Subject(s)
European Union/organization & administration , Gastroenterology/statistics & numerical data , Societies, Medical/organization & administration , 2019-nCoV Vaccine mRNA-1273/pharmacology , Administration, Intravenous , Antibiotic Prophylaxis/methods , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/therapeutic use , Cholecystectomy/methods , Cholecystectomy/standards , Clinical Trials as Topic , Colitis, Ulcerative/drug therapy , Crohn Disease , Emergency Treatment , Endoscopy/methods , Gastroenterology/organization & administration , Gastroparesis/surgery , Heterocyclic Compounds, 3-Ring/therapeutic use , Humans , Inflammatory Bowel Diseases/drug therapy , Inflammatory Bowel Diseases/immunology , Janus Kinase Inhibitors/therapeutic use , Myotomy/methods , Preoperative Care , Remission Induction , Treatment Outcome , Tumor Necrosis Factor Inhibitors/adverse effects , Tumor Necrosis Factor Inhibitors/therapeutic use , User-Computer InterfaceABSTRACT
The purpose of this study was to compare the effectiveness of Atazanavir/Ritonavir/Dolutegravir/Hydroxychloroquine and Lopinavir/Ritonavir/Hydroxychloroquine treatment regimens in COVID-19 patients based on clinical and laboratory parameters. We prospectively evaluated the clinical and laboratory outcomes of 62 moderate to severe COVID-19 patients during a 10-day treatment plan. Patients were randomly assigned to either KH (receiving Lopinavir/Ritonavir [Kaletra] plus Hydroxychloroquine) or ADH (receiving Atazanavir/Ritonavir, Dolutegravir, and Hydroxychloroquine) groups. During this period, clinical and laboratory parameters and outcomes such as intensive care unit (ICU) admission or mortality rate were recorded. Compared to the KH group, after the treatment period, patients in the ADH group had higher activated partial thromboplastin time (aPTT) (12, [95% confidence interval [CI]: 6.97, 17.06), p = <0.01), international normalized ratio (INR) (0.17, [95% CI: 0.07, 0.27), p = <0.01) and lower C-reactive protein (CRP) (-14.29, (95% CI: -26.87, -1.71), p = 0.03) and potassium (-0.53, (95% CI: -1.03, -0.03), p = 0.04) values. Moreover, a higher number of patients in the KH group needed invasive ventilation (6 (20%) vs. 1 (3.1%), p = 0.05) and antibiotic administration (27 (90%) vs. 21(65.6), p = 0.02) during hospitalization while patients in the ADH group needed more corticosteroid administration (9 (28.1%) vs. 2 (6.7%), p = 0.03). There was no difference in mortality rate, ICU admission rate, and hospitalization period between the study groups. Our results suggest that the Atazanavir/Dolutegravir treatment regimen may result in a less severe disease course compared to the Lopinavir/Ritonavir treatment regimen and can be considered as an alternative treatment option beside standard care. However, to confirm our results, larger-scale studies are recommended.
Subject(s)
Antiviral Agents/therapeutic use , Atazanavir Sulfate/therapeutic use , COVID-19 Drug Treatment , Heterocyclic Compounds, 3-Ring/therapeutic use , Hydroxychloroquine/therapeutic use , Lopinavir/therapeutic use , Oxazines/therapeutic use , Piperazines/therapeutic use , Pyridones/therapeutic use , Ritonavir/therapeutic use , Antiviral Agents/administration & dosage , Atazanavir Sulfate/administration & dosage , COVID-19/pathology , Drug Combinations , Drug Therapy, Combination , Female , Heterocyclic Compounds, 3-Ring/administration & dosage , Humans , Hydroxychloroquine/administration & dosage , Lopinavir/administration & dosage , Male , Middle Aged , Oxazines/administration & dosage , Piperazines/administration & dosage , Pyridones/administration & dosage , Ritonavir/administration & dosage , Treatment OutcomeSubject(s)
Arthritis, Rheumatoid/immunology , COVID-19 Vaccines/immunology , COVID-19/prevention & control , Immunocompromised Host/immunology , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/complications , BNT162 Vaccine , Heterocyclic Compounds, 3-Ring/therapeutic use , Humans , Immunization, Secondary , Immunogenicity, Vaccine/drug effects , Immunogenicity, Vaccine/immunology , Male , Methotrexate/therapeutic use , Middle Aged , Polycythemia Vera/complications , SARS-CoV-2 , Vasculitis, Leukocytoclastic, Cutaneous/complicationsABSTRACT
