Oxidative Damage and Post-COVID Syndrome: A Cross-Sectional Study in a Cohort of Italian Workers.

In addition to the acute symptoms after infection, patients and society are also being challenged by the long-term effects of COVID-19, known as long COVID. Oxidative stress, as a pivotal point in the pathophysiology of COVID-19, could potentially be also involved in the development of the post-COVID syndrome. The aim of the present study was to evaluate the relationship between changes in oxidative status and the persistence of long-COVID symptoms in workers with a previous mild COVID-19 infection. A cross-sectional study was conducted among 127 employees of an Italian university (80 with a previous COVID-19 infection, and 47 healthy subjects). The TBARS assay was used to detect malondialdehyde serum levels (MDA), while total hydroperoxide (TH) production was measured by a d-ROMs kit. A significant difference in mean serum MDA values was found between previously infected subjects and healthy controls and (4.9 µm vs. 2.8 µm, respectively). Receiver-operating characteristic (ROC) curves showed high specificity and good sensibility (78.7% and 67.5%, respectively) for MDA serum levels. A random forest classifier identified the hematocrit value, MDA serum levels, and IgG titer against SARS-CoV-2 as features with the highest predictive value in distinguishing 34 long-COVID from 46 asymptomatic post-COVID subjects. Oxidative damage persists in subjects with previous COVID-19 infection, suggesting a possible role of oxidative stress mediators in the pathogenesis of long COVID.

Evaluation of antibody response to SARS-CoV-2 variants after 2 doses of mRNA COVID-19 vaccine in a correctional facility.

The SARS-CoV-2 pandemic has posed a challenge for correctional facilities worldwide. People in such settings are more vulnerable to severe forms of infection and it is impossible to completely isolate inmates from the outside world. This study aimed to assess the antibody-mediated immune response in terms of neutralizing antibodies against Alpha, Beta, Gamma and Omicron (sub-lineage BA.1) variants of concern after two doses of mRNA vaccine in correctional officers and inmates from an Italian correctional facility. Most of the correctional officers (56.5%) and inmates (52.3% and 63.6%) retained their neutralizing activity toward the Alpha and Gamma variants, respectively. By contrast, the most striking reduction in comparison with the ancestral virus was found in the antibody response toward the Beta and Omicron variants, in both correctional officers (91.2% and 93.9%) and inmates (85.1% and 92.8%). In addition, subjects who had undergone primary vaccination and had previously been naturally infected had higher neutralizing antibody titers toward the 4 variants than negative subjects. Overall, our findings indicate that primary mRNA vaccination is able to induce neutralizing antibodies toward the ancestral virus, while titers toward variants may vary, depending on the mutations harboring by the variants. Although the correctional setting is often considered distinct or isolated from the wider society and sanitary system, the health of correctional workers and prisoners is inexorably linked to the public health of the country as a whole and it is of paramount importance to monitor the antibody response in these settings.

The neutralizing response to SARS-CoV-2 Omicron variants BA.1 and BA.2 in COVID-19 patients and homologous and heterologous vaccinees.

The rapid replacement of Omicron BA.1 by BA.2 sublineage is very alarming, raising the question of whether BA.2 can escape the immunity acquired after BA.1 infection. We compared the neutralizing activity toward the Omicron BA.1 and BA.2 sub-lineages in five groups: COVID-19 patients; subjects who had received two doses of mRNA vaccine; subjects naturally infected with SARS-CoV-2 who had received two doses of mRNA; and subjects who had received three doses of homologous or heterologous vaccine. The results obtained highlight the importance of vaccine boosters in eliciting neutralizing antibody responses against Omicron sub-lineages, and suggest that the adenovirus vectored vaccine elicits a lower response against BA.1 than against BA.2 sub-lineage.

Antibody Avidity and Neutralizing Response against SARS-CoV-2 Omicron Variant after Infection or Vaccination.

