In
December, 2019, reports emerged from Wuhan, China, of a severe acute
respiratory disease caused by severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2). By the end of April, 2020, over 3 million
people had been confirmed infected, with over 1 million in the USA
alone, and over 215 000 deaths. The symptoms associated with COVID-19
are diverse, ranging from mild upper respiratory tract symptoms to
severe acute respiratory distress syndrome. The major risk factors for
severe COVID-19 are shared with idiopathic pulmonary fibrosis (IPF),
namely increasing age, male sex, and comorbidities such as hypertension
and diabetes. However, the role of antifibrotic therapy in patients with
IPF who contract SARS-CoV-2 infection, and the scientific rationale for
their continuation or cessation, is poorly defined. Furthermore,
several licensed and potential antifibrotic compounds have been assessed
in models of acute lung injury and viral pneumonia. Data from previous
coronavirus infections such as severe acute respiratory syndrome and
Middle East respiratory syndrome, as well as emerging data from the
COVID-19 pandemic, suggest there could be substantial fibrotic
consequences following SARS-CoV-2 infection. Antifibrotic therapies that
are available or in development could have value in preventing severe
COVID-19 in patients with IPF, have the potential to treat severe
COVID-19 in patients without IPF, and might have a role in preventing
fibrosis after SARS-CoV-2 infection.
The virus, which causes atypical pneumonia progressing to acute lung
injury and acute respiratory distress syndrome (ARDS) in some
individuals, was named COVID-19 and spread rapidly through other
provinces in China. Before long the remainder of the world was affected
and on March 11, 2020, WHO assigned to COVID-19 a pandemic status.
suggested that the demographic most severely affected by COVID-19 was
elderly men, and other poor prognostic factors included a history of
smoking and the presence of comorbidities.
173 had severe disease. In this group, the median age was 52 years, 100
(57·8%) were male, 41 (23·7%) had a history of hypertension, 28 (16·2%)
had diabetes mellitus, and ten (5·8%) had coronary artery disease. Of
67 patients who were admitted to intensive care, required mechanical
ventilation, or died, the median age was 63 years, 45 (67%) were male,
and 39 (58%) had a comorbidity, of which the most common was
hypertension affecting 24 (36%) individuals. This description of the
group in whom SARS-CoV-2 infection is most lethal is also highly
representative of patients suffering with idiopathic pulmonary fibrosis
(IPF). IPF characteristically affects men in their seventh or eighth
decade of life,
IPF
is a progressive disease in which lung function inexorably declines,
leading to respiratory failure and eventually death with lung
transplantation being the only treatment that improves outcomes.
A large proportion of patients with IPF are treated with one of the two
available antifibrotic drugs, pirfenidone and nintedanib, that have
been shown to slow the rate of lung function decline.
Given the rapid global spread of the COVID-19 pandemic, and with
efforts largely focused on the management of the most acutely unwell
patients with COVID-19 pneumonia, the IPF clinical and research
communities have had little time to collect sufficient data to
thoroughly evaluate the potential risks and benefits of initiating and
continuing antifibrotic therapy in this setting. To our knowledge, there
are as yet no data reporting the incidence or mortality of SARS-CoV-2
infection in patients with IPF. Given that the risk factors for poor
outcomes in SARS-CoV-2 infection are common in this patient group, who
are further debilitated by reduced pulmonary reserve, it is possible
that the prognosis is even worse for patients with IPF than for the
general population.
In
this Personal View, we address the role of antifibrotic therapy in
patients with IPF who contract SARS-CoV-2 infection and the scientific
rationale for their use or discontinuation. We also consider the
potential novel role of antifibrotic therapy in the management of
patients without IPF who develop COVID-19 pneumonia, acute lung injury,
and ARDS. Finally, we consider the fibrotic consequences for patients
who survive COVID-19-related ARDS.
Conventional antifibrotic therapy in patients with IPF who are infected with SARS-CoV-2
Pirfenidone
and nintedanib are antifibrotic drugs that, despite having differing
modes of action, are similarly effective in attenuating the rate of lung
function decline by about 50%.
