COVID-19 in Schwangerschaft, Geburt und Wochenbett

Coronavirus disease 2019 (COVID-19) is an infectious disease that can lead to severe respiratory symptoms. Pregnant women have an increased risk for a severe course. Therefore, the Association of the Scientific Medical Societies in Germany (AWMF) Guidelines 015/092 "SARS-CoV-2 in pregnancy, childbirth, and the puerperium" were established to standardize care in the COVID-19 pandemic. The guideline group used data from the "COVID-19 related obstetrics and neonatal outcome study" (CRONOS) to generate evidence-based recommendations for action. CRONOS collects data from more than 130 affiliated maternity hospitals nationwide in Germany. According to the study, pregnant women positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are often asymptomatic;however, in 1 out of 25 detected infections there is a severe course requiring intensive medical treatment. Thromboembolism occurs in 1 out of 30 women hospitalized for COVID-19. An infection of the neonate of a mother infected peripartum is occasionally detected (about 1 out of 20 infants) and usually remains without consequence in the short-term outcome. Many other questions have been answered using CRONOS data. The registry is still open and recruiting and will also provide more in-depth information on different virus variants and vaccination in the future with more than 6000 cases. CRONOS is exemplary for an unprecedented cooperation of gynecologists during the pandemic.

COVID-19 in Schwangerschaft, Geburt und Wochenbett : Das CRONOS-Register COVID-19 in pregnancy, childbirth and puerperiumThe CRONOS registry

COVID(„coronavirus disease“)-19 ist eine Infektionserkrankung, die zu schweren respiratorischen Symptomen führen kann. Schwangere haben ein erhöhtes Risiko für einen schweren Verlauf. Für eine gute Betreuung in der COVID-19-Pandemie wurde daher die AWMF(Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften)-Leitlinie 015/092 „SARS-CoV‑2 in Schwangerschaft, Geburt und Wochenbett“ erstellt. Die Leitliniengruppe nutzte zur Erstellung von evidenzbasierten Handlungsempfehlungen die Daten der „Covid-19 Related Obstetrics and Neonatal Outcome Study“ (CRONOS). CRONOS sammelt deutschlandweit Daten aus mehr als 130 angeschlossenen Geburtenkliniken. SARS-CoV-2(„severe acute respiratory syndrome coronavirus 2“)-positive Schwangere sind demnach häufig asymptomatisch. Bei 1 von 25 erkannten Infektionen kommt es jedoch zu einem schweren Verlauf mit intensivmedizinischer Behandlung. Bei 1 von 30 stationär wegen COVID-19 behandelten Frauen kommt es zu einer Thromboembolie. Eine Infektion des Neugeborenen einer peripartal infizierten Mutter wird gelegentlich (etwa 1 von 20 Kindern) nachgewiesen und bleibt in der Regel ohne Konsequenz im Kurzzeit-Outcome. Viele weitere Fragestellungen wurden mithilfe von CRONOS beantwortet. Das weiter aktiv rekrutierende Register wird zukünftig mit mehr als 6000 Fällen auch tiefere Informationen zu verschiedenen Virusvarianten und zum Impfen liefern. CRONOS steht vorbildlich für eine beispiellose Kooperation von Ärztinnen und Ärzten der Frauenheilkunde in der Pandemie.

[COVID-19 in obstetric anesthesia : Prospective surveillance of peripartum infections with SARS-CoV-2 and peripartum course of disease in affected women]. / COVID-19 in der geburtshilflichen Anästhesie : Prospektive Erfassung von SARS-CoV-2-Infektionen zum Zeitpunkt der Geburt sowie des peripartalen Verlaufs SARS-CoV-2-positiver Schwangerer.