Background: The recently emerged SARS-CoV-2 Omicron variant exhibits several mutations on the spike protein, enabling it to escape the immunity elicited by natural infection or vaccines. Avidity is the strength of binding between an antibody and its specific epitope. The SARS-CoV-2 spike protein binds to its cellular receptor with high affinity and is the primary target of neutralizing antibodies. Therefore, protective antibodies should show high avidity. This study aimed at investigating the avidity of receptor-binding domain (RBD) binding antibodies and their neutralizing activity against the Omicron variant in SARS-CoV-2 infected patients and vaccinees. Methods: Samples were collected from 42 SARS-CoV-2 infected patients during the first pandemic wave, 50 subjects who received 2 doses of mRNA vaccine before the Omicron wave, 44 subjects who received 3 doses of mRNA vaccine, and 35 subjects who received heterologous vaccination (2 doses of adenovirus-based vaccine plus mRNA vaccine) during the Omicron wave. Samples were tested for the avidity of RBD-binding IgG and neutralizing antibodies against the wild-type SARS-CoV-2 virus and the Omicron variant. Results: In patients, RBD-binding IgG titers against the wild-type virus increased with time, but remained low. High neutralizing titers against the wild-type virus were not matched by high avidity or neutralizing activity against the Omicron variant. Vaccinees showed higher avidity than patients. Two vaccine doses elicited the production of neutralizing antibodies, but low avidity for the wild-type virus; antibody levels against the Omicron variant were even lower. Conversely, 3 doses of vaccine elicited high avidity and high neutralizing antibodies against both the wild-type virus and the Omicron variant. Conclusions: Repeated vaccination increases antibody avidity against the spike protein of the Omicron variant, suggesting that antibodies with high avidity and high neutralizing potential increase cross-protection against variants that carry several mutations on the RBD.

Immune response to SARS-CoV-2 Omicron variant in patients and vaccinees following homologous and heterologous vaccinations.

The SARS-CoV-2 Omicron variant has rapidly replaced the Delta variant of concern. This new variant harbors worrisome mutations on the spike protein, which are able to escape the immunity elicited by vaccination and/or natural infection. To evaluate the impact and susceptibility of different serum samples to the Omicron variant BA.1, samples from COVID-19 patients and vaccinated individuals were tested for their ability to bind and neutralize the original SARS-CoV-2 virus and the Omicron variant BA.1. COVID-19 patients show the most drastic reduction in Omicron-specific antibody response in comparison with the response to the wild-type virus. Antibodies elicited by a triple homologous/heterologous vaccination regimen or following natural SARS-CoV-2 infection combined with a two-dose vaccine course, result in highest neutralization capacity against the Omicron variant BA.1. Overall, these findings confirm that vaccination of COVID-19 survivors and booster dose to vaccinees with mRNA vaccines is the correct strategy to enhance the antibody cross-protection against Omicron variant BA.1.

Anti-neuronal antibodies against brainstem antigens are associated with COVID-19.

BACKGROUND: Understanding how SARS-CoV-2 affects respiratory centres in the brainstem may help to preclude assisted ventilation for patients in intensive care setting. Viral invasion appears unlikely, although autoimmunity has been implicated, the responsible antigens remain unknown. We previously predicted the involvement of three epitopes within distinct brainstem proteins: disabled homolog 1 (DAB1), apoptosis-inducing-factor-1 (AIFM1), and surfeit-locus-protein-1 (SURF1). METHODS: Here, we used microarrays to screen serum from COVID-19 patients admitted to intensive care and compared those with controls who experienced mild course of the disease. FINDINGS: The results confirm the occurrence of IgG and IgM antibodies against the hypothesised epitopes in COVID-19 patients. Importantly, while IgM levels were similar in both groups, IgG levels were significantly elevated in severely ill patients compared to controls, suggesting a pathogenic role of IgG. INTERPRETATION: The newly discovered anti-neuronal antibodies might be promising markers of severe disease and the targeted peptide epitopes might be used for targeted immunomodulation. Further work is needed to determine whether these antibodies may play a role in long-COVID. FUNDING: AF, CF and PR received support from the German Research Foundation (grants FL 379/22-1, 327654276-SFB 1315, FR 4479/1-1, PR 1274/8-1). SH, DR, and DB received support from the Ministry of Economy, State of Mecklenburg Western Pomerania, Germany (grant COVIDPROTECT: "Optimisation of diagnostic and therapeutic pathways for COVID-19 patients in MV"). SH received support from the Research Group Molecular Medicine University of Greifswald (FVMM, seed funding FOVB-2021-01). AV received support from the Else Kröner Fresenius Foundation and the Alzheimer Research Initiative.

Impact of COVID-19 emergency on the psychological well-being of susceptible individuals.

