Background
Convalescent plasma and hyperimmune immunoglobulin may reduce mortality in patients with respiratory virus diseases, and are currently being investigated in trials as a potential therapy ...for coronavirus disease 2019 (COVID‐19). A thorough understanding of the current body of evidence regarding the benefits and risks is required.
Objectives
To assess whether convalescent plasma or hyperimmune immunoglobulin transfusion is effective and safe in the treatment of people with COVID‐19.
Search methods
The protocol was pre‐published with the Center for Open Science and can be accessed here: osf.io/dwf53
We searched the World Health Organization (WHO) COVID‐19 Global Research Database, MEDLINE, Embase, Cochrane COVID‐19 Study Register, Centers for Disease Control and Prevention COVID‐19 Research Article Database and trials registries to identify ongoing studies and results of completed studies on 23 April 2020 for case‐series, cohort, prospectively planned, and randomised controlled trials (RCTs).
Selection criteria
We followed standard Cochrane methodology and performed all steps regarding study selection in duplicate by two independent review authors (in contrast to the recommendations of the Cochrane Rapid Reviews Methods Group).
We included studies evaluating convalescent plasma or hyperimmune immunoglobulin for people with COVID‐19, irrespective of disease severity, age, gender or ethnicity.
We excluded studies including populations with other coronavirus diseases (severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS)) and studies evaluating standard immunoglobulins.
Data collection and analysis
We followed recommendations of the Cochrane Rapid Reviews Methods Group regarding data extraction and assessment.
To assess bias in included studies, we used the assessment criteria tool for observational studies, provided by Cochrane Childhood Cancer. We rated the certainty of evidence using the GRADE approach for the following outcomes: all‐cause mortality at hospital discharge, improvement of clinical symptoms (7, 15, and 30 days after transfusion), grade 3 and 4 adverse events, and serious adverse events.
Main results
We included eight studies (seven case‐series, one prospectively planned, single‐arm intervention study) with 32 participants, and identified a further 48 ongoing studies evaluating convalescent plasma (47 studies) or hyperimmune immunoglobulin (one study), of which 22 are randomised.
Overall risk of bias of the eight included studies was high, due to: study design; small number of participants; poor reporting within studies; and varied type of participants with different severities of disease, comorbidities, and types of previous or concurrent treatments, including antivirals, antifungals or antibiotics, corticosteroids, hydroxychloroquine and respiratory support.
We rated all outcomes as very low certainty, and we were unable to summarise numerical data in any meaningful way. As we identified case‐series studies only, we reported results narratively.
Effectiveness of convalescent plasma for people with COVID‐19
The following reported outcomes could all be related to the underlying natural history of the disease or other concomitant treatment, rather than convalescent plasma.
All‐cause mortality at hospital discharge
All studies reported mortality. All participants were alive at the end of the reporting period, but not all participants had been discharged from hospital by the end of the study (15 participants discharged, 6 still hospitalised, 11 unclear). Follow‐up ranged from 3 days to 37 days post‐transfusion. We do not know whether convalescent plasma therapy affects mortality (very low‐certainty evidence).
Improvement of clinical symptoms (assessed by respiratory support)
Six studies, including 28 participants, reported the level of respiratory support required; most participants required respiratory support at baseline. All studies reported improvement in clinical symptoms in at least some participants. We do not know whether convalescent plasma improves clinical symptoms (very low‐certainty evidence).
Time to discharge from hospital
Six studies reported time to discharge from hospital for at least some participants, which ranged from four to 35 days after convalescent plasma therapy.
Admission on the intensive care unit (ICU)
Six studies included patients who were critically ill. At final follow‐up the majority of these patients were no longer on the ICU or no longer required mechanical ventilation.
Length of stay on the ICU
Only one study (1 participant) reported length of stay on the ICU. The individual was discharged from the ICU 11 days after plasma transfusion.
Safety of convalescent plasma for people with COVID‐19
Grade 3 or 4 adverse events
The studies did not report the grade of adverse events after convalescent plasma transfusion. Two studies reported data relating to participants who had experienced adverse events, that were presumably grade 3 or 4. One case study reported a participant who had moderate fever (38.9 °C). Another study (3 participants) reported a case of severe anaphylactic shock. Four studies reported the absence of moderate or severe adverse events (19 participants). We are very uncertain whether or not convalescent plasma therapy affects the risk of moderate to severe adverse events (very low‐certainty evidence).
