Use of corticosteroids in sepsis and infectious diseases: a narrative review

Article information

Korean J Intern Med. 2026;41(4):585-596

Publication date (electronic) : 2026 July 1

doi : https://doi.org/10.3904/kjim.2025.283

Jong Hun Kim

Division of Infectious Diseases, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Korea

Correspondence to: Jong Hun Kim, MD, PhD, Division of Infectious Diseases, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, 59 Yatap-ro, Bundang-gu, Seongnam 13496, Korea, Tel: +82-31-780-5029, Fax: +82-31-780-5583, E-mail: smonti1976@hotmail.com, https://orcid.org/0000-0001-6703-5804

Received 2025 August 17; Revised 2025 October 12; Accepted 2025 November 27.

Abstract

Graphical abstract

INTRODUCTION

A dysregulated host inflammatory response is common in acutely ill patients presenting with sepsis and septic shock secondary to various types of infections, including urinary tract infections, intra-abdominal infections, and community-acquired pneumonia (CAP) [1]. The clinical manifestations of a dysregulated host inflammatory response include severe hypotension, impaired tissue perfusion, and organ dysfunction, which commonly lead to multiorgan failure [1,2]. The pathophysiology of septic shock involves a complex interplay between infectious agents and host immune responses, together with multiple systemic factors [2]. Patients with septic shock often experience relative adrenal insufficiency, which leads to inadequate cortisol production to cope with the overwhelming inflammatory stress response [3]. In this regard, corticosteroids have been postulated to be beneficial because of their anti-inflammatory and immunomodulatory effects, owing to their potential contribution to stabilizing hemodynamics and improving clinical outcomes. The possible beneficial effects of corticosteroids have been investigated in clinical trials involving patients with septic shock. However, evidence regarding the benefits of corticosteroids has evolved as a subject of ongoing discussion. The literature shows mixed results regarding corticosteroid benefits because some studies indicate positive outcomes, such as faster shock resolution, shorter ventilation times, and reduced death rates. However, other studies have shown no significant mortality advantage because of critical illness variability and challenges in defining steroid treatment indications [4–7]. Consequently, the Surviving Sepsis Campaign guidelines provide cautious recommendations regarding the use of corticosteroids for septic shock in adult patients [8]. In addition, the coronavirus disease 2019 (COVID-19) outbreak created particular interest in the use of corticosteroid therapy. One pivotal trial, the RECOVERY trial, demonstrated a significant mortality benefit of dexamethasone in patients with severe COVID-19 requiring oxygen support [9]. Moreover, a recent clinical trial showed the survival benefit of corticosteroid use in patients with severe CAP [10]. This narrative review aimed to evaluate the role of corticosteroids in critically ill patients, including those with sepsis, septic shock, COVID-19, and severe CAP, based on an emerging body of evidence.

METHODS

PubMed was searched for the following terms: “sepsis,” “septic shock,” “community-acquired pneumonia,” “COVID-19,” “respiratory virus,” “steroid,” “corticosteroid,” “randomized trial,” “meta-analysis,” and resulting entries published up to June 2025 were investigated. Publications containing relevant content were selected for inclusion in this narrative review. The references of these publications were reviewed to identify additional relevant studies.

PATHOPHYSIOLOGY OF ADRENAL INSUFFICIENCY IN SEPSIS

The hypothalamic-pituitary-adrenal (HPA) axis, an integrated system involving the hypothalamic paraventricular nucleus (PVN), anterior pituitary gland, and adrenal cortex, plays a vital role in the host physiological stress response. In normal conditions, PVN will secrete corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) which act synergistically to stimulate the anterior pituitary to release adrenocorticotropin hormone (ACTH) [11]. When ACTH reaches the adrenal cortex, it promotes several processes that increase the biosynthesis and secretion of the glucocorticoid cortisol. It is released in a basal and pulsatile manner [12]. In the blood, cortisol is mainly bound to cortisol-binding globulins (CBGs). A small unbound, bioactive fraction of cortisol passes through cell membranes to reach cytosolic glucocorticoid receptors (GRs), mostly GRα and GRβ [13,14]. After a ligand binds to a GR, a conformational change occurs. The receptor dissociates from chaperone proteins in the cytoplasm. Finally, it is translocated to the nucleus and mitochondria. It binds to specific glucocorticoid response elements (GREs) to regulate gene expression via transactivation or cis-repression. One of the central mechanisms through which glucocorticoids mediate their anti-inflammatory effects involves the suppression of major transcriptional proteins that glucocorticoids inhibit. A key example is the inhibition of nuclear factor kappa B, a pivotal transcriptional regulator of pro-inflammatory cytokines, including interleukin 1, interleukin 6, and tumor necrosis factor-alpha [15]. While GRα mediates the anti-inflammatory and cardiovascular effects of cortisol, GRβ may exert proinflammatory effects. This system is regulated by a negative feedback loop in which free cortisol inhibits the release of CRH and ACTH [16].

