Atypical lymphocytes in the peripheral blood of COVID-19 patients: A prognostic factor for the clinical course of COVID-19.

BACKGROUND: Clinical observations have shown that there is a relationship between coronavirus disease 2019 (COVID-19) and atypical lymphocytes in the peripheral blood; however, knowledge about the time course of the changes in atypical lymphocytes and the association with the clinical course of COVID-19 is limited. OBJECTIVE: Our purposes were to investigate the dynamics of atypical lymphocytes in COVID-19 patients and to estimate their clinical significance for diagnosis and monitoring disease course. MATERIALS AND METHODS: We retrospectively identified 98 inpatients in a general ward at Kashiwa Municipal Hospital from May 1st, 2020, to October 31st, 2020. We extracted data on patient demographics, symptoms, comorbidities, blood test results, radiographic findings, treatment after admission and clinical course. We compared clinical findings between patients with and without atypical lymphocytes, investigated the behavior of atypical lymphocytes throughout the clinical course of COVID-19, and determined the relationships among the development of pneumonia, the use of supplemental oxygen and the presence of atypical lymphocytes. RESULTS: Patients with atypical lymphocytes had a significantly higher prevalence of pneumonia (80.4% vs. 42.6%, p < 0.0001) and the use of supplemental oxygen (25.5% vs. 4.3%, p = 0.0042). The median time to the appearance of atypical lymphocytes after disease onset was eight days, and atypical lymphocytes were observed in 16/98 (16.3%) patients at the first visit. Atypical lymphocytes appeared after the confirmation of lung infiltrates in 31/41 (75.6%) patients. Of the 13 oxygen-treated patients with atypical lymphocytes, approximately two-thirds had a stable or improved clinical course after the appearance of atypical lymphocytes. CONCLUSION: Atypical lymphocytes frequently appeared in the peripheral blood of COVID-19 patients one week after disease onset. Patients with atypical lymphocytes were more likely to have pneumonia and to need supplemental oxygen; however, two-thirds of them showed clinical improvement after the appearance of atypical lymphocytes.

Lymphopenia and neutrophilia at admission predicts severity and mortality in patients with COVID-19: a meta-analysis.

BACKGROUND: There is a compelling need to identify clinical and laboratory predictors of unfavorable clinical course and death in patients with coronavirus disease (COVID-19). A trend towards low lymphocyte count and high neutrophil counts in patients with poor outcomes has been reported by earlier studies. We aim to synthesize existing data evaluating the relationship between clinical outcomes and abnormal neutrophil and lymphocyte counts at admission in COVID-19 patients. METHODS: An electronic search was carried out in PubMed, China National Knowledge Infrastructure (CNKI) and Cochrane Central Register of Controlled Trials (CENTRAL) to identify eligible studies reporting frequency data on neutrophilia and lymphopenia at admission in hospitalization in COVID-19 patients. Pooled odds ratios of clinical outcomes for each parameter were calculated using Comprehensive Meta-Analysis. RESULTS: A total of 22 studies (4,969 patients) were included in this meta-analysis. Lymphopenia at admission was found to be significantly associated with increased odd of progression to severe disease (odds ratio [OR], 4.20; 95% confidence interval [95CI%], 3.46-5.09) and death (OR, 3.71; 95%CI, 1.63-8.44). Neutrophilia at admission was also found to be significantly associated with increased odd of progression to severe disease (OR, 7.99; 95%CI, 1.77-36.14) and death (OR, 7.87; 95%CI, 1.75-35.35). Subgroup analysis revealed that COVID-19 patients with severe lymphopenia (<0.5 x10×9/L) had 12-fold increased odds of in-hospital mortality. CONCLUSION: Admission lymphopenia and neutrophilia are associated with poor outcomes in patients with COVID-19. Regular monitoring and early and even more aggressive intervention shall hence be advisable in patients with low lymphocyte and high neutrophil counts. These variables may be useful in risk stratification models.

Coronavirus disease 2019 (COVID-19) related cytopenia: A protocol for systematic review and meta-analysis.

