Changes of Routine Hematological Parameters in COVID-19 Patients: Correlation with Imaging Findings, RT-PCR and Outcome

Treatment for coronavirus disease 2019 (COVID19) pneumonia remains empirical and the search for therapies that can improve outcomes continues. Melatonin has been shown to have anti-inflammatory, antioxidant, and immune-modulating effects that may address key pathophysiologic mechanisms in the development and progression of acute respiratory distress syndrome (ARDS), which has been implicated as the likely cause of death in COVID19. We aimed to describe the observable clinical outcomes and tolerability of high-dose melatonin (hdM) given as adjuvant therapy in patients admitted with COVID19 pneumonia. We conducted a retrospective descriptive case series of patients who: 1) were admitted to the Manila Doctors Hospital in Manila, Philippines, between March 5, 2020 and April 4, 2020; 2) presented with history of typical symptoms (fever, cough, sore throat, loss of smell and/or taste, myalgia, fatigue); 3) had admitting impression of atypical pneumonia; 4) had history and chest imaging findings highly suggestive of COVID19 pneumonia, and, 5) were given hdM as adjuvant therapy, in addition to standard and/or empirical therapy. One patient admitted to another hospital, who one of the authors helped co-manage, was included. He was the lone patient given hdM in that hospital during the treatment period. Main outcomes described were: time to clinical improvement, duration of hospital stay from hdM initiation, need for mechanical ventilation (MV) prior to cardiopulmonary resuscitation, and final outcome (death or recovery/discharge). Of 10 patients given hdM at doses of 36-72mg/day per os (p.o.) in 4 divided doses as adjuvant therapy, 7 were confirmed COVID19 positive (+) by reverse transcription polymerase chain reaction (RT-PCR) and 3 tested negative (-), which was deemed to be false (-) considering the patients’ typical history, symptomatology, chest imaging findings and elevated bio-inflammatory parameters. In all 10 patients given hdM, clinical stabilization and/or improvement was noted within 4-5 days after initiation of hdM. All hdM patients, including 3 with moderately severe ARDS and 1 with mild ARDS, survived; none required MV. The 7 COVID19(+) patients were discharged at an average of 8.6 days after initiation of hdM. The 3 highly probable COVID19 patients on hdM were discharged at an average of 7.3 days after hdM initiation. Average hospital stay of those not given hdM (non-hdM) COVID19(+) patients who were admitted during the same period and recovered was 13 days. To provide perspective, although the groups are not comparable, 12 of the 34 (35.3%) COVID19(+) non-hdM patients admitted during the same period died, 7/34 (20.6%) required MV; while 6 of 15 (40%) non-hdM (-) by RT-PCR but highly probable COVID19 pneumonia patients also died, 4/15 (26.7%) required MV. No significant side-effects were noted with hdM except for sleepiness, which was deemed favorable by all patients, most of whom had anxiety- and symptom-related sleeping problems previously. HdM may have a beneficial role in patients treated for COVID19 pneumonia, in terms of shorter time to clinical improvement, less need for MV, shorter hospital stay, and possibly lower mortality. HdM was well tolerated. This is the first report describing the benefits of hdM in patients being treated for COVID19 pneumonia. Being a commonly available and inexpensive sleep-aid supplement worldwide, melatonin may play a role as adjuvant therapy in the global war against COVID19.

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Postmortem brain 7T MRI with minimally invasive pathological correlation in deceased COVID-19 subjects

Insights into Imaging ◽

10.1186/s13244-021-01144-w ◽

2022 ◽

Vol 13 (1) ◽

Author(s):

Maria da Graça Morais Martin ◽

Vitor Ribeiro Paes ◽

Ellison Fernando Cardoso ◽

Carlos Eduardo Borges Passos Neto ◽

Cristina Takami Kanamura ◽

...