The integrity of the HPA axis may be compromised in the context of critical illnesses, such as septic shock. A characteristic of this dysregulation is a significant elevation in circulating free cortisol levels, which is related to disease severity [17]. However, hypercortisolemia frequently occurs independent of ACTH concentration [18]. This dissociation from both decreased ACTH and CBG levels, as well as diminished CBG-binding capacity, can contribute to elevated levels of free cortisol [19]. Despite increased expression of proopiomelanocortin (POMC), the precursor of ACTH, under CRH and AVP stimulation, impaired POMC processing leads to inadequate ACTH production. Inadequate ACTH production can further enhance ACTH-cortisol disconnection and ongoing adrenocortical steroidogenesis [20]. Thus, cortisol clearance may be impaired during sepsis. Inflammatory cytokines inhibit hepatic α-ring reductases and renal 11β-hydroxysteroid dehydrogenase type 2, the principal enzymes involved in cortisol inactivation [21]. Suppression of the negative feedback of cortisol is associated with a prolonged half-life of the hormone. Hepatic GRs may modulate this process; however, the exact mechanisms involved are not fully understood. In addition, sepsis changes the GR isoforms expression, which means GRβ is transcriptionally enhanced compared to GRα. This change in response is linked to the rise of GRβ, and at tissue level this is described as “glucocorticoid resistance” which is associated with diminished response to endogenous glucocorticoids [22]. When combined, mechanisms such as activation of the HPA axis, impairment of the HPA axis, and glucocorticoid resistance that occur in critical illness may lead to critical illness-related corticosteroid insufficiency (CIRCI) (Fig. 1).

Figure 1

Critical illness-related corticosteroid insufficiency. HPA axis, hypothalamic-pituitary-adrenal axis; ACTH, adrenocorticotropic hormone; GRβ, glucocorticoid receptor β.

In 2008, CIRCI was defined as inadequate corticosteroid activity for the severity of the patient’s critical illness by the Society of Critical Care Medicine (SCCM) and the European Society of Intensive Care Medicine (ESICM) [23]. CIRCI is associated with various severe conditions such as sepsis, septic shock, and severe pneumonia. Clinically, CIRCI often manifests as hemodynamic instability despite adequate fluid resuscitation, accompanied by fever and systemic inflammation. The reported incidence of CIRCI varies, ranging from 20 to 60%, among patients with septic shock admitted to intensive care units (ICUs), reflecting the possibility of a common incidence of CIRCI among critically ill patients [15]. However, no single test can be used to reliably diagnose CIRCI [24]. A rise in total serum cortisol of less than 9 μg/dL at 60 minutes following administration of 250 μg of intravenous (IV) cosyntropin, or a random total plasma cortisol level below 10 μg/dL may be used as indicators of suggesting CIRCI [24]. Nevertheless, the interpretation of these thresholds is limited, as total serum cortisol levels may vary widely in patients with septic shock, and the response to ACTH stimulation may be unreliable in critically ill patients [25,26]. Therefore, when clinical features are strongly suggestive of CIRCI, neither a cosyntropin stimulation test nor a random plasma cortisol level test is required to confirm CIRCI and initiate glucocorticoid therapy. For septic shock, corticosteroids are primarily used to reverse CIRCI and restore vascular responsiveness to achieve hemodynamic stability. However, for severe CAP and COVID-19, corticosteroids are used primarily to reduce hyperinflammation of the lung tissue that damages the alveolocapillary barrier, thereby limiting edema and acute respiratory distress syndrome (ARDS) progression and improving gas-exchange outcomes. Notably, CIRCI also occurs in severe CAP and COVID-19, indicating an overlap in the origins of the pathophysiological manifestations and medical benefits of corticosteroids.

