[Сardiac arrhythmias in people who have had a coronavirus infection COVID-19: A review].

Heart rhythm disorders are one of the most common complications of coronavirus infection. Heart rhythm disorders can develop in 6-17% of hospitalized patients, and in convalescents, COVID-19 can manifest itself up to 12 months after the completion of the acute phase of the disease. Among the mechanisms for the development of cardiac arrhythmias, there are a direct cytopathic effect of SARS-CoV-2 on the myocardium, systemic inflammatory response syndrome, electrolyte imbalance, hypoxia, the use of antibacterial, antimalarial and antiviral drugs, exudative pericarditis, autonomic dysfunction. The main COVID-19-mediated heart rhythm disorders are sinus tachycardia and bradycardia, atrial fibrillation, ventricular tachycardia, long QT syndrome. Despite a significant amount of research, the literature data on the prevalence of certain types of cardiac arrhythmias (especially in COVID-19 convalescents), as well as methods for their correction, are somewhat contradictory and need to be clarified. Taking into account the impact of arrhythmia on the quality of life and mortality, active monitoring of convalescents of coronavirus infection, identification and development of approaches to the treatment of heart rhythm disorders in patients who have had COVID-19, seem to be relevant and promising areas in modern cardiology.

Serodiagnosis of Borrelia miyamotoi disease by measuring antibodies against GlpQ and variable major proteins.

OBJECTIVES: Borrelia miyamotoi disease (BMD) is an emerging tick-borne disease in the Northern hemisphere. Serodiagnosis by measuring antibodies against glycerophosphodiester-phosphodiesterase (GlpQ) has been performed experimentally but has not been extensively clinically validated. Because we had previously shown the differential expression of antigenic variable major proteins (Vmps) in B. miyamotoi, our aim was to study antibody responses against GlpQ and Vmps in PCR-proven BMD patients and controls. METHODS: We assessed seroreactivity against GlpQ and four Vmps in a well-described, longitudinal cohort of sera from BMD patients (n=182), healthy blood donors (n=136) and controls (n=68). All samples were tested by ELISA and positive sera were tested by western blot, and antibody dynamics and diagnostic value were assessed. RESULTS: IgM antibodies against GlpQ and Vmps peaked between 11 and 20 days, and IgG between 21 and 50 days, after disease onset. Various combinations of GlpQ and Vmps increased sensitivity and/or specificity compared to single antigens. Notably, the GlpQ or variable large protein (Vlp)-15/16 combination yielded a sensitivity of 94.7% (95% CI: 75.4-99.7) 11-20 days after disease onset and a specificity of 96.6% (92.7-98.4) for IgM. A specificity of 100% (97.8-100) for IgM, and 98.3% for IgG (95.2-100), was found when positivity was defined as reactivity to GlpQ and any Vmp, with maximum sensitivities of 79% (56.7-91.5) for IgM and 86.7% (62.1-97.6) for IgG. CONCLUSIONS: We clearly demonstrate here the diagnostic potential of these seromarkers. Our findings will facilitate future epidemiological and clinical studies on BMD and lead to the development of a serologic test to be used in clinical practice.

Development and optimization of an in vitro cultivation protocol allows for isolation of Borrelia miyamotoi from patients with hard tick-borne relapsing fever.

