COVID-19 Respiratory Infections Research Articles

A-240 Validation of the OSOM Flu SARS-CoV-2 Combo Home Test

Abstract Background COVID-19 and Influenza respiratory infections often cause similar symptoms, however, treatment is different for each infection. Delay in diagnosis can be fatal in some cases, therefore rapid detection and differentiation are critical for appropriate medical treatment. The OSOM Flu SARS-CoV-2 Combo Home Test is a lateral flow immunoassay intended for the qualitative and differential detection of nucleocapsid protein from SARS-CoV-2 and influenza A/B proteins using self-collected anterior nasal swab samples (self-collection is only recommended for those 14 years of age and older). An interpretation card, included with the test, is used to reliably distinguish among possible testing results. Methods A prospective study was conducted at multiple geographically distinct sites in the U.S during the 2023-2024 season for the validation of the OSOM Flu SARS-CoV-2 Combo Home Test to detect SARS-CoV-2/Flu A/Flu B in self-collected anterior nasal swab samples. The study evaluated the performance in symptomatic individuals only. A total of 703 prospective samples were evaluable for SARS. For Flu A/B, four additional subject samples were unevaluable due to comparator results not being available and a total of 699 samples were included in the data analysis. The comparator tests were FDA 510(k)-cleared molecular assays. Results Influenza A was detected with a sensitivity of 93.1% (95% CI: 84.8%-97.0%) and a specificity of 99.5% (95% CI: 98.6% - 99.8%). Influenza B was detected with a sensitivity of 89.1% (95% CI: 77.0% - 95.3%) and a specificity of 99.7% (95% CI: 98.9% - 99.9%). SARS CoV-2 was detected with a sensitivity of 87.0% (95% CI 78.6% - 92.4%) and a specificity of 99.1% (95% CI: 97.9% - 99.6%) when Ct values are standardized and 10% of samples are considered low positives, having a Ct value of ≥ 30. Conclusions With respiratory infections often showing indistinguishable symptoms and the possibility of co infection, lowering the testing hurdles for individuals to be able to perform a rapid differential test at home without the aid from a healthcare worker is the most effective way to mitigate spread and patient management from a public health perspective. Comparing the OSOM Flu SARS-CoV-2 Combo Home test to the FDA cleared comparators in a clinical setting, the OSOM Flu SARS-CoV-2 Combo Home test retains acceptable sensitivity and specificity. Using self-collected anterior nasal swabs which are minimally invasive alongside the low cost of a lateral flow immunochromatographic assay remains the most effective way to perform the serial screening testing recommended by the CDC in situations where transmission and severe outcome risk is high.

Poor stress resilience in adolescence predicts higher risk of severe COVID-19 and other respiratory infections: A prospective cohort study of 1.4 million Swedish men

ObjectivesTo investigate the associations between stress resilience in late adolescence and later risk of severe COVID-19 and other lower respiratory infections. A secondary aim was to examine potential confounding between low cardiorespiratory fitness (CRF) and stress resilience in relation to respiratory infection. MethodsWe conducted a registry-based cohort study of 1.4 million Swedish men, undergoing military conscription between 1968 and 2005. All were assessed by a psychologist for stress resilience, receiving a score between 1 and 9. The outcomes were hospitalization or death due to COVID-19 from March 2020 to September 2021 and hospitalization due to bacterial or viral pneumonia from conscription until January 2020. A secondary aim was to examine potential confounding between low cardiorespiratory fitness (CRF) and stress resilience in relation to respiratory infection. ResultsPoor stress resilience in late adolescence is associated with later risk of severe lower respiratory infections. Using a high resilience score as the reference, the hazard ratio (95 % CI) for death due to COVID-19 for the lowest scores was 1.49 (1.01–2.18) adjusted for CRF and other confounders. The corresponding adjusted hazard ratios for hospitalization due to bacterial pneumonia were 2.28 (2.03–2.57) and for viral pneumonia 1.92 (1.33–2.79). No significant interaction was seen between stress resilience and CRF in the analysis. ConclusionsPoor stress resilience is a prospective factor for severe COVID-19 as well as for bacterial and viral respiratory pneumonia endpoints, independent of CRF. These findings imply an effect of late adolescent stress resilience on the immune system later in life.

Effectiveness of nutritional supplements (vitamins, minerals, omega-3, and probiotics) in preventing and treating COVID-19 and viral respiratory infections

BackgroundViral respiratory infections (VRIs) continue to be among the most common illnesses and are known to be one of the main reasons of medical consultations worldwide.COVID-19 remains a major public concern and a threat to global health. The current focus lies on the pivotal role of the human host's immunologic response in combating viral threats.This critical review aims to examine the current evidence on the potential benefit of nutritional supplements in the prevention and treatment of COVID-19 and viral respiratory infections (VRIs). MethodsThe study was performed in the Google-Scholar and PubMed databases with a main emphasis on publications between January 2000 and September 2023. Consequently, a total of 202 articles were included in this literature review, distributed as follows: 62 meta-analyses and systematic reviews, 20 randomized clinical trials, 11 clinical trials, 28 observational cohorts and 81 others. Of these, 44 % were published between 2020 and 2023. ResultsThe research indicates that Vitamin C may have a mitigating effect on VRIs, whereas a deficiency in Vitamin D might heighten susceptibility to COVID-19. Understanding the roles of Vitamins A, B, and E is hampered by limited data availability. Zinc supplementation and probiotics emerge as potential preventive measures for both COVID-19 and VRIs, with selenium and magnesium demonstrating promising results in treating VRIs. The recommendation for omega-3 fatty acid supplementation for COVID-19 treatment awaits further evidence. ConclusionCurrently, there is insufficient clinical evidence to definitively establish the efficacy of vitamin, mineral, probiotic and/or omega-3 supplementation for combating COVID-19 and VRIs.