BACKGROUND: In the current pandemic regarding the infection with the SARS-CoV-2-virus and COVID-19 as the disease, concerns about pregnant women, effects on childbirth and the health of the newborn remain high. Initially, due to the early manifestation of the disease in younger patients, high numbers of COVID-19 patients in women needing peripartum care were expected. OBJECTIVE: This article aims to provide a general overview over the beginning of the pandemic as well as the second wave of infections in Germany and Switzerland, regarding SARS-CoV­2 positive pregnant women hospitalized for childbirth. We therefore launched a registry to gain timely information over the dynamic situation during the SARS-CoV­2 pandemic in Germany. MATERIAL AND METHODS: As part of the COVID-19-related Obstetric Anesthesia Longitudinal Assessment (COALA) registry, centers reported weekly birth rates, numbers of suspected SARS-CoV­2 cases, as well as the numbers of confirmed cases between 16 March and 3 May 2020. Data acquisition was continued from 18 October 2020 till 28 February 2021. The data were analyzed regarding distribution of SARS-CoV­2 positive pregnant women hospitalized for childbirth between centers, calendar weeks and birth rates as well as maternal characteristics, course of disease and outcomes of SARS-CoV­2 positive pregnant women. RESULTS: A total of 9 German centers reported 2270 deliveries over 7 weeks during the first wave of infections including 3 SARS-CoV­2 positive cases and 9 suspected cases. During the second survey period, 6 centers from Germany and Switzerland reported 41 positive cases out of 4897 deliveries. One woman presented with a severe and ultimately fatal course of the disease, while another one needed prolonged ECMO treatment. Of the women 28 presented with asymptomatic infections and 6 neonates were admitted to a neonatal intensive care unit for further treatment. There was one case of neonatal SARS-CoV­2 infection. CONCLUSION: The number of pregnant women infected with SARS-CoV­2 was at a very low level at the time of delivery, with only sporadic suspected or confirmed cases. Due to the lack of comprehensive testing in the first survey period, however, a certain number of asymptomatic cases are to be assumed. Of the cases 68% presented as asymptomatic or as mild courses of disease but the data showed that even in young healthy patients without the presence of typical risk factors, serious progression can occur. These outcomes should raise awareness for anesthesiologists, obstetricians, pediatricians and intensive care physicians to identify severe cases of COVID-19 in pregnant women during childbirth and to take the necessary precautions to ensure the best treatment of mother and neonate. The prospective acquisition of data allowed a timely assessment of the highly dynamic situation and gain knowledge regarding this vulnerable group of patients.

Point of care diagnostic of hypercoagulability and platelet function in COVID-19 induced acute respiratory distress syndrome: a retrospective observational study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) associated coagulopathy (CAC) leads to thromboembolic events in a high number of critically ill COVID-19 patients. However, specific diagnostic or therapeutic algorithms for CAC have not been established. In the current study, we analyzed coagulation abnormalities with point-of-care testing (POCT) and their relation to hemostatic complications in patients suffering from COVID-19 induced Acute Respiratory Distress Syndrome (ARDS). Our hypothesis was that specific diagnostic patterns can be identified in patients with COVID-19 induced ARDS at risk of thromboembolic complications utilizing POCT. METHODS: This is a single-center, retrospective observational study. Longitudinal data from 247 rotational thromboelastometries (Rotem®) and 165 impedance aggregometries (Multiplate®) were analysed in 18 patients consecutively admitted to the ICU with a COVID-19 induced ARDS between March 12th to June 30th, 2020. RESULTS: Median age was 61 years (IQR: 51-69). Median PaO2/FiO2 on admission was 122 mmHg (IQR: 87-189), indicating moderate to severe ARDS. Any form of hemostatic complication occurred in 78 % of the patients with deep vein/arm thrombosis in 39 %, pulmonary embolism in 22 %, and major bleeding in 17 %. In Rotem® elevated A10 and maximum clot firmness (MCF) indicated higher clot strength. The delta between EXTEM A10 minus FIBTEM A10 (ΔA10) > 30 mm, depicting the sole platelet-part of clot firmness, was associated with a higher risk of thromboembolic events (OD: 3.7; 95 %CI 1.3-10.3; p = 0.02). Multiplate® aggregometry showed hypoactive platelet function. There was no correlation between single Rotem® and Multiplate® parameters at intensive care unit (ICU) admission and thromboembolic or bleeding complications. CONCLUSIONS: Rotem® and Multiplate® results indicate hypercoagulability and hypoactive platelet dysfunction in COVID-19 induced ARDS but were all in all poorly related to hemostatic complications..

