ABSTRACT
The pandemic caused by SARS-CoV-2 is still a major health problem. Newly emerging variants and long-COVID-19 represent a challenge for the global health system. In particular, individuals in developing countries with insufficient health care need easily accessible, affordable and effective treatments of COVID-19. Previous studies have demonstrated the efficacy of functional inhibitors of acid sphingomyelinase (FIASMA) against infections with various viruses, including early variants of SARS-CoV-2. This work investigated whether the acid sphingomyelinase inhibitors fluoxetine and sertraline, usually used as antidepressant molecules in clinical practice, can inhibit the replication of the former and recently emerged SARS-CoV-2 variants in vitro. Fluoxetine and sertraline potently inhibited the infection with pseudotyped virus like particles and SARS-CoV-2 variants D614G, alpha, delta, omicron BA.1 and omicron BA.5. These results highlight fluoxetine and sertraline as priority candidates for large-scale phase 3 clinical trials at different stages of SARS-CoV-2 infections, either alone or in combination with other medications.
Subject(s)
Severe Acute Respiratory Syndrome , Addison Disease , COVID-19ABSTRACT
The role of autoimmunity in post-acute sequelae of COVID-19 (PASC) is not well explored, although clinicians observe a growing population of convalescent COVID-19 patients with manifestation of post-acute sequelae of COVID-19. We analyzed the immune response in 40 post-acute sequelae of COVID-19 patients with non-specific PASC manifestation and 15 COVID-19 convalescent healthy donors. The phenotyping of lymphocytes showed a significantly higher number of CD8+ T cells expressing the Epstein-Barr virus induced G protein coupled receptor 2, chemokine receptor CXCR3 and C-C chemokine receptor type 5 playing an important role in inflammation and migration in PASC patients compared to controls. Additionally, a stronger, SARS-CoV-2 reactive CD8+ T cell response, characterized by IFN{gamma} production and predominant TEMRA phenotype but low SARS-CoV-2 avidity was detected in PASC patients compared to controls. Furthermore, higher titers of several autoantibodies were detected among PASC patients. Our data suggest that a persistent inflammatory response triggered by SARS-CoV-2 might be responsible for the observed sequelae in PASC patients. These results may have implications on future therapeutic strategies.
Subject(s)
Severe Acute Respiratory Syndrome , COVID-19 , InflammationABSTRACT
Type I interferons (IFN-I) exert pleiotropic biological effects during viral infections, balancing virus control versus immune-mediated pathologies and have been successfully employed for the treatment of viral diseases. Humans express twelve IFN-alpha () subtypes, which activate downstream signalling cascades and result in distinct patterns of immune responses and differential antiviral responses. Inborn errors in type I IFN immunity and the presence of anti-IFN autoantibodies account for very severe courses of COVID-19, therefore, early administration of type I IFNs may be protective against life-threatening disease. Here we comprehensively analysed the antiviral activity of all IFN subtypes against SARS-CoV-2 to identify the underlying immune signatures and explore their therapeutic potential. Prophylaxis of primary human airway epithelial cells (hAEC) with different IFN subtypes during SARS-CoV-2 infection uncovered distinct functional classes with high, intermediate and low antiviral IFNs. In particular IFN5 showed superior antiviral activity against SARS-CoV-2 infection. Dose-dependency studies further displayed additive effects upon co-administered with the broad antiviral drug remdesivir in cell culture. Transcriptomics of IFN-treated hAEC revealed different transcriptional signatures, uncovering distinct, intersecting and prototypical genes of individual IFN subtypes. Global proteomic analyses systematically assessed the abundance of specific antiviral key effector molecules which are involved in type I IFN signalling pathways, negative regulation of viral processes and immune effector processes for the potent antiviral IFN5. Taken together, our data provide a systemic, multi-modular definition of antiviral host responses mediated by defined type I IFNs. This knowledge shall support the development of novel therapeutic approaches against SARS-CoV-2.
