IMPACT OF THE COVID-19 PANDEMIC ON ADHERENCE TO DISEASE MODIFYING DRUGS AMONG PATIENTS WITH RHEUMATIC DISEASES: A POPULATION-BASED, INTERRUPTED TIME SERIES ANALYSIS

BackgroundAlthough studies have quantified adherence to medications among patients with rheumatic diseases (RD) during the COVID-19, lack of direct pre-pandemic comparison precludes understanding of impact of the pandemic.ObjectivesOur objective was to evaluate the effect of the COVID-19 pandemic on adherence to disease modifying drugs (DMARDs) including conventional synthetic (csDMARDs) and targeted synthetic (tsDMARDs).MethodsWe linked population-based health data on all physician visits, hospital admissions, and all dispensed medications, regardless of payer in British Columbia from 01/01/1996 to 3/31/2021. We identified prescriptions for csDMARDs (including methotrexate, hydroxychloroquine) and tsDMARDs, namely anti-TNFs (including infliximab, etanercept, adalimumab) and rituximab using drug identification numbers among indicated individuals with RD. We defined March 11, 2020, as the ‘index date' which corresponded to the date that mitigation measures for the COVID-19 pandemic were first introduced. We assessed adherence as proportion days covered (PDC), calculated monthly in the 12 months before and 12 months after the index date. We used interrupted time-series models, namely segmented regression to estimate changes and trends in adherence before and after the index date.ResultsOur analysis showed that the mean PDCs for all included DMARDs stayed relatively steady in the 12 months before and after mitigation measures were introduced (see Table 1). Adherence was highest among anti-TNFs, methotrexate, and azathioprine. Anti-TNFs were on a downward trajectory 12 months prior to the index date. Interrupted time-series modeling demonstrated statistically significant differences in the trends in PDCs post- vs. pre-mitigation measures for all anti-TNFS (slope [∂]: 1.38, standard error [SE]: 0.23), infliximab (∂: 1.35, SE: 0.23), adalimumab (∂: 0.82, SE: 0.25), and etanercept (∂: 1.07, SE: 0.25) (see Figure 1a). Conversely, the csDMARDs were on a flatter trajectory, and methotrexate (∂: -0.53, SE: 0.16), leflunomide (∂: 0.43, SE: 0.08), mycophenolate (∂: -1.26, SE: 0.48), cyclophosphamide (∂: 0.29, SE: 0.05), minocycline (∂: 0.04, SE: 0.02), chloroquine (∂: 0.02, SE: 0.00) showed statistically significant changes in estimated PDC trajectory after mitigation measures were introduced (see Figure 1b).ConclusionThis population-based study demonstrates that messaging and pandemic mitigation measures did not affect adherence to DMARDs.Table 1.Mean PDC 1 year before and after mitigation measures for the COVID-19 pandemic were introduced.MedicationMean PDC (%) 12 months before index dateMean PDC (%) 12 months after index datecsDMARDsmethotrexate28.926.8azathioprine21.819.5sulfasalazine16.214.9leflunomide14.313.0cyclosporine13.711.5hydroxychloroquine10.59.6mycophenolate4.52.9antimalarials4.43.9penicillamine3.53.4cyclophosphamide1.50.7chlorambucil1.20.4minocycline1.10.9gold0.50.2chloroquine0.10.0tsDMARDsanti-TNFs52.149.2infliximab41.838.3adalimumab40.336.8etanercept31.828.9rituximab3.42.9REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Impact of improving infection control and antibiotic stewardship practices on nosocomial infections and antimicrobial resistance in an oncology centre from India

