Adverse effects following anti-COVID-19 vaccination with mRNA-based BNT162b2 are alleviated by altering the route of administration and correlate with baseline enrichment of T and NK cell genes.

Ensuring high vaccination and even booster vaccination coverage is critical in preventing severe Coronavirus Disease 2019 (COVID-19). Among the various COVID-19 vaccines currently in use, the mRNA vaccines have shown remarkable effectiveness. However, systemic adverse events (AEs), such as postvaccination fatigue, are prevalent following mRNA vaccination, and the underpinnings of which are not understood. Herein, we found that higher baseline expression of genes related to T and NK cell exhaustion and suppression were positively correlated with the development of moderately severe fatigue after Pfizer-BioNTech BNT162b2 vaccination; increased expression of genes associated with T and NK cell exhaustion and suppression reacted to vaccination were associated with greater levels of innate immune activation at 1 day postvaccination. We further found, in a mouse model, that altering the route of vaccination from intramuscular (i.m.) to subcutaneous (s.c.) could lessen the pro-inflammatory response and correspondingly the extent of systemic AEs; the humoral immune response to BNT162b2 vaccination was not compromised. Instead, it is possible that the s.c. route could improve cytotoxic CD8 T-cell responses to BNT162b2 vaccination. Our findings thus provide a glimpse of the molecular basis of postvaccination fatigue from mRNA vaccination and suggest a readily translatable solution to minimize systemic AEs.

An overview of multimorbidity and polypharmacy in older people living with HIV.

The availability of effective antiretroviral therapy (ART) has revolutionized the care of people living with HIV (PLHIV). As a result, PLHIV now have a life expectancy comparable with that of the general population. PLHIV are increasingly confronted with age-related comorbidities and geriatric syndromes, including frailty and polypharmacy, which occur at a higher prevalence and set in at an earlier age compared with their uninfected counterparts. The underlying pathophysiology for multimorbidity and polypharmacy are multifactorial, multidimensional and complex. Therefore, regular review and optimization of risk factors to maintain physical function, social and psychological health is of utmost importance. With an ever-growing population of older PLHIV, there is a pressing need to provide holistic care to address these emerging issues. Accelerated aging observed in PLHIV suggests that early involvement of a multidisciplinary team, including geriatricians, and implementation of integrated models of care can potentially improve the care of older PLHIV, who are at increased risk of frailty and complex multimorbidity. This article reviews the current global situation, discusses the challenges involved and suggests approaches to deliver comprehensive care for older PLHIV. Geriatr Gerontol Int 2024; 24: 49-59.

National HIV programme testing recommendations.

In recognition of the morbidity and mortality associated with human immunodeficiency virus (HIV), the Joint United Nations Programme on HIV/acquired immunodeficiency syndrome (AIDS) (UNAIDS) aims to end the epidemic by setting and striving to achieve the ambitious 95-95-95 targets. However, Singapore is still not performing well in the first UNAIDS target. The National HIV Programme (NHIVP) developed this set of recommendations based on an adaptation of major international guidelines from the World Health Organization and the US Centers for Disease Control and Prevention. The goals of this recommendation are: (1) to increase the uptake of HIV testing; (2) to allow earlier detection and identification of individuals with unrecognised HIV infection; (3) to facilitate linkage to clinical services; and (4) reduce further transmission of HIV infection in Singapore.

Chronic sequelae complicate convalescence from both dengue and acute viral respiratory illness.

Long Covid has raised awareness of the potentially disabling chronic sequelae that afflicts patients after acute viral infection. Similar syndromes of post-infectious sequelae have also been observed after other viral infections such as dengue, but their true prevalence and functional impact remain poorly defined. We prospectively enrolled 209 patients with acute dengue (n = 48; one with severe dengue) and other acute viral respiratory infections (ARI) (n = 161), and followed them up for chronic sequelae up to one year post-enrolment, prior to the onset of the Covid-19 pandemic. Baseline demographics and co-morbidities were balanced between both groups except for gender, with more males in the dengue cohort (63% vs 29%, p<0.001). Except for the first visit, data on symptoms were collected remotely using a purpose-built mobile phone application. Mental health outcomes were evaluated using the validated SF-12v2 Health Survey. Almost all patients (95.8% of dengue and 94.4% of ARI patients) experienced at least one symptom of fatigue, somnolence, headache, concentration impairment or memory impairment within the first week of enrolment. Amongst patients with at least 3-months of follow-up, 18.0% in the dengue cohort and 14.6% in the ARI cohort experienced persistent symptoms. The median month-3 SF-12v2 Mental Component Summary Score was lower in patients who remained symptomatic at 3 months and beyond, compared to those whose symptoms fully resolved (47.7 vs. 56.0, p<0.001), indicating that patients who self-reported persistence of symptoms also experienced functionally worse mental health. No statistically significant difference in age, gender distribution or hospitalisation status was observed between those with and without chronic sequelae. Our findings reveal an under-appreciated burden of post-infection chronic sequelae in dengue and ARI patients. They call for studies to define the pathophysiology of this condition, and determine the efficacy of both vaccines as well as antiviral drugs in preventing such sequelae.

