COVID-19 vaccines: Keeping pace with SARS-CoV-2 variants.

As the SARS-CoV-2 pandemic evolves, new variants continue to emerge. Some highly transmissible variants, such as Delta, also raised concerns about the effectiveness provided by current vaccines. Understanding immunological correlates of protection and how laboratory findings correspond to clinical effectiveness is imperative to shape future vaccination strategies.

Public health actions to control new SARS-CoV-2 variants.

Recent reports suggest that some SARS-CoV-2 genetic variants, such as B.1.1.7, might be more transmissible and are quickly spreading around the world. As the emergence of more transmissible variants could exacerbate the pandemic, we provide public health guidance for increased surveillance and measures to reduce community transmission.

Clade I-Associated Mpox Cases Associated with Sexual Contact, the Democratic Republic of the Congo.

We report a cluster of clade I monkeypox virus infections linked to sexual contact in the Democratic Republic of the Congo. Case investigations resulted in 5 reverse transcription PCR-confirmed infections; genome sequencing suggest they belonged to the same transmission chain. This finding demonstrates that mpox transmission through sexual contact extends beyond clade IIb.

Mpox virus and transmission through sexual contact: Defining the research agenda.

In a Policy Forum piece, Dr. Nicola Low and colleagues define the research agenda for Mpox virus and transmission through sexual contact.

Estimating the global impact of coronavirus disease 2019 on people living with HIV.

PURPOSE OF REVIEW: The COVID-19 pandemic and public health response have directly and indirectly affected broader health outcomes, especially for those with existing chronic conditions, including HIV. We examine our current understanding of the global impact of COVID-19 on people with HIV (PWH). RECENT FINDINGS: The interaction between COVID-19 and HIV is complex, making it challenging to estimate its true impact on PWH. Evidence to date does not suggest that HIV confers a higher risk of acquiring SARS-CoV-2. However, once acquired, HIV increases the risk of severe COVID-19 and mortality, particularly in immunosuppressed viraemic individuals and in the context of traditional COVID-19 risk factors, including disparities in social determinants of health. In addition, COVID-19 vaccines may be less effective in the context of HIV infection with additional doses needed. The consequences of disruption of access to essential prevention and treatment services because of the pandemic are becoming evident and will likely adversely affect outcomes, risking decades of progress. SUMMARY: Given the increased mortality risk and reduced vaccine effectiveness seen in PWH, specific prevention and support measures are needed, including prioritization of vaccination and boosters, funding to mitigate the impact of pandemic and enabling integrated healthcare delivery during pandemics will be critical.

Non-pharmaceutical interventions for COVID-19: a systematic review on environmental control measures.

The purpose of this review was to identify the effectiveness of environmental control (EC) non-pharmaceutical interventions (NPIs) in reducing transmission of SARS-CoV-2 through conducting a systematic review. EC NPIs considered in this review are room ventilation, air filtration/cleaning, room occupancy, surface disinfection, barrier devices, [Formula: see text] monitoring and one-way-systems. Systematic searches of databases from Web of Science, Medline, EMBASE, preprint servers MedRxiv and BioRxiv were conducted in order to identify studies reported between 1 January 2020 and 1 December 2022. All articles reporting on the effectiveness of ventilation, air filtration/cleaning, room occupancy, surface disinfection, barrier devices, [Formula: see text] monitoring and one-way systems in reducing transmission of SARS-CoV-2 were retrieved and screened. In total, 13 971 articles were identified for screening. The initial title and abstract screening identified 1328 articles for full text review. Overall, 19 references provided evidence for the effectiveness of NPIs: 12 reported on ventilation, 4 on air cleaning devices, 5 on surface disinfection, 6 on room occupancy and 1 on screens/barriers. No studies were found that considered the effectiveness of [Formula: see text] monitoring or the implementation of one-way systems. Many of these studies were assessed to have critical risk of bias in at least one domain, largely due to confounding factors that could have affected the measured outcomes. As a result, there is low confidence in the findings. Evidence suggests that EC NPIs of ventilation, air cleaning devices and reduction in room-occupancy may have a role in reducing transmission in certain settings. However, the evidence was usually of low or very low quality and certainty, and hence the level of confidence ascribed to this conclusion is low. Based on the evidence found, it was not possible to draw any specific conclusions regarding the effectiveness of surface disinfection and the use of barrier devices. From these results, we further conclude that community agreed standards for well-designed epidemiological studies with low risk of bias are needed. Implementation of such standards would enable more confident assessment in the future of the effectiveness of EC NPIs in reducing transmission of SARS-CoV-2 and other pathogens in real-world settings. This article is part of the theme issue 'The effectiveness of non-pharmaceutical interventions on the COVID-19 pandemic: the evidence'.

