The initiation of the program Mental Health Support Program for Coronavirus Infection addressed the increased demand for mental health services in the province of Salamanca, resulting from the COVID-19 pandemic. The psychiatry service provided care for COVID-19 patients, their families, and healthcare workers who treated them, as these groups were identified as being at risk. This study aims to describe the assistance provided, including personnel and resources utilized, types of interventions carried out, and to assess the demand for mental health care and predominant symptoms and emotions experienced by patients. Billboards and the complex\'s intranet publicized the program. Specific clinical approach using telemedicine were provide from March 2020 to December 2021 to COVID-19 patients, their relatives, and healthcare workers. 216 patients were included with a mean age of 53.2 years, with women comprising 77.3% of this group. All the groups received treatment in similar proportions. Over a period of 730 h, a total of 1376 interventions were performed, with an average duration of 31.8 min per intervention. The program could treat 79.6% of these patients without requiring referrals to other services. When the program concluded, only 21 participants (9.7%) were discharged to the local mental health network to continue their mental health treatment. The program effectively reduced the burden on regular mental health services due to its ability to treat most patients without requiring referrals. The program was able to attend to most mental health requests with minimal involvement of the regular mental health service.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, causes a spectrum of symptoms ranging from mild upper to severe lower respiratory tract infections. However, the dynamics of nucleocapsid (N) protein antigenemia and RNAemia are not fully understood. We conducted a cohort study involving 117 patients with clinically confirmed COVID-19, focusing on the kinetics of antigenemia and RNAemia and their association with various clinical characteristics. The patients had a median age of 66.0 years (52.0-79.0 years), with a gender distribution of 46.2% male and 53.8% female. Antigenemia reached 100% in fatal cases during the first week after admission. The sensitivity/specificity of antigenemia for diagnosis were 64.7%/73.0% at admission, 69.1%/100% in Week 1, and 66.3%/100% in Week 2. Additionally, the rates of antigenemia in asymptomatic patients were 27.3% upon admission and 22.0% in Week 1, respectively; however, no antigenemia was in samples collected in Week 2. Viral RNAemia was not detected in asymptomatic patients, but RNAemia viral loads were elevated in fatal cases. Kaplan-Meier survival curves demonstrated a higher mortality rate when antigenemia concentrations were elevated in the follow-up samples (P = 0.005). Our study provides a comprehensive analysis of the kinetics of viral N-protein antigenemia and RNAemia according to disease severity and clinical classification. Our findings suggest that highest concentrations of antigenemia in fatal cases occur in the first week after admission, indicating that early elevated antigenemia may serve as a marker of mortality risk.

Dexamethasone is the standard of care for critically ill patients with COVID-19, but the mechanisms by which it decreases mortality and its immunological effects in this setting are not understood. Here we perform bulk and single-cell RNA sequencing of samples from the lower respiratory tract and blood, and assess plasma cytokine profiling to study the effects of dexamethasone on both systemic and pulmonary immune cell compartments. In blood samples, dexamethasone is associated with decreased expression of genes associated with T cell activation, including TNFSFR4 and IL21R. We also identify decreased expression of several immune pathways, including major histocompatibility complex-II signaling, selectin P ligand signaling, and T cell recruitment by intercellular adhesion molecule and integrin activation, suggesting these are potential mechanisms of the therapeutic benefit of steroids in COVID-19. We identify additional compartment- and cell- specific differences in the effect of dexamethasone that are reproducible in publicly available datasets, including steroid-resistant interferon pathway expression in the respiratory tract, which may be additional therapeutic targets. In summary, we demonstrate compartment-specific effects of dexamethasone in critically ill COVID-19 patients, providing mechanistic insights with potential therapeutic relevance. Our results highlight the importance of studying compartmentalized inflammation in critically ill patients.

Methicillin-resistant Staphylococcus (MRS) has been associated with neonatal infections, with colonization of the anovaginal tract being the main source of vertical transmission. The COVID-19 pandemic has altered the frequency of antibiotic usage, potentially contributing to changes in the dynamics of bacterial agents colonizing humans. Here we determined MRS colonization rates among pregnant individuals attending a single maternity in Rio de Janeiro, Brazil before (January 2019-March 2020) and during (May 2020-March 2021) the COVID-19 pandemic. Anovaginal samples (n = 806 [521 samples before and 285 during the pandemic]) were streaked onto chromogenic media. Colonies were identified by MALDI-TOF MS. Detection of mecA gene and SCCmec typing were assessed by PCR and antimicrobial susceptibility testing was done according to CLSI guidelines. After the onset of the pandemic, MRS colonization rates increased significantly (p < 0.05) from 8.6% (45) to 54.7% (156). Overall, 215 (26.6%) MRS isolates were detected, of which S. haemolyticus was the most prevalent species (MRSH, 84.2%; 181 isolates). SCCmec type V was the most frequent among MRS (63.3%; 136), and 31.6% (68) of MRS strains had a non-typeable SCCmec, due to new combinations of ccr and mecA complexes. Among MRS strains, 41.9% (90) were resistant to at least 3 different classes of antimicrobial agents, and 60% (54) of them were S. haemolyticus harboring SCCmec V. MRS colonization rates and the emergence of multidrug-resistant variants detected in this study indicate the need for continuing surveillance of this important pathogen within maternal and child populations.