Keyword(s):

Minimally Invasive ◽

Small Vessel Disease ◽

Ct Images ◽

Postmortem Brain ◽

Common Finding ◽

Pcr Analysis ◽

Tissue Sampling ◽

Imaging Findings ◽

Rt Pcr ◽

Brain Invasion

Abstract Background Brain abnormalities are a concern in COVID-19, so we used minimally invasive autopsy (MIA) to investigate it, consisting of brain 7T MR and CT images and tissue sampling via transethmoidal route with at least three fragments: the first one for reverse transcription polymerase chain reaction (RT-PCR) analysis and the remaining fixed and stained with hematoxylin and eosin. Two mouse monoclonal anti-coronavirus (SARS-CoV-2) antibodies were employed in immunohistochemical (IHC) reactions. Results Seven deceased COVID-19 patients underwent MIA with brain MR and CT images, six of them with tissue sampling. Imaging findings included infarcts, punctate brain hemorrhagic foci, subarachnoid hemorrhage and signal abnormalities in the splenium, basal ganglia, white matter, hippocampi and posterior cortico-subcortical. Punctate brain hemorrhage was the most common finding (three out of seven cases). Brain histological analysis revealed reactive gliosis, congestion, cortical neuron eosinophilic degeneration and axonal disruption in all six cases. Other findings included edema (5 cases), discrete perivascular hemorrhages (5), cerebral small vessel disease (3), perivascular hemosiderin deposits (3), Alzheimer type II glia (3), abundant corpora amylacea (3), ischemic foci (1), periventricular encephalitis foci (1), periventricular vascular ectasia (1) and fibrin thrombi (1). SARS-CoV-2 RNA was detected with RT-PCR in 5 out of 5 and IHC in 6 out 6 patients (100%). Conclusions Despite limited sampling, MIA was an effective tool to evaluate underlying pathological brain changes in deceased COVID-19 patients. Imaging findings were varied, and pathological features corroborated signs of hypoxia, alterations related to systemic critically ill and SARS-CoV-2 brain invasion.

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The Outgrowth of CLL Nurselike Cells in Vitro, and Its Relation to Clinical and Hematological Parameters.

Blood ◽

10.1182/blood.v114.22.2360.2360 ◽

2009 ◽

Vol 114 (22) ◽

pp. 2360-2360

Author(s):

Agata A Filip ◽

Dorota Koczkodaj ◽

Tomasz Kubiatowski ◽

Ewa Wasik-Szczepanek ◽

Anna Dmoszynska

Keyword(s):