Background: Improving basic infection control (IC) practices, diagnostics and anti-microbial stewardship (AMS) are key tools to handle antimicrobial resistance (AMR). Material(s) and Method(s): This is a retrospective study done over 6 years (2016-2021) in an oncology centre in North India with many on-going interventions to improve IC practices, diagnostics and AMS. This study looked into AMR patterns from clinical isolates, rates of hospital acquired infections (HAI) and clinical outcomes. Result(s): Over all, 98,915 samples were sent for culture from 158,191 admitted patients. Most commonly isolated organism was E. coli (n = 6951;30.1%) followed by Klebsiella pneumoniae (n = 5801;25.1%) and Pseudomonas aeroginosa (n = 3041;13.1%). VRE (Vancomycin resistant Enterococcus) rates fell down from 43.5% in Jan-June 2016 to 12.2% in July-Dec 2021, same was seen in CR (carbapenem resistant) Pseudomonas (23.0%-20.6%, CR Acinetobacter (66.6%-17.02%) and CR E. coli (21.6%-19.4%) over the same study period. Rate of isolation of Candida spp. from non-sterile sites also showed reduction (1.68 per 100 patients to 0.65 per 100 patients). Incidence of health care associated infections also fell from 2.3 to 1.19 per 1000 line days for CLABSI, 2.28 to 1.88 per 1000 catheter days for CAUTI. There was no change in overall mortality rates across the study period. Conclusion(s): This study emphasizes the point that improving compliance to standard IC recommendations and improving diagnostics can help in reducing the burden of antimicrobial resistance.Copyright © 2023 Indian Association of Medical Microbiologists

Distribution and drug resistance analysis of pathogenic bacteria in a hospital blood culture, 2018-2022

Objective: To analyze the distribution and drug resistance of pathogenic bacteria in blood culture specimens of patients with bloodstream infections before and after COVID-19 (2018-2019 and 2020-2021), and to provide scientific basis and reference for rational treatment and effective control of bloodstream infections in the post-epidemic period. Methods: Blood culture specimens were collected from patients in Zhongnan Hospital of Wuhan University in the two years before and after the COVID-19 outbreak (2018-2021). The Automated Blood Culture Systems were used to perform blood culture on blood specimens sent for clinical inspection, and the Vitek MS automatic bacterial identification mass spectrometer was used for strain identification and the Vitek 2 automatic bacterial drug susceptibility analyzer was used for drug susceptibility testing and drug resistance analysis. Results: Blood culture specimens were performed on 28 736 patients with suspected bloodstream infection submitted for inspection from January 2018 to December 2019, and a total of 2 181 strains of pathogenic bacteria were detected after removing duplicate strains, with a positive rate of 7.69%, including 1 046 strains of Gram-negative bacteria, accounting for 47.96%. From January 2020 to December 2021, blood culture specimens from 26 083 patients with suspected bloodstream infection were submitted for inspection, and a total of 2 111 strains of pathogenic bacteria were detected after excluding duplicate strains, with a positive rate of 8.09%, including 1 000 strains of Gram-negative bacteria accounted for 47.37%. The drug resistance of Klebsiella pneumoniae was relatively serious, and the sensitivity rate to ertapenem, polymyxin B and tigecycline was more than 90%. The main non-fermentative bacteria Acinetobacter baumannii was more than 50% sensitive to piperacillin/tazobactam, amikacin and polymyxin B. The sensitivity rates of Pseudomonas aeruginosa to piperacillin/tazobactam, ceftazidime, cefepime, amikacin, gentamicin, tobramycin, ciprofloxacin, levofloxacin, piperacillin and meropenem were more than 50%. Conclusions: In the two years before and after COVID-19, there are many types of pathogenic bacteria in bloodstream infection, but the distribution do not differ significantly. The pathogens of bloodstream infection are mainly distributed in ICU, hepatobiliary research institute, and nephrology department. Among them, Gram-negative bacteria such as Escherichia coli, Klebsiella pneumoniae and Acinetobacter baumannii are the main ones, and different pathogens showed great differences in drug resistance.

Drug-induced pericarditis

Though not common, drug-induced pericarditis is a serious condition, since pericardial tamponade, should it develop, may be life-threatening. As the number of drugs is constantly expanding, so does the proportion of those capable of causing pericarditis. The authors reviewed the relevant literature in the PubMed database and complemented it with information from the VigiBase database. In their article, the authors present current knowledge about the mechanisms of origin and level of risk of drug-induced pericarditis and discuss relevant information on individual drugs divided into 7 classes. Some medicines are associated with a high risk of developing pericarditis, a fact to be taken into account when treating patients with these agents. © 2022 Czech Society of Cardiology Z.S. All rights reserved.