Vitamin D deficiency in critically ill COVID-19 ARDS patients.

BACKGROUND & AIMS: Vitamin D's pleiotropic effects include immune modulation, and its supplementation has been shown to prevent respiratory tract infections. The effectivity of vitamin D as a therapeutic intervention in critical illness remains less defined. The current study analyzed clinical and immunologic effects of vitamin D levels in patients suffering from coronavirus disease 2019 (COVID-19) induced acute respiratory distress syndrome (ARDS). METHODS: This was a single-center retrospective study in patients receiving intensive care with a confirmed SARS-CoV-2 infection and COVID-19 ARDS. 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D serum levels, pro- and anti-inflammatory cytokines and immune cell subsets were measured on admission as well as after 10-15 days. Clinical parameters were extracted from the patient data management system. Standard operating procedures included the daily administration of vitamin D3 via enteral feeding. RESULTS: A total of 39 patients with COVID-19 ARDS were eligible, of which 26 were included in this study as data on vitamin D status was available. 96% suffered from severe COVID-19 ARDS. All patients without prior vitamin D supplementation (n = 22) had deficient serum levels of 25-hydroxyvitamin D. Vitamin D supplementation resulted in higher serum levels of 25-hydroxyvitamin D but not did not increase 1,25-dihydroxyvitamin D levels after 10-15 days. Clinical parameters did not differ between patients with sufficient or deficient levels of 25-hydroxyvitamin D. Only circulating plasmablasts were higher in patients with 25-hydroxyvitamin D levels ≥30 ng/ml (p = 0.029). Patients with 1,25-dihydroxyvitamin D levels below 20 pg/ml required longer mechanical ventilation (p = 0.045) and had a worse acute physiology and chronic health evaluation (APACHE) II score (p = 0.048). CONCLUSION: The vast majority of COVID-19 ARDS patients had vitamin D deficiency. 25-hydroxyvitamin D status was not related to changes in clinical course, whereas low levels of 1,25-dihydroxyvitamin D were associated with prolonged mechanical ventilation and a worse APACHE II score.

Biodistribution and serologic response in SARS-CoV-2 induced ARDS: A cohort study.

BACKGROUND: The viral load and tissue distribution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain important questions. The current study investigated SARS-CoV-2 viral load, biodistribution and anti-SARS-CoV-2 antibody formation in patients suffering from severe corona virus disease 2019 (COVID-19) induced acute respiratory distress syndrome (ARDS). METHODS: This is a retrospective single-center study in 23 patients with COVID-19-induced ARDS. Data were collected within routine intensive care. SARS-CoV-2 viral load was assessed via reverse transcription quantitative polymerase chain reaction (RT-qPCR). Overall, 478 virology samples were taken. Anti-SARS-CoV-2-Spike-receptor binding domain (RBD) antibody detection of blood samples was performed with an enzyme-linked immunosorbent assay. RESULTS: Most patients (91%) suffered from severe ARDS during ICU treatment with a 30-day mortality of 30%. None of the patients received antiviral treatment. Tracheal aspirates tested positive for SARS-CoV-2 in 100% of the cases, oropharyngeal swabs only in 77%. Blood samples were positive in 26% of the patients. No difference of viral load was found in tracheal or blood samples with regard to 30-day survival or disease severity. SARS-CoV-2 was never found in dialysate. Serologic testing revealed significantly lower concentrations of SARS-CoV-2 neutralizing IgM and IgA antibodies in survivors compared to non-survivors (p = 0.009). CONCLUSIONS: COVID-19 induced ARDS is accompanied by a high viral load of SARS-CoV-2 in tracheal aspirates, which remained detectable in the majority throughout intensive care treatment. Remarkably, SARS-CoV-2 RNA was never detected in dialysate even in patients with RNAemia. Viral load or the buildup of neutralizing antibodies was not associated with 30-day survival or disease severity.

