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1.
CA Cancer J Clin ; 71(1): 34-46, 2021 01.
Article in English | MEDLINE | ID: mdl-32997807

ABSTRACT

The delivery of cancer care has never changed as rapidly and dramatically as we have seen with the coronavirus disease 2019 (COVID-19) pandemic. During the early phase of the pandemic, recommendations for the management of oncology patients issued by various professional societies and government agencies did not recognize the significant regional differences in the impact of the pandemic. California initially experienced lower than expected numbers of cases, and the health care system did not experience the same degree of the burden that had been the case in other parts of the country. In light of promising trends in COVID-19 infections and mortality in California, by late April 2020, discussions were initiated for a phased recovery of full-scale cancer services. However, by July 2020, a surge of cases was reported across the nation, including in California. In this review, the authors share the response and recovery planning experience of the University of California (UC) Cancer Consortium in an effort to provide guidance to oncology practices. The UC Cancer Consortium was established in 2017 to bring together 5 UC Comprehensive Cancer Centers: UC Davis Comprehensive Cancer Center, UC Los Angeles Jonsson Comprehensive Cancer Center, UC Irvine Chao Family Comprehensive Cancer Center, UC San Diego Moores Cancer Center, and the UC San Francisco Helen Diller Family Comprehensive Cancer Center. The interventions implemented in each of these cancer centers are highlighted, with a focus on opportunities for a redesign in care delivery models. The authors propose that their experiences gained during this pandemic will enhance pre-pandemic cancer care delivery.


Subject(s)
COVID-19 , Cancer Care Facilities/organization & administration , Delivery of Health Care/organization & administration , Neoplasms/therapy , COVID-19/complications , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Testing , California/epidemiology , Global Health , Humans , Infection Control/methods , Infection Control/organization & administration , Neoplasms/complications , Neoplasms/diagnosis , Pandemics , Telemedicine/methods , Telemedicine/organization & administration
2.
CA Cancer J Clin ; 70(6): 480-504, 2020 11.
Article in English | MEDLINE | ID: mdl-32910493

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has given rise to a pandemic of unprecedented proportions in the modern era because of its highly contagious nature and impact on human health and society: coronavirus disease 2019 (COVID-19). Patients with cardiovascular (CV) risk factors and established CV disease (CVD) are among those initially identified at the highest risk for serious complications, including death. Subsequent studies have pointed out that patients with cancer are also at high risk for a critical disease course. Therefore, the most vulnerable patients are seemingly those with both cancer and CVD, and a careful, unified approach in the evaluation and management of this patient population is especially needed in times of the COVID-19 pandemic. This review provides an overview of the unique implications of the viral outbreak for the field of cardio-oncology and outlines key modifications in the approach to this ever-increasing patient population. These modifications include a shift toward greater utilization of cardiac biomarkers and a more focused CV imaging approach in the broader context of modifications to typical practice pathways. The goal of this strategic adjustment is to minimize the risk of SARS-CoV-2 infection (or other future viral outbreaks) while not becoming negligent of CVD and its important impact on the overall outcomes of patients who are being treated for cancer.


Subject(s)
Antineoplastic Agents/adverse effects , COVID-19/complications , Cardiovascular Diseases/etiology , Cross Infection/prevention & control , Neoplasms/complications , Neoplasms/therapy , Anthracyclines/adverse effects , COVID-19/physiopathology , COVID-19/prevention & control , COVID-19/transmission , Cardiovascular Diseases/diagnostic imaging , Cardiovascular Diseases/therapy , Humans , Proteasome Inhibitors/adverse effects , Protein Kinase Inhibitors/adverse effects , Radiotherapy/adverse effects , Receptor, ErbB-2/antagonists & inhibitors , Referral and Consultation , SARS-CoV-2 , Trastuzumab/adverse effects
3.
Semin Immunol ; 55: 101507, 2021 06.
Article in English | MEDLINE | ID: mdl-34716096

ABSTRACT

Coronaviruses are evolutionarily successful RNA viruses, common to multiple avian, amphibian and mammalian hosts. Despite their ubiquity and potential impact, knowledge of host immunity to coronaviruses remains incomplete, partly owing to the lack of overt pathogenicity of endemic human coronaviruses (HCoVs), which typically cause common colds. However, the need for deeper understanding became pressing with the zoonotic introduction of three novel coronaviruses in the past two decades, causing severe acute respiratory syndromes in humans, and the unfolding pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This renewed interest not only triggered the discovery of two of the four HCoVs, but also uncovered substantial cellular and humoral cross-reactivity with shared or related coronaviral antigens. Here, we review the evidence for cross-reactive B cell memory elicited by HCoVs and its potential impact on the puzzlingly variable outcome of SARS-CoV-2 infection. The available data indicate targeting of highly conserved regions primarily in the S2 subunits of the spike glycoproteins of HCoVs and SARS-CoV-2 by cross-reactive B cells and antibodies. Rare monoclonal antibodies reactive with conserved S2 epitopes and with potent virus neutralising activity have been cloned, underscoring the potential functional relevance of cross-reactivity. We discuss B cell and antibody cross-reactivity in the broader context of heterologous humoral immunity to coronaviruses, as well as the limits of protective immune memory against homologous re-infection. Given the bidirectional nature of cross-reactivity, the unprecedented current vaccination campaign against SARS-CoV-2 is expected to impact HCoVs, as well as future zoonotic coronaviruses attempting to cross the species barrier. However, emerging SARS-CoV-2 variants with resistance to neutralisation by vaccine-induced antibodies highlight a need for targeting more constrained, less mutable parts of the spike. The delineation of such cross-reactive areas, which humoral immunity can be trained to attack, may offer the key to permanently shifting the balance of our interaction with current and future coronaviruses in our favour.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Antibodies, Viral , Humans , Immunity, Humoral
4.
Cancer ; 130(1): 117-127, 2024 01 01.
Article in English | MEDLINE | ID: mdl-37755665

