Establishment of reference intervals for complete blood count in times of COVID-19 and vaccination.

Introduction: COVID-19 and vaccination may affect some parameters of the complete blood count (CBC). The aim of this study was to determine reference intervals (RI) of CBC in healthy population with different COVID-19 and vaccination backgrounds and compare them with those established previously. Materials and methods: A cross-sectional study was conducted in donors who attended the Traumatology Hospital "Dr. Victorio de la Fuente Narváez" (HTVFN) from June to September 2021. Reference intervals were established using the non-parametric method on Sysmex XN-1000. For differences between groups with different COVID-19 and vaccination backgrounds, non-parametric tests were used. Results: The RI were established in 156 men and 128 women. Haemoglobin (Hb), haematocrit (Hct), red blood cells (RBC), platelets (Plt), mean platelets volume (MPV), monocytes and relative neutrophils were higher in men than women (P < 0.001). The percentiles of Hb, Hct, RBC, MPV and relative monocytes showed higher values; Plt, white blood cells (WBC), lymphocytes, monocytes, neutrophils, eosinophils and absolute basophils, the 2.5th was higher and the 97.5th was lower; for lymphocytes and relative neutrophils, both percentiles had a trend toward lower values, compared to previous RI. Differences between groups with different COVID-19 and vaccination backgrounds, in lymphocytes (P = 0.038), neutrophils (P = 0.017) and eosinophils (P = 0.018) in men; Hct (P = 0.014), RDW (P = 0.023) in women and MPV (P = 0.001) in both, were not considered pathological. Conclusions: The RI for the CBC were established in a Mestizo-Mexican population with different COVID-19 and vaccination backgrounds, so should be updated and validated in different hospitals close to the HTVFN that use the same analyser.

How to diagnose COVID-19 in family practice? Usability of complete blood count as a COVID-19 diagnostic tool: a cross-sectional study in Turkey.

OBJECTIVE: COVID-19 is currently diagnosed in hospital settings. An easy and practical diagnosis of COVID-19 is needed in primary care. For this purpose, the usability of complete blood count in the diagnosis of COVID-19 was investigated. DESIGN: Retrospective, cross-sectional study. SETTING: Single-centre study in a tertiary university hospital in Erzurum, Turkey. PARTICIPANTS: Between March 2020 and February 2021, patients aged 18-70 years who applied to the hospital and underwent both complete blood count and reverse-transcription-PCR tests for COVID-19 were included and compared. Conditions affecting the test parameters (oncological-haematological conditions, chronic diseases, drug usage) were excluded. OUTCOME MEASURE: The complete blood count and COVID-19 results of eligible patients identified using diagnostic codes [U07.3 (COVID-19) or Z03.8 (observation for other suspected diseases and conditions)] were investigated. RESULTS: Of the 978 patients included, 39.4% (n=385) were positive for COVID-19 and 60.6% (n=593) were negative. The mean age was 41.5±14.5 years, and 53.9% (n=527) were male. COVID-19-positive patients were found to have significantly lower leucocyte, neutrophil, lymphocyte, monocyte, basophil, platelet and immature granulocyte (IG) values (p<0.001). Neutrophil/lymphocyte, neutrophil/monocyte and IG/lymphocyte ratios were also found to be significantly decreased (p<0.001). With logistic regression analysis, low lymphocyte count (OR 0.695; 95% CI 0.597 to 0.809) and low red cell distribution width-coefficient of variation (RDW-CV) (OR 0.887; 95% CI 0.818 to 0.962) were significantly associated with COVID-19 positivity. In receiver operating characteristic analysis, the cut-off values of lymphocyte and RDW-CV were 0.745 and 12.35, respectively. CONCLUSION: Although our study was designed retrospectively and reflects regional data, it is important to determine that low lymphocyte count and RDW-CV can be used in the diagnosis of COVID-19 in primary care.

COVID-19 with rheumatic diseases: a report of 5 cases.