Mortality Associated With Infectious Diseases in Dutch Nursing Homes

BackgroundAlthough older people in nursing homes have a larger susceptibility to infectious diseases, the extent to which infectious diseases contribute to their mortality is unknown. Therefore, we quantified the associations between seasonal infectious diseases and all-cause mortality in Dutch nursing homes. MethodsWe analyzed time series (January 2009 to December 2021) of the weekly sentinel surveillance of infectious diseases in Dutch nursing homes. A generalized linear model with binomial distribution and identity link was used to associate the proportion of all-cause mortality with the incidence of infections: COVID-19 (2020–2021), gastroenteritis (GE), influenza-like illness (ILI), and lower respiratory tract infections (LRTIs) at 0- to 4-week time-lags (mortality incidence at 0 to 4 weeks after infections incidence). ResultsOver 13 years, 81 nursing homes participated, with 20 to 35 homes each year (mean: 26). A total of 11,555 all-cause deaths occurred over 1,864,667 resident weeks, averaging a mortality incidence of 6.2 per 1000 resident weeks. All 4 tested infectious diseases exhibited a significant association with all-cause mortality in nursing homes (P ≤ .01). Collectively, these infectious diseases were associated with 18.6% (95% CI, 17.8%–19.3%) of all deaths. The association between mortality and ILI was significant in 7 of 12 ILI seasons. Yearly mortality associated with the specific infectious diseases was as follows: LRTI (10.2%; 95% CI, 9.6%–10.8%), ILI (8.2%; 95% CI, 7.5%–8.9%) (over the 7 of 12 significant seasons), COVID-19 (6.5%; 95% CI, 5.4%–7.7%) (over 2019–2021 as there was no previous SARS-CoV-2 circulation), and GE (2.3%; 95% CI, 2.0%–2.5%). Conclusion and ImplicationsIn nursing homes, the occurrence of seasonal respiratory and gastrointestinal infections is associated with nearly one-fifth of all-cause deaths. Although infection prevention and surveillance may already be performed in some nursing homes, it is vital to implement, and enhance targeted strategies like (hand) hygiene protocols, environmental cleaning practices, reducing droplet and aerosol transmission, and vaccination to effectively address specific infections.

Psychological and psychosocial determinants of COVID related face covering behaviours: A systematic review.

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has resulted in illness, deaths and societal disruption on a global scale. Societies have implemented various control measures to reduce transmission of the virus and mitigate its impact. Individual behavioural changes are crucial to the successful implementation of these measures. One commonly recommended measure to limit risk of infection is face covering. It is important to identify those factors that can predict the uptake and maintenance of face covering. We aimed to identify and synthesise the evidence on malleable psychological and psychosocial factors that determine uptake and adherence to face covering aimed at reducing the risk of infection or transmission of COVID-19. We searched various literature sources including electronic databases (Medline ALL, Child Development & Adolescent Studies, ERIC, PsycInfo, CINAHL & Web of Science), web searches, conference proceedings, government reports, other repositories of literature and grey literature. The search strategy was built around three concepts of interest including (1) context (terms relating to COVID19), (2) behaviour of interest and (3) terms related to psychological and psychosocial determinants of COVID Health-Related Behaviours and adherence or compliance with face covering, to capture malleable determines. Searches capture studies up until October 2021. Eligibility criteria included observational studies (both retrospective and prospective) and experimental studies that measure and report malleable psychological and psychosocial determinants and handwashing at an individual level, amongst the general public. Screening was supported by the Cochrane Crowd. Studies titles and abstracts were screened against the eligibility criteria by three independent screeners. Following this, all potentially relevant studies were screened at full-text level by the research team. All conflicts between screeners were resolved by discussion between the core research team. All data extraction was managed in EPPI-Reviewer software. All eligible studies, identified through full-text screening were extracted by one author. We extracted data on study information, population, determinant, behaviour and effects. A second author checked data extraction on 20% of all included papers. All conflicts were discussed by the two authors until consensus was reached. We assessed methodological quality of all included studies using an adapted version of the Joanna Briggs Institute Quality appraisal tool for cross-sectional studies. Our initial searches yielded 23,587 results, of which 23 were included in this review. The included studies were cross-sectional in design, came from nine countries and had a combined sample of 54,401 participants. The vast majority of studies had samples from the general public, with five of the studies focusing on specific samples. All included studies considered people over the age of 18. The quality of 10 of the studies was rated as unclear, 10 were rated as low, and 3 rated high risk of bias, predominately due to lack of reporting of recruitment, sample characteristics and methodology. Ten studies were included in the meta-analysis and 16 in the narrative synthesis. Findings from the meta-analysis indicated that knowledge of COVID-19 (0.341, 95% confidence interval [CI] = 0.06, 0.530, I 2 = 100%) was the malleable determinant most associated with face covering behaviour. Perceived susceptibility of COVID-19 (r = 0.088, 95% CI = -0.004, 0.180, I 2 = 80%) and COVID-related worry and anxiety (r = 0.064, 95% CI = -0.066, 0.191, I 2 = 93% had little to no effect on face covering behaviour. In the narrative synthesis, the strongest association was found between perceived benefits and effectiveness of behaviours and mask wearing behaviour. Understanding the effects of various malleable determinants on COVID-related face covering can aid in the development and implementation of interventions and public health campaigns to promote face covering behaviour in potential new waves of COVID-19 or other respiratory infections. Knowledge of COVID and perceived benefits of face coverings warrant further consideration in future research and policy.