The current pandemic has exerted an unprecedented psychological impact on the world population, and its effects on mental health are a growing concern. The present study aims to evaluate psychological well-being (PWB) during the COVID-19 crisis in university workers with one or more diseases likely to increase the risk of severe outcomes in the event of SARS-CoV-2 infection, defined as susceptible. 210 susceptible employees of an Italian University (aged 25-71 years) were recruited during the COVID-19 second wave (October-December 2020). A group comprising 90 healthy university employees (aged 26-69 years) was also recruited. The self-report Psychological General Well Being Index (PGWBI) was used to assess global PWB and the influence on six sub-domains: anxiety, depressed mood, positive well-being, self-control, general health, and vitality. We applied non-linear dimension-reduction techniques and regression methods to 45 variables in order to assess the main demographic, occupational, and general-health-related factors predicting PWB during the COVID-19 crisis. PGWBI score was higher in susceptible than in healthy workers, both as total score (mean 77.8 vs 71.3) and across almost all subscales. Age and jobs involving high social interaction before the pandemic were inversely associated with the PWB total score, general health, and self-control subscores. The current data suggest no decline in PWB during the second wave of COVID-19 health emergency in susceptible individuals of working age. Critically, higher risk for mental-health issues appears to be inversely related to age, particularly among individuals deprived of their previous level of social interaction at work.

Evaluation of the dual effects of antiviral drugs on SARS-CoV-2 receptors and the ACE2 receptor using structure-based virtual screening and molecular dynamics simulation.

The use of US FDA-approved drugs is preferred due to the need for lower costs and less time. In in silico medicine, repurposing is a quick and accurate way to screen US FDA-approved medications to find a therapeutic option for COVID-19 infection. Dual inhibitors possess dual inhibitory activity, which may be due to the inhibition of two different enzymes, and are considered better than combination therapy from the developmental and clinical perspectives. In this study, a molecular docking simulation was performed to identify the interactions of antiviral drugs with the critical residues in the binding site of the main SARS-CoV-2 protease, spike glycoprotein, and papain-like protease receptors compared to the angiotensin-converting enzyme-related carboxypeptidase (ACE2) receptor of host cells. Each of the receptors was docked with 70 US FDA-approved antiviral drugs using AutoDock Vina. A molecular dynamics (MD) simulation study was also used for 100 ns to confirm the stability behaviour of the ligand receptor complexes. Among the drugs that had the strongest interaction with the SARS-CoV-2 main protease, spike glycoprotein and papain-like protease receptors, and host cell ACE2 receptors, Simeprevir, Maraviroc and Saquinavir had dual inhibitory effects. The MD simulation study confirmed the stability of the strongest interactions between the antiviral drugs and the main protease, ACE2, spike glycoprotein, and papain-like protease receptors to 100 ns. However the results of MMPBSA analysis showed that the bond between Saquinavir and the ACE2 receptor was weak. Simeprevir and Maraviroc drugs had acceptable binding energies with dual receptors, especially the Simeprevir.Communicated by Ramaswamy H. Sarma.

COVID-19 Outbreak and BNT162b2 mRNA Vaccination Coverage in a Correctional Facility during Circulation of the SARS-CoV-2 Omicron BA.1 Variant in Italy.

Background. The recent spread of the highly mutated SARS-CoV-2 Omicron variant (B.1.1.529) has raised concerns about protection against COVID-19 in congregate settings such as prisons, characterized by a high risk of transmission and possible difficulties in obtaining adequate vaccination coverage. The present study aims to investigate the spread of an outbreak of COVID-19 in an Italian correctional facility during the dominant circulation of the Omicron BA.1 variant, and also considers BNT162b2 mRNA vaccination coverage among inmates. A COVID-19 screening campaign by RT-PCR was performed on 515 detainees from 4-30 January 2022, in response to an outbreak that began in the correctional facility. Furthermore, 101 serum samples collected from healthy inmates 21 days after having received the second dose of the BNT162b2 vaccine were tested for neutralizing antibodies against both the wild-type SARS-CoV-2 strain and the Omicron BA.1 variant. The global attack rate during the study period was 43.6% (RR 0.8), progressively reducing from unvaccinated inmates (62.7%, RR 1.8) to those who had one dose (52.3%, RR 1.5), two doses (full cycle) (45.0%, RR 1.3), and the third dose (booster) vaccinated group (31.4%, RR 0.7). The percentage of SARS-CoV-2 positive subjects among unvaccinated inmates was significantly higher than in the other groups (p < 0.001), while no significant difference was observed between inmates with one or two vaccine doses. Only two of the positive inmates were hospitalized for COVID-19. The geometric mean titer of neutralizing antibodies in the tested sub-group after two doses of vaccine was lower than in previous studies against the wild-type virus, and showed a complete lack of neutralization against the Omicron variant in 92.1% of individuals. The findings support the need to prioritize vaccination in correctional facilities, as a public health measure to increase the protection of inmates and consequently of prison workers and the community against COVID-19, in coordination with the other prevention strategies.

