Effect of mRNA vaccination on pulmonary sequelae after mild COVID-19 (preprint)

Background: Previous studies indicate a protective role for SARS-CoV-2 vaccination against development of pulmonary post-acute sequelae of COVID (PASC). We compared clinical, imaging, histopathology and ultrastructural features of pulmonary PASC with and without prior vaccination in a consecutive cohort of 54 unvaccinated, 17 partially vaccinated and 28 fully vaccinated patients who presented with dyspnea on exertion after mild COVID-19 (without hospitalization). Methods: Patients underwent full clinical evaluation including autoantibody (ANA/ENA) serology, high-resolution computed tomography (HRCT), bronchioloalveolar lavage fluid (BAL) analysis and transbronchial biopsy followed by histopathological and ultrastructural analysis and SARS-CoV-2 immunohistochemistry. Results: While vaccinated patients were younger (p=0.0056), included more active smokers (p=0.0135) and a longer interval since infection (35 vs. 17 weeks, p=0.0002), dyspnea on exertion and impaired lung function were not different between vaccinated and unvaccinated patients. Ground glass opacities in HRCT and centrilobular fibrosis were more frequent in unvaccinated patients (p=0.0154 and p=0.0353), but presence of autoantibodies, BAL lymphocytosis and bronchiolitis were common findings in all groups. While vaccination against SARS-CoV-2 is associated with a longer time span between infection and consultation along with a reduced frequency of ground glass opacities and centrilobular fibrosis, impaired lung function, bronchiolitis and presence of autoantibodies are comparable between vaccinated and unvaccinated patients. Residual virus was not detected in lung tissue in all but 1 patient. Conclusion: While differences between the investigated groups with regard to age, smoking status and SARS-CoV-2 variants have to be taken into account, a proposed protective role of SARS-CoV-2 vaccination against pulmonary PASC is so far not fully explained by clinical and histopathology findings.

Fever with atypical lymphocytosis: pearls and pitfalls in Epstein-Barr virus serology.

The heterophile antibody (also known as the Monospot) test is a useful screening tool for infectious mononucleosis (IM) resulting from primary Epstein-Barr virus (EBV) infection. However, up to 10% of patients with IM are heterophile negative. Heterophile-negative patients who have lymphocytosis or atypical lymphocytes on peripheral blood smear should be further tested for EBV serologies, which include testing for specific IgM and IgG antibodies against viral capsid antigens, early antigens and EBV nuclear antigen proteins. A diagnostic dilemma arises when the patient has clinical and laboratory features of IM, but is both heterophile negative and seronegative for IM, as illustrated in this case presentation. To avoid missed diagnoses of IM, misdiagnosis of mononucleosis-like illnesses and unnecessary testing, knowledge of test characteristics and the evolving course of EBV serologies is important to assure and inform both the physician and the patient.

Optic ataxia in a patient with HaNDL syndrome.

We present a woman in her 40s who arrived at the emergency room with hypertension and optic ataxia. Her medical history is only relevant for obesity. Her lumbar puncture revealed high intracranial pressure and lymphocytic pleocytosis, and her neuroimaging tests, including angiography and venography, were normal. The patient improved after a cerebrospinal fluid drainage with a lumbar puncture, and her clinical manifestations resolved in parallel to the lymphocytic pleocytosis.The patient was diagnosed with a syndrome of transient headache and neurological deficits with cerebrospinal fluid lymphocytosis and fully recovered 21 days after her discharge.

Monoclonal B-cell Lymphocytosis - a review of diagnostic criteria, biology, natural history, and clinical management.

Since first described almost two decades ago, there has been significant evolution in our definition and understanding of the biology and implications of monoclonal B-cell lymphocytosis (MBL). This review provides an overview of the definition, classification, biology, and natural history of MBL, mainly focused on the dominant CLL-like phenotype form of MBL. The increasingly recognized implications of MBL with respect to immune dysfunction are discussed, particularly in view of the COVID-19 pandemic, along with management recommendations for MBL in the clinic.

COVID-19 vaccine failure in chronic lymphocytic leukaemia and monoclonal B-lymphocytosis; humoural and cellular immunity.