EFFICACY OF STEROID FOR SEPTIC SHOCK

Corticosteroids have been used to treat septic shock for over four decades, and their use has changed with evolving evidence from clinical trials. An early randomized controlled trial (RCT) in 1976 [27] demonstrated a mortality benefit using supraphysiologically high doses of corticosteroids (dexamethasone 3 mg/kg or methylprednisolone nearly 2 g daily) in patients with septic shock. However, subsequent trials in the 1980s [28,29] using similarly high doses of corticosteroids, such as methylprednisolone at 30 mg/kg daily, failed to show any improvement in survival. Additionally, there is an increased risk of secondary infection-related death in patients treated with high-dose methylprednisolone [28]. As a result, corticosteroid use in patients with septic shock fell out of favor for more than a decade. Interest in corticosteroid therapy re-emerged in the 1990s with the introduction of a lower-dose corticosteroid regimen. A small-scale RCT [30] reported accelerated resolution of shock and potential mortality reduction with corticosteroid use, which led to clinical interest and further investigations in subsequent large-scale trials that sought to refine the indications, dosing strategies, and patient populations that are likely to benefit from corticosteroid therapy. The Hydrocortisone for Prevention of Septic Shock (HYPRESS) trial [31] showed that IV hydrocortisone 200 mg/day for 5 days, followed by dose tapering until day 11, did not prevent the progression from sepsis to septic shock, suggesting that corticosteroid therapy is not indicated in patients with sepsis who have not developed refractory shock and should be reserved for cases of refractory shock. Notably, four landmark RCTs were conducted to address the efficacy of corticosteroids in patients with septic shock. In 2002, a RCT by Annane et al. [4] demonstrated that the combination of hydrocortisone 50 mg IV every 6 hours plus fludrocortisone 50 μg enterally daily for 7 days was associated with reduced mortality, with the greatest benefit observed among patients with an inadequate response to the cosyntropin stimulation test in comparison with placebo (28-day mortality, corticosteroid group 53% vs. placebo group 63%, hazard ratio [HR] 0.67, 95% confidence interval [CI] 0.47 to 0.95, p = 0.02). The rate of vasopressor withdrawal within 28 days was higher in the patients who received the combination of hydrocortisone and fludrocortisone (corticosteroid group 57% vs. placebo group 40%, HR 1.91, 95% CI 1.29 to 2.84, p = 0.001). In 2008, the Corticosteroid Therapy of Septic Shock (CORTICUS) trial [5] demonstrated that while the use of hydrocortisone 50 mg IV every 6 hours without fludrocortisone for 5 days followed by tapering during a 6-day period did not confer a survival benefit (28-day mortality, hydrocortisone group 34.3% vs. placebo group 31.5%, p = 0.51), irrespective of cosyntropin stimulation test results (28-day mortality among patients with response to corticotropin, hydrocortisone group 28.8% vs. placebo group 28.7%, p = 1.00; 28-day mortality among patients without response to corticotropin, hydrocortisone group 39.2% vs. placebo group 36.1%, p = 0.69). However, faster shock reversal measured by the median time until reversal of shock was noted in the hydrocortisone group without regard to cosyntropin stimulation test results (for all patients, hydrocortisone group 3.3 days (95% CI 2.9 to 3.9 days) vs. placebo group 5.8 days (95% CI 5.2 to 6.9 days); for patients with response to corticotropin, hydrocortisone group 2.8 days (95% CI 2.1 to 3.3 days) vs. placebo group 5.8 days (95% CI 5.2 to 6.9 days); for patients without