Detection of Common Respiratory Infections, Including COVID-19, Using Consumer Wearable Devices in Health Care Workers: Prospective Model Validation Study.

The early detection of respiratory infections could improve responses against outbreaks. Wearable devices can provide insights into health and well-being using longitudinal physiological signals. The purpose of this study was to prospectively evaluate the performance of a consumer wearable physiology-based respiratory infection detection algorithm in health care workers. In this study, we evaluated the performance of a previously developed system to predict the presence of COVID-19 or other upper respiratory infections. The system generates real-time alerts using physiological signals recorded from a smartwatch. Resting heart rate, respiratory rate, and heart rate variability measured during the sleeping period were used for prediction. After baseline recordings, when participants received a notification from the system, they were required to undergo testing at a Northwell Health System site. Participants were asked to self-report any positive tests during the study. The accuracy of model prediction was evaluated using respiratory infection results (laboratory results or self-reports), and postnotification surveys were used to evaluate potential confounding factors. A total of 577 participants from Northwell Health in New York were enrolled in the study between January 6, 2022, and July 20, 2022. Of these, 470 successfully completed the study, 89 did not provide sufficient physiological data to receive any prediction from the model, and 18 dropped out. Out of the 470 participants who completed the study and wore the smartwatch as required for the 16-week study duration, the algorithm generated 665 positive alerts, of which 153 (23.0%) were not acted upon to undergo testing for respiratory viruses. Across the 512 instances of positive alerts that involved a respiratory viral panel test, 63 had confirmed respiratory infection results (ie, COVID-19 or other respiratory infections detected using a polymerase chain reaction or home test) and the remaining 449 had negative upper respiratory infection test results. Across all cases, the estimated false-positive rate based on predictions per day was 2%, and the positive-predictive value ranged from 4% to 10% in this specific population, with an observed incidence rate of 198 cases per week per 100,000. Detailed examination of questionnaires filled out after receiving a positive alert revealed that physical or emotional stress events, such as intense exercise, poor sleep, stress, and excessive alcohol consumption, could cause a false-positive result. The real-time alerting system provides advance warning on respiratory viral infections as well as other physical or emotional stress events that could lead to physiological signal changes. This study showed the potential of wearables with embedded alerting systems to provide information on wellness measures.

Psychological and psychosocial determinants of COVID-related handwashing behaviours: A systematic review.

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has resulted in illness, deaths and societal disruption on a global scale. Societies have implemented various control measures to reduce transmission of the virus and mitigate its impact. Individual behavioural changes are crucial to the successful implementation of these measures. One commonly recommended measure to limit risk of infection is frequent handwashing. It is important to identify those factors that can predict the uptake and maintenance of handwashing. We aimed to identify and synthesise the evidence on malleable psychological and psychosocial factors that determine uptake and adherence to handwashing aimed at reducing the risk of infection or transmission of COVID-19. We searched various literature sources including electronic databases (Medline ALL, Child Development & Adolescent Studies, ERIC, PsycInfo, CINAHL and Web of Science), web searches, conference proceedings, government reports, other repositories of literature and grey literature. The search strategy was built around three concepts of interest including (1) context (terms relating to COVID-19), (2) behaviour of interest and (3) terms related to psychological and psychosocial determinants of COVID Health-Related Behaviours and adherence or compliance with handwashing, to capture malleable determines. Searches capture studies up until October 2021. Eligibility criteria included observational studies (both retrospective and prospective) and experimental studies that measure and report malleable psychological and psychosocial determinants and handwashing at an individual level, amongst the general public. Screening was supported by the Cochrane Crowd. Titles and abstracts were screened against the eligibility criteria by three independent screeners. Following this, all potentially relevant studies were screened at full-text level by the research team. All conflicts between screeners were resolved by discussion between the core research team. All data extraction was managed in EPPI-Reviewer software. All eligible studies, identified through full-text screening were extracted by one author. We extracted data on study information, population, determinant, behaviour and effects. A second author checked data extraction on 20% of all included papers. All conflicts were discussed by the two authors until consensus was reached.We assessed methodological quality of all included studies using an adapted version of the Joanna Briggs Institute Quality appraisal tool for cross-sectional studies. Our initial searches yielded 23,587 results, of which 56 studies were included in this review. The included studies were cross sectional in design, came from 22 countries and had a combined sample of 199,376 participants. The vast majority of studies had samples from the general public, with eight of the studies focusing on specific samples. All included studies considered people over the age of 18. The quality of the majority of the studies was good (n = 30 rated low risk of bias), with 8 rated high risk of bias, predominately due to lack of reporting of recruitment, sample characteristics and methodology. Thirty-four studies were included in the narrative synthesis and 28 in the meta-analysis.Findings indicated that emotions about COVID-19 (worry [0.381, confidence interval [CI] = 0.270-0.482, I 2 = 92%) and anxiety (0.308, CI = 0.154-0.448, I 2 = 91%]), knowledge of COVID-19 (0.323, CI = 0.223-0.417, I 2 = 94%), and perceived social norms (0.303, CI = 0.184-0.413, I 2 = 92%) were among the malleable determinants most associated with handwashing. Perceived severity (0.006, CI = -0.011-0.023) and susceptibility of COVID-19 (0.041, CI = -0.034 to 0.115) had little to no effect on handwashing behaviour. Understanding the effects of various malleable determinants on COVID-related handwashing can aid in the development and implementation of interventions and public health campaigns to promote handwashing behaviour in potential new waves of COVID-19 or other respiratory infections. Emotions about COVID, knowledge of COVID and perceived social norms warrant further consideration in future research and policy.