ABSTRACT

BACKGROUND: With access to cancer care services limited because of coronavirus disease 2019 control measures, cancer diagnosis and treatment have been delayed. The authors explored changes in the counts of US incident cases by cancer type, age, sex, race, and disease stage in 2020. METHODS: Data were extracted from selected US population-based cancer registries for diagnosis years 2015-2020 using first-submission data from the North American Association of Central Cancer Registries. After a quality assessment, the monthly numbers of newly diagnosed cancer cases were extracted for six cancer types: colorectal, female breast, lung, pancreas, prostate, and thyroid. The observed numbers of incident cancer cases in 2020 were compared with the estimated numbers by calculating observed-to-expected (O/E) ratios. The expected numbers of incident cases were extrapolated using Joinpoint trend models. RESULTS: The authors report an O/E ratio <1.0 for major screening-eligible cancer sites, indicating fewer newly diagnosed cases than expected in 2020. The O/E ratios were lowest in April 2020. For every cancer site except pancreas, Asians/Pacific Islanders had the lowest O/E ratio of any race group. O/E ratios were lower for cases diagnosed at localized stages than for cases diagnosed at advanced stages. CONCLUSIONS: The current analysis provides strong evidence for declines in cancer diagnoses, relative to the expected numbers, between March and May of 2020. The declines correlate with reductions in pathology reports and are greater for cases diagnosed at in situ and localized stage, triggering concerns about potential poor cancer outcomes in the coming years, especially in Asians/Pacific Islanders. PLAIN LANGUAGE SUMMARY: To help control the spread of coronavirus disease 2019 (COVID-19), health care organizations suspended nonessential medical procedures, including preventive cancer screening, during early 2020. Many individuals canceled or postponed cancer screening, potentially delaying cancer diagnosis. This study examines the impact of the COVID-19 pandemic on the number of newly diagnosed cancer cases in 2020 using first-submission, population-based cancer registry database. The monthly numbers of newly diagnosed cancer cases in 2020 were compared with the expected numbers based on past trends for six cancer sites. April 2020 had the sharpest decrease in cases compared with previous years, most likely because of the COVID-19 pandemic.


Subject(s)
COVID-19 , Neoplasms , Male , Humans , Female , Pandemics , COVID-19/diagnosis , COVID-19/epidemiology , Neoplasms/diagnosis , Neoplasms/epidemiology , Neoplasms/pathology , Registries , COVID-19 Testing
5.
J Sleep Res ; : e14215, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38750610

ABSTRACT

The long-term effects of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection on sleep remain poorly known. We evaluated the association between probable post-COVID-19 condition and changes in sleep quality and quantity before and after SARS-CoV-2 infection in a consecutive sample of non-hospitalized adults. Individuals were identified with SARS-CoV-2 infection in 2020 at the central laboratory of a tertiary hospital in Porto and followed as outpatients. We included patients diagnosed with SARS-CoV-2 infection ≥3 months before this evaluation, with no missing data on key variables (n = 2445). Participants completed a questionnaire that included sociodemographic, clinical, and infection-related questions. We computed changes in sleep-related parameters referred to 1 month before diagnosis and 1 week before the questionnaire. Multinomial logistic regression models were fitted to compute crude and adjusted odds ratios and 95% confidence intervals (95% CIs). Compared to the pre-infection period, those with probable post-COVID-19 condition reported a greater decrease in hours of sleep, had a 2.60 (95% CI 2.02-3.34) higher adjusted odds of perceiving their sleep quality as worsened and experienced a significant increase in number of days with sleeping disturbances as defined according to multiple items. The association between post-COVID-19 condition and indicators of poor sleep health requires special attention from healthcare professionals and services. It is essential that appropriate multidisciplinary care is provided to mitigate the physical, psychological, social, and professional impact of sleeping problems in these already burdened patients.

