Table 2.
Characteristics of the included studies in the revision
| Original study | Sample size | Age in years | Males, % | Time of depressive symptoms assessment | Time of inflammatory marker assessment | Diagnostic tool for depressive symptoms | Inflammatory markers | Findings | Modified Newcastle Ottawa Scale |
|---|---|---|---|---|---|---|---|---|---|
| Ahmed et al., 2021 [110] | 182 | > 18 | 46 | Six months’ follow-up | Hospital admission | SCL90 depression subscale | WBC, LYM, NEU, MON, PLT, NLR, CRP, and ferritin | NEU, PLT, and NLR were not significantly associated with SCL90 subscale for depression score | Low risk of bias |
| Benedetti et al., 2021 [26] | 42 | > 18 | 67 | Three months’ follow-up | Emergency department admission | ZSDS | CRP and SII | SII measured in the emergency department, significantly predicted worse self-rated depressive symptoms (β = 0.411, Wald = 9.02, p < 0.001), widespread lower diffusivity along the main axis of WM tracts, and abnormal functional connectivity among resting state networks | Low risk of bias |
| Garcia et al., 2021 [118] | 27 | > 60 | 70 | Acute COVID-19 | During hospitalization | GSD | IL-6, IL-1β, and TNF-α | No significant correlation between IL-6, IL-1β, and TNF-α and GDS scale scores was found | High risk of bias |
| Gonzales et al., 2022 [113] | 1851 | > 18 | 59 | Acute COVID-19 | Hospital admission | Clinical interview according to ICD-10 criteria | IL-6 and CRP | IL-6 serum levels were significantly higher in the group of patients with depressive symptoms than in patients without, even after adjusting for several confounders (114 ± 225 pg/mL vs. 86 ± 202 pg/mL, p = 0.02). Similar results were obtained for CRP (102.14 ± 3.93 mg/L vs. 90.79 ± 2.32 mg/L, p = 0.01) | Low risk of bias |
| Guo et al., 2020 [98] | 103 | > 18 | 57 | Acute COVID-19 | At hospitalization admission and ± three days of fulfilling the on-line survey | PHQ-9 | WBC, LYM, NEU, MON, PLT, CRP, and ESR | Levels of CRP correlated positively with the PHQ-9 total score of patients who presented symptoms of depression (r = 0.37, p = 0.003). Moreover, the change of CRP level from baseline inversely correlated with the PHQ-9 total score (r = − 0.31, p = 0.002), indicative of improvement of depression symptoms | Low risk of bias |
| He et al., 2021 [111] | 77 | > 18 | 49 | Acute COVID-19 | During hospitalization | PHQ-9 | IL-2, IL-4, IL-6, IL-10, TNF-α, IFN, CD3+T, CD4+T, CD8+T, CD4+/CD8+, WBC, LYM, NEU, PLT, ESR, and HS-CRP | Patients with moderate depressive symptoms had higher CD8+counts [27.6 (24.4–32.2) vs. 21.9 (16.1–27.5)] and lower CD4+/CD8+ratios [1.6 (1.2–1.9) vs. 2.2 (1.7–2.9)] than patients with non-moderate depressive symptoms (p < 0.05) | High risk of bias |
| Hu et al., 2020 [112] | 70 | > 18 | 51 | Acute COVID-19 | During hospitalization within 1 week of the date on which the questionnaire was completed | PHQ-9 | IL-1β, IL-6, IL-8, IL-10, TNF-α, CRP, WBC, LYM, NEU, and NLR | PHQ-9 score for depression was significantly related to the level of IL-1β (r=0.50, p<0.001) and to NLR (r=0.36, p<0.01). A multivariate regression model showed that result showed that sex (β = 0.31, p < 0.01), IL-1β (β = 0.41, p < 0.001), and self-perceived illness severity (β = 0.39, p < 0.001) were related to the PHQ-9 score | Low risk of bias |
| Al-Jassas., 2022 [34] | 60 | 25–59 | 100 | Acute COVID-19 | During hospitalization | HDRS | CRP, IL-6, and IL-10 | The HDRS scores showed positive significant associations with CRP (r = 0.547, p < 0.001), IL-6 (r = 0.480, p < 0.001), and IL-10 (r = 0.532, p < 0.001) | Low risk of bias |