Sequencing analysis of SARS-CoV-2 cases in Slovenian long-term care facilities to support outbreak control.

Residents of long-term care facilities (LTCFs) are at high risk of morbidity and mortality due to COVID-19, especially when new variants of concern (VOC) emerge. To provide intradisciplinary data in order to tailor public health interventions during future epidemics, available epidemiologic and genomic data from Slovenian LTCFs during the initial phases of the COVID-19 pandemic was analyzed. The first part of the study included SARS-CoV-2 reverse-transcription Real-Time PCR (rtRT-PCR) positive LTCF residents, from 21 facilities with COVID-19 outbreaks occurring in October 2020. The second part of the study included SARS-CoV-2 rtRT-PCR positive LTCF residents and staff between January and April 2021, when VOC Alpha emerged in Slovenia. Next-generation sequencing (NGS) was used to acquire SARS-CoV-2 genomes, and lineage determination. In-depth phylogenetic and mutational profile analysis were performed and coupled with available field epidemiological data to assess the dynamics of SARS-CoV-2 introduction and transmission. 370/498 SARS-CoV-2 positive residents as well as 558/699 SARS-CoV-2 positive residents and 301/358 staff were successfully sequenced in the first and second part of the study, respectively. In October 2020, COVID-19 outbreaks in the 21 LTCFs were caused by intra-facility transmission as well as multiple independent SARS-CoV-2 introductions. The Alpha variant was confirmed in the first LTCF resident approximately 1.5 months after the first Alpha case was identified in Slovenia. The data also showed a slower replacement of existing variants by Alpha in residents compared to staff and the general population. Multiple SARS CoV-2 introductions as well as intra-facility spreading impacted disease transmission in Slovenian LTCFs. Timely implementation of control measures aimed at limiting new introductions while controlling in-facility transmission are of paramount importance, especially as new VOCs emerge. Sequencing, in conjunction with epidemiological data, can facilitate the determination of the need for future improvements in control measures to protect LTCF residents from COVID-19 or other respiratory infections.

Niclosamide: A career builder

My contribution to honoring Professor Kinam Park celebrates and resonates with his scholarly career in drug delivery, his commitment to encouraging the next generation(s), and his efforts to keep us focused on clinically effective formulations. To do this I take as my example, niclosamide, a small molecule protonophore that, uniquely, can “target” all cell membranes, both plasma and organelle. As such, it acts upstream of many cell pathways and so has the potential to affect many of the essential events that a cell, and particularly a diseased cell or other entities like a virus, use to stay alive and prosper. Literature shows that it has so far been discovered to positively influence (at least): cancer, bacterial and viral infection, metabolic diseases such as Type II diabetes, NASH and NAFLD, artery constriction, endometriosis, neuropathic pain, rheumatoid arthritis, sclerodermatous graft-versus-host disease, systemic sclerosis, Parkinson's, and COPD. With such a fundamental action and broad-spectrum activity, I believe that studying niclosamide in all its manifestations, discovering if and to what extent it can contribute positively to disease control (and also where it can't), formulating it as effective therapeutics, and testing them in preclinical and clinical trials is a career builder for our next generation(s).The article is divided into two parts: Part I introduces niclosamide and other proton shunts mainly in cancer and viral infections and reviews an exponentially growing literature with some concepts and physicochemical properties that lead to its proton shunt mechanism. Part II focuses on repurposing by reformulation of niclosamide. I give two examples of “carrier-free formulations”, — one for cancer (as a prodrug therapeutic of niclosamide stearate for i.v. and other administration routes, exemplified by our recent work on Osteosarcoma in mice and canine patients), and the other as a niclosamide solution formulation (that could provide the basis for a preventative nasal spray and early treatment option for COVID19 and other respiratory virus infections).My goal is to excite and enthuse, encourage, and motivate all involved in the drug development and testing process in academia, institutes, and industry, to learn more about this interesting molecule and others like it. To enable such endeavors, I give many proposed ideas throughout the document, that have been stimulated and inspired by gaps in the literature, urgent needs in disease, and new studies arising from our own work. The hope is that, by reading through this document and studying the suggested topics and references, the drug delivery and development community will continue our lineage and benefit from our legacy to achieve niclosamide's potential as an effective contributor to the treatment and control of many diseases and conditions.