6.
Infection ; 2024 Feb 21.
Article in English | MEDLINE | ID: mdl-38381306

ABSTRACT

PURPOSE: This aimed to identify the factors associated with severe/critical coronavirus disease 2019 (COVID-19) infection in rheumatoid arthritis (RA) patients. METHODS: Two-hundred RA patients diagnosed according to the American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) classification criteria with proven COVID-19 infection were recruited and categorized according to the world health organization (WHO) COVID-19 severity grading into 2 groups: patients with mild/moderate COVID-19 (n = 164) and patients with severe/critical COVID-19 (n = 36). Comparison between both groups was done to identify the risk factors associated with severe/critical infection. Incidence of RA disease activity flare defined as increase in clinical disease activity index (CDAI) more than 10 points following infection was calculated. RESULTS: Multivariate analysis identified history of previous serious infection, age > 60 years, and diabetes as factors positively associated, whereas COVID-19 vaccination was negatively associated with severe/critical infection. Following COVID-19 infection, the number of patients with severe/critical COVID-19 who had high RA disease activity and the incidence of flares was significantly higher in comparison to patients with mild/moderate COVID-19 (P < 0.001 and 0.003; respectively). CONCLUSION: Age > 60 years, diabetes, and history of previous serious infections are risk factors for severe/critical COVID-19, while vaccination has a protective role in RA patients. Infection particularly when severe is associated with risk of disease flare.

7.
BMC Infect Dis ; 24(1): 112, 2024 Jan 22.
Article in English | MEDLINE | ID: mdl-38254046

ABSTRACT

BACKGROUND: The World Health Organization (WHO) declared Coronavirus Disease 2019 (COVID-19) a global pandemic on March 11, 2020. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection has killed millions of people and had a terrible effect on society. The transmembrane protease serine 2 (TMPRSS2) enzyme is essential in the initial phases of the interplay between the SARSCoV-2 and the host cells by assisting viral entrance. METHODS: This observational case-control study involved 150 participants, 100 adult patients with COVID-19, 50 of whom appeared healthy and had no history of or symptoms of COVID-19 infection when the study was conducted. Between January and April 2022, patients were taken as inpatients in isolation units or through recruitment from the COVID-19 clinic at Kasr Al-Ainy Cairo University Hospitals. According to the National Institutes of Health guidelines (2021), they were categorised into three categories: mild, moderate, and severe. TMPRSS2 p.(Val197Met) variant genotyping was evaluated using TaqMan Real-Time PCR. RESULTS: The study showed a substantial difference between the mild and severe COVID-19 patient groups regarding their TMPRSS2 (p.Val197Met) genotypes (P value = 0.046). The C allele was significantly more prevalent in the mild, moderate and severe COVID-19 patient categories (77.8%, 89.7% and 91.7%, respectively) and the control group (80%). Meanwhile, the T allele was more prevalent in the mild (22.2%) and control (20%) groups. There was a statistically significant difference in allelic distribution between the mild and severe groups (P value = 0.034). CONCLUSION: The study showed a connection between the TMPRSS2 gene variant p.(Val197Met) and the degree of illness. We concluded that the T(mutant) allele was protective against severe COVID-19 because it was linked to lesser disease severity.


Subject(s)
COVID-19 , Serine Endopeptidases , Adult , Humans , Alleles , Case-Control Studies , COVID-19/genetics , Genotype , SARS-CoV-2/pathogenicity , Serine Endopeptidases/genetics , United States
8.
BMC Infect Dis ; 24(1): 88, 2024 Jan 15.
Article in English | MEDLINE | ID: mdl-38225630

ABSTRACT

BACKGROUND: The Omicron wave of Coronavirus disease 2019 (COVID-19) remains the dominant strain worldwide. The studies of nutritional status in geriatric people with COVID-19 Omicron variant are limited. Thus, the aim of this study was to investigate the incidence of poor nutritional status among Omicron infected older patients, and to explore the correlation between the nutritional status and the severity of Omicron infection in older patients. METHODS: This is a retrospective cross-sectional study. According to the clinical symptoms, patients were divided into two groups: mild and moderate to severe. Mini Nutritional Assessment short-form (MNA-SF) was conducted when patients were admitted and poor nutritional status was defined as MNA-SF score of 0-11. The inflammatory markers including neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR) and systemic inflammatory index (SII) were calculated and compared between two groups. RESULTS: Total of 324 patients were enrolled, with median [interquartile range (IQR)] age of 73 (17) years. Overall, 241 cases were mild, 83 cases were moderate to severe at the time of diagnosis and that 54.3% of patients had poor nutritional status. Patients with poor nutritional status were found to be older (P < 0.001) and less vaccinated (P < 0.001), with a longer virus shedding duration (P = 0.022), more comorbidities (≥ 2) (P = 0.004) and higher value of NLR (P < 0.001), PLR (P < 0.001) and SII (P = 0.012). Vaccination, cycle threshold value in ORF1ab gene (OR CT value) and female, higher MNA-SF score was negatively connected with probability of moderate to severe infection. For every 1 score increase in MNA-SF, the odds ratio of moderate to severe infection decreased by 14.8% [adjusted odds ratio (aOR), 0.852; 95% confidence interval (CI): 0.734-0.988; P = 0.034]. CONCLUSIONS: Older patients with poor nutritional status are more likely to develop moderate to severe Omicron infection.