There is biological and epidemiological support for the concept that
acute exacerbations of IPF could be triggered by respiratory viral
infections. Wootton and colleagues
found that a small proportion of patients with acute exacerbation of
IPF had evidence of viral infection, including coronavirus infection
(human coronavirus OC43). Acute exacerbations of IPF are also more
common in the northern hemisphere's winter and spring months,
supporting the theory that they might be mediated by respiratory tract
infections. Pirfenidone is a pyridone with a poorly understood mechanism
of action and nintedanib is a tyrosine kinase inhibitor. Although both
drugs have pleiotropic effects, neither is immunosuppressive per se, and
so there is no rationale for their discontinuation in the face of viral
or bacterial infection. Of relevance, data from the INPULSIS II study
there remains the suggestion that nintedanib could reduce the incidence
of acute exacerbation of IPF. Future studies analysing the effect of
the COVID-19 pandemic on the incidence of acute exacerbation of IPF will
be informative in establishing the postulated link with viral
infection.
As of April, 2020,
pirfenidone and nintedanib are commercially available only in oral form
and so cannot be used in patients who are intubated and mechanically
ventilated, clearly restricting their use in those individuals with
severe COVID-19 on the intensive care unit (ICU). An inhaled formulation
of pirfenidone is under evaluation in patients with COVID-19 (NCT04282902).
Further, pirfenidone should be avoided if patients have an estimated
glomerular filtration rate of less than 30 mL/min per 1·73 m2. Although only 12 (1·6%) of 752 patients in the cohort reported by Guan and colleagues
had a creatinine concentration of 133 μmol/L or higher, this proportion
rose to six (4·3%) of 138 patients with severe COVID-19, and data from
Wuhan showed that of 52 patients admitted to the ICU, 15 (28·8%)
developed acute kidney injury and nine (17·3%) required renal
replacement.
These data imply that patients with mild SARS-CoV-2 infection are less
likely to experience renal dysfunction, but with increasing severity of
COVID-19 disease this renal dysfunction might become an important
consideration when considering antifibrotic therapies. Both pirfenidone
and nintedanib can be associated with hepatotoxicity, and liver
dysfunction is common in patients infected with SARS-CoV-2. Elevated
concentrations of liver enzymes were observed in 168 (22%) of 757
patients with confirmed COVID-19 and 56 (39%) of 142 patients with
severe disease.
Concomitant use of antibiotics for superimposed bacterial infection is
likely to heighten the risk of liver dysfunction, and so in the context
of a hospitalised patient who has IPF and severe COVID-19 with deranged
liver function tests, temporarily withholding antifibrotic therapy
pending resolution of liver dysfunction might be necessary, although
this should be assessed on a case-by-case basis.
There
is anecdotal evidence of an increased risk of acute pulmonary embolism
in patients with COVID-19 and anticoagulant therapy might be associated
with improved outcomes in patients with severe COVID-19 and
coagulopathy.
This observation has relevance to patients prescribed nintedanib, as
this drug confers a theoretically increased risk of bleeding when
concomitantly administered with full-dose anticoagulation. In this
context, the balance of risk and benefit is likely to tip in the
direction of withholding antifibrotic therapy, particularly in the
acutely unwell patient with low physiological reserve. Unfortunately, in
a proportion of patients with IPF who contract SARS-CoV-2 infection,
the patient and their medical team might consider escalation to
intensive care to not be in their best interests, and that the focus
should be on palliative care. In this setting, antifibrotic therapy
could be withdrawn in some cases to minimise the side-effects of
pharmacotherapy.
The case for antifibrotic therapy in patients without IPF in the treatment of COVID-19
The
rationale for using antifibrotic therapy is based on the spectrum of
pulmonary fibrotic disease observed in COVID-19, ranging from fibrosis
associated with organising pneumonia to severe acute lung injury, in
which there is evolution to widespread fibrotic change.
with anecdotal reports of severe fibrotic organising pneumonia. In some
cases, abnormal immune mechanisms initiate and promote pulmonary
fibrosis, possibly as a consequence of a cytokine storm.
