Personal historical perspective of HIV: part 11.

All animal life on earth is thought to have a common origin and have common genetic mechanisms. Evolution has enabled differentiation of species. Pathogens likewise have evolved within various species and mostly come to a settled dynamic equilibrium such that co-existence results (pathogens ideally should not kill their hosts). Problems arise when pathogens jump species because the new host had not developed any resistance. These infections from related species are known as zoonoses. COVID-19 is the latest example of a virus entering another species but HIV (and various strains of influenza) were previous examples. HIV entered the human population from monkeys in Africa. These two papers outline the underlying principle of HIV and the differing epidemiologies in Africa, the USA and in Edinburgh. The underlying immunosuppression of HIV in Africa was initially hidden behind common infections and HIV first came to world awareness in focal areas of the USA as a disease seemingly limited to gay males. The epidemic of intravenous drug abuse in Edinburgh was associated with overlapping epidemics of bloodborne viruses like hepatitis B, hepatitis C and HIV.

COVID-19 in South Korea.

A novel coronavirus (severe acute respiratory syndrome-CoV-2) that initially originated from Wuhan, China, in December 2019 has already caused a pandemic. While this novel coronavirus disease (COVID-19) frequently induces mild diseases, it has also generated severe diseases among certain populations, including older-aged individuals with underlying diseases, such as cardiovascular disease and diabetes. As of 31 March 2020, a total of 9786 confirmed cases with COVID-19 have been reported in South Korea. South Korea has the highest diagnostic rate for COVID-19, which has been the major contributor in overcoming this outbreak. We are trying to reduce the reproduction number of COVID-19 to less than one and eventually succeed in controlling this outbreak using methods such as contact tracing, quarantine, testing, isolation, social distancing and school closure. This report aimed to describe the current situation of COVID-19 in South Korea and our response to this outbreak.

Impact of the First Year of the COVID-19 Pandemic on Pediatric Emergency Department Attendance in a Tertiary Center in South Italy: An Interrupted Time-Series Analysis.

BACKGROUND: The evidence shows a reduction in pediatric emergency department (PED) flows during the early stages of the COVID-19 pandemic. Using interrupted time-series analysis, we evaluated the impact of different stages of the pandemic response on overall and cause-specific PED attendance at a tertiary hospital in south Italy. Our methods included evaluations of total visits, hospitalizations, accesses for critical illnesses and four etiological categories (transmissible and non-transmissible infectious diseases, trauma and mental-health) during March-December 2020, which were compared with analogous intervals from 2016 to 2019; the pandemic period was divided into three segments: the "first lockdown" (FL, 9 March-3 May), the "post-lockdown" (PL, 4 May-6 November) and the "second lockdown" (SL, 7 November-31 December). Our results showed that attendance dropped by a mean of 50.09% during the pandemic stages, while hospitalizations increased. Critical illnesses decreased during FL (incidence rate ratio -IRR- 0.37, 95% CI 0.13, 0.88) e SL (IRR 0.09, 95% CI 0.01, 0.74) and transmissible disease related visits reduced more markedly and persistently (FL: IRR 0.18, 95% CI 0.14, 0.24; PL: IRR 0.20, 95% CI 0.13, 0.31, SL: IRR 0.17, 95% CI 0.10, 0.29). Non-infectious diseases returned to pre-COVID-19 pandemic levels by PL. We concluded that that the results highlight the specific effect of the late 2020 containment measures on transmissible infectious diseases and their burden on pediatric emergency resources. This evidence can inform resource allocation and interventions to mitigate the impact of infectious diseases on pediatric populations and the health-care system.

Rhinocladiella mackenziei cerebral phaeohyphomycosis with a definitive outcome.

A right-handed man in his early 60s with hypertension controlled by a single prescription medication presented with left-sided heaviness and intermittent right occipital headache. Initial diagnostic workup was unremarkable. CT revealed an enhancing lesion located in the right parietal lobe, with mild mass effect on the right occipital horn, indicative of a brain abscess. The patient was initially treated with a course of empirical antibiotics, including ceftriaxone, vancomycin, metronidazole and dexamethasone. The neurosurgery team aspirated the abscess the following day and extracted yellow pus that was sampled for bacterial and fungal cultures. These cultures returned positive for Rhinocladiella mackenziei, prompting a discontinuation of the empirical antibiotics and initiation of intravenous liposomal amphotericin B for 4 weeks. Intravenous posaconazole was added to the patient's existing therapy regimen, which was substituted with oral isavuconazole on discharge. The patient continues to take isavuconazole, and follow-up imaging has demonstrated regression of the abscess.