Covid-19 Fatigue: Diagnosis and Treatment for the Osteopathic Physician

The novel coronavirus disease 2019 (COVID-19) has given rise to a global pandemic, as well as a multitude of long-term sequelae that continue to perplex physicians around the world, including in the United States. Among the most common and impactful long-haul symptoms experienced by survivors is COVID-19 fatigue. This review will use long COVID-19, post-acute COVID-19 syndrome (PCS), and PostAcute Sequelae of COVID-19 (PASC) as synonymous terms to refer to the chronic symptomatology;chronic fatigue associated with PASC will be referred to as COVID-19 fatigue. While the knowledge and research on the exact pathophysiological mechanisms involved in the disease is still limited, parallels have been drawn between fatigue as a component of long COVID-19 and myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS). Current studies suggest applying principles of pathophysiology, diagnosis, and treatment similar to those for ME/CFS in order to aid in managing chronic fatigue in COVID-19 survivors, particularly in the primary care setting. The osteopathic family physician can use the proposed pharmacologic agents, along with osteopathic manipulative treatment (OMT), as therapeutic modalities that can be tailored to each patient's unique case. Nevertheless, research on proven successful treatments is still scarce. For that reason, it is essential that COVID-19 fatigue is recognized early, especially since its longitudinal impacts may be debilitating for many. This review of the available literature on COVID-19 fatigue aims to help provide quality care and lessen the disease burden experienced by patients.Copyright © 2023 by the American College of Osteopathic Family Physicians. All rights reserved.

The Thyroid Pathologist Meets Therapeutic Pharmacology.

The effects of many pharmacological agents on thyroid function are well known. Direct influences on measurements of thyroid function tests are also described. However, certain classes of drugs produce morphological changes in the gland. This review focuses on the significance of the following drug classes for the thyroid pathologist: iodine, antithyroid drugs, psychotropic drugs, antibiotics, cardiotropic drugs, antidiabetic drugs, and immunomodulatory agents. Radioactive iodine initially induces mild histologic changes; however, the long-term effects include marked follicular atrophy, fibrosis, and nuclear atypia-changes that vary depending on the pre-therapy condition of the gland. Some psychotropic drugs have been associated with a spectrum of inflammatory changes throughout the gland. The tetracycline class of antibiotics, namely minocycline, can lead to a grossly black thyroid gland with pigment seen in both colloid and follicular epithelial cells while variably present within thyroid nodules. The surgical pathologist most commonly sees an amiodarone-affected gland removed for hyperthyroidism, and the histologic findings again depend on the pre-therapy condition of the gland. While GLP-1 receptor agonists carry an FDA black box warning for patients with a personal or family history of multiple endocrine neoplasia or medullary thyroid carcinoma, the C cell hyperplasia originally noted in rats has not borne out in human studies. Finally, thyroiditis and hypothyroidism are well known complications of checkpoint inhibitor therapy, and rare cases of severe thyroiditis requiring urgent thyroidectomy have been reported with unique histologic findings. In this review, we describe the histologic findings for these drugs and more, in many cases including their functional consequences.

Assessing the potential anti-neuroinflammatory effect of minocycline in chronic low back pain: Protocol for a randomized, double-blind, placebo-controlled trial.