response to corticotropin, hydrocortisone group 3.9 days (95% CI 3.0 to 5.2 days) vs. placebo group 6.0 days (95% CI 4.9 to 9.0 days). In 2018, two RCTs were reported. The Adjunctive Corticosteroid Treatment in Critically Ill Patients with Septic Shock (ADRENAL) trial [6] found that a 7-day IV infusion of hydrocortisone 200 mg daily did not improve survival in comparison to placebo (90-day mortality, hydrocortisone group 27.9% vs. placebo group 28.8%, odds ratio [OR] 0.95, 95% CI 0.82 to 1.10, p = 0.50). However, the use of hydrocortisone was associated with a more rapid resolution of shock (median duration: hydrocortisone group 3 days vs. placebo group 4 days, p < 0.001), reduced duration of mechanical ventilation (median duration: hydrocortisone group 6 days vs. placebo group 7 days, p < 0.001), and decreased need for blood transfusions (hydrocortisone group 37.0% vs. placebo group 41.7%, p = 0.004), with minimal adverse events. Another trial, the Activated Protein C and Corticosteroids for Human Septic Shock (APROCCHSS) trial [7] demonstrated that mortality was lower in the patients who received the combination of hydrocortisone 50 mg IV every 6 hours and fludrocortisone 50 μg enterally daily for 7 days over placebo (90-day mortality, corticosteroid group 43.0% vs. placebo group 49.1%, relative risk (RR) of death in the corticosteroid group 0.88, 95% CI 0.78 to 0.99, p = 0.03). In addition, the number of vasopressor-free days to day 28 was higher in patients who received steroids (corticosteroid group, 17 days vs. placebo group, 15 days; p < 0.001), reflecting faster shock reversal in the hydrocortisone-plus-fludrocortisone group. The findings from the four landmark RCTs are shown in Table 1. Although these landmark RCTs varied in design, the primary endpoint was 28- or 90-day mortality, with time-to-shock reversal as a key secondary outcome. Only trials incorporating both hydrocortisone and fludrocortisone (Annane et al. [4] and APROCCHSS [7]) demonstrated a mortality benefit. In contrast, trials using hydrocortisone alone (CORTICUS [5], ADRENAL [6]) showed no survival advantage, although all landmark RCTs [4–7] reported a more rapid shock reversal with corticosteroid therapy. The observed survival benefit of adding fludrocortisone to hydrocortisone in French trials [4,7] raises questions regarding the role of fludrocortisone. However, the exact explanation is not clearly understood, as the mineralocorticoid activity provided by 200 mg of hydrocortisone is considered sufficient, particularly among critically ill vasopressor-dependent patients in whom enteral absorption of fludrocortisone may be limited [32]. Another hypothesis is that the difference in illness severity, evidenced by the nearly double mortality rate in the APROCCHSS trial [7] (overall 90 day all-cause-mortality 45.9%) compared with the ADRENAL trial [6] (overall 90 day all-cause-mortality 28.3%), may partly explain the discrepancies in outcomes [22]. Additionally, in a secondary analysis of the ADRENAL trial [33], patients were classified as immune adaptive-prevalent or immune innate-prevalent based on transcriptome gene expression. Immune innate-prevalent patients with pulmonary sepsis who were treated with hydrocortisone had higher mortality when compared with placebo (OR 5.55, 95% credible interval 1.81 to 21.12), however, there was no increased mortality in immune adaptive-prevalent patient with pulmonary sepsis who were treated with hydrocortisone (OR 1.01, 95% credible interval 0.29 to 3.38). Thus, the corticosteroid treatment response among patients with septic shock may vary based on the immune endotype, which may have had an impact on treatment outcomes.

