Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 5 de 5
Filter
1.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-318933

ABSTRACT

Non-classical actions of Vitamin D are involved in regulation of the immune system including a role in mitigation of excessive inflammation. We hypothesized that vitamin D deficiency existing prior to SARS-CoV-2 infection could contribute to patients developing severe pulmonary compromise as a result of dysfunctional hyperinflammation. Serum vitamin D concentrations of patients experiencing such severe COVID-19 manifestations that they required ICU care at any point of their hospitalization were compared to serum vitamin D concentrations of patients achieving discharge without the need for any ICU care. Having serum vitamin D < 20 ng/mL was significantly associated with increased COVID-19 severity, p=0.001. It is conjectured that population groups know to have low serum vitamin D should be prospectively screened for deficiency and if found emergently treated. Such action could both decrease the maximum severity suffered by infected individuals and lessen the strain on medical resources by decreasing the percentage of COVID-19 hospital admissions requiring ICU care.

2.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-311067

ABSTRACT

Background: Severity of illness and mortality from coronavirus disease 2019 (COVID-19) is consistently lower in women than in men. While this outcome difference is not well understood, focus on sex as a biologic factor may suggest potential therapeutic intervention for this disease. We assessed whether adding progesterone, a steroid hormone with immune-modulatory properties, to standard of care, would improve clinical outcomes of hospitalized men with moderate to severe COVID-19.Method: We conducted a Phase 1, randomised, open-label, controlled trial at a large academic hospital in Los Angeles, CA, USA, of subcutaneous progesterone in men hospitalized with confirmed COVID-19 and evidence of lower respiratory tract involvement. Patients were randomly assigned (1:1), using block randomization and a computer-generated randomization sequence, to receive standard of care (SOC) plus progesterone (100 mg subcutaneously twice daily for up to five days) or SOC alone. In addition to assessment of safety, the primary outcome was change in clinical status based on a 7-point ordinal scale noted at baseline compared to that on Day 7 of the trial. Control patients with significant clinical deterioration or absence of clinical improvement by Day 7 were permitted to cross over to receive progesterone therapy. Intention to treat analysis was performed and the patient’s last clinical assessment prior to receiving the study drug was imputed as the Day 7 assessment. Findings: Forty-two patients were enrolled in the study from April 27 to August 20, 2020;22 were randomised to the control group and 20 to the progesterone group. Of the 20 patients in the progesterone group, two withdrew from the study prior to receiving progesterone and were excluded from analysis. There was an overall improvement in clinical status from baseline to Day 7 in patients in the progesterone group as compared to controls (95% CI: 0-2;P = 0·010). There were no serious adverse events attributable to progesterone.Interpretation: Progesterone at a dose of 100 mg, twice daily by subcutaneous injection in addition to standard of care may represent a safe and novel approach for the treatment in men with moderate to severe COVID-19.Trial Registration: This trial was registered at ClinicalTrials.gov, NCT04365127.Funding Statement: The Institut Biochimique SA (IBSA, Lugano, Switzerland)Declaration of Interests: SG, YM, SP, TK, DN, JH, SC, RIG, JM, CB, ML, VT report grants and nonfinancial support from Institut Biochimique SA (IBSA, Lugano, Switzerland), during the conduct of the study;SG,SP report patent pending on method of use of progesterone agonist for treatment of COVID-19 VT reports grants from NIH/NIAID ACTT (ACTT 1-3), outside the submitted work. DS, HG declare no competing interests.Ethics Approval Statement: This study was approved by the Cedars-Sinai Institutional Review Board (IRB).

3.
EJHaem ; 2(4): 700-710, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1525456

ABSTRACT

Patients with sickle cell disease (SCD) have a high prevalence of RBC alloimmunization. However, underlying mechanisms are poorly understood. Given that proinflammatory type 1 interferons (IFNα/ß) and interferon stimulated genes (ISGs) promote alloimmunization in mice, we hypothesized that IFNα/ß may contribute to the increased frequency of alloimmunization in patients with SCD. To investigate this, expression of ISGs in blood leukocytes and peripheral blood mononuclear cells (PBMCs) of previously transfused SCD patients with or without alloimmunization and race-matched healthy controls were quantified, and IFNα/ß gene scores were calculated. IFNα/ß gene scores of SCD leukocytes and plasma cytokines were elevated, compared to controls (gene score, p < 0.01). Upon stimulation with IFNß, isolated PBMCs from patients with SCD had elevated ISGs and IFNα/ß gene scores (p < 0.05), compared to stimulated PBMCs from controls. However, IFNß-stimulated and unstimulated ISG expression did not significantly differ between alloimmunized and non-alloimmunized patients. These findings indicate that patients with SCD express an IFNα/ß gene signature, and larger studies are needed to fully determine its role in alloimmunization. Further, illustration of altered IFNα/ß responses in SCD has potential implications for IFNα/ß-mediated viral immunity, responses to IFNα/ß-based therapies, and other sequelae of SCD.

4.
Chest ; 160(1): 74-84, 2021 07.
Article in English | MEDLINE | ID: covidwho-1258346

ABSTRACT

BACKGROUND: Severity of illness in COVID-19 is consistently lower in women. A focus on sex as a biological factor may suggest a potential therapeutic intervention for this disease. We assessed whether adding progesterone to standard of care (SOC) would improve clinical outcomes of hospitalized men with moderate to severe COVID-19. RESEARCH QUESTION: Does short-term subcutaneous administration of progesterone safely improve clinical outcome in hypoxemic men hospitalized with COVID-19? STUDY DESIGN AND METHODS: We conducted a pilot, randomized, open-label, controlled trial of subcutaneous progesterone in men hospitalized with confirmed moderate to severe COVID-19. Patients were randomly assigned to receive SOC plus progesterone (100 mg subcutaneously twice daily for up to 5 days) or SOC alone. In addition to assessment of safety, the primary outcome was change in clinical status on day 7. Length of hospital stay and number of days on supplemental oxygen were key secondary outcomes. RESULTS: Forty-two patients were enrolled from April 2020 to August 2020; 22 were randomized to the control group and 20 to the progesterone group. Two patients from the progesterone group withdrew from the study before receiving progesterone. There was a 1.5-point overall improvement in median clinical status score on a seven-point ordinal scale from baseline to day 7 in patients in the progesterone group as compared with control subjects (95% CI, 0.0-2.0; P = .024). There were no serious adverse events attributable to progesterone. Patients treated with progesterone required three fewer days of supplemental oxygen (median, 4.5 vs 7.5 days) and were hospitalized for 2.5 fewer days (median, 7.0 vs 9.5 days) as compared with control subjects. INTERPRETATION: Progesterone at a dose of 100 mg, twice daily by subcutaneous injection in addition to SOC, may represent a safe and effective approach for treatment in hypoxemic men with moderate to severe COVID-19. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT04365127; URL: www.clinicaltrials.gov.


Subject(s)
COVID-19 , Progesterone/administration & dosage , SARS-CoV-2/isolation & purification , COVID-19/physiopathology , COVID-19/therapy , Clinical Protocols/standards , Drug Monitoring , Humans , Hypoxia/diagnosis , Hypoxia/etiology , Injections, Subcutaneous , Male , Middle Aged , Oxygen Inhalation Therapy/methods , Pilot Projects , Progestins/administration & dosage , Severity of Illness Index , Treatment Outcome
SELECTION OF CITATIONS
SEARCH DETAIL