A single-center experience of early administration of tocilizumab and corticosteroids in patients with COVID-19 pneumonia.

BACKGROUND: We investigated the therapeutic response of tocilizumab (TCZ) therapy in patients with coronavirus disease 2019 (COVID-19) pneumonia. METHODS: This observational retrospective study included 205 patients with confirmed COVID-19 pneumonia with SpO2˂93% and a markedly increased level of at least two biomarkers of inflammation. The TCZ was given in combination with corticosteroids. Clinical and laboratory results were analyzed and compared before TCZ therapy and 7 d after. RESULTS: The mean value of C-reactive protein (CRP) was significantly lower (p=0.001) on the seventh day after administration of TCZ compared with before (10.7 and 173.6 mg/L, respectively). Only in 9/205 (4.3%) patients, the CRP level did not decrease during the week-long period, and this was related to disease progression. The mean level of interleukin-6 before TCZ administration was 88±113 pg/mL, while after it was 32.7±21.7 pg/mL (p=0.01). After 7 d of TCZ therapy, almost 50% of patients who needed high-flow oxygen or ventilation support started to receive low-flow oxygen, while 73/205 (35.6%) patients who received low-flow oxygen before TCZ administration did not receive further oxygen support anymore (p=0.001). Although they received TCZ treatment, 38/205 (18.5%) severely sick patients died. CONCLUSIONS: Tocilizumab improves clinical outcomes in hospitalized COVID-19 patients. These advantages were evident independent of the patient's comorbidities and were in addition to the advantages of systemic corticosteroids. In COVID-19 patients at risk of cytokine storms, TCZ appears to be an effective therapy choice.

Antioxidant Genetic Profile Modifies Probability of Developing Neurological Sequelae in Long-COVID.

Understanding the sequelae of COVID-19 is of utmost importance. Neuroinflammation and disturbed redox homeostasis are suggested as prevailing underlying mechanisms in neurological sequelae propagation in long-COVID. We aimed to investigate whether variations in antioxidant genetic profile might be associated with neurological sequelae in long-COVID. Neurological examination and antioxidant genetic profile (SOD2, GPXs and GSTs) determination, as well as, genotype analysis of Nrf2 and ACE2, were conducted on 167 COVID-19 patients. Polymorphisms were determined by the appropriate PCR methods. Only polymorphisms in GSTP1AB and GSTO1 were independently associated with long-COVID manifestations. Indeed, individuals carrying GSTP1 Val or GSTO1 Asp allele exhibited lower odds of long-COVID myalgia development, both independently and in combination. Furthermore, the combined presence of GSTP1 Ile and GSTO1 Ala alleles exhibited cumulative risk regarding long-COVID myalgia in carriers of the combined GPX1 LeuLeu/GPX3 CC genotype. Moreover, individuals carrying combined GSTM1-null/GPX1LeuLeu genotype were more prone to developing long-COVID "brain fog", while this probability further enlarged if the Nrf2 A allele was also present. The fact that certain genetic variants of antioxidant enzymes, independently or in combination, affect the probability of long-COVID manifestations, further emphasizes the involvement of genetic susceptibility when SARS-CoV-2 infection is initiated in the host cells, and also months after.

SOD2 rs4880 and GPX1 rs1050450 polymorphisms do not confer risk of COVID-19, but influence inflammation or coagulation parameters in Serbian cohort.

Objectives: Due to the role of oxidative stress in the pathophysiology of COVID-19, it is biologically plausible that inter-individual differences in patients' clinical manifestations might be affected by antioxidant genetic profile. The aim of our study was to assess the distribution of antioxidant genetic polymorphisms Nrf2 rs6721961, SOD2 rs4880, GPX1 rs1050450, GPX3 rs8177412, and GSTP1 (rs1695 and rs1138272) haplotype in COVID-19 patients and controls, with special emphasis on their association with laboratory biochemical parameters.Methods: The antioxidant genetic polymorphisms were assessed by appropriate PCR methods in 229 COVID-19 patients and 229 matched healthy individuals.Results: Among examined polymorphisms, only GSTP1 haplotype was associated with COVID-19 risk (p = 0.009). Polymorphisms of SOD2 and GPX1 influenced COVID-19 patients' laboratory biochemical profile: SOD2*Val allele was associated with increased levels of fibrinogen (p = 0.040) and ferritin (p = 0.033), whereas GPX1*Leu allele was associated with D-dimmer (p = 0.009).Discussion: Our findings regarding the influence of SOD2 and GPX1 polymorphisms on inflammation and coagulation parameters might be of clinical importance. If confirmed in larger cohorts, these developments could provide a more personalized approach for better recognition of patients prone to thrombosis and those for the need of targeted antiox-idant therapy.

GSTO1, GSTO2 and ACE2 Polymorphisms Modify Susceptibility to Developing COVID-19.

Based on the close relationship between dysregulation of redox homeostasis and immune response in SARS-CoV-2 infection, we proposed a possible modifying role of ACE2 and glutathione transferase omega (GSTO) polymorphisms in the individual propensity towards the development of clinical manifestations in COVID-19. The distribution of polymorphisms in ACE2 (rs4646116), GSTO1 (rs4925) and GSTO2 (rs156697) were assessed in 255 COVID-19 patients and 236 matched healthy individuals, emphasizing their individual and haplotype effects on disease development and severity. Polymorphisms were determined by the appropriate qPCR method. The data obtained showed that individuals carrying variant GSTO1*AA and variant GSTO2*GG genotypes exhibit higher odds of COVID-19 development, contrary to ones carrying referent alleles (p = 0.044, p = 0.002, respectively). These findings are confirmed by haplotype analysis. Carriers of H2 haplotype, comprising GSTO1*A and GSTO2*G variant alleles were at 2-fold increased risk of COVID-19 development (p = 0.002). Although ACE2 (rs4646116) polymorphism did not exhibit a statistically significant effect on COVID-19 risk (p = 0.100), the risk of COVID-19 development gradually increased with the presence of each additional risk-associated genotype. Further studies are needed to clarify the specific roles of glutathione transferases omega in innate immune response and vitamin C homeostasis once the SARS-CoV-2 infection is initiated in the host cell.

