Somatic loss of ATM is a late event in pancreatic tumorigenesis.

Understanding the timing and spectrum of genetic alterations that contribute to the development of pancreatic cancer is essential for effective interventions and treatments. The aim of this study was to characterize somatic ATM alterations in noninvasive pancreatic precursor lesions and invasive pancreatic adenocarcinomas from patients with and without pathogenic germline ATM variants. DNA was isolated and sequenced from the invasive pancreatic ductal adenocarcinomas and precursor lesions of patients with a pathogenic germline ATM variant. Tumor and precursor lesions from these patients as well as colloid carcinoma from patients without a germline ATM variant were immunolabeled to assess ATM expression. Among patients with a pathogenic germline ATM variant, somatic ATM alterations, either mutations and/or loss of protein expression, were identified in 75.0% of invasive pancreatic adenocarcinomas but only 7.1% of pancreatic precursor lesions. Loss of ATM expression was also detected in 31.0% of colloid carcinomas from patients unselected for germline ATM status, significantly higher than in pancreatic precursor lesions [pancreatic intraepithelial neoplasms (p = 0.0013); intraductal papillary mucinous neoplasms, p = 0.0040] and pancreatic ductal adenocarcinoma (p = 0.0076) unselected for germline ATM status. These data are consistent with the second hit to ATM being a late event in pancreatic tumorigenesis. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Intraparenchymal metastases as a cause for local recurrence of pancreatic cancer.

Using CODA, a technique for three-dimensional reconstruction of large tissues, Kiemen et al. report observation of a microscopic focus of pancreatic cancer found in the vasculature of grossly normal human pancreas tissue resected adjacent to a large tumour. They use TP53 and SMAD4 staining to relate the small focus to the primary tumour. This report describes a represents a probable case of intraparenchymal metastasis of pancreatic cancer, revealing a probable cause of local recurrence.

A single-center review of pre-exposure prophylaxis with tixagevimab-cilgavimab in solid organ transplant recipients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) continues to negatively impact solid organ transplant recipients (SOTr). Data on the use of tixagevimab-cilgavimab (tix-cil) in vaccinated SOTr during circulation of Omicron and its subvariants are limited. Therefore, this single-center review was conducted to evaluate tix-cil efficacy in multiple organ transplant groups during a study period where Omicron B.1.1.529, BA.2.12.1, and BA.5 predominated. METHODS: In this single-center retrospective study, we evaluated the incidence of COVID-19 infection in adult SOTr who did or did not receive pre-exposure prophylaxis (PrEP) with tix-cil. SOTr were included if they were at least 18 years of age and met emergency use authorization criteria for tix-cil use. The primary outcome analyzed was the incidence of COVID-19 infection. RESULTS: Ninety SOTr met inclusion criteria and comprised of two groups, tix-cil PrEP (n = 45) and no tix-cil PrEP (n = 45). Of SOTr who received tix-cil PrEP, three (6.7%) developed COVID-19 infection, compared to eight (17.8%) in the no tix-cil PrEP group (p = .20). Of the 11 SOTr diagnosed with COVID-19, 15 (82.2%) were fully vaccinated against COVID-19 prior to transplantation. Moreover, 18.2% and 81.8% of the COVID-19 cases observed were asymptomatic and mild-to-moderate, respectively. DISCUSSION: Our study results, which included months when BA.5 was in increased circulation, suggest no significant difference in COVID-19 infection with or without use of tix-cil PrEP in our solid organ transplant groups. As the COVID-19 pandemic continues to evolve, clinical utility of tix-cil should be evaluated against new, emerging strains.

Examination of ATM, BRCA1, and BRCA2 promoter methylation in patients with pancreatic cancer.

BACKGROUND: Pancreatic cancer is a lethal disease with a poor 5-year survival rate. Pathogenic germline variants in the coding regions of ATM, BRCA1, and BRCA2 are found in up to 4.8% of pancreatic cancer patients. Germline promoter methylation and gene silencing arising from a germline variant or through other mechanisms have been described as a cause of tumor suppressor gene inactivation. METHODS: We measured the level of promoter methylation of the ATM, BRCA1, and BRCA2 genes in peripheral blood lymphocytes from 655 patients with pancreatic cancer using real-time PCR. RESULTS: No evidence of germline promoter methylation of any of these genes was found. Promoter methylation levels were minimal with no patient having promoter methylation greater than 3.4%, 3.3%, and 7.6% for ATM, BRCA1 and BRCA2, respectively, well below levels found in patients who have inherited promoter methylation (∼50%). CONCLUSIONS: We found no evidence of germline promoter methylation for the pancreatic susceptibility genes ATM, BRCA1 and BRCA2 in patients with pancreatic cancer. This study reveals that constitutive germline methylation of promoter CpG islands is rare in pancreatic cancer.