BACKGROUND: In December 2019, the novel coronavirus pneumonia was detected in Wuhan and named COVID-19. It is an international outbreak of the respiratory illness caused by severe acute respiratory syndrome coronavirus 2. Recent papers pointed out the cytopenia in COVID-19 patients including lymphopenia, neutrophilia, thrombocytopenia and lower level of hemoglobin had prognostic significance. This systemic review and meta-analysis summaries the latest evidence from available data and determine the hematological abnormality caused by severe acute respiratory syndrome coronavirus 2 and potential efficacy on the outcomes in patients with COVID-19. METHODS: This protocol for a systematic reviews and meta-analysis will be performed according to the preferred reporting items for systematic reviews and meta-analysis protocols 2015 guidelines. The database of Cochrane Library, PUBMED, EMBASE, Medline, Web of Science, Google Scholar, CNKI, WanFang, as well as gray literatures from the inception to present will be comprehensively and systematically searched without limitations of regions or language. The main study outcomes will be the mortality of COVID-19 patients. The meta-analysis was performed by RevMan V.5.3 program and Stata V.12.0 software after 2 reviewers independently selected literature, data extraction, bias risk evaluation and study quality assessment. Any disagreement will be resolved by consensus to the third researcher. RESULTS: This systematic review and meta-analysis may help provide clarify on the effect of cytopenia in patients with COVID-19. The result will be published at a peer-reviewed journal. CONCLUSIONS: This proposed study will evaluate the existing evidence on the effectiveness of cytopenia in COVID-19 patients. ETHIC AND DISSEMINATION: The content of this article does not involve moral approval or ethical review because no individual data will be collected. PROSPERO REGISTRATION: CRD42020187524.

Haematological manifestations of COVID-19: From cytopenia to coagulopathy.

Emerging data from the management of patients with coronavirus disease 2019 (COVID-19) suggests multi-systemic involvement, including the hemopoietic system. The haematological manifestations of COVID-19 include blood count anomalies notably lymphopenia and neutrophilia which are of prognostic significance. Hyperferritinemia and elevated lactate dehydrogenase have also been associated with increased mortality. Furthermore, there is considerable evidence of a distinct coagulopathy associated with COVID-19 characterised by elevated D-dimers and an increased risk of thrombotic events. This comprehensive review summarises the latest evidence from published studies and discusses the implications of the various haematological manifestations of COVID-19 with a view to guiding clinical management and risk stratification in this rapidly evolving pandemic.

Endothelial Shear Stress Enhancements: A Potential Solution for Critically Ill Covid-19 Patients (preprint)

Rationale: Most critically ill Covid-19 patients succumb to multiple organ failure and / or cardiac arrest as a result of comorbid endothelial dysfunction disorders which had probably aggravated by conventional mechanical assist devices. Even worse, mechanical ventilators prevent the respiratory pump from performing its crucial function as a potential generator of endothelial shear stress (ESS) which controls microcirculation and hemodynamics since birth. The purpose of this work is to bring our experience with ESS enhancement and pulmonary vascular resistance (PVR) management as a potential therapeutic solution in acute respiratory distress syndrome (ARDS). We propose a noninvasive device composed of thoracic and infradiaphragmatic compartments that will be pulsated in an alternating frequency (20/40 bpm) with low-pressure pneumatic generator (0.1-0.5 bar). Oxygen supply, nasogastric ± endotracheal tubes are considered. Proof-of-concept: prototypes were tested in pediatric models of refractory cardiac arrest (≥20min), showed restoration of hemodynamics (BP≥100 mm Hg) and urine output, regardless of heartbeats, pharmacological supports and mechanical ventilation. Conclusions ESS enhancement represents a more effective treatment to increase tissue oxygenation and improve hemodynamic in ARDS. A cost-effective method which could be induced with a non-invasive pulsatile device adaptable to cardiopulmonary-circulatory biophysics to maintain a fully functional respiratory pump and avoid confrontation of the opposite hydraulic circuits.