In Vitro Virucidal Effects of Ultraviolet Light Prototypes on RNA viruses.

Ultraviolet-C (UVC) has been used to cause virus inactivation. The virucidal activity of three UV light lamps [UVC high frequencies (HF), UVC+B LED and UVC+A LED] was evaluated against the enveloped feline coronavirus (FCoVII), a surrogate model of SARS-CoV-2, the enveloped vesicular stomatitis virus (VSV), and the naked encephalomyocarditis virus (EMCV). Virucidal assays were performed at different time points of UV-light exposure (i.e., 5, 30 minutes and 1, 6, and 8 hours), placing each virus 180 cm below the perpendicular irradiation of the lamp and 1 and 2 meters from the perpendicular axis. We found that the UVC HF lamp had virucidal effects (≥96.8% of virus inactivation) against FCoVII, VSV and EMCV after 5 minutes of irradiation at each distance analyzed. Moreover, the UVC+B LED lamp had the highest inhibitory effects on FCoVII and VSV infectivity (≥99% of virus inactivation) when these viruses were settled below the perpendicular axis of the lamp for 5 minutes. Conversely, the UVC+A LED lamp was the least effective, achieving ≥85.9% inactivation of enveloped RNA viruses after 8 hours of UV exposure. Overall, UV light lamps, and in particular UVC HF and UVC+B LED ones, had a rapid and strong virucidal activity against distinct RNA viruses, including coronaviruses.

Evaluation of the Factors Associated with Reinfections towards SARS-CoV-2 Using a Case Control Design.

OBJECTIVE: The risk of reinfection with SARS-CoV-2 has been rapidly increased with the circulation of concerns about variants. So, the aim of our study was to evaluate the factors that increase the risk of this reinfection in healthcare workers compared to those who have never been positive and those who have had only one positivity. METHODS: A case-control study was carried out at the Teaching Hospital Policlinico Umberto I in Rome, Sapienza University of Rome, in the period between 6 March 2020 and 3 June 2022. Cases are healthcare workers who have developed a reinfection with the SARS-CoV-2 virus, while controls were either healthcare workers who tested positive once or those who have never tested positive for SARS-CoV-2. RESULTS: 134 cases and 267 controls were recruited. Female gender is associated with a higher odds of developing reinfection (OR: 2.42; 95% CI: 1.38-4.25). Moreover, moderate or high alcohol consumption is associated with higher odds of reinfection (OR: 1.49; 95% CI: 1.19-1.87). Diabetes is also associated with higher odds of reinfection (OR: 3.45; 95% CI: 1.41-8.46). Finally, subjects with increased red blood cell counts have higher odds of reinfection (OR: 1.69; 95% CI: 1.21-2.25). CONCLUSION: From the prevention point of view, these findings indicate that particular attention should be paid to subjects with diabetes mellitus, women and alcoholic drinkers. These results could also suggest that contact tracing represents a fundamental approach model against the SARS-CoV-2 pandemic, together with the health information of participants.

Synergistic Effect between SARS-CoV-2 Wave and COVID-19 Vaccination on the Occurrence of Mild Symptoms in Healthcare Workers.

BACKGROUND: Since the beginning of the pandemic, five variants of epidemiological interest have been identified, each of them with its pattern of symptomology and disease severity. The aim of this study is to analyze the role of vaccination status in modulating the pattern of symptomatology associated with COVID-19 infection during four waves. METHODS: Data from the surveillance activity of healthcare workers were used to carry out descriptive analysis, association analyses and multivariable analysis. A synergism analysis between vaccination status and symptomatology during the waves was performed. RESULTS: Females were found at a higher risk of developing symptoms. Four SARS-CoV-2 waves were identified. Pharyngitis and rhinitis were more frequent during the fourth wave and among vaccinated subjects while cough, fever, flu syndrome, headache, anosmia, ageusia, arthralgia/arthritis and myalgia were more frequent during the first three waves and among unvaccinated subjects. A correlation was found between vaccination and the different waves in terms of developing pharyngitis and rhinitis. CONCLUSION: Vaccination status and viruses' mutations had a synergic effect in the mitigation of the symptomatology caused by SARS-CoV-2 in healthcare workers.

Anti-N SARS-CoV-2 assays for evaluation of natural viral infection.