Generation and characterization of a cell line from an intraductal tubulopapillary neoplasm of the pancreas.

Intraductal tubulopapillary neoplasm (ITPN) is a distinct precancerous lesion in the pancreas with unique clinical and molecular features. Although in vitro studies in two-dimensional culture have led to numerous important insights in pancreatic cancer, such models are currently lacking for precancerous lesions. In this study, we report the generation and characterization of a cell line from a human pancreatic ITPN. Neoplastic cells were initially cultured in a three-dimensional organoid system, followed by transfer to two-dimensional culture. RNA sequencing revealed a gene expression profile consistent with pancreatic ductal origin, and whole genome sequencing identified many somatic mutations (including in genes involved in DNA repair and Wnt signaling) and structural rearrangements. In vitro characterization of the tumorigenic potential demonstrated a phenotype between that of normal pancreatic ductal cells and cancer cell lines. This cell line represents a valuable resource for interrogation of unique ITPN biology, as well as precancerous pancreatic lesions more generally.

Prevalence of Germline Mutations Associated With Cancer Risk in Patients With Intraductal Papillary Mucinous Neoplasms.

BACKGROUND & AIMS: Many patients with pancreatic adenocarcinoma carry germline mutations associated with increased risk of cancer. It is not clear whether patients with intraductal papillary mucinous neoplasms (IPMNs), which are precursors to some pancreatic cancers, also carry these mutations. We assessed the prevalence of germline mutations associated with cancer risk in patients with histologically confirmed IPMN. METHODS: We obtained nontumor tissue samples from 315 patients with surgically resected IPMNs from 1997 through 2017, and we sequenced 94 genes with variants associated with cancer risk. Mutations associated with increased risk of cancer were identified and compared with individuals from the Exome Aggregation Consortium. RESULTS: We identified 23 patients with a germline mutation associated with cancer risk (7.3%; 95% confidence interval, 4.9-10.8). Nine patients had a germline mutation associated with pancreatic cancer susceptibility (2.9%; 95% confidence interval, 1.4-5.4). More patients with IPMNs carried germline mutations in ATM (P < .0001), PTCH1 (P < .0001), and SUFU (P < .0001) compared with controls. Patients with IPMNs and germline mutations associated with pancreatic cancer were more like to have concurrent invasive pancreatic carcinoma compared with patients with IPMNs without these mutations (P < .0320). CONCLUSIONS: In sequence analyses of 315 patients with surgically resected IPMNs, we found that almost 3% to carry mutations associated with pancreatic cancer risk. More patients with IPMNs and germline mutations associated with pancreatic cancer had concurrent invasive pancreatic carcinoma compared with patients with IPMNs without these mutations. Genetic analysis of patients with IPMNs might identify those at greatest risk for cancer.

Clostridium difficile disease in solid organ transplant recipients: a recommended treatment paradigm.

PURPOSE OF REVIEW: Organ transplant recipients have an increased incidence of Clostridium difficile disease and lower clinical response rates compared with the general population. Transplant specific treatment approaches are not defined. Therefore, a review of therapeutics in the transplant population is needed. RECENT FINDINGS: A literature review on the current therapies for C. difficile was performed focusing on the evidence in transplant recipients and immunosuppressed populations. SUMMARY: Transplant patients warrant an aggressive approach to treatment. The authors propose a suggested treatment paradigm for therapy.

Chemopreventive role of olive oil in colon carcinogenesis by targeting noncoding RNAs and methylation machinery.