Subject(s)
COVID-19 , Malnutrition , Humans , Female , Aged , Nutritional Status , Retrospective Studies , Cross-Sectional Studies , Malnutrition/epidemiology , Nutrition Assessment , COVID-19/epidemiology
9.
Clin Chem Lab Med ; 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38641917

ABSTRACT

OBJECTIVES: To survey the World Wide Web for critical limits/critical values, assess changes in quantitative low/high thresholds since 1990-93, streamline urgent notification practices, and promote global accessibility. METHODS: We identified Web-posted lists of critical limits/values at university hospitals. We compared 2023 to 1990-93 archived notification thresholds. RESULTS: We found critical notification lists for 26 university hospitals. Laboratory disciplines ranged widely (1-10). The median number of tests was 62 (range 21-116); several posted policies. The breadth of listings increased. Statistically significant differences in 2023 vs. 1990 critical limits were observed for blood gas (pO2, pCO2), chemistry (glucose, calcium, magnesium), and hematology (hemoglobin, platelets, PTT, WBC) tests, and for newborn glucose, potassium, pO2, and hematocrit. Twenty hospitals listed ionized calcium critical limits, which have not changed. Fourteen listed troponin (6), troponin I (3), hs-TnI (3), or troponin T (2). Qualitative critical values expanded across disciplines, encompassing anatomic/surgical pathology. Bioterrorism agents were listed frequently, as were contagious pathogens, although only three hospitals listed COVID-19. Only one notification list detailed point-of-care tests. Two children's hospital lists were Web-accessible. CONCLUSIONS: Urgent notifications should focus on life-threatening conditions. We recommend that hospital staff evaluate changes over the past three decades for clinical impact. Notification lists expanded, especially qualitative tests, suggesting that automation might improve efficiency. Sharing notification lists and policies on the Web will improve accessibility. If not dependent on the limited scope of secondary sources, artificial intelligence could enhance knowledge of urgent notification and critical care practices in the 21st Century.

10.
Bull Math Biol ; 86(3): 31, 2024 02 14.
Article in English | MEDLINE | ID: mdl-38353870

ABSTRACT

To characterize Coronavirus Disease 2019 (COVID-19) transmission dynamics in each of the metropolitan statistical areas (MSAs) surrounding Dallas, Houston, New York City, and Phoenix in 2020 and 2021, we extended a previously reported compartmental model accounting for effects of multiple distinct periods of non-pharmaceutical interventions by adding consideration of vaccination and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants Alpha (lineage B.1.1.7) and Delta (lineage B.1.617.2). For each MSA, we found region-specific parameterizations of the model using daily reports of new COVID-19 cases available from January 21, 2020 to October 31, 2021. In the process, we obtained estimates of the relative infectiousness of Alpha and Delta as well as their takeoff times in each MSA (the times at which sustained transmission began). The estimated infectiousness of Alpha ranged from 1.1x to 1.4x that of viral strains circulating in 2020 and early 2021. The estimated relative infectiousness of Delta was higher in all cases, ranging from 1.6x to 2.1x. The estimated Alpha takeoff times ranged from February 1 to February 28, 2021. The estimated Delta takeoff times ranged from June 2 to June 26, 2021. Estimated takeoff times are consistent with genomic surveillance data.


Subject(s)
COVID-19 , SARS-CoV-2 , United States/epidemiology , Humans , SARS-CoV-2/genetics , COVID-19/epidemiology , COVID-19/prevention & control , Mathematical Concepts , Models, Biological , Vaccination
11.
Curr Genomics ; 25(1): 12-25, 2024 Feb 23.
Article in English | MEDLINE | ID: mdl-38544825