Serious adverse events
One study (3 participants) reported one serious adverse event. As described above, this individual had severe anaphylactic shock after receiving convalescent plasma. Six studies reported that no serious adverse events occurred. We are very uncertain whether or not convalescent plasma therapy affects the risk of serious adverse events (very low‐certainty evidence).
Authors' conclusions
We identified eight studies (seven case‐series and one prospectively planned single‐arm intervention study) with a total of 32 participants (range 1 to 10). Most studies assessed the risks of the intervention; reporting two adverse events (potentially grade 3 or 4), one of which was a serious adverse event. We are very uncertain whether convalescent plasma is effective for people admitted to hospital with COVID‐19 as studies reported results inconsistently, making it difficult to compare results and to draw conclusions. We identified very low‐certainty evidence on the effectiveness and safety of convalescent plasma therapy for people with COVID‐19; all studies were at high risk of bias and reporting quality was low.
No RCTs or controlled non‐randomised studies evaluating benefits and harms of convalescent plasma have been completed. There are 47 ongoing studies evaluating convalescent plasma, of which 22 are RCTs, and one trial evaluating hyperimmune immunoglobulin. We will update this review as a living systematic review, based on monthly searches in the above mentioned databases and registries. These updates are likely to show different results to those reported here.
Background
Convalescent plasma and hyperimmune immunoglobulin may reduce mortality in patients with viral respiratory diseases, and are currently being investigated in trials as potential therapy for ...coronavirus disease 2019 (COVID‐19). A thorough understanding of the current body of evidence regarding the benefits and risks is required.
Objectives
To continually assess, as more evidence becomes available, whether convalescent plasma or hyperimmune immunoglobulin transfusion is effective and safe in treatment of people with COVID‐19.
Search methods
We searched the World Health Organization (WHO) COVID‐19 Global Research Database, MEDLINE, Embase, Cochrane COVID‐19 Study Register, Centers for Disease Control and Prevention COVID‐19 Research Article Database and trial registries to identify completed and ongoing studies on 4 June 2020.
Selection criteria
We followed standard Cochrane methodology.
We included studies evaluating convalescent plasma or hyperimmune immunoglobulin for people with COVID‐19, irrespective of study design, disease severity, age, gender or ethnicity.
We excluded studies including populations with other coronavirus diseases (severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS)) and studies evaluating standard immunoglobulin.
Data collection and analysis
We followed standard Cochrane methodology.
To assess bias in included studies, we used the Cochrane 'Risk of bias' tool for randomised controlled trials (RCTs), the Risk of Bias in Non‐randomised Studies ‐ of Interventions (ROBINS‐I) tool for controlled non‐randomised studies of interventions (NRSIs), and the assessment criteria for observational studies, provided by Cochrane Childhood Cancer for non‐controlled NRSIs.
Main results
This is the first living update of our review. We included 20 studies (1 RCT, 3 controlled NRSIs, 16 non‐controlled NRSIs) with 5443 participants, of whom 5211 received convalescent plasma, and identified a further 98 ongoing studies evaluating convalescent plasma or hyperimmune immunoglobulin, of which 50 are randomised. We did not identify any completed studies evaluating hyperimmune immunoglobulin.
Overall risk of bias of included studies was high, due to study design, type of participants, and other previous or concurrent treatments.
Effectiveness of convalescent plasma for people with COVID‐19
We included results from four controlled studies (1 RCT (stopped early) with 103 participants, of whom 52 received convalescent plasma; and 3 controlled NRSIs with 236 participants, of whom 55 received convalescent plasma) to assess effectiveness of convalescent plasma. Control groups received standard care at time of treatment without convalescent plasma.
All‐cause mortality at hospital discharge (1 controlled NRSI, 21 participants)
We are very uncertain whether convalescent plasma has any effect on all‐cause mortality at hospital discharge (risk ratio (RR) 0.89, 95% confidence interval (CI) 0.61 to 1.31; very low‐certainty evidence).
