Could platelet mass index (PMI) be a new prognostic biomarker for COVID-19?

Aim: Although most patients with COVID-19 experience respiratory tract infections, severe reactions to the virus may cause coagulation abnormalities that mimic other systemic coagulopathies associated with severe infections, such as disseminated intravascular coagulation and thrombotic microangiopathy. Fluctuations in platelet markers, which are an indicator of the acute phase response for COVID-19, are of clinical importance. The aim of this study is to evaluate the relationship between disease severity and Platelet Mass Index (MPI) parameters in COVID-19 patients. Material(s) and Method(s): This retrospective observational study was conducted with patients who were diagnosed with COVID-19 in a tertiary hospital. The study was continued with the remaining 280 patients. All laboratory data were scanned retrospectively from patient files and hospital information system. Result(s): A very high positive correlation was found between PMI and PLT. The PMI value in women was significantly higher than in men. It was observed that PMI did not differ significantly in terms of mortality, intubation, CPAP and comorbidity. PMI vs. Pneumonia Ct Severity Score, biochemistry parameters (AST, CRP), hemogram parameters (WBC, HGB, HCT, MCV, LYM, MPV EO) and coagulation factors (aPTT and FIB) at various levels of positive/negative, weak and strong, and significant relationship was found. There was no significant relationship between hormone and D-dimer when compared with PMI. Discussion(s): Although platelet count alone does not provide information about the prognosis of the disease, PMI may guide the clinician as an indicator of lung damage in seriously ill patients.Copyright © 2022, Derman Medical Publishing. All rights reserved.

Cuban Vaccines Abdala and Mambisa against Covid-19

Intro: With the first case of COVID-19 in Cuba on March 11, 2020, the Center for Genetic Engineering and Biotechnology in Havana began an extensive vaccine program. Two vaccines based on RBD recombinant protein were developed, one for systemic administration "Abdala" and one mucosal vaccine "Mambisa". Abdala received the EUA in July 2021 and "Mambisa" completed its clinical development as a booster dose for convalescent subjects. Method(s): Two doses (25 and 50 microg) and two schedules (0-14-28 and 1-28-56 days) were evaluated in phase I clinical trials with volunteers 19 to 54 years old. The phase II and III clinical trials were also double-blind, randomized, and placebo-controlled, and included respectively 660 and 48,000 volunteers from 19 to 80 years. The anti-RBD titers were evaluated using a quantitative ELISA system developed at the Center for Immunoassay, Havana Cuba, and ELECSYS system from Roche. The RBD to ACE2 plate-based binding competitive ELISA was performed to determine the inhibitory activity of the anti-RBD polyclonal sera on the binding of the hFc-ACE2 coated plates. The neutralization antibody titers were detected by a traditional virus microneutralization assay (MN50). Finding(s): The Abdala vaccine reached 92.28% efficacy. The epidemic was frankly under control in Cuba after the vaccine introduction having reached the highest levels of cases and mortality in July 2021 with the dominance of the Delta strain. The peak of the Omicron wave, unlike other countries, did not reach half of the cases of the Delta wave with a significant reduction in mortality. The mucosal vaccine candidate "Mambisa" completed its clinical development as a booster dose for convalescent subjects reaching the trial end-point. Conclusion(s): Vaccine composition based on RBD recombinant antigen alone is sufficient to achieve high vaccine efficacy comparable to mRNA and live vaccine platforms. The vaccine also protects against different viral variants including Delta and Omicron strains.Copyright © 2023

Relationship between Sars-Cov-2 Viral Load, Antigen Positivity and Infectious Titer

Intro: Performance of SARS-CoV-2 antigen tests is described relative to RT-PCR cycle threshold (Ct) values. However, Ct values may not be consistent between tests from different manufacturers, or even between runs. Here we correlate the Roche Elecsys SARS-CoV-2 Antigen assay results to a quantitative RT-PCR readout as a more reproducible measure of viral load. Additionally, we look at the relationship between the antigen test results, viral load and infectious titer. Method(s): Longitudinal nasopharyngeal swab samples from patients (N=452) with severe Covid-19 pneumonia collected between 03 April and 28 May 2020 in a randomized, double-blind, placebo controlled, multicenter study to evaluate the safety and efficacy of Tocilizumab (COVACTA), were assessed for SARS-CoV-2 viral load (RNA copies/ mL) and a qualitative and semi-quantitative readout of Elecsys SARS-CoV-2 Antigen assay. Viral culture experiments were performed to determine the infectious titer (TCID50/ mL) in a subset of samples. Agreement analysis was performed to compare the results of the assays. Please note that the current intended use of Elecsys SARS-CoV-2 Antigen assay is the qualitative detection of SARS-CoV-2 antigen. Finding(s): We observed high negative percent agreement between the Elecsys SARS-CoV-2 Antigen assay results and the RT-PCR results, while the positive percent agreement was only high in samples exceeding a certain viral load and at earlier time points from symptom onset. Infectious titer values and both the antigen assay semi-quantitative readout and the quantitative RT-PCR results correlated well. Positive percent agreement of RT-PCR and antigen results in relation to infectious titer was very high in both cases, while negative percent agreement was moderate to low. Conclusion(s): These data show that in patients with high viral load the Elecsys SARS-CoV-2 Antigen assay correlates well qualitatively and quantitatively with the presence of SARS-CoV-2 RNA and infectious virus as determined by RT-PCR and viral culture, respectively.Copyright © 2023

Rituximab and Covid-19 Vaccines, Are They Fit for Purpose?