Recommendations for the use of antiretroviral therapy in adults living with HIV in Singapore.

Since the advent of combination antiretroviral therapy (ART), the mortality attributable to HIV infection has been reduced by 80%. Newer antiretroviral agents are highly efficacious, have minimal side effects as compared to older drugs, and can be formulated as combination tablets, which reduces patients' pill burden. Despite these advances, 680,000 people died of AIDS-related illnesses worldwide in 2020. The National ART and Monitoring Recommendations by the National HIV Programme are created to guide physicians on the prescribing of ART based on the patients' needs. These recommendations are based on international guidelines and tailored to the local context and unique domestic considerations. It is hoped that with the publication of these recommendations, the care of people living with HIV can be enhanced, bringing us closer to the ending of HIV in our lifetime.

Gut Ruminococcaceae levels at baseline correlate with risk of antibiotic-associated diarrhea.

Antibiotic-associated diarrhea (AAD) affects a significant proportion of patients receiving antibiotics. We sought to understand if differences in the gut microbiome would influence the development of AAD. We administered a 3-day course of amoxicillin-clavulanate to 30 healthy adult volunteers, and analyzed their stool microbiome, using 16S rRNA gene sequencing, at baseline and up to 4 weeks post antibiotic administration. Lower levels of gut Ruminococcaceae were significantly and consistently observed from baseline until day 7 in participants who developed AAD. Overall, participants who developed AAD experienced a greater decrease in microbial diversity. The probability of AAD could be predicted based on qPCR-derived levels of Faecalibacterium prausnitzii at baseline. Our findings suggest that a lack of gut Ruminococcaceae influences development of AAD. Quantification of F. prausnitzii in stool prior to antibiotic administration may help identify patients at risk of AAD, and aid clinicians in devising individualized treatment regimens to minimize such adverse effects.

Risk of hepatitis B virus (HBV) reactivation in hepatitis B surface antigen negative/hepatitis B core antibody positive patients receiving rituximab-containing combination chemotherapy without routine antiviral prophylaxis.

The use of rituximab has been associated with increased risk of hepatitis B virus (HBV) reactivation in patients who are hepatitis B surface antigen (HBsAg) negative and antihepatitis B core antibody (anti-HBc) positive. We aim to determine the rate of HBV reactivation in this group of patients who received rituximab-containing combination chemotherapy without concomitant antiviral prophylaxis and to identify potential risk factors for reactivation. Sixty-two HBsAg negative/anti-HBc positive patients with B-cell lymphoma treated with rituximab-based immunochemotherapy from 2006 to 2009 were included. None of the patients received concomitant antiviral prophylaxis. In this cohort, 48 (77%) patients received rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), eight (13%) received rituximab with cyclophosphamide, vincristine and prednisolone, and six (10%) received other chemotherapy regimens. Two patients suffered HBV reactivation; both were above 70 years of age, received R-CHOP chemotherapy and were negative for antihepatitis B surface antibody (anti-HBs) at baseline. One of the two patients reactivated shortly after completion of R-CHOP chemotherapy while the other reactivated during rituximab maintenance treatment. Thus, the overall reactivation rate in this cohort of patients is 3% (2/62), 4% (2/48), and 25% (1/4) in patients who received R-CHOP chemotherapy and who received rituximab maintenance, respectively. The rate of HBV reactivation is low in patients who are HBsAg negative/anti-HBc positive receiving rituximab-based combination chemotherapy without concomitant antiviral prophylaxis. However, elderly patients, particularly those without anti-HBs, seemed particularly at risk.

Early Recognition of Coronavirus 2019 Disease (COVID-19) Infection in Surgical Inpatients: The Importance of a Risk-Stratified Approach for Early Testing and Isolation.