Epigenetic therapy induced by dietary components has become a strong interest in the field of cancer prevention. Olive oil, a potent dietary chemopreventive agent, control colon cancer, however, its role in epigenetic therapy remains unclear. Thus, we aimed to investigate the effect of olive oil in a preclinical model of colon cancer by targeting genetic and epigenetic mechanisms. DMH was used to induce colon cancer in rats; while olive oil was given to separate group of rats along with DMH treatment. Tumor burden and incidence in DMH and DMH + olive oil-treated rats was observed by macroscopic examination and histoarchitectural studies. Potent anti-inflammatory, anti-angiogenic and pro-apoptotic activity of olive oil was explored by gene expression and immunohistochemical studies. The effect of olive oil on epigenetic alterations was examined by detecting promoter methylation with MS-HRM and dysregulation of miRNA by TaqMan MicroRNA Assay. We observed that olive oil administration lowered tumor incidence and inhibited the development of tumors in DMH-treated rats. Olive oil markedly decreased the expression of inflammatory and angiogenic markers and restored the expression of pro-apoptotic markers in DMH-treated rats. Furthermore, the inverse relationship between gene expression and DNA methylation, deviant miRNA pattern and miRNA silencing mediated by aberrant DNA methylation was also seen in DMH-treated rats, which was potentially reversible upon olive oil treatment. Our study concludes that olive oil may play a role in the epigenetic therapy by altering NF-κB and apoptotic pathways via targeting noncoding RNAs and methylation machinery that affecting epigenome to prevent colon carcinogenesis.

Clostridium difficile infection in solid organ transplant recipients.

PURPOSE OF REVIEW: Clostridium difficile infection (CDI) is a major healthcare-associated infection that causes significant morbidity and an economic impact in the United States. In this review, we provide an overview of Clostridium difficile infection in solid organ transplant recipients with an emphasis on recent literature. RECENT FINDINGS: C. difficile in solid organ transplant population has unique risk factors. Fecal microbiota transplantation has shown favorable results in treatment of recurrent C. difficile in this population. Preliminary data from animal studies suggests excellent efficacy with immunization against C. difficile toxins. SUMMARY: Over the last decade, number of individuals receiving solid organ transplants has increased exponentially making peri-transplant complications a common occurrence.C. difficile is a frequent cause of morbidity in solid organ transplant recipients. Early and accurate diagnosis of C. difficile requires a stepwise approach. Differentiating between asymptomatic carriage and infection is a diagnostic challenge. Microbial diversity is inversely proportional to risk of C. difficile infection. Antimicrobial stewardship programs help to retain microbial diversity in individuals susceptible to CDI. Recurrent or relapsing C. difficile infection require fecal microbiota transplantation for definitive cure.

Alterations in K-ras, APC and p53-multiple genetic pathway in colorectal cancer among Indians.

The incidence of colorectal cancer (CRC) is increasing rapidly in Asian countries during the past few decades, but no comprehensive analysis has been done to find out the exact cause of this disease. In this study, we investigated the frequencies of mutations and expression pattern of K-ras, APC (adenomatosis polyposis coli) and p53 in tumor, adjoining and distant normal mucosa and to correlate these alterations with patients clinicopathological parameters as well as with the survival. Polymerase chain reaction (PCR)-restriction digestion was used to detect mutations in K-ras and PCR-SSCP (Single Strand Conformation Polymorphism) followed by DNA sequencing was used to detect mutations in APC and p53 genes. Immunohistochemistry was used to detect the expression pattern of K-ras, APC and p53 proteins. The frequencies of mutations of K-ras, APC and p53 in 30 tumor tissues samples were 26.7 %, 46.7 % and 20 %, respectively. Only 3.3 % of tumors contained mutations in all the three genes. The most common combination of mutation was APC and p53 whereas mutation in both p53 and K-ras were extremely rare. There was no association between the mutations and expression pattern of K-ras, APC and p53 (p>0.05). In Indians, the frequency of alterations of K-ras and APC is similar as in Westerns, whereas the frequency of p53 mutation is slightly lower. The lack of multiple mutations in tumor specimens suggests that these genetic alterations might have independent influences on CRC development and there could be multiple alternative genetic pathways to CRC in our present study cohort.

Investigating the Glucagon-like Peptide-1 and Its Receptor in Human Brain: Distribution of Expression, Functional Implications, Age-related Changes and Species Specific Characteristics.

