The COVID-19 pandemic started in December 2019 in Wuhan, China, with reports of viral pneumonia and acute respiratory distress syndrome (ARDS) in December of 2019. Since its emergence, COVID-19 has infected more than 600 million people globally and has caused in excess of 6.5 million deaths worldwide as of September 30, 2022.1
Postacute sequelae of COVID-19, also known as long COVID, may effect up to 30% of survivors.2 Pulmonary fibrosis as a postacute sequela of COVID-19 has the potential to become a global health crisis.2 Data from relatively recent pre–COVID-19 coronavirus outbreaks (SARS in 2003 and MERS in 2012) demonstrate persistent radiographic and pulmonary function test abnormalities after the resolution of acute illness.3,4 Considering the genetic similarity of COVID-19 to SARS and MERS, and the massive, worldwide reach and spread of the pandemic, the burden of pulmonary fibrosis morbidity and mortality may have a significant global and societal impact.
In this issue of Infectious Disease in Clinical Practice, Kebede et al5 presented their detailed meta-analysis of the eligible trials on COVID-19–associated pulmonary fibrosis in “The global prevalence of pulmonary fibrosis among post–COVID-19 follow-up patients. Systematic review and meta-analysis: 2021.”
This is an ambitious and worthy undertaking that may lead to additional investigation and impact guidelines for screening. A high pooled prevalence of 50.04% is reported from the meta-analysis of studies from China, Pakistan, and Egypt in 2020 and 2021.5 A wide range of prevalence is reported from 31% to 41% in Egypt to 43% to 85% in China.
The mechanism for COVID-19–associated pulmonary fibrosis still remains speculative, but ARDS, a well-known precursor of pulmonary fibrosis, was present in up to 40% of patients before the introduction of effective treatments and vaccines.6 The key feature distinguishing COVID-19 ARDS/pneumonia/respiratory failure is the longer duration of mechanical ventilation: 14 days versus 4 days as compared with influenza and other causes.7 The severity of acute illness, and particularly the length of mechanical ventilation, correlates with the presence of pulmonary fibrosis.8
Some of the studies included in the meta-analysis were completed in the earlier phase of the pandemic and likely did not account for the emergence of new variants and the introduction of widespread vaccination and effective treatments. These meta-analysis data may not be extrapolated to the current state of COVID-19 infection as the prevalence of severe disease and ARDS has changed worldwide, and the new variants have emerged. The Omicron variant is shown to cause fewer post COVID-19 sequelae compared WITH the Delta variant.9
An important public health issue is the screening and management of COVID-19 survivors. Currently, the screening is driven by the severity of acute COVID-19 illness, presence of symptoms at follow-up, and the level of suspicion. The screening and diagnostic approach usually includes imaging, specifically high-resolution computer tomography, and pulmonary function tests. Based on the sheer magnitude of the pandemic, the number of survivors of COVID-19 pneumonia and ARDS is likely to be in the millions. Well-designed cohort studies are needed to define the groups that are at risk for poor prognosis and require targeted screening and follow-up.
1. Johns Hopkins University Center for Systems Science and Engineering (CSSE); Our World in Data, September 30, 2022.
2. Mylvaganam RJ, Bailey JI, Sznajder JI, et al. Center Consortium. Recovering from a pandemic: pulmonary fibrosis after SARS-CoV-2 infection. Eur Respir Rev
3. Hui DS, Joynt GM, Wong KT, et al. Impact of severe acute respiratory syndrome (SARS) on pulmonary function, functional capacity and quality of life in a cohort of survivors. Thorax
4. Das KM, Lee EY, al Jawder SE, et al. Acute Middle East respiratory syndrome coronavirus: temporal lung changes observed on the chest radiographs of 55 patients. AJR Am J Roentgenol
5. Worku Misganaw K, Getaneh Baye M, Bantalem Tilaye A, et al. The global prevalence of pulmonary fibrosis among post–COVID-19 follow-up patients. Systematic review and meta-analysis: 2021, Infectious Disease in Clinical Practice, TBD: In this issue.
6. Wu C, Chen X, Cai Y, et al. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern Med
7. Grant RA, Morales-Nebreda L, Markov NS, et al. Circuits between infected macrophages and T cells in SARS-CoV-2 pneumonia. Nature
8. McGroder CF, Zhang D, Choudhury MA, et al. Pulmonary fibrosis 4 months after COVID-19 is associated with severity of illness and blood leucocyte telomere length. Thorax
9. Antonelli M, Pujol JC, Spector TD, et al. Risk of long COVID associated with delta versus omicron variants of SARS-CoV-2. Lancet