Time to death (1 RCT, 103 participants; 1 controlled NRSI, 195 participants)
We are very uncertain whether convalescent plasma prolongs time to death (RCT: hazard ratio (HR) 0.74, 95% CI 0.30 to 1.82; controlled NRSI: HR 0.46, 95% CI 0.22 to 0.96; very low‐certainty evidence).
Improvement of clinical symptoms, assessed by need for respiratory support (1 RCT, 103 participants; 1 controlled NRSI, 195 participants)
We are very uncertain whether convalescent plasma has any effect on improvement of clinical symptoms at seven days (RCT: RR 0.98, 95% CI 0.30 to 3.19), 14 days (RCT: RR 1.85, 95% CI 0.91 to 3.77; controlled NRSI: RR 1.08, 95% CI 0.91 to 1.29), and 28 days (RCT: RR 1.20, 95% CI 0.80 to 1.81; very low‐certainty evidence).
Quality of life
No studies reported this outcome.
Safety of convalescent plasma for people with COVID‐19
We included results from 1 RCT, 3 controlled NRSIs and 10 non‐controlled NRSIs assessing safety of convalescent plasma. Reporting of adverse events and serious adverse events was variable. The controlled studies reported on adverse events and serious adverse events only in participants receiving convalescent plasma. The duration of follow‐up varied. Some, but not all, studies included death as a serious adverse event.
Grade 3 or 4 adverse events (13 studies, 201 participants)
The studies did not report the grade of adverse events. Thirteen studies (201 participants) reported on adverse events of possible grade 3 or 4 severity. The majority of these adverse events were allergic or respiratory events. We are very uncertain whether or not convalescent plasma therapy affects the risk of moderate to severe adverse events (very low‐certainty evidence).
Serious adverse events (14 studies, 5201 participants)
Fourteen studies (5201 participants) reported on serious adverse events. The majority of participants were from one non‐controlled NRSI (5000 participants), which reported only on serious adverse events limited to the first four hours after convalescent plasma transfusion. This study included death as a serious adverse event; they reported 15 deaths, four of which they classified as potentially, probably or definitely related to transfusion. Other serious adverse events reported in all studies were predominantly allergic or respiratory in nature, including anaphylaxis, transfusion‐associated dyspnoea, and transfusion‐related acute lung injury (TRALI). We are very uncertain whether or not convalescent plasma affects the number of serious adverse events.
Authors' conclusions
We are very uncertain whether convalescent plasma is beneficial for people admitted to hospital with COVID‐19. For safety outcomes we also included non‐controlled NRSIs. There was limited information regarding adverse events. Of the controlled studies, none reported on this outcome in the control group. There is only very low‐certainty evidence for safety of convalescent plasma for COVID‐19.
While major efforts to conduct research on COVID‐19 are being made, problems with recruiting the anticipated number of participants into these studies are conceivable. The early termination of the first RCT investigating convalescent plasma, and the multitude of studies registered in the past months illustrate this. It is therefore necessary to critically assess the design of these registered studies, and well‐designed studies should be prioritised. Other considerations for these studies are the need to report outcomes for all study arms in the same way, and the importance of maintaining comparability in terms of co‐interventions administered in all study arms.
There are 98 ongoing studies evaluating convalescent plasma and hyperimmune immunoglobulin, of which 50 are RCTs. This is the first living update of the review, and we will continue to update this review periodically. These updates may show different results to those reported here.
Cardiovascular disease is the leading cause of death worldwide, and cardiovascular disease burden is increasing in low-resource settings and for lower socioeconomic groups. Machine learning ...algorithms are being developed rapidly and incorporated into clinical practice for cardiovascular disease prediction and treatment decisions. Significant opportunities for reducing death and disability from cardiovascular disease worldwide lie with accounting for the social determinants of cardiovascular outcomes. This study reviews how social determinants of health are being included in machine learning algorithms to inform best practices for the development of algorithms that account for social determinants.
A systematic review using 5 databases was conducted in 2020. English language articles from any location published from inception to April 10, 2020, which reported on the use of machine learning for cardiovascular disease prediction that incorporated social determinants of health, were included.
Most studies that compared machine learning algorithms and regression showed increased performance of machine learning, and most studies that compared performance with or without social determinants of health showed increased performance with them. The most frequently included social determinants of health variables were gender, race/ethnicity, marital status, occupation, and income. Studies were largely from North America, Europe, and China, limiting the diversity of the included populations and variance in social determinants of health.