Occurrence and transmission potential of asymptomatic and presymptomatic SARS-CoV-2 infections: Update of a living systematic review and meta-analysis.

BACKGROUND: Debate about the level of asymptomatic Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection continues. The amount of evidence is increasing and study designs have changed over time. We updated a living systematic review to address 3 questions: (1) Among people who become infected with SARS-CoV-2, what proportion does not experience symptoms at all during their infection? (2) What is the infectiousness of asymptomatic and presymptomatic, compared with symptomatic, SARS-CoV-2 infection? (3) What proportion of SARS-CoV-2 transmission in a population is accounted for by people who are asymptomatic or presymptomatic? METHODS AND FINDINGS: The protocol was first published on 1 April 2020 and last updated on 18 June 2021. We searched PubMed, Embase, bioRxiv, and medRxiv, aggregated in a database of SARS-CoV-2 literature, most recently on 6 July 2021. Studies of people with PCR-diagnosed SARS-CoV-2, which documented symptom status at the beginning and end of follow-up, or mathematical modelling studies were included. Studies restricted to people already diagnosed, of single individuals or families, or without sufficient follow-up were excluded. One reviewer extracted data and a second verified the extraction, with disagreement resolved by discussion or a third reviewer. Risk of bias in empirical studies was assessed with a bespoke checklist and modelling studies with a published checklist. All data syntheses were done using random effects models. Review question (1): We included 130 studies. Heterogeneity was high so we did not estimate a mean proportion of asymptomatic infections overall (interquartile range (IQR) 14% to 50%, prediction interval 2% to 90%), or in 84 studies based on screening of defined populations (IQR 20% to 65%, prediction interval 4% to 94%). In 46 studies based on contact or outbreak investigations, the summary proportion asymptomatic was 19% (95% confidence interval (CI) 15% to 25%, prediction interval 2% to 70%). (2) The secondary attack rate in contacts of people with asymptomatic infection compared with symptomatic infection was 0.32 (95% CI 0.16 to 0.64, prediction interval 0.11 to 0.95, 8 studies). (3) In 13 modelling studies fit to data, the proportion of all SARS-CoV-2 transmission from presymptomatic individuals was higher than from asymptomatic individuals. Limitations of the evidence include high heterogeneity and high risks of selection and information bias in studies that were not designed to measure persistently asymptomatic infection, and limited information about variants of concern or in people who have been vaccinated. CONCLUSIONS: Based on studies published up to July 2021, most SARS-CoV-2 infections were not persistently asymptomatic, and asymptomatic infections were less infectious than symptomatic infections. Summary estimates from meta-analysis may be misleading when variability between studies is extreme and prediction intervals should be presented. Future studies should determine the asymptomatic proportion of SARS-CoV-2 infections caused by variants of concern and in people with immunity following vaccination or previous infection. Without prospective longitudinal studies with methods that minimise selection and measurement biases, further updates with the study types included in this living systematic review are unlikely to be able to provide a reliable summary estimate of the proportion of asymptomatic infections caused by SARS-CoV-2. REVIEW PROTOCOL: Open Science Framework (https://osf.io/9ewys/).

