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1.
iScience ; : 105082, 2022.
Article in English | ScienceDirect | ID: covidwho-2007783

ABSTRACT

The SARS-CoV-2 virus has triggered a worldwide pandemic. According to the BioGrid database, CLN7 (MFSD8) is thought to interact with several viral proteins. The aim of this work was to investigate a possible involvement of CLN7 in the infection process. Experiments on a CLN7-deficient HEK293T cell line exhibited a 90% reduced viral load compared to wild-type cells. This observation may be linked to the finding that CLN7 ko cells have a significantly reduced GM1 content in their cell membrane. GM1 is found highly enriched in lipid rafts, which are thought to play an important role in SARS-CoV-2 infection. In contrast, overexpression of CLN7 led to an increase in viral load. This study provides evidence that CLN7 is involved in SARS-CoV-2 infection. This makes it a potential pharmacological target for drug development against COVID-19. Furthermore, it provides insights into the physiological function of CLN7 where still only little is known about.

2.
Inn Med (Heidelb) ; 63(8): 840-850, 2022 Aug.
Article in German | MEDLINE | ID: covidwho-1971659

ABSTRACT

There are currently no strategies available on how to deal with Long-COVID (COVID "coronavirus disease"). COVID-19 vaccination could be both a preemptive and a therapeutic option for the future. The evaluation of the available studies is complicated by varying definitions. There are, however, indications that (complete) COVID-19 vaccination is able not only to prevent symptomatic infection but also to reduce the risk of Long-COVID. In some patients with Long-COVID, symptoms are modified after (first and/or second) COVID-19 vaccination; however, there is no clear evidence for a real therapeutic effect on Long-COVID.


Subject(s)
COVID-19 , COVID-19/complications , COVID-19/prevention & control , COVID-19 Vaccines/therapeutic use , Humans , SARS-CoV-2 , Vaccination
4.
Die Innere Medizin ; : 1-10, 2022.
Article in German | EuropePMC | ID: covidwho-1929225

ABSTRACT

Strategien zum Umgang mit Long-COVID (COVID „coronavirus disease“) sind bislang nicht verfügbar. Eine der aktuell geprüften Optionen ist die COVID-19-Impfung, sowohl präventiv als auch therapeutisch. Die Bewertung der vorhandenen Studien ist durch uneinheitliche Definitionen erschwert. Es gibt jedoch Hinweise, dass die (vollständige) COVID-19-Impfung nicht nur die symptomatische Infektion verhindern kann, sondern auch das Risiko für Long-COVID bei Durchbruchinfektionen zu reduzieren vermag. Bei Patienten mit Long-COVID führt die anschließende (einfache und/oder zweifache) COVID-19-Impfung teilweise zu einer Symptommodifikation, die bisweilen nur passager ist. Ein therapeutischer Effekt kann aus der vorliegenden Evidenz allerdings nicht sicher abgeleitet werden.

5.
EJHaem ; 1(1): 376-383, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-1898850

ABSTRACT

The clinical course of coronavirus disease 2019 (COVID-19) varies from mild symptoms to acute respiratory distress syndrome, hyperinflammation, and coagulation disorder. The hematopoietic system plays a critical role in the observed hyperinflammation, particularly in severely ill patients. We conducted a prospective diagnostic study performing a blood differential analyzing morphologic changes in peripheral blood of COVID-19 patients. COVID-19 associated morphologic changes were defined in a training cohort and subsequently validated in a second cohort (n = 45). Morphologic aberrations were further analyzed by electron microscopy (EM) and flow cytometry of lymphocytes was performed. We included 45 COVID-19 patients in our study (median age 58 years; 82% on intensive care unit). The blood differential showed a specific pattern of pronounced multi-lineage aberrations in lymphocytes (80%) and monocytes (91%) of patients. Overall, 84%, 98%, and 98% exhibited aberrations in granulopoiesis, erythropoiesis, and thrombopoiesis, respectively. Electron microscopy revealed the ultrastructural equivalents of the observed changes and confirmed the multi-lineage aberrations already seen by light microscopy. The morphologic pattern caused by COVID-19 is characteristic and underlines the serious perturbation of the hematopoietic system. We defined a hematologic COVID-19 pattern to facilitate further independent diagnostic analysis and to investigate the impact on the hematologic system during the clinical course of COVID-19 patients.