Seawater nasal wash to reduce symptom duration and viral load in COVID-19 and upper respiratory tract infections: a randomized controlled multicenter trial

PurposeThe objective was to assess the efficacy of seawater nasal wash on symptom duration, intranasal viral load, household transmission in COVID-19 and URTIs.MethodsThis prospective, randomized, controlled, multicentric, parallel study included 355 mild/moderate COVID-19 and URTI adults with rhinologic symptoms ≤ 48h. Active group performed 4-daily nasal washes with undiluted isotonic seawater versus control group (without nasal wash). Symptoms were self-assessed daily using the WURSS-21 questionnaire for 3 weeks. Viral load was measured by RT-PCR on nasopharyngeal swabs collected on Day 0, Day 5, Day 14 and Day 21. Digital droplet PCR was additionally performed for SARS-CoV-2.ResultsOverall COVID-19 subjects recovered earlier the ability to accomplish daily activities in the active group (– 1.6 day, p = 0.0487) with earlier improvement of taste (– 2 days, p = 0.0404). COVID-19 subjects with severe nasal symptoms at D0 showed the earliest resolution of anosmia (– 5.2 days, p = 0.0281), post-nasal drip (– 4.1 days, p = 0.0102), face pain/heaviness (– 4.5 days, p = 0.0078), headache (– 3.1 days, p = 0.0195), sore throat (– 3.3 days, p = 0.0319), dyspnea (– 3.1 days, p = 0.0195), chest congestion (– 2.8 days, p = 0.0386) and loss of appetite (– 4.5 days, p = 0.0186) with nasal wash. In URTIs subjects, an earlier resolution of rhinorrhea (– 3.5 days, p = 0.0370), post-nasal drip (– 3.7 days, p = 0.0378), and overall sickness (– 4.3 days, p = 0.0248) was reported with nasal wash.Evolution towards more severe COVID-19 was lower in active vs control, with earlier viral load reduction in youngest subjects (≥ 1.5log10 copies/10000 cells at Day 5: 88.9% vs 62.5%, p = 0.0456). In the active group, a lower percentage of SARS-CoV-2 positive household contacts (0–10.7%) was reported vs controls (3.2–16.1%) among subjects with Delta variant (p = 0.0413).ConclusionThis trial showed the efficacy and safety of seawater nasal wash in COVID-19 and URTIs.Trial registrationTrial registry ClinicalTrials.gov: NCT04916639. Registration date: 04.06.2021.

The Demographic and Clinical Characteristics of the Co-infection for the Detection of SARSCOV- 2 and Influenza A Virus by rRT-PCR

The potential for co-infection with COVID-19 and other respiratory infections raises the possibility that a new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mimics the influenza A virus regarding methods and modes of transmission, clinical features, related immune responses, and seasonal coincidence. This study aimed to investigate the presence of SARS-CoV-2 and influenza A virus coinfections inadmitted patients of a tertiary care hospital. In this study, the total included 589 admitted patients in our tertiary care hospital. The detectionof co-infection between SARS-CoV-2 and influenza A virus by real-time reverse-transcriptase polymerase chain reaction (rRT-PCR) in a patientduring the second wave of the COVID-19 pandemic. There were 207 (35.1%) patients infected with SARS-CoV-2 and 43 (7.3%) patientsinfected with the influenza A virus. Only 6 (1.0%) patients were infected with SARS-CoV-2 and influenza A viruses. The females were morelikely to be infected with SARS-CoV-2 than non-infected SARS-CoV-2 case-patients (60.9% (n = 126) vs. 31.4% (n = 120), and also with theinfluenza A virus compared with influenza-negative patients (40.9% (n = 223) vs. 55.9% (n = 24). In conclusion, our results strongly suggestthat influenza A co-infects with SARS-CoV-2. The patients with SARS-CoV-2 and influenza A co-infection had similar clinical characteristics asthose with SARS-CoV-2 infection alone. Comorbidities, like hypertension and diabetes, and increasing age make patients more susceptible toSARS-CoV-2 and influenza A coinfections.

Lesions of the heart and parenchymatous organs in patients with COVID-19 and other acute respiratory infections

Based on available literature, this study aimed to critically assess the effect of SARS-CoV-2 and other respiratory viruses on the heart and parenchymatous internal organs, identify their common and distinctive features, assess the frequency of cytokine storm and “post-infection” syndrome, and identify risk factors for severe systemic reaction and damage to internal organs, particularly the heart.
 In the databases of MEDLINE/PubMed, eLibrary, Web of Science, CyberLeninka, and Openmedcom.ru, primary information (full-text and abstract databases) in English and Russian was searched using selected keywords from 2003 to 2023.
 Acute respiratory viral infection pathogens can cause not only respiratory but also cardinal, gastroenterological, neurological, and other complications.
 Acute respiratory viral infections have many similarities in their effects on parenchymal organs. The emergence of new viruses requires in-depth study, and it is important to consider both the distinctive features of the clinical picture of viral infections and the general patterns of influence on internal organs. In the medium term, patients who have COVID-19 may have complex heart damage in the form of a decrease in ventricular ejection fraction, appearance of pericardial effusion, and development of various types of focal myocardial lesions. The combined nature of damage to the heart and parenchymal organs is influenced by background diseases, nature of the course of viral infection, and features of therapy. The features of lesions of parenchymal organs and the heart after acute respiratory viral infection require further study, including their effect on the development of late complications.