The indirect impacts of nonpharmacological COVID-19 control measures on other infectious diseases in Yinchuan, Northwest China: a time series study.

BACKGROUND: Various nonpharmaceutical interventions (NPIs) against COVID-19 continue to have an impact on socioeconomic and population behaviour patterns. However, the effect of NPIs on notifiable infectious diseases remains inconclusive due to the variability of the disease spectrum, high-incidence endemic diseases and environmental factors across different geographical regions. Thus, it is of public health interest to explore the influence of NPIs on notifiable infectious diseases in Yinchuan, Northwest China. METHODS: Based on data on notifiable infectious diseases (NIDs), air pollutants, meteorological data, and the number of health institutional personnel in Yinchuan, we first fitted dynamic regression time series models to the incidence of NIDs from 2013 to 2019 and then estimated the incidence for 2020. Then, we compared the projected time series data with the observed incidence of NIDs in 2020. We calculated the relative reduction in NIDs at different emergency response levels in 2020 to identify the impacts of NIPs on NIDs in Yinchuan. RESULTS: A total of 15,711 cases of NIDs were reported in Yinchuan in 2020, which was 42.59% lower than the average annual number of cases from 2013 to 2019. Natural focal diseases and vector-borne infectious diseases showed an increasing trend, as the observed incidence in 2020 was 46.86% higher than the estimated cases. The observed number of cases changed in respiratory infectious diseases, intestinal infectious diseases and sexually transmitted or bloodborne diseases were 65.27%, 58.45% and 35.01% higher than the expected number, respectively. The NIDs with the highest reductions in each subgroup were hand, foot, and mouth disease (5854 cases), infectious diarrhoea (2157 cases) and scarlet fever (832 cases), respectively. In addition, it was also found that the expected relative reduction in NIDs in 2020 showed a decline across different emergency response levels, as the relative reduction dropped from 65.65% (95% CI: -65.86%, 80.84%) during the level 1 response to 52.72% (95% CI: 20.84%, 66.30%) during the level 3 response. CONCLUSIONS: The widespread implementation of NPIs in 2020 may have had significant inhibitory effects on the incidence of respiratory infectious diseases, intestinal infectious diseases and sexually transmitted or bloodborne diseases. The relative reduction in NIDs during different emergency response levels in 2020 showed a declining trend as the response level changed from level 1 to level 3. These results can serve as essential guidance for policy-makers and stakeholders to take specific actions to control infectious diseases and protect vulnerable populations in the future.

Diagnosis of Multisystem Inflammatory Syndrome in Children by a Whole-Blood Transcriptional Signature.

BACKGROUND: To identify a diagnostic blood transcriptomic signature that distinguishes multisystem inflammatory syndrome in children (MIS-C) from Kawasaki disease (KD), bacterial infections, and viral infections. METHODS: Children presenting with MIS-C to participating hospitals in the United Kingdom and the European Union between April 2020 and April 2021 were prospectively recruited. Whole-blood RNA Sequencing was performed, contrasting the transcriptomes of children with MIS-C (n = 38) to those from children with KD (n = 136), definite bacterial (DB; n = 188) and viral infections (DV; n = 138). Genes significantly differentially expressed (SDE) between MIS-C and comparator groups were identified. Feature selection was used to identify genes that optimally distinguish MIS-C from other diseases, which were subsequently translated into RT-qPCR assays and evaluated in an independent validation set comprising MIS-C (n = 37), KD (n = 19), DB (n = 56), DV (n = 43), and COVID-19 (n = 39). RESULTS: In the discovery set, 5696 genes were SDE between MIS-C and combined comparator disease groups. Five genes were identified as potential MIS-C diagnostic biomarkers (HSPBAP1, VPS37C, TGFB1, MX2, and TRBV11-2), achieving an AUC of 96.8% (95% CI: 94.6%-98.9%) in the discovery set, and were translated into RT-qPCR assays. The RT-qPCR 5-gene signature achieved an AUC of 93.2% (95% CI: 88.3%-97.7%) in the independent validation set when distinguishing MIS-C from KD, DB, and DV. CONCLUSIONS: MIS-C can be distinguished from KD, DB, and DV groups using a 5-gene blood RNA expression signature. The small number of genes in the signature and good performance in both discovery and validation sets should enable the development of a diagnostic test for MIS-C.