ABSTRACT

Background: Altered cytokine levels have been associated with poor outcomes among COVID-19 patients. TNF-α, IL-8 and IL-10 are key cytokines in COVID-19 pathogenesis, and CXCR-2 is a major chemokine receptor involved in inflammatory response. Polymorphisms in the genes of these proteins are proposed to influence disease outcomes. In this study, we aimed to find out the association of genetic polymorphisms in TNF-α, IL-8, IL-10 and CXCR-2 genes with susceptibility to and mortality of COVID-19. Methods: The present case-control study was conducted on 230 subjects, among whom 115 were clinically diagnosed and RT-PCR-confirmed COVID-19 patients and 115 healthy control subjects. The polymorphisms in TNFα -308 G>A (rs1800629), IL-8 -251T>A (rs4073), CXCR2 +785 C>T (rs2230054) genes were detected by ARMS -PCR assay whereas for IL-10 (-1082 G>A), rs1800896 G>A allele-specific PCR assay was used and their association with COVID-19 susceptibility and mortality was estimated by multivariate analysis. The results were analyzed for risk of infection and mortality through different inheritance models. Results: Frequencies of TNF-α rs1800629 GA, AA, IL-8 rs4073 TA, AA, IL-10 (-1082 G>A), rs1800896 GA and GG, and CXCR2 rs2230054 CT genotypes were significantly higher in COVID-19 patients compared to the control group (p < 0.05). Furthermore, COVID-19 patients had a higher frequency of the polymorphic A allele of TNF-α, the A allele of IL-8, the G allele of IL-10, and the T allele of CXCR2. The risk of susceptibility to COVID-19 was significantly associated with TNF-α rs1800629 GA, GA+AA genotypes and the A allele, IL-8 rs4073 TA, AA genotypes and A allele, IL-10 rs1800872 GA and CC genotypes and C allele, and CXCR2 rs2230054 CT and CT+CC genotypes. TNF-α-GA and AA genotypes and A allele, IL-8 TA and AA genotypes and A allele and CXCR-2 CC and CT genotypes have significant associations with mortality risk in COVID-19 patients, while GA and GG genotypes of the IL-10 are shown to confer significant protection against mortality from COVID-19. Conclusion: The findings of this study provide important insights into the COVID-19 disease and susceptibility risk. The polymorphisms in TNFα -308 G>A (rs1800629), IL-8 -251T>A (rs4073), IL-10 (-1082 G>A), rs1800896 and CXCR2 +785 C>T (rs2230054) are associated with the risk of susceptibility to COVID-19 and with mortality in COVID-19 patients. Further studies with larger sample sizes are necessary to confirm our findings.

12.
Biol Pharm Bull ; 47(5): 965-966, 2024.
Article in English | MEDLINE | ID: mdl-38763750

ABSTRACT

The emergence of coronavirus disease 2019 (COVID-19), a novel identified pneumonia resulting from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, has significantly impacted and posed significant challenges to human society. The papain-like protease (PLpro) found in the nonstructural protein 3 of SARS-CoV-2 plays a vital role in viral replication. Moreover, PLpro disrupts the host immune response by cleaving ubiquitin and interferon-stimulated gene 15 from host proteins. Consequently, PLpro has emerged as a promising drug target against SARS-CoV-2 infection. Computational studies have reported that ciclesonide can bind to SARS-CoV-2 PLpro. However, the inhibitory effects of ciclenoside on the PLpro have not been experimentally evaluated. Here, we evaluated the inhibitory effects of synthetic glucocorticoids (sGCs), including ciclesonide, on SARS-CoV-2 PLpro in vitro assay. Ciclesonide significantly inhibited the enzymatic activity of PLpro, compared with other sGCs and its IC50 was 18.4 ± 1.89 µM. These findings provide insights into the development of PLpro inhibitors.


Subject(s)
Pregnenediones , SARS-CoV-2 , Pregnenediones/pharmacology , SARS-CoV-2/drug effects , Humans , COVID-19 Drug Treatment , Coronavirus Papain-Like Proteases/antagonists & inhibitors , Coronavirus Papain-Like Proteases/metabolism , Antiviral Agents/pharmacology , Molecular Docking Simulation , Coronavirus 3C Proteases/antagonists & inhibitors , Coronavirus 3C Proteases/metabolism , Glucocorticoids/pharmacology , COVID-19/virology
13.
Biol Pharm Bull ; 47(5): 967-977, 2024.
Article in English | MEDLINE | ID: mdl-38763751

ABSTRACT

Ensitrelvir is a noncovalent inhibitor of the main protease (Mpro) of severe acute respiratory syndrome coronavirus 2. Acquisition of drug resistance in virus-derived proteins is a serious therapeutic concern, and drug resistance occurs due to amino acid mutations. In this study, we computationally constructed 24 mutants, in which one residue around the active site was replaced with alanine and performed molecular dynamics simulations to the complex of Mpro and ensitrelvir to predict the residues involved in drug resistance. We evaluated the changes in the entire protein structure and ligand configuration in each of these mutants and estimated which residues were involved in ensitrelvir recognition. This method is called a virtual alanine scan. In nine mutants (S1A, T26A, H41A, M49A, L141A, H163A, E166A, V186A, and R188A), although the entire protein structure and catalytic dyad (cysteine (Cys)145 and histidine (His)41) were not significantly moved, the ensitrelvir configuration changed. Thus, it is considered that these mutants did not recognize ensitrelvir while maintaining Mpro enzymatic activities, and Ser1, Thr26, His41, Met49, Leu141, His163, Glu166, Val186, and Arg188 may be related to ensitrelvir resistance. The ligand shift noted in M49A was similar to that observed in M49I, which has been shown to be experimentally ensitrelvir resistant. These findings suggest that our research approach can predict mutations that incite drug resistance.