INTRODUCTION: Both preclinical studies, and more recent clinical imaging studies, suggest that glia-mediated neuroinflammation may be implicated in chronic pain, and therefore might be a potential treatment target. However, it is currently unknown whether modulating neuroinflammation effectively alleviates pain in humans. This trial tests the hypothesis that minocycline, an FDA-approved tetracycline antibiotic and effective glial cell inhibitor in animals, reduces neuroinflammation and may reduce pain symptoms in humans with chronic low back pain. METHODS AND ANALYSIS: This study is a randomized, double-blind, placebo-controlled clinical trial. Subjects, aged 18-75, with a confirmed diagnosis of chronic (≥ six months) low back pain (cLBP) and a self-reported pain rating of at least four out of ten (for at least half of the days during an average week) are enrolled via written, informed consent. Eligible subjects are randomized to receive a 14-day course of either active drug (minocycline) or placebo. Before and after treatment, subjects are scanned with integrated Positron Emission Tomography/Magnetic Resonance Imaging (PET/MRI) using [11C]PBR28, a second-generation radiotracer for the 18 kDa translocator protein (TSPO), which is highly expressed in glial cells and thus a putative marker of neuroinflammation. Pain levels are evaluated via daily surveys, collected seven days prior to the start of medication, and throughout the 14 days of treatment. General linear models will be used to assess pain levels and determine the treatment effect on brain (and spinal cord) TSPO signal. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT03106740).

SARS-CoV-2 induces "cytokine storm" hyperinflammatory responses in RA patients through pyroptosis.

Background: The coronavirus disease (COVID-19) is a pandemic disease that threatens worldwide public health, and rheumatoid arthritis (RA) is the most common autoimmune disease. COVID-19 and RA are each strong risk factors for the other, but their molecular mechanisms are unclear. This study aims to investigate the biomarkers between COVID-19 and RA from the mechanism of pyroptosis and find effective disease-targeting drugs. Methods: We obtained the common gene shared by COVID-19, RA (GSE55235), and pyroptosis using bioinformatics analysis and then did the principal component analysis(PCA). The Co-genes were evaluated by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and ClueGO for functional enrichment, the protein-protein interaction (PPI) network was built by STRING, and the k-means machine learning algorithm was employed for cluster analysis. Modular analysis utilizing Cytoscape to identify hub genes, functional enrichment analysis with Metascape and GeneMANIA, and NetworkAnalyst for gene-drug prediction. Network pharmacology analysis was performed to identify target drug-related genes intersecting with COVID-19, RA, and pyroptosis to acquire Co-hub genes and construct transcription factor (TF)-hub genes and miRNA-hub genes networks by NetworkAnalyst. The Co-hub genes were validated using GSE55457 and GSE93272 to acquire the Key gene, and their efficacy was assessed using receiver operating curves (ROC); SPEED2 was then used to determine the upstream pathway. Immune cell infiltration was analyzed using CIBERSORT and validated by the HPA database. Molecular docking, molecular dynamics simulation, and molecular mechanics-generalized born surface area (MM-GBSA) were used to explore and validate drug-gene relationships through computer-aided drug design. Results: COVID-19, RA, and pyroptosis-related genes were enriched in pyroptosis and pro-inflammatory pathways(the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome complex, death-inducing signaling complex, regulation of interleukin production), natural immune pathways (Network map of SARS-CoV-2 signaling pathway, activation of NLRP3 inflammasome by SARS-CoV-2) and COVID-19-and RA-related cytokine storm pathways (IL, nuclear factor-kappa B (NF-κB), TNF signaling pathway and regulation of cytokine-mediated signaling). Of these, CASP1 is the most involved pathway and is closely related to minocycline. YY1, hsa-mir-429, and hsa-mir-34a-5p play an important role in the expression of CASP1. Monocytes are high-caspase-1-expressing sentinel cells. Minocycline can generate a highly stable state for biochemical activity by docking closely with the active region of caspase-1. Conclusions: Caspase-1 is a common biomarker for COVID-19, RA, and pyroptosis, and it may be an important mediator of the excessive inflammatory response induced by SARS-CoV-2 in RA patients through pyroptosis. Minocycline may counteract cytokine storm inflammation in patients with COVID-19 combined with RA by inhibiting caspase-1 expression.

Hypothesized neuroprotective effect of minocycline against COVID-19-induced stroke and neurological dysfunction: possible role of matrix metalloprotease signaling pathway.

