Epidemiological Profile of Hospitalized Patients with Cystic Fibrosis in Brazil Due to Severe Acute Respiratory Infection during the COVID-19 Pandemic and a Systematic Review of Worldwide COVID-19 in Those with Cystic Fibrosis

Abstract

Since the onset of the coronavirus disease, COVID-19 pandemic, concern arose for those who might be at higher risk of a worse COVID-19 prognosis, such as those with cystic fibrosis (CF). In this context, we evaluated the features of hospitalized patients with CF due to severe acute respiratory infection (SARI) in Brazil and we also performed a systematic review including all the studies published from the beginning of the first case of COVID-19 (17 November 2019) to the date of this search (23 May 2022) which included, concomitantly, patients with CF and COVID-19 in the worldwide population. In our Brazilian data, we evaluated the period from December 2019 to March 2022, and we included 33 demographical and clinical patients' features. We classified the patients into groups: (G1) SARI due to another viral infection than severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (23; 5.4%), (G2) SARI due to an unknown etiological agent (286; 67.1%), and (G3) SARI due to SARS-CoV-2 infection (117; 27.5%). The individuals in G3 tended to be older, especially over 50 years old, and presented a higher prevalence of dyspnea, peripheral capillary oxygen saturation (SpO₂) <95%, and cardiopathy. The highest prevalence for intensive care unit (ICU) treatment (52; 44.4%) and invasive mechanical ventilation (29; 24.8%) was for patients in G3. Almost half of the patients in G3 died (51; 43.6%); in contrast, none in G1 died. However, we observed 43 (15.0%) deaths in G2. In addition, 12 (4.2%) and one (0.9%) death not associated with SARI occurred, respectively, in the G2 and G3. The patients who died due to SARS-CoV-2 infection had a higher frequency of SpO₂ <95% (46; 90.2%), ICU treatment (34; 66.7%), and invasive mechanical ventilation (27; 52.9%) when compared to those who recovered. The systematic review comprised a total of 31 papers published as observational studies. These studies comprised 661,386 patients in total, including children, adults, and elderly age groups. However, only 19,150 (2.9%) patients were diagnosed with CF and, from these patients, 2523 (0.4%) were diagnosed with both CF and COVID-19. It was observed that the most common outcome was the need for hospitalization (n = 322 patients with CF), and the need for oxygen support (n = 139 patients with CF). One hundred patients with CF needed intensive care units, fifty patients needed non-invasive mechanical ventilation support, and only three patients were described as receiving invasive mechanical ventilation support. Deaths were described in 38 patients with CF. Importantly, lung-transplanted patients with CF represented an increased risk of death in one publication; in accordance, another study described that lung transplantation and moderate to severe lung disease were independent risk factors for severe outcomes after SARS-CoV-2 infection. In contrast with the literature, in conclusion, Brazilian patients in G3 presented a severe phenotype, even though most of the other studies did not observe worse outcomes in patients with CF and COVID-19.

Keywords: Brazil; CFTR; SARS-CoV-2; epidemiology; mucoviscidosis; p.Phe508del; severity; systematic review; worldwide.

Figure 1

Distribution of the hospitalized patients with cystic fibrosis due to severe acute respiratory infection in Brazil during the coronavirus disease, COVID-19 pandemic. We showed the Brazilian states and Federal District (FD). We presented the data using the number of individuals (N). AC, Acre; AL, Alagoas; AM, Amazonas; AP, Amapá; BA, Bahia; CE, Ceará; ES, Espírito Santo; GO, Goiás; MA, Maranhão; MS, Mato Grosso do Sul; MT, Mato Grosso; MG, Minas Gerais; PA, Pará; PB, Paraíba; PA, Paraná; PE, Pernambuco; PI, Piauí; RJ, Rio de Janeiro; RN; Rio Grande do Norte; RS, Rio Grande do Sul; RR, Roraima; RO, Rondônia; Santa Catarina; SP, São Paulo; SE, Sergipe; TO, Tocantins; IBGE, Instituto Brasileiro Geografia e Estatística.

Figure 2

Cumulative number of cases for severe acute respiratory infection (SARI) due to an unknown etiological agent group (A) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (B) group by month of coronavirus disease, COVID-19 pandemic considering the outcomes (number (n) of deaths and number of clinical recoveries). We obtained the data from 29 December 2019 to 20 March 2022.

Figure 3

Description of the clinical symptoms and comorbidities of the hospitalized patients with cystic fibrosis according to the severe acute respiratory infection groups in Brazil during the coronavirus disease, COVID-19 pandemic. (A) Clinical symptoms; (B) comorbidities. We presented the data using the percentage (%). We presented the p for the significant association only and performed the statistical analysis using the chi-square test or Fisher’s exact test. We adopted an alpha error of 0.05. SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; %, percentage; SpO₂, peripheral arterial oxygen saturation.

Figure 4

Association between the need for an intensive care unit, the need for mechanical ventilation, and the death of the hospitalized patients with cystic fibrosis according to the severe acute respiratory infection (SARI) groups in Brazil during the coronavirus disease, COVID-19 pandemic. p for the need for an intensive care unit = < 0.001; p for the need for mechanical ventilation = 0.007; p for death = < 0.001. We presented the data using the number of patients (N) and percentage (%). We performed the statistical analysis using the Fisher’s exact test. We adopted an alpha error of 0.05. SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; %, percentage.

Figure 5

Association between clinical symptoms and comorbidities of the hospitalized patients with cystic fibrosis and SARS-CoV-2 infection in Brazil according to the outcome during the coronavirus disease, COVID-19 pandemic. (A) Clinical symptoms; (B) comorbidities. We presented the data using the percentage (%). We performed the statistical analysis using the chi-square test and Fisher’s exact test. We adopted an alpha error of 0.05. *, p with a significant value. SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; %, percentage; SpO₂, peripheral arterial oxygen saturation; OR, odds ratio; 95%CI, 95% confidence interval. Fever—OR = 0.368 (95%CI = 0.170 to 0.797); SpO₂—OR = 3.258 (95%CI = 1.111 to 9.556).

Figure 6

Association between the need for intensive care unit and mechanical ventilatory support with risk of death in hospitalized patients with cystic fibrosis and SARS-CoV-2 infection in Brazil during the coronavirus disease, COVID-19 pandemic. We presented the data using the number of patients (N) and percentage (%). We performed the statistical analysis using the chi-square test for the mechanical ventilatory support and Fisher’s exact test for the intensive care unit. We adopted an alpha error of 0.05. We presented the significant p value as red color. SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; %, percentage.