BACKGROUND: The 2019 coronavirus (COVID-19) epidemic, required the development of different diagnostic tests. While reverse transcriptase real-time PCR (RT-PCR) remains the first-line test of choice in acute infection diagnosis, anti-N antibodies serological assays provide a valuable tool to differentiate natural SARS-CoV-2 immunological response from that induced by vaccination, thus the goal of our study was to evaluate three serological tests agreement for these antibodies detection. METHODS: Three anti-N different tests were examined in 74 sera from patients referred or not COVID infection: immunochromatographic rapid test (Panbio™ COVID-19 IgG/IgM Rapid Test Device Abbott, Germany), ELISA kit (NovaLisa® SARS-CoV-2 IgG and IgM NovaTech Immunodiagnostic GmbH, Germany) and ECLIA immunoassay (Elecsys® Anti-SARS-CoV-2 Roche Diagnostics, Manheim, Germany). RESULTS: Qualitative comparison of the three analytical methods revealed a moderate agreement between ECLIA immunoassay and immunochromatographic rapid test (Cohen kappa coefficient κ = 0.564). Correlation analysis indicated weak positive correlation between total Ig (IgT) detected by ECLIA immunoassay and IgG by ELISA test (p < 0.0001), the analysis of ECLIA IgT and IgM ELISA detected, showed no statistical correlation. CONCLUSION: Comparison between of three analytical systems available for anti-N SARS-CoV-2 IgG and IgM antibodies showed a general agreement when compared to detect total and G class immunoglobulins, while doubtful or discordant results have been highlighted for IgT and IgM class. Anyway, all the tests examined provide reliable results to assess the serological status of SARS-CoV-2 infected patients.

Alterations in the Expression of IFN Lambda, IFN Gamma and Toll-like Receptors in Severe COVID-19 Patients.

Contradictory results have been reported regarding interferon (IFN) lambda (λ1-3) and IFN gamma (γ) production in COVID-19 patients. To gain insight into the roles played by these IFNs in SARS-CoV-2 infection, IFNλ1-3 and IFNγ mRNA expression was evaluated in peripheral blood mononuclear cells (PBMCs) (n = 32) and in cells of paired bronchoalveolar lavages (BALs) (n = 12). Lower IFNλ1-3 values (p < 0.001 for IFNλ1 and 3 and p = 0.013 for IFNλ2) in the PBMCs of severely ill patients were found compared to healthy donors (n = 15). Reduced levels of IFNγ were also detected in patients' PBMCs (p < 0.01) and BALs (p = 0.041) compared to healthy donors. The presence of secondary bacterial infections was associated with decreased IFNλ amounts in PBMCs (p = 0.001, p = 0.015 and p = 0.003, respectively) but increased concentrations of IFNλ3 (p = 0.022) in BALs. Patients with alterations in C-reactive protein, lactate dehydrogenase and D-dimer levels had decreased IFNλ1 and 3 (p = 0.003 and p < 0.001) and increased IFNγ (p = 0.08) in PBMCs. Analyzing Toll-like receptors (TLRs) involved in IFN production, we found that TLR3 was highly expressed (p = 0.033) in patients with bacterial superinfections, while TLR7 and 8 (p = 0.029 and p = 0.049) were reduced in BALs of deceased patients. Overall, severe COVID-19 might be characterized by dysregulation in IFNγ, IFNλ and TLR3, 7 and 8 production.

Natural Flavonoid Derivatives Have Pan-Coronavirus Antiviral Activity.

The SARS-CoV-2 protease (3CLpro) is one of the key targets for the development of efficacious drugs for COVID-19 treatment due to its essential role in the life cycle of the virus and exhibits high conservation among coronaviruses. Recent studies have shown that flavonoids, which are small natural molecules, have antiviral activity against coronaviruses (CoVs), including SARS-CoV-2. In this study, we identified the docking sites and binding affinity of several natural compounds, similar to flavonoids, and investigated their inhibitory activity towards 3CLpro enzymatic activity. The selected compounds were then tested in vitro for their cytotoxicity, for antiviral activity against SARS-CoV-2, and the replication of other coronaviruses in different cell lines. Our results showed that Baicalein (100 µg/mL) exerted strong 3CLpro activity inhibition (>90%), whereas Hispidulin and Morin displayed partial inhibition. Moreover, Baicalein, up to 25 µg/mL, hindered >50% of SARS-CoV-2 replication in Vero E6 cultures. Lastly, Baicalein displayed antiviral activity against alphacoronavirus (Feline-CoV) and betacoronavirus (Bovine-CoV and HCoV-OC43) in the cell lines. Our study confirmed the antiviral activity of Baicalein against SARS-CoV-2 and demonstrated clear evidence of its pan-coronaviral activity.

