate a reduction in neutralizing antibody titres across all groups six months post-vaccination and show a marked reduction in the serological binding and neutralizing response targeting Omicron compared to other viral variants. We also highlight the increase in cross-protective neutralizing antibody responses against Omicron induced by a third dose (booster) of vaccine. These data illustrate how key virological factors such as immune escape mutation combined with host factors such as age and sex of the vaccinated individuals influence the strength and duration of cross-protective serological immunity for COVID-19.

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

Calcitriol, the active form of vitamin D, is a promising candidate for COVID-19 prophylaxis

COVID-19, the disease caused by SARS-CoV-2 (1), was declared a pandemic by the World Health Organization (WHO) in March 2020 (2). While awaiting a vaccine, several antivirals are being used to manage the disease with limited success (3, 4). To expand this arsenal, we screened 4 compound libraries: a United States Food and Drug Administration (FDA) approved drug library, an angiotensin converting enzyme-2 (ACE2) targeted compound library, a flavonoid compound library as well as a natural product library. Of the 121 compounds identified with activity against SARS-CoV-2, 7 were shortlisted for validation. We show for the first time that the active form of Vitamin D, calcitriol, exhibits significant potent activity against SARS-CoV-2. This finding paves the way for consideration of host-directed therapies for ring prophylaxis of contacts of SARS-CoV-2 patients.

Infectious disease trends among immunocompromised hosts

With our rapidly ageing population and advancing treatments for patients with haematological, oncologic and rheumatological diseases, there are increasing numbers of immunocompromised patients presenting to primary care and general hospitals with opportunistic infections. This review considers the trends of these infections across four representative subgroups: fungal infections following haematopoietic stem cell transplant; viral infections post solid organ transplant; mycobacterial infections during treatment with targeted biological agents; and bacterial infections as a cause of fever in neutropenia. We also consider the impact of host, pathogens, environments and treatments on the epidemiology and outcomes of these infections.

Tracking the emergence of pandemic Influenza A/H1N1/2009 and its interaction with seasonal influenza viruses in Singapore

<p><b>INTRODUCTION</b>Since the emergence of the pandemic influenza A/H1N1/2009 virus in April 2009, diagnostic testing in many countries has revealed the rapid displacement and then replacement of circulating seasonal influenza viruses by this novel virus.</p><p><b>MATERIALS AND METHODS</b>In-house seasonal and pandemic influenza-specific polymerase chain reaction assays were introduced and/or developed at the Molecular Diagnosis Centre (MDC) at the National University Hospital (NUH), Singapore. These assays have been used to test all samples received from in-patients, out-patients, staff and visitors for suspected pandemic influenza A/H1N1/2009 infection.</p><p><b>RESULTS</b>Prior to the arrival of the pandemic A/H1N1/2009 virus in Singapore at the end of May 2009, seasonal influenza A/H3N2 predominated in this population, with very little seasonal influenza A/H1N1 and B viruses detected. Within about 1 month of its arrival in Singapore (mainly during June to July 2009), this pandemic virus rapidly displaced seasonal influenza A/H3N2 to become the predominant strain in the Singaporean population served by MDC/NUH.</p><p><b>CONCLUSIONS</b>Realtime molecular techniques have allowed the prompt detection of different influenza subtypes during this current pandemic, which has revealed the displacement/replacement of previously circulating seasonal subtypes with A/H1N1/2009. Although some of this may be explained by immunological cross-reactivity between influenza subtypes, more studies are required.</p>

Methicillin-resistant Staphylococcus aureus control at the National University Hospital, Singapore: a historical perspective

<p><b>INTRODUCTION</b>The National University Hospital (NUH) was the first restructured public hospital in Singapore. As the most recently established hospital in Singapore, it has a unique record of alert organisms including methicillin-resistant Staphylococcus aureus (MRSA).</p><p><b>MATERIALS AND METHODS</b>We performed a critical review of multiple data sources including surveillance reports, task force reports, published abstracts and manuscripts concerning MRSA in NUH.</p><p><b>RESULTS</b>Three themes emerged: 1) the MRSA rates have remained relatively stable through the life of the hospital despite the increased complexity of patients and intermittent intensified control efforts; 2) the major MRSA task forces were driven by surgeons and 3) a scientific approach to epidemiology has a critical role in understanding and planning interventions.</p><p><b>CONCLUSION</b>Although containment of MRSA can be accomplished to a certain degree through mobilisation of existing resources, higher goals such as eradication would require massive infusions of infrastructural, scientific and human resources to have a chance of success.</p>

Twentieth century influenza pandemics in Singapore

<p><b>INTRODUCTION</b>Singapore was substantially affected by three 20th Century pandemics. This study describes the course of the pandemics, and the preventive measures adopted.</p><p><b>MATERIALS AND METHODS</b>We reviewed and researched a wide range of material including peer-reviewed journal articles, Ministry of Health reports, Straits Settlements reports and newspaper articles. Monthly mortality data were obtained from various official sources in Singapore.</p><p><b>RESULTS</b>The 1918 epidemic in Singapore occurred in 2 waves--June to July, and October to November--resulting in up to 3500 deaths. The 1957 epidemic occurred in May, and resulted in widespread morbidity, with 77,000 outpatient attendances in government clinics alone. The 1968 epidemic occurred in August and lasted a few weeks, with outpatient attendances increasing by more than 65%. The preventive measures instituted by the Singapore government during the pandemics included the closure of schools, promulgation of public health messages, setting up of influenza treatment centres, and screening at ports. Students, businessmen and healthcare workers were all severely affected by the pandemics.</p><p><b>CONCLUSIONS</b>Tropical cities should be prepared in case of a future pandemic. Some of the preventive measures used in previous pandemics may be applicable during the next pandemic.</p>

Screening for vancomycin-resistant enterococci using stools sent for Clostridium difficile cytotoxin assay is effective: results of a survey of 300 Patients in a large Singapore Teaching Hospital

<p><b>INTRODUCTION</b>To assess the efficacy of screening stools sent for Clostridium difficile cytotoxin assay (CDTA) for surveillance of vancomycin-resistant enterococci (VRE).</p><p><b>MATERIALS AND METHODS</b>From April to May 2005, all stools submitted for CDTA were also cultured for VRE using vancomycin containing culture media. Isolates were identified to species level and vancomycin resistance confirmed, followed by polymerase chain reaction (PCR) for detection of vancomycin resistance genes and DNA fingerprinting. Over 2 consecutive days during that period, stool specimens or rectal swabs were also obtained from all patients in high-risk units (haematology, oncology, renal and intensive care). Fifty-one patients in each group were compared in terms of VRE risk factors previously identified.</p><p><b>RESULTS AND DISCUSSION</b>The prevalence of VRE in both groups was similar [3/204 (1.5%) in the CDTA arm and 1/97 (1.0%) in the high-risk arm; P = 1.0, Fisher's exact test]. Prevalence of risk factors for VRE colonisation, including age, duration of hospitalisation, exposure to antibiotics, exposure to surgical procedures, presence of malignancy and diabetes mellitus was similar in both groups (P > 0.05). Only renal failure (P < 0.05) was more common in the high-risk group. All 4 isolates of VRE identified were genetically distinct by variable number tandem repeat (VNTR) typing; 3 were Enterococcus faecium (2 with the vanB gene, 1 with vanA) and one E. faecalis.</p><p><b>CONCLUSION</b>Less than 2% of our high-risk patients are VRE carriers. In-hospital VRE screening using stools sent for CDTA is a simple, reasonable surrogate for screening individual high-risk patients as the patient risk profile is similar and the yield comparable in a low-prevalence setting.</p>