Covid-19
Meta-analysis: Therapeutic-Dose Heparin Improves 28-Day Mortality in COVID-19 Hospitalized Patients
6 Jan, 2025 | 12:00h | UTCBackground: High rates of thrombotic events and systemic inflammation among COVID-19 hospitalized patients led researchers to test whether intensified anticoagulation strategies could reduce morbidity and mortality. Previous trials yielded conflicting results, partly due to varying doses of anticoagulants—prophylactic, intermediate, or therapeutic—and heterogeneous patient severity. This comprehensive investigation, conducted by the WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group, aimed to clarify the benefits and risks of escalated anticoagulation dosing in patients hospitalized for COVID-19.
Objective: To estimate whether higher-dose anticoagulation (therapeutic or intermediate) improves 28-day all-cause mortality compared with lower-dose anticoagulation (prophylactic or intermediate), and to evaluate secondary outcomes, including progression to mechanical ventilation, thromboembolic events, and major bleeding.
Methods: This prospective meta-analysis included randomized trials comparing higher- versus lower-dose anticoagulation for hospitalized COVID-19 patients. Investigators collected trial-level summary data, focusing primarily on heparins. Dosing categories—therapeutic, intermediate, and prophylactic—were predefined. The main outcome was 28-day mortality; secondary outcomes included progression to invasive mechanical ventilation (IMV), venous or arterial thrombotic events, and major hemorrhage. Data were analyzed using a fixed-effects model, with odds ratios (ORs) pooled across trials.
Results: Overall, 22 trials (over 11 000 total participants) contributed data, primarily evaluating heparins. For therapeutic versus prophylactic-dose heparin, 28-day mortality was significantly reduced (OR, 0.77; 95% CI, 0.64–0.93), especially among patients requiring low-flow oxygen or no supplemental oxygen. Therapeutic dose reduced thromboembolic events (OR 0.48; 95% CI, 0.36-0.64) but increased major bleeding (OR 1.90; 95% CI, 1.19-3.05) compared to prophylactic dose. In contrast, when therapeutic was compared to intermediate-dose heparin, the summary OR for 28-day mortality was 1.21 (CI, 0.93–1.58), suggesting a potential trend toward higher mortality that did not reach statistical significance. Intermediate versus prophylactic-dose comparisons revealed no conclusive mortality difference (OR, 0.95; CI, 0.76–1.19). Across all higher-dose arms, thromboembolic events decreased, while the risk of major bleeding increased, underscoring the delicate risk–benefit balance. Subgroup analyses by respiratory support level, D-dimer, and baseline severity did not indicate strong interaction effects, although sample sizes were limited in more severe illness subgroups.
Conclusions: Therapeutic-dose heparin reduces 28-day mortality relative to prophylactic-dose in hospitalized patients with COVID-19, mainly among those not requiring invasive ventilation. Mortality was similar or potentially worse when therapeutic was compared to intermediate-dose. Clinicians must weigh the lower rate of thrombotic complications against the higher bleeding risk, particularly in critically ill patients.
Implications for Practice: Although higher anticoagulant dosing appears beneficial for certain hospitalized COVID-19 patients, especially those with mild to moderate respiratory compromise, individualized assessment remains key. Current guidelines broadly recommend prophylactic dosing for the critically ill and suggest considering higher doses only in carefully selected patients. Evolving viral variants and changes in standard of care further complicate direct application of these findings to present-day hospital settings.
Study Strengths and Limitations: Strengths include prospective planning, collaboration with multiple trials, and a large pooled sample. Limitations encompass heterogeneity in dose definitions, partial reliance on published data where individual-level parameters could not be fully harmonized, and potential temporal changes in COVID-19 clinical profiles. Moreover, bleeding severity beyond major hemorrhage was not universally reported, limiting robust safety assessments.
Future Research: Further studies should focus on individualized anticoagulant strategies that consider biomarkers (for example, D-dimer) and evolving treatment protocols. Investigations examining optimal timing, duration, and post-discharge management will help refine anticoagulation practices.
Reference:
The WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group. Anticoagulation Among Patients Hospitalized for COVID-19: A Systematic Review and Prospective Meta-analysis. Annals of Internal Medicine. DOI: https://doi.org/10.7326/ANNALS-24-00800
Shappell CN, Anesi GL. Anticoagulation for COVID-19: Seeking Clarity and Finding Yet More Gray. Annals of Internal Medicine. DOI: https://doi.org/10.7326/ANNALS-24-03244
Review: Acute Respiratory Distress Syndrome
28 Nov, 2024 | 13:06h | UTCIntroduction: Acute respiratory distress syndrome (ARDS) is a severe inflammatory lung condition characterized by diffuse alveolar damage, leading to hypoxemia and respiratory failure. Since its initial description in 1967, the understanding and definition of ARDS have significantly evolved, integrating advances in basic science and clinical practice. A newly recommended global definition expands diagnostic criteria to enhance early recognition and management, especially in resource-limited settings. This review summarizes current insights into the epidemiology, pathophysiology, and evidence-based management of ARDS, highlighting key updates and future research priorities.