Gene Expression ◽

Serum Level ◽

Ex Vivo ◽

Hematological Parameters ◽

Tp53 Gene ◽

Leukemic Cells ◽

Rt Pcr ◽

Gene Status

Abstract Abstract 2360 Poster Board II-337 Introduction: Despite their longevity in vivo, CLL lymphocytes die rapidly when put to in vitro cultures, what proves that the resistance to apoptosis is not an intrinsic feature of leukemic cells, but depends on environmental signals. Recently it was shown that mononuclear cells from peripheral blood of CLL patients differentiate in vitro into large, adherent cells that grow in close contact with CLL lymphocytes. They were termed “nurselike cells” (NLCs), because they support leukemic lymphocyte survival in culture. The presence of the cells morphologically and phenotypically similar to NLCs was demonstrated in peripheral lymphatic organs of CLL patients. It may suggest their role in CLL lymphocytes protection in vivo and, as a consequence, point the new target in CLL treatment. Patients and Methods: The study included the group of 65 previously untreated CLL patients, 24 women and 41 men, aged from 36 to 86 yrs. 12 patients (18%) were diagnosed with stage 0 according to Rai, 15 patients (23%) with stage I, 30 patients (46%) with stage II, 5 patients (8%) with stage III and 3 patients (5%) with stage IV. Peripheral blood lymphocytes ex vivo were examined for CD14, CD38, BCL2 and ZAP70 expression by flow cytometry and for BCL2, SURVIVIN and ZAP70 gene expression by RT-PCR. TP53 gene status was assessed by FISH. Lymphocytes of 20 patients were assayed for apoptosis-related gene expression by means of cDNA macroarrays (Clontech). To generate NLCs, PB leukemic cells were cultured in vitro for 14 days on standard medium (RPMI 1640 with L-glutamine, 15% FCS, antibiotics/antimycotics; cell density 3 × 106/ml) and the outgrowth and number of NLCs was assessed in relation to clinical and hematological parameters. NLCs were identified morphologically and by CD31/VIMENTIN protein expression. Results: In 58 cases (89%) the outgrowth of NLCs was observed, while their number differed in cultures of the cells of different patients: in 49 cultures (84.5%) there were over 20 NLCs/mm2 (up to 52 NLCs/mm2), and in 9 cases (15.5%) less than 20 NLCs/mm2. Positive correlation was shown between NLC number and B2M serum level (p=0.044) and absolute monocyte count (p=0.019). Significantly higher NLC number was observed in case of patients with higher CD14+ cell number (p<0.0001) and higher SURVIVIN gene expression assessed by RT-PCR (p<0.0001) and macroarrays (p=0.013). We found no statistically significant relation of NLCs number and: the Rai stage of the disease, WBC, lymphocyte count, LDH serum level, BCL2, CD38 and ZAP70 expression and TP53 gene status. During the follow-up period of 6 years we observed the tendency for longer overall survival in patients that produce less than 20 NLCs/mm2 (fig. 1), but it was not statistically significant. Conclusions: The number of NLC cells obtained in vitro from PBL of CLL patients correlates with B2M serum level and SURVIVIN gene expression in CLL cells ex vivo. High B2M level is a marker of poor prognosis. SURVIVIN represents a family of IAP (Inhibitor of APoptosis) proteins. While rare in PBL of CLL patients, its expression is typical for proliferating leukemic cells pool in pseudofollicle microenvironment. SURVIVIN inhibits apoptosis by blocking caspase-3 and -7. Considering the protective role of NLC cells towards CLL lymphocytes in vitro, these results altogether with observed tendency to shorter survival of patients generating high NLCs number may prove the presence of supportive mechanisms exerted by NLCs in vivo. Disclosures: No relevant conflicts of interest to declare.

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Incidentally Discovered COVID-19 in Low Suspicion Patients

10.21203/rs.3.rs-23821/v1 ◽

2020 ◽

Author(s):

Nicholas Xiao ◽

Samir Abboud ◽

Danielle M McCarthy ◽

Nishant Parekh

Keyword(s):

Respiratory Symptoms ◽

Gastrointestinal Symptoms ◽

International Travel ◽

Imaging Findings ◽

Rt Pcr ◽

Abdominal Ct ◽

Clinical Criteria ◽

Time Of Presentation ◽

Current Paradigm

Abstract PurposeThe COVID-19 pandemic has been responsible for thousands of deaths worldwide. Testing remains at a premium, and criteria for testing remains reserved for those with lower respiratory infection symptoms and/or a known high-risk exposure. The role of imaging in COVID-19 is rapidly evolving, however few algorithms include imaging criteria, and it is unclear what should be done in low-suspicion patients with positive imaging findings.MethodsFrom 03/01/2020-03/20/2020, a retrospective review of all patients with suspected COVID-19 on imaging was performed. Imaging was interpreted by a board-certified, fellowship trained radiologist. Patients were excluded if COVID-19 infection was suspected at the time of presentation, was the reason for imaging, or if any lower respiratory symptoms were present.ResultsEight patients with suspected COVID-19 infection on imaging were encountered. Seven patients received testing due to suspicious imaging findings with subsequent lab-confirmed COVID-19. No patients endorsed prior exposure to COVID-19, or recent international travel. COVID-19 was suggested in six patients incidentally on abdominal CT and two on chest radiography. At the time of presentation, no patients were febrile and seven endorsed gastrointestinal symptoms. Five COVID-19 patients eventually developed respiratory symptoms and required intubation. Two patients expired during the admission.ConclusionsPatients with imaging findings suspicious for COVID-19 warrant prompt RT-PCR testing even in low clinical suspicion cases. The prevalence of disease in the population may be underestimated by the current paradigm of RT-PCR testing with the current clinical criteria of lower respiratory symptoms and exposure risk.

