ABSTRACT
Introduction: Prominent prognostic parameters that reflect the severity of coronavirus disease 2019 (COVID-19) to adopt an appropriate therapeutic approach are not fully identified. This systematic review and meta-analysis aimed to explore the association between lymphocyte variation and disease severity in COVID-19 individuals. Methods: We searched Web of Science, Scopus, PubMed, EMBASE and WHO website to retrieve studies investigating lymphocyte subset counts in non-severe and severe cases of COVID-19. The pooled standardized mean difference (SMD) between two groups and the pooled average count of each lymphocyte subset were assessed by employing a random-effect model. Results: Thirty-nine investigations on 5087 participants, including 3578 non-severe patients and 1509 severe patients, were included. The pooled analysis showed that non-severe patients had higher total T lymphocytes (SMD = 1.01;95% CI: 0.82, 1.20;I2 = 75.7%), T helper cells (SMD = 1.07;95% CI: 0.85, 1.28;I2 = 85.4%), T cytotoxic cells (SMD = 1.07;95% CI: 0.82, 1.32;I2 = 87.1%), B cells (SMD = 0.72;95% CI: 0.45, 0.98;I2 = 79.7%), and natural killer cells (SMD = 0.65;95% CI: 0.47, 0.84;I2 = 63.1%) than severe patients and the average count of the corresponding lymphocyte signatures in non-severe patients/severe patients were 878.88/448.40, 493.12/268.96, 311.91/158.91, 177.09/110.37, and 155.02/103.09 cells/mu L, respectively. Conclusion: Lymphopenia may be a dilemma in COVID-19 management because over-activation of lymphocytes may lead to cytokine storm or acute respiratory distress syndrome (ARDS). In contrast, lymphopenia may increase SARS-CoV-2 amplification and COVID-19 severity. Therefore, novel therapies targeting lymphocyte proliferation or contraction may counterbalance lymphocyte counts in these patients.
ABSTRACT
Objective: The aim of this study was to evaluate the influence of adding a 10-day course of levamisole (LVM) to the standard care compared with standard care alone, on the clinical status of COVID-19 patients with mild to moderate disease. Methods: In this randomized open-label trial, we enrolled non-hospitalized patients with mild to moderate COVID-19 at nine health centers in Tehran province, Iran, in 2021. Patients were randomly assigned to receive a 10-day course of LVM with standard care (n=185) or standard care alone (n=180) in a 1:1 ratio. On days 1 to 10, LVM was administered orally at a dosage of 50 mg. The participants were called and followed on days 1, 3, 5, 7, 9, and 14. The measured parameters were general health condition, hospitalization rate, signs and symptoms, and adverse events. The generalized estimating equations model was used for analysis. Results: Among 507 randomized patients, 473 patients started the experiment and received LVM plus standard care or received the standard care alone;385 patients included in the analysis;346 (98%) patients completed the trial. The median age of the patients was 40 years [IQR: 32-50.75];and 201 (55.1%) patiens were male. The mean age, sex ratio, and frequency of the underlying diseases of the patients in the two study groups had no statistically significant differences (P>0.05). Compared to the control group, LVM improved the general health condition of the patients (B=-0.635;95% CI:-0.041,-0.329;P<0.001). Patients receiving LVM compared with standard care group had significantly lower odds of developing fever (OR=0.260;95% CI: 0.113,0.599;P=0.002), chills (OR=0.223;95% CI: 0.076,0.648;P=0.006), fatigue (OR=0.576;95% CI: 0.346,0.960;P=0.034), and myalgia (OR=0.544;95% CI: 0.317,0.932;P=0.027). No significant difference was observed in the rate of hospitalization. Although the intervention group had greater adverse effects than the control group, the difference was not statistically significant. Conclusion: Findings of this study suggest that LVM has clinical benefits in improving patients’ health condition with mild to moderate COVID-19. © 2022 Tehran University of Medical Sciences.