COVID-19 epidemiology and performance of the WHO clinical algorithm to diagnose COVID-19 in people with HIV from Ukraine.

BACKGROUND: The two main objectives were to evaluate the COVID-19 point prevalence and the test performance of the WHO case definition to diagnose COVID-19 clinically in people with HIV in West Ukraine. METHODS: Multicenter cross-sectional study in Lviv, Ukraine, from October 2020-November 2021. COVID-19 unvaccinated people with HIV were included regardless of COVID-19 symptoms at routine clinical visits and had standardized medical, quality of life (EQ(5D)) and SARS-CoV-2 serology assessments. Reported symptoms indicating potential COVID-19 events at inclusion or between March 2020 and inclusion were classified by the WHO case definition as suspected, probable or confirmed. A clinical COVID-19 case was defined as being SARS-CoV-2 seropositive with at least a suspected COVID-19 according to the WHO case definition. The primary endpoints were the clinical COVID-19 prevalence and the test characteristics of the WHO case definition with SARS-CoV-2 serology as reference. (Clinicaltrials.gov:NCT04711954). RESULTS: The 971 included people with HIV were median 40 years, 38.8% women, 44.8% had prior AIDS, and 55.6% had comorbidities. SARS-CoV-2 seroprevalence was 40.1% (95%CI:37.0-43.1) and 20.5% (95%CI:18.0-23.1) had clinical COVID-19 median 4 months (IQR:2-7) before inclusion. Clinical COVID-19 occurred less frequently in people with HIV with tuberculosis history, injecting drug use, CD4+ T-cells <200/mL and unemployment. The quality of life was not impacted after COVID-19. An at least probable COVID-19 classification by the WHO case definition had 44.1% sensitivity (95%CI:38.7-49.7), 85.2% specificity (95%CI:81.5-88.4), 66.6% positive predictive value (95%CI:59.8-73.0) and 69.5% negative predictive value (95%CI:65.5-73.3) to diagnose COVID-19. CONCLUSIONS: COVID-19 unvaccinated people with HIV from Ukraine had a significant COVID-19 rate and using the WHO case definition had insufficient diagnostic accuracy to diagnose these cases. The lower burden in vulnerable people with HIV was unexpected but might reflect a shielding effect.

Development of a Model for Preliminary Diagnosis of Human Granulocytic Anaplasmosis.

Background: Human granulocytic anaplasmosis (HGA) is a vector-borne natural focal disease that is not officially registered in Ukraine. The first 13 cases of HGA in adults in Ukraine were identified in 2007. The purpose of our study was to develop a predictive model of HGA based on clinical and laboratory characteristics to develop a three-level standard case definition of HGA. Materials and Methods: Researchers examined 498 patients with suspected tick-borne infections and carried out a retrospective clinical and epidemiological analysis of 60 cases recruited from Lviv regional infectious disease hospitals. Logistic regression was used to create a model of the probability of the diagnosis of HGA depending on the presence of certain clinical and laboratory factors that, when examined, together may help to confirm a case of HGA. For logistic regression, eight clinical and laboratory factors were selected: history of tick bite, hyperthermia, signs of pharyngitis, changes in chest X-ray picture (enhancement of the pulmonary pattern and enlargement of the lung root boundaries), increased bilirubin (˃21 µmol/L), increased alanine aminotransferase (ALT ˃36 U/L), erythema migrans, and detected Lyme disease. Results: In the presence of all eight factors, the probability of HGA is 95.7%. When the five main signs are absent-signs of pharyngitis, changes in chest X-ray picture, increased bilirubin and ALT, and a history of tick bite-the probability of HGA in the patient dramatically decreases to 6.8%, meaning that HGA might be excluded. Conclusions: Based on the analysis of epidemiological, clinical, and laboratory signs, criteria for establishing a suspected, probable, and confirmed diagnosis of HGA have been developed to improve diagnosis.

Prospective evaluation of hepatitis C virus antibody detection in whole blood collected on dried blood spots with the INNOTEST® HCV Ab IV enzyme immunoassay.

