associated with more severe forms of the disease. By exploring the immunological responses,
the reader will understand the deleterious effects of a maladaptive immune response to
COVID-19 and how various pathways can be targeted for therapies such as immune
modulation (for example, IL-6 inhibitors), as well as vaccine development (for example,
spike protein).
With COVID-19 infection, a variable pathological process occurs in the lung. In those who are
critically ill, it is now well-established from post mortem examinations that the lungs have
evidence of diffuse alveolar damage with lymphoid infiltration of the interstitium and capillary
or arteriolar microthromboses. In those with less respiratory compromise, this is reflected in the
lung tissue by lymphocytic-type pneumonia with atypical hyperplasia of type II pneumocytes.
Describing the variety of patterns of lung injury helps respiratory teams appreciate the likely
severity of the disease, the benefits of suggested therapeutics and the potential long-term
consequences, such as lung fibrosis in those who have been ventilated for longer periods.
Another fundamental chapter of this Monograph is the patient perspective, which presents the
powerful narrative of a COVID-19 survivor [5]. They detail their hospital experience in the
general ward as well as in the ICU. At the start of the pandemic, many advocated early
intubation and some clinicians were reticent to consider high-flow oxygenation or noninvasive
measures for respiratory support, partly due to the fear of aerosolisation of the COVID-19
virus. More recent observational studies have demonstrated the utility of high-flow oxygenation
and perhaps even noninvasive therapy to help reduce the need for invasive ventilation [6].
Proning has been a central part of our supportive therapy for awake and ventilated patients,
and thanks to trial data [7–11], we are now equipped with therapeutics [12].
The rapid response to the virus in terms of the design and swift implementation of large
international clinical trials to ascertain the effects of differing therapeutics was a major
accomplishment and success [13]. Barriers that prevented collaborative work disappeared,
and respiratory scientists and clinicians around the world worked as one. Currently, we are
able to offer: dexamethasone, which RCTs have shown to have mortality benefits
remdesivir, an anti-viral drug that inhibits viral RNA transcription and tocilizumab and
sarilumab, which are monoclonal antibodies that block the IL-6 receptor, thus instigating a
reduction in pro-inflammatory cytokines [7–11, 14].
With the advent of large, adaptive platform trials, recommendations have been made pertaining
to the role of therapeutic versus prophylactic anticoagulation in COVID-19 patients [15]. The
suggestion is that therapeutic anticoagulation should be strongly considered in moderately unwell
general ward patients with a low risk of bleeding. Patients receiving high-flow oxygenation,
NIV or invasive ventilation should, conversely, be offered prophylactic anticoagulation.
For those who survive COVID-19, there is emerging evidence of the persistence of diverse
symptoms after the acute phase of the disease. These enduring symptoms may be respiratory
in nature but many patients also suffer from extra-respiratory post-COVID sequelae. This
chapter of the Monograph offers a comprehensive guide to post-COVID sequelae, together
with the rationale and benefits of rehabilitation in this typically younger cohort of patients, in
order to support their return to being productive members of society [16].
Predictably, the COVID-19 pandemic has had a detrimental effect on society, not only on the
physical health of some of those significantly affected but also upon mental and economic
x https://doi.org/10.1183/2312508X.10017521
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