INTRODUCTION
Coronavirus disease 2019 (COVID-19) is a respiratory tract infection
caused by a novel member of human coronavirus, the severe acute
respiratory syndrome coronavirus 2 (SARS-CoV-2)
(1). It causes a wide spectrum of clinical
manifestations ranging from asymptomatic cases to patients with mild,
uncomplicated illness and severe cases, with or without pneumonia
(2). Hospitalization and oxygen support,
and admission to an intensive care unit are required in 14% and 5% of
the patients, respectively (1). Gastrointestinal symptoms and positive
viral nucleic acid testing on rectal swabs are considered as indicators
of infection in digestive system and fecal-oral transmission of COVID-19
(3). Moreover, skin symptoms, including
exanthems, may appear during the evolution of the disease leading to
differential diagnosis with drug hypersensitivity reactions (DHRs) (4).
In critically ill patients, COVID-19 can be complicated by acute
respiratory distress syndrome (ARDS), septic shock, and multi-organ
dysfunction syndrome (1). In such
patients, in response to viral infection, the excessive activation and
expansion of T lymphocytes and macrophages lead to an overproduction of
cytokines, which causes a cytokine storm and a hyperinflammatory state
(5, 6).
Acute hyperinflammation may activate coagulation cascade and inhibit
fibrinolytic reaction, thus promoting thrombosis. Coagulopathy and
thrombocytopenia are serious complications which increase the risk of
haemorrhage and thrombosis and progress to disseminated intravascular
coagulation (DIC) (7).
The periodically updated World Health Organisation interim guidance
allows reliable comparison of investigational therapeutic interventions
as part of randomized controlled trials, provides recommendations for
the management and forms the basis of many institutional or national
protocols (1). Unfortunately, none of the
drugs used for COVID-19 have been proven to be truly effective yet;
besides, no specific antiviral drugs have been approved for COVID-19 by
health authorities (8,9). At the moment, there is no specific treatment
for COVID-19, and standard practice of care focuses on treating the
clinical symptoms with supportive care
(1).
In this review, diagnosis and management of DHRs, which are expected to
be caused by current or candidate repurposed and off-label drugs used
for COVID-19 treatment mostly based on prior knowledge, are discussed
(8,10,11). Drugs in this review are classified into four groups
according to their potential roles in different phases of the disease as
antiviral drugs, antiviral and/or immunomodulatory drugs used in viral
pneumonia; anti-cytokine and anti-inflammatory drugs considered during
macrophage activation syndrome (MAS) and cytokine storm;
anti-inflammatory drugs in ARDS; and anti-aggregant and anti-coagulant
drugs in coagulopathy (Figure 1). Information of DHRs due to the use of
additional drugs for various purposes can be found in the relevant
European Academy of Allergy and Clinical Immunology (EAACI) resources
(12-20).
Since emerging recent findings are dynamically changing the clinical
interventions, it is expected that the list of drugs determined
according to current knowledge may change with upcoming recommendations
in future.