Влияние вакцинации против гриппа, пневмококковой инфекции и SARS-CoV-2 на заболеваемость и тяжесть течения COVID‑19 у медицинских работников отдельного учреждения (эпидемиологические исследования)

Objective. To study the effect of influenza, pneumococcal and SARS-CoV-2 vaccination on the incidence and severity of COVID-19 course in health care workers. Patients and Methods. We examined 547 health care workers divided into group 1 (no history of influenza and pneumococcal vaccination, n = 281) and groups vaccinated between August and October 2020 (before SARS-CoV-2 epidemic II): Group 2 against influenza (n = 98), Group 3 against pneumococcal infection (n = 60), and Group 4 against influenza and pneumococcus (n = 108). Between March and August 2021 (before the SARS-CoV-2 epidemic III outbreak), 98.6% of all employees were vaccinated against COVID-19. We compared COVID-19 incidence rates during Periods II and III epidemic rises (2020–2022) as a function of influenza and pneumococcal vaccination. Results. It was found that with combined vaccination against influenza and pneumococcal infection in the group of medical workers at high risk of infection, the risk of COVID-19 morbidity within 4–5 months was 2 times lower (1.6% vs. 13.2%, p < 0.05) compared to the unvaccinated. Comparative data on COVID-19 incidence in the II and III periods of epidemic rises showed that COVID-19 in medical workers in the III period was registered 36.1% lower in comparison with the index in the II period – 11.2 and 7.1%, respectively (p < 0.05). We found that when comparing II and III periods of epidemic rises among medical workers, the proportion of persons with COVID-19 with moderate forms of disease who received combined vaccination against influenza and pneumococcal infection decreases more than 2-fold (p < 0.05), including in the category with a high risk of infection. Conclusion. The presented data indicate a positive effect of combined vaccination against pneumococcal infection and influenza on the incidence and severity of COVID-19. The proposed approach can be used in public health practice as a method of nonspecific prevention of COVID-19 and other acute respiratory viral infections. Key words: influenza vaccine, pneumococcal vaccine, combined vaccination, epidemic rise, COVID-19

Assessment of the state of children after COVID-19 and other acute respiratory infections using the ISARIC COVID-19 survey

Introduction. The state of children had suffered from COVID-19 causes various persistent symptoms affecting on patient well-being and quality of life which is a significant healthcare issue. 
 The aim of the work. To assess health and well-being of children following COVID-19 and other acute respiratory infections. 
 Materials and methods. This is a case-control study including children with history of PCR-confirmed COVID-19 (n = 261) and other acute respiratory infections (n = 198). Patients were assessed 6 months and 1 year after the infection using the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) COVID-19 questionnaire for children. The prevalence of symptoms including fatigue, weakness, lack of energy, as well as the emotional well-being, social relationships, and social activity of children was evaluated. 
 Results. Children with history of COVID-19 in six months had significantly higher rates of weakness and decreased school attendance compared to children with other acute respiratory infections. 12 months after infection, children in the case group were significantly more likely to experience poor concentration, weakness, a decreased sense of belonging and school attendance. However, 12 months after infection, control group had significantly higher rates of fatigue. 
 Conclusion. Children with a history of mild COVID-19 and other acute respiratory infections may experience ongoing health problems for 1 year after the infection, requiring greater attention from healthcare professionals and family members.

Alnuctamab (ALNUC; BMS-986349; CC-93269), a 2+1 B-Cell Maturation Antigen (BCMA) × CD3 T-Cell Engager (TCE), Administered Subcutaneously (SC) in Patients (Pts) with Relapsed/Refractory Multiple Myeloma (RRMM): Updated Results from a Phase 1 First-in-Human Clinical Study

