ABSTRACT
Vitamin D is a fundamental regulator of host defences by activating genes related to innate and adaptive immunity. Previous research shows a correlation between the levels of vitamin D in patients infected with SARS-CoV-2 and the degree of disease severity. This work investigates the impact of the genetic background related to vitamin D pathways on COVID-19 severity. For the first time, the Portuguese population was characterized regarding the prevalence of high impact variants in genes associated with the vitamin D pathways. This study enrolled 517 patients admitted to two tertiary Portuguese hospitals. The serum concentration of 25 (OH)D, was measured in the hospital at the time of patient admission. Genetic variants, 18 variants, in the genes AMDHD1, CYP2R1, CYP24A1, DHCR7, GC, SEC23A, and VDR were analysed. The results show that polymorphisms in the vitamin D binding protein encoded by the GC gene are related to the infection severity (p = 0.005). There is an association between vitamin D polygenic risk score and the serum concentration of 25 (OH)D (p = 0.04). There is an association between 25 (OH)D levels and the survival and fatal outcomes (p = 1.5e-4). The Portuguese population has a higher prevalence of the DHCR7 RS12785878 variant when compared with its prevalence in the European population (19% versus 10%). This study shows a genetic susceptibility for vitamin D deficiency that might explain higher severity degrees in COVID-19 patients. These results reinforce the relevance of personalized strategies in the context of viral diseases.Trial registration: NCT04370808.
Subject(s)
COVID-19/blood , COVID-19/diagnosis , Polymorphism, Genetic , Vitamin D Deficiency/blood , Vitamin D/analogs & derivatives , Vitamin D/blood , Vitamin D/genetics , Aged , Biomarkers , Cholestanetriol 26-Monooxygenase/genetics , Cytochrome P450 Family 2/genetics , Female , Genetic Predisposition to Disease , Hospitalization , Humans , Male , Middle Aged , Oxidoreductases Acting on CH-CH Group Donors/genetics , Portugal/epidemiology , Prevalence , Severity of Illness Index , Vesicular Transport Proteins/genetics , Vitamin D-Binding Protein/genetics , Vitamin D3 24-Hydroxylase/geneticsABSTRACT
We report a case of a man with chronic hepatitis C infection treated with remdesivir for COVID-19, resulting in lowered HCV viral load, followed by a rebound after its discontinuation. Concomitant treatment with tocilizumab possibly caused loss of anti-HBs.
ABSTRACT
Organizing pneumonia (OP) is a sub-acute process of pulmonary tissue repair secondary to lung injury, defined histopathologically by intra-alveolar buds of granulation tissue within the lumen of distal pulmonary airspaces. It can be either cryptogenic or secondary (SOP) to different clinical conditions, namely infections. Despite being nonspecific, its diagnosis can be made by the association of clinical and imaging criteria. We report two cases of OP associated to SARS-CoV-2 pneumonia, admitted at a Portuguese tertiary hospital unit dedicated to COVID-19. Both patients presented with severe respiratory failure with need of invasive mechanical ventilation. After initial recovery, there was worsening of dyspnea and hypoxemic respiratory failure with increase in inflammatory markers. Chest CT revealed an OP pattern. Other conditions such as superinfection, auto-immune disease and iatrogenic etiology, were excluded and corticotherapy at a dose of 1 mg/kg/day was administered. Chest CT follow up of both our patients showed complete resolution of OP pattern, with mild to moderate residual pulmonary fibrosis without honeycombing. There is no OP to SARS-CoV-2 case series yet published describing the progress of patients after corticotherapy, although the association between systemic corticosteroids and lower all-cause mortality in patients with COVID-19 has been recently established. It is possible that, as has been described with other viruses, OP secondary to SARS-CoV-2 represents an immunological process after initial infection, presenting with elevation of inflammatory markers and cytokines storm in the bloodstream and lung tissue, which may explain the favorable response to corticosteroids.
ABSTRACT
The 2019 coronavirus pandemic has united scientific and medical communities in a worldwide quest for understanding the pathophysiology of this rapidly spreading disease in order to develop effective treatments. We present a case of a 46-year-old woman with breast cancer who was found positive for SARS-CoV-2 in a screening test and developed massive rhabdomyolysis (creatinine kinase 87,456 U/liter) as well as new-onset lymphopenia and signs of lung disease starting on the 16th day of clinical surveillance, one month after the last administration of chemotherapy. Nasopharyngeal swab was still positive for SARS-CoV-2 RNA and serology revealed antibody response against the virus. Considering the possibility of a systemic inflammatory response in the setting of post-chemotherapy immune reconstitution, we avoided aggressive fluid administration and initiated treatment with methylprednisolone and hydroxychloroquine, resulting in rapid clearance of pulmonary infiltrates and creatinine kinase. Complete resolution after corticosteroid treatment may provide clinicians with a viable treatment option in similar situations and adds to the growing body of evidence pointing to dysregulated immune response as a major contributing factor to disease severity.