OBJECTIVES: Borrelia miyamotoi has been shown to infect humans in Eurasia and North America causing hard tick-borne relapsing fever (HTBRF). In vitro cultivation of B. miyamotoi was described recently; but clinical isolation of relapsing fever Borrelia is cumbersome. Our aim was to develop a straightforward protocol enabling B. miyamotoi isolation directly from the blood of patients. METHODS: Modified Kelly-Pettenkorfer (MKP-F) medium, with or without anticoagulants, or blood from healthy human volunteers, was spiked with B. miyamotoi spirochaetes in vitro. Subsequently, either media or plasma was used for cultivation directly, or after an additional centrifugation step. This isolation protocol was tested in a clinical setting on patients suspected of HTBRF. RESULTS: Dipotassium-EDTA, trisodium citrate and lithium heparin inhibited growth of B. miyamotoi at concentrations ≥250 µg/mL, 2.5 mM and 1 IU/mL, respectively. However, when plasma originating from human blood containing B. miyamotoi spirochaetes was subjected to an additional centrifugation step at 8000 g, suspended and inoculated into fresh MKP-F media, positive cultures were observed within 2 weeks. Of importance, this straightforward protocol allowed for isolation of B. miyamotoi from six out of nine patients with confirmed HTBRF. CONCLUSIONS: Direct culture from K2-EDTA, trisodium citrate and lithium heparin plasma containing B. miyamotoi is hampered due to anticoagulants. Using a simple centrifugation protocol we were able to circumvent this detrimental effect, allowing for the first clinical isolation of B. miyamotoi. This will be of value for future research on the pathogenesis, genetics, diagnosis, therapy and epidemiology of HTBRF and other tick-borne relapsing fevers.

[Follow-up of patients with Ixodes tick-borne borrelioses caused by Borrelia miyamotoi or Borrelia burgdorferi sensu lato]. / Katamnez bol'nykh iksodovymi kleshchevymi borreliozami, vyzvannymi Borrelia miyamotoi ili Borrelia burgdorferi sensu lato.

Ixodes tick-borne borrelioses (ITBB) are caused by two different spirochetes: Borrelia from the group of Borrelia burgdorferi sensu lato, the agents of the classic Lyme borreliosis (LB), and Borrelia miyamotoi that belongs to the group of Borrelia causing tick-borne relapsing fevers. ITBB caused by B. miyamotoi (BM-ITBB) is a previously unknown infectious disease discovered in Russia. It is known that the LB sequelae may reduce the long-term life guality of convalescents. AIM: To study the follow-up of those who have recovered from new BM-ITBB infection in comparison with persons who have had LB. SUBJECTS AND METHODS: The investigation enrolled 41 patients with BM-ITBB and 41 patients with LB who were treated at the Republican Infectious Diseases Hospital of Udmurtia. Within a year after the disease, they were followed up through clinical and instrumental examination of cardiac performance, expanded biochemical analysis of blood and urine, which could; estimate kidney and liver functions, and psychological questioning. RESULTS: Asthenic syndrome and complaints about and objective signs of cardiac dysfunctions persisted supraventricular extrasystoles, left ventricular diastolic dysfunction, and elevated and/or unstable systolic blood pressure were detected in 20-30% of the convalescents for a long time. Kidney dysfunctions were manifested in albuminuria and the decrease of glomerular filtration rate. A year following the disease, 10-20% patients had persistently elevated concentrations of alanine aminotransferase, aspartate aminotransferase, and C-reactive protein and had higher levels of total cholesterol and low-density lipoproteins. The pathological consequences of ITBB were polymorphic and varied in different patients; in general, only 68% of them showed health improvement. CONCLUSION: We assume that a significant role in the pathogenesis of BM-ITBB and LB is played by vascular endothelial damage possibly associated with the inflammatory and autoimmune aspects of an immune response in Borrelia infection. The consequences of this damage may persist and even intensify during a year, which provokes chronic dysfunction of the heart, kidney, or liver in a number of convalescents.

[Relapsing (recurrent) disease caused by Borrelia miyamotoi].

AIM: To clarify the clinical, laboratory, and epidemiological characteristics of relapsing Ixodes tick-borne borreliosis (ITB) caused by Borrelia miyamotoi. SUBJECTS AND METHODS: Retrospective clinical observation was made in 79 inpatients of the Republican Infectious Diseases Hospital (Udmurt Republic), who had been diagnosed with B. miyamotoi-caused disease verified by real-time polymerase chain reaction. The latter and enzyme immunoassay ruled out possible vector-borne coinfections (ITB caused by B. burgdorferi sensu lato; tick-borne encephalitis; anaplasmosis; and ehrlichiosis). RESULTS: The recurrent course of the disease was observed in 8 (10%) of the 79 patients. The relapsing fever curve was noted in 6 of the 8 patients; 4 patients had 2 episodes of fever and 2 patients had 3 episodes; the wave-like continuous type of fever cannot enable one to estimate the specific number of episodes in 2 more cases. Relapses occurred in all the 8 patients before antibiotic treatment. Febrile syndrome (weakness, headache, chill, fever, sweating, dizziness, nausea, vomiting, myalgia, and arthralgia) was leading in patients with relapses. These patients were less frequently observed to have signs of organ dysfunctions than those with one episode of fever. The values of clinical and biochemical blood tests and urinalyses were normal and near-normal in the majority of patients on hospital admission. CONCLUSION: Relapsing B. miyamotoi infection cases detected in the directed study proved to be unrecognized by practical health authorities during the first and sometimes second episodes of fever. This indicates that the prevalence of this disease is essentially underestimated and there is a need to increase physicians' alertness and awareness and to introduce adequate diagnostic methods.