Torque teno virus (TTV): A gentle spy virus of immune status, predictive marker of seroconversion to COVID-19 vaccine in kidney and lung transplant recipients.

To date, no comprehensive marker to monitor the immune status of patients is available. Given that Torque teno virus (TTV), a known human virome component, has previously been identified as a marker of immunocompetence, it was retrospectively investigated whether TTV viral load may also represent a marker of ability to develop antibody in response to COVID-19-BNT162B2 vaccine in solid organ transplant recipients (SOT). Specifically, 273 samples from 146 kidney and 26 lung transplant recipients after successive doses of vaccine were analyzed. An inverse correlation was observed within the TTV copy number and anti-Spike IgG antibody titer with a progressive decrease in viremia the further away from the transplant date. Analyzing the data obtained after the second dose, a significant difference in TTV copy number between responsive and nonresponsive patients was observed, considering a 5 log10 TTV copies/mL threshold to discriminate between the two groups. Moreover, for 86 patients followed in their response to the second and third vaccination doses a 6 log10 TTV copies/mL threshold was used to predict responsivity to the booster dose. Although further investigation is necessary, possibly extending the analysis to other patient categories, this study suggests that TTV can be used as a good marker of vaccine response in transplant patients.

Nirmatrelvir and COVID-19: development, pharmacokinetics, clinical efficacy, resistance, relapse, and pharmacoeconomics.

Nirmatrelvir/ritonavir (N/R) is one of the most effective antiviral drugs against SARS-CoV-2. The preclinical development, pharmacodynamics and pharmacokinetics of N/R are reviewed herein. Randomized clinical trials have been conducted exclusively with pre-Omicron variants of concern, but in vitro studies show that efficacy against all Omicron sublineages is preserved, as confirmed by post-marketing observational studies. Nevertheless, investigations of large viral genome repositories have shown that mutation in the main protease causing resistance to N/R are increasingly frequent. In addition, virological and clinical rebounds after N/R discontinuation have been reported in immunocompetent patients. This finding is of concern when translated to immunocompromised patients, in whom N/R efficacy has not been formally investigated in clinical trials. Economical sustainability and perspectives for this therapeutic arena are discussed.

Prevalence of SARS-CoV-2 infection and associated risk factors: A testing program and nested case-control study conducted at Sapienza University of Rome between March and June 2021.

Background: To safely resume in-person activities during the COVID-19 pandemic, Sapienza University of Rome implemented rigorous infection prevention and control measures, a successful communication campaign and a free SARS-CoV-2 testing program. In this study, we describe the University's experience in carrying out such a program in the context of the COVID-19 response and identify risk factors for infection. Methods: Having identified resources, space, supplies and staff, from March to June 2021 Sapienza offered to all its enrollees a molecular test service (8.30 AM to 4 PM, Monday to Thursday). A test-negative case-control study was conducted within the program. Participants underwent structured interviews that investigated activity-related exposures in the 2 weeks before testing. Multivariable conditional logistic regression analyses were performed. Adjusted odds ratios (aORs) and 95% confidence intervals (95% CIs) were calculated. Results: A total of 8,959 tests were administered, of which 56 were positive. The detection trend followed regional tendencies. Among 40 cases and 80 controls, multivariable analysis showed that a known exposure to a COVID-19 case increased the likelihood of infection (aOR: 8.39, 95% CI: 2.38-29.54), while having a job decreased it (aOR: 0.23, 95% CI: 0.06-0.88). Of factors that almost reached statistical significance, participation in activities in the university tended to reduce the risk (aOR: 0.32, 95% CI: 0.09-1.06), while attendance at private gatherings showed an increasing risk trend (aOR: 3.48, 95% CI: 0.95-12.79). Age, gender, activities in the community, visiting bars or restaurants, and use of public transportation were not relevant risk factors. When those students regularly attending the university campus were excluded from the analysis, the results were comparable, except that attending activities in the community came close to having a statistically significant effect (aOR: 8.13, 95% CI: 0.91-72.84). Conclusions: The testing program helped create a safe university environment. Furthermore, promoting preventive behavior and implementing rigorous measures in public places, as was the case in the university setting, contributed to limit the virus transmission.

Comparison by Age of the Local Interferon Response to SARS-CoV-2 Suggests a Role for IFN-ε and -ω.

