Drug‐induced organ injury in coronavirus disease 2019 pharmacotherapy: Mechanisms and challenges in differential diagnosis and potential protective strategies

Abstract

The world is currently facing an unprecedented pandemic caused by a newly recognized and highly pathogenic coronavirus disease 2019 (COVID‐19; induced by SARS‐CoV‐2 virus), which is a severe and ongoing threat to global public health. Since COVID‐19 was officially declared a pandemic by the World Health Organization in March 2020, several drug regimens have rapidly undergone clinical trials for the management of COVID‐19. However, one of the major issues is drug‐induced organ injury, which is a prominent clinical challenge. Unfortunately, most drugs used against COVID‐19 are associated with adverse effects in different organs, such as the kidney, heart, and liver. These side effects are dangerous and, in some cases, they can be lethal. More importantly, organ injury is also a clinical manifestation of COVID‐19 infection. These adverse reactions are increasingly recognized as outcomes of COVID‐19 infection. Therefore, the differential diagnosis of drug‐induced adverse effects from COVID‐19‐induced organ injury is a clinical complication. This review highlights the importance of drug‐induced organ injury, its known mechanisms, and the potential therapeutic strategies in COVID‐19 pharmacotherapy. We review the potential strategies for the differential diagnosis of drug‐induced organ injury. This information can facilitate the development of therapeutic strategies, not only against COVID‐19 but also for future outbreaks of other emerging infectious diseases.

Unknown adverse drug reactions from spontaneous reports in a hospital setting: characterization, follow-up, and contribution to the pharmacovigilance system

“…In fact, a safety alert note about the possible risk of drug interaction was issued by the EMA ( European Medicine Agency, 2020 ). However, probably because no increased risk on mortality and life-threatening arrhythmias with this treatment was described in some studies during the COVID-19 pandemic ( Huang, et al, 2020 ; Bernardini, et al, 2021 ) and the difficulties to distinguish between mortality and cardiac arrhythmias due to COVID-19 from those related to its treatment ( Kochav, et al, 2020 ; Ommati, et al, 2021 ), no further measures were taken by the pharmacovigilance authorities. Regarding thrombotic events with COVID-19 vaccines there is some scientific evidence that support this association ( Bilotta et al, 2021 ).…”

Safety of Drugs Used during the First Wave of COVID-19: A Hospital-Registry-Based Study

“…Alternative causes were difficult to assess given the novelty of the disease, along with the possibility that COVID-19 itself could explain some of the signs or symptoms registered as ADRs, including cases of well-known ADRs such as diarrhea in patients receiving lopinavir/ritonavir, as well as some cases of hepatitis. The inflammation–drug interaction in these patients has been highlighted as a plausible mechanism of injury to the liver (or other organs) [ 12 , 21 ].…”

“…In another study with propensity-matching of groups, there were no differences in in-hospital mortality, life-threatening arrhythmias, or incidence of pulseless electrical activity arrest between a group of patients treated with hydroxychloroquine and azithromycin and untreated control groups, although QTc intervals were longer in patients receiving both treatments, and one patient developed drug-related ventricular tachycardia [ 9 ]. Once again, it is also challenging to distinguish mortality and cardiac arrhythmias due to COVID-19 from those related to its treatment [ 10 , 12 ].…”

“…Although in absolute terms the incidence of cardiac events related to each of them is low—especially in short-term treatments—the risk is expected to increase when they are used in combination (pharmacodynamic interaction) or in the presence of other risk factors [ 6 , 7 , 8 , 9 , 10 , 11 ]. Furthermore, their use in patients with a still-unknown pathology (e.g., coronavirus disease 2019 (COVID-19)) could be associated with a different adverse drug reaction (ADR) profile [ 12 ].…”

Mouthwashes and the Effect on the Viral Load of SARS-CoV-2 in Saliva: A Literature Review

“…In Japan, they are even considered natural products and their use in food is widespread [40]. Cyclodextrins can be considered safe for ingestion because they are not generally absorbed from the gastrointestinal tract, and are currently used in conjunction with remdesivir, a drug approved by the Food and Drug Administration (FDA) against COVID-19 [40], [41].…”