Chronic lymphocytic leukaemia (CLL) is associated with immunocompromise and high risk of severe COVID-19 disease and mortality. Monoclonal B-cell lymphocytosis (MBL) patients also have immune impairment. We evaluated humoural and cellular immune responses in 181 patients with CLL (160) and MBL (21) to correlate failed seroconversion [<50 AU/ml SARS-CoV-2 II IgG assay, antibody to spike protein; Abbott Diagnostics)] following each of two vaccine doses with clinical and laboratory parameters. Following first and second doses, 79.2% then 45% of CLL, and 50% then 9.5% of MBL patients respectively remained seronegative. There was significant association between post dose two antibody level with pre-vaccination reduced IgM (p < 0.0001), IgG2 (p < 0.035), and IgG3 (p < 0.046), and CLL therapy within 12 months (p < 0.001) in univariate analysis. By multivariate analysis, reduced IgM (p < 0.0002) and active therapy (p < 0.0002) retained significance. Anti-spike protein levels varied widely and were lower in CLL than MBL patients, and both lower than in normal donors. Neutralisation activity showed anti-spike levels <1000 AU/ml were usually negative for both an early viral clade and the contemporary Delta variant and 72.9% of CLL and 53.3% of MBL failed to reach levels ≥1000 AU/ml. In a representative sample, ~80% had normal T-cell responses. Failed seroconversion occurred in 36.6% of treatment-naïve patients, in 78.1% on therapy, and in 85.7% on ibrutinib.

Brescia-COVID Respiratory Severity Scale (BRCSS) and Quick SOFA (qSOFA) score are most useful in showing severity in COVID-19 patients.

In this study, we compare the predictive value of clinical scoring systems that are already in use in patients with Coronavirus disease 2019 (COVID-19), including the Brescia-COVID Respiratory Severity Scale (BCRSS), Quick SOFA (qSOFA), Sequential Organ Failure Assessment (SOFA), Multilobular infiltration, hypo-Lymphocytosis, Bacterial coinfection, Smoking history, hyper-Tension, and Age (MuLBSTA) and scoring system for reactive hemophagocytic syndrome (HScore), for determining the severity of the disease. Our aim in this study is to determine which scoring system is most useful in determining disease severity and to guide clinicians. We classified the patients into two groups according to the stage of the disease (severe and non-severe) and adopted interim guidance of the World Health Organization. Severe cases were divided into a group of surviving patients and a deceased group according to the prognosis. According to admission values, the BCRSS, qSOFA, SOFA, MuLBSTA, and HScore were evaluated at admission using the worst parameters available in the first 24 h. Of the 417 patients included in our study, 46 (11%) were in the severe group, while 371 (89%) were in the non-severe group. Of these 417 patients, 230 (55.2%) were men. The median (IQR) age of all patients was 44 (25) years. In multivariate logistic regression analyses, BRCSS in the highest tertile (HR 6.1, 95% CI 2.105-17.674, p = 0.001) was determined as an independent predictor of severe disease in cases of COVID-19. In multivariate analyses, qSOFA was also found to be an independent predictor of severe COVID-19 (HR 4.757, 95% CI 1.438-15.730, p = 0.011). The area under the curve (AUC) of the BRCSS, qSOFA, SOFA, MuLBSTA, and HScore was 0.977, 0.961, 0.958, 0.860, and 0.698, respectively. Calculation of the BRCSS and qSOFA at the time of hospital admission can predict critical clinical outcomes in patients with COVID-19, and their predictive value is superior to that of HScore, MuLBSTA, and SOFA. Our prediction is that early interventions for high-risk patients, with early identification of high-risk group using BRCSS and qSOFA, may improve clinical outcomes in COVID-19.

COVID-19 Vaccine Failure in Chronic Lymphocytic Leukemia and Monoclonal B-Lymphocytosis; Humoral and Cellular Immunity (preprint)