| Huarcaya‐Victoria et al., 2021 [116] | 318 | > 18 | 61 | Three months’ follow-up | At the beginning of hospitalization | PHQ-9 | NLR and MLR | NLR was significantly higher in patients with clinically relevant symptoms of depression (11.4, 95% CI 8.8–14.1 vs. 8.52, 95% CI 7.62–9.42; p = 0.041) | Low risk of bias |
| Kahve et al., 2021 [114] | 175 | > 18 | 61 | Acute COVID-19 | The day of hospitalization or the next day | BDI | ESR, CRP, NLR, IL-6, and ferritin | No significant relationship was found between ferritin, ERS, CRP, IL-6, NLR levels and depressive symptoms severity | Low risk of bias |
| Li et al., 2021 [117] | 66 | > 17 | 42 | Acute COVID-19 | During hospitalization | ZSDS | WBC, LYM, NEU, and NLR | NEU (2.91, 95% CI 2.36–3.44 109/L vs. 3.34, 95% CI 3.22–4.69 109/L; p = 0.028) and NLR (1.74 ± 0.52 2.22 ± 0.91; p = 0.043) were increased in the group with depressive symptoms. Correlation analysis indicated that Self-Rating Depression Scale score was positively related to NEU count and NLR (respectively r = 0.366, p = 0.016 and r = 0.330, p = 0.031) | High risk of bias |
| Mazza et al., 2020 [13] | 402 | > 18 | 66 | One month’s follow-up | Emergency department admission | ZSDS | CRP, NLR, MLR, and SII | SII, which reflects the immune response and systemic inflammation based on peripheral lymphocyte, neutrophil, and platelet counts, positively associated with scores of depressive symptoms at follow-up (β = 0.411, F = 5.18, p = 0.023) | Low risk of bias |
| Mazza et al., 2021 [10] | 226 | > 18 | 66 | Three months’ follow-up | Emergency department admission | ZSDS | CRP, NLR, MLR, and SII | SII predicted self-rated depressive symptomatology at 3 months’ follow-up (χ2=42.417, p<0.001); and changes of SII predicted changes of depression during follow-up (Wald = 6.881, p = 0.009) | Low risk of bias |
| Wu et al., 2021 [120] | 57 | > 18 | 35 | Acute COVID-19 | During hospitalization | PHQ-9 | INF-γ, TNF, IL-10, IL-5, IL-4, IL-2, CD3+, CD4+, CD8+, and CD4+/CD8+ | The counts of CD4+T lymphocytes and CD4/CD8 significantly correlated with the PHQ-9 scores (r = 0.378, p = 0.004). After 2 weeks of treatment, significant associations remained (r = 0.644, p = 0.002) between the changes in the level of CD4+ T lymphocytes and PHQ-9 scores in the patients with depression and anxiety | Low risk of bias |
| Yuan et al., 2020 [115] | 96 | > 18 | 50 | One week after negative virus test | During hospitalization | ZSDS | WBC, NEU, LYM, MON, NLR, HS-CRP, and IL-6 | The results suggested that patients with self-reported depression exhibited increased immune response, as indicated by increased WBC (6.0 ± 1.5 109/L vs. 6.7 ± 1.5 109/L; p = 0.016), NEU (3.3 ± 0.9 109/L vs. 4.1 ± 1.2 109/L; p < 0.001), NLR (1.8 ± 0.6 vs. 2.4 ± 0.9; p < 0.001), and CRP (0.1 ± 0.1 mg/dL vs. 0.2 ± 0.3 mg/dL; p = 0.035) | Low risk of bias |
| Zhou et al., 2021 [119] | 65 | > 21 | 48 | Acute COVID-19 | During hospitalization | ZSDS | LYM and IL-6 | There was significant statistically lower LYM in the patients with relevant depressive symptoms when compared to patients without (1.43 vs. 1.79, p = 0.01) | Low risk of bias |
BDI Beck's Depression Inventory, CD Cluster of Differentiation, COVID Coronavirus Disease 2019, CRP C-reactive protein, ESR erythrocyte sedimentation rate, HDRS Hamilton Rating Scale for Depression, ICD International Classification of Diseases, IFN interferon, IL interleukin, LYM lymphocyte, MLR monocyte/lymphocyte ratio, MON monocyte, NEU neutrophil, NLR neutrophil/lymphocyte ratio, PHQ-9 Patient Health Questionnaire-9, PLT platelet, SII Systemic Immune-Inflammatory Index, TNF tumor necrosis factor, WBC white blood cell count, ZSDS Zung Self-Rating Depression Scale