Given their flexibility, machine learning approaches may provide an opportunity to incorporate the complex nature of social determinants of health. The limited variety of sources and data in the reviewed studies emphasize that there is an opportunity to include more social determinants of health variables, especially environmental ones, that are known to impact cardiovascular disease risk and that recording such data in electronic databases will enable their use.
Background
Monoclonal antibodies (mAbs) are laboratory‐produced molecules derived from the B cells of an infected host. They are being investigated as a potential therapy for coronavirus disease 2019 ...(COVID‐19).
Objectives
To assess the effectiveness and safety of SARS‐CoV‐2‐neutralising mAbs for treating patients with COVID‐19, compared to an active comparator, placebo, or no intervention. To maintain the currency of the evidence, we will use a living systematic review approach.
A secondary objective is to track newly developed SARS‐CoV‐2‐targeting mAbs from first tests in humans onwards.
Search methods
We searched MEDLINE, Embase, the Cochrane COVID‐19 Study Register, and three other databases on 17 June 2021. We also checked references, searched citations, and contacted study authors to identify additional studies. Between submission and publication, we conducted a shortened randomised controlled trial (RCT)‐only search on 30 July 2021.
Selection criteria
We included studies that evaluated SARS‐CoV‐2‐neutralising mAbs, alone or combined, compared to an active comparator, placebo, or no intervention, to treat people with COVID‐19. We excluded studies on prophylactic use of SARS‐CoV‐2‐neutralising mAbs.
Data collection and analysis
Two authors independently assessed search results, extracted data, and assessed risk of bias using the Cochrane risk of bias tool (RoB2). Prioritised outcomes were all‐cause mortality by days 30 and 60, clinical progression, quality of life, admission to hospital, adverse events (AEs), and serious adverse events (SAEs). We rated the certainty of evidence using GRADE.
Main results
We identified six RCTs that provided results from 17,495 participants with planned completion dates between July 2021 and December 2031. Target sample sizes varied from 1020 to 10,000 participants. Average age was 42 to 53 years across four studies of non‐hospitalised participants, and 61 years in two studies of hospitalised participants.
Non‐hospitalised individuals with COVID‐19
Four studies evaluated single agents bamlanivimab (N = 465), sotrovimab (N = 868), regdanvimab (N = 307), and combinations of bamlanivimab/etesevimab (N = 1035), and casirivimab/imdevimab (N = 799). We did not identify data for mortality at 60 days or quality of life. Our certainty of the evidence is low for all outcomes due to too few events (very serious imprecision).
Bamlanivimab compared to placebo
No deaths occurred in the study by day 29. There were nine people admitted to hospital by day 29 out of 156 in the placebo group compared with one out of 101 in the group treated with 0.7 g bamlanivimab (risk ratio (RR) 0.17, 95% confidence interval (CI) 0.02 to 1.33), 2 from 107 in the group treated with 2.8 g (RR 0.32, 95% CI 0.07 to 1.47) and 2 from 101 in the group treated with 7.0 g (RR 0.34, 95% CI 0.08 to 1.56). Treatment with 0.7 g, 2.8 g and 7.0 g bamlanivimab may have similar rates of AEs as placebo (RR 0.99, 95% CI 0.66 to 1.50; RR 0.90, 95% CI 0.59 to 1.38; RR 0.81, 95% CI 0.52 to 1.27). The effect on SAEs is uncertain. Clinical progression/improvement of symptoms or development of severe symptoms were not reported.
Bamlanivimab/etesevimab compared to placebo
There were 10 deaths in the placebo group and none in bamlanivimab/etesevimab group by day 30 (RR 0.05, 95% CI 0.00 to 0.81). Bamlanivimab/etesevimab may decrease hospital admission by day 29 (RR 0.30, 95% CI 0.16 to 0.59), may result in a slight increase in any grade AEs (RR 1.15, 95% CI 0.83 to 1.59) and may increase SAEs (RR 1.40, 95% CI 0.45 to 4.37). Clinical progression/improvement of symptoms or development of severe symptoms were not reported.