Axial spondylarthritis following COVID-19 infection.

Although SARS-CoV-2 syndrome primarily affects the lungs, systemic manifestations have been reported. New rheumatic immune-mediated inflammatory diseases have been reported following SARS-CoV-2 infection. We present a case of a woman in her mid-30s who developed inflammatory back pain due to bilateral sacroiliitis with erosions after contracting SARS-CoV-2 infection. Her inflammatory markers on presentation were normal. MRI of the sacroiliac joints demonstrated bone marrow oedema and erosive changes in both sacroiliac joints. As the patient was intolerant to non-steroidal anti-inflammatory drugs, adalimumab 40 mg subcutaneous (SC) injection was administered, which improved her symptoms in 8 weeks. However, due to the drug's side effects, SC adalimumab was switched to intravenous infliximab. The patient is currently tolerating her intravenous infliximab well and has experienced significant improvement in her symptoms. We reviewed the current literature on the prevalence of axial spondyloarthropathy after SARS-CoV-2 infection.

Molecular detection of monkeypox and related viruses: challenges and opportunities.

The recent widespread emergence of monkeypox (mpox), a rare and endemic zoonotic disease by monkeypox virus (MPXV), has made global headlines. While transmissibility (R0 ≈ 0.58) and fatality rate (0-3%) are low, as it causes prolonged morbidity, the World Health Organization has declared monkeypox as a public health emergency of international concern. Thus, effective containment and disease management require quick and efficient detection of MPXV. In this bioinformatic overview, we summarize the numerous molecular tests available for MPXV, and discuss the diversity of genes and primers used in the polymerase chain reaction-based detection. Over 90 primer/probe sets are used for the detection of poxviruses. While hemagglutinin and A-type inclusion protein are the most common target genes, tumor necrosis factor receptor and complement binding protein genes are frequently used for distinguishing Clade I and Clade II of MPXV. Problems and possibilities in the detection of MPXV have been discussed.

Monoclonal antibodies for prophylaxis and therapy of respiratory syncytial virus, SARS-CoV-2, human immunodeficiency virus, rabies and bacterial infections: an update from the World Association of Infectious Diseases and Immunological Disorders and the Italian Society of Antinfective Therapy.

Monoclonal antibodies (mABs) are safe and effective proteins produced in laboratory that may be used to target a single epitope of a highly conserved protein of a virus or a bacterial pathogen. For this purpose, the epitope is selected among those that play the major role as targets for prevention of infection or tissue damage. In this paper, characteristics of the most important mABs that have been licensed and used or are in advanced stages of development for use in prophylaxis and therapy of infectious diseases are discussed. We showed that a great number of mABs effective against virus or bacterial infections have been developed, although only in a small number of cases these are licensed for use in clinical practice and have reached the market. Although some examples of therapeutic efficacy have been shown, not unlike more traditional antiviral or antibacterial treatments, their efficacy is significantly greater in prophylaxis or early post-exposure treatment. Although in many cases the use of vaccines is more effective and cost-effective than that of mABs, for many infectious diseases no vaccines have yet been developed and licensed. Furthermore, in emergency situations, like in epidemics or pandemics, the availability of mABs can be an attractive adjunct to our armament to reduce the impact. Finally, the availability of mABs against bacteria can be an important alternative, when multidrug-resistant strains are involved.

Optimal Dosing and Timing of High-Dose Corticosteroid Therapy in Hospitalized Patients With COVID-19: Study Protocol for a Retrospective Observational Multicenter Study (SELECT).

