The epidemiology and clinical impact of COVID-19-associated candidemia (CAC) remained uncertain, leaving gaps in understanding its prevalence, risk factors and outcomes.

A systematic review and meta-analysis were conducted by searching PubMed, Embase and Scopus for reports of CAC prevalence, risk factors and clinical outcomes up to June 18, 2024. The generalised linear mixed model was employed to determine the prevalence and 95% confidence intervals (CIs). The risk factors and clinical outcomes were compared between patients with and without CAC using the inverse variance method.

From 81 studies encompassing 29 countries and involving 351,268 patients, the global prevalence of CAC was 4.33% (95% Cl, 3.16%-5.90%) in intensive care unit (ICU) patients. In ICUs, the pooled prevalence of CAC in high-income countries was significantly higher than that of lower-middle-income countries (5.99% [95% Cl, 4.24%-8.40%] vs. 2.23% [95% Cl, 1.06%-4.61%], p = 0.02). Resistant Candida species, including C. auris, C. glabrata (Nakaseomyces glabratus) and C. krusei (Pichia kudriavzveii), constituted 2% of ICU cases. The mortality rate for CAC was 68.40% (95% Cl, 61.86%-74.28%) among ICU patients. Several risk factors were associated with CAC, including antibiotic use, central venous catheter placement, dialysis, mechanical ventilation, tocilizumab, extracorporeal membrane oxygenation and total parenteral nutrition. Notably, the pooled odds ratio of tocilizumab was 2.59 (95% CI, 1.44-4.65).

The prevalence of CAC is substantial in the ICU setting, particularly in high-income countries. Several risk factors associated with CAC were identified, including several that are modifiable, offering the opportunity to mitigate the risk of CAC.

In this study, the effect of tocilizumab (TCZ) on lung tissue in lung ischemia-reperfusion (I/R) injury in rats was investigated.

A total of 24 Wistar rats were divided into 4 equal groups, with 6 rats in each group: Left lung I/R was applied to I/R groups. In the I/R groups, the left lung hilum was clamped for 45 minutes, and then the clamp was removed and reperfused for 120 minutes. In the TCZ groups, 4 mg/kg and 8 mg/kg of TCZ were administered intraperitoneally to the rats 30 minutes before surgery.

The tumor necrosis factor-alpha mean value was not statistically significant between the groups (P = .091). Statistically significant results were observed between group I/R-TCZ (8 mg/kg) and group I/R for catalase. (P = .005). Statistically significant results were observed between group I/R-TCZ (8 mg/kg) and group I/R for malondialdehyde. (P = .009). The difference in total ischemia score between group I/R-TCZ (4 mg/kg) and group I/R-TCZ (8 mg/kg) and group I/R was statistically significant (P < .001). In terms of alveolar hemorrhage, there was a statistically significant difference between group I/R-TCZ (4 mg/kg) and group I/R-TCZ (8 mg/kg) and group I/R (P = .01 and P = .002, respectively). There was a statistically significant difference between group I/R-TCZ (8 mg/kg) and group I/R in terms of neutrophil accumulation (P = .01). In terms of interstitial edema, there was a statistically significant difference between group I/R-TCZ (4 mg/kg) and group I/R-TCZ (8 mg/kg) and group I/R (P = .006 and P = .001, respectively). In terms of pulmonary edema, there was a statistically significant difference between group I/R-TCZ (4 mg/kg) and group I/R-TCZ (8 mg/kg) and group I/R (P = .01 and P = .009, respectively).

Lung tissue may be affected by I/R injury and this damage can be reversed with the use of TCZ.

COVID-19, an emerging disease raised as a pandemic, urgently needed treatment choices. Some options have been confirmed as lifesaving treatments, but long-term complications must be clearly illustrated. Bacterial endocarditis is a less frequent disease among patients infected with SARS_COV_2 compared to other cardiac comorbidities in these patients. This case report discusses bacterial endocarditis as a potential adverse effect after administering tocilizumab, corticosteroids, and COVID-19 infection.