Casirivimab/imdevimab compared to placebo
Casirivimab/imdevimab may reduce hospital admissions or death (2.4 g: RR 0.43, 95% CI 0.08 to 2.19; 8.0 g: RR 0.21, 95% CI 0.02 to 1.79). We are uncertain of the effect on grades 3‐4 AEs (2.4 g: RR 0.76, 95% CI 0.17 to 3.37; 8.0 g: RR 0.50, 95% CI 0.09 to 2.73) and SAEs (2.4 g: RR 0.68, 95% CI 0.19 to 2.37; 8.0 g: RR 0.34, 95% CI 0.07 to 1.65). Mortality by day 30 and clinical progression/improvement of symptoms or development of severe symptoms were not reported.
Sotrovimab compared to placebo
We are uncertain whether sotrovimab has an effect on mortality (RR 0.33, 95% CI 0.01 to 8.18) and invasive mechanical ventilation (IMV) requirement or death (RR 0.14, 95% CI 0.01 to 2.76). Treatment with sotrovimab may reduce the number of participants with oxygen requirement (RR 0.11, 95 % CI 0.02 to 0.45), hospital admission or death by day 30 (RR 0.14, 95% CI 0.04 to 0.48), grades 3‐4 AEs (RR 0.26, 95% CI 0.12 to 0.60), SAEs (RR 0.27, 95% CI 0.12 to 0.63) and may have little or no effect on any grade AEs (RR 0.87, 95% CI 0.66 to 1.16).
Regdanvimab compared to placebo
Treatment with either dose (40 or 80 mg/kg) compared with placebo may decrease hospital admissions or death (RR 0.45, 95% CI 0.14 to 1.42; RR 0.56, 95% CI 0.19 to 1.60, 206 participants), but may increase grades 3‐4 AEs (RR 2.62, 95% CI 0.52 to 13.12; RR 2.00, 95% CI 0.37 to 10.70). 80 mg/kg may reduce any grade AEs (RR 0.79, 95% CI 0.52 to 1.22) but 40 mg/kg may have little to no effect (RR 0.96, 95% CI 0.64 to 1.43). There were too few events to allow meaningful judgment for the outcomes mortality by 30 days, IMV requirement, and SAEs.
Hospitalised individuals with COVID‐19
Two studies evaluating bamlanivimab as a single agent (N = 314) and casirivimab/imdevimab as a combination therapy (N = 9785) were included.
Bamlanivimab compared to placebo
We are uncertain whether bamlanivimab has an effect on mortality by day 30 (RR 1.39, 95% CI 0.40 to 4.83) and SAEs by day 28 (RR 0.93, 95% CI 0.27 to 3.14). Bamlanivimab may have little to no effect on time to hospital discharge (HR 0.97, 95% CI 0.78 to 1.20) and mortality by day 90 (HR 1.09, 95% CI 0.49 to 2.43). The effect of bamlanivimab on the development of severe symptoms at day 5 (RR 1.17, 95% CI 0.75 to 1.85) is uncertain. Bamlanivimab may increase grades 3‐4 AEs at day 28 (RR 1.27, 95% CI 0.81 to 1.98). We assessed the evidence as low certainty for all outcomes due to serious imprecision, and very low certainty for severe symptoms because of additional concerns about indirectness.
Casirivimab/imdevimab with usual care compared to usual care alone
Treatment with casirivimab/imdevimab compared to usual care probably has little or no effect on mortality by day 30 (RR 0.94, 95% CI 0.87 to 1.02), IMV requirement or death (RR 0.96, 95% CI 0.90 to 1.04), nor alive at hospital discharge by day 30 (RR 1.01, 95% CI 0.98 to 1.04). We assessed the evidence as moderate certainty due to study limitations (lack of blinding). AEs and SAEs were not reported.
Authors' conclusions
The evidence for each comparison is based on single studies. None of these measured quality of life. Our certainty in the evidence for all non‐hospitalised individuals is low, and for hospitalised individuals is very low to moderate. We consider the current evidence insufficient to draw meaningful conclusions regarding treatment with SARS‐CoV‐2‐neutralising mAbs.
Further studies and long‐term data from the existing studies are needed to confirm or refute these initial findings, and to understand how the emergence of SARS‐CoV‐2 variants may impact the effectiveness of SARS‐CoV‐2‐neutralising mAbs. Publication of the 36 ongoing studies may resolve uncertainties about the effectiveness and safety of SARS‐CoV‐2‐neutralising mAbs for the treatment of COVID‐19 and possible subgroup differences.