BACKGROUND: In hospitalized patients with COVID-19, the dosing and timing of corticosteroids vary widely. Low-dose dexamethasone therapy reduces mortality in patients requiring respiratory support, but it remains unclear how to treat patients when this therapy fails. In critically ill patients, high-dose corticosteroids are often administered as salvage late in the disease course, whereas earlier administration may be more beneficial in preventing disease progression. Previous research has revealed that increased levels of various biomarkers are associated with mortality, and whole blood transcriptome sequencing has the ability to identify host factors predisposing to critical illness in patients with COVID-19. OBJECTIVE: Our goal is to determine the most optimal dosing and timing of corticosteroid therapy and to provide a basis for personalized corticosteroid treatment regimens to reduce morbidity and mortality in hospitalized patients with COVID-19. METHODS: This is a retrospective, observational, multicenter study that includes adult patients who were hospitalized due to COVID-19 in the Netherlands. We will use the differences in therapeutic strategies between hospitals (per protocol high-dose corticosteroids or not) over time to determine whether high-dose corticosteroids have an effect on the following outcome measures: mechanical ventilation or high-flow nasal cannula therapy, in-hospital mortality, and 28-day survival. We will also explore biomarker profiles in serum and bronchoalveolar lavage fluid and use whole blood transcriptome analysis to determine factors that influence the relationship between high-dose corticosteroids and outcome. Existing databases that contain routinely collected electronic data during ward and intensive care admissions, as well as existing biobanks, will be used. We will apply longitudinal modeling appropriate for each data structure to answer the research questions at hand. RESULTS: As of April 2023, data have been collected for a total of 1500 patients, with data collection anticipated to be completed by December 2023. We expect the first results to be available in early 2024. CONCLUSIONS: This study protocol presents a strategy to investigate the effect of high-dose corticosteroids throughout the entire clinical course of hospitalized patients with COVID-19, from hospital admission to the ward or intensive care unit until hospital discharge. Moreover, our exploration of biomarker and gene expression profiles for targeted corticosteroid therapy represents a first step towards personalized COVID-19 corticosteroid treatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT05403359; https://clinicaltrials.gov/ct2/show/NCT05403359. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/48183.

How do psychobehavioural variables shed light on heterogeneity in COVID-19 vaccine acceptance? Evidence from United States general population surveys on a probability panel and social media.

OBJECTIVES: To (1) understand what behaviours, beliefs, demographics and structural factors predict US adults' intention to get a COVID-19 vaccination, (2) identify segments of the population ('personas') who share similar factors predicting vaccination intention, (3) create a 'typing tool' to predict which persona people belong to and (4) track changes in the distribution of personas over time and across the USA. DESIGN: Three surveys: two on a probability-based household panel (NORC's AmeriSpeak) and one on Facebook. SETTING: The first two surveys were conducted in January 2021 and March 2021 when the COVID-19 vaccine had just been made available in the USA. The Facebook survey ran from May 2021 to February 2022. PARTICIPANTS: All participants were aged 18+ and living in the USA. OUTCOME MEASURES: In our predictive model, the outcome variable was self-reported vaccination intention (0-10 scale). In our typing tool model, the outcome variable was the five personas identified by our clustering algorithm. RESULTS: Only 1% of variation in vaccination intention was explained by demographics, with about 70% explained by psychobehavioural factors. We identified five personas with distinct psychobehavioural profiles: COVID Sceptics (believe at least two COVID-19 conspiracy theories), System Distrusters (believe people of their race/ethnicity do not receive fair healthcare treatment), Cost Anxious (concerns about time and finances), Watchful (prefer to wait and see) and Enthusiasts (want to get vaccinated as soon as possible). The distribution of personas varies at the state level. Over time, we saw an increase in the proportion of personas who are less willing to get vaccinated. CONCLUSIONS: Psychobehavioural segmentation allows us to identify why people are unvaccinated, not just who is unvaccinated. It can help practitioners tailor the right intervention to the right person at the right time to optimally influence behaviour.

Surveillance of Viral Respiratory Infections in the Neonatal Intensive Care Unit-Evolution in the Last 5 Years.

Viral respiratory infections (VRIs) in very low birthweight infants can be associated with high rates of morbidity. The COVID-19 pandemic has exerted a strong impact on viral circulation. The purpose of this study is to report on VRIs during NICU admission in infants below 32 weeks' gestation and compare data collected between the pre-and post-COVID-19 pandemic periods. A prospective surveillance study was conducted at a tertiary NICU between April 2016 and June 2022. The COVID-19 post-pandemic period was established as being from March 2020 onwards. Respiratory virus detection was performed by real-time multiplex PCR assays in nasopharyngeal aspirates (NPAs). A total of 366 infants were enrolled. There were no statistical differences between periods regarding infants' birth weight, gestational age, gender distribution, or rates of bronchopulmonary dysplasia. Among the 1589 NPA collected during the pre-COVID-19 period, 8.9% were positive, and among the 1147 NPA collected during the post-pandemic period, only 3% were positive (p < 0.005). The type of viruses detected did not differ according to the study period (pre-COVID19 vs. post-COVID-19): rhinovirus (49.5% vs. 37.5%), adenovirus (22.6% vs. 25%), and human coronavirus (12.9% vs. 16.7%). SARS-CoV-2 was only detected in one patient. In conclusion, the viral profile causing VRI during the pre-COVID-19 and post-COVID-19 era was similar. However, the total number of VRI dropped significantly, most probably due to the global increase in infection prevention measures.