Children generally develop a mild disease after SARS-CoV-2 infection whereas older adults are at risk of developing severe COVID-19. Recent transcriptomic analysis showed pre-activated innate immunity in children, resulting in a more effective anti-SARS-CoV-2 response upon infection. To further characterize age-related differences, we studied type I and III interferon (IFN) response in SARS-CoV-2 infected and non-infected individuals of different ages. Specifically, levels of expression of type I (IFN-α, -ß, -ε and -ω), type III (IFN-λ1, -λ2 and -λ3) IFNs and of the IFN-stimulated genes, ISG15 and ISG56 were quantified in nasopharyngeal cells from diagnostic swabs. Basal transcription of type I/III IFN genes was highest among children and decreased with age. Among SARS-CoV-2-infected individuals, only IFN-ε and -ω levels were significantly higher in children and young adults whereas ISGs were overexpressed in infected adults. The occurrence of symptoms in children and the need for hospitalization in adults were associated to higher transcription of several IFN genes. Starting from a pre-activated transcription level, the expression of type I and III IFNs was not highly up-regulated in children upon SARS-CoV-2 infection; young adults activated IFNs' transcription at intermediate levels whereas older adults were characterized by higher ISGs and lower IFN-ε and -ω relative expression levels. Overall, our findings contribute to recognize components of a protective IFN response as a function of age, in the context of SARS-CoV-2 infection.

Evaluation of humoral and cellular response to four vaccines against COVID-19 in different age groups: A longitudinal study.

To date there has been limited head-to-head evaluation of immune responses to different types of COVID-19 vaccines. A real-world population-based longitudinal study was designed with the aim to define the magnitude and duration of immunity induced by each of four different COVID-19 vaccines available in Italy at the time of this study. Overall, 2497 individuals were enrolled at time of their first vaccination (T0). Vaccine-specific antibody responses induced over time by Comirnaty, Spikevax, Vaxzevria, Janssen Ad26.COV2.S and heterologous vaccination were compared up to six months after immunization. On a subset of Comirnaty vaccinees, serology data were correlated with the ability to neutralize a reference SARS-CoV-2 B strain, as well as Delta AY.4 and Omicron BA.1. The frequency of SARS-CoV-2-specific CD4+ T cells, CD8+ T cells, and memory B cells induced by the four different vaccines was assessed six months after the immunization. We found that mRNA vaccines are stronger inducer of anti-Spike IgG and B-memory cell responses. Humoral immune responses are lower in frail elderly subjects. Neutralization of the Delta AY.4 and Omicron BA.1 variants is severely impaired, especially in older individuals. Most vaccinees display a vaccine-specific T-cell memory six months after the vaccination. By describing the immunological response during the first phase of COVID-19 vaccination campaign in different cohorts and considering several aspects of the immunological response, this study allowed to collect key information that could facilitate the implementation of effective prevention and control measures against SARS-CoV-2.

Assessment of Anxiety, Depression, Work-Related Stress, and Burnout in Health Care Workers (HCWs) Affected by COVID-19: Results of a Case-Control Study in Italy.

This study aims to investigate whether HCWs infected with COVID-19 may experience potential psychological consequences and a higher incidence of depression, anxiety, work-related stress, and burnout compared to non-infected HCWs. A case-control study with 774 participants was conducted comparing COVID-19-infected HCWs (cases) and non-infected HCWs (controls) from the Occupational Medicine Unit at the Teaching Hospital Policlinico Umberto I, who were administered the same questionnaire including Hospital Anxiety and Depression Scale, Copenhagen Burnout Inventory and Karasek's Job Content Questionnaire. No differences in the levels of burnout and decision latitude were found between the two groups. Cases showed higher level of anxiety and job demand compared to controls. In contrast, levels of depression in the case group were significantly lower compared to the control group. The results are indicating the need for workplace health promotion activities based on stress and burnout management and prevention. Multiple organizational and work-related interventions can lower the impact of mental health-related issues in the COVID-19 pandemics, including the improvement of workplace infrastructures, as well as the adoption of correct and shared anti-contagion measures, which must include regular personal protective equipment supply, and the adoption of training programs that deal with mental health-related issues.

