New frontiers in sickle cell disease: The role of antiviral therapies and emerging drugs in managing viral infections

Table 1 Studies reported blood borne viral infections in sickle cell disease patients

Ref.	Type of study	Participants	Results
Namasopo et al[28], 2013	Cross-sectional study	SCD patients aged from 1 to 18 years	Out of 244 SCD patients, 85 patients had no history of transfusion; out of which 1 (1.1%) was HCV positive and 84 (98.9%) were HCV negative 159 had history of transfusion out of which 5 (3.2%) were HCV positive. The patients who had undergone transfusion were likely to be HCV positive but the above difference was not statistically significant
Diarra et al[29], 2013	Prospective study	133 SCD patients	At the time of enrolment, viral infection prevalence in patients was 1% for HIV, 3% for HBV and 1% for HCV. After blood transfusion seroconversion was noticed for one each for HIV, HBV and HCV. They recommended that improvisation should be made in blood transfusion safety norms in Mali for sickle cell anaemia patients
Alkindi et al[30], 2019	Retrospective study (data from electronic patients’ records)	Total 1000 SCD patients with mean age 295 years ± 10.4 years	Out of the 1000 SCD patients, 23 (2.3%) had positive serology for HBV surface antigen, of whom 16 (1.6%) were HBV DNA positive and no SCD patient had HIV positive
Odaibo et al[27], 2021	Case-control study carried out at Ibadan, Nigeria	1017 cases of SCD and 1017 controls	Prevalence rates of HIV was 0.6%, HBV was 6.1% and HCV was 1.6%. The highest prevalence was observed in the 20-29 age group for HCV, 30-39 age group for HBV infection and 40-49 age group for HIV infection
Shayo et al[31], 2021	Cross-sectional multisite hospital-based study	SCD patients ≥ 16 years	Total 185 (56.9%) females and 140 males were tested. Out of the above participants, 6 (1.8%) and 4 (1.2%) were having HIV and HBV infections respectively
Mawuli et al[32], 2022	Cross-sectional hospital-based study	SCD patients ≤ 19 years to ≥ 50 years	Total 51 (36%) males and 90 (64%) females were tested. The 12 patients (9%) had prevalence of HCV antibodies among 141 SCD patients at Greater Accra Region of Ghana

HBV: Hepatitis B virus; HCV: Hepatitis C virus; HIV: Human immunodeficiency virus; SCD: Sickle cell disease.

Table 2 Data from articles reporting respiratory viral infections in sickle cell disease patients

Ref.	Type of study	Participants	Results
Inusa et al[34], 2010	Survey from April 2009 and August 2009	Among the 2200 children with SCD, 21 cases of H1N1 were identified	Half of the patients were admitted to the hospital, and a 25% of them developed ACS
Sadreameli et al[36], 2014	Laboratory confirmed cases of RSV from 1993 to 2011	Total 64 SCD children < 18 years with RSV and 91 with seasonal influenza	All SCD children with RSV infection and the majority of those having influenza (89%, P = 0.006) were hospitalized. Mechanical ventilation was necessary in some RSV cases, but not in any influenza cases. The sole reported death occurred in a 15-year-old patient who had an RSV infection
Rostad et al[37],2021	Retrospective, nested, case control study (2012 to 2019)	Total 160/2636 (6.1%) SCD patients < 18 years positive for RSV	The hospitalization rate due to RSV in children under five was 20.7 per 1000 person-years. Children with RSV were significantly younger (3.8 years) than not having RSV (7.6 years) (P < 0.001). Among RSV infected children, 22 children (13.8%) developed ACS, and nine (5.6%) required intensive care, with no significant difference compared to RSV negative children with SCD
Strouse et al[38], 2010	Retrospective cohort	Total 123 teenagers with SCD < 22 years diagnosed with influenza B and H1N1	SCD patients having influenza were generally younger and had a lower likelihood of having asthma. In contrast, H1N1 patients more frequently experienced ACS, severe pain, and required intensive care. Treated with antiviral medications and transfusions (administered to 10% of H1N1 patients compared to 3% of those with influenza) (P = 0.045)
George et al[39], 2011	Retrospective chart review	Total 48 SCD children with H1N1	Most common diagnosed condition among SCD patients was ACS. There were no instances of mechanical ventilation or reported deaths. A prior occurrence of ACS was linked to a higher probability of hospital admission
Colombatti et al[40], 2011	Retrospective survey	Total 17 SCD children < 17 infected with H1N1	Total 8 patients (47%) experienced ACS; 8 patients (47%) had flu-like symptoms accompanied by vaso-occlusive crisis; and 1 patient (6%) had splenic sequestration
Telfer et al[42], 2020	Survey	Total 166 SCD, 26 thalassemia, and 3 rare inherited anemia patients with confirmed COVID-19	No patients needed mechanical ventilation. No report of death in this study
Singh et al[43], 2021	Retrospective cohort	Total 312 SCD and 312 SCT (trait) with COVID-19	SCD individuals had an increased risk of getting hospital admission compared to SCT. The fatality rate did not show a significant difference. No comparisons were made between adults and children
Minniti et al[35], 2021	Cohort	Total 66 SCD patients with COVID-19	Patients over 50 years old had elevated serum creatinine, lactate dehydrogenase, and D-dimer are the risk factors for death, regardless of their genotype or gender. Of these patients, 75% needed hospitalization, and 10.6% passed away. No deaths occurred among children
Haghpanah et al[41], 2021	Systematic review and metanalysis	Total 48636 patients with hemoglobinopathies (b-thal and SCD)	In SCD patients, the rate of COVID-19 incidence is higher as compared to general population

ACS: Acute chest syndrome; COVID-19: Coronavirus disease 2019; H1N1: Influenza A; RSV: Respiratory syncytial virus; SCD: Sickle cell disease; SCT: Sickle cell trait.