Objectives: Studies reported associations of inflammatory markers with the severity of COVID-19, but conclusions were inconsistent. We aimed to provide an overview of the association of inflammatory markers with the severity of COVID-19. Methods: We searched PubMed, Embase, Cochrane Library, Wanfang and China National Knowledge Infrastructure (CNKI) database until March 20, 2020. Weighted mean difference (WMD) and 95% confidence intervals (CIs) were pooled using random or fixed-effects models. Results: A total of 16 studies comprising 3962 patients with COVID-19 were included in our analysis. Random-effect results demonstrated that patients with COVID-19 in the nonsevere group had lower levels for CRP (WMD = À41.78 mg/l, 95% CI = [À52.43, À31.13], P < 0.001), PCT (WMD = À0.13 ng/ml, 95% CI = [À0.20, À0.05], P < 0.001), IL-6 (WMD = À21.32 ng/l, 95% CI = [À28.34, À14.31], P < 0.001), ESR (WMD = À8 mm/h, 95% CI = [À14, À2], P = 0.005), SAA (WMD = À43.35 mg/ml, 95% CI = [À80.85, À5.85], P = 0.020) and serum ferritin (WMD = À398.80 mg/l, 95% CI = [À625.89, À171.71], P < 0.001), compared with those in the severe group. Moreover, survivors had a lower level of IL-6 than non-survivors (WMD = À4.80 ng/ml, 95% CI = [À5.87, À3.73], P < 0.001). These results were consistent through sensitivity analysis and publication bias assessment. Conclusions: The meta-analysis highlights the association of inflammatory markers with the severity of COVID-19. Measurement of inflammatory markers might assist clinicians to monitor and evaluate the severity and prognosis of COVID-19.

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The backbone of ovarian cancer treatment is platinum-based chemotherapy and aggressive surgical debulking. New therapeutic approaches using immunotherapy via immune checkpoint blockade, which have demonstrated clinical efficacy in other tumor types, have been less promising in ovarian cancer. To increase their clinical efficacy, checkpoint inhibitors are now being tested in clinical trials in combination with chemotherapy. Here, we evaluated the impact of cisplatin on tumor immunogenicity and its in vivo roles when used alone or in combination with anti-PD-L1, in two novel murine ovarian cancer cell models. The 2F8 and its platinum-resistant derivative 2F8cis model, display distinct inflammatory profiles and chemotherapy sensitivities, and mirror the primary and recurrent human disease, respectively. Acute and chronic exposure to cisplatin enhances tumor immunogenicity by increasing calreticulin, MHC class I, antigen presentation and T cell infiltration. Cisplatin also upregulates PD-L1 expression in vitro and in vivo, demonstrating a dual, paradoxical immune modulatory effect and supporting the rationale for combination with immune checkpoint blockade. One of the pathways activated by cisplatin treatment is the cGAS/STING pathway. Chronic cisplatin treatment led to upregulation of cGAS and STING proteins in 2F8cis compared to parental 2F8 cells, while acute exposure to cisplatin further increases cGAS and STING levels in both 2F8 and 2F8cis cells. Overexpression of cGAS/STING modifies tumor immunogenicity by upregulating PD-L1, MHC I and calreticulin in tumor cells. Anti-PD-L1 alone in a platinum-sensitive model or with cisplatin in a platinum-resistant model increases survival. These studies have high translational potential in ovarian cancer.