Subject(s)
COVID-19 , Metabolism, Inborn Errors , Virus DiseasesABSTRACT
The current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has created a significant threat to global health. While respiratory aerosols or droplets are considered as the main route of human-to-human transmission, secretions expelled by infected individuals can also contaminate surfaces and objects, potentially creating the risk of fomite-based transmission. Consequently, frequently touched objects such as paper currency and coins have been suspected as a potential transmission vehicle. To assess the risk of SARS-CoV-2 transmission by banknotes and coins, we examined the stability of SARS-CoV-2 and bovine coronavirus (BCoV), as surrogate with lower biosafety restrictions, on these different means of payment and developed a touch transfer method to examine transfer efficiency from contaminated surfaces to skin. Although we observed prolonged virus stability, our results, including a novel touch transfer method, indicate that the transmission of SARS-CoV-2 via contaminated coins and banknotes is unlikely and requires high viral loads and a timely order of specific events.
Subject(s)
Severe Acute Respiratory SyndromeABSTRACT
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted from person-to-person by close contact, small aerosol respiratory droplets and potentially via contact with contaminated surfaces. Here, we investigated the effectiveness of commercial UVC-LED disinfection boxes in inactivating SARS-CoV-2 contaminated surfaces of personal items. We contaminated glass, metal and plastic samples representing the surfaces of personal items such as smartphones, coins or credit cards with SARS-CoV-2 formulated in an organic matrix mimicking human respiratory secretions. For disinfection, the samples were placed at different distances from UVC emitting LEDs inside commercial UVC-LED disinfection boxes and irradiated for different time periods (up to 10 minutes). High viral loads of SARS-CoV-2 were effectively inactivated on all surfaces after 3 minutes of irradiation. Even 10 seconds of UVC-exposure strongly reduced viral loads. Thus, UVC-LED boxes proved to be an effective method for disinfecting SARS-CoV-2 contaminated surfaces that are typically found on personal items.
Subject(s)
Coronavirus Infections , Spinal Muscular Atrophies of ChildhoodABSTRACT
The newly emerged coronavirus, which was designated as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the COVID-19 disease. High effective and well-tolerated medication for hospitalized and non-hospitalized patients is urgently needed. Traditional herbal medicine substances were discussed as promising candidates for the complementary treatment of viral diseases and recently suggested for the treatment of COVID-19. In the present study, we investigated aqueous licorice root extract for its neutralizing activity against SARS-CoV-2 in vitro, identified the active compound glycyrrhizin and uncovered the respective mechanism of viral neutralization. We demonstrated that glycyrrhizin, the primary active ingredient of the licorice root, potently neutralizes SARS-CoV-2 by inhibiting the viral main protease. Our experiments highlight glycyrrhizin as a potential antiviral compound that should be further investigated for the treatment of COVID-19.
Subject(s)
COVID-19ABSTRACT
BackgroundWhen patients with chronic kidney disease are infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) they can face two specific problems: Virus-specific immune responses may be impaired and remdesivir, an antiviral drug described to shorten the time to recovery, is contraindicated. Antiviral treatment with convalescent plasma could be an alternative treatment option. MethodsIn this case series we present two kidney transplant recipients and two patients dependent on haemodialysis who were infected with SARS-CoV-2 and received convalescent plasma. Antibodies against the spike 1 protein of SARS-CoV-2 were determined sequentially by IgG ELISA and neutralization assay and specific T cell responses by interferon-gamma ELISpot. ResultsPrior to treatment, in three patients antibodies were undetectable by ELISA (ratio < 1.1), corresponding to low neutralizing antibody titers ([≤] 1:40). One patient was also negative to the ELISpot and two showed weak responses. After convalescent plasma treatment we observed an increase of SARS-CoV-2-specific antibodies (IgG ratio and neutralization titer) and of specific T cell responses. After intermittent clinical improvement one kidney transplant recipient again developed typical symptoms at day 12 after treatment and received a second cycle of convalescent plasma treatment. Altogether, three patients clinically improved and could be discharged from hospital. However, one multimorbid female in her early eighties deceased. ConclusionsOur data suggest that the success of convalescent plasma therapy may only be temporary in patients with chronic kidney disease; which requires an adaptation of the treatment regimen. Close monitoring after treatment is needed for this patient group.