In a pivotal trial (EPIC-HR), a 5-day course of oral ritonavir-boosted nirmatrelvir, given early during symptomatic SARS-CoV-2 infection (within three days of symptoms onset), decreased hospitalization and death by 89.1% and nasal viral load by 0.87 log relative to placebo in high-risk individuals. Yet, nirmatrelvir/ritonavir failed as post-exposure prophylaxis in a trial, and frequent viral rebound has been observed in subsequent cohorts. We develop a mathematical model capturing viral-immune dynamics and nirmatrelvir pharmacokinetics that recapitulates viral loads from this and another clinical trial (PLATCOV). Our results suggest that nirmatrelvir\'s in vivo potency is significantly lower than in vitro assays predict. According to our model, a maximally potent agent would reduce the viral load by approximately 3.5 logs relative to placebo at 5 days. The model identifies that earlier initiation and shorter treatment duration are key predictors of post-treatment rebound. Extension of treatment to 10 days for Omicron variant infection in vaccinated individuals, rather than increasing dose or dosing frequency, is predicted to lower the incidence of viral rebound significantly.

We sought to investigate the incidence of severe COVID-19 outcomes after treatment with antivirals and neutralising monoclonal antibodies, and estimate the comparative effectiveness of treatments in community-based individuals. We conducted a retrospective cohort study investigating clinical outcomes of hospitalisation, intensive care unit admission and death, in those treated with antivirals and monoclonal antibodies for COVID-19 in Scotland between December 2021 and September 2022. We compared the effect of various treatments on the risk of severe COVID-19 outcomes, stratified by most prevalent sub-lineage at that time, and controlling for comorbidities and other patient characteristics. We identified 14,365 individuals treated for COVID-19 during our study period, some of whom were treated for multiple infections. The incidence of severe COVID-19 outcomes (inpatient admission or death) in community-treated patients (81% of all treatment episodes) was 1.2% (n = 137/11894, 95% CI 1.0-1.4), compared to 32.8% in those treated in hospital for acute COVID-19 (re-admissions or death; n = 40/122, 95% CI 25.1-41.5). For community-treated patients, there was a lower risk of severe outcomes (inpatient admission or death) in younger patients, and in those who had received three or more COVID-19 vaccinations. During the period in which BA.2 was the most prevalent sub-lineage in the UK, sotrovimab was associated with a reduced treatment effect compared to nirmaltrelvir + ritonavir. However, since BA.5 has been the most prevalent sub-lineage in the UK, both sotrovimab and nirmaltrelvir + ritonavir were associated with similarly lower incidence of severe outcomes than molnupiravir. Around 1% of those treated for COVID-19 with antivirals or neutralising monoclonal antibodies required hospital admission. During the period in which BA.5 was the prevalent sub-lineages in the UK, molnupiravir was associated with the highest incidence of severe outcomes in community-treated patients.

Currently approved vaccines have been successful in preventing the severity of COVID-19 and hospitalization. These vaccines primarily induce humoral immune responses; however, highly transmissible and mutated variants, such as the Omicron variant, weaken the neutralization potential of the vaccines, thus, raising serious concerns about their efficacy. Additionally, while neutralizing antibodies (nAbs) tend to wane more rapidly than cell-mediated immunity, long-lasting T cells typically prevent severe viral illness by directly killing infected cells or aiding other immune cells. Importantly, T cells are more cross-reactive than antibodies, thus, highly mutated variants are less likely to escape lasting broadly cross-reactive T cell immunity. Therefore, T cell antigen-based human coronavirus (HCoV) vaccines with the potential to serve as a supplementary weapon to combat emerging SARS-CoV-2 variants with resistance to nAbs are urgently needed. Alternatively, T cell antigens could also be included in B cell antigen-based vaccines to strengthen vaccine efficacy. This review summarizes recent advancements in research and development of vaccines containing T cell antigens or both T and B cell antigens derived from proteins of SARS-CoV-2 variants and/or other HCoVs based on different vaccine platforms.

Respiratory infections such as Coronavirus disease 2019 are a substantial worldwide health challenge, frequently resulting in severe sickness and death, especially in susceptible groups. Conventional drug development for respiratory infections faces obstacles such as extended timescales, substantial expenses, and the rise of resistance to current treatments. Drug repurposing is a potential method that has evolved to quickly find and reuse existing medications for treating respiratory infections. Drug repurposing utilizes medications previously approved for different purposes, providing a cost-effective and time-efficient method to tackle pressing medical needs. This chapter summarizes current progress and obstacles in repurposing medications for respiratory infections, focusing on notable examples of repurposed pharmaceuticals and their probable modes of action. The text also explores the significance of computational approaches, high-throughput screening, and preclinical investigations in identifying potential candidates for repurposing. The text delves into the significance of regulatory factors, clinical trial structure, and actual data in confirming the effectiveness and safety of repurposed medications for respiratory infections. Drug repurposing is a valuable technique for quickly increasing the range of treatments for respiratory infections, leading to better patient outcomes and decreasing the worldwide disease burden.

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SARS-CoV-2, the causative virus of the COVID-19 pandemic, follows SARS and MERS as recent zoonotic coronaviruses causing severe respiratory illness and death in humans. The recurrent impact of zoonotic coronaviruses demands a better understanding of their fundamental molecular biochemistry. Nucleoside modifications, which modulate many steps of the RNA lifecycle, have been found in SARS-CoV-2 RNA, although whether they confer a pro- or anti-viral effect is unknown. Regardless, the viral RNA-dependent RNA polymerase will encounter these modifications as it transcribes through the viral genomic RNA. We investigated the functional consequences of nucleoside modification on the pre-steady state kinetics of SARS-CoV-2 RNA-dependent RNA transcription using an in vitro reconstituted transcription system with modified RNA templates. Our findings show that N6-methyladenosine and 2\'O-methyladenosine modifications slow the rate of viral transcription at magnitudes specific to each modification, which has the potential to impact SARS-CoV-2 genome maintenance.