The coronavirus disease 2019 (COVID-19), the result of an infection with the new virus, SARS-CoV-2, is rapidly spreading worldwide. It is largely unknown whether the occurrence of COVID-19 in patients with rheumatic immune diseases has some specific manifestations, or makes them more prone to rapidly progress into severe COVID-19. In this case report, we describe the clinical features of 5 rheumatic immune disease patients with the concomitant presence of COVID-19. Amongst these patients, 4 had rheumatoid arthritis (RA) and 1 had systemic sclerosis (SSc). Two patients had a history of close contact with a COVID-19 patient. The age of the patients ranged between 51 and 79 years. Fever (80%), cough (80%), dyspnea (40%), and fatigue (20%) were the most common presenting symptoms. Laboratory investigations revealed leukopenia and lymphopenia in 2 patients. In all the patients, chest computerized tomography (CT) revealed patchy ground glass opacities in the lungs. During the hospital stay, the condition of two patients remained the same (i.e., mild COVID-19), two patients progressed to the severe COVID-19, and one patient worsened to the critically ill COVID-19. These patients were treated with antiviral agents for COVID-19, antibiotics for secondary bacterial infections, and immunomodulatory agents for rheumatic immune diseases. All the patients responded well, were cured of COVID-19, and subsequently discharged.

Complete blood count derived inflammation indexes predict outcome in COVID-19 patients: a study in Indonesia.

INTRODUCTION: Inflammation plays a vital role in the pathophysiology of COVID-19. Complete blood count (CBC) is a routine test performed on patients. It provides information regarding the inflammatory process and can be used as a predictor of outcome. This study aimed to explore the correlation between different complete blood count (CBC)-derived inflammation indexes at hospital admission, such as neutrophil to lymphocyte ratio (NLR), derived NLR (dNLR), platelet to lymphocyte ratio (PLR), monocyte to lymphocyte ratio (MLR), neutrophil to lymphocyte × platelet ratio (NLPR), aggregate index of systemic inflammation (AISI), systemic inflammation response index (SIRI), and systemic immune-inflammation index (SII), to in-hospital mortality in confirmed COVID-19 patients. METHODOLOGY: A retrospective observational study was performed at Ulin Referral Hospital of South Kalimantan with 445 COVID-19 patients from April to November 2020. The patients were divided into two groups, non-survivor and survivor. A receiver operating characteristic (ROC) curve was used to determine the cut-off values. Bivariate analysis was performed using the Chi Square test, the risk ratio was calculated, and logistics regression was determined. RESULTS: Increase of NLR, dNLR, PLR, MLR, NLPR, MLR, AISI, SIRI, and SII from cut-off values were significantly correlated with patient survival outcome. The cut off values were 6.90, 4.10, 295, 0.42, 0.037, 1,422, 1.80, and 2,504 respectively. NLPR was dominant in predicting in-hospital mortality (OR: 6.668, p = 0.000) with a 28.1% sensitivity and 95.9% specificity. CONCLUSIONS: CBC-derived inflammation indexes were associated with the survival outcome of confirmed COVID-19 patients and NLPR was a dominant variable.

Multiparameter mobile blood analysis for complete blood count using contrast-enhanced defocusing imaging and machine vision.

Blood analysis through complete blood count is the most basic medical test for disease diagnosis. Conventional blood analysis requires bulky and expensive laboratory facilities and skilled technicians, limiting the universal medical use of blood analysis outside well-equipped laboratory environments. Here, we propose a multiparameter mobile blood analyzer combined with label-free contrast-enhanced defocusing imaging (CEDI) and machine vision for instant and on-site diagnostic applications. We designed a low-cost and high-resolution miniature microscope (size: 105 mm × 77 mm × 64 mm, weight: 314 g) that comprises a pair of miniature aspheric lenses and a 415 nm LED for blood image acquisition. The analyzer, adopting CEDI, can obtain both the refractive index distributions of the white blood cell (WBC) and hemoglobin spectrophotometric information, enabling the analyzer to supply rich blood parameters, including the five-part WBC differential count, red blood cell (RBC) count, and mean corpuscular hemoglobin (MCH) quantification with machine vision algorithms and the Lambert-Beer law. We have shown that our assay can analyze a blood sample within 10 minutes without complex staining, and measurements (30 samples) from the analyzer have a strong linear correlation with clinical reference values (significance level of 0.0001). This study provides a miniature, light weight, low-cost, and easy-to-use blood analysis technique that overcomes the challenge of simultaneously realizing FWD count, RBC count, and MCH analysis using a mobile device and has great potential for integrated surveillance of various epidemic diseases, including coronavirus infection, invermination, and anemia, especially in low- and middle-income countries.

