Antibody Response and Maternofetal Antibody Transfer in SARS-CoV-2-Positive Pregnant Women: A Multicenter Observational Study.

Introduction Awareness of SARS-CoV-2 infection in pregnant women and the potential risk for infection of their neonates is increasing. The aim of this study was to examine the immune status of affected women and evaluate the dynamics of placental antibody transfer. Materials and Methods The study included 176 women with SARS-CoV-2 infection during pregnancy who delivered between April 2020 and December 2021 at eight obstetric maternity sites. Demographic data, maternal and neonatal characteristics were summarized. Antibody testing for IgA and IgG in maternal blood sera and umbilical cord samples was evaluated and IgG transfer ratios were calculated. Values were related to the time of infection during pregnancy and birth. Results The percentage of IgG positive women increased from 29.0% (95% CI 23.8 - 37.8) at presentation with a positive PCR test result to 75.7% (95% CI 71.6 - 79.8), the percentage of IgG positive umbilical cord blood samples increased from 17.1% (95% CI 13.0 - 21.3) to 76.4% (95% CI 72.2 - 80.7) at more than six weeks after infection. Regression lines differed significantly between maternal and fetal IgG responses (p < 0.0001). Newborns react with a latency of about one week; umbilical cord blood antibody concentrations are highly correlated with maternal concentration levels (ρ = 0.8042; p < 0.0001). IgG transplacental transfer ratios were dependent on infection-to-birth interval. Two of the umbilical cord blood samples tested positive for IgA. Conclusions These findings confirm vertical SARS-CoV-2 transmission is rare; however, antibodies are transferred to the fetus soon after infection during pregnancy. Since transplacental antibody transfer might have a protective value for neonatal immunization this information may be helpful when counseling affected women.

Antibody Response and Maternofetal Antibody Transfer in SARS-CoV-2-Positive Pregnant Women: A Multicenter Observational Study Immunantwort und Antikörper-Transfer zwischen Mutter und Kind bei schwangeren Frauen mit SARS-CoV-2-Infektion: eine multizentrische Beobachtungsstudie

Introduction Awareness of SARS-CoV-2 infection in pregnant women and the potential risk for infection of their neonates is increasing. The aim of this study was to examine the immune status of affected women and evaluate the dynamics of placental antibody transfer. Materials and Methods The study included 176 women with SARS-CoV-2 infection during pregnancy who delivered between April 2020 and December 2021 at eight obstetric maternity sites. Demographic data, maternal and neonatal characteristics were summarized. Antibody testing for IgA and IgG in maternal blood sera and umbilical cord samples was evaluated and IgG transfer ratios were calculated. Values were related to the time of infection during pregnancy and birth. Results The percentage of IgG positive women increased from 29.0% (95% CI 23.8 – 37.8) at presentation with a positive PCR test result to 75.7% (95% CI 71.6 – 79.8), the percentage of IgG positive umbilical cord blood samples increased from 17.1% (95% CI 13.0 – 21.3) to 76.4% (95% CI 72.2 – 80.7) at more than six weeks after infection. Regression lines differed significantly between maternal and fetal IgG responses (p < 0.0001). Newborns react with a latency of about one week;umbilical cord blood antibody concentrations are highly correlated with maternal concentration levels (ρ = 0.8042;p < 0.0001). IgG transplacental transfer ratios were dependent on infection-to-birth interval. Two of the umbilical cord blood samples tested positive for IgA. Conclusions These findings confirm vertical SARS-CoV-2 transmission is rare;however, antibodies are transferred to the fetus soon after infection during pregnancy. Since transplacental antibody transfer might have a protective value for neonatal immunization this information may be helpful when counseling affected women.

Ciprofloxacin-Resistant Pseudomonas aeruginosa Lung Abscess Complicating COVID-19 Treated with the Novel Oral Fluoroquinolone Delafloxacin.