Prevalence of SARS-CoV-2 infection and associated risk factors: A testing program and nested case-control study conducted at Sapienza University of Rome between March and June 2021

Background To safely resume in-person activities during the COVID-19 pandemic, Sapienza University of Rome implemented rigorous infection prevention and control measures, a successful communication campaign and a free SARS-CoV-2 testing program. In this study, we describe the University's experience in carrying out such a program in the context of the COVID-19 response and identify risk factors for infection. Methods Having identified resources, space, supplies and staff, from March to June 2021 Sapienza offered to all its enrollees a molecular test service (8.30 AM to 4 PM, Monday to Thursday). A test-negative case-control study was conducted within the program. Participants underwent structured interviews that investigated activity-related exposures in the 2 weeks before testing. Multivariable conditional logistic regression analyses were performed. Adjusted odds ratios (aORs) and 95% confidence intervals (95% CIs) were calculated. Results A total of 8,959 tests were administered, of which 56 were positive. The detection trend followed regional tendencies. Among 40 cases and 80 controls, multivariable analysis showed that a known exposure to a COVID-19 case increased the likelihood of infection (aOR: 8.39, 95% CI: 2.38–29.54), while having a job decreased it (aOR: 0.23, 95% CI: 0.06–0.88). Of factors that almost reached statistical significance, participation in activities in the university tended to reduce the risk (aOR: 0.32, 95% CI: 0.09–1.06), while attendance at private gatherings showed an increasing risk trend (aOR: 3.48, 95% CI: 0.95–12.79). Age, gender, activities in the community, visiting bars or restaurants, and use of public transportation were not relevant risk factors. When those students regularly attending the university campus were excluded from the analysis, the results were comparable, except that attending activities in the community came close to having a statistically significant effect (aOR: 8.13, 95% CI: 0.91–72.84). Conclusions The testing program helped create a safe university environment. Furthermore, promoting preventive behavior and implementing rigorous measures in public places, as was the case in the university setting, contributed to limit the virus transmission.

Neuro-Axonal Damage and Alteration of Blood-Brain Barrier Integrity in COVID-19 Patients.

Neurofilament light chain (NfL) is a specific biomarker of neuro-axonal damage. Matrix metalloproteinases (MMPs) are zinc-dependent enzymes involved in blood-brain barrier (BBB) integrity. We explored neuro-axonal damage, alteration of BBB integrity and SARS-CoV-2 RNA presence in COVID-19 patients with severe neurological symptoms (neuro-COVID) as well as neuro-axonal damage in COVID-19 patients without severe neurological symptoms according to disease severity and after recovery, comparing the obtained findings with healthy donors (HD). Overall, COVID-19 patients (n = 55) showed higher plasma NfL levels compared to HD (n = 31) (p < 0.0001), especially those who developed ARDS (n = 28) (p = 0.0005). After recovery, plasma NfL levels were still higher in ARDS patients compared to HD (p = 0.0037). In neuro-COVID patients (n = 12), higher CSF and plasma NfL, and CSF MMP-2 levels in ARDS than non-ARDS group were observed (p = 0.0357, p = 0.0346 and p = 0.0303, respectively). SARS-CoV-2 RNA was detected in four CSF and two plasma samples. SARS-CoV-2 RNA detection was not associated to increased CSF NfL and MMP levels. During COVID-19, ARDS could be associated to CNS damage and alteration of BBB integrity in the absence of SARS-CoV-2 RNA detection in CSF or blood. CNS damage was still detectable after discharge in blood of COVID-19 patients who developed ARDS during hospitalization.

Assessment of Anxiety, Depression, Work-Related Stress, and Burnout in Health Care Workers (HCWs) Affected by COVID-19: Results of a Case–Control Study in Italy

This study aims to investigate whether HCWs infected with COVID-19 may experience potential psychological consequences and a higher incidence of depression, anxiety, work-related stress, and burnout compared to non-infected HCWs. A case–control study with 774 participants was conducted comparing COVID-19-infected HCWs (cases) and non-infected HCWs (controls) from the Occupational Medicine Unit at the Teaching Hospital Policlinico Umberto I, who were administered the same questionnaire including Hospital Anxiety and Depression Scale, Copenhagen Burnout Inventory and Karasek’s Job Content Questionnaire. No differences in the levels of burnout and decision latitude were found between the two groups. Cases showed higher level of anxiety and job demand compared to controls. In contrast, levels of depression in the case group were significantly lower compared to the control group. The results are indicating the need for workplace health promotion activities based on stress and burnout management and prevention. Multiple organizational and work-related interventions can lower the impact of mental health-related issues in the COVID-19 pandemics, including the improvement of workplace infrastructures, as well as the adoption of correct and shared anti-contagion measures, which must include regular personal protective equipment supply, and the adoption of training programs that deal with mental health-related issues.

Serological Response and Relationship with Gender-Sensitive Variables among Healthcare Workers after SARS-CoV-2 Vaccination.