Background/Aims Since the COVID-19 outbreak the rheumatology community have been concerned about the risk of SARS-CoV-2 infection in patients prescribed immunosuppressing medications. Data suggests that patients receiving Rrtuximab are at increased risk of developing severe outcomes from COVID-19 (1). In our unit all patients receiving rituximab were selected to receive a targeted vaccination and booster programme with all patients receiving at least 2 vaccinations and up to 3 booster vaccinations. We studied the efficacy of the COVID-19 vaccines in rituximab patients, by checking the the Roche Elecsys Anti-SARS-CoV-2-S (Spike) IgG/IgM total antibody levels post vaccination. Our aim was to assess the vaccination response in patients receiving rituximab and to offer advice on continued shielding or alternatively passive immunization with tixagevimab/cilgavimab in those patients who did not mount a response. Methods Taking 39 patients currently on rituximab therapy, we measured Anti- SARS-CoV-2-S (Spike) antibody levels post vaccination. We recorded whether the test was positive or negative, and the numerical result. We recorded rituximab dates of administration and dates of vaccines. We also recorded diagnosis, co-prescribed DMARDs, immunoglobulin levels, white cell and lymphocyte counts. We took record of whether or not the patient subsequently contracted COVID-19, required a hospital admission, ICU or died. Results Of our 39 patients, 21 had Anti-SARS-CoV-2-S (Spike) antibody levels checked. Of these patients, 7 (33%) had a negative spike protein result. Of the patients with a positive result, 8 (38%) had an antibody level between 0-250U/ML, and only 6 (28.6%) had a level >250U/ML (The manufacturer advises that a level above 0.8U/ML is a positive result). Of patients with a negative result, 1 patient had received 3 vaccines, 5 patients had received 4, and 1 patient had 5. All of the patients had received a vaccine >4 weeks prior to receiving the drug. Two patients were co-prescribed Belimumab, 3 were co-prescribed low-dose methotrexate and 2 were not on additional disease modifying agents. The diagnoses of these patients were, 2 patients with SLE, 4 with SPRA, and 1 MPO Vasculitis. There were no significant findings in lymphocyte count, white cell count or immunoglobulin levels. Conclusion These findings suggest that our current COVID-19 vaccination and booster programme may not provide adequate response in patients receiving rituximab therapy. Despite this being a small cohort, these results show that 33% of patients have not mounted a vaccine response and this is concerning. We suggest that vaccine response should be checked in all patients receiving rituximab therapy and those patients who do not mount a vaccine response should be offered passive immunity and advised of possible additional risks regarding COVID-19 exposure.

SARS-CoV-2 ANTIBODY RESPONSES POST-INFECTION IN PREGNANCY BY VACCINATION STATUS

Background: We evaluated SARS-CoV-2 antibody binding and neutralization responses at delivery among pregnant persons with prior SARS-CoV-2 infection by vaccine status. Method(s): We enrolled participants with evidence of prior SARS-CoV-2 infection detected in pregnancy (anti-nucleocapsid [anti-N] IgG+ on enrollment or prior RT-PCR+ or antigen+) and followed them through delivery. Maternal delivery and cord blood samples were tested for SARS-CoV-2 binding antibodies to spike (anti-S) (from vaccination and/or infection) and anti-N (from infection only) IgG by Abbott Architect followed by neutralizing antibodies (classified as neutralizing if serum dilution inhibited infection by 50% [ND50 heat] >=20 and R2 >=0.9) if sample volume allowed. Positive IgG thresholds were Abbott index >=1.4 for anti-N and >=50 AU/mL for anti-S. Chi-squared test was used to compare differences in proportions between groups. Wilcoxon rank sum test was used to compare medians. Result(s): Among 71 participants with delivery and cord samples, median age was 33 years (interquartile range [IQR] 30-35) and median gestational age was 31.7 weeks (IQR 18.0-37.9) at enrollment in pregnancy. By delivery, 17 (24%) participants were unvaccinated, 21 (30%) were partially vaccinated or had completed a primary series, and 33 (46%) were boosted. Median time from infection (RT-PCR+ or antigen+ result) to delivery was 16.7 weeks (IQR 9.7- 24.3). At delivery, 33 (46%) of maternal (median 3.2 index) and 37 (52%) of cord samples (median 3.1 index) were anti-N IgG+. Participants with >=1 vaccine were more likely to be anti-S IgG+ than those unvaccinated (100% vs. 82%, p< 0.01), have higher median anti-S IgG+ (25,000 vs 1,019 AU/ml, p< 0.01), and have neutralizing antibodies (100% vs. 81%, p< 0.01) with higher median log10 neutralization (1:4.00 vs 1:2.41, p< 0.01) at delivery. Similarly, cord blood from participants with >=1 vaccine was more likely to be anti-S IgG+ than those unvaccinated (100% vs. 82%, p< 0.01), have higher median anti-S IgG+ (25,000 vs 1,188 AU/ml, p< 0.01), and have neutralizing antibodies (100% vs. 75%, p< 0.01) with higher median log10 neutralization (1:4.00 vs 1:2.41, p< 0.01) at delivery. Conclusion(s): Among pregnant people with prior SARS-CoV-2 infection detected during pregnancy, maternal and cord blood antibody binding and neutralization responses were higher among those receiving SARS-CoV-2 vaccination prior to delivery. (Table Presented).

