Objective: This systematic review and meta-analysis aims to explore overall prevalence of burnout among physicians during early and late COVID-19 pandemic and geographical differences in burnout.Methods: This review was registered prospectively with PROSPERO (CRD42022327959). A comprehensive search of several databases, including Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, PsycINFO, and Scopus, spanning from December 2019 to May 2022 was conducted. Eligible studies included physicians or medical professionals including physicians that worked directly or indirectly with COVID-19 patients, whilst reporting burnout outcomes using a validated scale. Literature that did not include physicians or did not occur in a hospital setting were excluded. Literature including medical students were also excluded.Results: Forty-five observational studies were included, all of which were cross-sectional studies. The pooled estimate of overall prevalence of burnout was 54.60% (95% CI: 46.7, 62.2). Mean emotional exhaustion, depersonalization, and personal accomplishment was found to be 22.06% (95% CI: 18.19, 25.94), 8.72 (95% CI: 6.48, 10.95) and 31.18 (95% CI: 27.33, 35.03) respectively. Frontline workers displayed higher rates of burnout than second-line healthcare workers (HCW) (OR: 1.64, 95% CI: 1.13, 2.37). Studies from the early pandemic period reported burnout prevalence of 60.7% (95% CI: 48.2, 72) compared to a prevalence of 49.3% (95% CI: 37.7, 60.9) from the late pandemic period. Geographically, burnout was highest amongst Middle East and North Africa (MENA) studies (66.6%, 95% CI: 54.7, 78.5), followed by Europe (48.8%, 95% CI: 40.3, 57.3) and then South America (42%, 95% CI: –0.4, 84.4). Lastly, burnout prevalence overall (OR = 0.77, 95% CI: 0.36, 1.67) emotional exhaustion (MD = –0.36, 95% CI: –4.64, 3.91), depersonalization (MD = –0.31, 95% CI: –1.80, 1.18), and personal accomplishment (MD = 0.55, 95% CI: –0.73, 1.83) were found comparable between physicians and nurses.Conclusion: COVID-19 has had significant consequences on HCW burnout. Further research is needed to examine early signs of burnout and to develop effective coping strategies.

Dysregulation of glutamate homeostasis is a well-established core feature of neuropsychiatric disorders. Extracellular glutamate concentration is regulated by glutamate transporter 1 (GLT-1). The discovery of a beta-lactam antibiotic, ceftriaxone (CEF), as a safe compound with unique ability to upregulate GLT-1 sparked the interest in testing its efficacy as a novel therapeutic agent in animal models of neuropsychiatric disorders with hyperglutamatergic states. Indeed, more than 100 preclinical studies have shown the efficacy of CEF in attenuating the behavioral manifestations of various hyperglutamatergic brain disorders such as ischemic stroke, amyotrophic lateral sclerosis (ALS), seizure, Huntington’s disease, and various aspects of drug use disorders. However, despite rich and promising preclinical data, only one large-scale clinical trial testing the efficacy of CEF in patients with ALS is reported. Unfortunately, in that study, there was no significant difference in survival between placebo- and CEF-treated patients. In this review, we discussed the translational potential of preclinical efficacy of CEF based on four different parameters: (1) initiation of CEF treatment in relation to induction of the hyperglutamatergic state, (2) onset of response in preclinical models in relation to onset of GLT-1 upregulation, (3) mechanisms of action of CEF on GLT-1 expression and function, and (4) non-GLT-1-mediated mechanisms for CEF. Our detailed review of the literature brings new insights into underlying molecular mechanisms correlating the preclinical efficacy of CEF. We concluded here that CEF may be clinically effective in selected cases in acute and transient hyperglutamatergic states such as early drug withdrawal conditions.