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.
Adult ; Bacterial Infections ; complications ; Communicable Diseases ; etiology ; Female ; Fever ; etiology ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Humans ; Immunocompromised Host ; Immunosuppressive Agents ; adverse effects ; Male ; Middle Aged ; Mycoses ; etiology ; Neutropenia ; etiology ; Opportunistic Infections ; epidemiology ; etiology ; Organ Transplantation ; adverse effects ; Virus Diseases ; etiology

Adult ; Aged ; Antimalarials ; therapeutic use ; Female ; Humans ; Immune Reconstitution Inflammatory Syndrome ; drug therapy ; JC Virus ; immunology ; Leukoencephalopathy, Progressive Multifocal ; drug therapy ; Male ; Mefloquine ; therapeutic use ; Middle Aged ; Treatment Outcome

INTRODUCTION: Omicron is the latest SARS-CoV-2 variant of concern, the pathogen that causes COVID-19. Since its emergence in late 2021, Omicron has displaced other circulating variants and caused successive waves of infection worldwide throughout 2022. Omicron is characterised by the rapid emergence of many subvariants and high rates of infection in people with vaccine- and/or infection induced immunity. This review article will consolidate current knowledge regarding Omicron subvariants, the role of boosters, and future vaccine development. METHOD: This narrative review is based on a literature search using PubMed. Search terms related to Omicron were used and priority was given to published peer-reviewed articles over pre-prints. RESULTS: Studies indicate that vaccinations and boosters are important to reduce disease severity, hospitalisation, and death from Omicron. A variety of factors, such as differing host factors, circulating variants, and forces of infection, can influence the benefit of repeated booster administration. Next-generation bivalent vaccines have now been approved in some countries including Singapore and have demonstrated the ability to induce broad variant protection. Future third-generation vaccines involving mucosal vaccines and/or pan-sarbecovirus vaccines may provide broader and longer-lasting protection. CONCLUSION Due to current high levels of vaccine- and infection-induced immunity, it is likely that rates of severe illness, hospitalisation, and death due to Omicron will continue to moderate. Nevertheless, the virus is ever-changing, and public health policies, especially those related to vaccinations, will also have to continually evolve and adapt as COVID-19 transitions to endemicity.
Humans ; SARS-CoV-2 ; COVID-19/prevention & control* ; Vaccines ; Hospitalization

INTRODUCTIONChronic bacterial, viral and parasitic infections contribute to the morbidity and mortality associated with human immunodeficiency virus (HIV) infection. This study investigated risk factors and time-trends of the seroprevalence of cytomegalovirus (CMV), toxoplasmosis and hepatitis A total antibody; and co-infection with syphilis, hepatitis B and hepatitis C among newly diagnosed HIV individuals in Singapore.

MATERIALS AND METHODSThis was a cross-sectional study. A random sample of 50% of HIV infected patients who visited the Communicable Disease Centre (CDC), Singapore for first-time care from January 2006 to December 2011 were analysed.

RESULTSAmong the 793 study subjects, 93.4% were male; 77.9% of them were of Chinese ethnicity; mean age at HIV diagnosis was 41.4 years; and the mean baseline CD4+ T-cell count was 222 cells/mm³. The prevalence of sero-reactivity for CMV was 96.8%; hepatitis A: 40.9%; and toxoplasmosis: 23.7%. Co-infection with syphilis was identified in 12.3%; hepatitis B: 8.1%; and hepatitis C: 2%. Among those co-infected with hepatitis C, 73.3% of them were intravenous drug user (IVDU). Syphilis co-infection was significantly more common among men who have sex with men (MSM) (multivariate OR: 2.53, 95% CI, 1.31 to 4.90, P = 0.006).

CONCLUSIONThis study described the baseline rates of HIV co-infection with syphilis, hepatitis B and C in Singapore, and sero-reactivity to CMV, toxoplasmosis and hepatitis A. The increased rates compared to the general population may have important consequences for disease progression, response to antiretroviral treatment and long-term general health.