A population framework for predicting the proportion of people infected by the far-field airborne transmission of SARS-CoV-2 indoors.

The number of occupants in a space influences the risk of far-field airborne transmission of SARS-CoV-2 because the likelihood of having infectious and susceptible people both correlate with the number of occupants. This paper explores the relationship between occupancy and the probability of infection, and how this affects an individual person and a population of people. Mass-balance and dose-response models determine far-field transmission risks for an individual person and a population of people after sub-dividing a large reference space into 10 identical comparator spaces. For a single infected person, the dose received by an individual person in the comparator space is 10 times higher because the equivalent ventilation rate per infected person is lower when the per capita ventilation rate is preserved. However, accounting for population dispersion, such as the community prevalence of the virus, the probability of an infected person being present and uncertainty in their viral load, shows the transmission probability increases with occupancy and the reference space has a higher transmission risk. Also, far-field transmission is likely to be a rare event that requires a high emission rate, and there are a set of Goldilocks conditions that are just right when equivalent ventilation is effective at mitigating against transmission. These conditions depend on the viral load, because when they are very high or low, equivalent ventilation has little effect on transmission risk. Nevertheless, resilient buildings should deliver the equivalent ventilation rate required by standards as minimum.

On the Effect of Age on the Transmission of SARS-CoV-2 in Households, Schools, and the Community.

BACKGROUND: There is limited information on the effect of age on the transmission of SARS-CoV-2 infection in different settings. METHODS: We reviewed published studies/data on detection of SARS-CoV-2 infection in contacts of COVID-19 cases, serological studies, and studies of infections in schools. RESULTS: Compared to younger/middle-aged adults, susceptibility to infection for children younger than 10 years is estimated to be significantly lower, while estimated susceptibility to infection in adults older than 60 years is higher. Serological studies suggest that younger adults (particularly those younger than 35 years) often have high cumulative incidence of SARS-CoV-2 infection in the community. There is some evidence that given limited control measures, SARS-CoV-2 may spread robustly in secondary/high schools, and to a lesser degree in primary schools, with class size possibly affecting that spread. There is also evidence of more limited spread in schools when some mitigation measures are implemented. Several potential biases that may affect these studies are discussed. CONCLUSIONS: Mitigation measures should be implemented when opening schools, particularly secondary/high schools. Efforts should be undertaken to diminish mixing in younger adults, particularly individuals aged 18-35 years, to mitigate the spread of the epidemic in the community.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Transmission Dynamics Should Inform Policy.

It is generally agreed that striking a balance between resuming economic and social activities and keeping the effective reproductive number (R0) below 1 using nonpharmaceutical interventions is an important goal until and even after effective vaccines become available. Therefore, the need remains to understand how the virus is transmitted in order to identify high-risk environments and activities that disproportionately contribute to its spread so that effective preventative measures could be put in place. Contact tracing and household studies, in particular, provide robust evidence about the parameters of transmission. In this Viewpoint, we discuss the available evidence from large-scale, well-conducted contact-tracing studies from across the world and argue that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission dynamics should inform policy decisions about mitigation strategies for targeted interventions according to the needs of the society by directing attention to the settings, activities, and socioeconomic factors associated with the highest risks of transmission.

Outcomes of Coronavirus Disease 2019 (COVID-19) Related Hospitalization Among People With Human Immunodeficiency Virus (HIV) in the ISARIC World Health Organization (WHO) Clinical Characterization Protocol (UK): A Prospective Observational Study.