Introduction : ALNUC, a 2+1 TCE with bivalent binding to BCMA, is under investigation in a phase 1 trial (NCT03486067) in pts with triple-class exposed RRMM previously treated with ≥ 3 lines of therapy (LOTs). IV-administered ALNUC demonstrated durable responses (median duration of response, 33.6 mo). However, due to a high frequency of cytokine release syndrome (CRS; 76% of pts), including grade ≥ 3 events (7% of pts), the trial pivoted to SC administration of ALNUC. This resulted in a markedly improved safety profile, allowing escalation to higher target doses, while showing promising antitumor activity (Wong SW et al. EHA 2023. Abstract P883). We present updated data for SC ALNUC in pts with RRMM treated in the phase 1 study. Methods : Pts with RRMM who had received ≥ 3 LOTs, including an immunomodulatory drug (IMiD ®), a proteasome inhibitor, and an anti-CD38 therapy, were eligible. SC ALNUC was given on day (D) 1, 4, 8, 15, and 22 of cycle 1 (C1), QW in C2-3, Q2W in C4-6, and Q4W in C7 and beyond (28-d cycles). Step-up doses were given on C1D1 (3 mg) and C1D4 (6 mg), and target doses (10, 15, 30, or 60 mg) on C1D8 and thereafter. Target doses of 10, 30, and 60 mg were tested in dose expansion. Safety and tolerability were primary objectives. Secondary objectives included preliminary efficacy and pharmacokinetics. The data cutoff for the results included herein was Apr 3, 2023; updated data will be presented. Results : Of 73 pts treated with SC ALNUC in dose escalation (target dose: 10 mg, n = 6; 15 mg, n = 4; 30 mg, n = 6; 60 mg, n = 7) and dose expansion (target dose: 10 mg, n = 19; 30 mg, n = 21; 60 mg, n = 10), median age was 64 y; 58% were male. Pts had median of 4 prior regimens (range, 3-14); 96% were refractory to last LOT, 100%/78% had triple-class/penta-drug exposed MM, and 63%/19% had triple-class/penta-drug refractory MM. Median follow-up was 7.4 mo (range, 0.5-19.9). All-grade/grade ≥ 3 treatment-emergent adverse events (TEAEs) occurred in 99%/81% of pts; most common were CRS (56%/0%), neutropenia (55%/45%), anemia (47%/27%), and thrombocytopenia (37%/16%). All-grade/grade ≥ 3 infections occurred in 62%/16% of pts; infections occurring in ≥ 10% of pts were COVID-19 (23%/3%) and upper respiratory tract infections (12%/0%). Infections of special interest included grade 2 cytomegalovirus reactivation in 1 pt (1.3%); there were no grade ≥ 3 infections of special interest. Median time to CRS was 3 d (range, 1-20), with a median duration of 2 d (range, 1-11). CRS was most common after the first step-up dose (40% of pts). Of 887 doses administered at the fourth dose and beyond, the frequency of CRS per dose was < 1%. Two pts had grade 1 neurotoxicity suspected related to SC ALNUC; no grade ≥ 2 neurotoxicity was observed. One pt discontinued treatment due to a TEAE (grade 3 metastatic colon cancer not suspected related to treatment); 1 treatment-related death (cerebral hemorrhage) occurred at the 60-mg target dose. Overall response rate (ORR) was 54% (39 of 72 efficacy-evaluable pts treated with SC ALNUC) across all doses, with responses deepening over time (Figure). ORR was 63% (27/43) at target doses ≥ 30 mg and 69% (18/26) at the 30-mg target dose. Median time to response was 1.2 mo (range, 0.9-4.0) and 77% (30/39) of responses were ongoing at data cutoff. Among efficacy-evaluable pts, median PFS was 10.1 mo (95% CI, 2.8-16.6) across all dose levels. For the 30-mg target dose, at a median follow up of 9.3 mo, median PFS was not reached (95% CI, 4.7-NA) with a 12-mo PFS of 53% (95% CI, 30-71). Among the 39 pts who achieved a response, 28/28 pts (100%) with evaluable minimal residual disease (MRD) samples were MRD-negative (10 −5 sensitivity by flow cytometry) at C2D1, C4D1, C6D1, or C8D1; of the 18 pts who achieved a response at the 30-mg target dose, 14/14 pts (100%) with available MRD data were MRD-negative. Preliminary population pharmacokinetic analysis estimated ~60% SC ALNUC bioavailability with a 14-d half-life. Observed trough concentrations at the 30-mg target dose exceeded levels predicted for efficacy by C2D1. Hallmark pharmacodynamic effects of TCEs were observed. Conclusions : SC ALNUC continued to demonstrate a safety profile consistent with the drug class and a low rate of severe infections. Across doses, responses were durable and deepened over time, with a high proportion of responders achieving MRD negativity. High antitumor activity was observed at target doses ≥ 30 mg and specifically at the 30-mg target dose. Enrollment in the phase 1 study is ongoing.

COVID-19 Impact on the AAPI Population in Pima County

The Together We Thrive Project (TWT) goal was to increase the capability of the Asian American and Pacific Islanders (AAPI’s) to deal with COVID-19 and other respiratory infections in Pima County, Arizona, U.S.A. It is the second most populated county in the state. There was little published information available about the COVID-19 impact on the AAPI populations and the communities’ needs in the county. The TWT Project conducted a needs assessment. The assessment survey results assisted the project in producing strategies and activities that address the needs. Fifty-six percent of the AAPI respondents had gotten COVID-19 during the pandemic. A third of the those who gotten the virus had long-lasting effects. The COVID-19 pandemic had significantly impacted Pima County AAPI population socially, mentally, physically, and economically

Bacterial respiratory infections in patients with COVID-19: A retrospective study from a tertiary care center in Lebanon

BackgroundDespite multiple reports of increased incidence of bacterial respiratory tract infections following COVID-19 globally, the microbiology is not yet fully elucidated. In this study, we describe the microbiology of bacterial infections and the prevalence of multidrug resistant organisms (MDROs) in hospitalized COVID-19 patients with community-acquired pneumonia (CAP), and hospital-acquired pneumonia (HAP) which includes both non-ventilated hospital acquired pneumonia (NVHAP) and ventilator-associated pneumonia (VAP). To our knowledge, this is the first study that compares the microbiology of VAP and NVHAP in COVID-19 patients. MethodsThis is a longitudinal retrospective cohort study conducted at the American University of Beirut Medical Center (AUBMC), a tertiary-care centre in Lebanon. Adult patients with confirmed COVID-19 and concurrent bacterial respiratory infections with an identifiable causative organism who were hospitalized between March 2020 and September 2021 were included. Bacterial isolates identified in hospital-acquired pneumonia (HAP) were divided into 3 groups based on the time of acquisition of pneumonia after admission: hospital day 3–14, 15–28 and 29–42. ResultsOut of 1674 patients admitted with COVID-19, 159 (9.5%) developed one or more respiratory infections with an identifiable causative organism. Overall, Gram-negative bacteria were predominant (84%) and Stenotrophomonas maltophilia was the most common pathogen, particularly in HAP. Among 231 obtained isolates, 59 (26%) were MDROs, seen in higher proportion in HAP, especially among patients with prolonged hospital stay (> 4 weeks). Non-fermenter Gram-negative bacilli (NFGNB) (OR = 3.52, p-value<0.001), particularly S. maltophilia (OR = 3.24, p-value = 0.02), were significantly more implicated in VAP compared to NVHAP. ConclusionsNFGNB particularly S. maltophilia were significantly associated with COVID-19 VAP. A high rate of bacterial resistance (25%), especially among Gram-negative bacteria, was found which may compromise patients’ outcomes and has important implications in guiding therapeutic decisions in COVID-19 patients who acquire bacterial respiratory infections.