Pro- and Anti-Inflammatory Responses in Severe COVID-19-Induced Acute Respiratory Distress Syndrome-An Observational Pilot Study.

Objectives: The severity of Coronavirus Disease 2019 (COVID-19) is largely determined by the immune response. First studies indicate altered lymphocyte counts and function. However, interactions of pro- and anti-inflammatory mechanisms remain elusive. In the current study we characterized the immune responses in patients suffering from severe COVID-19-induced acute respiratory distress syndrome (ARDS). Methods: This was a single-center retrospective study in patients admitted to the intensive care unit (ICU) with confirmed COVID-19 between March 14th and May 28th 2020 (n = 39). Longitudinal data were collected within routine clinical care, including flow-cytometry of lymphocyte subsets, cytokine analysis and growth differentiation factor 15 (GDF-15). Antibody responses against the receptor binding domain (RBD) of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike protein were analyzed. Results: All patients suffered from severe ARDS, 30.8% died. Interleukin (IL)-6 was massively elevated at every time-point. The anti-inflammatory cytokine IL-10 was concomitantly upregulated with IL-6. The cellular response was characterized by lymphocytopenia with low counts of CD8+ T cells, natural killer (NK) and naïve T helper cells. CD8+ T and NK cells recovered after 8 to 14 days. The B cell system was largely unimpeded. This coincided with a slight increase in anti-SARS-CoV-2-Spike-RBD immunoglobulin (Ig) G and a decrease in anti-SARS-CoV-2-Spike-RBD IgM. GDF-15 levels were elevated throughout ICU treatment. Conclusions: Massively elevated levels of IL-6 and a delayed cytotoxic immune defense characterized severe COVID-19-induced ARDS. The B cell response and antibody production were largely unimpeded. No obvious imbalance of pro- and anti-inflammatory mechanisms was observed, with elevated GDF-15 levels suggesting increased tissue resilience.

[Obstetric Anesthesia During the SARS-CoV-2 Pandemic - a Brief Overview of Published Recommendations for Action by National and International Specialist Societies and Committees]. / Geburtshilfliche Anästhesie während der SARS-CoV-2-Pandemie: Übersicht der Handlungsempfehlungen.

The most common human corona viruses cause common colds. But three of these viruses cause more serious, acute diseases; Middle East Respiratory Syndrome (MERS by MERS-CoV), Severe Acute Respiratory Syndrome (SARS) by SARS-CoV and COVID-19 by SARS-CoV-2. The current outbreak was classified by the WHO as a "global public health emergency". Despite all efforts to reduce the surgical lists and to cancel or postpone non-time-critical surgical interventions, some surgical and anesthetic interventions outside of intensive care medicine are still necessary and must be performed. This is particularly true for obstetric interventions and neuraxial labor analgesia. Workload in the delivery room is presumably not going to decrease and planned cesarean sections cannot be postponed. In the meantime, the clinical course and outcome of some COVID-19 patients with an existing pregnancy or peripartum courses have been reported. There are already numerous recommendations from national and international bodies regarding the care of such patients. Some of these recommendations will be summarized in this manuscript. The selection of aspects should by no means be seen as a form of prioritization. The general treatment principles in dealing with COVID-19 patients and the recommendations for action in intensive care therapy also apply to pregnant and postpartum patients. In this respect, there are naturally considerable redundancies and only a few aspects apply strictly or exclusively to the cohort of obstetric patients. In summary, at present it must be stated that the general care recommendations that also apply to non-COVID-19 patients are initially valid with regard to obstetric anesthesia. Nevertheless, the special requirements on the part of hygiene and infection protection result in special circumstances that should be taken into account when caring for pregnant patients from an anesthetic point of view. These relate to both medical aspects, but also to a particular extent logistics issues with regard to spatial separation, staffing and material resources.