Poor Respiratory Health Following Relapsing SARS-CoV-2 Infection in Children with Cystic Fibrosis: Authors' Reply.

To the Editor: We thank Mandal et al. for their interest in our report and insightful comments on our findings and summary of mechanisms for better immunity against SARS-CoV-2 in children with CF [1, 2]. It was suggested that prolonged and repeated viral PCR positivity in our patients is likely due to prolonged viral shedding. Prolonged shedding has been described in literature, and limited studies where culture has been attempted for prolonged PCR positivity, suggest that virus is probably nonviable [3]. However, risk of prolonged shedding is more in older patients and least in children, and mostly, prolonged shedding has been described in asymptomatic patients. Recurrent infections of SARS-CoV-2 have been well reported with symptomatic disease [4]. Both of our patients had severe symptoms during the first two episodes. Since we did not perform viral culture and strain identification during the episodes, it is difficult to conclude with confidence whether the episodes were persistent/reinfection or there was prolonged shedding.

Mandal et al. have suggested that COVID-19 is mild in children with CF [1]. We do not fully agree with that notion. Though initial reports of COVID-19 in CF patients suggested that the disease may not be as severe as expected, these reports were from developed countries and before the period of delta variant [5]. A recent large prospective series of Italian cohort of 236 CF patients had 18% hospitalizations and 2.5% mortality, which is significantly higher than the general population of similar age group (median age 25 y) [6]. Risk factors of severe COVID-19 amongst the cohort were low FEV1 predicted (< 40%), home oxygen support, underweight, organ transplant, diabetes, and liver disease; while the use of dornase alpha and long-term azithromycin were associated with reduced risk [6]. Children with CF in India are frequently malnourished, and have low lung function, which places them at high risk for severe COVID-19 [7]. Both the patients in our series had poor lung health and case 1 had severe malnutrition.