Monocyte Distribution Width (MDW) as a biomarker of sepsis: An evidenced-based laboratory medicine approach.

Monocyte Distribution Width (MDW) is a new generation cell blood count parameter providing a measure of monocyte anisocytosis. In the last decades, it has emerged as a reliable biomarker of sepsis in the acute setting, especially emergency department, and intensive care unit. MDW has several advantages over commonly used sepsis biomarkers, including low-cost, ease and speed of measurement. The clinical usefulness of MDW has been established in several studies and some clinical laboratory medicines have already implemented it in their routine. In this article, we describe the analytical and clinical features of MDW to guide its appropriate use in clinical practice by integrating the research evidence with real-world laboratory experience. The proper use of a biomarker is critical for improving patients' care and outcome as well as ensuring healthcare quality.

SARS-CoV-2 and Plasmodium falciparum coinfection: a case report.

BACKGROUND: A rare case of coinfection of Plasmodium falciparum and SARS-CoV-2 disease in Croatia is presented in this report. METHODS: We tracked epidemiological and laboratory findings in a patient with SARS-CoV-2 and Plasmodium falciparum coinfection. A complete blood count was performed using the Sysmex XN-2000 analyser (Sysmex Corporation, Kobe, Japan), coagulation analyses were performed using the BCS XP coagulometer (Siemens Healthineers AG, Erlangen, Germany). Procalcitonin (PCT) and Interleukin-6 (IL-6) were measured by electrochemiluminescence immunoassay (ECLIA) using the Cobas e411 (Roche Diagnostics GmbH, Mannheim, Germany) analyser and high sensitivity troponin I (hsTnI) was measured using the Dimension EXL with LM analyser (Siemens Healthcare Diagnostics, Newark, USA). All other biochemistry analyses were performed using the Olympus AU680 (Beckman Coulter, Brea, California, USA) analyser. White blood cell differential analysis has been performed by examining the blood smear using the CellaVision DM1200 (CellaVision AB, Lund, Sweden) automatic analyser. RESULTS: Even though the patient's initial health condition was disturbed, as a result of the physician's comprehensive anamnesis accompanied by laboratory findings, prompt diagnosis and appropriate therapy were assured, and consequently, the patient recovered. CONCLUSION: In a pandemic, testing each febrile patient for the SARS-CoV-2 virus is of essential importance. However, the possibility of coinfection with another infectious disease agent cannot be disregarded.

The COVID-19 vaccine did not affect the basal immune response and menstruation in female athletes.

The COVID-19 pandemic restricted the regular training and competition program of athletes. Vaccines against COVID-19 are known to be beneficial for the disease; however, the unknown side effects of vaccines and postvaccination reactions have made some athletes hesitant to get vaccinated. We investigated the changes in inflammatory responses and menstrual cycles of female athletes before and after vaccination. Twenty female athletes were enrolled in this study. Blood was collected from each subject before the first COVID-19 vaccination and after the first and second vaccinations. Laboratory data, including white blood cell, neutrophil, lymphocyte, and platelet counts, and inflammatory markers, including NLR (neutrophil-to-lymphocyte ratio), PLR (platelet lymphocyte ratio), RPR (red cell distribution width to platelet ratio), SII (systemic immune-inflammation index), and NeuPla (neutrophil-platelet ratio), were analyzed statistically. The menstrual changes before and after vaccination and the side effects were collected by questionnaires. No significant changes in the laboratory data were found after the first and second shots when compared to those at prevaccination: white blood cell, neutrophil, lymphocyte, platelet, NLR, PLR, SII, RPR, and NeuPla (p > 0.05). In addition, there were no significant changes in the menstruation cycle or days of the menstrual period (p > 0.05). All side effects after vaccination were mild and subsided in 2 days. The blood cell counts, inflammatory markers, and menstruation of female athletes were not affected by COVID-19 vaccines.