PURPOSE: We report the development of a lung abscess caused by a ciprofloxacin-resistant Pseudomonas aeruginosa in a patient with COVID-19 on long-term corticosteroid therapy. Successful antimicrobial treatment included the novel oral fluoroquinolone delafloxacin suggesting an oral administration option for ciprofloxacin-resistant Pseudomonas aeruginosa lung abscess. Case Presentation. An 86-year-old male was admitted to the hospital with fever, dry cough, and fatigue. PCR testing from a nasopharyngeal swab confirmed SARS-CoV-2 infection. An initial CT scan of the chest showed COVID-19 typical peripheral ground-glass opacities of both lungs. The patient required supplemental oxygen, and anti-inflammatory treatment with corticosteroids was initiated. After four weeks of corticosteroid therapy, the follow-up CT scan of the chest suddenly showed a new cavernous formation in the right lower lung lobe. The patient's condition deteriorated requiring high-flow oxygen support. Consequently, the patient was transferred to the intensive care unit. Empiric therapy with intravenous piperacillin/tazobactam was started. Mycobacterial and fungal infections were excluded, while all sputum samples revealed cultural growth of P. aeruginosa. Antimicrobial susceptibility testing showed resistance to meropenem, imipenem, ciprofloxacin, gentamicin, and tobramycin. After two weeks of treatment with intravenous piperacillin/tazobactam, the clinical condition improved significantly, and supplemental oxygen could be stopped. Subsequently antimicrobial treatment was switched to oral delafloxacin facilitating an outpatient management. CONCLUSION: Our case demonstrates that long-term corticosteroid administration in severe COVID-19 can result in severe bacterial coinfections including P. aeruginosa lung abscess. To our knowledge, this is the first reported case of a P. aeruginosa lung abscess whose successful therapy included oral delafloxacin. This is important because real-life data for the novel drug delafloxacin are scarce, and fluoroquinolones are the only reliable oral treatment option for P. aeruginosa infection. Even more importantly, our case suggests an oral therapy option for P. aeruginosa lung abscess in case of resistance to ciprofloxacin, the most widely used fluoroquinolone in P. aeruginosa infection.

[Guideline S1: Long COVID: Diagnostics and treatment strategies]. / Leitlinie S1: Long COVID: Differenzialdiagnostik und Behandlungsstrategien.

This guideline comprises the state of science at the time of the editorial deadline. In view of the high turnover of knowledge the guideline is designed as a living guideline. The main objective was to provide a tool for the use in primary care, being considered well suited as a first point of entry and for the provision of care. The guideline gives recommendations on the differential diagnosis of symptoms following SARS-CoV­2 infection, on their therapeutic options, as well as for guidance and care of the patients concerned. It also offers advice concerning return to daily life and rehabilitation. Long COVID being a very variable condition, we chose an interdisciplinary approach.

Virus-induced senescence is a driver and therapeutic target in COVID-19.

Derailed cytokine and immune cell networks account for the organ damage and the clinical severity of COVID-19 (refs. 1-4). Here we show that SARS-CoV-2, like other viruses, evokes cellular senescence as a primary stress response in infected cells. Virus-induced senescence (VIS) is indistinguishable from other forms of cellular senescence and is accompanied by a senescence-associated secretory phenotype (SASP), which comprises pro-inflammatory cytokines, extracellular-matrix-active factors and pro-coagulatory mediators5-7. Patients with COVID-19 displayed markers of senescence in their airway mucosa in situ and increased serum levels of SASP factors. In vitro assays demonstrated macrophage activation with SASP-reminiscent secretion, complement lysis and SASP-amplifying secondary senescence of endothelial cells, which mirrored hallmark features of COVID-19 such as macrophage and neutrophil infiltration, endothelial damage and widespread thrombosis in affected lung tissue1,8,9. Moreover, supernatant from VIS cells, including SARS-CoV-2-induced senescence, induced neutrophil extracellular trap formation and activation of platelets and the clotting cascade. Senolytics such as navitoclax and a combination of dasatinib plus quercetin selectively eliminated VIS cells, mitigated COVID-19-reminiscent lung disease and reduced inflammation in SARS-CoV-2-infected hamsters and mice. Our findings mark VIS as a pathogenic trigger of COVID-19-related cytokine escalation and organ damage, and suggest that senolytic targeting of virus-infected cells is a treatment option against SARS-CoV-2 and perhaps other viral infections.

Prevalence of RT-qPCR-detected SARS-CoV-2 infection at schools: First results from the Austrian School-SARS-CoV-2 prospective cohort study.