Table 1

Summary of the studies evaluating the efficacy of corticosteroids in patients with septic shock

Following landmark RCTs, several meta-analyses demonstrated the efficacy of corticosteroids in patients with septic shock. In 2023, a meta-analysis analyzed individual patient data from 17 trials and 90-day mortality data from 9 trials [34]. Although 90-day mortality was similar between the group of all hydrocortisone and placebo group (RR 0.93, 95% CI 0.82 to 1.04, p = 0.22), a reduction of 90-day mortality was reported when the group of hydrocortisone plus fludrocortisone was compared with the placebo group (RR 0.88, 95% CI 0.81 to 0.97). The group of all hydrocortisone had more vasopressor-free days in comparison with the placebo group (mean difference 1.24 days, 95% CI 0.74 to 1.73). In 2024, a Bayesian network meta-analysis of 17 trials using aggregate data [34,35] reported that all-cause mortality at last follow up was lowest with combination of hydrocortisone and fludrocortisone (RR 0.85, 95% CI 0.72 to 0.99), followed by hydrocortisone alone (RR 0.97, 95% CI 0.87 to 1.07), when compared with placebo or usual care. Furthermore, despite being limited mostly by indirect evidence, the combination of hydrocortisone and fludrocortisone was associated with a 12% reduction in allcause mortality compared with hydrocortisone alone (RR 0.88, 95% CI 0.74 to 1.03). Another meta-analysis in 2025 showed that when compared with control, use of hydrocortisone plus fludrocortisone was associated with reduction of in-hospital mortality (40.8% vs. 42.8%; OR, 0.86; 95% CI, 0.80 to 0.92) and increased vasopressor-free days [36]. Fludrocortisone is a mineralocorticoid that acts via the mineralocorticoid receptor (MR) to increase vascular reactivity, sodium and water retention, and volume status, thereby promoting shock reversal [37]. In critical illness, hyperreninemic hypoaldosteronism can occur and is associated with increased acute organ dysfunction, hypotension, and poor outcomes; the failure to produce enough aldosterone despite high renin levels compared to the expected quantity results in the dissociation of the two and is usually viewed as a functional aldosterone deficiency [38] Therefore, in these circumstances, fludrocortisone may alleviate hypotension through specific action on MRs, potentially contributing to shock reversal. At the same time, patients with septic shock receiving hydrocortisone also activate the MR as an MR agonist [32,38]. While certain randomized clinical trials (Annane et al. [4], APROCCHSS [7]) and recent meta-analyses [34,35] demonstrated the mortality benefits of hydrocortisone plus fludrocortisone when compared with placebo, a previous study [39] reported no difference in mortality and vasopressor-free days between the hydrocortisone and hydrocortisone plus fludrocortisone groups among septic shock patients. Furthermore, recent studies [40,41] have shown that there was no significant difference in the number of days free from vasopressor therapy between the hydrocortisone and hydrocortisone plus fludrocortisone groups among patients with septic shock. Therefore, while it may be considered to use hydrocortisone or hydrocortisone plus fludrocortisone for septic shock, a large randomized trial with sufficient power is needed to assess the role of fludrocortisone in this regard.

The SCCM has published guidelines that reflect the accumulating evidence of corticosteroid use in patients with septic shock over time. In 2021, the Surviving Sepsis Guidelines suggested using IV corticosteroids (IV hydrocortisone 200 mg/day ad ministered as 50 mg IV every 6 h or as a continuous infusion) for adults with septic shock and an ongoing requirement for vasopressor therapy; however, the co-administration of fludrocortisone has not been addressed [8]. In 2024, guidelines based on a systematic review and meta-analysis by the SCCM suggested the administration of corticosteroids to adult patients with septic shock [42]. The most common doses of corticosteroids analyzed in the guidelines were IV hydrocortisone 200–300 mg/day administered in divided doses or a continuous infusion for 5–7 days, with or without a taper. However, the guideline panels recommended against the administration of high-dose or short-duration corticosteroids (> 400 mg per day hydrocortisone equivalent for < 3 days) for adult patients with septic shock, as subgroup analyses did not support their use given the risk of adverse effects. Furthermore, owing to the lack of an effect of mineralocorticoid potency based on panel analysis, no specific recommendation for fludrocortisone use was provided. Thus, the regimen of hydrocortisone 200 mg IV per day, administered either as a continuous infusion or 50 mg IV every 6 hours, with or without fludrocortisone 50 μg enterally daily for 7 days or until ICU discharge, was suggested for adult patients with septic shock [42], as a recent meta-analysis found no significant differences in shortterm mortality or vasopressor-free days between bolus and continuous hydrocortisone administration in septic shock patients [43].