In the first case, a 51-year-old Iranian female housewife was admitted to the hospital with fever, weakness, and monoarthritis symptoms. The second case is a 63-year-old Iranian woman who is a housewife admitted with weakness, shortness of breath, and extreme sweating. Both cases tested positive for Polymerase chain reaction (PCR) less than one month ago and were treated with tocilizumab and corticosteroid. Both patients were suspected of infective endocarditis. Methicillin-resistant Staphylococcus aureus (MRSA) was detected in the blood cultures of both patients. The diagnosis of endocarditis is confirmed for both cases. Cases are subjected to open-heart surgery, a mechanical valve is placed, and they are treated with medication. In subsequent visits, their condition was reported to be improving.

Adjacent to cardiovascular inclusion as COVID-19 disease complications, secondary infection taken after the organisation of immunocompromising specialists can result in basic maladies and conditions counting infective endocarditis.

To compare the outcomes of single versus double doses of tocilizumab in patients with severe COVID-19, especially on different types of oxygenation requirements.

This cross-sectional study was carried out from January 2020 to March 2020. Patients diagnosed with COVID-19, who received at least one dose of tocilizumab, were included. The dependent variable was tocilizumab dose (single versus double). The primary outcome variable was oxygen demand on the first and last day of hospitalization. A series of comparisons between patients administered one dose of tocilizumab versus 2 doses were conducted.

Herein, 80 patients with severe COVID-19 infection were included, of whom 68.8% received one dose of tocilizumab, while 31.3% received a double dose. Two-thirds of the patients were male, with an overall average age of 58 years. In patients receiving 2 doses, oxygen demand tended to worsen by the seventh day, while in those who received one dose. The group that received 2 doses had a longer length of hospital stay.

This study could not capture the additional value of the second dose for different health outcomes. However, the results can inform clinician from experience when facing uncertainty due to new virus or variant.

Since December 2019, a novel coronavirus that represents a serious threat to human lives has emerged. There is still no definite treatment for severe cases of the disease caused by this virus, named coronavirus disease 2019 (COVID-19). One of the most considered treatment strategies targets the exaggerated immune regulator, and interleukin (IL)-6 is a crucial pro-inflammatory mediator. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases show an elevated level of IL-6 related to disease severity. IL-6 activity can be inhibited by the following: IL-6 itself, IL-6 signaling pathways such as Janus kinase and signal transducer and activator of transcription (JAK-STAT), gp130, IL-6R, and downstream activated ILs, such as IL-17 and IL-6 cytokine. Currently, according to these studies and their results, IL-6 blockade with anti-IL-6 or its receptor antibodies such as tocilizumab in COVID-19 is beneficial in severe cases and may reduce the mortality rate. JAK-STAT inhibitors block the cytokine storm by inhibiting several crucial pro-inflammatory mediators such as TNF-α and IL-6 and have shown various results in clinical trials. IL-6 induces IL-17 secretion, and IL-17 is involved in the pathogenesis of inflammatory processes. Clinical trials of anti-IL-17 drugs are currently recruiting, and anti-gp130 antibody is preclinical. However, this agent has shown positive effects in inflammatory bowel disease clinical trials and could be tested for SARS-CoV-2. This study aimed to review the role of IL-6 in the cytokine storm and studies regarding IL-6 and blockade of its inflammatory pathways in COVID-19 to determine if any of these agents are beneficial for COVID-19 patients.