Lessons learned from the COVID-19 pandemic: Improving initial investigations with the implementation of a COVID-19 blood request panel.

BACKGROUND: During the COVID-19 pandemic, the Hillingdon Hospitals NHS Foundation Trust produced trust guidelines for the initial blood investigation of COVID-19 inpatients. However, insufficient education meant inconsistent adherence to this guidance. OBJECTIVE: To examine whether the implementation of a COVID-19 blood request panel improves adherence to local trust guidelines. METHOD: Between March and April 2020, initial blood investigations performed for positive COVID-19 cases were compared to guidelines. Results were presented locally and a COVID-19 panel was added to the electronic system that provided prompts for appropriate investigations. A re-audit between May and June 2020 was conducted to assess adherence post-intervention. RESULTS: 383 patients were identified in the initial audit cohort and a sample of 20 patients were re-audited. Adherence to Full Blood Count, Urea and Electrolytes, C-reactive Protein and Liver Function Tests increased to 100% from 99.7% (p = 0.8), 99.2% (p = 0.69), 98.7% (p = 0.61), and 96.6% (p = 0.4) respectively. Coagulation screen adherence increased to 90% from 72.8% (p = 0.09). Appropriate requesting of D dimers increased to 50% from 19.9% (p = 0.001). Inappropriate troponin requesting decreased to 26.3% from 38.9% (p = 0.23). CONCLUSION: A user-friendly COVID-19 panel of investigations resulted in improved adherence to guidelines. Clear communication and education are essential to help alleviate uncertainty during a pandemic.

Routine laboratory parameters, including complete blood count, predict COVID-19 in-hospital mortality in geriatric patients.

To reduce the mortality of COVID-19 older patients, clear criteria to predict in-hospital mortality are urgently needed. Here, we aimed to evaluate the performance of selected routine laboratory biomarkers in improving the prediction of in-hospital mortality in 641 consecutive COVID-19 geriatric patients (mean age 86.6 ± 6.8) who were hospitalized at the INRCA hospital (Ancona, Italy). Thirty-four percent of the enrolled patients were deceased during the in-hospital stay. The percentage of severely frail patients, assessed with the Clinical Frailty Scale, was significantly increased in deceased patients compared to the survived ones. The age-adjusted Charlson comorbidity index (CCI) score was not significantly associated with an increased risk of death. Among the routine parameters, neutrophilia, eosinopenia, lymphopenia, neutrophil-to-lymphocyte ratio (NLR), C-reactive protein, procalcitonin, IL-6, and NT-proBNP showed the highest predictive values. The fully adjusted Cox regressions models confirmed that high neutrophil %, NLR, derived NLR (dNLR), platelet-to-lymphocyte ratio (PLR), and low lymphocyte count, eosinophil %, and lymphocyte-to-monocyte ratio (LMR) were the best predictors of in-hospital mortality, independently from age, gender, and other potential confounders. Overall, our results strongly support the use of routine parameters, including complete blood count, in geriatric patients to predict COVID-19 in-hospital mortality, independent from baseline comorbidities and frailty.

Increased monocyte distribution width in COVID-19 and sepsis arises from a complex interplay of altered monocyte cellular size and subset frequency.