Angiotensin Converting Enzyme (Ace) Levels in Irish Population after Covid

Background ACE is a potent pro-inflammatory modulator that controls chemokines and adhesion molecules, and elevated ACE activity associated with immunoinflammatory conditions, including cardiovascular diseases (CVD) and diabetes. The ACE inhibitors are recommended as primary treatment for these illnesses. ACE is a peptidyl-dipeptidase that catalyses Angiotensin I to Angiotensin II, whilst inactivating bradykinin during blood pressure regulation via the Renin-Angiotensin System. The purpose of this study is to establish a reference interval (RI) for ACE in the Irish population after COVID, and to examine if there is an underlying correlation between ACE concentrations and a range of biomarkers. Methods Serum samples of 200 randomly selected patients were obtained from several Irish hospitals in March 2022 (in compliance withGuidance on Anonymisation and Pseudonymisation, June 2019). We analysed for ACE (Buhlmann reagents), HBA1C, 25OHD and other biomarkers on the Abbott Architect ci8200. Full Blood Count was measured on Sysmex CS-2500. The statistical analysis used the EP Evaluator 11.3.0.23 and SPSS 22.0 software. Results The RI based on the central 95% of data was 8-78 U/L. This is higher than the RI proposed by the manufacturer (20-70 U/L) but is very close to our RI (5-79 U/L) from 2019. We found a significant positive correlation between ACE concentration and HBA1c, Urea, Creatinine, White Blood Cells (p<0.0001), Glucose (p=0.02), LDL (p=0.03), Neutrophils (p=0.003), Lymphocytes (p=0.001). A significant negative correlation was observed with 25OHD (p<0.0001). Conclusions This study did not show any notable change in the RI for ACE after COVID in Ireland. The significant positive correlations with HBA1c and other biomarkers may indicate the importance for ACE testing for diabetic management and progression, but further studies will be needed. Patients' overall health and medical history should always be considered when evaluating ACE results, including Vitamin D levels.

Comparison of biomarkers of COVID-19 patients with the alpha variant (B.1.1.7), the delta variant (B.1.617), and no mutation detected

Objectives: We aimed to compare biomarkers of COVID-19 patients with the Alpha variant (B.1.1.7), the Delta variant (B.1.617), and no mutation detected in our study. Method(s): A total of 600 patients with positive COVID PCR test and Alpha, Delta variant and no mutation detected with Covid PCR mutation test were included in the study. Troponin I, creatinine, Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LDH), fibrinogen, D-dimer, ferritin, number of lymphocytes, lymphocytes (%), platelet (PLT), mean platelet volume (MPV), platelet distribution width (PDW), trombosite ratio in the blood (PCT), C-reactive protein (CRP) values were analyzed retrospectively. The age, gender, and hospitalization of the patients were evaluated concurrently. Result(s): Age, troponin, creatinine, LDH, PLT, MPV, and D-dimer were laboratory parameters that vary significantly with COVID-19 virus mutation. Age, troponin, LDH, and MPV values were lower in patients with Delta variant according to patients with the Alpha variant. Lymphocytes (N) and lymphocytes (%) values were lower in hospitalized patients relative to outpatients while age, troponin, LDH, CRP, and D-dimer values were higher in hospitalized patients than outpatients irrespective of mutation. Creatinine values were higher only in hospitalized patients with no mutation detected while ferritin and fibrinogen values were higher in hospitalized patients with Delta variant and no mutation detected. Conclusion(s): Age, troponin, creatinine, LDH, PLT, MPV, D-dimer, fibrinogen, ferritin, CRP, lymphocytes (N), and lymphocytes (%) values can guide to evaluate the diagnosis and hospitalization of patients with future different mutations.Copyright © 2023 by Prusa Medical Publishing.