6.
Virus Res ; 316: 198791, 2022 07 15.
Article in English | MEDLINE | ID: covidwho-1815257

ABSTRACT

The emergence of the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) represents an unprecedented threat for the human population, necessitating rapid and effective intervention measures. Given the main infection route by airborne transmission, significant attention has been bestowed upon the use of antiseptic mouthrinses as a way to possibly reduce infectious viral titers. However, clinical evaluations are still sparse. Thus, we evaluated a wide variety of antiseptic agents that can be used as mouthrinses for their antiviral effects in vitro and their respective mode of action. One of the most promising antiseptic agents (benzalkoniumchloride, BAC) was used in a randomized placebo-controlled clinical trial with subsequent analysis of viral loads by RT-qPCR and virus rescue in cell culture. Mechanistic analysis revealed that treatment with BAC and other antiseptic agents efficiently inactivated SARS-CoV-2 in vitro by primarily disrupting the viral envelope, without affecting viral RNA integrity. However, the clinical application only resulted in a mild reduction of viral loads in the oral cavity. These results indicate that gargling with mouthrinses comprising single antiseptic agents may play a minor role towards a potential reduction of transmission rates and thus, these findings are of utmost importance when considering alternative COVID-19 prevention strategies.


Subject(s)
Anti-Infective Agents, Local , COVID-19 , Anti-Infective Agents, Local/pharmacology , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Humans , SARS-CoV-2 , Viral Load
7.
Infection ; 2022 Apr 11.
Article in English | MEDLINE | ID: covidwho-1783016

ABSTRACT

BACKGROUND: The immune response to COVID-19-vaccination differs between naïve vaccinees and those who were previously infected with SARS-CoV-2. Longitudinal quantitative and qualitative serological differences in these two distinct immunological subgroups in response to vaccination are currently not well studied. METHODS: We investigate a cohort of SARS-CoV-2-naïve and COVID-19-convalescent individuals immediately after vaccination and 6 months later. We use different enzyme-linked immunosorbent assay (ELISA) variants and a surrogate virus neutralization test (sVNT) to measure IgG serum titers, IgA serum reactivity, IgG serum avidity and neutralization capacity by ACE2 receptor competition. RESULTS: Anti-receptor-binding domain (RBD) antibody titers decline over time in dually vaccinated COVID-19 naïves whereas titers in single dose vaccinated COVID-19 convalescents are higher and more durable. Similarly, antibody avidity is considerably higher among boosted COVID-19 convalescent subjects as compared to dually vaccinated COVID-19-naïve subjects. Furthermore, sera from boosted convalescents inhibited the binding of spike-protein to ACE2 more efficiently than sera from dually vaccinated COVID-19-naïve subjects. CONCLUSIONS: Long-term humoral immunity differs substantially between dually vaccinated SARS-CoV-2-naïve and COVID-19-convalescent individuals. Booster vaccination after COVID-19 induces a more durable humoral immune response in terms of magnitude and quality as compared to two-dose vaccination in a SARS-CoV-2-naïve background.

8.
iScience ; 25(4): 104076, 2022 Apr 15.
Article in English | MEDLINE | ID: covidwho-1739821

ABSTRACT

SARS-CoV-2 Omicron is the first pandemic variant of concern exhibiting an abrupt accumulation of mutations particularly in the receptor-binding domain that is a critical target of vaccination induced and therapeutic antibodies. Omicron's mutations did only marginally affect the binding of ACE2, and the two antibodies Sotrovimab and CR3022 but strongly impaired the binding of Casirivimab and Imdevimab. Moreover, as compared with Wuhan, there is reduced serum reactivity and a pronounced loss of competitive surrogate virus neutralization (sVN) against Omicron in naïve vaccinees and in COVID-19 convalescents after infection and subsequent vaccination. Finally, although the booster vaccination response conferred higher titers and better sVN, the effect was nonetheless significantly lower compared with responses against Wuhan. Overall, our data suggest that the antigenicity of Omicrons receptor binding motive has largely changed but antibodies such as Sotrovimab targeting other conserved sites maintain binding and therefore hold potential in prophylaxis and treatment of Omicron-induced COVID-19.