Little evidence on coronavirus disease 2019 (COVID-19) in people living with HIV (PLWH) is currently available. We reported clinical and viroimmunological data of all HIV-positive patients admitted to our center with COVID-19 from March 1 to May 12, 2020. Overall, five patients were included: all were virologically-suppressed on antiretroviral therapy and CD4+ count was greater than 350 cell/mm3 in all but two patients. Although all patients had evidence of pneumonia on admission, only one developed respiratory failure. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was never detected from nasopharyngeal swabs in two patients, whereas in the others, viral clearance occurred within a maximum of 43 days. Immunoglobulin G production was elicited in all patients and neutralizing antibodies in all but one patient. Specific-T-cell response developed in all patients but was stronger in those with the more severe presentations. Similarly, the highest level of proinflammatory cytokines was found in the only patient experiencing respiratory failure. Despite a mild presentation, patients with more pronounced immunosuppression showed high degrees of both cytokines production and immune activation. Our study did not find an increased risk and severity of COVID-19 in PLWH. Adaptative cellular immune response to SARS-CoV-2 appeared to correlate to disease severity. The mild clinical picture showed in advanced HIV patients, despite a significant T-cell activation and inflammatory profile, suggests a potential role of HIV-driven immunological dysregulation in avoiding immune-pathogenetic processes. However, other possible explanations, as a protective role of certain antiretroviral drugs, should be considered. Further larger studies are needed to better clarify the impact of HIV infection on COVID-19.
Subject(s)
Anti-Retroviral Agents/therapeutic use , COVID-19 Drug Treatment , HIV Infections/drug therapy , SARS-CoV-2/drug effects , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , CD4 Lymphocyte Count , Coinfection/virology , Cytokines/blood , Female , HIV Integrase Inhibitors/therapeutic use , Heterocyclic Compounds, 3-Ring/therapeutic use , Humans , Immunity, Humoral/immunology , Male , Middle Aged , Oxazines/therapeutic use , Piperazines/therapeutic use , Pyridones/therapeutic use , RNA, Viral/analysis , Reverse Transcriptase Inhibitors/therapeutic use , Risk , Severity of Illness Index , Tenofovir/therapeutic use , Transgender PersonsSubject(s)
Coronavirus Infections/complications , HIV Infections/complications , Pneumonia, Viral/complications , Transgender Persons , Adenine/analogs & derivatives , Adenine/therapeutic use , Adult , Alanine , Anti-HIV Agents/therapeutic use , Antiviral Agents/therapeutic use , Betacoronavirus , COVID-19 , Coronavirus Infections/drug therapy , Coronavirus Infections/physiopathology , Dideoxynucleosides/therapeutic use , Drug Combinations , Emtricitabine , Female , HIV Infections/drug therapy , Heterocyclic Compounds, 3-Ring/therapeutic use , Heterocyclic Compounds, 4 or More Rings/therapeutic use , Humans , Lamivudine/therapeutic use , Lopinavir/therapeutic use , Male , Middle Aged , Oxazines , Pandemics , Piperazines , Pneumonia, Viral/drug therapy , Pneumonia, Viral/physiopathology , Pyridones , Ritonavir/therapeutic use , SARS-CoV-2 , Tenofovir/therapeutic use , COVID-19 Drug TreatmentABSTRACT
Ion channels are necessary for correct lysosomal function including degradation of cargoes originating from endocytosis. Almost all enveloped viruses, including coronaviruses (CoVs), enter host cells via endocytosis, and do not escape endosomal compartments into the cytoplasm (via fusion with the endolysosomal membrane) unless the virus-encoded envelope proteins are cleaved by lysosomal proteases. With the ongoing outbreak of severe acute respiratory syndrome (SARS)-CoV-2, endolysosomal two-pore channels represent an exciting and emerging target for antiviral therapies. This review focuses on the latest knowledge of the effects of lysosomal ion channels on the cellular entry and uncoating of enveloped viruses, which may aid in development of novel therapies against emerging infectious diseases such as SARS-CoV-2.