EFFECTS OF COVID-19 mRNA VACCINATION ON HIV VIREMIA AND RESERVOIR SIZE IN PWH ON ART

Background: Transient viremia has been reported after COVID-19 mRNA vaccination in ART-suppressed PWH, suggesting a stimulatory effect on the HIV reservoir. A recent study also reported that Nef-specific CD8+ T cells increased and acquired granzyme-B effector function following COVID-19 mRNA vaccination, and that this correlated with markers of immune-mediated suppression of HIV-transcribing cells. That study however did not investigate HIV viremia, nor did it detect significant reservoir size changes in the 13 participants assessed. We investigated changes in HIV viremia and reservoir size following COVID-19 mRNA vaccination in 62 ART-treated PWH. Method(s): Participants (55 male;7 female) were sampled pre-vaccination, and one month after the first and second doses. Plasma HIV loads (pVL) were measured using the Cobas 6800 (LLOQ 20 copies/mL). Intact and total HIV copies/million CD4+ T cells were measured using the Intact Proviral DNA Assay. Anti-SARS-CoV-2 S serum antibody concentrations were measured using the Roche Elecsys Anti-S assay. Result(s): Pre-vaccination, 82% of participants had pVL < 20 copies/mL (max 110 copies/mL). No significant changes in pVL were observed post-vaccination (all p >0.4): one month post-first and second doses, 79% and 85% of participants had pVL < 20 copies/mL (max 183 and 79 copies/mL), respectively. Pre-vaccination, the median intact reservoir size was 80 (IQR:28-197;n=46) HIV copies/million CD4+ T cells. Intact reservoir size did not change significantly post-vaccination (all p >0.2): one month post-first and second doses, medians were 85 (IQR: 29-184;n=46) and 65 (IQR:22-168;n=29) copies/million CD4+ T cells, respectively. No significant changes in total, nor 5' and 3' defective proviral burdens were observed post-vaccination (all p >0.1), nor were any significant changes observed in any outcome upon stratification by sex, COVID-19 vaccine regimen, or ART regimen (here, multiple tests were addressed using q-values). Finally, no correlations were observed between the SARS-CoV-2 anti-S antibody response magnitude, and either the magnitude of change in reservoir size, nor the observation of detectable viremia, following the first and second vaccine doses (all p >0.2). Conclusion(s): Despite evidence that COVID-19 mRNA vaccination may induce HIV-specific immune responses, we observed no measurable changes in reservoir size nor lasting plasma viremia following COVID-19 mRNA immunization, regardless of anti-SARS-CoV-2 antibody response magnitude. (Figure Presented).

COVID-19 and androgenic status: testosterone or dihydrotestosterone have a pivotal role?

The aim of our study is analysis of the androgenic status including testosterone (T) and dihydrotestosterone (DHT) in men hospitalized with coronavirus disease 2019 (COVID-19) and them relationship with the course of the disease. This is a monocentric prospective study performed on 125 male patients hospitalized for COVID-19. We conducted hematological examination, blood biochemical profile, hemostasis analysis and hormonal examination (T and DHT levels) lung and chest computed tomography and also assessed outcomes of hospitalization. Low DHT serum level was found only in 18 patients (14.4%). Subjects with low DHT were significantly older compare to subjects with normal DHT. At the same time in patients with normal DHT white blood cells (WBC) count, neutrophils at admission were higher than in patients with low DHT. No correlation was observed between T and DHT serum blood levels. C-reactive protein (CRP) has a weak positive correlation of DHT serum blood concentration (r = 0.22;p = 0.016). The inverse pattern was obtained for T serum blood concentration (r = -0.285;p = 0.001). After divided all males according to T concentrations we conducted next correlation analysis for DHT and CRP in two different groups: with normal T levels and with low T levels. We found that in males with normal T DHT levels are not correlated with CRP (r = 0.095;p = 0.462). However, in males with low T DHT and CRP had weak positive correlation with r = 0.317 (p = 0.012). Higher DHT concentrations are associated with higher CRP levels, however correlation is weak and in patients with normal T is absent, that may indicate anti-inflammatory effect of T and possible proinflammatory effect of DHT.Copyright © 2023 The Author(s).

Anti-SARS-CoV-2 antibody responses in convalescent plasma donors with varying clinical manifestation severity of COVID-19