Convalescent plasma (CP) from blood donors with antibodies to severe acute respiratory syndrome coronavirus 2 may benefit patients with COVID-19 by providing immediate passive immunity via ...transfusion or by being used to manufacture hyperimmune immunoglobulin preparations. Optimal product characteristics (including neutralizing antibody titers), transfusion volume, and administration timing remain to be determined. Preliminary COVID-19 CP safety data are encouraging, but establishing the clinical efficacy of CP requires an ongoing international collaborative effort. Preliminary results from large, high-quality randomized trials have recently started to be reported.
Background
Convalescent plasma and hyperimmune immunoglobulin may reduce mortality in patients with viral respiratory diseases, and are being investigated as potential therapies for coronavirus ...disease 2019 (COVID‐19). A thorough understanding of the current body of evidence regarding benefits and risks of these interventions is required.
Objectives
Using a living systematic review approach, to assess whether convalescent plasma or hyperimmune immunoglobulin transfusion is effective and safe in the treatment of people with COVID‐19; and to maintain the currency of the evidence.
Search methods
To identify completed and ongoing studies, we searched the World Health Organization (WHO) COVID‐19 Global literature on coronavirus disease Research Database, MEDLINE, Embase, the Cochrane COVID‐19 Study Register, the Epistemonikos COVID‐19 L*OVE Platform, and trial registries. Searches were done on 17 March 2021.
Selection criteria
We included randomised controlled trials (RCTs) evaluating convalescent plasma or hyperimmune immunoglobulin for COVID‐19, irrespective of disease severity, age, gender or ethnicity. For safety assessments, we also included non‐controlled non‐randomised studies of interventions (NRSIs) if 500 or more participants were included.
We excluded studies that included populations with other coronavirus diseases (severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS)), as well as studies evaluating standard immunoglobulin.
Data collection and analysis
We followed standard Cochrane methodology.
To assess bias in included studies, we used the Cochrane 'Risk of Bias 2' tool for RCTs, and for NRSIs, the assessment criteria for observational studies, provided by Cochrane Childhood Cancer. We rated the certainty of evidence, using the GRADE approach, for the following outcomes: all‐cause mortality, improvement and worsening of clinical status (for individuals with moderate to severe disease), development of severe clinical COVID‐19 symptoms (for individuals with asymptomatic or mild disease), quality of life (including fatigue and functional independence), grade 3 or 4 adverse events, and serious adverse events.
Main results
We included 13 studies (12 RCTs, 1 NRSI) with 48,509 participants, of whom 41,880 received convalescent plasma. We did not identify any completed studies evaluating hyperimmune immunoglobulin. We identified a further 100 ongoing studies evaluating convalescent plasma or hyperimmune immunoglobulin, and 33 studies reporting as being completed or terminated.
Individuals with a confirmed diagnosis of COVID‐19 and moderate to severe disease
Eleven RCTs and one NRSI investigated the use of convalescent plasma for 48,349 participants with moderate to severe disease. Nine RCTs compared convalescent plasma to placebo treatment or standard care alone, and two compared convalescent plasma to standard plasma (results not included in ).
Effectiveness of convalescent plasma
We included data on nine RCTs (12,875 participants) to assess the effectiveness of convalescent plasma compared to placebo or standard care alone.
Convalescent plasma does not reduce all‐cause mortality at up to day 28 (risk ratio (RR) 0.98, 95% confidence interval (CI) 0.92 to 1.05; 7 RCTs, 12,646 participants; high‐certainty evidence). It has little to no impact on clinical improvement for all participants when assessed by liberation from respiratory support (RR not estimable; 8 RCTs, 12,682 participants; high‐certainty evidence). It has little to no impact on the chance of being weaned or liberated from invasive mechanical ventilation for the subgroup of participants requiring invasive mechanical ventilation at baseline (RR 1.04, 95% CI 0.57 to 1.93; 2 RCTs, 630 participants; low‐certainty evidence). It does not reduce the need for invasive mechanical ventilation (RR 0.98, 95% CI 0.89 to 1.08; 4 RCTs, 11,765 participants; high‐certainty evidence). We did not identify any subgroup differences.