Subject(s)
Alanine , Catalytic Domain , Coronavirus 3C Proteases , Drug Resistance, Viral , Molecular Dynamics Simulation , SARS-CoV-2 , Coronavirus 3C Proteases/metabolism , Coronavirus 3C Proteases/genetics , Coronavirus 3C Proteases/antagonists & inhibitors , Coronavirus 3C Proteases/chemistry , SARS-CoV-2/drug effects , Alanine/genetics , Drug Resistance, Viral/genetics , Humans , Mutation , COVID-19 Drug Treatment , Protease Inhibitors/pharmacology , Indazoles , Triazines , Triazoles
14.
Biol Pharm Bull ; 47(5): 930-940, 2024.
Article in English | MEDLINE | ID: mdl-38692871

ABSTRACT

The coronavirus disease 2019 (COVID-19) is caused by the etiological agent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19, with the recurrent epidemics of new variants of SARS-CoV-2, remains a global public health problem, and new antivirals are still required. Some cholesterol derivatives, such as 25-hydroxycholesterol, are known to have antiviral activity against a wide range of enveloped and non-enveloped viruses, including SARS-CoV-2. At the entry step of SARS-CoV-2 infection, the viral envelope fuses with the host membrane dependent of viral spike (S) glycoproteins. From the screening of cholesterol derivatives, we found a new compound 26,27-dinorcholest-5-en-24-yne-3ß,20-diol (Nat-20(S)-yne) that inhibited the SARS-CoV-2 S protein-dependent membrane fusion in a syncytium formation assay. Nat-20(S)-yne exhibited the inhibitory activities of SARS-CoV-2 pseudovirus entry and intact SARS-CoV-2 infection in a dose-dependent manner. Among the variants of SARS-CoV-2, inhibition of infection by Nat-20(S)-yne was stronger in delta and Wuhan strains, which predominantly invade into cells via fusion at the plasma membrane, than in omicron strains. The interaction between receptor-binding domain of S proteins and host receptor ACE2 was not affected by Nat-20(S)-yne. Unlike 25-hydroxycholesterol, which regulates various steps of cholesterol metabolism, Nat-20(S)-yne inhibited only de novo cholesterol biosynthesis. As a result, plasma membrane cholesterol content was substantially decreased in Nat-20(S)-yne-treated cells, leading to inhibition of SARS-CoV-2 infection. Nat-20(S)-yne having a new mechanism of action may be a potential therapeutic candidate for COVID-19.


Subject(s)
Antiviral Agents , COVID-19 , Cholesterol , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , SARS-CoV-2/drug effects , Antiviral Agents/pharmacology , Humans , COVID-19/virology , Cholesterol/metabolism , Vero Cells , Chlorocebus aethiops , Spike Glycoprotein, Coronavirus/metabolism , Animals , Virus Internalization/drug effects , Betacoronavirus/drug effects , Pandemics , COVID-19 Drug Treatment , Coronavirus Infections/drug therapy , Coronavirus Infections/virology , Angiotensin-Converting Enzyme 2/metabolism , Pneumonia, Viral/drug therapy , Pneumonia, Viral/virology
15.
J Infect Chemother ; 2024 Mar 02.
Article in English | MEDLINE | ID: mdl-38437982

ABSTRACT

In the diagnosis of coronavirus disease 2019 (COVID-19), several types of instruments and reagents for SARS-CoV-2 nucleic acid testing have been introduced to meet clinical needs. We evaluated the clinical performances of ID NOW™ COVID-19 2.0 (ID NOW™ 2.0), which is capable of detecting SARS-CoV-2 within 12 min as part of point-of-care testing (POCT). Patients who displayed COVID-19 related symptoms, and who were tested for screening purposes, were recruited to this study. Two nasopharyngeal swabs were collected and tested using the ID NOW™ 2.0 test. Reference testing was performed using the cobas 8800 or 6800 (reagents: cobas SARS-CoV-2 and Flu A/B). A total of 38 samples and 46 samples were tested positive and negative, respectively, by the reference test. The ID NOW™ 2.0 showed a sensitivity of 94.7% (95% CI: 82.3-99.4) and a specificity of 100% (95% CI: 92.3-100). Samples that were positive by reference testing had cycle threshold (Ct) values ranging from 11.90 to 35.41. Among these reference positive samples, two samples were negative by ID NOW™ 2.0 with Ct values of 35.25 and 35.41. For samples with Ct values < 35, the sensitivity of ID NOW™ 2.0 was 100%. In Japan, the restrictions related to COVID-19 have been relaxed, however the COVID-19 epidemic still continues. ID NOW™ 2.0 is expected to be used as a rapid and reliable alternative to laboratory-based RT-PCR methods.