Background: In the ongoing coronavirus disease 2019 (COVID-19) pandemic, resuming provision of surgical services poses a challenge given that patients may have acute surgical pathologies with concurrent COVID-19 infection. We utilized a risk-stratified approach to allow for early recognition and isolation of potential COVID-19 infection in surgical patients, ensuring continuity of surgical services during a COVID-19 outbreak. Patients and Methods: Over a four-month period from January to April 2020, surgical patients admitted with concurrent respiratory symptom, infiltrates on chest imaging, or suspicious travel/epidemiologic history were placed in a dedicated ward in which they were tested for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). If emergency operations were necessary prior to the exclusion of COVID-19, patients were managed as per suspected cases of COVID-19, with appropriate precautions and full personal protective equipment (PPE). Results: From January through April 2020, a total of 8,437 patients were admitted to our surgical department; 5.9% (498/8437) required peri-operative testing for SARS-CoV-2. Because testing was in-house with turnaround within 24 hours, only a small number of emergency operations (n = 10) were conducted for suspected COVID-19 cases prior to results; none tested positive. The testing yield was lower in surgical inpatients compared with medical inpatients (odds ratio [OR] = 0.20, 95% confidence interval [CI], 0.12-0.32, p < 0.001). Three operations were conducted in known COVID-19 cases; all healthcare workers (HCWs) used full PPE. A risk-stratified testing strategy picked up previously unsuspected COVID-19 in six cases; 66.7% (4/6) were asymptomatic at presentation. Although 48 HCWs were exposed to these six cases, delayed diagnosis was averted and no evidence of spread to patients or HCWs was detected. Conclusion: A risk-stratified approach allowed for early recognition, testing, and isolation of potential COVID-19 infection in surgical patients, ensuring continuity of surgical services.

Cohort study to evaluate the effect of vitamin D, magnesium, and vitamin B12 in combination on progression to severe outcomes in older patients with coronavirus (COVID-19).

OBJECTIVES: The aim of this study was to determine clinical outcomes of older patients with coronavirus (COVID-19) who received a combination of vitamin D, magnesium, and vitamin B12 (DMB) compared with those who did not. We hypothesized that fewer patients administered this combination would require oxygen therapy, intensive care support, or a combination of both than those who did not. METHODS: This was a cohort observational study of all consecutive hospitalized patients ≥50 y of age with COVID-19 in a tertiary academic hospital. Before April 6, 2020, no patients received the (DMB) combination. After this date, patients were administered 1000 IU/d oral vitamin D3, 150 mg/d oral magnesium, and 500 mcg/d oral vitamin B12 upon admission if they did not require oxygen therapy. Primary outcome was deterioration leading to any form of oxygen therapy, intensive care support, or both. RESULTS: Between January 15 and April 15, 2020, we identified 43 consecutive patients ≥50 y of age with COVID-19. Seventeen patients received DMB before onset of primary outcome and 26 patients did not. Baseline demographic characteristics between the two groups were significantly different by age. In univariate analysis, age and hypertension had a significant influence on outcome. After adjusting for age or hypertension separately in a multivariate analysis, the intervention group retained protective significance. Fewer treated patients than controls required initiation of oxygen therapy during hospitalization (17.6 vs 61.5%, P = 0.006). DMB exposure was associated with odds ratios of 0.13 (95% confidence interval [CI], 0.03-0.59) and 0.20 (95% CI, 0.04-0.93) for oxygen therapy, intensive care support, or both on univariate and multivariate analyses, respectively. CONCLUSIONS: A vitamin D / magnesium / vitamin B12 combination in older COVID-19 patients was associated with a significant reduction in the proportion of patients with clinical deterioration requiring oxygen support, intensive care support, or both. This study supports further larger randomized controlled trials to ascertain the full benefit of this combination in ameliorating the severity of COVID-19.

Staphylococcal driveline infections are the predominant type of left ventricular assist device associated infections in Singapore.

BACKGROUND: Left ventricular assist device (LVAD) associated infections (LVADIs) have substantial morbidity and mortality. We aim to describe the incidence and epidemiology of LVADIs in an Asian cohort. This is currently not well studied. METHODS: We conducted a retrospective review of 52 patients who underwent LVAD implantation from 1 May 2009-31 December 2014 in National Heart Centre Singapore. LVADIs were defined based on definitions proposed by the International Society for Heart and Lung Transplantation. RESULTS: There were 39 males and 13 females. Seventy-three percent had Heartmate II LVAD implant while 27% received Heartware HVAD. Eighty-one percent were implanted as bridge to heart transplantation, 19% as destination therapy. Forty-five episodes of LVADIs occurred in 25 patients. Overall LVADI incidence was 47.5 cases per 100 patient-years. Driveline infections (58%) were the commonest type of LVADI. The commonest causative organisms were coagulase-negative staphylococci (33%), Staphylococcus aureus (31%) and Corynebacterium species (19%). Twelve percent of patients with LVADI required surgical debridement and one patient required pump exchange due to pump pocket infection. All-cause mortality was 13%. CONCLUSIONS: The findings of our study add to the understanding and epidemiology of LVADIs, particularly in the Asian setting. This can contribute to the development of evidence based strategies to prevent and manage LVADIs.