9.
J Infect Dis ; 225(2): 190-198, 2022 01 18.
Article in English | MEDLINE | ID: covidwho-1630684

ABSTRACT

BACKGROUND: From a public health perspective, effective containment strategies for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) should be balanced with individual liberties. METHODS: We collected 79 respiratory samples from 59 patients monitored in an outpatient center or in the intensive care unit of the University Hospital Regensburg. We analyzed viral load by quantitative real-time polymerase chain reaction, viral antigen by point-of-care assay, time since onset of symptoms, and the presence of SARS-CoV-2 immunoglobulin G (IgG) antibodies in the context of virus isolation from respiratory specimens. RESULTS: The odds ratio for virus isolation increased 1.9-fold for each log10 level of SARS-CoV-2 RNA and 7.4-fold with detection of viral antigen, while it decreased 6.3-fold beyond 10 days of symptoms and 20.0-fold with the presence of SARS-CoV-2 antibodies. The latter was confirmed for B.1.1.7 strains. The positive predictive value for virus isolation was 60.0% for viral loads >107 RNA copies/mL and 50.0% for the presence of viral antigen. Symptom onset before 10 days and seroconversion predicted lack of infectivity with negative predictive values of 93.8% and 96.0%. CONCLUSIONS: Our data support quarantining patients with high viral load and detection of viral antigen and lifting restrictive measures with increasing time to symptom onset and seroconversion. Delay of antibody formation may prolong infectivity.


Subject(s)
COVID-19/diagnosis , SARS-CoV-2 , Seroconversion , Viral Load , Adult , Antibodies, Viral , Antigens, Viral , COVID-19/immunology , Female , Humans , Male , Public Health , RNA, Viral , SARS-CoV-2/isolation & purification , SARS-CoV-2/pathogenicity , Severity of Illness Index
10.
iScience ; 25(2): 103694, 2022 Feb 18.
Article in English | MEDLINE | ID: covidwho-1591609

ABSTRACT

Heterologous SARS-CoV-2 vaccine approaches with a second mRNA-based vaccine have been favored in the recommendations of many countries over homologous vector-based ChAdOx1 nCoV-19 vaccination after reports of thromboembolic events and lower efficacy of this regimen. In the middle of 2021, the SARS-CoV-2 Delta variant of concern (VoC) has become predominant in many countries worldwide. Data addressing the neutralization capacity of a heterologous ChAdOx1 nCoV-19/mRNA-based vaccination approach against the Delta VoC in comparison to the widely used homologous mRNA-based vaccine regimen are limited. Here, we compare serological immune responses of a cohort of ChAdOx1 nCoV-19/BNT162b2-vaccinated participants with those of BNT162b2/BNT162b2 vaccinated ones and show that neutralization capacity against the Delta VoC is significantly increased in sera of ChAdOx1 nCoV-19/BNT162b2-vaccinated participants. This overall effect can be attributed to ChAdOx1 nCoV-19/BNT162b2-vaccinated women, especially those with more severe adverse effects leading to sick leave following second immunization.

11.
Virchows Arch ; 479(1): 97-108, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1574264

ABSTRACT

Between April and June 2020, i.e., during the first wave of pandemic coronavirus disease 2019 (COVID-19), 55 patients underwent long-term treatment in the intensive care unit at the University Hospital of Regensburg. Most of them were transferred from smaller hospitals, often due to the need for an extracorporeal membrane oxygenation system. Autopsy was performed in 8/17 COVID-19-proven patients after long-term treatment (mean: 33.6 days). Autopsy revealed that the typical pathological changes occurring during the early stages of the disease (e.g., thrombosis, endothelitis, capillaritis) are less prevalent at this stage, while severe diffuse alveolar damage and especially coinfection with different fungal species were the most conspicuous finding. In addition, signs of macrophage activation syndrome was detected in 7 of 8 patients. Thus, fungal infections were a leading cause of death in our cohort of severely ill patients and may alter clinical management of patients, particularly in long-term periods of treatment.


Subject(s)
COVID-19/microbiology , Coinfection , Lung Diseases, Fungal/microbiology , Lung/microbiology , Multiple Organ Failure/microbiology , Adult , Aged , COVID-19/drug therapy , COVID-19/mortality , COVID-19/pathology , COVID-19/therapy , Cause of Death , Extracorporeal Membrane Oxygenation , Female , Humans , Intensive Care Units , Lung/pathology , Lung/virology , Lung Diseases, Fungal/mortality , Lung Diseases, Fungal/pathology , Macrophage Activation Syndrome/microbiology , Macrophage Activation Syndrome/pathology , Male , Middle Aged , Multiple Organ Failure/mortality , Multiple Organ Failure/pathology , Multiple Organ Failure/virology , Risk Factors , Time Factors , Treatment Outcome
12.
J Clin Med ; 10(8)2021 Apr 08.
Article in English | MEDLINE | ID: covidwho-1526826