Key Recommendations:
- New Global Definition of ARDS: Adoption of an expanded definition that includes patients receiving high-flow nasal oxygen (HFNO) support and allows diagnosis using pulse oximetry and thoracic ultrasonography. This makes ARDS identification feasible in diverse clinical environments, including those with limited resources.
- Established Critical Care Interventions: Emphasis on early implementation of proven strategies such as low tidal volume ventilation (6 mL/kg predicted body weight) with plateau pressures ≤30 cm H₂O, prone positioning for patients with PaO₂/FiO₂ <150 mm Hg, and conservative fluid management after initial resuscitation. These interventions have consistently reduced mortality and are recommended as standard care.
- Personalized Approaches and Phenotyping: Recognition of the heterogeneity in ARDS pathophysiology underscores the need for personalized treatment strategies. Identification of hyper-inflammatory and hypo-inflammatory phenotypes may guide targeted therapies and improve outcomes, although prospective validation is required.
- Impact of COVID-19 on ARDS: Acknowledgment of the significant increase in ARDS incidence due to the COVID-19 pandemic. While COVID-19 ARDS shares similarities with traditional ARDS, notable differences in endothelial dysfunction and immune response highlight the necessity for tailored management approaches in these patients.
- Pharmacologic Interventions: Updated guidelines provide conditional recommendations for the use of corticosteroids in ARDS, particularly in early moderate to severe cases. Ongoing research into pharmacologic agents such as statins, mesenchymal stromal cells, and other cell-based therapies shows potential but requires further clinical trials to establish efficacy.
- Future Research Priorities: Identification of key areas for investigation, including the long-term sequelae of ARDS, optimization of non-invasive and invasive ventilation strategies, exploration of genetic and environmental risk factors, and development of rapid biomarker assays for real-time phenotyping and targeted therapy.
Conclusion: The evolving definition and understanding of ARDS aim to improve early detection and standardization of care across various clinical settings. Reinforcing established critical care interventions while advancing personalized and novel therapeutic approaches holds promise for reducing mortality and enhancing long-term patient outcomes. Continuous research into the pathophysiology and management of ARDS, enriched by insights from the COVID-19 pandemic, is essential to address ongoing challenges and improve patient care.
Cohort Study: Lower Risk of Cardiovascular Complications in Post–COVID-19 Vaccine Myocarditis Compared to Conventional Etiologies
7 Sep, 2024 | 20:36h | UTCStudy Design and Population: This French nationwide cohort study included 4,635 individuals aged 12-49 hospitalized for myocarditis between December 2020 and June 2022. The cohort was divided into three groups: 558 patients with post–COVID-19 mRNA vaccine myocarditis, 298 with post–COVID-19 infection myocarditis, and 3,779 with conventional myocarditis.
Main Findings: At 18 months of follow-up, the frequency of cardiovascular events was significantly lower in the postvaccine myocarditis group (5.7%) compared to conventional myocarditis (13.2%) with a weighted hazard ratio (wHR) of 0.55 (95% CI, 0.36-0.86). Hospital readmission for myopericarditis occurred in 3.2% of postvaccine cases, 4.0% of post–COVID-19 cases, and 5.8% of conventional cases. The all-cause mortality rate was 0.2% for postvaccine myocarditis, 1.3% for post–COVID-19 myocarditis, and 1.3% for conventional myocarditis.
Implications for Practice: Postvaccine myocarditis patients, primarily young males, experience fewer complications compared to conventional myocarditis, but long-term follow-up is still needed. These findings should guide future mRNA vaccine recommendations and clinical management for myocarditis patients.
Reference: Semenzato L. et al. (2024). Long-term Prognosis of Myocarditis Attributed to COVID-19 mRNA Vaccination, SARS-CoV-2, or Conventional Etiologies. JAMA, Online. DOI: http://doi.org/10.1001/jama.2024.16380
Link: https://jamanetwork.com/journals/jama/fullarticle/2822933
RCT: Lack of significant effect of Paxlovid (nirmatrelvir–ritonavir) on symptom alleviation in Covid-19
26 Apr, 2024 | 11:49h | UTCStudy Design and Population:
This phase 2–3 randomized clinical trial investigated the efficacy of nirmatrelvir in combination with ritonavir for treating mild-to-moderate Covid-19 in adults. Participants, both vaccinated and unvaccinated, were enrolled based on their risk factors for severe Covid-19. The study included 1296 adults who had confirmed Covid-19 with symptom onset within the past 5 days. They were randomly assigned to receive either nirmatrelvir–ritonavir or placebo every 12 hours for 5 days.
Main Findings:
The primary endpoint was the time to sustained alleviation of all targeted Covid-19 signs and symptoms. Results showed that the median time to alleviation was 12 days for the treatment group and 13 days for the placebo group, a difference that was not statistically significant (P=0.60). Hospitalizations and deaths were slightly lower in the treatment group (0.8%) compared to the placebo group (1.6%), but this difference was also not statistically significant. Adverse events were similar across both groups, with dysgeusia and diarrhea being the most common in the treatment group.