Although
it might be unrealistic to separate these profibrotic pathways in
individual patients, in whom there is a variable mixture of
immunologically mediated damage and classical acute lung injury,
antifibrotic therapy could provide value in inhibiting both broad
pathways. However, this hypothesis must be advanced with important
caveats, all of which need to be addressed if existing antifibrotic
agents are to be applied in the current pandemic. These drugs do not
address the immune dysregulation of SARS-CoV-2 infection, nor can they
be expected to attenuate the prothrombotic aspects of this complex
pathogenic process. If antifibrotic therapy is to have a role, it is
likely to take the form of inclusion in combination regimens, once
effective anti-inflammatory treatments have been identified. Combination
therapy could, in principle, address major anti-inflammatory and
antifibrotic pathways while attenuating their fibrotic consequences.
A
further uncertainty relates to the rapidity with which antifibrotic
agents act. Antifibrotic therapies are exclusively used in chronic
fibrotic disorders—mostly in IPF but also for progressive pulmonary
fibrotic disease in disorders other than IPF.
Outcomes have generally been evaluated at 1 year follow-up, with
changes in forced vital capacity (FVC) being the uniform primary
endpoint. However, it is striking that in pivotal trials of nintedanib,
both in IPF (the INPULSIS trials)
early separations in FVC trends between treatment and placebo groups
were shown, with significant differences at 4–6 weeks. No similar early
trends exist in the pirfenidone data, but FVC separations were evident
at 3 months in the ASCEND trial.
A decline in FVC occurs slowly in chronic fibrotic lung disease and,
thus, the observed early separation of FVC trends seem to indicate that
antifibrotic agents attenuate profibrotic pathways shortly after their
introduction. However, it might be overly optimistic to expect these
agents to add value in ventilated patients, in whom the opportunity for
effective treatment has already passed. The use of antifibrotic therapy
in COVID-19 might be contingent on the identification of biomarkers
early in the disease course to identify patients with a poor prognosis
who are likely to progress to pulmonary fibrosis and acute lung injury.
It
must also be stressed that the use of antifibrotic therapy in COVID-19
can be based only on extrapolation from chronic lung disease. In this
regard, there are suggestive data that relate to both major profibrotic
pathways: immunologically mediated damage, and acute exacerbations in
patients with IPF who have the histological, imaging, and clinical
profile of acute lung injury.
The efficacy of antifibrotic therapy in different pulmonary fibrotic disorders
Before
2019, nintedanib and pirfenidone had been studied exclusively in IPF.
However, it has become increasingly apparent that distinct patient
subgroups in other interstitial lung diseases show relentless disease
progression, similar to IPF, despite traditional treatments (eg,
corticosteroids and mycophenolic acid) used to suppress immune
dysregulation. These patient subsets, amalgamated as the progressive
fibrotic phenotype, were not able to access antifibrotic drugs confined
by regulators to patients with IPF. With this background, patients with
progressive pulmonary fibrosis in a wide variety of interstitial lung
disorders were combined in the placebo-controlled INBUILD trial of
nintedanib,
an approach similar to that in basket oncological trials. In the
landmark publication, active treatment was associated with a reduction
in FVC decline of about 60%. Importantly, treatment effects were shown
to be strikingly similar within each of the five core disease groups,
one of which consisted of patients with connective tissue
disease-associated interstitial lung disease.