Chronic lymphocytic leukemia (CLL) is associated with immunocompromise and high risk of severe COVID-19 disease and mortality. Monoclonal B-Lymphocytosis (MBL) patients also have immune impairment. We evaluated humoral and cellular immune responses in 181 patients with CLL (160) and MBL (21) to correlate failed seroconversion (<50AU/mL SARS-CoV-2 II IgG assay, antibody to spike protein, Abbott Diagnostics) following each of 2 vaccine doses with clinical and laboratory parameters. Following first and second doses, 79.2% then 45% of CLL, and 50% then 9.5% of MBL respectively remained seronegative, indicating 2 vaccine doses are crucial. There was significant association between post-dose 2 antibody level with pre-vaccination reduced IgM (p<0.0001), IgG2 (p<0.035), IgG3 (p<0.046), and CLL therapy within 12 months (p<0.001) in univariate analysis. By multivariate analysis, reduced IgM (p<0.0002) and active therapy (p<0.0002) retained significance. There was no significant correlation with age, gender, CLL duration, IgG, IgA or lymphocyte subsets. Anti-spike protein levels varied widely and were lower in CLL, than MBL, and both lower than normal donors. Neutralization activity showed anti-spike levels <1000AU/mL were usually negative for both an early viral clade and the contemporary Delta variant. There were 72.9% of CLL and 53.3% of MBL who failed to reach anti-spike levels >1000AU/mL. In a representative subset of 32 CLL patients, 80% had normal T-cell responses by IFN{gamma} and IL-2 FluoroSpot assay. Failed seroconversion occurred in 36.6%% of treatment-naive patients, 52.9% treatment-naive with reduced IgM, 78.1% on therapy, and 85.7% on ibrutinib. Vaccination failure is very common in CLL, including early-stage disease.

Chronic lymphocytic leukemia; an incidental finding in a COVID-19 patient. (preprint)

We report a case of 57 years old male, with no prior comorbids functional class I, presented with a history of fever for one week along with shortness of breath and cough for 5 days. Upon workup his baseline CBC reported bicytopenia along with marked lymphocytosis which raised the suspicion and to confirm the diagnosis, his acute leukemia comprehensive panel was done which reported an incidental finding of Chronic lymphocytic leukemia along with concomitant COVID PCR positive. This patient also presented with Tumor Lysis Syndrome and Acute kidney Injury.

COVID-19 in children: a case series from Nigeria.

INTRODUCTION: The global spread of COVID-19 remains unabated in the past few months with a rise in the number of available literature on the novel virus. There are very few paediatric studies and are mainly from developed countries with a paucity of information on the clinical manifestation of COVID-19 disease in African children, including Nigeria. METHODS: We described the clinical presentation, laboratory findings, treatment and outcome in a group of five Nigerian children managed at a COVID-19 isolation and treatment centre in Nigeria. RESULTS: We managed a total of five children with an age range of 3 months to 8 years in the last four weeks (16th April to 15th May 2020). Three of the five children were males. All the children had close contact with family members that tested positive for COVID-19. Out of the five children, one had moderate disease, three had mild symptomatic disease, and one was asymptomatic. Two out of the five children had lymphocytosis. Out of the four children who had chest radiograph, two had features of pneumonia. CONCLUSION: COVID-19 is not uncommon in Nigerian children, and all had a confirmed family member with COVID-19. Besides, contrary to leucopaenia with lymphopaenia observed in the adult's population, we found lymphocytosis in this cohort and about 50.0% had pneumonic changes on chest radiograph.

Clinical, Laboratory, and Chest CT Features of Severe Versus Non-Severe Pediatric Patients with COVID‐19 Infection Among Different Age Groups (preprint)

Background: The aim of this study was to compare the clinical, laboratory, and chest computed tomography (CT) findings between severe and non-severe patients as well as between different age groups of pediatric patients with confirmed COVID-19.Method: This study was performed on 55 pediatric patients with confirmed COVID-19 hospitalized in Namazi and Ali Asghar Hospitals, Shiraz, Iran. Patients were divided into severe (n=27) and non-severe (n=28) groups. Also, they were categorized into three age groups: aged less than two years, 3-12 years and 13-17 years.  CT scans, laboratory, and clinical features were taken from all patients at the admission time. Abnormal chest CT in COVID-19 pneumonia was found to show one of the following findings: ground-glass opacities (GGO), bilateral involvement, peripheral and diffuse distribution.Result: Fever (79.2%) and dry cough (75.5%) were the most common clinical symptoms. Severe COVID-19 patients showed lymphocytosis compared to non-severe ones (P = 0.028). C-reactive protein (CRP) was shown to be significantly lower in patients aged less than two years than those aged 3-12 and 13-17 years old (P = 0.009). It was also shown that O2 saturation was significantly increased, as age increased (P = 0.015). Also, severe patients had significantly higher CT abnormalities compared to non-severe ones (48.0% compared to 17.9%, respectively) (P = 0.019).Conclusion: Lymphocytosis and abnormal CT findings are among the factors most associated with COVID-19 severity. It was, moreover, showed that the severity of the COVID-19, O2 saturation, and respiratory distress were improved as the age of confirmed COVID-19 pediatric patients increased.