Severe Acute Respiratory Syndrome Coronavirus-2 (COVID-19) is a respiratory disease that causes dysfunction in respiration. Since late 2019, this virus has infected and killed millions of people around the world and imposed many medical and therapeutic problems in the form of a pandemic. According to recent data, COVID-19 disease can increase the risk of stroke, which can be deadly or cause many neurological disorders after the disease. During the last two years, many efforts have been made to introduce new therapies for management of COVID-19-related complications, including stroke. To achieve this goal, several conventional drugs have been investigated for their possible therapeutic roles. Minocycline, a broad-spectrum, long-acting antibiotic with anti-inflammatory and antioxidant properties, is one such conventional drug that should be considered for treating COVID-19-related stroke, as indirect evidence indicates that it exerts neuroprotective effects, can modulate stroke occurrence, and can play an effective and strategic role in management of the molecular signals caused by stroke and its destructive consequences. The matrix metalloprotease (MMP) signaling pathway is one of the main signaling pathways involved in the occurrence and exacerbation of stroke; however, its role in COVID-19-induced stroke and the possible role of minocycline in the management of this signaling pathway in patients with COVID-19 is unclear and requires further investigation. Based on this concept, we hypothesize that minocycline might act via MMP signaling as a neuroprotective agent against COVID-19-induced neurological dysfunction, particularly stroke.

Abdominal Wall Fungal Co-infection-Mucormycosis Associated with COVID-19: A Case Report

Aim and objective: To present a rare case of abdominal wall fungal coinfection with Mucormycosis in a patient of COVID-19. Materials and methods: A 33-year-old female operated case of laparoscopic ectopic pregnancy removal with salpingectomy and tubectomy, at postoperative day 5 had redness and pus discharge from the operative site and was diagnosed with abdominal wall cellulitis. She underwent local exploration and wound wash. On postoperative day 21, the patient came to the emergency room with cellulitis, and pain at the port insertion site. On examination, we highlight BP 90/50 mm Hg and blood test analysis with HB-8.3, leucocyte count 29.91 × 109/L, CRP 333 mg/L. Results: CT scan revealed necrotizing fasciitis. She underwent wide local excision and debridement. Post debridement the next day during dressing, the wound showed a cotton fluffy appearance at the edges and part of the base with black necrotic areas. A wound swab was sent for fungal culture, KOH mount, pus culture, and tissue for histopathology. In the meantime, she was started on empirical antifungal amphotericin B, meropenem, and minocycline antibiotics. On history, the patient remarked that she did have fever, sore throat, and cough for 5 days, 4 weeks before laparoscopic ectopic pregnancy removal. Also one of her family members had tested positive for COVID-19. COVID antibodies test was done which were reactive: 1.96. Tissue histopathology revealed mucormycosis. MRI abdomen findings showed a 15 cm large defect involving the entire thickness of subcutaneous fat. A high degree of suspicion and promptness in starting antifungal treatment prevented the fatal outcome. Conclusion: COVID-19 is associated with immune dysregulation and consequently life-threatening infections. The prolonged and indiscriminate use of steroids for the treatment of COVID-19 could contribute to this problem of fungal superinfection of mucormycosis. It seems prudent to have a very high suspicion supplemented with thorough clinical examination and low threshold for imaging in order to diagnose secondary fungal infections, such as mucormycosis. Early so that the treatment can be instituted as soon as possible.