EFFICACY OF STEROID FOR CAP

Adjunctive glucocorticoid therapy for CAP may benefit from the anti-inflammatory effects of corticosteroids, which may mitigate pulmonary injury. Therefore, many scientific studies have investigated the efficacy of corticosteroid therapy in patients with CAP. A Cochrane meta-analysis, which was published in 2017 and involved 17 RCTs with 2264 participants, found that low-dose corticosteroid use was associated with a reduced risk of all-cause death in adults with severe CAP (RR 0.58, 95% CI 0.40 to 0.84). However, it did not show a significant mortality benefit in patients with nonsevere CAP (RR 0.95, 95% CI 0.45 to 2.00) [44]. Subsequent randomized trials explored the role of corticosteroids in patients with severe CAP. The ESCAPe trial was published in 2022 [45]. A randomized trial conducted in 586 ICU patients who met the criteria for severe CAP according to the Infectious Diseases Society of America/American Thoracic Society (IDSA/ATS) [46] looked at a 20-day tapering course of IV methylprednisolone (started at 40 mg/day) vs placebo. The primary endpoint, 60-day all-cause mortality, did not differ significantly between the two groups (16% in the treatment group vs. 18% in the placebo group; adjusted OR 0.90, 95% CI 0.57 to 1.40). Similarly, no significant differences were found in secondary outcomes, including vasopressor-dependent shock, ARDS development, ventilator-free days, ICU and hospital lengths of stay, or in-hospital mortality. In contrast, the CAPE COD trial [10], published in 2023, demonstrated a significant survival benefit. This study randomized ICU-admitted adults with severe CAP who received either IV hydrocortisone (200 mg daily for 4 or 7 days based on clinical improvement, followed by tapering over a total course of 8–14 days) or placebo. The data from 795 randomized patients revealed that the 28-day mortality was significantly lower in the hydrocortisone group (6.2%) compared to placebo (11.9%), corresponding to an absolute risk reduction of 5.6 percentage points (95% CI −9.6 to −1.7; p = 0.006). Additionally, hydrocortisone therapy was associated with significantly reduced need for endotracheal intubation and vasopressor support (HR 0.59, 95% CI 0.40 to 0.86 and HR 0.59, 95% CI 0.43 to 0.82, respectively). A subsequent meta-analysis published in 2023, which included 7 randomized trials—including data from the ESCAPe [45] and CAPE COD [10] trials (total n = 1,689)—reported a significant reduction in 30-day mortality among patients with severe CAP treated with low-dose corticosteroids compared to placebo (10% vs. 16%; RR 0.61, 95% CI 0.44 to 0.85) [47]. In line with this evidence, the 2024 guidelines of the SCCM, based on a systematic review of 18 randomized trials, recommend the use of corticosteroids in hospitalized adults with severe bacterial CAP, citing a reduction in hospital mortality (RR 0.62, 95% CI 0.45 to 0.85) [42].However, the REMAP-CAP trial [48], published in 2025, yielded discordant findings. This study enrolled ICU patients with severe CAP who were randomized to receive either a 7-day course of IV hydrocortisone (50 mg every 6 h) or no corticosteroid therapy. Contrary to previous findings from the CAPE COD trial [10], the 90-day mortality was higher in the hydrocortisone group (15%; 78/521) than in the control group (9.8%; 12/122), and the adjusted OR did not indicate a survival benefit of hydrocortisone therapy across predefined subgroups, including those with or without influenza or vasopressor-dependent shock. The reasons underlying such discrepancies among the major trials, namely, ESCAPe [45], CAPE COD [10], and REMAP-CAP [48], remain uncertain. The findings of the three RCTs are presented in Table 2. Potential explanations include unmeasured differences in baseline patient characteristics or selection biases not captured in the reported data. Further investigation is warranted to elucidate these factors [49]. Nonetheless, a recent meta-analysis [50], including REMAP-CAP data as well as ESCAPe and CAPE COD data, showed that corticosteroids reduced short-term mortality in hospitalized patients with CAP. Furthermore, the updated ATS CAP guidelines published online in 2025 [51] suggest administering systemic corticosteroids for adult inpatients with severe CAP after careful evaluation of the aforementioned recent clinical trials, including the REMAP CAP data and meta-analysis [50]. Therefore, on the basis of expert opinion [49], recent meta-analysis [50], and the updated ATS CAP guidelines published online in 2025 [51], the use of low-dose corticosteroids (hydrocortisone) may be conditionally supported in hospitalized patients with severe CAP, particularly for patients presenting with respiratory failure of less than 24 hours duration and elevated serum C-reactive protein (> 204 mg/L) as per the protocol used in the CAPE COD trial, if influenza has been excluded and serum glucose can be controlled [49].