ABSTRACT
In the ongoing SARS CoV-2 pandemic effective measures are needed, and guidance based on the methodological framework of the European committee for standardization (CEN) can help to choose effective disinfectants on an immediate basis. This study demonstrates that two commercially available formulations for surface disinfection and one formulation for hand disinfection claiming virucidal activity against enveloped viruses are effectively inactivating SARS-CoV-2. This study emphasizes that chemical disinfectants claiming virucidal activity against enveloped viruses are an effective choice to target enveloped SARS-CoV-2 as a preventive measure.
ABSTRACT
The SARS-Cov-2 pandemic is triggering a global health emergency alert, and recent research is indicating the relevance of aerosols in the spread of SARS-CoV-2. Thus, in this study antiseptic mouthwashes based on the actives chlorhexidine (CHX) and octenidine (OCT) were investigated regarding their efficacy against SARS-CoV-2 using EN 14476. Based on the requirement of EN 14476 (i.e. reduction of viral titer by [≥] 4 log 10), the OCT-based formulation was effective within only 15 sec against SARS-CoV-2, and thus constitutes an interesting candidate for future clinical studies to prove its effectiveness in a potential prevention of SARS-CoV-2 transmission by aerosols.
ABSTRACT
Long-term antibody responses and neutralizing activities following SARS-CoV-2 infections have not yet been elucidated. We quantified immunoglobulin M (IgM) and G (IgG) antibodies recognizing the SARS-CoV-2 receptor-binding domain (RBD) of the spike (S) or the nucleocapsid (N) protein, and neutralizing antibodies during a period of six months following COVID-19 disease onset in 349 symptomatic COVID-19 patients, which were among the first world-wide being infected. The positivity rate and magnitude of IgM-S and IgG-N responses increased rapidly. High levels of IgM-S/N and IgG-S/N at 2-3 weeks after disease onset were associated with virus control and IgG-S titers correlated closely with the capacity to neutralize SARS-CoV-2. While specific IgM-S/N became undetectable 12 weeks after disease onset in most patients, IgG-S/N titers showed an intermediate contraction phase, but stabilized at relatively high levels over the six months observation period. At late time points the positivity rates for binding and neutralizing SARS-CoV-2-specific antibodies was still over 70%. Taken together, our data indicate sustained humoral immunity in recovered patients who suffer from symptomatic COVID-19, suggesting prolonged immunity.
Subject(s)
COVID-19ABSTRACT
SARS-CoV-2 RNA has been detected in the human breast milk of infected mothers, raising concerns regarding the safety of breastfeeding upon infection. We here show that holder pasteurization inactivates SARS-CoV-2 and provides an alternative and safe option for infected mothers to continue feeding breast milk to their infants.
ABSTRACT
The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently the most pressing medical and socioeconomic challenge. Constituting important correlates of protection, determination of virus-neutralizing antibodies (NAbs) is indispensable for convalescent plasma selection, vaccine candidate evaluation, and immunity certificates. In contrast to standard serology ELISAs, plaque reduction neutralization tests (PRNTs) are laborious, time-consuming, expensive, and restricted to specialized laboratories. To replace microscopic counting-based SARS-CoV-2 PRNTs by a novel assay exempt from genetically modified viruses, which are inapplicable in most diagnostics departments, we established a simple, rapid, and automated SARS-CoV-2 neutralization assay employing an in-cell ELISA (icELISA) approach. After optimization of various parameters such as virus-specific antibodies, cell lines, virus doses, and duration of infection, SARS-CoV-2-infected cells became amenable as direct antigen source for quantitative icELISA. Using commercially available nucleocapsid protein-specific antibodies, viral infection could easily be quantified in human and highly permissive Vero E6 cells by icELISA. Antiviral agents such as human sera containing NAbs or antiviral interferons dose-dependently reduced the SARS-CoV-2-specific signal. Applying increased infectious doses, the icNT was superior to PRNT in discriminating convalescent sera with high from those with intermediate neutralizing capacities. The SARS-CoV-2 icELISA test allows rapid (<48h in total, read-out in seconds) and automated quantification of virus infection in cell culture to evaluate the efficacy of NAbs as well as antiviral drugs, using reagents and equipment present in most routine diagnostics departments. We propose the icELISA and the icNT for COVID-19 research and diagnostics.