In this subgroup, pathogenetic profibrotic pathways driven by immune
dysregulation might have similarities to those pathways in SARS-CoV-2
infection. Whether or not this speculation is confirmed, the key
conclusion from the INBUILD study was that nintedanib therapy appears to
inhibit fibrogenesis across a wide range of pulmonary disorders. In a
parallel study of pirfenidone therapy in unclassifiable interstitial
lung disease and idiopathic non-specific interstitial pneumonia,
the choice of home spirometry as the primary endpoint might have led
the study to not meet its prespecified criteria for success, but a key
secondary endpoint—FVC trends measured in pulmonary function
laboratories—was equivalent to the primary endpoint in the INBUILD
trial,
and the pirfenidone treatment effects were similar to those of
nintedanib. These trials potentially suggest that antifibrotic therapy,
when used early in SARS-CoV-2 infection, might have major benefits in
reducing fibrotic damage driven by immune dysregulation. However, to
have a major impact on outcome, interventions must also address the
serious issue of acute lung injury.
The potential benefits of antifibrotic therapy in the prevention of acute lung injury
From
the outset, it must be acknowledged that data in this area are
suggestive but inconclusive, in part because acute lung injury is
difficult to study. Putative treatment benefits with antifibrotic
therapy in reducing the prevalence of acute exacerbations of IPF were
observed in patients already established on antifibrotic therapy.
The applicability of these data to COVID-19 depends on the rapidity of
action of antifibrotic drugs and their introduction before severe acute
lung injury has supervened (ie, before assisted ventilation).
In
IPF, acute exacerbations have an almost uniformly poor outcome. This
phenotype has the clinical, imaging, and histological characteristics of
diffuse alveolar damage (ie, ARDS), overlaid on features of IPF. In the
INPULSIS IPF trials of nintedanib,
there were strong trends towards a reduction in the frequency of acute
exacerbations when the two trials were pooled. However, in the pooled
analysis, investigator-defined frequency of acute exacerbations were not
significantly different between nintedanib and placebo. The widespread
uncertainty about this finding relates to the small number of events:
the difference was significant in only one of the two trials. Some
credibility is added by the fact that significance increased when the
pooled adjudicated analysis was confined to episodes judged by an expert
panel to be genuine acute exacerbations, despite the reduction in
numbers of events. Although these observations were merely suggestive,
they do at least provide a theoretical basis for the early use of
antifibrotic therapy in COVID-19.
Much
the same can be argued from data in small cohorts of patients with IPF
undergoing resection of lung cancer, a frequent trigger of fatal acute
exacerbations in IPF. In three Japanese studies, perioperative
pirfenidone therapy was given to patients 4 weeks before surgery and for
a variable time afterwards. Clinical outcomes were compared between
patients receiving and not receiving pirfenidone, although these
evaluations were neither placebo controlled nor randomised. Treatment
with pirfenidone was associated with significant reductions in both
postoperative mortality
In
summary, we hypothesise that a clinical trial of antifibrotic therapy
in COVID-19 before ventilation is warranted. Formal controlled
evaluation is essential to assess unexpected adverse effects, even
though existing antifibrotic agents have not, in general, exhibited
life-threatening toxicity. In advancing this argument, we stress that
there is currently no basis for empirical off-licence treatment. The
assumptions made in this Personal View are that antifibrotic therapy has
a very rapid effect, that treatment benefits in other forms of lung
fibrosis will be applicable to fibrosis triggered by severe viral
infection, and that efficacy might depend on the combination with
anti-inflammatory treatment.
Novel antifibrotic drugs for the treatment of severe COVID-19
There
has been an enormous increase in the number of compounds being assessed
for the treatment of pulmonary fibrosis, many with effects on the
immunoinflammatory system. Indeed, a number of early antifibrotic
studies focused on key antiviral proteins, such as IFN-β and IFN-γ.
and this finding is important given that pulmonary vascular disease
could play an important role in severe COVID-19 disease. Indeed,
circulating IFN-γ and CXCL10 concentrations are raised in patients with
severe COVID-19.
Furthermore, much of the data generated in preclinical studies for
antifibrotic therapy include use of the bleomycin animal model of
pulmonary fibrosis. There are numerous issues with this strategy for
research into IPF therapies, not least because this model is of the
fibrotic response following acute lung injury, rather than the de-novo
progressive fibrosis. However, acute lung injury and ARDS are the major
cause of mortality in COVID-19. Therefore, it is possible that
antifibrotic therapies developed for chronic fibrotic lung diseases
using bleomycin models might actually be beneficial in COVID-19, both in
the acute phase of the illness and in preventing long-term
complications. There are two important issues to consider when trying to
determine whether a novel antifibrotic drug would be harmful or
beneficial in the context of SAR-CoV-2-related illness (table).