Analysis of avian disease transmission risk and prevention measures in China

Many zoonotic diseases are found in wild animals and present a serious risk to human health, in particularly the virus carried by birds flying freely around the world is hard to control. There are three main bird migration routes which cover the most areas of China. It is important to investigate and fully understand the types of avian transmitted diseases in key areas on the bird migration routines and its impacts on both birds and human health. However, no literature is available in how about the risk of virus carried by migrating birds, and how to predict and reduce this risk of virus spreading to human being so far. In this paper, we first reviewed the main pathogen types carried by birds, including coronaviruses, influenza viruses, parasites, Newcastle disease virus (NDV), etc., and then discussed the spread risk of avian viruses to human being and animals in key areas of biosafety prevention. We also analyzed and discussed the risk of cross-spread of diseases among different bird species in nature reserves located on bird migration routes which provide sufficient food sources for migratory birds and attract numerous birds. Diseases transmitted by wild birds pose a serious threat to poultry farms, where high density of poultry may become avian influenza virus (AIV) reservoirs, cause a risk of avian influenza outbreaks. Airports are mostly built in suburban areas or remote areas with good ecological environment. There are important transit places for bird migration and densely populated areas, which have serious risk of disease transmission. Finally, this paper puts forward the following prevention suggestions from three aspects. First, establish and improve the monitoring and prediction mechanism of migratory birds, and use laser technology to prevent contact between wild birds and poultry. Second, examine and identify virus types carried by birds in their habitats and carry out vaccination. Third, protect the ecological environment of bird habitat, and keep wild birds in their natural habitat, so as to reduce the contact between wild birds and human and poultry, and thus reduce the risk of virus transmission.

AI for Drug Repurposing in the Pandemic Response

Given the time criticality of finding treatments for the novel COVID-19 pandemic disease, drug repurposing has proved to be a vital strategy as the first response while de novo drug and vaccine developments are underway. Furthermore, Artificial Intelligence (AI) has also accelerated drug development in general. Key desirable features of AI that support a rapid and sustained response along the pandemic timeline include technical flexibility and efficiency (i.e. speed, resource-efficiency, algorithm adaptability), and clinical applicability and acceptability (i.e. scientific rigor, physiological applicability and practical implementation of proposed drugs). This chapter reviews a selection of AI-based applications used in drug development targeting COVID-19, including IDentif.AI-a small data platform for a rapid identification of optimal drug combinations, to illustrate the potential of AI in drug repurposing. The benefits and limitations of using Real-World Data are also discussed. The response to the COVID-19 pandemic has offered multiple learnings which highlight the need to strengthen both short- and long-term strategies in developing AI technologies, scientific and regulatory frameworks as well as worldwide collaborations to enable effective preparedness for future epidemic and pandemic risks. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.

Introduction to the Special Issue on Immunology

For many science teachers and science teacher educators, COVID-19 made clear a need to focus on the socioscientific issues. [...]it subverts and undercuts the goals of having inquiry in the standards as it was intended. [...]the lack of ability to address things outside the standards leads to a lesser engagement with inquiry as it becomes more a poorly implemented default than a carefully crafted learning objective. [...]it is one with no explicit link to the NGSS. [...]teachers have made a choice either to teach about IDE outside the content mandated by the NGSS-perhaps under the cover of inquiry-or to avoid instruction on the most relevant and immediate socioscientific issue in students' lives. [...]current events have prompted a resurgence of this discussion (Zucker and Noyce 2020). [...]examination and discussion of how the NGSS might be understood or implemented in more adaptive ways is both timely and productive for scholars and policy makers who have a vested interest in the sufficiency or potential shortcomings of the dominant set of science education standards.