Changing Features of COVID-19: Characteristics of Infections with the SARS-CoV-2 Delta (B.1.617.2) and Alpha (B.1.1.7) Variants in Southern Italy.

Differences in the demographic and clinical characteristics of patients infected with the Alpha and Delta SARS-CoV-2 variants of concern in a large region of Southern Italy were assessed. Two cohorts of positive patients were compared. The Alpha group consisted of 11,135 subjects diagnosed between 21 March and 21 April 2021, and the Delta group consisted of 499 positive subjects diagnosed between 21 July and 21 August 2021. A descriptive and statistical analysis of the demographic and clinical characteristics of the two groups was performed. The proportion of patients with mild and moderate infections was significantly higher in the Delta than in the Alpha group (p < 0.001). In fully vaccinated patients, the proportion of symptomatic individuals was significantly higher in the Delta than in the Alpha group. The Delta group showed odds ratios of 3.08 (95% CI, 2.55-3.72) for symptomatic infection and 2.66 (95% CI, 1.76-3.94) for hospitalization. Improving COVID-19 vaccination rates is a priority, since infection with the SARS-CoV-2 Delta variant has a significant impact on patient outcomes. Additional targeted prevention strategies such as social distancing, the use of masks in indoor settings irrespective of vaccination status, and the use of a sanitary passport could be crucial to contain further spread of SARS-CoV-2 infection.

Coronavirus Disease (COVID-19) Pandemic: The Psychological Well-Being in a Cohort of Workers of a Multinational Company.

BACKGROUND: The aim of the present study was to evaluate the psychological well-being (PWB) during the coronavirus disease (COVID-19) pandemic in workers of a multinational company. METHODS: Employees (aged ≥18 years) were recruited from Latin American, North American, New Zealand, and European sites of a multinational company operative during all the pandemic period. The self-reported Psychological General Well-Being Index was used to assess the global PWB and the effects on six subdomains: anxiety, depressed mood, positive well-being, self-control, general health, and vitality. The influencing role of age, gender, geographical location, COVID-19 epidemiology, and restrictive measures adopted to control the pandemic was explored. RESULTS: A total of 1335 workers completed the survey. The aggregate median PWB global score was in a positive range, with significantly better outcomes detected in the Mexican and Colombian Latin American sites compared with the other worldwide countries (p < 0.001). Among the European locations, a significantly higher PWB score was determined in Spain compared with the German and French sites (p < 0.05). Comparable geographical trends were demonstrated for all the PWB subdomains. Male workers had a significantly better PWB compared with females (p < 0.05), whereas a negative correlation emerged with aging (p = 0.01). COVID-19 epidemiology and pandemic control measures had no clear effects on PWB. CONCLUSION: Monitoring PWB and the impact of individual and pandemic-related variables may be helpful to clarify the mental health effects of pandemic, define targeted psychological-supporting measures, also in the workplace, to face such a complex situation in a more constructive way.

Efficacy of the Measures Adopted to Prevent COVID-19 Outbreaks in an Italian Correctional Facility for Inmates Affected by Chronic Diseases.

Background: COVID-19 outbreaks in prisons and jails may affect both inmates and correctional workers. An observational study has been performed to investigate the efficacy of specific procedures and of a serial testing approach adopted for the COVID-19 prevention in an Italian correctional facility (Bari, Apulia) for inmates affected by chronic diseases. Methods: Two SARS-CoV-2 antigen testing campaigns were carried out for all the prisoners and correctional workers, including correctional officers (CO), administrative staff (AS), correctional health care workers (HCW), and operators working with people completing their sentence outside the prison (OOP). Antigen testing was conducted on nasopharyngeal swab specimens, using a fluorescence immunoassay for the qualitative detection of nucleocapsid SARS-CoV-2 antigen. All subjects positive to the antigen test underwent confirmation by rRT-PCR test. Results: In total, 426 new and residential inmates were tested during the first campaign and 480 during the second campaign. Only two new inmates resulted positive at the first campaign, while no positive cases were observed at the second campaign or outside of the testing campaigns. In total, 367 correctional workers were tested at the first campaign and 325 at the second. At the first, 4 CO and 2 HCW showed positive test results, while no new positive cases were observed at the second. Moreover, 1 CO and 1 HCW resulted positive outside of the testing campaigns for the onset of symptoms while at home. Conclusion: The implementation of a full risk management plan in a correctional facility, including both a strict protocol for the application of preventive measures and a serial testing approach, seems to be able to prevent COVID-19 outbreaks in both inmates and correctional workers.