Severe acute respiratory coronavirus-2 (SARS-CoV-2) still presents a public threat and puts extra strain on healthcare facilities. Without an effective antiviral drug, all available treatment options are considered supportive. Tocilizumab as a treatment option has to date shown variable results. In this retrospective study, we aimed to assess predictors of mortality of COVID-19 patients (n = 300) on tocilizumab and the clinical effectiveness of this drug. The results showed that ICU admission OR = 64.6 (95% CI: 8.2, 507.4); age of the patient OR = 1.1 (95% CI: 1.0, 1.1); and number of tocilizumab doses administered by the patient OR(two doses) = 4.0 (95% CI: 1.5, 10.9), OR(three doses) = 1.5 (95% CI: 0.5, 5.1), and OR(four doses or more) = 7.2 (95% CI: 2.0, 25.5) presented strong correlation factors that may be linked to COVID-19 mortality. Furthermore, our study showed the beneficial effects of early administration of tocilizumab OR = 1.2 (95% CI: 1.1, 1.4) and longer hospital length of stay OR = 0.974 (95% CI: 0.9, 1.0) in reducing COVID-19 mortalities. High blood D-dimer concentration OR = 1.1 (95% CI: 1.0, 1.2) and reciprocal blood phosphate concentration OR = 0.008 (95% CI: 0.0, 1.2) were correlated to high mortality under SARS-CoV-2 infection. The short-term effect of a single dose of tocilizumab was a significant increase in blood BUN and liver enzymes (ALT, AST, and LDH) above their normal ranges. Furthermore, it significantly reduced CRP blood concentration, but not to normal levels (13.90 to 1.40 mg/dL, p < 0.001). Assessing the effect of different doses of tocilizumab (in terms of the number of doses, total mg, and total mg/kg administered by the patients) indicated that administering more than one dose may lead to increases in ICU length of stay and hospital length of stay of up to 14 and 22 days after the last dose of tocilizumab (6 to 14, p = 0.06, and 10 to 22, p < 0.001), with no improvement in 28- and 90-day mortality, as confirmed by Kaplan−Meier analysis. There were also clear correlations and trends between the number of doses of tocilizumab and increased blood CO2, MCV, RDW, and D-dimer concentrations and between number of doses of tocilizumab and decreased CRP, AST, and hemoglobin concentrations. Microbiology analysis showed a significant increase in the incidence of infection after tocilizumab administration (28 to 119, p < 0.001) with a median time of incidence within 6 days of the first dose of tocilizumab. A significant correlation was also found between the number of tocilizumab doses and the number of incidences of infections after tocilizumab administration r (298) = 0.396, p = 1.028 × 10−12. Based on these results and depending on the pharmacokinetic parameters of the drug, we recommend single-dose administration of tocilizumab as the optimal dosage for COVID-19 patients who do not have active bacterial infection or liver diseases, to be administered as soon as the patient is admitted to the hospital.

Previous studies suggested that patients with comorbidities including cancer had a higher risk of mortality or developing more severe forms of COVID-19. The interaction of cancer and COVID-19 is unrecognized and potential long-term effects of COVID-19 on cancer outcome remain to be explored. Furthermore, whether COVID-19 increases the risk of cancer in those without previous history of malignancies, has not yet been studied. Cancer progression, recurrence and metastasis depend on the complex interaction between the tumor and the host inflammatory response. Extreme proinflammatory cytokine release (cytokine storm) and multi-organ failure are hallmarks of severe COVID-19. Besides impaired T-Cell response, elevated levels of cytokines, growth factors and also chemokines in the plasma of patients in the acute phase of COVID-19 as well as tissue damage and chronic low-grade inflammation in "long COVID-19" syndrome may facilitate cancer progression and recurrence. Following a systemic inflammatory response syndrome, some counterbalancing compensatory anti-inflammatory mechanisms will be activated to restore immune homeostasis. On the other hand, there remains the possibility of the integration of SARS- CoV-2 into the host genome, which potentially may cause cancer. These mechanisms have also been shown to be implicated in both tumorigenesis and metastasis. In this review, we are going to focus on potential mechanisms and the molecular interplay, which connect COVID-19, inflammation, and immune-mediated tumor progression that may propose a framework to understand the possible role of COVID-19 infection in tumorgenesis and cancer progression.