ABSTRACT

Serological testing is crucial in detection of previous infection and in monitoring convalescent and vaccine-induced immunity. During the Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) pandemic, numerous assay platforms have been developed and marketed for clinical use. Several studies recently compared clinical performance of a limited number of serological tests, but broad comparative evaluation is currently missing. Within this study, a panel of 161 sera from SARS-CoV-2 infected, seasonal CoV-infected and SARS-CoV-2 naïve subjects was enrolled to evaluate 16 ELISA/ECLIA-based and 16 LFA-based tests. Specificities of all ELISA/ECLIA-based assays were acceptable and generally in agreement with the providers' specifications, but sensitivities were lower as specified. Results of the LFAs were less accurate as compared to the ELISAs, albeit with some exceptions. We found a sporadic unequal immune response for different antigens and thus recommend the use of a nucleocapsid protein (N)- and spike protein (S)-based test combination when maximal sensitivity is necessary. Finally, the quality of the immune response in terms of neutralization should be tested using S-based IgG tests.

14.
Infection ; 50(2): 439-446, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1437345

ABSTRACT

BACKGROUND: The long-term course of immunity among individuals with a history of COVID-19, in particular among those who received a booster vaccination, has not been well defined so far. METHODS: SARS-CoV-2-specific antibody levels were measured by ELISA over 1 year among 136 health care workers infected during the first COVID-19 wave and in a subgroup after booster vaccination approximately 1 year later. Furthermore, spike-protein-reactive memory T cells were quantified approximately 7 months after the infection and after booster vaccination. Thirty healthy individuals without history of COVID-19 who were routinely vaccinated served as controls. RESULTS: Levels of SARS-CoV-2-specific IgM- and IgA-antibodies showed a rapid decay over time, whereas IgG-antibody levels decreased more slowly. Among individuals with history of COVID-19, booster vaccination induced very high IgG- and to a lesser degree IgA-antibodies. Antibody levels were significantly higher after booster vaccination than after recovery from COVID-19. After vaccination with a two-dose schedule, healthy control subjects developed similar antibody levels as compared to individuals with history of COVID-19 and booster vaccination. SARS-CoV-2-specific memory T cell counts did not correlate with antibody levels. None of the study participants suffered from a reinfection. CONCLUSIONS: Booster vaccination induces high antibody levels in individuals with a history of COVID-19 that exceeds by far levels observed after recovery. SARS-CoV-2-specific antibody levels of similar magnitude were achieved in healthy, COVID-19-naïve individuals after routine two-dose vaccination.


Subject(s)
COVID-19 , Antibodies, Viral , COVID-19/prevention & control , Follow-Up Studies , Humans , SARS-CoV-2 , Vaccination
15.
Clin Oral Investig ; 24(10): 3707-3713, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-1384470

ABSTRACT

OBJECTIVES: SARS-CoV-2 is mainly transmitted by inhalation of droplets and aerosols. This puts healthcare professionals from specialties with close patient contact at high risk of nosocomial infections with SARS-CoV-2. In this context, preprocedural mouthrinses with hydrogen peroxide have been recommended before conducting intraoral procedures. Therefore, the aim of this study was to investigate the effects of a 1% hydrogen peroxide mouthrinse on reducing the intraoral SARS-CoV-2 load. METHODS: Twelve out of 98 initially screened hospitalized SARS-CoV-2-positive patients were included in this study. Intraoral viral load was determined by RT-PCR at baseline, whereupon patients had to gargle mouth and throat with 20 mL of 1% hydrogen peroxide for 30 s. After 30 min, a second examination of intraoral viral load was performed by RT-PCR. Furthermore, virus culture was performed for specimens exhibiting viral load of at least 103 RNA copies/mL at baseline. RESULTS: Ten out of the 12 initially included SARS-CoV-2-positive patients completed the study. The hydrogen peroxide mouthrinse led to no significant reduction of intraoral viral load. Replicating virus could only be determined from one baseline specimen. CONCLUSION: A 1% hydrogen peroxide mouthrinse does not reduce the intraoral viral load in SARS-CoV-2-positive subjects. However, virus culture did not yield any indication on the effects of the mouthrinse on the infectivity of the detected RNA copies. CLINICAL RELEVANCE: The recommendation of a preprocedural mouthrinse with hydrogen peroxide before intraoral procedures is questionable and thus should not be supported any longer, but strict infection prevention regimens are of paramount importance. TRIAL REGISTRATION: German Clinical Trials Register (ref. DRKS00022484).