Adult ; Coinfection ; epidemiology ; Cross-Sectional Studies ; Cytomegalovirus ; isolation & purification ; Cytomegalovirus Infections ; blood ; epidemiology ; Female ; HIV Infections ; epidemiology ; Hepacivirus ; isolation & purification ; Hepatitis, Viral, Human ; blood ; epidemiology ; Humans ; Male ; Odds Ratio ; Risk Factors ; Seroepidemiologic Studies ; Singapore ; epidemiology ; Syphilis ; blood ; epidemiology ; Time Factors ; Toxoplasmosis ; blood ; epidemiology

Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 and was declared a global pandemic by the World Health Organization on 11 March 2020. A definitive diagnosis of COVID-19 is made after a positive result is obtained on reverse transcription-polymerase chain reaction assay. In Singapore, rigorous contact tracing was practised to contain the spread of the virus. Nasal swabs and chest radiographs (CXR) were also taken from individuals who were suspected to be infected by COVID-19 upon their arrival at a centralised screening centre. From our experience, about 40% of patients who tested positive for COVID-19 had initial CXR that appeared "normal". In this case series, we described the temporal evolution of COVID-19 in patients with an initial "normal" CXR. Since CXR has limited sensitivity and specificity in COVID-19, it is not suitable as a first-line diagnostic tool. However, when CXR changes become unequivocally abnormal, close monitoring is recommended to manage potentially severe COVID-19 pneumonia.
Adult ; Betacoronavirus ; Clinical Laboratory Techniques ; Coronavirus Infections ; complications ; diagnosis ; diagnostic imaging ; Female ; Humans ; Lung ; diagnostic imaging ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral ; complications ; diagnostic imaging ; Radiography ; Sensitivity and Specificity

INTRODUCTION: There is a paucity of information on the cytokine, complement, endothelial activation, and coagulation profiles of multisystem inflammatory syndrome in adults (MIS-A), a rare but serious complication following recovery from SARS-CoV-2 infection. We aim to examine the immune biomarker and coagulation profiles in association with the clinical presentation and course of MIS-A. METHOD: The clinical features of MIS-A patients admitted to our tertiary hospital were documented. Their levels of interleukin (IL)-1β, IL-6, IL-10, IL-17, IL-18, interferon-α (IFN-α), IFN-γ, interferon gamma-induced protein 10 (IP-10), tumour necrosis factor (TNF)-α, monocyte chemoattractant protein (MCP)-1, complement activation product (complement 5a [C5a]), and endothelial biomarker intercellular adhesion molecule-1 (ICAM-1) levels were assayed. The haemostatic profile was assessed with standard coagulation testing and thromboelastography. RESULTS: Three male patients were diagnosed with MIS-A at our centre from January to June 2022 with a median age of 55 years. All had tested positive for SARS-CoV-2 12-62 days prior to MIS-A presentation, with gastrointestinal and cardiovascular systems as the most commonly involved. Levels of IL-6, IL-10, IL-18, IP-10 and MCP-1 were raised whereas IL-1β, IFN-α, IFN-γ, IL-17 and TNF-α remained normal. Markedly elevated levels of C-reactive protein (CRP), ferritin and ICAM-1 were present in all. C5a was elevated in 2 patients. A hypercoagulable state was demonstrated by raised levels of D-dimer, factor VIII, von Willebrand factor antigen, and ristocetin cofactor with corresponding raised parameters in thromboelastography in the 2 patients who had their coagulation profile assessed. CONCLUSION MIS-A patients demonstrate activation of pro-inflammatory cytokines, endotheliopathy, complement hyperactivation and hypercoagulability.
Humans ; Adult ; Male ; Middle Aged ; COVID-19/complications* ; Interleukin-10 ; Interleukin-18 ; Intercellular Adhesion Molecule-1 ; Interleukin-17 ; Chemokine CXCL10 ; Interleukin-6 ; SARS-CoV-2 ; Connective Tissue Diseases ; Hemostatics

INTRODUCTION: Acute respiratory distress syndrome (ARDS) in COVID-19 is associated with a high mortality rate, though outcomes of the different lung compliance phenotypes are unclear. We aimed to measure lung compliance and examine other factors associated with mortality in COVID-19 patients with ARDS. METHODS: Adult patients with COVID-19 ARDS who required invasive mechanical ventilation at 8 hospitals in Singapore were prospectively enrolled. Factors associated with both mortality and differences between high (<40mL/cm H RESULTS: A total of 102 patients with COVID-19 who required invasive mechanical ventilation were analysed; 15 (14.7%) did not survive. Non-survivors were older (median 70 years, interquartile range [IQR] 67-75 versus median 61 years, IQR 52-66; CONCLUSION COVID-19 ARDS patients with higher compliance on the day of intubation and a longitudinal decrease over time had a higher risk of death.
COVID-19 ; Humans ; Lung Compliance ; Phenotype ; Respiratory Distress Syndrome/therapy* ; SARS-CoV-2