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Chest X-Ray findings and visual quantitative assessment of COVID-19 pneumonia

10.21203/rs.3.rs-32480/v1 ◽

2020 ◽

Author(s):

Michaela Cellina ◽

Marcello Orsi ◽

Marta Panzeri ◽

Giulia van der Byl ◽

Giancarlo Oliva

Keyword(s):

Severity Score ◽

Quantitative Assessment ◽

X Rays ◽

Imaging Findings ◽

Rt Pcr ◽

Disease Evolution ◽

X Ray ◽

Radiological Score ◽

Chest X Ray

Abstract AimTo assess the most common chest X-Ray findings and distribution in patients with confirmed diagnosis of COVID-19; to verify the repeatability of a radiological severity score, based on visual quantitative assessment; to assess the evolution of chest X-Ray findings at follow-up; to evaluate chest X-Ray sensitivity.MethodsWe analysed chest X-Rays at baseline of 110 consecutive COVID-19 patients (79 males, 31 females; mean age: 64±16 years) with RT-PCR confirmation, who presented to our ED.Two radiologists evaluated the imaging findings and distribution.A severity score, based on the extension of lung abnormalities, was assigned by two other radiologists, independently, to the baseline and follow-up X-Rays, executed in 77/110 cases; interobserver agreement was calculated. Chest X-Ray sensitivity was assessed, with RT-PCR as gold standard.ResultsInterobserver agreement was excellent for baseline and follow-up X-Rays (Cohen's K=0.989, p<0.001, Cohen's K=0.985, p<0.001, respectively). The mean score at baseline was 2.87±1.7 for readers 1 and 2. We observed radiological worsening in 52/77 (67%) patients, with significantly higher scores at follow-up (mean score: 4.27±2.15 for reader 1 and 4.28±2.14 for reader 2, respectively); p<0.001.Ground glass opacities were the most common findings (97/110, 88%). Abnormalities showed bilateral involvement in 67/110 (61%), with prevalent peripheral distribution (48/110, 43.5%).The X-Ray sensitivity for the detection of COVID-19 infection was 91%.ConclusionChest X-Ray highlighted imaging findings in line with those previously reported for chest CT. The use of a radiological score can result in clearer communication with Clinicians and a more precise assessment of disease evolution.

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COVID-19 pneumonia: a pictorial review of CT findings and differential diagnosis

Egyptian Journal of Radiology and Nuclear Medicine ◽

10.1186/s43055-021-00415-2 ◽

2021 ◽

Vol 52 (1) ◽

Author(s):

Fattane Shirani ◽

Azin Shayganfar ◽

Somayeh Hajiahmadi

Keyword(s):

Differential Diagnosis ◽

Ct Scan ◽

Screening Tool ◽

False Negative ◽

Imaging Findings ◽

Rt Pcr ◽

Negative Results ◽

Ct Findings ◽

Pictorial Review ◽

False Negative Results

Abstract Background The gold standard for verifying COVID-19 mostly depends on microbiological tests like real-time polymerase chain reaction (RT-PCR). However, the availability of RT-PCR kits can be known as a problem and false negative results may be encountered. Although CT scan is not a screening tool for the diagnosis of COVID-19 pneumonia, given the widespread acquisition of it in the pandemic state, familiarity with different CT findings and possible differential diagnosis is essential in this regard. Main text In this review, we introduced the typical and atypical CT features of COVID-19 pneumonia, and discussed the main differential diagnosis of COVID-19 pneumonia. Conclusions The imaging findings in this viral pneumonia showed a broad spectrum, and there are no pathognomonic imaging findings for COVID-19 pneumonia. Although CT scan is not a diagnostic and screening tool, familiarity with different imaging findings and their differential diagnosis can be helpful in a rapid and accurate decision-making.