Background/Aim. Plasma containing a high titer of anti-SARS-CoV-2 antibodies, donated from individuals who re-covered from COVID-19, has the potential to be used as initial therapy for patients who have been infected (passive immunization). It is a challenge to find suitable donors. The aim of the study was to successively monitor antibody titer in donations and to investigate the correlation between an-tibody titer and the severity of the clinical manifestations. Methods. The retrospective study was conducted from May 1 to October 31, 2020, at the Blood Transfusion Insti-tute of Vojvodina. Donors had to meet certain criteria for inclusion in the study: proven SARS-CoV-2 infection, de-tected SARS-CoV-2 antibodies in the serum/plasma, ful-fillment of general criteria for performing plasmapheresis, and adequate laboratory findings. Results. During the study, 651 apheresis plasma units were collected and divided into two equal doses. Plasma was donated by 311 COVID-19 convalescents, including 208 (66.9%) men and 103 (33.1%) women. There were 15 (4.8%) plasma donors with asymptomatic infection, 235 (75. 6%) with a mild form of illness, 45 (14.5%) with a moderate form of illness, 16 (5.1%) with a severe form of illness, and none with a critical form of illness. Anti-SARS-CoV-2 IgG antibodies were pre-sent in the plasma of donors for more than 6 months after the disease. Plasma donors with a more severe clinical mani-festation of COVID-19 had stable antibody levels for a longer period. However, the Pearson correlation of clinical severity and antibody titer did not confirm a statistically sig-nificant correlation between the variables. Conclusion. An-ti-SARS-CoV-2 antibodies were present in the sample of re-covered patients, plasma donors, for more than 6 months after the disease. Even though no statistically significant correlation was found between the anti-SARS-CoV-2 anti-body titer and the clinical severity of COVID-19, in patients with a more severe clinical manifestations of the disease, stable antibody levels were maintained for a longer period.Copyright © 2022 Inst. Sci. inf., Univ. Defence in Belgrade. All rights reserved.

Seroprevalence of SARS-CoV-2 (COVID-19) antibodies in tertiary care hospital of Karachi, Pakistan

Objective: To find the trend of seropositivity of antiSARS-CoV-2 antibodies in registered patients for COVID-19 in Dow Diagnostic Reference and Research laboratory Methodology: A total of 5247 patients were enrolled for SARS CoV2 antibodies analysis from 01 August to 31 December, 2020. Patient consent was attained and questionnaire forms were filled. Samples were tested for anti-SARS-CoV-2 antibodies on (Roche Cobase 601). Result(s): In 5247 patient's samples, seropositivity of SARS CoV2 was found in 2425 (46.2%) samples. Seroprevalence in males was 28.4% (n;1491) as compared to females, who showed 17% (n;934). The age group G3 (> 46 to 60 years) showed higher seropositivity (n = 604/1118, 54%) as related to other age groups. Out of total reactive patients, only 30% (n;727) reported recent symptoms while 70% (n;1697) were asymptomatic. Fever was observed to be the most common symptom followed by dry cough. The most commonly affected areas were East 2353 (44%), South 855 (16.01%), Malir 793 (14.85%), Center zone 589 (11.03%) and Korangi area 378 (7.08%). The frequency of seropositivity showed an increasing pattern in the six months from August 2020 to December 2020. It was found to be 11.5% in August, 13.6% in September, 13.9% in October, and 42.5% in December 2020. Conclusion(s): The trend of seropositivity revealed a gradual upward course in the duration of study period. Nearly, two thirds of the patients were asymptomatic indicating the fact that many individuals were silently exposed to the infection and developed antibodies through their natural defense mechanism.Copyright © 2023, Pakistan Medical Association. All rights reserved.

Pre-Endoscopic viral screening of children during the Covid-19 pandemic

Aim: Transmission of SARS-CoV-2 infection can easily occur through direct or close contact with infected people, just as with other infectious diseases. Therefore, it is important to detect it prior to the intervention for protecting the health of both the healthcare worker and the patient. In the study, it was aimed to determine the seropositivity rates of acute respiratory syndrome coronavirus 2, hepatitis A, hepatitis B, hepatitis C virus and human immune deficiency virus infections among children who underwent gastrointestinal endoscopy. Material(s) and Method(s): The study was conducted at the Department of Pediatric Gastroenterology of the Karabuk University in Turkey from December 2020 to December of 2021. A total of 175 children were included in the study. The study was divided into three age groups as follows: 1-6 years old, 7-12 years old and 13-18 years old. All children were screened for acute respiratory syndrome coronavirus 2, hepatitis A, hepatitis B, hepatitis C virus and human immune deficiency virus infections. Result(s): The median age was 12.5 years (1-18). The seroprevalence of acute respiratory syndrome coronavirus 2, Anti-HAV IgM, Anti-HAV IgG, HBsAg, Anti-HBs, Anti-HCV, Anti-HIV and were detected 0.57%, 0.57%, 42.8%, 0%, 58.8%, 1.1% and 0 % respectively. The seroprevalence of Anti-HAV IgG was significantly higher in children aged 1-6 years than in the group aged 13-18 years (95.7 vs 25.2: chi2=48.1, p=0.001). Discussion(s): Although seroprevalence rates prior to endoscopy were low in this study, viral screening, except for hepatitis A infection, is essential for the safety of both patients and healthcare.Copyright © 2022, Derman Medical Publishing. All rights reserved.

