Thalassaemia is paradoxically associated with a reduced risk of in‐hospital complications and mortality in COVID‐19: Data from an international registry

Abstract

Although numerous patient‐specific co‐factors have been shown to be associated with worse outcomes in COVID‐19, the prognostic value of thalassaemic syndromes in COVID‐19 patients remains poorly understood. We studied the outcomes of 137 COVID‐19 patients with a history of transfusion‐dependent thalassaemia (TDT) and transfusion independent thalassaemia (TIT) extracted from a large international cohort and compared them with the outcomes from a matched cohort of COVID‐19 patients with no history of thalassaemia. The mean age of thalassaemia patients included in our study was 41 ± 16 years (48.9% male). Almost 81% of these patients suffered from TDT requiring blood transfusions on a regular basis. 38.7% of patients were blood group O. Cardiac iron overload was documented in 6.8% of study patients, whereas liver iron overload was documented in 35% of study patients. 40% of thalassaemia patients had a history of splenectomy. 27.7% of study patients required hospitalization due to COVID‐19 infection. Amongst the hospitalized patients, one patient died (0.7%) and one patient required intubation. Continuous positive airway pressure (CPAP) was required in almost 5% of study patients. After adjustment for age‐, sex‐ and other known risk factors (cardiac disease, kidney disease and pulmonary disease), the rate of in‐hospital complications (supplemental oxygen use, admission to an intensive care unit for CPAP therapy or intubation) and all‐cause mortality was significantly lower in the thalassaemia group compared to the matched cohort with no history of thalassaemia. Amongst thalassaemia patients in general, the TIT group exhibited a higher rate of hospitalization compared to the TDT group (p = 0.001). In addition, the rate of complications such as acute kidney injury and need for supplemental oxygen was significantly higher in the TIT group compared to the TDT group. In the multivariable logistic regression analysis, age and history of heart or kidney disease were all found to be independent risk factors for increased in‐hospital, all‐cause mortality, whereas the presence of thalassaemia (either TDT or TIT) was found to be independently associated with reduced all‐cause mortality. The presence of thalassaemia in COVID‐19 patients was independently associated with lower in‐hospital, all‐cause mortality and few in‐hospital complications in our study. The pathophysiology of this is unclear and needs to be studied in vitro and in animal models.

Beauty and the beast: host microRNA-155 versus SARS-CoV-2

“…In our initial review on the HbE/β-thalassemia trait conferring resistance against SARS-CoV-2 infection, subsequently supported in independent reports, we proposed miR-155 as the mediator for this protection [5,[136][137][138]. Supporting an antiviral effect for the HbE/β-thalassemia trait, akin to its anti-malarial effect, red blood cell precursors in Thai carriers of HbE/β-thalassemia trait were significantly less susceptible to DENV infection [5,139].…”

“…Elevated miR-155 levels with repression of relevant target genes could convincingly account for the favorable inflammatory profile (Ets-1 repression with lower PAI-1 levels), better lipidemic and metabolic profile (SOCS1), better ambulatory blood pressure control (lower AT1R expression), and EPO-mediated renoprotection against ischemic injury through the SOCS1/JAK2/Y343/STAT5 axis, altogether leading to overall better CV health, repeatedly reported in HbE/β-thalassemia carrier state [151][152][153]. An advantageous basal health condition in thalassemia carriers at the time of the initiation of SARS-CoV-2 infection, may potentially lead to a more favorable COVID-19 outcome [138]. MiR-155 can thus eloquently engender HbE/β-thalassemia's protective effects in malaria, DENV, and SARS-CoV-2 (Fig.…”

Iron dysregulation and inflammatory stress erythropoiesis associates with long-term outcome of COVID-19

“…Reports that iron overload in the context of β-thalassemia protects from severe disease and mortality in individuals infected with SARS-CoV-2 (ref. 76 ) suggest a potential protective effect of increased iron availability, and preliminary reports on the impact of COVID-19 on patients enrolled in the IRONMAN clinical trial of intravenous ferric derisomaltose treatment for heart failure 77 show significantly reduced COVID-19-related severe adverse events in the iron-treated group (2.1%) than the usual care group (5.3%, P = 0.007) 78 . This suggests a potential role for iron supplementation in COVID-19.…”

Clinical outcome and humoral immune responses of β-thalassemia major patients with severe iron overload to SARS-CoV-2 infection and vaccination: a prospective cohort study

“…It may well be that a more sustained humoral immune response among patients with β-TM during infection represents an underlying protective mechanism against SARS-CoV-2 infection severity. 26 , 27 Of note, T-cell immune responses play essential roles for the control of SARS-CoV-2 infection and specifically for preventing severe COVID-19. 28 Thus, it will be of interest to further investigate T-cell immunity at baseline, as well as after infection and vaccination in patients with β-TM, being aware of the fact that iron availability can affect T–cell differentiation, activation and cytokine expression.…”