Introduction: Emerging evidence has shown that the glucagon-like peptide-1 (GLP-1) agonist can be used to treat Alzheimer disease; however, knowledge of its neural targets is limited. To understand the neural substrates of GLP-1, we have done whole brain mapping for GLP-1 and its receptor (GLP-1R), in 30 human brains. Methods: GLP-1 expression was studied by immuno-histochemistry and confirmed by the western blot method. The GLP-1R gene expression was studied by reverse transcription polymerase chain reaction. Results: GLP-1 expression was observed in most of the cortical areas (maximum in frontal, prefrontal and parietal cortex), diencephalon, and brainstem, but not in the cerebellum. Protein expression studies validated these results. The highest expression of GLP-1R was found in the frontal cortex. The orbitofrontal cortex and cerebellum had negligible expression. Hippocampus demonstrated a significant presence of GLP-1R but patchy immunoreactivity to GLP-1. GLP-1R presence in most of the human cortical regions and absence in the cerebellum is the major deviation from the animal brain. Sites that might be of interest in Alzheimer have been identified. GLP-1 demonstrated an age-related decline in most of the areas after the fifth decade. At 60 years, GLP-1 was not found in any of the cortical areas except in the prefrontal cortex; however, it was present in the sub-cortical areas. Conclusion: Age-related profiling of GLP-1 in various brain areas has been analyzed, which can have an important bearing on understanding Alzheimer disease. This study provides a detailed description of GLP-1 and an brain mapping for the first time and may lead to novel treatment options targeting the GLP-1 receptors. Highlights: Glucagon like peptide-1 (GLP-1) agonist can be used for treating Alzheime'rs disease.GLP-1 gene expression was seen in cortical areas, diencephalon and brainstem, but not in cerebellum.Hippocampus demonstrated significant presence of GLP-1R but patchy immunoreactivity to GLP-1.GLP-1 demonstrated age related decline in most of the areas after fifth decade.A detailed description of GLP-1 and amp; GLP-1R locations was given which may lead to novel treatment options. Plain Language Summary: Emerging evidence has shown that the glucagon like peptide-1 (GLP1-1) agonist can be used for treating Alzheimer's disease but knowledge of its neural targets is limited. To understand the neural substrates of GLP-1, we have done whole brain mapping for GLP-1 and its receptor (GLP-1R), in 30 human brains. GLP-1 expression was studied by immuno-histochemistry and confirmed by western blot method. GLP-1R gene expression was studied by RT-PCR. GLP-1 expression was seen in most of the cortical areas (maximum in frontal, prefrontal & amp; parietal cortex), diencephalon and brainstem, but not in cerebellum. Protein expression studies validated these results. Highest expression of GLP-1R was found in the frontal cortex. The orbito-frontal cortex and cerebellum had negligible expression. Hippocampus demonstrated significant presence of GLP-1R but patchy immunoreactivity to GLP-1. GLP-1R presence in most of the human cortical regions and absence in cerebellum is the major deviation from the animal brain. Sites which might be of interest in Alzheimer's have been identified. GLP-1 demonstrated age related decline in most of the areas after 5 th decade. At 60 years GLP-1 was not found in any of the cortical areas except in the prefrontal cortex but it was present in the sub-cortical areas. Age related profiling of GLP-1 in various brain areas has been analysed, which can have important bearing on understanding the Alzheimer's. This study provides detailed description of GLP-1 and ations by complete human brain mapping for the first time and may lead to novel treatment options targeting the GLP-1 receptors.

Algal bioplastics: current market trends and technical aspects.

Abstract: Plastics are undebatably a hot topic of discussion across international forums due to their huge ecological footprint. The onset of COVID-19 pandemic has exacerbated the issue in an irreversible manner. Bioplastics produced from renewable sources are a result of lookout for sustainable alternatives. Replacing a ton of synthetic plastics with biobased ones reduces 1.8 tons CO2 emissions. Here, we begin with highlighting the problem statement-Plastic accumulation and its associated negative impacts. Microalgae outperforms plants and microbes, when used to produce bioplastic due to superior growth rate, non-competitive nature to food, and simultaneous wastewater remediation. They have minimal nutrient requirements and less dependency on climatic conditions for cultivation. These are the reasons for current boom in the algal bioplastic market. However, it is still not at par in price with the petroleum-based plastics. A brief market research has been done to better evaluate the current global status and future scope of algal bioplastics. The objective of this review is to propose possible solutions to resolve the challenges in scale up of bioplastic industry. Various bioplastic production technologies have been comprehensively discussed along with their optimization strategies. Overall studies discussed show that in order to make it cost competitive adopting a multi-dimensional approach like algal biorefinery is the best way out. A holistic comparison of any bio-based alternative with its conventional counterpart is imperative to assess its impact upon commercialization. Therefore, the review concludes with the life cycle assessment of bioplastics and measures to improve their inclusivity in a circular economy.