Vaccine-induced immunity is a key strategy in the long-term control of the COVID-19 pandemic. The aim of our study was to explore the relationship between mRNA vaccine-induced antibodies and gender-sensitive variables among healthcare workers. Two thousand-sixty-five volunteers who received the BNT162b2 vaccine were enrolled in the study and followed up. Demographic, clinical, and social variables (educational level, marital status, occupation, childcare) were evaluated through a self-administered questionnaire. Anti-Spike (S) IgG were measured at 1 month (T1) and at 5 months (T2) after the second vaccine dose. At T1, median anti-S IgG values were 693 [394->800] AU/mL (1 AU = 2.6 BAU). Values > 800 AU/mL (2080 BAU/mL) were directly associated with a previous COVID-19 (p < 0.001) infection and inversely with age (p < 0.001), smoking habit (p < 0.001), and autoimmune diseases (p < 0.001). At T2, a significant decreasing in anti-S IgG values was observed (187 [81-262] AU/mL), with a median decrease of 72 [60-82]%. On multivariate data analysis, a reduction of more than 82% was directly associated with male sex (p < 0.021), age (p < 0.001), smoking (p = 0.038), hypertension (p = 0.042), and, inversely, with previous COVID-19 infection (p < 0.001) and being "cohabiting" (p = 0.005). Our findings suggest that demographic, clinical, and social variables play a role in anti-S IgG values decreasing in long-term follow up and should be considered to find personalized vaccine schedules.

The non-functional ACE2 isoform, but not the SARS-CoV-2 receptor, is induced as an interferon-stimulated gene, in SARS-CoV-2 infected adults.

The recently discovered truncated, non-functional, ACE2 transcript (dACE2), but not the full-length ACE2 (f-lACE2), is induced by IFNs in differentiated airway cells. We measured expression of both ACE2 isoforms in SARS-CoV-2 positive and negative subjects, in relation to Interferon-stimulated genes. A significant activation of dACE2 transcript was found, in SARS-CoV-2 positive adults either hospitalized or not, showing a positive correlation with ISG15; f-lACE2 expression was weakly activated and not ISG-related. We confirmed a specific activation of dACE2 transcript in nasopharyngeal cells, related to the mucosal IFN response.

Anti-IFN-α/-ω neutralizing antibodies from COVID-19 patients correlate with downregulation of IFN response and laboratory biomarkers of disease severity.

A significant number of COVID-19 patients were shown to have neutralizing antibodies (NAB) against IFN; however, NAB specificity, fluctuation over time, associations with biochemical and hematological parameters, and IFN gene expression are not well characterized. Binding antibodies (BAB) to IFN-α/-ß were screened in COVID-19 patients' serum. All BAB positive sera, and a subset of respiratory samples, were tested for NAB against IFN-α/-ß/-ω, using an antiviral bioassay. Transcript levels of IFN-α/-ß/-ω and IFN-stimulated genes (ISGs) were quantified. Anti-IFN-I BAB were found in 61 out of 360 (17%) of patients. Among BAB positive sera, 21.3% had a high NAB titer against IFN-α. A total of 69.2% of anti-IFN-α NAB sera displayed cross-reactivity to IFN-ω. Anti-IFN-I NAB persisted in all patients. NAB to IFN-α were also detected in 3 out of 17 (17.6%) of respiratory samples. Anti-IFN-I NAB were higher in males (p = 0.0017), patients admitted to the ICU (p < 0.0001), and patients with a fatal outcome (p < 0.0001). NAB were associated with higher levels of CRP, LDH, d-Dimer, and higher counts of hematological parameters. ISG-mRNAs were reduced in patients with persistently NAB titer. NAB are detected in a significant proportion of severe COVID-19. NAB positive patients presented a defective IFN response and increased levels of laboratory biomarkers of disease severity.

High frequency of neutralizing antibodies to type I Interferon in HIV-1 patients hospitalized for COVID-19.

The presence of anti-IFN neutralizing antibodies (NAB) has been reported in critically ill COVID-19 patients. We found that 87.5% (7/8) of HIV-1 patients co-infected with SARS-CoV-2 had serum anti-IFN-I NAB against IFN-α subtypes, IFN-ß and/or IFN-ω. Anti-IFN-I NAB were also detected in oropharyngeal samples. Patients with NAB were males, and those with high serum anti-IFN-α/ω NAB titer had severe illness and exhibited reduction in the expression of IFN-stimulated genes. Thus, high titer of anti-IFN-α/ω NAB may contribute to the greater severity of COVID-19 in HIV-1 infected patients.