Seroprevalence of COVID-19 among out patients with chronic respiratory disease in a tertiary care hospital in India

Background: Unexpectedly, COVID-19 was less prevalent in Chronic Respiratory Disease(CRD) than in the general population (Gupta N et al. Lung India. 2021;38(5):454-9). The vaccine and infection-related immune status of CRD patients is unknown. Aims and Objectives: Our primary objective was to study the cross sectional seroprevalence among chronic respiratory disease patients attending the Pulmonary medicine outpatients service and comparing it with the national seroprevalence data. Method(s): Consecutive subjects with CRD were recruited. History of past COVID 19 infection and other relevant information was obtained. Blood sample was taken for Roche Elecsys SARS-CoV-2 assay to detect anti-N and anti-S antibodies. Result(s): We recruited 364 patients(Asthma & COPD-100 each, Bronchiectasis, ILD & PTB-sequelae- 50 each and other restrictive diseases-14). The overall seroprevalence in CRD(Anti-S) was 85.16%, which was significantly higher than the 4th national serosurvey seroprevalence of 67.60%(p=0.001) (ICMR, Ministry of Health and Family Welfare;2021). Asthma had the highest seroprevalence, which was higher than COPD [93% vs 78%, p=0.027] and bronchiectasis [93% vs 80%, p=0.018]. Seroprevalence dropped with increasing age: <40 yrs: 93%, 41-60 yrs: 87% and >= 61 yrs: 77% (p=0.004). Patients on inhaled-steroids had higher seroprevalence than those without (89% vs 80%;p=0.026) and those on inhaled-anticholinergics (89% VS 79%;p=0.013). Conclusion(s): COVID-19 seroprevalence is higher in CRD than in the general population. Asthmatics had the highest prevalence and the seroprevalence dropped with increasing age.

Humoral immune responses to SARS-CoV-2 vaccines in an ozanimod open-label extension study

Background: Ozanimod, an oral sphingosine 1-phosphate receptor modulator, is approved in the European Union and United States for the treatment of moderately to severely active ulcerative colitis (UC) and relapsing multiple sclerosis (RMS). A previous analysis of data from UC and multiple sclerosis (MS) open-label extension (OLE) studies showed that most patients with confirmed coronavirus infection (COVID-19) had nonserious infections, recovered, and did not require ozanimod discontinuation. Some immunomodulators and biologics may attenuate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine response;therefore, this analysis evaluated humoral immune responses and predictors of response to SARS-CoV-2 vaccination in patients with RMS treated with ozanimod. Method(s): RMS participants who completed a phase 1-3 ozanimod trial could enter an OLE trial (DAYBREAK;NCT02576717) of ozanimod 0.92 mg/d. This analysis (January 2020-October 2021) included DAYBREAK participants receiving mRNA or non-mRNA SARS-CoV-2 vaccines (1-2 doses, vaccine-dependent) with no evidence of recent infection (ie, nucleocapsid antibody negative). Receptor binding domain (RBD) antibody titers were analysed (Elecsys Anti-SARS-CoV-2 assay;Roche Diagnostics, Basel, Switzerland) prevaccination, after 1 dose, and <4, 4-8, 8-12, and >12 weeks after full vaccination. Fisher's exact tests and regression models determined association with seroconversion and log2 antibody levels. Result(s): Demographics were similar between the mRNA and nonmRNA vaccine recipients (Table). Seroconversion (>=0.8 U/mL spike RBD antibody) occurred in 100% (80/80) of fully vaccinated mRNA recipients and 62% (18/29) of fully vaccinated non-mRNA vaccine recipients. Higher spike RBD antibody levels were seen with mRNA (grand mean: 512.6 U/mL, range: 1.3-4572.0) vs non-mRNA (grand mean: 39.3 U/mL, range: 0.4-368.5) vaccines at all time points studied. Vaccination with a non-mRNA vaccine predicted lower antibody levels (beta: -5.90 [95% CI: -6.99 to -4.82];P<0.0001) and less seroconversion (Fisher's exact: P<0.0001), whereas age, sex, body mass index, and absolute lymphocyte count (ALC) did not. Conclusion(s): Participants receiving ozanimod developed humoral immune response to SARS-CoV-2 vaccines, with 100% seroconversion after mRNA vaccination;this was independent of demographic characteristics and ALC levels at time of vaccination. However, some participants developed lower antibody concentrations and may benefit from booster doses. These findings provide important information for physicians managing ozanimod-treated patients with UC or MS.

