Search

High efficacy in terms of protection from severe COVID-19 has been demonstrated for several SARS-CoV-2 vaccines. However, patients with compromised immune status develop a weaker and less stable immune response to vaccination. Strong immune response may not always translate into clinical benefit, therefore it is important to synthesise evidence on modified schemes and types of vaccination in these population subgroups for guiding health decisions. As the literature on COVID-19 vaccines continues to expand, we aimed to scope the literature on multiple subgroups to subsequently decide on the most relevant research questions to be answered by systematic reviews.To provide an overview of the availability of existing literature on immune response and long-term clinical outcomes after COVID-19 vaccination, and to map this evidence according to the examined populations, specific vaccines, immunity parameters, and their way of determining relevant long-term outcomes and the availability of mapping between immune reactivity and relevant outcomes.We searched the Cochrane COVID-19 Study Register, the Web of Science Core Collection, and the World Health Organization COVID-19 Global literature on coronavirus disease on 6 December 2021. SELECTION CRITERIA: We included studies that published results on immunity outcomes after vaccination with BNT162b2, mRNA-1273, AZD1222, Ad26.COV2.S, Sputnik V or Sputnik Light, BBIBP-CorV, or CoronaVac on predefined vulnerable subgroups such as people with malignancies, transplant recipients, people undergoing renal replacement therapy, and people with immune disorders, as well as pregnant and breastfeeding women, and children. We included studies if they had at least 100 participants (not considering healthy control groups); we excluded case studies and case series.We extracted data independently and in duplicate onto an online data extraction form. Data were represented as tables and as online maps to show the frequency of studies for each item. We mapped the data according to study design, country of participant origin, patient comorbidity subgroup, intervention, outcome domains (clinical, safety, immunogenicity), and outcomes. MAIN RESULTS: Out of 25,452 identified records, 318 studies with a total of more than 5 million participants met our eligibility criteria and were included in the review. Participants were recruited mainly from high-income countries between January 2020 and 31 October 2021 (282/318); the majority of studies included adult participants (297/318). Haematological malignancies were the most commonly examined comorbidity group (N = 54), followed by solid tumours (N = 47), dialysis (N = 48), kidney transplant (N = 43), and rheumatic diseases (N = 28, 17, and 15 for mixed diseases, multiple sclerosis, and inflammatory bowel disease, respectively). Thirty-one studies included pregnant or breastfeeding women. The most commonly administered vaccine was BNT162b2 (N = 283), followed by mRNA-1273 (N = 153), AZD1222 (N = 66), Ad26.COV2.S (N = 42), BBIBP-CorV (N = 15), CoronaVac (N = 14), and Sputnik V (N = 5; no studies were identified for Sputnik Light). Most studies reported outcomes after regular vaccination scheme. The majority of studies focused on immunogenicity outcomes, especially seroconversion based on binding antibody measurements and immunoglobulin G (IgG) titres (N = 179 and 175, respectively). Adverse events and serious adverse events were reported in 126 and 54 studies, whilst SARS-CoV-2 infection irrespective of severity was reported in 80 studies. Mortality due to SARS-CoV-2 infection was reported in 36 studies. Please refer to our evidence gap maps for more detailed information.Up to 6 December 2021, the majority of studies examined data on mRNA vaccines administered as standard vaccination schemes (two doses approximately four to eight weeks apart) that report on immunogenicity parameters or adverse events. Clinical outcomes were less commonly reported, and if so, were often reported as a secondary outcome observed in seroconversion or immunoglobulin titre studies. As informed by this scoping review, two effectiveness reviews (on haematological malignancies and kidney transplant recipients) are currently being conducted.