INTRODUCTION: Pregnant women are reported to be at increased risk of severe coronavirus disease 2019 (COVID-19) due to underlying immunosuppression during pregnancy. However, the clinical course of COVID-19 in pregnancy and risk of vertical and horizontal transmission remain relatively unknown. We aim to describe and evaluate outcomes in pregnant women with COVID-19 in Singapore. METHODS: Prospective observational study of 16 pregnant patients admitted for COVID-19 to 4 tertiary hospitals in Singapore. Outcomes included severe disease, pregnancy loss, and vertical and horizontal transmission. RESULTS: Of the 16 patients, 37.5%, 43.8% and 18.7% were infected in the first, second and third trimesters, respectively. Two gravidas aged ≥35 years (12.5%) developed severe pneumonia; one patient (body mass index 32.9kg/m2) required transfer to intensive care. The median duration of acute infection was 19 days; one patient remained reverse transcription polymerase chain reaction (RT-PCR) positive >11 weeks from diagnosis. There were no maternal mortalities. Five pregnancies produced term live-births while 2 spontaneous miscarriages occurred at 11 and 23 weeks. RT-PCR of breast milk and maternal and neonatal samples taken at birth were negative; placenta and cord histology showed non-specific inflammation; and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immunoglobulins were elevated in paired maternal and umbilical cord blood (n=5). CONCLUSION The majority of COVID-19 infected pregnant women had mild disease and only 2 women with risk factors (obesity, older age) had severe infection; this represents a slightly higher incidence than observed in age-matched non-pregnant women. Among the women who delivered, there was no definitive evidence of mother-to-child transmission via breast milk or placenta.
Abortion, Spontaneous/epidemiology* ; Adult ; COVID-19/transmission* ; COVID-19 Nucleic Acid Testing ; COVID-19 Serological Testing ; Cohort Studies ; Disease Transmission, Infectious/statistics & numerical data* ; Female ; Fetal Blood/immunology* ; Humans ; Infectious Disease Transmission, Vertical/statistics & numerical data* ; Live Birth/epidemiology* ; Maternal Age ; Milk, Human/virology* ; Obesity, Maternal/epidemiology* ; Placenta/pathology* ; Pregnancy ; Pregnancy Complications, Infectious/physiopathology* ; Pregnancy Outcome/epidemiology* ; Pregnancy Trimester, First ; Pregnancy Trimester, Second ; Prospective Studies ; RNA, Viral/analysis* ; Risk Factors ; SARS-CoV-2 ; Severity of Illness Index ; Singapore/epidemiology* ; Umbilical Cord/pathology* ; Young Adult

The coronavirus disease 2019 (COVID-19) is typically diagnosed by specific assays that detect viral nucleic acid from the upper respiratory tract; however, this may miss infections involving only the lower airways. Computed tomography (CT) has been described as a diagnostic modality in the COVID-19 diagnosis and treatment plan. We present a case series with virologically confirmed COVID-19 pneumonia. Variable CT features were observed: consolidation with ground-glass opacities, ground-glass opacities with subpleural reticular bands, and an anterior-posterior gradient of lung abnormalities resembling that of acute respiratory distress syndrome. Evolution of CT findings was observed in one patient, where there was interval resolution of bilateral lung consolidation with development of bronchiolectasis and subpleural fibrotic bands. While sensitive for detecting lung parenchymal abnormalities in COVID-19 pneumonia, the use of CT for initial diagnosis is discouraged and should be reserved for specific clinical indications. Interpretation of chest CT findings should be correlated with duration of symptoms to better determine the disease stage and aid in patient management.
Aged ; Betacoronavirus ; Coronavirus Infections ; diagnosis ; Diagnosis, Differential ; Female ; Humans ; Lung ; diagnostic imaging ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral ; diagnosis ; Tomography, X-Ray Computed ; methods

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.
COVID-19 ; Humans ; Lung/diagnostic imaging* ; Radiography, Thoracic ; Retrospective Studies ; SARS-CoV-2 ; Singapore