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TO STUDY THE SIGNIFICANCE OF VARIOUS BIOCHEMICAL AND ND HEMATOLOGICAL PARAMETERS IN COVID CASES IN INDIA IN 2 WAVE OF COVID-19 PANDEMIC: STUDY FROM PUNE, MAHARASHTRA

10.36106/ijar/8700524 ◽

2021 ◽

pp. 14-17

Author(s):

Aruna Chhikara

Keyword(s):

Middle Age ◽

Hematological Parameters ◽

Clinical Manifestations ◽

Control Group ◽

Surrogate Markers ◽

Rt Pcr ◽

Course Of Disease ◽

Indian Context ◽

Infectivity Rate ◽

D Dimer

COVID -19 infection is an ongoing pandemic. The world has already witness two waves and a third one is imminent. Also the COVID 19 infection is now presenting with numerous manifestation besides respiratory symptom. Thus it becomes essential to study surrogate markers or various biochemical and hematological parameters and their signicance in these cases. Data available so far is mostly from other nations with only a limited number of studies from Indian context. Thus the present study was conducted to evaluate the signicance of laboratory parameters in predicting cases infected with COVID 19 and also the correlation of these parameters with gender and course of disease. 557 subjects were included in this study from Pune, Maharashtra. The groups were divided into cases and controls on basis of RT PCR results and clinical manifestations. The control group had 442 subjects and the cases were 135 in number. The inammatory markers (CRP, D-dimer and ferritin) were signicantly high in cases as compared to controls. Among cases 40 % patients belonged to young age (<45 years), 38% to middle age (45 -59 years) and 22 % to elderly group (>60 years). This shows high infectivity rate in st younger group as compared to 1 wave. NLR was higher in cases as compared to controls. CRP, D-dimer and ferritin were signicantly higher in cases as compared to controls

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Hematological abnormalities and comorbidities are associated with COVID-19 severity among hospitalized patients: Experience from Bangladesh

PLoS ONE ◽

10.1371/journal.pone.0255379 ◽

2021 ◽

Vol 16 (7) ◽

pp. e0255379

Author(s):

Md. Ashrafur Rahman ◽

Yeasna Shanjana ◽

Md. Ismail Tushar ◽

Tarif Mahmud ◽

Ghazi Muhammad Sayedur Rahman ◽

...

Keyword(s):

Hematological Parameters ◽

Treatment Protocol ◽

Blood Parameters ◽

Rt Pcr ◽

C Reactive Protein ◽

Reactive Protein ◽

Hematological Abnormalities ◽

Positive Correlations ◽

Patients Experience ◽

D Dimer

Background The hematological abnormalities are assumed to be involved in the disease progression of COVID-19. However, the actual associations between specific blood parameters and COVID-19 are not well understood. Here we aimed to assess the correlations between hematological parameters and the severity of COVID-19. Methods We included COVID-19 patients who were admitted to Evercare Hospital Ltd, Dhaka, Bangladesh, between November 10, 2020, to April 12, 2021, with a confirmed case of RT-PCR test. We recorded demographic information, clinical data, and routine hematological examination results of all COVID-19 patients. We performed statistical analyses and interpretation of data to compare severe COVID-19 patients (SCP) and non-severe COVID-19 patients (NSCP). Results The age and BMI of the admitted COVID-19 patients were 48.79±8.53 years and 25.82±3.75 kg/m2. This study included a total of 306 hospitalized COVID-19 patients. Among them, NSCP and SCP were 198 and 108, respectively. And we recorded 12 deaths from SCP. We observed the alterations of several hematological parameters between SCP and NSCP. Among them, we noticed the increased levels of C-reactive protein (CRP), d-dimer, and ferritin showed good indicative value to evaluate the severity of COVID-19. Also, there were positive correlations among these parameters. Moreover, we found correlations between the outcomes of COVID-19 patients with patient’s demographics and comorbid diseases. Conclusion Based on our results, CRP, d-dimer, and ferritin levels at admission to hospitals represent simple assessment factors for COVID-19 severity and the treatment decisions at the hospital setup. These blood parameters could serve as indicators for the prognosis and severity of COVID-19. Therefore, our study findings might help to develop a treatment protocol for COVID-19 patients at the hospital setup.