BACKGROUND: Acute respiratory distress syndrome (ARDS) represents the most severe course of COVID‐19 (caused by the SARS‐CoV‐2 virus), usually resulting in a prolonged stay in an intensive care unit (ICU) and high mortality rates. Despite the fact that most affected individuals need invasive mechanical ventilation (IMV), evidence on specific ventilation strategies for ARDS caused by COVID‐19 is scarce. Spontaneous breathing during IMV is part of a therapeutic concept comprising light levels of sedation and the avoidance of neuromuscular blocking agents (NMBA). This approach is potentially associated with both advantages (e.g. a preserved diaphragmatic motility and an optimised ventilation‐perfusion ratio of the ventilated lung), as well as risks (e.g. a higher rate of ventilator‐induced lung injury or a worsening of pulmonary oedema due to increases in transpulmonary pressure). As a consequence, spontaneous breathing in people with COVID‐19‐ARDS who are receiving IMV is subject to an ongoing debate amongst intensivists. OBJECTIVES: To assess the benefits and harms of early spontaneous breathing activity in invasively ventilated people with COVID‐19 with ARDS compared to ventilation strategies that avoid spontaneous breathing. SEARCH METHODS: We searched the Cochrane COVID‐19 Study Register (which includes CENTRAL, PubMed, Embase, Clinical Trials.gov WHO ICTRP, and medRxiv) and the WHO COVID‐19 Global literature on coronavirus disease to identify completed and ongoing studies from their inception to 2 March 2022. SELECTION CRITERIA: Eligible study designs comprised randomised controlled trials (RCTs) that evaluated spontaneous breathing in participants with COVID‐19‐related ARDS compared to ventilation strategies that avoided spontaneous breathing (e.g. using NMBA or deep sedation levels). Additionally, we considered controlled before‐after studies, interrupted time series with comparison group, prospective cohort studies and retrospective cohort studies. For these non‐RCT studies, we considered a minimum total number of 50 participants to be compared as necessary for inclusion. Prioritised outcomes were all‐cause mortality, clinical improvement or worsening, quality of life, rate of (serious) adverse events and rate of pneumothorax. Additional outcomes were need for tracheostomy, duration of ICU length of stay and duration of hospitalisation. DATA COLLECTION AND ANALYSIS: We followed the methods outlined in the Cochrane Handbook for Systematic Reviews of Interventions. Two review authors independently screened all studies at the title/abstract and full‐text screening stage. We also planned to conduct data extraction and risk of bias assessment in duplicate. We planned to conduct meta‐analysis for each prioritised outcome, as well as subgroup analyses of mortality regarding severity of oxygenation impairment and duration of ARDS. In addition, we planned to perform sensitivity analyses for studies at high risk of bias, studies using NMBA in addition to deep sedation level to avoid spontaneous breathing and a comparison of preprints versus peer‐reviewed articles. We planned to assess the certainty of evidence using the GRADE approach. MAIN RESULTS: We identified no eligible studies for this review. AUTHORS' CONCLUSIONS: We found no direct evidence on whether early spontaneous breathing in SARS‐CoV‐2‐induced ARDS is beneficial or detrimental to this particular group of patients. RCTs comparing early spontaneous breathing with ventilatory strategies not allowing for spontaneous breathing in SARS‐CoV‐2‐induced ARDS are necessary to determine its value within the treatment of severely ill people with COVID‐19. Additionally, studies should aim to clarify whether treatment effects differ between people with SARS‐CoV‐2‐induced ARDS and people with non‐SARS‐CoV‐2‐induced ARDS.