Table 2

Three recent randomized controlled trials evaluating the efficacy of corticosteroids in patients with severe community acquired pneumonia

EFFICACY OF STEROID FOR RESPIRATORY VIRUS INFECTION INCLUDING COVID-19

In a cohort study of 50 adults hospitalized with respiratory syncytial virus (RSV) infection, systemic corticosteroids were administered to 66% of the patients (n = 33). Treatment typically consisted of dexamethasone at doses of 4–10 mg or methylprednisolone at 40–60 mg, administered every six hours for a period of 1 to 2 days, after which an oral prednisone taper was administered. The mean duration of the corticosteroid therapy was 11 days. Notably, corticosteroid use did not lead to a reduction in peak viral load or the duration of viral shedding associated with RSV [52]. Consequently, current evidence does not support the use of low-dose corticosteroids in critically ill patients with RSV infections requiring hospitalization [53]. Meta-analyses and observational studies have been conducted on influenza. In an observation study of 288 cases of hospitalized influenza A viral pneumonia [54], patients who received corticosteroids had a significantly higher 60-day mortality (adjusted HR 1.98, 95% CI, 1.03 to 3.79, p = 0.04) when compared with the patients who did not receive corticosteroids. In addition, a Cochrane review of 21 observational studies involving 9,536 hospitalized patients with influenza pneumonia found that corticosteroid use was associated with significantly higher mortality when compared with patients who did not receive corticosteroids (OR 3.90, 95% CI 2.31 to 6.60) [55]. Therefore, based on meta-analyses and observational studies, the use of low-dose corticosteroids is not recommended for the management of patients hospitalized with influenza pneumonia [53]. For COVID-19 infection, the RECOVERY trial (n = 6,425) [9] randomized hospitalized patients with COVID-19 pneumonia to receive either standard care alone or standard care plus 6 mg dexamethasone daily for 10 days. The addition of dexamethasone significantly reduced 28-day mortality among patients requiring mechanical ventilation (29% vs. 41%; RR 0.64, 95% CI 0.51 to 0.81) and those receiving supplemental oxygen (23% vs. 26%; RR 0.82, 95% CI 0.72 to 0.94). In contrast, no mortality benefit was observed among patients who did not receive oxygen at the time of randomization, although a non-significant trend toward increased mortality was noted (18% vs. 14%; RR 1.19, 95% CI 0.92 to 1.55). A meta-analysis conducted by the WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group combined data from seven randomized clinical trials involving 1,703 critically ill COVID-19 patients. The analysis demonstrated that 28-day mortality was significantly lower among those treated with corticosteroids compared to those who received standard care alone (32.7% vs. 41.5%; OR 0.66, 95% CI 0.53–0.82; p < 0.001) [56]. Accordingly, the IDSA guidelines recommend the use of dexamethasone in hospitalized patients with severe or critical COVID-19 who require supplemental oxygen support [57]. In contrast, corticosteroid therapy is not recommended for COVID-19 patients with mild to moderate illnesses who do not require oxygen support.

ADVERSE EFFECTS OF CORTICOSTEROIDS

Adverse effects, such as hyperglycemia, muscle weakness, hypernatremia, superinfection, and gastrointestinal bleeding, may occur due to the use of corticosteroids [58,59]. Therefore, close monitoring is recommended when patients are administered corticosteroids.

CONCLUSION

A growing body of evidence has demonstrated the clinical utility of corticosteroids in the management of critically ill patients with septic shock, severe CAP, and COVID-19. The results are summarized in Table 3. However, the judicious use of corticosteroids in conjunction with clinical assessment is required. Further studies are required to determine the optimal role of corticosteroid therapy in various clinical settings.

Table 3

Common corticosteroid regimens suggested in the management for septic shock, severe community-acquired pneumonia, and COVID-19 infection

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