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A Diagnostic Model to Predict SARS-CoV-2 Positivity in Emergency Department Using Routine Admission Hematological Parameters

Diagnostics ◽

10.3390/diagnostics11091566 ◽

2021 ◽

Vol 11 (9) ◽

pp. 1566

Author(s):

Rossana Soloperto ◽

Giovanna Guiotto ◽

Giuseppe Tozzi ◽

Maurizio Fumi ◽

Angelo Tozzi

Keyword(s):

Emergency Department ◽

Hematological Parameters ◽

False Negative ◽

Diagnostic Errors ◽

High Sensitivity ◽

Nasopharyngeal Swab ◽

Diagnostic Model ◽

Rt Pcr ◽

Early Management ◽

Cumulative Score

Early detection of SARS-CoV-2 in the emergency department (ED) is a crucial necessity, especially in settings of overcrowding: establishing a pre-diagnostic test probability of infection would help to triage patients and reduce diagnostic errors, and it could be useful in resource-limited countries. Here, we established and validated a clinical predictor of infection based on routine admission hematological parameters. The diagnostic model was developed by comparing 85 consecutive patients with symptomatic COVID-19 confirmed by RT-PCR with 85 symptomatic, SARS-CoV-2-negative controls. Abnormal hematological parameters significantly (p < 0.05) associated with SARS-CoV-2 infection were used to derive a “cumulative score” between 0 and 16. The model was validated in an independent cohort of 170 SARS-CoV-2-positive patients. Several routine hematology parameters were significantly (p < 0.05) associated with SARS-CoV-2 infection. A “cumulative score” score ≥7 discriminated COVID-19-postive patients from controls with a sensitivity of 94% and specificity of 100% (p < 0.001). The high sensitivity of the predictive model was confirmed in the prospective validation set, and the cumulative score (i) predicted SARS-CoV-2 positivity even when the first oro-nasopharyngeal swab RT-PCR result was reported as a false negative in both cohorts and (ii) resulted to be independent from disease severity. The cumulative score based on routine blood parameters can be used to predict an early and accurate diagnosis of SARS-CoV-2 infection in symptomatic patients, thereby facilitating triage and optimizing early management and isolation from the COVID-19 free population, particularly useful in overcrowding situations and in resource-poor settings.

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Alteration of biomarkers of expired and cured COVID- 19 ICU patients in a tertiary care hospital

Bioresearch Communications ◽

10.3329/brc.v7i2.54378 ◽

2021 ◽

Vol 7 (2) ◽

pp. 1031-1037

Author(s):

Abu Hasan ◽

Rummana Rahim ◽

Mizanur Rahman

Keyword(s):

Biochemical Parameters ◽

Target Genes ◽

Hematological Parameters ◽

Tertiary Care ◽

Care Hospital ◽

Rt Pcr ◽

C Reactive Protein ◽

Protein Ratio ◽

Reactive Protein ◽

D Dimer

Coronavirus Disease 2019 (COVID-19) is a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2). This is a retrospective observational study aimed to find the alteration of some biochemical and hematological parameters of 121 COVID-19 patients admitted in intensive care unit (ICU) of Evercare Hospital Dhaka during May to December 2020. Methods: Retrospective biochemical, hematological and molecular (COVID-19 RT-PCR Ct value) markers were analyzed on COVID-19 patients in ICU and compared on those who died in the ICU and those cured. Results: Comparison of viral titer assessed by RT-PCR Ct values of target genes of SARS-CoV-2 among cured and expired patients did not show any significant differences. However, biochemical parameters such as CRP, Ferritin and hematological parameters such as WBC, absolute neutrophil, absolute lymphocyte, D-dimer showed significant differences among cured and expired patients. Patients who died in ICU mean CRP, Ferritin, D-dimer, WBC, absolute neutrophil were 10.39, 7694.30, 3196, 16.38, 15.12 respectively, compared to cured patients 0.93, 457.57, 773, 11.24, 8.86 respectively, with 95% confidence interval (95% CI). Platelets and absolute lymphocytes were observed decreased in expired patients compared to cured. Further, elevated level of neutrophil to lymphocyte ratio (NLR) and reduced level of lymphocyte to C-reactive protein ratio (LCR) has significant correlation with disease severity. Conclusion: These findings indicate that biochemical parameters such as CRP, Ferritin and hematological parameters such as CBC, D-Dimer, NLR, LCR can be monitored to identify severity and fatality of COVID-19 patients and thus, may help in improving disease outcome. Bioresearch Commu. 7(2): 1031-1037, 2021 (June)

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