BACKGROUND: With potential antiviral and anti‐inflammatory properties, Janus kinase (JAK) inhibitors represent a potential treatment for symptomatic severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. They may modulate the exuberant immune response to SARS‐CoV‐2 infection. Furthermore, a direct antiviral effect has been described. An understanding of the current evidence regarding the efficacy and safety of JAK inhibitors as a treatment for coronavirus disease 2019 (COVID‐19) is required. OBJECTIVES: To assess the effects of systemic JAK inhibitors plus standard of care compared to standard of care alone (plus/minus placebo) on clinical outcomes in individuals (outpatient or in‐hospital) with any severity of COVID‐19, and to maintain the currency of the evidence using a living systematic review approach. SEARCH METHODS: We searched the Cochrane COVID‐19 Study Register (comprising MEDLINE, Embase, ClinicalTrials.gov, World Health Organization (WHO) International Clinical Trials Registry Platform, medRxiv, and Cochrane Central Register of Controlled Trials), Web of Science, WHO COVID‐19 Global literature on coronavirus disease, and the US Department of Veterans Affairs Evidence Synthesis Program (VA ESP) Covid‐19 Evidence Reviews to identify studies up to February 2022. We monitor newly published randomised controlled trials (RCTs) weekly using the Cochrane COVID‐19 Study Register, and have incorporated all new trials from this source until the first week of April 2022. SELECTION CRITERIA: We included RCTs that compared systemic JAK inhibitors plus standard of care to standard of care alone (plus/minus placebo) for the treatment of individuals with COVID‐19. We used the WHO definitions of illness severity for COVID‐19. DATA COLLECTION AND ANALYSIS: We assessed risk of bias of primary outcomes using Cochrane's Risk of Bias 2 (RoB 2) tool. We used GRADE to rate the certainty of evidence for the following primary outcomes: all‐cause mortality (up to day 28), all‐cause mortality (up to day 60), improvement in clinical status: alive and without need for in‐hospital medical care (up to day 28), worsening of clinical status: new need for invasive mechanical ventilation or death (up to day 28), adverse events (any grade), serious adverse events, secondary infections. MAIN RESULTS: We included six RCTs with 11,145 participants investigating systemic JAK inhibitors plus standard of care compared to standard of care alone (plus/minus placebo). Standard of care followed local protocols and included the application of glucocorticoids (five studies reported their use in a range of 70% to 95% of their participants; one study restricted glucocorticoid use to non‐COVID‐19 specific indications), antibiotic agents, anticoagulants, and antiviral agents, as well as non‐pharmaceutical procedures. At study entry, about 65% of participants required low‐flow oxygen, about 23% required high‐flow oxygen or non‐invasive ventilation, about 8% did not need any respiratory support, and only about 4% were intubated. We also identified 13 ongoing studies, and 9 studies that are completed or terminated and where classification is pending. Individuals with moderate to severe disease Four studies investigated the single agent baricitinib (10,815 participants), one tofacitinib (289 participants), and one ruxolitinib (41 participants). Systemic JAK inhibitors probably decrease all‐cause mortality at up to day 28 (95 of 1000 participants in the intervention group versus 131 of 1000 participants in the control group; risk ratio (RR) 0.72, 95% confidence interval (CI) 0.57 to 0.91; 6 studies, 11,145 participants; moderate‐certainty evidence), and decrease all‐cause mortality at up to day 60 (125 of 1000 participants in the intervention group versus 181 of 1000 participants in the control group; RR 0.69, 95% CI 0.56 to 0.86; 2 studies, 1626 participants; high‐certainty evidence). Systemic JAK inhibitors probably make little or no difference in improvement in clinical status (discharged alive or hospitalised, but no longer requiring ongoing medical care) (801 of 1000 participants in the intervention group versus 778 of 1000 participants in the control group; RR 1.03, 95% CI 1.00 to 1.06; 4 studies, 10,802 participants; moderate‐certainty evidence). They probably decrease the risk of worsening of clinical status (new need for invasive mechanical ventilation or death at day 28) (154 of 1000 participants in the intervention group versus 172 of 1000 participants in the control group; RR 0.90, 95% CI 0.82 to 0.98; 2 studies, 9417 participants; moderate‐certainty evidence). Systemic JAK inhibitors probably make little or no difference in the rate of adverse events (any grade) (427 of 1000 participants in the intervention group versus 441 of 1000 participants in the control group; RR 0.97, 95% CI 0.88 to 1.08; 3 studies, 1885 participants; moderate‐certainty evidence), and probably decrease the occurrence of serious adverse events (160 of 1000 participants in the intervention group versus 202 of 1000 participants in the control group; RR 0.79, 95% CI 0.68 to 0.92; 4 studies, 2901 participants; moderate‐certainty evidence). JAK inhibitors may make little or no difference to the rate of secondary infection (111 of 1000 participants in the intervention group versus 113 of 1000 participants in the control group; RR 0.98, 95% CI 0.89 to 1.09; 4 studies, 10,041 participants; low‐certainty evidence). Subgroup analysis by severity of COVID‐19 disease or type of JAK inhibitor did not identify specific subgroups which benefit more or less from systemic JAK inhibitors. Individuals with asymptomatic or mild disease We did not identify any trial for this population. AUTHORS' CONCLUSIONS: In hospitalised individuals with moderate to severe COVID‐19, moderate‐certainty evidence shows that systemic JAK inhibitors probably decrease all‐cause mortality. Baricitinib was the most often evaluated JAK inhibitor. Moderate‐certainty evidence suggests that they probably make little or no difference in improvement in clinical status. Moderate‐certainty evidence indicates that systemic JAK inhibitors probably decrease the risk of worsening of clinical status and make little or no difference in the rate of adverse events of any grade, whilst they probably decrease the occurrence of serious adverse events. Based on low‐certainty evidence, JAK inhibitors may make little or no difference in the rate of secondary infection. Subgroup analysis by severity of COVID‐19 or type of agent failed to identify specific subgroups which benefit more or less from systemic JAK inhibitors. Currently, there is no evidence on the efficacy and safety of systemic JAK inhibitors for individuals with asymptomatic or mild disease (non‐hospitalised individuals).