First, what is the effect of antifibrotic molecules on viral
internalisation and replication? And second, what is their effect on
mitigating the cytokine storm that seems to be responsible for
complications in severe COVID-19 such as ARDS?
TablePotential link between antiviral mechanisms and antifibrotic drugs
A
major target for antifibrotic therapies is the TGF-β pathway. There are
a number of drugs in development that target various molecules in this
pathway, including those against αvβ6 integrin (BG00011 [Biogen,
Cambridge, MA, USA]; PLN-74809 [Pliant Therapeutics, San Francisco, CA,
USA]) and galectins (TD139 [Galecto Biotech, Copenhagen, Denmark]).
These are particularly interesting candidates because the SARS-CoV-2
spike protein contains an Arg-Gly-Asp integrin-binding domain and a
number of coronaviruses contain an N-terminal galectin fold,
raising the possibility that therapies that inhibit integrins or galectins might be of benefit in treating COVID-19 (figure).
There are some experimental data to support the use of these three
drugs in viral-induced lung injury. Mice that do not express the αvβ6
integrin or treated with an αvβ6 blocking antibody are protected from a
number of viral infections, including influenza and sendai virus.
Reassuringly, given the role of TGF-β in immunity and host defence,
inhibiting epithelial integrins does not appear to increase the risk of
viral infection in several animal models.
Furthermore, IL-1, which has been identified as a key component of the
cytokine storm in COVID-19 and other viruses, might mediate its affects
through Arg-Gly-Asp binding integrins.
Similarly, there is a well described role for galectins in viral
infections. Gal-3 is upregulated in lung epithelial cells after
influenza A infection and promotes binding to Streptococcus pneumonia.
Two
recent network analyses of protein–protein interactions identified that
mTOR might be an anti-SARS-CoV-2 target and that rapamycin could be
repurposed for this indication (figure).
and is commonly used in transplant medicine. In an experimental animal
model of H1N1 influenza, rapamycin in combination with oseltamivir
reduced viral replication and the NLRP3 inflammasome.
PRM-151
(Roche, Basel, Switzerland) is an analogue of SAP (also known as PTX2),
which is a member of the pentraxin family of proteins that includes CRP
and PTX3, and has shown promising results in a phase 2 trial for IPF.
which has also been therapeutically targeted in IPF (CC-90001; Celgene,
Summit, NJ, USA). This selective JNK1 inhibitor has been shown to
prevent fibrosis in some experimental animal models,
H5N1 influenza infection leads to upregulation of cytokines such as
TNFα, IFN-β, and IL-6 via phosphorylation of JUN, and genetic targeting
of JNK1 improved survival and reduced bronchoalveolar lavage cytokines
in mice.
In studies with dengue virus, which is also a positive-sense,
single-stranded RNA virus, in a viral animal model, a JNK inhibitor
reduced viral liver injury and markers of severe disease, such as
leucopenia and cellular apoptosis.
On
March 30, 2020, Vicore Pharma submitted a clinical trial application
for C21 (an agonist of AT2R) in IPF and this drug has been given
approval for a phase 2 study in COVID-19 (EudraCT 2017-004923-63). The
role of angiotensin in SARS-CoV-2 is well documented, if somewhat poorly
understood understood.
Membrane bound ACE2 is the primary receptor for SARS-CoV-2, but is shed
into the serum by ADAM17 where it acts to catalyse the hydrolysis of
Ang II to Ang 1–7. This cleavage prevents the harmful effects of Ang II,
which the conventional AT1R inhibitors, the artans, exploit in the
treatment of hypertension. The role of AT1R inhibitors in COVID-19 is
controversial, with studies suggesting that these treatments might
increase ACE2 concentrations.