Effectiveness and safety of dalbavancin off label treatment during pandemic

Background: Dalbavancin is a lipoglycopeptide antibiotic approved for treatment of acute bacterial skin infection by GRAM +, also used for his long half-life in bone infection. Case Report: A 72 years old patient was admitted to hospital with low-grade fever for 40 days and back pain after two hospitalization for COVID19 infection and ischemic stroke. Blood examinations showed: elevated white blood cells count, increased inflammatory markers and anemia. CT showed bilateral pleural effusion, MRI configured vertebral alteration (D7-D9) suggesting infectious spondylodiscitis, blood and pleural liquid culture evidenced Staphylococcus Aureus MSSA. Levoxacin 500mg2/day and linezolid 600mg2/day IV were started with clinical improvement. Following the patient request, he was discharged with oral Linezolid. Two weeks later he showed worsening back pain and high inflammatory index. Levoxacin 500mg and Rifampicin 600mg were administered 2/day, soon Rifampicin substituted with Minocycline 100mg/day for side effect onset. After 4 week, MRI confirmed worsening of inflammatory state. Based on proven efficacy, Dalbavancin 1500mg/day IV on day 1 and 8 was started, with Minocycline for 24 week, with significant improvement in followup MRI;pleural effusion and inflammatory markers decreased. Conclusions: This case shows high efficacy of dalbavancin in spondylodiscitis pyogenic infection and pleural empyema, avoiding complications and high cost of long-term hospitalization during pandemic. In particular condition the use off label of dalbavancin is a safe and cost effective treatment.

Repurposing tetracyclines for acute respiratory distress syndrome (ARDS) and severe COVID-19: a critical discussion of recent publications.

INTRODUCTION: Drug repurposing can be a successful approach to deal with the scarcity of cost-effective therapies in situations such as the COVID-19 pandemic. Tetracyclines have previously shown efficacy in preclinical acute respiratory distress syndrome (ARDS) models and initial predictions and experimental reports suggest a direct antiviral activity against SARS-CoV2. Furthermore, a few clinical reports indicate their potential in COVID-19 patients. In addition to the scarcity and limitations of the scientific evidence, the effectiveness of tetracyclines in experimental ARDS has been proven extensively, counteracting the overt inflammatory reaction and fibrosis sequelae due to a synergic combination of pharmacological activities. AREAS COVERED: This paper discusses the scientific evidence behind the application of tetracyclines for ARDS/COVID-19. EXPERT OPINION: The benefits of their multi-target pharmacology and their safety profile overcome the limitations, such as antibiotic activity and low commercial interest. Immunomodulatory tetracyclines and novel chemically modified non-antibiotic tetracyclines have therapeutic potential. Further drug repurposing studies in ARDS and severe COVID-19 are necessary.

The Anticancer Potential of Doxycycline and Minocycline-A Comparative Study on Amelanotic Melanoma Cell Lines.

Malignant melanoma is still a serious medical problem. Relatively high mortality, a still-growing number of newly diagnosed cases, and insufficiently effective methods of therapy necessitate melanoma research. Tetracyclines are compounds with pleiotropic pharmacological properties. Previously published studies on melanotic melanoma cells ascertained that minocycline and doxycycline exerted an anti-melanoma effect. The purpose of the study was to assess the anti-melanoma potential and mechanisms of action of minocycline and doxycycline using A375 and C32 human amelanotic melanoma cell lines. The obtained results indicate that the tested drugs inhibited proliferation, decreased cell viability, and induced apoptosis in amelanotic melanoma cells. The treatment caused changes in the cell cycle profile and decreased the intracellular level of reduced thiols and mitochondrial membrane potential. The exposure of A375 and C32 cells to minocycline and doxycycline triggered the release of cytochrome c and activated initiator and effector caspases. The anti-melanoma effect of analyzed drugs appeared to be related to the up-regulation of ERK1/2 and MITF. Moreover, it was noticed that minocycline and doxycycline increased the level of LC3A/B, an autophagy marker, in A375 cells. In summary, the study showed the pleiotropic anti-cancer action of minocycline and doxycycline against amelanotic melanoma cells. Considering all results, it could be concluded that doxycycline was a more potent drug than minocycline.

Evaluation of minocycline combined with favipiravir therapy in coronavirus disease 2019 patients: A case-series study.