BACKGROUND: When the SARS-CoV-2 pandemic began, no uniform treatment and care strategies for critically ill COVID-19 patients were yet available. National and international treatment recommendations were formulated under time pressure, initially on the basis of indirect evidence from the treatment of similar diseases. In this article, we give an overview of the content, currency, and methodological quality of the existing national and international guidelines, with special attention to the care of critically ill patients. METHODS: Guidelines were identified by a comprehensive search, the included guidelines were assessed in standardized fashion with the AGREE II guideline assessment instrument and according to the AMWF rulebook criteria, and the core recommendations of the included and methodologically high-quality guidelines were compared. RESULTS: Nine of the 97 guidelines that were identified fulfilled the content criteria for inclusion, and 6 of these fulfilled the qualitative criteria; these 6 guidelines still differed, however, in the topics to which they devoted the most attention, as well as in their methodological quality and currency. The treatment strategies for patients with severe respiratory failure (lung-protective ventilation strategies and rescue measures) deviated little from established standards. Uniform recommendations were made, among other things, for the administration of dexamethasone, which was recommended in all of the guidelines for patients requiring oxygen treatment, as well as for antithrombotic drug prophylaxis and for the prone positioning of ventilated patients. Many recommendations were based on insufficient evidence, and some were contradictory, e.g., those regarding antibiotic treatment or the choice between high-flow oxygen administration via nasal canula (HFNC) and noninvasive ventilation (NIV). CONCLUSION: The consultation of multiple high-quality international guidelines and guideline recommendations shared in online portals such as MagicApp are helpful sources of information for clinicians. In view of the continuing lack of strong evidence, further research on intensive care treatments is needed (aspects of ventilation, positioning therapy, and the role of extracorporeal membrane oxygenation [ECMO]).

Background: The surge in patients during the COVID-19 pandemic has exacerbated the looming problem of staff shortage in German ICUs possibly leading to worse outcomes for patients. Methods: Within the German Evidence Ecosystem CEOsys network, we conducted an online national mixed-methods survey assessing the standard of care in German ICUs treating patients with COVID-19. Results: A total of 171 German ICUs reported a median ideal number of patients per intensivist of 8 (interquartile range, IQR = 3rd quartile - 1st quartile = 4.0) and per nurse of 2.0 (IQR = 1.0). For COVID-19 patients, the median target was a maximum of 6.0 (IQR = 2.0) patients per intensivist or 2.0 (IQR = 0.0) patients per nurse. Targets for intensivists were rarely met by 15.2% and never met by 3.5% of responding institutions. Targets for nursing staffing could rarely be met in 32.2% and never in 5.3% of responding institutions.Conclusions: Shortages of staffing in the critical care setting are eminent during the COVID-19 pandemic and might not only negatively affect patient outcomes, but also staff wellbeing and healthcare costs. A joint effort that scrutinizes the demands and structures of our health care system seems fundamental to be prepared for the future.