High seroprevalence of anti-SARS-CoV-2 antibodies in the capital of Chad

Background. Since the start of the COVID-19 pandemic, Chad has had 7,417 confirmed cases and 193 deaths, one of the lowest in Africa. Objective. This study assessed SARS-CoV-2 immunity in N'Djamena. Methods. In August-October 2021, eleven N'Djamena hospitals col-lected outpatient data and samples. IgG antibodies against SARS-CoV-2 nucleocapsid protein were identified using ELISA. "Bambino Gesu" Laboratory, Rome, Italy, performed external quality control with chemiluminescence assay. Results. 25-34-year-old (35.2%) made up the largest age group at 31.9+/-12.6 years. 56.4% were women, 1.3 women/men. The 7th district had 22.5% and the 1st 22.3%. Housewives and students dominated. Overall seroprevalence was 69.5% (95% CI: 67.7-71.3), females 68.2% (65.8-70.5) and males 71.2% (68.6-73.8). >44-year-old had 73.9% seroprevalence. Under-15s were 57.4% positive. Housewives (70.9%), civil servants (71.5%), and health workers (9.7%) had the highest antibody positivity. N'Djamena's 9th district had 73.1% optimism and the 3rd district had 52.5%. Seroprevalences were highest at Good Samaritan Hospital (75.4%) and National General Referral Hospital (74.7%). Conclusion. Our findings indicate a high circulation of SARS-CoV-2 in N'Djamena, despite low mortality and morbidity after the first two COVID-19 pandemic waves. This high seroprevalence must be considered in Chad's vaccine policy.Copyright © 2022 The Authors and PAGEPRESS PUBLICATIONS.

Prognostic value of the SII Systemic Immune-Inflammation Index a novel biomarker in coronavirus disease 2019 patient's disease progression to fatality

Objective: To identify a novel biomarker with high prognostic value SII Systemic Immune-Inflammation Index in the disease progression of COVID-19 patients with its cost effectiveness and less time consuming. Methodology: This cross-sectional study was carried out from November 2021 to February 2022 at the Mardan Medical Complex, Khyber Pakhtunkhwah, Pakistan. The receiver operating characteristic (ROC) curve analysis was used to discover the ideal cut-off values for predictors for disease severity stage, i.e. asymptomatic, mild, moderate, severe, critical, based on their greatest Youden's index. The SII (platelet X neutrophil count/lymphocyte counts) formula was used to compute the systemic immune inflammation index. Result(s): Of the 311 cases studied, 233 were included;155 (66.52%) were male and 78 (33.47%) females. Median age was 38 years (IQR: 18 - 79). Patients had a significant increase in various blood parameters, with an increase in SII index between admission and hospitalization. Normal patients had a SII median 398 (IQR: 312 - 567) upon admission, while abnormal patients had a SII median 659 (IQR: 475 - 1540). Throughout hospitalization, SII index of asymptomatic patients median was 684 (IQR: 470 - 933);cut-off value >= 358, mild patients median 909 (IQR: 183 - 1930);cut-off value >= 501, moderate patients median >= 992 (IQR: 248 - 6099);cut-off value >= 903, severe patients median 1063 (IQR: 104 - 5014);cut-off value >= 1147, critical patients median 1230 (IQR: 100 - 8438);cut-off value >= 1481. Conclusion(s): SII was found to be a significant predictor of COVID-19 patients' severity progression to fatality as an independent prognostic factor. SII is being recommended as a low-cost and less time-consuming blood test for COVID-19 patients.Copyright © 2023, Pakistan Medical Association. All rights reserved.

The Gender Difference and Correlations of Neutrophil-to-Lymphocyte Ratio and D-Dimer among Hospitalized Patients with Covid-19 in North Macedonia

Introduction: Coronavirus disease has had a catastrophic effect on the world's demographics, resulting in more than 5.8 million deaths worldwide and more than 422 million confirmed cases reported globally. The aim of this study was to assess the utility of the neutrophil-lymphocyte ratio (NLR), a simple, widely available, and inexpensive laboratory examination, as a reliable inflammatory biomarker for COVID-19 patients. By comparing the NLR with the D-dimer plasma level, we also want to analyze gender differences between hematological and hemostatic parameters in patients with COVID-19. Method(s): This study was carried in 2021 in Public Health Organization Clinical Hospital "Dr. Trifun Panovski" in Bitola in 2021. Our study describes the laboratory characteristics of 40 COVID-19 patients hospitalized in the Department of Infective Diseases. Result(s): The overall mean count of white blood cells count was 9 +/- 0.28 x 109. The overall mean of NLR was 9.3 +/- 5.6. The overall mean of CRP and D-dimer was 58.7 +/- 41.22 mg/l and 5624 +/- 1944 FEU ng/ml, respectively. NLR, CRP and D-dimer in the male and female groups in patients with COVID-19 did not show statistically significant differences. We confirmed a significant correlation between NLR and D-dimer levels in patients with COVID-19. Conclusion(s): NLR was found to correlate well with the established inflammatory marker CRP and coagulation marker D-Dimer, which is capable of predicting severe COVID-19. Therefore, NLR that is easily calculated at the emergency department using routine laboratory tests, even in a remote area, may serve as a practical and cost-effective marker for guiding the physician in awareness regarding the need for intensive care.Copyright © 2022, Central Medical Library Medical University - Sofia. All rights reserved.