The aim of this study was to investigate the efficacy and safety of minocycline (MIN) and favipiravir combination therapy in patients with coronavirus disease 2019 (COVID-19) admitted to our hospital in Fukui Prefecture, Japan, in March and April of 2020. In this retrospective study, a favipiravir monotherapy group (Control group, n = 9) was compared with a combined favipiravir plus MIN therapy group (MIN group, n = 12). No severe cases were present. The primary comparative endpoints evaluated were duration of fever, duration of hospitalization, duration from treatment initiation to severe acute respiratory syndrome coronavirus 2 polymerase chain reaction (PCR)-negative results, and changes in cytokine and chemokine production. Median duration from start of treatment to negative PCR test was significantly shorter in the MIN group than in the Control group. Mean rates of cytokine and chemokine reduction were significantly greater for interleukin-6 and interleukin-8 in the MIN group. No difference in adverse event rates were seen between groups, and only minor adverse events were encountered. MIN has been reported to have not only broad antibacterial activity, but also antiviral and anti-inflammatory activity. The present results support the efficacy and safety of MIN plus favipiravir therapy for the treatment of COVID-19.

Concomitant use of dexamethasone and tetracyclines: a potential therapeutic option for the management of severe COVID-19 infection?

Introduction: The global coronavirus disease-2019 (COVID-19) pandemic has posed a critical challenge to the research community as well as to the healthcare systems. Severe COVID-19 patients are at a higher risk of developing serious complications and mortality. There is a dire need for safe and effective pharmacotherapy for addressing unmet needs of these patients. Concomitant use of dexamethasone and tetracyclines, by virtue of their immunomodulatory and other relevant pharmacological properties, offers a potential strategy for synergy aimed at improving clinical outcomes.Areas covered: Here we review the potential benefits of combining dexamethasone and tetracyclines (minocycline or doxycycline) for the management of severe COVID-19 patients. We have critically examined the evidence obtained from in silico, experimental, and clinical research. We have also discussed the plausible mechanisms, advantages, and drawbacks of this proposed combination therapy for managing severe COVID-19.Expert opinion: The concomitant use of dexamethasone and one of the tetracyclines among severe COVID-19 patients offers several advantages in terms of additive immunomodulatory effects, cost-effectiveness, wide-availability, and well-known pharmacological properties including adverse-effect profile and contraindications. There is an urgent need to facilitate pilot studies followed by well-designed and adequately-powered multicentric clinical trials to generate conclusive evidence related to utility of this approach.

Tetracyclines in COVID-19 patients quarantined at home: Literature evidence supporting real-world data from a multicenter observational study targeting inflammatory and infectious dermatoses.

Tetracyclines (TetraC) are widely used in dermatology for both inflammatory and infectious dermatoses; recently both in vivo and in vitro studies started to suggest also a potential antiviral effect. During COVID-19 outbreak, several dermatological patients contracted SARS-CoV-2 experiencing only mild symptoms, but no protocol were approved. A multicenter prospective observational study that enrolled COVID-19 patients visited with teledermatology and undergoing TetraC was performed. About 38 adult outpatients (M/F: 20/18, age 42.6 years [21-67]) were enrolled. During the TetraC treatment, symptoms resolved in all patients within 10 days. Remarkably, ageusia and anosmia disappeared in the first week of TetraC treatment. TetraC seem a promising drug to treat COVID-19 outpatients with mild symptoms.

Repurposing minocycline for COVID-19 management: mechanisms, opportunities, and challenges.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly grown into a public health emergency that has placed the national health systems as well as scientific research communities under enormous pressures. Drug repurposing or repositioning is a well-known strategy that seeks to deploy existing licensed drugs for newer indications and provides the quickest possible transition from bench to clinics for unmet therapeutic needs. Given the current, urgent, and dire need for effective therapies against novel coronavirus-19, this approach is particularly appealing. AREAS COVERED: Here, we review the significant anti-inflammatory, immunomodulatory, and antiviral properties of minocycline as potential mechanisms for efficacy against the novel coronavirus and highlight the promises and pitfalls of this approach. EXPERT OPINION: As compared to other agents being investigated for COVID-19, minocycline offers distinct advantages in terms of potential efficacy in patients with life-threatening acute respiratory distress syndrome (ARDS) and myocardial injury, well-known safety and interaction profile, relatively low costs, and widespread availability. We call upon public and private funders to facilitate urgent and rigorous research efforts before evidence-based recommendations for its widespread use can be made.