BACKGROUND: The role of schools in the SARS-CoV-2 pandemic is much debated. We aimed to quantify reliably the prevalence of SARS-CoV-2 infections at schools detected with reverse-transcription quantitative polymerase-chain-reaction (RT-qPCR). METHODS: This nationwide prospective cohort study monitors a representative sample of pupils (grade 1-8) and teachers at Austrian schools throughout the school year 2020/2021. We repeatedly test participants for SARS-CoV-2 infection using a gargling solution and RT-qPCR. We herein report on the first two rounds of examinations. We used mixed-effects logistic regression to estimate odds ratios and robust 95% confidence intervals (95% CI). FINDINGS: We analysed data on 10,734 participants from 245 schools (9465 pupils, 1269 teachers). Prevalence of SARS-CoV-2 infection increased from 0·39% at round 1 (95% CI 028-0·55%, 28 September-22 October 2020) to 1·39% at round 2 (95% CI 1·04-1·85%, 10-16 November). Odds ratios for SARS-CoV-2 infection were 2·26 (95% CI 1·25-4·12, P = 0·007) in regions with >500 vs. ≤500 inhabitants/km2, 1·67 (95% CI 1·42-1·97, P<0·001) per two-fold higher regional 7-day community incidence, and 2·78 (95% CI 1·73-4·48, P<0·001) in pupils at schools with high/very high vs. low/moderate social deprivation. Associations of regional community incidence and social deprivation persisted in a multivariable adjusted model. Prevalence did not differ by average number of pupils per class nor between age groups, sexes, pupils vs. teachers, or primary (grade 1-4) vs. secondary schools (grade 5-8). INTERPRETATION: This monitoring study in Austrian schools revealed SARS-CoV-2 infection in 0·39%-1·39% of participants and identified associations of regional community incidence and social deprivation with higher prevalence. FUNDING: BMBWF Austria.

Sensitivity and specificity of the antigen-based anterior nasal self-testing programme for detecting SARS-CoV-2 infection in schools, Austria, March 2021.

This study evaluates the performance of the antigen-based anterior nasal screening programme implemented in all Austrian schools to detect SARS-CoV-2 infections. We combined nationwide antigen-based screening data obtained in March 2021 from 5,370 schools (Grade 1-8) with an RT-qPCR-based prospective cohort study comprising a representative sample of 244 schools. Considering a range of assumptions, only a subset of infected individuals are detected with the programme (low to moderate sensitivity) and non-infected individuals mainly tested negative (very high specificity).

Processing Hundreds of SARS-CoV-2 Samples with an In-House PCR-Based Method without Robotics.

The SARS-CoV-2 pandemic has required the development of multiple testing systems to monitor and control the viral infection. Here, we developed a PCR test to screen COVID-19 infections that can process up to ~180 samples per day without the requirement of robotics. For this purpose, we implemented the use of multichannel pipettes and plate magnetics for the RNA extraction step and combined the reverse transcription with the qPCR within one step. We tested the performance of two RT-qPCR kits as well as different sampling buffers and showed that samples taken in NaCl or PBS are stable and compatible with different COVID-19 testing systems. Finally, we designed a new internal control based on the human RNase P gene that does not require a DNA digestion step. Our protocol is easy to handle and reaches the sensitivity and accuracy of the standardized diagnostic protocols used in the clinic to detect COVID-19 infections.

qSOFA score poorly predicts critical progression in COVID-19 patients.

BACKGROUND: In December 2019, the new virus infection coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged. Simple clinical risk scores may improve the management of COVID-19 patients. Therefore, the aim of this pilot study was to evaluate the quick Sequential Organ Failure Assessment (qSOFA) score, which is well established for other diseases, as an early risk assessment tool predicting a severe course of COVID-19. METHODS: We retrospectively analyzed data from adult COVID-19 patients hospitalized between March and July 2020. A critical disease progress was defined as admission to intensive care unit (ICU) or death. RESULTS: Of 64 COVID-19 patients, 33% (21/64) had a critical disease progression from which 13 patients had to be transferred to ICU. The COVID-19-associated mortality rate was 20%, increasing to 39% after ICU admission. All patients without a critical progress had a qSOFA score ≤ 1 at admission. Patients with a critical progress had in only 14% (3/21) and in 20% (3/15) of cases a qSOFA score ≥ 2 at admission (p = 0.023) or when measured directly before critical progression, respectively, while 95% (20/21) of patients with critical progress had an impairment oxygen saturation (SO2) at admission time requiring oxygen supplementation. CONCLUSION: A low qSOFA score cannot be used to assume short-term stable or noncritical disease status in COVID-19.