Seroprevalence of SARS-CoV-2 antibodies among primary healthcare workers in the Republic of Srpska, Bosnia & Herzegovina: A cross-sectional study.

Healthcare workers (HCW) in primary healthcare centres in the Republic of Srpska, Bosnia and Herzegovina, are on the first combat line with COVID-19. This study aimed to assess the seroprevalence of SARS-CoV-2 among HCW at the primary healthcare centres and to analyse the risk exposure to COVID-19, clinical signs and vaccination status. A cross-sectional study was conducted among HCW at the selected primary healthcare centres between 19 March and 30 April 2021. Antibodies against the SARS-CoV-2 virus were detected by enzyme-linked immunosorbent assay (ELISA). A total of 1,023 HCW (mean age 45 years; 71% female) were included in the study. The anti-SARS-CoV-2 antibodies were detected in 69.5% of all participants. There was a significant difference in seropositivity among primary healthcare centres from different geographical regions. As many as 432 (42%) of all participants had confirmed COVID-19 symptoms before the study and, 84.8% of them were seropositive. This study showed that 702 primary HCW were vaccinated with any of these vaccines: Sputnik V, Sinopharm, Pfizer/Biontech. High titre of SARS-CoV-2 antibodies was found amongst those who received one (92.6%) or both (97.2%) doses of vaccines. In this study, we report high prevalence of SARS-CoV-2 antibody among HCW in primary healthcare in the Republic of Srpska, Bosnia and Herzegovina during the third pandemic wave.

GSTP1 and GSTM3 Variant Alleles Affect Susceptibility and Severity of COVID-19.

Based on the premise that oxidative stress plays an important role in severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection, we speculated that variations in the antioxidant activities of different members of the glutathione S-transferase family of enzymes might modulate individual susceptibility towards development of clinical manifestations in COVID-19. The distribution of polymorphisms in cytosolic glutathione S-transferases GSTA1, GSTM1, GSTM3, GSTP1 (rs1695 and rs1138272), and GSTT1 were assessed in 207 COVID-19 patients and 252 matched healthy individuals, emphasizing their individual and cumulative effect in disease development and severity. GST polymorphisms were determined by appropriate PCR methods. Among six GST polymorphisms analyzed in this study, GSTP1 rs1695 and GSTM3 were found to be associated with COVID-19. Indeed, the data obtained showed that individuals carrying variant GSTP1-Val allele exhibit lower odds of COVID-19 development (p = 0.002), contrary to carriers of variant GSTM3-CC genotype which have higher odds for COVID-19 (p = 0.024). Moreover, combined GSTP1 (rs1138272 and rs1695) and GSTM3 genotype exhibited cumulative risk regarding both COVID-19 occurrence and COVID-19 severity (p = 0.001 and p = 0.025, respectively). Further studies are needed to clarify the exact roles of specific glutathione S-transferases once the SARS-CoV-2 infection is initiated in the host cell.

The Influence of Different Risk Factors on COVID-19 Outcomes in Adult Patients - An Observational-Descriptive Study.

OBJECTIVE: The aim of our study was to investigate the predictors of morbidity (age, gender, smoking habits, obesity and the presence of chronic diseases) and COVID-19 outcomes. SUBJECTS AND METHODS: The research was an observational descriptive study, conducted at The Family Medicine Education Center, The Primary Health Care Center, Banja Luka, in the period from 26th June to 31st December 2020. During the research period, seven family medicine teams followed their patients with COVID- 19, and recorded possible predictors for morbidity and their influence on the disease outcome. RESULTS: The study included 934 patients, 46.90% of whom were male. The majority of subjects were non-smokers and overweight. Diabetes was found in 5.57% patients, hypertension in 29.44%, chronic respiratory diseases in 5.25%, cancer in 4.39% patients. In the observed sample, 29.23% subjects contracted pneumonia, 18.52% were hospitalized, while 19 (2.03%) patients with severe clinical features had a fatal outcome. Multivariable regression analysis showed a high risk of pneumonia in male patients [OR=2.45, 95% CI (1.73- 3.46)], elderly [OR=1.07, 95% CI (1.06-1.09)] and obese patients with Body Mass Index ≥30.0 kg/m2 [OR=2.55, 95% CI (1.73- 3.77)]. Male gender [OR=2.19, 95% CI (1.11-4.31)], older age [OR=1.08, 95% CI (1.05-1.11)] and hypertension [OR=2.51, 95% CI (1.06-5.91)] were the most important predictors for the development of severe clinical features in COVID 19. The statistically significant predictors of mortality were male gender [OR=7.16, 95% CI (1.56-32.86)] and older age [OR=1.12, 95% CI (1.06-1.18]. CONCLUSION: Being familiar with the predictors of morbidity and poor outcome in COVID-19 is helpful for carrying out preventive measures, early diagnosis and treatment of risk groups of patients.