Introduction

Children with cystic fibrosis (CF)–related chronic lung disease are predisposed to severe pulmonary infections with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Though initial reports demonstrated asymptomatic and mild SARS-CoV-2 infection in children with CF, larger series have described all degrees of severity including intensive care admission especially in post-transplant patients [1,2,3]. Children with CF from developing countries frequently have advanced lung disease [4]. The authors’ unit runs a weekly CF clinic with nearly 200 children in regular follow-up cared by clinical specialists, physiotherapist, nutritionist, and specialist nurse. Presentation of two children with CF with COVID-19 are described here.

Case 1

A 9-y-old boy (homozygous F508del, Staphylococcus aureus colonization, BMI -2.18 z-score, CF-related liver disease, on regular azithromycin) had no pulmonary exacerbation in the last 11 mo. He developed fever, increased cough, and fast breathing for 3 d. He received intravenous piperacillin–tazobactam and amikacin for 14 d, but did not improve. At presentation to the authors’ hospital, respiratory specimen was positive for SARS-CoV-2 reverse-transcriptase polymerase chain reaction (RT-PCR). He required noninvasive ventilation for 2 d, followed by high-flow nasal canula (HFNC) support. Inflammatory markers showed no significant abnormalities (Supplementary Table S1). Chest radiograph showed hyperinflation, mucous plugging, and interstitial shadows (Fig. 1a). As per the institutional protocol, he received remdesivir (5 d), hydrocortisone, and cefoperazone–sulbactam and vancomycin for 14 d. Child became afebrile on day 8 of admission. He was discharged after 14 d while still SARS-CoV-2 RT-PCR positive.

Fig. 1
figure 1

Chest radiograph of (a) case 1 and (b) case 2 at the time of first admission showing interstitial infiltrates with background chronic lung disease changes

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Within 4 d of discharge, he again developed intermittent fever spikes and increased cough. But he was brought to the authors’center with breathing difficulty and persistent fever after 20 d. His SARS-CoV-2 RT-PCR was still positive. He received oxygen by facemask and intravenous antibiotics. Sputum culture grew E. coli. He was also diagnosed with CF-related diabetes (CFRD) and allergic bronchopulmonary aspergillosis during this admission (Supplementary Table S1). SARS-CoV-2 RT-PCR turned negative by day 10 of hospital stay.

He had another pulmonary exacerbation at 3 mo, but this time, SARS-CoV-2 RT-PCR was negative. Sputum cultures grew E. coli, Klebsiella pneumoniae,and methicillin-resistant Staphylococcus aureus. He was discharged after 20 d of treatment.

Case 2

An 18-mo-old boy (diagnosed by elevated sweat chloride, heterozygous c.1333delA, BMI -0.90 z score, on regular azithromycin) had last pulmonary exacerbation 7 mo back. He had increased cough for 3 d, and fever, fast breathing, and desaturations for 1 d. He had hypoxia with bilateral crepitations and wheeze. His SARS-CoV-2 RT-PCR was positive. Inflammatory markers were not elevated (Supplementary Table S1). Chest radiograph showed interstitial infiltrates (Fig. 1b). He received HFNC support for 4 d and oxygen was gradually tapered. He received meropenem, vancomycin, and prednisolone (1 mg/kg/d). He was discharged after 14 d with negative SARS-CoV-2 RT-PCR.

Thirty-four days following discharge, the child received antibiotics for 10 d for pulmonary exacerbation locally.While on treatment, he again developed fever, worsening cough, fast breathing, and wheezing for 3 d. He was admitted to the authors’center; respiratory sample was positive for SARS-CoV-2. He was treated with intravenous antibiotics, HFNC (20 L/min), and prednisolone. He was discharged after 14 d with negative SARS-CoV-2 RT-PCR. There was no fresh SARS-CoV-2 infection in the house. IgG against SARS-CoV-2 was significantly elevated.

After 3 mo from the first episode, he again had increased cough, fast breathing, and wheezing, which was managed in the outpatient setting with oral antibiotics and a short course of prednisolone.

Discussion

Two children with CF with severe SARS-CoV-2 infection have been discussed. While the first case had persistent infection, the second might have had recurrent infection due to SARS-CoV-2. Both had frequent pulmonary exacerbations following initial COVID-19. In published literature, a significant proportion of CF patients require hospitalization (29%) when they develop COVID-19 as compared to overall pediatric age group (0.1%–2.2%) [1, 5]. Oxygen requirement was reported in 6% and 29% in two studies [1, 2]. Both the cases had severe disease.

Prolonged shedding of SARS-CoV-2 up to 120 d has been described in immunocompromised adults [6]. The first case described here had SARS-CoV-2 RT-PCR positive till 55 d of onset of symptoms. The second case had one negative SARS-CoV-2 RT-PCR in between, so it is difficult to conclude if the second episode was re-infection or persistent infection. CF-related innate–immune dysfunction, use of steroids, and new-onset diabetes could cause prolonged viral shedding [7, 8].

Viral infection in children with CF can cause pulmonary exacerbations due to direct infection, as well as secondary bacterial infection [9]. Both of the above-mentioned cases had poor respiratory health with pulmonary exacerbations after SARS-CoV-2 infection, despite having well-controlled disease in the previous year. Case 1 also had new onset CFRD. New-onset type 1 diabetes has been seen with COVID-19; the presence of SARS-CoV-2 receptors on pancreatic exocrine cells, use of steroids, and infection-related stress response have been the postulated mechanisms [10].

Conclusion

Children with CF having significant lung morbidity can develop severe infection and repeated pulmonary exacerbations. Strict preventive measures should be taken to protect children with CF from SARS-CoV-2.