Long-term symptom profiles after COVID-19 vs other acute respiratory infections: an analysis of data from the COVIDENCE UK study

Long COVID is a well recognised, if heterogeneous, entity. Acute respiratory infections (ARIs) due to other pathogens may cause long-term symptoms, but few studies compare post-acute sequelae between SARS-CoV-2 and other ARIs. We aimed to compare symptom profiles between people with previous SARS-CoV-2 infection, people with previous non-COVID-19 ARIs, and contemporaneous controls, and to identify clusters of long-term symptoms. COVIDENCE UK is a prospective, population-based UK study of ARIs in adults. We analysed data for 16potential long COVID symptoms and health-related quality of life (HRQoL), reported between January 21 and February 15, 2021, by participants unvaccinated against SARS-CoV-2. We classified participants as having previous SARS-CoV-2 infection or previous non-COVID-19 ARI (≥4 weeks prior) or no reported ARI. We compared symptoms by infection status using logistic and fractional regression, and identified symptom clusters using latent class analysis (LCA). This study is registered with ClinicalTrials.gov, NCT04330599. We included 10,171 participants (1311 [12.9%] with SARS-CoV-2 infection, 472 [4.6%] with non-COVID-19 ARI). Both types of infection were associated with increased prevalence/severity of most symptoms and decreased HRQoL compared with no infection. Participants with SARS-CoV-2 infection had increased odds of problems with taste/smell (odds ratio 19.74, 95% CI 10.53-37.00) and lightheadedness or dizziness (1.74, 1.18-2.56) compared with participants with non-COVID-19 ARIs. Separate LCA models identified three symptom severity groups for each infection type. In the most severe groups (representing 22% of participants for both SARS-CoV-2 and non-COVID-19 ARI), SARS-CoV-2 infection presented with a higher probability of problems with taste/smell (probability 0.41 vs 0.04), hair loss (0.25 vs 0.16), unusual sweating (0.38 vs 0.25), unusual racing of the heart (0.43 vs 0.33), and memory problems (0.70 vs 0.55) than non-COVID-19 ARI. Both SARS-CoV-2 and non-COVID-19 ARIs are associated with a wide range of symptoms more than 4 weeks after the acute infection. Research on post-acute sequelae of ARIs should extend from SARS-CoV-2 to include other pathogens. Barts Charity.

Governmental Non-Pharmaceutical Interventions during the COVID-19 Pandemic and the COPD Exacerbation and Respiratory Infection Rate in Patients with Alpha-1 Antitrypsin Deficiency

During the COVID-19 pandemic the number of hospital admissions due to chronic obstructive pulmonary disease (COPD) exacerbations was significantly reduced. The reason for this decline is not fully understood. Governmental non-pharmaceutical interventions (NPI’s), an increase in community treated exacerbations, or healthcare avoidance by patients, are potential reasons. For the current study, the impact of Dutch governmental NPI’s on the COPD exacerbations and respiratory infections rate in patients with severe alpha-1 antitrypsin deficiency (AATD) was analyzed. The patients participated in the NCT04204252 study, a randomized controlled trial evaluating the efficacy and safety of inhaled alpha-1 antitrypsin. Data collected in the time-period from March 2020 until February 2022 was analyzed. In this period the Dutch government imposed variable NPI’s to contain the spread of SARS-CoV-2. Patients were required to document their daily symptoms in an electronic diary. The strictness of the governmental NPI’s was measured by the COVID-19 Stringency Index. 19 patients participated in this study during the analysis period. A total of 40 respiratory infections and COPD exacerbations occurred. The Spearman’s correlation coefficient of the monthly average COVID-19 Stringency Index and respiratory infections and COPD exacerbations rate was −0.316 (p = 0.132). When months known for a low respiratory infection rate were excluded, the correlation coefficient was −0.625 (p = 0.010). This study showed a significant negative correlation between the COPD exacerbations and respiratory infection rate and the COVID-19 Stringency Index in patients with AATD related COPD in the autumn-winter months.

Revisiting the personal protective equipment components of transmission-based precautions for the prevention of COVID-19 and other respiratory virus infections in healthcare.

The COVID-19 pandemic highlighted some potential limitations of transmission-based precautions. The distinction between transmission through large droplets vs aerosols, which have been fundamental concepts guiding infection control measures, has been questioned, leading to considerable variation in expert recommendations on transmission-based precautions for COVID-19. Furthermore, the application of elements of contact precautions, such as the use of gloves and gowns, is based on low-quality and inconclusive evidence and may have unintended consequences, such as increased incidence of healthcare-associated infections and spread of multidrug-resistant organisms. These observations indicate a need for high-quality studies to address the knowledge gaps and a need to revisit the theoretical background regarding various modes of transmission and the definitions of terms related to transmission. Further, we should examine the implications these definitions have on the following components of transmission-based precautions: (i) respiratory protection, (ii) use of gloves and gowns for the prevention of respiratory virus infections, (iii) aerosol-generating procedures and (iv) universal masking in healthcare settings as a control measure especially during seasonal epidemics. Such a review would ensure that transmission-based precautions are consistent and rationally based on available evidence, which would facilitate decision-making, guidance development and training, as well as their application in practice.