However, a study has shown that the risk of severe COVID-19 was
significantly decreased in patients who took AT1R blockers before
hospitalisation compared with patients who took no drugs (odds ratio
0·343, 95% CI 0·128–0·916, p=0·025).
however, C21 has been shown to have anti-inflammatory properties in
experimental animal models of acute lung injury and the role of C21 in
viral infection is not known (table).
Potential
antifibrotic therapies might have beneficial effects in the treatment
of COVID-19 through a range of different mechanisms, such as preventing
viral uptake and replication, inhibiting viral signalling, and through
beneficial effects on the renin–angiotensin system (figure).
Although there is clearly much work to be done before these drugs could
be considered safe, let alone beneficial in the context of COVID-19,
the medical community should be reassured that there is biological
rationale to suggest that antifibrotic therapies might have potential as
novel therapeutics for severe COVID-19.
COVID-19, ARDS, and pulmonary fibrosis
Although
many patients who develop ARDS survive the acute phase of the illness, a
substantial proportion die as a result of progressive pulmonary
fibrosis.
Importantly, in an autopsy study of 159 patients with ARDS, fibrosis
was noted in three (4%) of 82 patients with a disease duration of less
than 1 week, 13 (24%) of 54 patients with a disease duration of between
weeks 1 and 3, and 14 (61%) of 23 patients with a disease duration of
greater than 3 weeks, suggesting that to be effective, any potential
antifibrotic intervention should be considered within the first week of
ARDS onset.
A substantial proportion of patients who develop ARDS will experience
residual long-term impairment of lung function and CT evidence of
pulmonary fibrosis,
The extent of reticulation on CT correlates with quality of life and
lung function measures of pulmonary restriction, such as FVC and the
diffusion of the lung for carbon monoxide, with approximately 25% of
survivors exhibiting physiological evidence of restrictive lung disease.
Important mediators include the dysregulated release of matrix
metalloproteinases during the inflammatory phase of ARDS, which causes
epithelial and endothelial injury
It remains unclear why certain individuals are able to recover from
such an insult, whereas in others there is a shift to unchecked cellular
proliferation with the accumulation of fibroblasts and myofibroblasts
and the excessive deposition of collagen alongside other components of
the extracellular matrix to result in progressive pulmonary fibrosis.
The
prevalence of post-COVID-19 fibrosis will become apparent in time, but
early analysis from patients with COVID-19 on discharge from hospital
suggests a high rate of fibrotic lung function abnormalities. Overall,
51 (47%) of 108 patients had impaired gas transfer and 27 (25%) had
reduced total lung capacity. This was much worse in patients with severe
disease.
Until mature data are available, it is important to draw on the
experience of previous coronavirus outbreaks. Although the global
outbreak of SARS in 2003, caused by SARS-CoV,
affected far fewer individuals than the current COVID-19 pandemic,
there are clear parallels. In a study of 75 patients who were
consecutively hospitalised and met criteria for SARS, as defined by
fever with a temperature of 38°C or higher, cough or shortness of
breath, and new pulmonary infiltrates, the frequency of ARDS was 20% by
week 3 of admission.
Patients requiring admission to ICU with SARS had significantly more
restricted lung function at 6 months after disease onset than those 6
months following ward-based treatment.
Across the entire cohort and regardless of whether ICU admission was
required, impairment of gas diffusion was observed in 17 (16%) and
abnormal chest radiographs were present in 33 (30%) of SARS survivors.
In an early follow-up study of patients with SARS, 15 (62%) of 24
patients had CT evidence of pulmonary fibrosis at a mean follow-up
duration of 37 days after hospital discharge.
Patients at higher risk of developing post-SARS fibrosis were older and
more likely to have required ICU care than patients without post-SARS
fibrosis. In a follow-up study of 36 patients surviving Middle East
respiratory syndrome coronavirus infection, 12 (33%) had radiographic
evidence of pulmonary fibrosis; these patients were older and had longer
ICU admissions.