INTRODUCTION: Dried blood spots (DBS) have potential to improve access to screening for antibodies to hepatitis C virus (HCV). However, although several studies on off-label use of DBS have been performed, to date no HCV antibody serology test is formally approved for use with DBS. This study evaluated the performance of the INNOTEST® HCV Ab IV enzyme immunoassay in paired DBS and plasma samples, to determine whether DBS may be added to the intended use. METHODS: Adults with no history of HCV treatment were prospectively enrolled from two sites in Ukraine. DBS were prepared from fingerstick whole blood (fDBS) and venous whole blood (vDBS) samples. Undiluted and serially diluted DBS and plasma samples were tested. RESULTS: Samples from 149 HCV positive and 151 HCV negative participants were included. Sensitivity and specificity of the INNOTEST® HCV Ab IV assay were both 100 % (95 % confidence intervals 95.7-100) for samples collected on fDBS or vDBS compared with plasma as the reference standard. In all undiluted samples, negative and positive percentage agreement and overall rate of agreement were 100 % between all sample types (Cohen's kappa coefficient of 1). In serially diluted samples, agreement was high (>95 %) between fDBS and vDBS, and as expected, positive percentage agreement between both DBS sample types and plasma was lower (>66 %). CONCLUSIONS: Performance of the INNOTEST® HCV Ab IV assay in DBS was acceptable, thus whole blood collected on DBS may represent an alternative sample type for this assay in settings where venous blood collection is not possible.

Seroprevalence of Old World Hantaviruses and Crimean Congo Hemorrhagic Fever Viruses in Human Populations in Northwestern Ukraine.

In Ukraine, a retrospective review of clinical case reports by public health officials suggest that human cases of febrile illnesses associated with hemorrhage may be due to infections of Crimean-Congo hemorrhagic fever virus (CCHFV) and Old World hantaviruses. In a serosurvey of 966 healthy individuals in the Lviv Oblast, Ukraine, bordering Poland, we found that 1.6% showed cross-reactivity to hantaviral antigens by an immunofluorescence assay (IFA) and 1.7% of the study participants had antibodies cross-reactive to CCHFV by enzyme-linked immunosorbent assay (ELISA). Demographic variables and history of exposures obtained through questionnaires were assessed by logistic regression models for association with seroprevalence for both viruses with no significant risk factors found. Analysis of spatial distribution identified two clusters of samples positive for antibodies to both hantaviruses and CCHFV, which, however, were not statistically significant (p > 0.05). In general, the study results suggest that the population of the study area is exposed to hantaviruses and CCHFV. Further surveillance for respective pathogens in Ukraine is warranted and prospective surveillance of febrile patients with unidentified febrile illness.

Prevalence of Anaplasma phagocytophilum in Ixodes ricinus and Dermacentor reticulatus and Coinfection with Borrelia burgdorferi and Tick-Borne Encephalitis Virus in Western Ukraine.

Introduction: Tick-borne encephalitis virus (TBEV) and Borrelia burgdorferi, the causative agent of Lyme disease (LD), are widespread in Western Ukraine. However, relatively little is known about Anaplasma phagocytophilum in this region. This study examined patterns of infection with A. phagocytophilum in two tick vectors compared with the better studied TBEV and B. burgdorferi.Materials: Ticks were collected in three different ecosystems of the Western Ukraine during 2009-2014. Samples were examined for pathogen detection using real-time polymerase chain reaction (PCR), and logistic regression models were developed to assess the significance of different factors. Results: Among the three selected ecological systems of the Western region of Ukraine, 5130 ticks belonging to Ixodes ricinus and Dermacentor reticulatus were collected between 2009 and 2014. They were grouped into 366 pools and were tested by PCR for A. phagocytophilum. A subsample (1620 ticks, 162 pools) of the ticks was concurrently tested by PCR for A. phagocytophilum, B. burgdorferi, and TBEV. Overall, there was no trend in the proportion of positive ticks across years (p > 0.05). However, the prevalence of A. phagocytophilum was higher (27.4%) in I. ricinus than in D. reticulatus (15.9%) (OR = 2.69; 95% CI, 1.52-4.94 (Lower, Upper 95% CI)). Infection was more common in forested habitats (OR = 1.89; 95% CI, 1.07-3.36) and during the later summer-early autumn (3.78; 95% CI, 1.79-8.06). B. burgdorferi was found in 29.3% and 31.9% of I. ricinus and D. reticulatus, respectively; and TBEV was found in 6.3% and 14.5% of I. ricinus and D. reticulatus. Coinfection of A. phagocytophilum and B. burgdorferi occurred more often than chance and was more frequent than any other combination of pathogens (p = 0.031). Conclusions: Our study is the first to explore the potential relationship between the ecosystems, vectors, and the presence of Human Granulocytic Anaplasmosis (HGA) and other tick-borne infections in Western Ukraine. Anaplasma demonstrated a greater prevalence in I. ricinus in the forested area in Western Ukraine. Altogether, HGA, LD, and tick-borne encephalitis (TBE) pathogens are actively circulating in these ecosystems and have the potential to coinfect vectors that might increase the risk of transmitting multiple pathogens to humans during host feeding by individual ticks.