Clostridioides difficile Toxin B PCR Cycle Threshold as a Predictor of Toxin Testing in Stool Specimens from Hospitalized Adults.

Rapid, accurate detection of Clostridioides difficile toxin may potentially be predicted by toxin B PCR cycle threshold (tcdB Ct). We investigated the validity of this approach in an inpatient adult population. Patients who tested positive by C. difficile PCR (Cepheid GeneXpert) from December 2016 to October 2020 (n = 368) at a tertiary medical center were included. All stool samples were further tested by rapid glutamate dehydrogenase (GDH)/toxin B EIA and cell cytotoxin neutralization assay (CCNA). Receiver operating characteristic curves were analyzed. The area under the curve for tcdB Ct predicting toxin result by EIA was 0.795 (95% confidence interval (CI) 0.747−0.843) and by CCNA was 0.771 (95% CI 0.720−0.822). The Youden Ct cutoff for CCNA was ≤27.8 cycles (sensitivity 65.0%, specificity 77.2%). For specimens with Ct ≤ 25.0 cycles (n = 115), CCNA toxin was positive in >90%. The negative predictive value of tcdB Ct for CCNA was no greater than 80% regardless of cutoff chosen. In summary, very low Ct values (≤25.0) could have limited value as a rapid indicator of positive toxin status by CCNA in our patient population. A broad distribution of Ct values for toxin-negative and toxin-positive specimens precluded more robust prediction. Additional data are needed before broader application of Ct values from qualitatively designed assays to clinical laboratory reporting.

Functional CDKN2A assay identifies frequent deleterious alleles misclassified as variants of uncertain significance.

Pathogenic germline CDKN2A variants are associated with an increased risk of pancreatic ductal adenocarcinoma (PDAC). CDKN2A variants of uncertain significance (VUSs) are reported in up to 4.3% of patients with PDAC and result in significant uncertainty for patients and their family members as an unknown fraction are functionally deleterious, and therefore, likely pathogenic. Functional characterization of CDKN2A VUSs is needed to reclassify variants and inform clinical management. Twenty-nine germline CDKN2A VUSs previously reported in patients with PDAC or in ClinVar were evaluated using a validated in vitro cell proliferation assay. Twelve of the 29 CDKN2A VUSs were functionally deleterious (11 VUSs) or potentially functionally deleterious (1 VUS) and were reclassified as likely pathogenic variants. Thus, over 40% of CDKN2A VUSs identified in patients with PDAC are functionally deleterious and likely pathogenic. When incorporating VUSs found to be functionally deleterious, and reclassified as likely pathogenic, the prevalence of pathogenic/likely pathogenic CDKN2A in patients with PDAC reported in the published literature is increased to up to 4.1% of patients, depending on family history. Therefore, CDKN2A VUSs may play a significant, unappreciated role in risk of pancreatic cancer. These findings have significant implications for the counselling and care of patients and their relatives.

Role of Cyclooxygenase-2 in colorectal cancer patients.

Cyclooxygenase-2 (COX-2) is an inducible enzyme which triggers the biosynthesis of prostaglandins. COX-2 is activated in response to inflammatory stimuli and is one of the major molecules that is involved in the development and progression of colorectal cancer (CRC). Consistent with such a conceptual framework, it has been shown that COX-2 inhibitors prevent the carcinogenesis of CRC and aid in the treatment of sporadic or familial cases of CRC as shown by an overall increase in the survival rate. However, prolonged use of these inhibitors is associated with increase risk of development of cardiovascular complications, implying that further research is required to identify COX-2 inhibitors that are associated with lower risks of such complications.

Frame to Improve the Fit of N95 Filtering Face Mask Respirators.

OBJECTIVE: Test a device that can improve upon the seal of filtering face mask respirators (FFRs). METHODS: A 3-D prototype for a fit improvement frame (FIF) was created and quantitative fit testing was performed for FFRs with and without the FIF. RESULTS: Thirty eight volunteers underwent fit testing. The overall fit pass rate was 100% for the 3M model 1860 masks, 50% for the 3M model 8511 masks, 13% for the BYD CARE model DE2322, and 7% for the Honeywell DC300N95. When using the FIF the overall passing rate increase to 87% for the DE2322 + FIF (P < 0.01) and for the DC300N95 + FIF the passing rate increase to 73% (P < 0.01). CONCLUSION: The FIF is effective in improving the mask fit of a common flat fold N95 masks and potentially other N95 masks.