We did not identify any studies reporting quality of life, and therefore, do not know whether convalescent plasma has any impact on quality of life. One RCT assessed resolution of fatigue on day 7, but we are very uncertain about the effect (RR 1.21, 95% CI 1.02 to 1.42; 309 participants; very low‐certainty evidence).
Safety of convalescent plasma
We included results from eight RCTs, and one NRSI, to assess the safety of convalescent plasma. Some of the RCTs reported on safety data only for the convalescent plasma group.
We are uncertain whether convalescent plasma increases or reduces the risk of grade 3 and 4 adverse events (RR 0.90, 95% CI 0.58 to 1.41; 4 RCTs, 905 participants; low‐certainty evidence), and serious adverse events (RR 1.24, 95% CI 0.81 to 1.90; 2 RCTs, 414 participants; low‐certainty evidence).
A summary of reported events of the NRSI (reporting safety data for 20,000 of 35,322 transfused participants), and four RCTs reporting safety data only for transfused participants (6125 participants) are included in the full text.
Individuals with a confirmed diagnosis of SARS‐CoV‐2 infection and asymptomatic or mild disease
We identified one RCT reporting on 160 participants, comparing convalescent plasma to placebo treatment (saline).
Effectiveness of convalescent plasma
We are very uncertain about the effect of convalescent plasma on all‐cause mortality (RR 0.50, 95% CI 0.09 to 2.65; very low‐certainty evidence). We are uncertain about the effect of convalescent plasma on developing severe clinical COVID‐19 symptoms (RR not estimable; low‐certainty evidence).
We identified no study reporting quality of life.
Safety of convalescent plasma
We do not know whether convalescent plasma is associated with a higher risk of grade 3 or 4 adverse events (very low‐certainty evidence), or serious adverse events (very low‐certainty evidence).
This is a living systematic review. We search weekly for new evidence and update the review when we identify relevant new evidence. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review.
Authors' conclusions
We have high certainty in the evidence that convalescent plasma for the treatment of individuals with moderate to severe disease does not reduce mortality and has little to no impact on measures of clinical improvement. We are uncertain about the adverse effects of convalescent plasma. While major efforts to conduct research on COVID‐19 are being made, heterogeneous reporting of outcomes is still problematic. There are 100 ongoing studies and 33 studies reporting in a study registry as being completed or terminated. Publication of ongoing studies might resolve some of the uncertainties around hyperimmune immunoglobulin therapy for people with any disease severity, and convalescent plasma therapy for people with asymptomatic or mild disease.
Abstract Introduction Fibrinogen may be reduced following traumatic injury due to loss from haemorrhage, increased consumption and reduced synthesis. In the absence of clinical trials, guidelines for ...fibrinogen replacement are based on expert opinion and vary internationally. We aimed to determine prevalence and predictors of low fibrinogen on admission in major trauma patients and investigate association of fibrinogen levels with patient outcomes. Patients and methods Data on all major trauma patients (January 2007–July 2011) identified through a prospective statewide trauma registry in Victoria, Australia were linked with laboratory and transfusion data. Major trauma included any of the following: death after injury, injury severity score (ISS) >15, admission to intensive care unit requiring mechanical ventilation, or urgent surgery for intrathoracic, intracranial, intra-abdominal procedures or fixation of pelvic or spinal fractures. Associations between initial fibrinogen level and in-hospital mortality were analysed using multiple logistic regression. Results Of 4773 patients identified, 114 (2.4%) had fibrinogen less than 1 g/L, 283 (5.9%) 1.0–1.5 g/L, 617 (12.9%) 1.6–1.9 g/L, 3024 (63.4%) 2–4 g/L and 735 (15%) >4 g/L. Median fibrinogen was 2.6 g/L (interquartile range 2.1–3.4). After adjusting for age, gender, ISS, injury type, pH, temperature, Glasgow Coma Score (GCS), initial international normalised ratio and platelet count, the lowest fibrinogen categories, compared with normal range, were associated with increased in-hospital mortality (adjusted odds ratio OR for less than 1 g/L 3.28 95% CI 1.71–6.28, p < 0.01, 1–1.5 g/L adjusted OR 2.08 95% CI 1.36–3.16, p < 0.01 and 1.6–1.9 g/L adjusted OR 1.39 95% CI 0.97–2.00, p = 0.08). Predictors of initial fibrinogen <1.5 g/L were younger age, lower GCS, systolic blood pressure <90 mmHg, chest decompression, penetrating injury, ISS >25 and lower pH and temperature. Conclusions Initial fibrinogen levels less than the normal range are independently associated with higher in-hospital mortality in major trauma patients. Future studies are warranted to investigate whether earlier and/or greater fibrinogen replacement improves clinical outcomes.