Given approximately 30% of survivors of SARS and Middle East
respiratory syndrome experienced persistent radiological and
physiological abnormalities consistent with fibrotic lung disease, the
repercussions of COVID-19 could include a large cohort of individuals
with pulmonary fibrosis and persistent and potentially progressive
physiological impairment. Long-term follow-up studies will be required
to establish the true prevalence of post-COVID-19 fibrosis.
A
further complicating factor in the COVID-19 pandemic is that many
patients around the world will be receiving anti-interleukin therapies
for severe disease, including anakinra or anti-IL-6 therapies, either
through participation in clinical trials (NCT04332913; NCT04322773; NCT04331795; NCT04315298; NCT04324021) or as off-licence therapies.
and inhibiting IL-1 could possibly prevent the development of
post-COVID-19 fibrosis, the role of anti-IL-6 strategies is less clear.
Although IL-6 is generally considered to be a profibrotic molecule,
an experimental study with the bleomycin model of pulmonary fibrosis
suggested that inhibiting IL-6 in the early phase of lung injury
promotes fibrosis and that inhibition in the later stages of injury at
the onset of the fibrotic phase might ameliorate fibrosis.
and pirfenidone reduces serum and lung IL-6 concentrations in murine
models of pulmonary fibrosis, providing further biological rationale for
the use of pirfenidone in COVID-19.
Given
the scale of the COVID-19 pandemic and the number of people requiring
invasive ventilation worldwide, post-COVID-19 fibrosis is likely to be a
substantial problem. The effects of anti-interleukin therapy in the
long term, although potentially beneficial, are completely unknown and
could lead to worse fibrosis. Ultimately, the interstitial lung disease
community should pull together to investigate the long-term consequences
of COVID-19 and develop evidence-based strategies to deal with this
emerging problem.
Conclusion
The
COVID-19 pandemic is bringing huge economic, social, and health-care
challenges. As the wave of viral infection recedes, other problems will
emerge that will need to be addressed. In this context, it is important
to try and predict and prepare for these challenges. Many of the
epidemiological risk factors and biological processes that lead to
viral-induced ARDS are shared with IPF. In addition, many of the current
and emerging antifibrotic drugs could have therapeutic potential for
treating severe COVID-19 and preventing the long-term fibrotic
consequences that might follow this pandemic. Ultimately, we hope the
observations highlighted in this Personal View will help the respiratory
and critical care communities to work together on well designed studies
of antifibrotic therapies for severe COVID-19 pneumonia.
Search strategy and selection criteria
Contributors
All
authors did the literature search and drafted sections of the
manuscript. RGJ combined and edited the drafts, prepared the figures,
and supervised the manuscript. All authors subsequently revised the
manuscript.
Declaration of interests
This
Personal View was not funded by any organisation. PMG reports grants,
personal fees, and non-financial support from Boehringer Ingelheim;
personal fees and non-financial support from Roche Pharmaceuticals; and
personal fees from Teva, outside of the submitted work. AUW reports
personal fees and non-financial support from Boehringer Ingelheim and
Roche Pharmaceuticals; and personal fees from Blade, outside of the
submitted work. RGJ reports grants from AstraZeneca, Biogen, Galecto,
and GlaxoSmithKline; personal fees from Boehringer Ingelheim, Daewoong,
Galapagos, Heptares, Promedior, and Roche; grants and personal fees from
Pliant; non-financial support from NuMedii and Redx; and other from
Action for Pulmonary Fibrosis, outside of the submitted work.
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COVID-19 Resource Centre
Access the latest 2019 novel coronavirus disease (COVID-19) content from across The Lancet journals as it is published.
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El 11 de Marzo realice una aproximacion al tema con JC Sanchis sobre este tema: Interferon y Rividmanina de la hepatitis C aplicada al cornovirus, al leer que habina casos que se provoca fibrosis en el pulmon, relacionandolo con la fibrosis del higado de la Hepatitis C
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