BACKGROUND: Evidence is conflicting about how human immunodeficiency virus (HIV) modulates coronavirus disease 2019 (COVID-19). We compared the presentation characteristics and outcomes of adults with and without HIV who were hospitalized with COVID-19 at 207 centers across the United Kingdom and whose data were prospectively captured by the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) World Health Organization (WHO) Clinical Characterization Protocol (CCP) study. METHODS: We used Kaplan-Meier methods and Cox regression to describe the association between HIV status and day-28 mortality, after separate adjustment for sex, ethnicity, age, hospital acquisition of COVID-19 (definite hospital acquisition excluded), presentation date, 10 individual comorbidities, and disease severity at presentation (as defined by hypoxia or oxygen therapy). RESULTS: Among 47 592 patients, 122 (0.26%) had confirmed HIV infection, and 112/122 (91.8%) had a record of antiretroviral therapy. At presentation, HIV-positive people were younger (median 56 vs 74 years; P < .001) and had fewer comorbidities, more systemic symptoms and higher lymphocyte counts and C-reactive protein levels. The cumulative day-28 mortality was similar in the HIV-positive versus HIV-negative groups (26.7% vs. 32.1%; P = .16), but in those under 60 years of age HIV-positive status was associated with increased mortality (21.3% vs. 9.6%; P < .001 [log-rank test]). Mortality was higher among people with HIV after adjusting for age (adjusted hazard ratio [aHR] 1.47, 95% confidence interval [CI] 1.01-2.14; P = .05), and the association persisted after adjusting for the other variables (aHR 1.69; 95% CI 1.15-2.48; P = .008) and when restricting the analysis to people aged <60 years (aHR 2.87; 95% CI 1.70-4.84; P < .001). CONCLUSIONS: HIV-positive status was associated with an increased risk of day-28 mortality among patients hospitalized for COVID-19.

How to detect and reduce potential sources of biases in studies of SARS-CoV-2 and COVID-19.

In response to the coronavirus disease (COVID-19) pandemic, public health scientists have produced a large and rapidly expanding body of literature that aims to answer critical questions, such as the proportion of the population in a geographic area that has been infected; the transmissibility of the virus and factors associated with high infectiousness or susceptibility to infection; which groups are the most at risk of infection, morbidity and mortality; and the degree to which antibodies confer protection to re-infection. Observational studies are subject to a number of different biases, including confounding, selection bias, and measurement error, that may threaten their validity or influence the interpretation of their results. To assist in the critical evaluation of a vast body of literature and contribute to future study design, we outline and propose solutions to biases that can occur across different categories of observational studies of COVID-19. We consider potential biases that could occur in five categories of studies: (1) cross-sectional seroprevalence, (2) longitudinal seroprotection, (3) risk factor studies to inform interventions, (4) studies to estimate the secondary attack rate, and (5) studies that use secondary attack rates to make inferences about infectiousness and susceptibility.

A Subgroup of Patients With Hospital-acquired Pneumonia Do Not Require Broad-spectrum Gram-negative Antimicrobial Coverage.

Among 200 patients developing hospital-acquired pneumonia (HAP) outside the intensive care unit, 61% were treated empirically without broad-spectrum Gram-negative coverage, with clinical cure in 69.7%. Lower disease severity markers (systemic inflammatory response syndrome, hypoxia, tachypnoea, neutrophilia) and the absence of diabetes mellitus and prior doxycycline treatment (but not the time to HAP onset) identified patients not requiring broad-spectrum Gram-negative coverage.

Non-typeable Haemophilus influenzae-associated early pregnancy loss: an emerging neonatal and maternal pathogen.

OBJECTIVES: There is increasing evidence indicating an association between invasive non-typeable Haemophilus influenzae (NTHi) infection in pregnancy and early pregnancy loss. As the diagnosis relies on microbiological investigation of post-mortem placental and foetal samples, a significant proportion of NTHi-related pregnancy loss remains unrecognised. To better characterise NTHi in septic abortion, we report NTHi cases associated with early pregnancy loss. METHODS: We reviewed all post-mortems at <24 weeks gestation with histologically proven acute chorioamnionitis on placental histology and enrolled cases with at least one matched foetal and placental sample culture positive for NTHi. The study was approved by the NHS Lothian Caldicott Guardian. RESULTS: In our cohort, invasive NTHi has accounted for 20% of infections associated with early pregnancy loss prior to 24 weeks gestation. All patients were young and healthy pregnant women at < 20 weeks' gestation who presented with abdominal pain, PV bleed /discharge and were septic at the time of presentation. One patient with previous history of miscarriage who presented with cervical incompetence had more severe pathology suggestive of early intrauterine pneumonia. CONCLUSION: The burden of invasive NTHi disease in early pregnancy loss is likely to be much larger than currently recognised. NTHi should be considered in pregnant women presenting with abdominal pain and PV bleed/discharge in whom clinical signs of sepsis are present. Active surveillance should be considered in this patient group including septic abortion to capture the true prevalence of this emerging pathogen to inform preventative and therapeutic approaches.