Omicron SARS-CoV-2 variant outbreak in vaccinated liver transplant (LT) recipients in 2022: A large spread of infection, a mild disease

Background: From January 2022 the Omicron SARS-CoV-2 variant became the dominant circulating variant worldwide, showing increased transmissibility and the ability to evade immunity. Booster vaccinations improved the protective effects of neutralizing antibodies and might have lowered the risk of hospitalization and mortality, as recently observed. Aim: to evaluate the prevalence and outcome of Omicron-related infection in a cohort of liver transplant (LT) recipients. Material and Methods: From January to September 2022, we enrolled in a longitudinal study all LT recipients who became SARS-CoV-2 infected (95% vaccinated;88% receiving a 1st booster dose and 25% a 2nd booster). All patients were included in a protocol of testing anti-spike (a-S) and anti-nucleocapsid (a-N) antibodies titres before/after each dose (Elecsys Anti-SARS-CoV-2, Roche Diagnostic). Diagnostic criteria for SARS-CoV-2 infection were 1) presence of a positive nasopharyngeal swab (NFS) by PCR or antigenic assays or 2) presence of a-N seroconversion (if previously a-N negative). Reinfection was defined by a new NFS positivity or an increased value of a-N titre. Results: Overall, 201 LT-recipients have been infected by SARS-CoV-2 (62% males, median age=61yr, 50% viral-etiology, 35% with HCC, all received a CNI-based regimen, plus MMF=63%). Most of infections were diagnosed by NFS (72%);mild flu-like symptoms were observed in 59% of our LT recipients;72% of them remained untreated, while 28% received antivirals (11%) or monoclonal antibodies (17%). Fifteen LT recipients were hospitalized, 6 of them for interstitial pneumonia and 2 (both with previous lung diseases) died for COVID-19. Conclusions: A mild or asymptomatic infection occurred frequently in our LT recipients with a less severe outcome than the past waves. A possible explanation could be the high prevalence of vaccinated patients in our cohort. Interestingly, the overall prevalence of SARS Cov2 infection might be underestimated without a careful monitoring of SARS-CoV-2 serology against nucleocapsid.

Could tear be an alternative specimen for SARS-CoV-2 detection?

Objectives: For a definitive diagnosis of COVID-19, respiratory tract samples are evaluated by polymerase chain reaction (PCR). In our study, PCR using a tear sample was used to diagnose COVID-19, and it was questioned whether it was a screening method. Unlike the general practice, Schirmer strips were used instead of a swab for tear sample collection in this study. In addition, the diagnostic values of serum procalcitonin (PCT), C-reactive protein (CRP), and Neutrophil (NEU) count in predicting COVID-19 disease from tears were also questioned. Method(s): A total of 94 patients who were positive for COVID-19 by PCR test were included in this study. Tear samples were obtained from patients with Schirmer strips, commonly used in eye examination, and studied with the PCR technique. CRP, PCT value, and NEU count were also compared between the positive and negative groups of the PCR. The obtained data were analyzed using the R Studio software, and the results were considered statistically significant for p<0.05. Result(s): Of these patients, 61 (64.9%) tear PCR was negative, and 33 (35.1%) tear PCR was positive. The mean age was 61.72 +/- 17.62 years. The patients were divided into two groups: tear PCR positive and negative. There was no significant age difference between these groups. As a result of ROC Analysis;When serum PCT, CRP, and NEU % values were examined in predicting COVID-19 disease from tears, it was seen that CRP (p=0.027) and especially PCT (p=0.003) values of patients with PCR-positive were significantly higher. Conclusion(s): PCR study on tears collected with Schirmer strips is a different and non-invasive method, but it was concluded that the proposed method could not be used as a screening test. In addition, significantly higher serum PCT values were found in patients with COVID-19 positivity in tears (p<0.05). Copyright © 2022 the author(s), published by De Gruyter.

The relationship between plasminogen activator inhibitor-1 levels and the course of disease in COVID-19 patients

Objectives: Studies have shown that fibrinolysis activity is insufficient in COVID-19 patients. Plasminogen activator inhibitor-1 (PAI-1) is an important antifibrinolytic molecule that plays a key role in the fibrinolytic system. In our study;we aimed to evaluate serum PAI-1 and other biochemical parameters of COVID-19 patients in terms of disease course and mortality. Method(s): A total of 40 COVID-19 patients were hospitalized in the service and intensive care unit (ICU) of our hospital from October to December 2020 and 20 healthy volunteers were included in our study. The patients were grouped as those who transferred to the ICU from the service and transferred to service from the ICU. The first and second values of the same patients in both the service and the ICU were analyzed by SPSS. Result(s): The PAI-1 levels of the patients in the ICU were significantly higher than the levels of the same patients in the service and the healthy control group (p<0.001). IL-6, ferritin, and D-dimer levels in the ICU of the same patients were significantly higher than the levels of service and healthy control group (p<0.001). A positive correlation was found between initial serum PAI-1 and D-dimer levels in patients hospitalized in the service (p=0.039) and initial serum ferritin and IL-6 levels in the ICU (p=0.031). Conclusion(s): In our study, we found that PAI-1 levels increased significantly with the increase in mortality in COVID-19 patients. Copyright © 2022 the author(s), published by De Gruyter.