Predicting clinical outcomes in COVID-19 using radiomics on chest radiographs.

OBJECTIVES: For optimal utilization of healthcare resources, there is a critical need for early identification of COVID-19 patients at risk of poor prognosis as defined by the need for intensive unit care and mechanical ventilation. We tested the feasibility of chest X-ray (CXR)-based radiomics metrics to develop machine-learning algorithms for predicting patients with poor outcomes. METHODS: In this Institutional Review Board (IRB) approved, Health Insurance Portability and Accountability Act (HIPAA) compliant, retrospective study, we evaluated CXRs performed around the time of admission from 167 COVID-19 patients. Of the 167 patients, 68 (40.72%) required intensive care during their stay, 45 (26.95%) required intubation, and 25 (14.97%) died. Lung opacities were manually segmented using ITK-SNAP (open-source software). CaPTk (open-source software) was used to perform 2D radiomics analysis. RESULTS: Of all the algorithms considered, the AdaBoost classifier performed the best with AUC = 0.72 to predict the need for intubation, AUC = 0.71 to predict death, and AUC = 0.61 to predict the need for admission to the intensive care unit (ICU). AdaBoost had similar performance with ElasticNet in predicting the need for admission to ICU. Analysis of the key radiomic metrics that drive model prediction and performance showed the importance of first-order texture metrics compared to other radiomics panel metrics. Using a Venn-diagram analysis, two first-order texture metrics and one second-order texture metric that consistently played an important role in driving model performance in all three outcome predictions were identified. CONCLUSIONS: Considering the quantitative nature and reliability of radiomic metrics, they can be used prospectively as prognostic markers to individualize treatment plans for COVID-19 patients and also assist with healthcare resource management. ADVANCES IN KNOWLEDGE: We report on the performance of CXR-based imaging metrics extracted from RT-PCR positive COVID-19 patients at admission to develop machine-learning algorithms for predicting the need for ICU, the need for intubation, and mortality, respectively.

Machine learning based predictors for COVID-19 disease severity.

Predictors of the need for intensive care and mechanical ventilation can help healthcare systems in planning for surge capacity for COVID-19. We used socio-demographic data, clinical data, and blood panel profile data at the time of initial presentation to develop machine learning algorithms for predicting the need for intensive care and mechanical ventilation. Among the algorithms considered, the Random Forest classifier performed the best with [Formula: see text] for predicting ICU need and [Formula: see text] for predicting the need for mechanical ventilation. We also determined the most influential features in making this prediction, and concluded that all three categories of data are important. We determined the relative importance of blood panel profile data and noted that the AUC dropped by 0.12 units when this data was not included, thus indicating that it provided valuable information in predicting disease severity. Finally, we generated RF predictors with a reduced set of five features that retained the performance of the predictors trained on all features. These predictors, which rely only on quantitative data, are less prone to errors and subjectivity.

The time to offer treatments for COVID-19.

Background: COVID-19 has several overlapping phases. Treatments to date have focused on the late stage of disease in hospital. Yet, the pandemic is by propagated by the viral phase in out-patients. The current public health strategy relies solely on vaccines to prevent disease.Methods: We searched the major national registries, pubmed.org, and the preprint servers for all ongoing, completed and published trial results.Results: As of 2/15/2021, we found 111 publications reporting findings on 14 classes of agents, and 9 vaccines. There were 62 randomized controlled studies, the rest retrospective observational analyses. Only 21 publications dealt with outpatient care. Remdesivir and high titer convalescent plasma have emergency use authorization for hospitalized patients in the U.S.A. There is also support for glucocorticoid treatment of the COVID-19 respiratory distress syndrome. Monoclonal antibodies are authorized for outpatients, but supply is inadequate to treat all at time of diagnosis. Favipiravir, ivermectin, and interferons are approved in certain countries.Expert Opinion: Vaccines and antibodies are highly antigen specific, and new SARS-Cov-2 variants are appearing. We call on public health authorities to authorize treatments with known low-risk and possible benefit for outpatients in parallel with universal vaccination.