[The blood coagulation system and microcirculatory disorders in ixodid tick-borne borreliosis caused by Borrelia miyamotoi].

AIM: To study blood coagulation and microcirculatory disorders as a possible cause of transient dysfunctions of organs (the kidney, liver, heart, lung, etc.) in patients with ixodid tick-borne borreliosis caused by Borrelia miyamotoi (Bmt). SUBJECTS AND METHODS; Twenty-four patients with Lyme disease (LD) and 28 Bmt patients treated at Izhevsk City Hospital (Udmurtia) were examined in the study. Platelet counts and the presence of D-dimers were determined; activated partial thromboplastin time, prothrombin time, thrombin time, fibrinogen and antithrombin III levels, and Factor XIIa-dependent fibrin clot lysis time were measured. Slit lamp microscopy of the conjunctiva was. also carried out. Results. Platelet counts'were less than 150,000 per pL of blood in 43% of the Bmt patients. All the Bmt patients had at least one abnormal coagulation parameter of the eight ones that were tested; 64% of them had marked coagulation disorders with three or more abnormal laboratory findings. In contrast, all the eight parameters were normal in 71% of the LD patients. The other seven LD patients had only one or two abnormal coagulation parameters (p < 0.001 in comparison with Bmt patients). Microscopic examination of eye capillary blood flow revealed pathological findings that included aggregates of erythrocytes and obstructed and/or sinuous capillaries in 22 (79%) of the Bmt patients, but none of the LD patients. A total of 14 Bmt patients had both coagulation and microcirculatory abnormalities. Eleven of them also had transient signs of organ dysfunction. CONCLUSION: As far as Borrelia secrete no known toxins, we hypothesized that uncovered disorders of blood coagulation and microcirculation in Bmt patients may contribute to organ dysfunction.

[Clinical presentation of "new" tick-borne borreliosis caused by Borrelia miyamotoi].

AIM: The objective of this study was to confirm the role of B. miyamotoi in the etiology of ITBB-WOEM in Udmurtia and to investigate in detail the clinical presentation of this "new" disease. MATERIALS AND METHODS: 50 adult patients with ITBB-WOEM treated in Republic Hospital for Infectious Diseases, Udmurtia, in 2010-2011 had PCR-confirmed infection by B. miyamotoi. The laboratory evidence of co-infection by other pathogens, including tick-borne encephalitis virus, B. burgdorferi sensu lato, A. phagocytophilum, E. chaffeensis, and E. muris, were absent. RESULTS: All patients had a tick bite from 10 to 18 days before the acute disease onset. The main clinical signs were high fever, fatigue, headache, chill, and sweat. Clinical, biochemical, and instrumental investigations also showed the signs of functional impairment of various organs: the liver (in about half of the patients), kidney (in 10 patients), heart (6 patients), etc. In contrast, acute ITBB with erythema migrans was usually a localized infection without a pronounced intoxication syndrome and impairments of the organs. CONCLUSION: ITBB-WOEM caused by B. miyamotoi is a systemic disease that is clinically closer to relapsing fevers transmitted by argasid ticks than to Lyme borreliosis. The number of B. miyamotoi infections in Russia may be comparable with that of Lyme disease cases, so the investigations of epidemiology, clinical presentation and therapy of this "new" disease are urgently requested.