Investigation of a healthcare-associated Candida tropicalis candidiasis cluster in a haematology unit and a systematic review of nosocomial outbreaks.

BACKGROUND: Non-albicans Candida spp. are an emerging cause of hospital-acquired bloodstream infections, associated with high mortality due to the challenges in diagnosis and delayed treatment. OBJECTIVES: We aimed to investigate a cluster of healthcare-associated invasive candidiasis caused by C tropicalis and review the literature of healthcare-associated outbreaks or clusters caused by C tropicalis. METHODS: An investigation was performed to determine clinical presentation, treatment outcomes and the factors contributing to C tropicalis candidemia occurrence. We searched the Medline database via PubMed and Ovid using the keywords of "Candida tropicalis" combined with "outbreak" or "clustering" or "clusters," and we limited the search to studies conducted from January 1989 to January 2019. RESULTS: We report two related cases of C tropicalis candidemia among patients with AML following a period of neutropenia, who had erythematous skin rash as a first manifesting sign of candidiasis. C tropicalis was isolated from blood and skin cultures of both patients, which were identical by pulsed-field gel electrophoresis typing. Our systematic review of outbreaks caused by C tropicalis suggests that (a) most reported outbreaks have occurred in neonatal and adult ICUs; (b) patients who receive total parenteral therapy, antibiotics and those who have indwelling catheters and recent surgery are at high risk of infection; and (c) environmental and healthcare personnel surveillance suggest that cross-contamination is a major risk factor. CONCLUSION: Control of nosocomial outbreaks caused by C tropicalis should include better infection control measures, education of healthcare professionals especially working in adult and neonatal intensive care and haematology units.

Current mentorship practices in the training of the next generation of clinical microbiology and infectious disease specialists: an international cross-sectional survey.

The purpose of this study was to describe the current practice of mentorship in clinical microbiology (CM) and infectious diseases (ID) training, to identify possible areas for improvement and to assess the factors that are associated with satisfactory mentorship. An international cross-sectional survey containing 35 questions was answered by 317 trainees or specialists who recently completed clinical training. Overall, 179/317 (56%) trainees were satisfied with their mentors, ranging from 7/9 (78%) in non-European countries, 39/53 (74%) in Northern Europe, 13/22 (59%) in Eastern Europe, 61/110 (56%) in Western Europe, 37/76 (49%) in South-Western Europe to 22/47 (47%) in South-Eastern Europe. However, only 115/317 (36%) respondents stated that they were assigned an official mentor during their training. In multivariable logistic regression analysis, the satisfaction of trainees was significantly associated with having a mentor who was a career model (OR 6.4, 95%CI 3.5-11.7), gave constructive feedback on work performance (OR 3.3, 95%CI 1.8-6.2), and knew the family structure of the mentee (OR 5.5, 95%CI 3.0-10.1). If trainees felt overburdened, 70/317 (22%) felt that they could not talk to their mentors. Moreover, 67/317 (21%) stated that they could not talk to their mentor when unfairly treated and 59/317 (19%) felt uncertain. Training boards and authorities responsible for developing and monitoring CM&ID training programmes should invest in the development of high-quality mentorship programmes for trainees in order to contribute to the careers of the next generation of professionals.