Clinical characteristics and mortality of patients with hematologic malignancies and COVID-19: a systematic review.

OBJECTIVE: Hematologic cancer patients with Coronavirus Disease 2019 (COVID-19) tend to have a more serious disease course than observed in the general population. Herein, we comprehensively reviewed existing literature and analyzed clinical characteristics and mortality of patients with hematologic malignancies and COVID-19. MATERIALS AND METHODS: Through searching PubMed until June 03, 2020, we identified 16 relevant case studies (33 cases) from a total of 45 studies that have reported on patients with COVID-19 and hematologic malignancies. We investigated the clinical and laboratory characteristics including type of hematologic malignancies, initial symptoms, laboratory findings, and clinical outcomes. Then, we compared those characteristics and outcomes of patients with hematologic malignancies and COVID-19 to the general population infected with COVID-19. RESULTS: The median age was 66-year-old. Chronic lymphocytic leukemia was the most common type of hematologic malignancy (39.4%). Fever was the most common symptom (75.9%). Most patients had normal leukocyte counts (55.6%), lymphocytosis (45.4%), and normal platelet counts (68.8%). In comparison to patients with COVID-19 without underlying hematologic malignancies, dyspnea was more prevalent (45.0 vs. 24.9%, p=0.025). Leukocytosis (38.9 vs. 9.8%, p=0.001), lymphocytosis (45.4 vs. 8.2%, p=0.001), and thrombocytopenia (31.3 vs. 11.4%, p=0.036) were significantly more prevalent and lymphopenia (18.2 vs. 57.4%, p=0.012) less prevalent in patients with hematologic malignancies. There were no clinical and laboratory characteristics predicting mortality in patients with hematologic malignancies. Mortality was much higher in patients with hematologic malignancies compared to those without this condition (40.0 vs. 3.6%, p<0.001). CONCLUSIONS: Co-occurrence of hematologic malignancies and COVID-19 is rare. However, due to the high mortality rate from COVID-19 in this vulnerable population, further investigation on tailored treatment and management is required.

Clinical and demographic characteristics of patients with COVID-19 infection: Statistics from a single hospital in Iran.

Coronavirus disease 2019 (COVID-19) has caused a global pandemic in early 2020. This infectious disorder has a heterogeneous course ranging from asymptomatic disorder to a critical situation needing intensive cares. In the current study, we present a report of affected patients admitted in a single hospital in Iran. Eighty-two hospitalized patients with COVID-19 were assessed. Demographic, clinical, and paraclinical parameters were gathered and statistically analyzed. The median age (IQR) of the patients was 57.32 (45.75, 70) years. At primary evaluation, fever was present in 45.12% of the affected individuals. The most common clinical symptoms were dyspnea (81.71%) and cough (65.85%). Totally, 12 (14.63%) and 14 (17.07%) of patients had low and high WBC counts, respectively. Lymphopenia was detected in 36 (43.9%) of patients, while 6 (7.32%) of patients had lymphocytosis. High levels of Il-6 were detected in 4 (4.88%) of patients. CRP levels were elevated in 69 (84.1%) of patients. The median (IQR) of hospitalization was 7 (5, 9) days. Totally, 26 patients (31%) were hospitalized in ICU. All patients were discharged with good health conditions except for one patient who died. The current study shows the heterogeneous clinical manifestations and paraclinical parameters of COVID-19 patients.

Review of clinical characteristics and laboratory findings of COVID-19 in children-Systematic review and Meta-analysis (preprint)