Patients with myelodysplastic syndromes (MDS) often need extended periods of red blood cell or platelet transfusion support, with the goal to manage symptoms of anemia and thrombocytopenia, ...respectively, and improve quality of life. Many questions about the optimal approach to transfusion management in MDS, especially in the outpatient setting, remain unanswered, including hemoglobin and platelet thresholds for transfusion. Restrictive transfusion approaches are often practised, but whether these are appropriate for outpatients with MDS, who are often older and may be frail, is not known. Current schedules for transfusion-dependent patients are burdensome, necessitating frequent visits to hospitals for sample collection and blood administration. Questions of optimal schedule and dosage are being explored in clinical trials, including the recently completed REDDS study. Patient-reported outcomes and functional assessments are increasingly being incorporated into research in this area so that we can better understand and improve transfusion support for patients with MDS.
Tranexamic acid (TXA) is an antifibrinolytic agent originally developed for the management of bleeding in the setting of postpartum hemorrhage (PPH). Over the last 15 years, there has been ...accumulating evidence on the use of TXA for the treatment of active bleeding in a variety of clinical contexts. Clinical trials have shown that the efficacy and safety of TXA for the treatment of bleeding differ according to the clinical context in which it is being administered, timing of administration, and dose. Early administration is important for efficacy, particularly in trauma and PPH. Further studies are needed to understand the mechanisms by which TXA provides benefit, optimal modes of administration and dosing, and its effect in some clinical settings, such as spontaneous intracerebral hemorrhage. There is no evidence that TXA increases the risk of thrombotic events in patients with major bleeding overall. However, there is evidence of increased risk of venous thrombosis in patients with gastrointestinal bleeding. There is also evidence of increased risk of seizures with the use of higher doses. This review summarizes the current evidence for the use of TXA for patients with active bleeding and highlights the importance of generating evidence of efficacy and safety of hemostatic interventions specific to the bleeding contexts—as findings from 1 clinical setting may not be generalizable to other contexts—and that of individual patient assessment for bleeding, thrombotic, and other risks, as well as important logistical and other practical considerations, to optimize care and outcomes in these settings.
•Father support moderated the association between perceived discrimination and CRP among sexual minorities (SMs).•Mother support did not moderate the association between perceived discrimination and ...CRP among heterosexuals or SMs.•Father support may protect against the effects of perceived discrimination on indices of cardiovascular risk among SMs.
Exposure to sexual orientation-related discrimination among sexual minorities may lead to elevated levels of C-reactive protein (CRP) as compared to their heterosexual counterparts. However, little is known about factors that may buffer the association between discrimination and CRP among sexual minorities versus heterosexuals. The current study examined if the association between discrimination, sexual orientation, and CRP differed across levels of social support from one’s father/father-figure or mother/mother-figure between sexual minorities and heterosexuals.
Data came from Wave IV of the National Longitudinal Study of Adolescent to Adult Health (Add Health). The sample sizes for father support and mother support was 3167 and 3575, respectively. Participants ranged in age from 24 to 33 years. Stratified linear regression models examined if father and mother support moderated the association between discrimination and CRP among sexual minorities and heterosexuals.
Father support significantly moderated the association between discrimination and CRP among sexual minorities but not heterosexuals. Sexual minorities with higher father support and who experienced discrimination had lower CRP as compared to those with lower father support and who experienced discrimination. Mother support did not moderate the association between discrimination and CRP among either sexual minorities or heterosexuals.
Father support may mitigate the negative effects of stress from discrimination on CRP among sexual minorities. Future research should further examine the potential differential role that father support may play in reducing cardiovascular risk among sexual minorities versus heterosexuals who experience discrimination.
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