Systematic Review

Cystic Fibrosis in the SARS-CoV-2/COVID-19 Pandemic

Hannah R. Mathew; May Y. Choi; Michael D. Parkins; Marvin J. Fritzler


BMC Pulm Med. 2021;21(173) 

In This Article


Six studies were included in this review, reporting on a total of 339 individuals with CF who developed COVID-19. Information collected by the European Cystic Fibrosis Society Patient Registry (ECFSPR) on SARS-CoV-2 infection in 1236 individuals with CF from 30 countries was also included.[17]

CF and COVID-19 Sudies

In a multinational cohort study of 40 individuals with CF from eight participating countries, the incidence of SARS-CoV-2 infection was 0.07%, which is approximately one-half of the 0.15% rate reported in the general population.[18] The median age of the infected cohort was 33 years, which was higher than the median age of the general CF population, with only one patient (3%) under the age of 16; this is reflective of the lower reportage of pediatric cases of COVID-19 diagnosed in the non-CF population.[24] The CF individuals in this cohort comprised of a heterogeneous population with various severe comorbidities and included those who were pregnant (3%) and had lung transplants (28%). The transplant recipient subgroup was 6 years post-transplant on average, with a range from 1 to 15 years. Of the 40 reported cases, 31 (78%) were symptomatic, and 24 (60%) were febrile at presentation. Thirteen (33%) received supplemental oxygen, four (10%) were admitted to the Intensive Care Unit (ICU), and one (3%) received invasive ventilatory support. The patient who received invasive ventilatory support was post-transplantation at the time of infection; however, information was not available on the number of years post-transplant or pre-infection immunosuppressant regimen. The clinical features of COVID-19 (e.g., fever, dry cough, myalgia) in CF appeared to be comparable to the general population affected by the SARS-CoV-2 virus.

Similar results were reported in a subsequently published multinational cohort study of 181 individuals with CF from 19 countries, including 40 from the previous study.[19] Thirty-two (18%) in the cohort were post-transplantation, with 28 (88%) lung transplantations, 2 (6%) liver transplantations, one (3%) lung and liver transplantation, and one (3%) lung and kidney transplantation. Eleven (6%) of the 181 individuals were admitted to the ICU, seven (64%) of whom were post-transplantation. Those individuals whose status was post-transplantation had a significantly higher risk of hospitalization, as evidenced by 74% of the post-transplantation subgroup and 46% of the non-transplantation subgroup requiring hospital care (p = 0.009). There were seven deaths (4%) in the cohort, three (43%) of whom were post-transplantation. Furthermore, individuals with a forced expiratory volume in 1 s (FEV1) less than 70% experienced significantly higher rates of hospitalization than those above 70% (p = 0.001).

In a study of 31 individuals with CF who acquired COVID-19 in France, the calculated incidence was 0.41%, which was 93% less than the general population at the time of the study.[20] The median age of the COVID-19 cohort was higher than that of the general CF population, which was reflective of the age-related findings of the 40-patient multinational cohort study.[18] Twelve individuals (39%) were post-transplant, and all were using oral corticosteroids in their immunosuppressant medication regimen. Three (10%) were asymptomatic; however, among the remaining 28, the most prevalent features at presentation were fever, fatigue, and worsened cough. Nineteen individuals within the cohort (61%) were hospitalized, and of the twelve (39%) who were post-transplantation—eleven (92%) were hospitalized. Of the four individuals (13%) that were admitted to the ICU, three (75%) were post-transplantation. Moreover, individuals who were post-transplantation received supplemental oxygen at significantly higher rates, as among seven of those (23%) who received supplemental oxygen therapy, six (86%) were post-transplantation. Eighteen (58%) individuals were on long-term azithromycin, with five (16%) receiving additional doses.

A study from Spain at the peak of the first pandemic wave reported eight CF individuals who acquired SARS-CoV-2 confirmed by reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR).[21] The study found the incidence of COVID-19 was 0.32% in their population of individuals with CF, which was less than the 0.49% rate in the general Spanish population. Two individuals (25%) were under 18 years of age, while the remaining six were adults. Neither of the two individuals under 18 were hospitalized, while all adults in the cohort did. Four of the adults (66%) received oxygen supplementation, but none received mechanical ventilation. Like the previous studies, one individual (13%) who was post-transplantation received intensive care support. Five in the cohort (63%) received azithromycin as part of their medical management. Ultimately, all eight of the described CF individuals recovered from infection.

Regarding the pediatric CF population, in a multinational cohort study of 105 CF children who had SARS-CoV-2 infection, the median age was 10 years and 2 (2%) were post-transplantation, with both making full recoveries.[22] The median best FEV1 among the 87 children in the cohort above the age of five within the 12 months leading up to infection was 94%. Of the 89 children for whom symptomatology data was available, 26 (29%) were asymptomatic, and the most common clinical features included fever and altered cough. COVID-19 symptoms in the cohort were similar to those reported for non-CF pediatric populations with SARS-CoV-2 infection. Of the 82 children for whom information on level of care was available, 24 (29%) were hospitalized, and one child in the cohort was admitted to the ICU (1%). Of the hospitalized patients whose respiratory support data was available, 6/21 (29%) received supplemental oxygen, 2/20 (10%) received non-invasive ventilation, and 1/20 (5%) received invasive ventilation. The median FEV1 of the children who were hospitalized was significantly lower than those who were treated at a community care level (p = 0.002). There were no deaths in the cohort directly ascribed to COVID-19. Thirty-one children (30%) were on long-term azithromycin.

In the responses to a survey sent to physicians of the Pediatric Assembly of the European Respiratory Society (ERS), 14 children with CF who acquired COVID-19 were briefly described,[23] but there was no documentation of individuals post-transplantation in this sample. Four individuals (29%) experienced pulmonary exacerbation, five (36%) exhibited infection of the upper airway, two (14%) developed pneumonia, and one (7%) was merely febrile at presentation. Seven individuals in the pediatric cohort (50%) were hospitalized, with three of the seven (43%) admitted to the pediatric ICU and the remaining four (57%) to a pediatric ward. One individual (7%) received invasive ventilation therapy, and two (14%) received supplemental oxygen. There were no reported deaths within the sample population. Of the 14, three (21%) of the children received azithromycin as part of their infection treatment.

According to the ECFSPR, 1236 cases of COVID-19 in individuals with CF were reported in 30 European countries.[17] Of these, 946 (77%) cases were documented with at least partial data. The most prevalent age category was 18–29 years, and 56% had a FEV1 > 70. The most common symptoms were increased cough, fever, and fatigue. Of the 582 individuals with documented severities, 550 (95%) were mild or asymptomatic, 23 were (4%) severe cases, and 9 (2%) were critical. With respect to treatment, 217 individuals (23%) were hospitalized; 30 of these (14%) were admitted to the ICU. At the time of reporting, 866 (92%) individuals were fully recovered from infection, 39 (4%) had ongoing infection, and 13 (1%) died.