Myocardial injury in severe COVID-19 is similar to pneumonias of other origin: results from a multicentre study.

AIMS: COVID-19, a respiratory viral disease causing severe pneumonia, also affects the heart and other organs. Whether its cardiac involvement is a specific feature consisting of myocarditis, or simply due to microvascular injury and systemic inflammation, is yet unclear and presently debated. Because myocardial injury is also common in other kinds of pneumonias, we investigated and compared such occurrence in severe pneumonias due to COVID-19 and other causes. METHODS AND RESULTS: We analysed data from 156 critically ill patients requiring mechanical ventilation in four European tertiary hospitals, including all n = 76 COVID-19 patients with severe disease course requiring at least ventilatory support, matched to n = 76 from a retrospective consecutive patient cohort of severe pneumonias of other origin (matched for age, gender, and type of ventilator therapy). When compared to the non-COVID-19, mortality (COVID-19 = 38.2% vs. non-COVID-19 = 51.3%, P = 0.142) and impairment of systolic function were not significantly different. Surprisingly, myocardial injury was even more frequent in non-COVID-19 (96.4% vs. 78.1% P = 0.004). Although inflammatory activity [C-reactive protein (CRP) and interleukin-6] was indifferent, d-dimer and thromboembolic incidence (COVID-19 = 23.7% vs. non-COVID-19 = 5.3%, P = 0.002) driven by pulmonary embolism rates (COVID-19 = 17.1% vs. non-COVID-19 = 2.6%, P = 0.005) were higher. CONCLUSIONS: Myocardial injury was frequent in severe COVID-19 requiring mechanical ventilation, but still less frequent than in similarly severe pneumonias of other origin, indicating that cardiac involvement may not be a specific feature of COVID-19. While mortality was also similar, COVID-19 is characterized with increased thrombogenicity and high pulmonary embolism rates.

Management of patients with SARS-CoV-2 infections and of patients with chronic lung diseases during the COVID-19 pandemic (as of 9 May 2020) : Statement of the Austrian Society of Pneumology (ASP).

The coronavirus disease 2019 (COVID-19) pandemic is currently a challenge worldwide. In Austria, a crisis within the healthcare system has so far been prevented. The treatment of patients with community-acquired pneumonia (CAP), including SARS-CoV­2 infections, should continue to be based on evidence-based CAP guidelines during the pandemic; however, COVID-19 specific adjustments are useful. The treatment of patients with chronic lung diseases has to be adapted during the pandemic but must still be guaranteed.

[Is there a post-COVID syndrome?] / Gibt es ein Post-COVID-Syndrom?

For critically ill COVID-19 patients surviving the acute phase of the disease could possibly only mean having overcome the first stage of a long and challenging path. Physical, cognitive and psychological consequences seem to be realistic; however, do residual symptoms in patients who have returned to microbiological normalization constitute a post-COVID syndrome and which symptoms are principally possible in this context and are able to cause such a syndrome? It is no novelty that critically ill patients often still sustain functional limitations over a long period after discharge from hospital, in many cases even over many years. In most cases of COVID-19 it is too early for the diagnosis of a post-COVID syndrome. For this the symptoms would have to have lasted over a period of at least 6 months; therefore, only a post-infection fatigue can currently be spoken of. On top of this, even if patients recover physically they could be at particular risk of suffering from long-term mental health problems or perceive a reduced quality of life. Such findings exist not only after ARDS as many intensive care unit patients sustain long-term disorders, which is also known as post-intensive care syndrome (PICS). To sum up, there is sufficient evidence for the possible existence of a post-COVID syndrome or for the justification to correspondingly designate these possible sequelae with persisting symptoms in this way. In any case, all efforts that enable a complete functional recovery and a return to a life after corona are justified.