INTRODUCTION: Monocyte distribution width (MDW), a parameter generated alongside full blood counts (FBC) in new-generation haematology analysers, has been proposed as a diagnostic test for severe infection/sepsis. It represents the standard deviation (SD) of the monocyte mean volume (MMV). METHODS: This study aimed to compare monocyte volumetric parameters retrieved by the UniCel DxH 900 haematology analyser (MMV and MDW) against corresponding parameters from the same sample measured using flow cytometry (forward scatter [FSC] mean and SD) in combination with phenotypic characterization of monocyte subtypes. We analysed blood samples from healthy individuals (n = 11) and patients with conditions associated with elevated MDW: sepsis (n = 26) and COVID-19 (n = 15). RESULTS: Between-instrument comparisons of monocyte volume parameters (MMV vs. FSC-mean) showed relatively good levels of correlation, but comparisons across volume variability parameters (MDW vs. FSC-SD) were poor. Stratification on sample type revealed this lack of correlation only within the sepsis group. Flow cytometry analysis revealed that in healthy controls intermediate monocytes are the largest and non-classical the smallest cells. In each disease state, however, each monocyte subset undergoes different changes in volume and frequency that together determine the overall configuration of the monocyte population. Increased MDW was associated with reduced classical monocyte frequency and increased intermediate monocyte size. In COVID-19, the range of monocyte sizes (smallest to largest) reduced, whereas in sepsis it increased. CONCLUSION: Increased MDW in COVID-19 and sepsis has no single flow cytometric phenotypic correlate. It represents-within a single value-the delicate equipoise between monocyte subset frequency and size.

Complete blood cells count abnormalities in COVID-19 patients and their prognostic significance: Single center study in Makkah, Saudi Arabia.

OBJECTIVES: To evaluate the role of different peripheral blood count parameters as a cheap and rapid test in determination of coronavirus disease -19 (COVID-19) severity and patients' outcome. METHODS: The data of 462 confirmed COVID-19 patients who attended at the Security Force Hospital, Makkah, Saudi Arabia, from October 2020 to March 2021 was retrospectively reviewed and C. Patients with viral infection and respiratory diseases other than COVID-19 were excluded from the study. Complete blood count parameters were compared in accordance with the severity of the clinical presentation, age, and disease outcome. RESULTS: A total of 277 (60%) were male and 185 (40%) female. Clinically, 32 (6.9%) had severe illness and 430 (93.1%) showed moderate clinical disease. Organ failure occurred in 2.8% of the patients. There was significant leucocytosis, neutrophilia, lymphopenia, high neutrophil-lymphocyte (N/L) ratio, and anemia in patients with severe COVID-19 diseases as well as in non-survivors' cases (p<0.001). Similarly, the inflammatory markers (C-reactive protein [CRP] and serum ferritin) were significantly elevated in the above-mentioned 2 groups (p<0.001). Significant decrease of the platelets count was detectable in clinically severe cases and non-survivors (p<0.01). Older age (>60 years) was associated with high leucocyte, neutrophil count, lymphopenia, anemia, organ failure, and poor outcome. CONCLUSION: Leucocytosis, neutrophilia, lymphopenia, and high N/L ratio together with elevated serum level of ferritin and CRP are eminent features of COVID-19 severity. The inclusion of these parameters in the regimens for patients' categorization on admission will enable early effective intervention and proper decision making during clinical case management.

Thrombocytopenia: the good, the bad and the ugly.

New thrombocytopenia may be associated with a variety of conditions and diagnosis can be challenging. Presentation can vary from life-threatening bleeding or thrombosis to an incidental finding in an asymptomatic patient. New thrombocytopenia requires urgent investigation. Investigations are mainly guided by findings from the clinical history, physical examination, full blood count and blood film analysis. Aside from the actively bleeding patient, rare but life-threatening causes of thrombocytopenia must be identified early as they require urgent treatment. These include thrombotic thrombocytopenic purpura, disseminated intravascular coagulation, suspicion of new acute promyelocytic leukaemia, and vaccine-induced prothrombotic immune thrombocytopenia. Here, we discuss how to approach a patient with new thrombocytopenia, along with key differentials not to be missed.