Anti-platelet factor 4 antibodies causing VITT do not cross-react with SARS-CoV-2 spike protein.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a severe adverse effect of ChAdOx1 nCoV-19 COVID-19 vaccine (Vaxzevria) and Janssen Ad26.COV2.S COVID-19 vaccine, and it is associated with unusual thrombosis. VITT is caused by anti-platelet factor 4 (PF4) antibodies activating platelets through their FcγRIIa receptors. Antibodies that activate platelets through FcγRIIa receptors have also been identified in patients with COVID-19. These findings raise concern that vaccination-induced antibodies against anti-SARS-CoV-2 spike protein cause thrombosis by cross-reacting with PF4. Immunogenic epitopes of PF4 and SARS-CoV-2 spike protein were compared using in silico prediction tools and 3D modeling. The SARS-CoV-2 spike protein and PF4 share at least 1 similar epitope. Reactivity of purified anti-PF4 antibodies from patients with VITT was tested against recombinant SARS-CoV-2 spike protein. However, none of the affinity-purified anti-PF4 antibodies from 14 patients with VITT cross-reacted with SARS-CoV-2 spike protein. Sera from 222 polymerase chain reaction-confirmed patients with COVID-19 from 5 European centers were tested by PF4-heparin enzyme-linked immunosorbent assays and PF4-dependent platelet activation assays. We found anti-PF4 antibodies in sera from 19 (8.6%) of 222 patients with COVID-19. However, only 4 showed weak to moderate platelet activation in the presence of PF4, and none of those patients developed thrombotic complications. Among 10 (4.5%) of 222 patients who had COVID-19 with thrombosis, none showed PF4-dependent platelet-activating antibodies. In conclusion, antibodies against PF4 induced by vaccination do not cross-react with the SARS-CoV-2 spike protein, indicating that the intended vaccine-induced immune response against SARS-CoV-2 spike protein is not the trigger of VITT. PF4-reactive antibodies found in patients with COVID-19 in this study were not associated with thrombotic complications.

Application of an Innovative Model for the Risk Management of COVID-19 in a Multinational Manufacturing Company

The COVID-19 incidence in 61 manufacturing plants in Europe (EU), North America (NA) and Latin-America (LATAM) was compared with the incidence observed in the countries where the plants are located in order to evaluate the application of an innovative model for COVID-19 risk management. Firstly, a network of local and global teams was created, including an external university occupational physician team for scientific support. In July 2020, global prevention guidelines for the homogenous management of the pandemic were applied, replacing different site or regional procedures. A tool for COVID-19 monitoring was implemented to investigate the relationship between the incidence rates inside and outside the plants. In the period of May–November 2020, 565 confirmed cases (EU 330, NA 141, LATAM 94) were observed among 20,646 workers with different jobs and tasks, and in the last two months 85% EU and 70% NA cases were recorded. Only in 10% of cases was a possible internal origin of the contagion not excluded. In the EU and NA, unlike LATAM, the COVID-19 incidence rates inside the sites punctually followed the rising trend outside. In conclusion, the model, combining a global approach with the local application of the measures, maintains the sustainability in the manufacturing industry.

COVID19 outbreak in Lombardy, Italy: An analysis on the short-term relationship between air pollution, climatic factors and the susceptibility to SARS-CoV-2 infection.

Short-term exposure to air pollution, as well as to climate variables have been linked to a higher incidence of respiratory viral diseases. The study aims to assess the short-term influence of air pollution and climate on COVID19 incidence in Lombardy (Italy), during the early stage of the outbreak, before the implementation of the lockdown measures. The daily number of COVID19 cases in Lombardy from February 25th to March 10th, 2020, and the daily average concentrations up to 15 days before the study period of particulate matter (PM10, PM2.5), O3, SO2, and NO2 together with climate variables (temperature, relative humidity - RH%, wind speed, precipitation), were analyzed. A univariable mixed model with a logarithm transformation as link function was applied for each day, from 15 days (lag15) to one day (lag1) before the day of detected cases, to evaluate the effect of each variable. Additionally, change points (Break Points-BP) in the relationship between incident cases and air pollution or climatic factors were estimated. The results did not show a univocal relationship between air quality or climate factors and COVID19 incidence. PM10, PM2.5 and O3 concentrations in the last lags seem to be related to an increased COVID19 incidence, probably due to an increased susceptibility of the host. In addition, low temperature and low wind speed in some lags resulted associated with increased daily COVID19 incidence. The findings observed suggest that these factors, in particular conditions and lags, may increase individual susceptibility to the development of viral infections such as SARS-CoV-2.