OBJECTIVE: To conduct a systematic review and meta-analysis to assess the prevalence of various clinical symptoms and laboratory findings of COVID-19 in children. METHODS: PubMed, MEDLINE, and SCOPUS databases were searched to include studies conducted between January 1, 2020, and July 15, 2020 which reported data about clinical characteristics and laboratory findings in laboratory-confirmed diagnosis of COVID-19 in pediatric patients. Random effects meta-analysis using generalized linear mixed models was used to estimate the pooled prevalence. RESULTS: The most prevalent symptom of COVID-19 in children was 46.17% (95%CI 39.18-53.33%), followed by cough (40.15%, 95%CI 34.56-46.02%). Less common symptoms were found to be dyspnea, vomiting, nasal congestion/rhinorrhea, diarrhea, sore throat/pharyngeal congestion, headache, and fatigue. The prevalence of asymptomatic children was 17.19% (95%CI 11.02-25.82%). The most prevalent laboratory findings in COVID-19 children were elevated Creatinine Kinase (26.86%, 95%CI 16.15-41.19%) and neutropenia (25.76%, 95%CI 13.96-42.58%). These were followed by elevated LDH, thrombocytosis, lymphocytosis, neutrophilia, elevated D Dimer, Elevated CRP, elevated ESR, leukocytosis, elevated AST and leukopenia. There was a low prevalence of elevated ALT and lymphopenia in children with COVID- 19. CONCLUSIONS AND RELEVANCE: This study provides estimates of the pooled prevalence of various symptoms and laboratory findings of COVID-19 in the pediatric population.

COVID-19-Associated Encephalitis: Systematic Review of Case ReportsFindings on Cytokine-Immune-Mediated Inflammation as an Underlying Mechanism (preprint)

Background : Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily attacks the respiratory system resulting to a disease called coronavirus disease 19 (COVID-19), several studies also reported the involvement of the central nervous system along the course of the disease, one of which manifest as encephalitis. This study aims to determine the clinical profile, laboratory, and imaging results of encephalitis associated with COVID-19.Methods : Three databases namely, PubMed / Medline, Embase, and Scopus were systematically used in the search for this literature, in order to gather case reports and case series related to COVID-19-associated encephalitis published from January 1, 2019 to July 20, 2020.Result: There were 24 studies with 33 cases included in this review. The most reported neurological symptoms were disorientation / confusion (72.72%), decreased consciousness (54.54%), and seizures (27.27%). The laboratory examination showed an increase in the levels of C-reactive protein (48.48%), lactate dehydrogenase (30.3%), and lymphophenia (27.27%). The brain imaging examination did not show any pathological findings in half of the cases (51.51%). EEG (electroencephalography) showed a generalized decrease in 45.45% of the cases. The CSF analysis showed an increase in the levels of protein (42.42%) and lymphocytosis (24.24%). Positive cerebrospinal fluid polymerase chain reaction (PCR) was only found in 3 cases, while the most widely used pharmacological agent was hyroxychloroquine (48.48%). Intravenous steroids were given in 8 cases, while immunotherapy such as plasmapheresis and intravenous immunoglobulin were given in 10 cases. Fifteen patients were reported to be discharged from the hospital in stable conditions, while four mortality cases were recorded. Conclusion: The clinical, laboratory, and imaging findings in this review supported the hypothesis that the process of cytokine-immune mediated inflammation was the cause of cerebral damage in COVID-19-associated encephalitis, rather than direct invasion. However, due to the limited availabile facilities in this study, further research and examination are needed to confirm the hypothesis 

The Clinical Characteristics and Outcomes of Patients with Moderate-to-Severe Coronavirus Disease 2019 Infection and Diabetes in Daegu, South Korea.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a global pandemic that had affected more than eight million people worldwide by June 2020. Given the importance of the presence of diabetes mellitus (DM) for host immunity, we retrospectively evaluated the clinical characteristics and outcomes of moderate-to-severe COVID-19 in patients with diabetes. METHODS: We conducted a multi-center observational study of 1,082 adult inpatients (aged ≥18 years) who were admitted to one of five university hospitals in Daegu because of the severity of their COVID-19-related disease. The demographic, laboratory, and radiologic findings, and the mortality, prevalence of severe disease, and duration of quarantine were compared between patients with and without DM. In addition, 1:1 propensity score (PS)-matching was conducted with the DM group. RESULTS: Compared with the non-DM group (n=847), patients with DM (n=235) were older, exhibited higher mortality, and required more intensive care. Even after PS-matching, patients with DM exhibited more severe disease, and DM remained a prognostic factor for higher mortality (hazard ratio, 2.40; 95% confidence interval, 1.38 to 4.15). Subgroup analysis revealed that the presence of DM was associated with higher mortality, especially in older people (≥70 years old). Prior use of a dipeptidyl peptidase-4 inhibitor or a renin-angiotensin system inhibitor did not affect mortality or the clinical severity of the disease. CONCLUSION: DM is a significant risk factor for COVID-19 severity and mortality. Our findings imply that COVID-19 patients with DM, especially if elderly, require special attention and prompt intensive care.