Objective.The aim of this retrospective study was to assess the suitability of routine data gathered with a computerized anesthesia record keeping system in investigating predictors for intraoperative hypoxemia (SpO2 < 90%) during one-lung ventilation (OLV) in pulmonary surgery. Methods.Over a four-year period data of 705 patients undergoing thoracic surgery (pneumonectomy: 78; lobectomy: 292; minor pulmonary resections: 335) were recorded online using an automated anesthesia record-keeping system. Twenty-six patient-related, surgery-related and anesthesia-related variables were studied for a possible association with the occurrence of intraoperative hypoxemia during OLV. Data were analyzed using univariate and multivariate (logistic regression) analysis (p< 0.05). The model’s discriminative power on hypoxemia was checked with a receiver operating characteristic (ROC) curve. Calibration was tested using the Hosmer-Lemeshow goodness-of-fit test. Results.An intraoperative incidence of hypoxemia during OLV was found in 67 patients (9.5%). Using logistic regression with a forward stepwise algorithm, body-mass-index (BMI, p= 0.018) and preoperative existing pneumonia (p= 0.043) could be detected as independent predictors having an influence on the incidence of hypoxemia during OLV. An acceptable goodness-of-fit could be observed using cross validation for the model (C = 8.21, p= 0.370, degrees of freedom, df 8; H = 3.21, p= 0.350, df 3), the discriminative power was poor with an area under the ROC curve of 0.58 [0.51–0.66]. Conclusions.In contrast to conventional performed retrospective studies, data were directly available for analyses without any manual intervention. Due to incomplete information and imprecise definitions of parameters, data of computerized anesthesia records collected in routine are helpful but not satisfactory in evaluating risk factors for hypoxemia during OLV.

Background: Early treatment with rt-PA is critical for favorable outcome of acute stroke. However, only a very small proportion of stroke patients receive this treatment, as most arrive at hospital too late to be eligible for rt-PA therapy. Methods and Findings: We developed a ‘‘Mobile Stroke Unit’’, consisting of an ambulance equipped with computed tomography, a point-of-care laboratory system for complete stroke laboratory work-up, and telemedicine capabilities for contact with hospital experts, to achieve delivery of etiology-specific and guideline-adherent stroke treatment at the site of the emergency, well before arrival at the hospital. In a departure from current practice, stroke patients could be differentially treated according to their ischemic or hemorrhagic etiology even in the prehospital phase of stroke management. Immediate diagnosis of cerebral ischemia and exclusion of thrombolysis contraindications enabled us to perform prehospital rt-PA thrombolysis as bridging to later intra-arterial recanalization in one patient. In a complementary patient with cerebral hemorrhage, prehospital diagnosis allowed immediate initiation of hemorrhage-specific blood pressure management and telemedicine consultation regarding surgery. Call-to-therapy-decision times were 35 minutes. Conclusion: This preliminary study proves the feasibility of guideline-adherent, etiology-specific and causal treatment of acute stroke directly at the emergency site.

The aim of this retrospective study was to assess the suitability of routine data gathered with a computerized anesthesia record keeping system in investigating predictors for intraoperative hypoxemia (SpO290%) during one-lung ventilation (OLV) in pulmonary surgery.Over a four-year period data of 705 patients undergoing thoracic surgery (pneumonectomy: 78; lobectomy: 292; minor pulmonary resections: 335) were recorded online using an automated anesthesia record-keeping system. Twenty-six patient-related, surgery-related and anesthesia-related variables were studied for a possible association with the occurrence of intraoperative hypoxemia during OLV. Data were analyzed using univariate and multivariate (logistic regression) analysis (p0.05). The model's discriminative power on hypoxemia was checked with a receiver operating characteristic (ROC) curve. Calibration was tested using the Hosmer-Lemeshow goodness-of-fit test.An intraoperative incidence of hypoxemia during OLV was found in 67 patients (9.5%). Using logistic regression with a forward stepwise algorithm, body-mass-index (BMI, p = 0.018) and preoperative existing pneumonia (p = 0.043) could be detected as independent predictors having an influence on the incidence of hypoxemia during OLV. An acceptable goodness-of-fit could be observed using cross validation for the model (C = 8.21, p = 0.370, degrees of freedom, df 8; H = 3.21, p = 0.350, df 3), the discriminative power was poor with an area under the ROC curve of 0.58 [0.51-0.66].In contrast to conventional performed retrospective studies, data were directly available for analyses without any manual intervention. Due to incomplete information and imprecise definitions of parameters, data of computerized anesthesia records collected in routine are helpful but not satisfactory in evaluating risk factors for hypoxemia during OLV.