16.
Endocr J ; 71(5): 499-514, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38462511

ABSTRACT

We investigated the impact of the Coronavirus disease 2019 (COVID-19) pandemic on the management of endocrine and metabolic disorders in Japan. We conducted a cross-sectional nationwide questionnaire survey targeting board-certified endocrinologists under the auspices of the Japan Endocrine Society. The questionnaire consisted of multiple-choice questions and open-ended responses. Out of approximately 2,700 specialists, 528 (19.5%) opted to participate, suggesting a high level of interest in COVID-19 management among endocrinologists. The study found that almost half of participants had encountered cases of endocrine and metabolic disorders following COVID-19 infection or vaccination. Conditions related to thyroid diseases, glucose metabolism disorders/diabetes, and hypothalamic-pituitary disorders were particularly prevalent. Diabetes and obesity were identified as having high rates of severe cases or fatalities due to COVID-19. The study also highlighted challenges in routine diagnosis and treatment, emphasizing the potential benefits of combining remote consultations with in-person visits to optimize the frequency of examinations and check-ups during infectious disease outbreak which disrupts access to healthcare providers. The insights obtained from this survey are expected to contribute to ensuring appropriate healthcare provision for patients with endocrine and metabolic disorders by using flexible consultation formats, particularly even in the conditions where medical access may be limited due to future outbreaks of emerging or re-emerging infectious diseases.


Subject(s)
COVID-19 , Endocrine System Diseases , Metabolic Diseases , SARS-CoV-2 , Humans , COVID-19/epidemiology , Japan/epidemiology , Cross-Sectional Studies , Metabolic Diseases/epidemiology , Endocrine System Diseases/epidemiology , Endocrine System Diseases/therapy , Surveys and Questionnaires , Female , Male , Societies, Medical , Endocrinologists , Adult , Middle Aged , Endocrinology/organization & administration , Practice Patterns, Physicians'/statistics & numerical data
17.
Endocr J ; 71(3): 305-312, 2024 Mar 28.
Article in English | MEDLINE | ID: mdl-38246654

ABSTRACT

Coronavirus disease 2019 (COVID-19) due to a severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection can include various systemic organ disorders including endocrinopathies and neurological manifestations. We report the case of a 65-year-old Japanese man who developed isolated adrenocorticotropic hormone (ACTH) deficiency and encephalopathy following SARS-CoV-2 infection. Two weeks after his COVID-19 diagnosis, he was emergently admitted to our hospital because of subacute-onset delirium. On admission, he presented hyponatremia (128 mEq/L) and secondary adrenal insufficiency (ACTH <1.5 pg/mL, cortisol 0.53 µg/dL). Brain imaging and laboratory examinations including SARS-CoV-2 polymerase chain reaction testing in the cerebrospinal fluid revealed no abnormalities. His consciousness level worsened despite the amelioration of hyponatremia by intravenous hydrocortisone (100 mg/day), but his neurological presentations completely resolved after three consecutive days of high-dose (400 mg/day) hydrocortisone. His encephalopathy did not deteriorate during hydrocortisone tapering. He continued 15 mg/day hydrocortisone after discharge. His encephalopathy might have developed via a disturbance of the autoimmune system, or a metabolic effect associated with adrenal insufficiency, although the time lag between the hyponatremia's improvement and the patient's neurological response to the steroid was incompatible with common cases of delirium concurrent with adrenal insufficiency. At 13 months after his hospitalization, the patient's neurological symptoms have not recurred and he has no endocrinological dysfunctions other than the remaining ACTH deficiency. A thorough consideration of the immunological and metabolic characteristics of SARS-CoV-2 is advisable when clinicians treat patients during and even after their COVID-19 disease period.


Subject(s)
Adrenal Insufficiency , Adrenocorticotropic Hormone/deficiency , Brain Diseases , COVID-19 , Delirium , Endocrine System Diseases , Genetic Diseases, Inborn , Hypoglycemia , Hyponatremia , Male , Humans , Aged , Hydrocortisone/therapeutic use , COVID-19/complications , COVID-19 Testing , Hyponatremia/complications , SARS-CoV-2 , Adrenal Insufficiency/complications , Adrenal Insufficiency/drug therapy , Brain Diseases/etiology , Brain Diseases/complications , Delirium/etiology , Delirium/complications
18.
J Water Health ; 22(3): 601-611, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38557574

ABSTRACT

Coronavirus disease 2019 (COVID-19) is an infectious viral disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that emerged at the end of 2019. SARS-CoV-2 can be transmitted through droplets, aerosols, and fomites. Disinfectants such as alcohol, quaternary ammonium salts, and chlorine-releasing agents, including hypochlorous acid, are used to prevent the spread of SARS-CoV-2 infection. In the present study, we investigated the efficacy of ionless hypochlorous acid water (HOCl) in suspension and by spraying to inactivate SARS-CoV-2. The virucidal efficacy of HOCl solution in tests against SARS-CoV-2 was evaluated as 50% tissue culture infectious dose. Although the presence of organic compounds influenced the virucidal efficacy, HOCl treatment for 20 s was significantly effective to inactivate Wuhan and Delta strains in the suspension test. HOCl atomization for several hours significantly reduced the SARS-CoV-2 attached to plastic plates. These results indicate that HOCl solution with elimination containing NaCl and other ions may have high virucidal efficacy against SARS-CoV-2. This study provides important information about the virucidal efficacy and use of HOCl solution.