Associations between presence of Bartonella species deoxyribonucleic acid and complete blood cell count and serum biochemical changes in client-owned cats.

BACKGROUND: Infection with Bartonella species is common in cats but reported effects of bacteremia on laboratory variables differ. OBJECTIVES: Evaluate for associations between Bartonella bacteremia and CBC and serum biochemical changes in sick and healthy cats throughout the United States. ANIMALS: A total of 3964 client-owned cats. METHODS: Retrospective cohort study using submissions to a commercial laboratory between 2011 and 2017. Serum biochemistry and CBC abnormalities (categorized as above or below reference intervals), age, and location (high- or low-risk state for Ctenocephalides felis) in presumed healthy and sick cats were evaluated for associations with presence of Bartonella spp. DNA, detected by PCR. Univariate and multivariable logistic regression analyses were performed. RESULTS: Bartonella spp. DNA was amplified from 127 (3.2%) of 3964 cats; 126 (99.2%) of 127 were from high flea risk states and 121 (95.3%) of 127 were presumed sick. Fever of unknown origin was the most common PCR panel requested. In the multivariable analysis, neutrophilia, decreased ALP activity, clinical status (presumed sick), and young age (≤2 years) each were positively associated whereas neutropenia and hyperproteinemia both were negatively associated with Bartonella spp. bacteremia. Presence of Bartonella spp. DNA had no association with test results for other infectious disease agents. CONCLUSIONS AND CLINICAL IMPORTANCE: In both healthy and sick cats, active Bartonella infections had minimal association with clinically relevant laboratory abnormalities. However, based on these results, in areas considered high risk for C. felis, active infection with Bartonella spp. is a reasonable differential diagnosis for cats presented with unexplained fever and neutrophilia, particularly if the cat is young.

Multi-Cellular Immunological Interactions Associated With COVID-19 Infections.

To rapidly prognosticate and generate hypotheses on pathogenesis, leukocyte multi-cellularity was evaluated in SARS-CoV-2 infected patients treated in India or the United States (152 individuals, 384 temporal observations). Within hospital (<90-day) death or discharge were retrospectively predicted based on the admission complete blood cell counts (CBC). Two methods were applied: (i) a "reductionist" one, which analyzes each cell type separately, and (ii) a "non-reductionist" method, which estimates multi-cellularity. The second approach uses a proprietary software package that detects distinct data patterns generated by complex and hypothetical indicators and reveals each data pattern's immunological content and associated outcome(s). In the Indian population, the analysis of isolated cell types did not separate survivors from non-survivors. In contrast, multi-cellular data patterns differentiated six groups of patients, including, in two groups, 95.5% of all survivors. Some data structures revealed one data point-wide line of observations, which informed at a personalized level and identified 97.8% of all non-survivors. Discovery was also fostered: some non-survivors were characterized by low monocyte/lymphocyte ratio levels. When both populations were analyzed with the non-reductionist method, they displayed results that suggested survivors and non-survivors differed immunologically as early as hospitalization day 1.

Ex Vivo and In Vivo CD46 Receptor Utilization by Species D Human Adenovirus Serotype 26 (HAdV26).