Subject(s)
Betacoronavirus , Coronavirus Infections , Pandemics , Pneumonia, Viral , Adult , Aged , Aged, 80 and over , COVID-19 , Female , Humans , Hydrogen Peroxide , Male , Middle Aged , Mouthwashes , Pilot Projects , Prospective Studies , SARS-CoV-2 , Viral Load , Young Adult
16.
J Infect Dis ; 225(2): 190-198, 2022 01 18.
Article in English | MEDLINE | ID: covidwho-1370780

ABSTRACT

BACKGROUND: From a public health perspective, effective containment strategies for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) should be balanced with individual liberties. METHODS: We collected 79 respiratory samples from 59 patients monitored in an outpatient center or in the intensive care unit of the University Hospital Regensburg. We analyzed viral load by quantitative real-time polymerase chain reaction, viral antigen by point-of-care assay, time since onset of symptoms, and the presence of SARS-CoV-2 immunoglobulin G (IgG) antibodies in the context of virus isolation from respiratory specimens. RESULTS: The odds ratio for virus isolation increased 1.9-fold for each log10 level of SARS-CoV-2 RNA and 7.4-fold with detection of viral antigen, while it decreased 6.3-fold beyond 10 days of symptoms and 20.0-fold with the presence of SARS-CoV-2 antibodies. The latter was confirmed for B.1.1.7 strains. The positive predictive value for virus isolation was 60.0% for viral loads >107 RNA copies/mL and 50.0% for the presence of viral antigen. Symptom onset before 10 days and seroconversion predicted lack of infectivity with negative predictive values of 93.8% and 96.0%. CONCLUSIONS: Our data support quarantining patients with high viral load and detection of viral antigen and lifting restrictive measures with increasing time to symptom onset and seroconversion. Delay of antibody formation may prolong infectivity.


Subject(s)
COVID-19/diagnosis , SARS-CoV-2 , Seroconversion , Viral Load , Adult , Antibodies, Viral , Antigens, Viral , COVID-19/immunology , Female , Humans , Male , Public Health , RNA, Viral , SARS-CoV-2/isolation & purification , SARS-CoV-2/pathogenicity , Severity of Illness Index
18.
Infection ; 49(6): 1307-1311, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1235789

ABSTRACT

Coronavirus disease 2019 (Covid-19) vaccination is essential to fight the pandemic. Health care workers (HCWs) are prioritized to get vaccinated, yet uptake of recommended vaccinations is known to be low in this group. In a tertiary care university hospital with a high number of Covid-19 patients in intensive care, 59.5% of surveyed staff (N = 2454) were willing to get vaccinated, 21.4% were unsure and 18.7% refused. Vaccine hesitancy was higher in female, younger and healthy employees without contact to Covid-19 patients; nurses (53.3%) were much less willing to get vaccinated compared to physicians (82.7%).


Subject(s)
COVID-19 Vaccines , COVID-19 , Attitude , Cross-Sectional Studies , Female , Germany , Hospitals , Humans , SARS-CoV-2 , Tertiary Healthcare , Vaccination
20.
Viruses ; 13(4)2021 04 10.
Article in English | MEDLINE | ID: covidwho-1178435

ABSTRACT

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) RNA is detected by reverse-transcription quantitative real-time PCR (RT-qPCR) from respiratory specimens. This study compares throat washings (TW), nasopharyngeal swabs (NS) and oropharyngeal swabs (OS). A total of 102 samples from 34 adult patients with confirmed SARS-CoV-2 infection were analysed by RT-qPCR with absolute quantification. The median concentrations and diagnostic sensitivities were 5.8×104 copies/mL, 85% (NS), 1.4×104, 79% (OS) and 4.3×103, 85% (TW). Concentration differences were significant between NS and TW (P = 0.019). Saliva (SA) was available from 21 patients (median 3.4×103). OS and TW can be considered for SARS-CoV-2 diagnostics, although with slightly lower concentrations.


Subject(s)
COVID-19/diagnosis , Pharynx/virology , SARS-CoV-2/isolation & purification , Specimen Handling/methods , Adult , Aged , Aged, 80 and over , COVID-19 Nucleic Acid Testing , Female , Humans , Male , Middle Aged , RNA, Viral/analysis , RNA, Viral/genetics , SARS-CoV-2/genetics , Saliva/virology , Sensitivity and Specificity , Viral Load , Young Adult
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