Subject(s)
COVID-19 , Disinfectants , Humans , SARS-CoV-2 , COVID-19/prevention & control , Hypochlorous Acid/pharmacology , Water , Disinfectants/pharmacology
19.
BMC Nephrol ; 25(1): 143, 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38649863

ABSTRACT

BACKGROUND: The clinical manifestations and prognosis of hemodialysis patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) during the Omicron wave of the pandemic infection were still unclear. This study investigated the clinical characteristics of patients undergoing maintenance hemodialysis (MHD) infected with it. METHODS: This retrospective single-center study included 151 patients undergoing MHD. Healthcare workers were selected as control group were assessed from December 1, 2022 to March 31, 2023. Clinical data, laboratory test results, treatment protocols, and prognoses were collected and analyzed. RESULTS: The study population included 146 patients with MHD, 93 (63.7%) of whom were infected with SARS-CoV-2. The number of non-severe, severe, and critical cases was 84 (90.3%), 4 (4.3%), and 5 (5.3%), respectively. Six patients (6.5%) died during the study period. The main symptoms of SARS-CoV-2 infection, including fever, cough, and fatigue, were less common in patients with MHD than the controls. During SARS-CoV-2 infection, the C-reactive protein (2.9 vs. 11.8 mg/dl, p < 0.0001) and ferritin levels(257.7 vs. 537 ng/l, p < 0.0001) were elevated. The hemoglobin(113vs 111 g/L, p = 0.0001) and albumin levels(39.4 vs. 36.1 g/L, p < 0.0001) decreased. Generally, it took two months for the hemoglobin levels to recover. Positivity rate for SARS-COV-2 serum immunoglobin G (IgG) antibodies and IgG titers were lower in dialysis patients than the controls. Age was positively associated with disease severity, while age and hyponatremia were associated with death. CONCLUSIONS: Patients with MHD and COVID-19 were primarily classified as non-severe. SARS-CoV-2 infection would soon lead to the increase of inflammation related acute response protein in dialysis patients, and then lead to the decrease of hemoglobin and albumin. About 9.6% in HD patients were severe cases and had poor prognosis. Advanced age and hyponatremia were associated with disease severity and prognosis.


Subject(s)
COVID-19 , Renal Dialysis , SARS-CoV-2 , Humans , COVID-19/epidemiology , COVID-19/therapy , Male , Retrospective Studies , Female , Middle Aged , Aged , Beijing/epidemiology , Adult , Pandemics , Kidney Failure, Chronic/therapy , Kidney Failure, Chronic/epidemiology , Prognosis , C-Reactive Protein/metabolism , C-Reactive Protein/analysis
20.
BMC Pulm Med ; 24(1): 34, 2024 Jan 15.
Article in English | MEDLINE | ID: mdl-38225613

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) has affected individuals worldwide, and patients with cancer are particularly vulnerable to COVID-19-related severe illness, respiratory failure, and mortality. The relationship between COVID-19 and cancer remains a critical concern, and a comprehensive investigation of the factors affecting survival among patients with cancer who develop COVID-19-related respiratory failure is warranted. We aim to compare the characteristics and outcomes of COVID-19-related acute respiratory failure in patients with and without underlying cancer, while analyzing factors affecting in-hospital survival among cancer patients. METHODS: We conducted a retrospective observational study at Taipei Veterans General Hospital in Taiwan from May to September 2022, a period during which the omicron variant of the severe acute respiratory syndrome coronavirus 2 was circulating. Eligible patients had COVID-19 and acute respiratory failure. Clinical data, demographic information, disease severity markers, treatment details, and outcomes were collected and analyzed. RESULTS: Of the 215 enrolled critically ill patients with COVID-19, 65 had cancer. The patients with cancer were younger and had lower absolute lymphocyte counts, higher ferritin and lactate dehydrogenase (LDH) concentrations, and increased vasopressor use compared with those without cancer. The patients with cancer also received more COVID-19 specific treatments but had higher in-hospital mortality rate (61.5% vs 36%, P = 0.002) and longer viral shedding (13 vs 10 days, P = 0.007) than those without cancer did. Smoking [odds ratio (OR): 5.804, 95% confidence interval (CI): 1.847-39.746], elevated LDH (OR: 1.004, 95% CI: 1.001-1.012), vasopressor use (OR: 5.437, 95% CI: 1.202-24.593), and new renal replacement therapy (OR: 3.523, 95% CI: 1.203-61.108) were independent predictors of in-hospital mortality among patients with cancer and respiratory failure. CONCLUSION: Critically ill patients with cancer experiencing COVID-19-related acute respiratory failure present unique clinical features and worse clinical outcomes compared with those without cancer. Smoking, elevated LDH, vasopressor use, and new renal replacement therapy were risk factors for in-hospital mortality in these patients.


Subject(s)
COVID-19 , Neoplasms , Respiratory Distress Syndrome , Respiratory Insufficiency , Humans , COVID-19/complications , SARS-CoV-2 , Critical Illness , Neoplasms/complications , Respiratory Insufficiency/etiology , Respiratory Insufficiency/therapy , Retrospective Studies
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