Human adenovirus serotype 26 (Ad26) is used as a gene-based vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and HIV-1. However, its primary receptor portfolio remains controversial, potentially including sialic acid, coxsackie and adenovirus receptor (CAR), integrins, and CD46. We and others have shown that Ad26 can use CD46, but these observations were questioned on the basis of the inability to cocrystallize Ad26 fiber with CD46. Recent work demonstrated that Ad26 binds CD46 with its hexon protein rather than its fiber. We examined the functional consequences of Ad26 for infection in vitro and in vivo. Ectopic expression of human CD46 on Chinese hamster ovary cells increased Ad26 infection significantly. Deletion of the complement control protein domain CCP1 or CCP2 or the serine-threonine-proline (STP) region of CD46 reduced infection. Comparing wild-type and sialic acid-deficient CHO cells, we show that the usage of CD46 is independent of its sialylation status. Ad26 transduction was increased in CD46 transgenic mice after intramuscular (i.m.) injection but not after intranasal (i.n.) administration. Ad26 transduction was 10-fold lower than Ad5 transduction after intratumoral (i.t.) injection of CD46-expressing tumors. Ad26 transduction of liver was 1,000-fold lower than that ofAd5 after intravenous (i.v.) injection. These data demonstrate the use of CD46 by Ad26 in certain situations but also show that the receptor has little consequence by other routes of administration. Finally, i.v. injection of high doses of Ad26 into CD46 mice induced release of liver enzymes into the bloodstream and reduced white blood cell counts but did not induce thrombocytopenia. This suggests that Ad26 virions do not induce direct clotting side effects seen during coronavirus disease 2019 (COVID-19) vaccination with this serotype of adenovirus. IMPORTANCE The human species D Ad26 is being investigated as a low-seroprevalence vector for oncolytic virotherapy and gene-based vaccination against HIV-1 and SARS-CoV-2. However, there is debate in the literature about its tropism and receptor utilization, which directly influence its efficiency for certain applications. This work was aimed at determining which receptor(s) this virus uses for infection and its role in virus biology, vaccine efficacy, and, importantly, vaccine safety.

Distinguishing Incubation and Acute Disease Stages of Mild-to-Moderate COVID-19.

While numerous studies have already compared the immune responses against SARS-CoV-2 in severely and mild-to-moderately ill COVID-19 patients, longitudinal trajectories are still scarce. We therefore set out to analyze serial blood samples from mild-to-moderately ill patients in order to define the immune landscapes for differently progressed disease stages. Twenty-two COVID-19 patients were subjected to consecutive venipuncture within seven days after diagnosis or admittance to hospital. Flow cytometry was performed to analyze peripheral blood immune cell compositions and their activation as were plasma levels of cytokines and SARS-CoV-2 specific immunoglobulins. Healthy donors served as controls. Integrating the kinetics of plasmablasts and SARS-CoV-2 specific antibodies allowed for the definition of three disease stages of early COVID-19. The incubation phase was characterized by a sharp increase in pro-inflammatory monocytes and terminally differentiated cytotoxic T cells. The latter correlated significantly with elevated concentrations of IP-10. Early acute infection featured a peak in PD-1+ cytotoxic T cells, plasmablasts and increasing titers of virus specific antibodies. During late acute infection, immature neutrophils were enriched, whereas all other parameters returned to baseline. Our findings will help to define landmarks that are indispensable for the refinement of new anti-viral and anti-inflammatory therapeutics, and may also inform clinicians to optimize treatment and prevent fatal outcomes.

Endothelial injury in COVID-19 and septic patients.

Systemic inflammatory response, as observed in sepsis and severe COVID-19, may lead to endothelial damage. Therefore, we aim to compare the extent of endothelial injury and its relationship to inflammation in both diseases. We included patients diagnosed with sepsis (SEPSIS group, n = 21), mild COVID-19 (MILD group, n = 31), and severe COVID-19 (SEVERE group, n = 24). Clinical and routine laboratory data were obtained, circulating cytokines (INF-γ, TNF-α, and IL-10) and endothelial injury markers (E-Selectin, Tissue Factor (TF) and von Willebrand factor (vWF)) were measured. Compared to the SEPSIS group, patients with severe COVID-19 present similar clinical and laboratory data, except for lower circulating IL-10 and E-Selectin levels. Compared to the MILD group, patients in the SEVERE group showed higher levels of TNF-α, IL-10, and TF. There was no clear relationship between cytokines and endothelial injury markers among the three studied groups; however, in SEVERE COVID-19 patients, there is a positive relationship between INF-γ with TF and a negative relationship between IL-10 and vWF. In conclusion, COVID-19 and septic patients have a similar pattern of cytokines and endothelial dysfunction markers. These findings highlight the importance of endothelium dysfunction in COVID-19 and suggest that endothelium should be better evaluated as a therapeutic target for the disease.