Implications for Practice:
The findings indicate that nirmatrelvir–ritonavir treatment does not significantly reduce the time to symptom alleviation for Covid-19 compared to placebo among vaccinated or unvaccinated adults. These results suggest that further research is needed to explore the potential benefits of this treatment in specific subpopulations or in combination with other interventions.
Reference (free full-text):
RCT: Lower oxygenation target improves days alive without life support in severe COVID-19 hypoxemia
21 Mar, 2024 | 13:46h | UTCStudy Design and Population: This multicenter randomized clinical trial investigated the impact of different oxygenation targets on the survival of adult patients with COVID-19 and severe hypoxemia in the ICU. Conducted across 11 European ICUs from August 2020 to March 2023, the study involved 726 patients requiring at least 10 L/min of oxygen or mechanical ventilation. Participants were randomly assigned to receive an oxygenation target of either 60 mm Hg (lower oxygenation group, n=365) or 90 mm Hg (higher oxygenation group, n=361) for up to 90 days.
Main Findings: The primary outcome was the number of days alive without life support at 90 days post-intervention. Patients in the lower oxygenation group achieved a median of 80.0 days alive without life support compared to 72.0 days in the higher oxygenation group, a difference that was statistically significant (P=0.009). Although there was a slight reduction in mortality at 90 days in the lower oxygenation group (30.2% vs 34.7% in the higher group), this was not statistically significant. No significant differences were observed in the proportion of patients with serious adverse events or the number of days alive and out of hospital.
Implications for Practice: Targeting a lower Pao2 of 60 mm Hg in ICU patients with COVID-19 and severe hypoxemia appears to increase the days alive without life support compared to a higher target of 90 mm Hg, without increasing serious adverse events. This finding suggests that a lower oxygenation target could be more beneficial for this patient population, potentially guiding clinical practice in managing oxygen therapy for severe COVID-19 cases.
Reference
Reference: Nielsen FM et al. (2024). Randomized Clinical Trial: Effect of Oxygenation Targets on Survival Without Life Support in COVID-19 Patients with Severe Hypoxemia. JAMA, Published online March 19, 2024. DOI: 10.1001/jama.2024.2934. Access the study here: [Link]
Multinational Study | No correlation between Covid-19 and onset of type 1 diabetes in children
8 Aug, 2023 | 13:32h | UTC
Opinion | Bad science needs to be called out: the medical profession loses trust when bad studies are used to promote policy
1 Aug, 2023 | 14:29h | UTCBad Science Needs to Be Called Out – Sensible Medicine
Related: Did Republicans die more during the pandemic bc they didn’t get the vax? – By Dr. Vinay Prassad
Original Study: Excess Death Rates for Republican and Democratic Registered Voters in Florida and Ohio During the COVID-19 Pandemic – JAMA Internal Medicine
Critical Appraisal | Did Republicans die more during the pandemic bc they didn’t get the vax?
1 Aug, 2023 | 14:28h | UTCDid Republicans die more during the pandemic bc they didn’t get the vax? – By Dr. Vinay Prassad
Related: Bad Science Needs to Be Called Out – Sensible Medicine
Original Study: Excess Death Rates for Republican and Democratic Registered Voters in Florida and Ohio During the COVID-19 Pandemic – JAMA Internal Medicine
Opinion Video | Critical analysis of the data behind Covid-19 booster shots
31 Jul, 2023 | 14:40h | UTCOriginal Publication: Correspondence | Potential “healthy vaccinee bias” in a study of BNT162b2 vaccine against Covid-19
Mitigating neurological, cognitive, and psychiatric sequelae of COVID-19-related critical illness
26 Jul, 2023 | 13:28h | UTC
Correspondence | Potential “healthy vaccinee bias” in a study of BNT162b2 vaccine against Covid-19
21 Jul, 2023 | 13:43h | UTC
Commentary from the author on Twitter (thread – click for more)
Our correspondence is out in @njem written w @VPrasadMDMPH & Ram Duriseti
We show v strong evidence of healthy vaccinee bias in an Israeli study of Pfizer booster vs covid death, which wasn't disclosed
Could explain ALL reported benefit of the booster🧵https://t.co/F3WeafvUnw pic.twitter.com/b29YQ0lblh
— Tracy Høeg, MD, PhD (@TracyBethHoeg) July 20, 2023
Review | Post-COVID Conditions
7 Jul, 2023 | 16:21h | UTCPost-COVID Conditions – Mayo Clinic Proceedings
Consensus Statement 2023 Update | Timing of elective surgery and risk assessment after SARS-CoV-2 infection
30 Jun, 2023 | 15:00h | UTCTiming of elective surgery and risk assessment after SARS-CoV-2 infection: 2023 update – Anaesthesia
Commentary on Twitter
🔓"In most circumstances, surgery should proceed unless risk assessment indicates that the risk of proceeding exceeds the risk of delay."@Assoc_Anaes @RCoANews @UkFssa @RCSnews @elboghdadly @doctimcook @justin_kua @NigelMercer @rmoonesinghe
🔗https://t.co/gfjymze0oi pic.twitter.com/D8bEfAHBD7
— 𝘈𝘯𝘢𝘦𝘴𝘵𝘩𝘦𝘴𝘪𝘢 (@Anaes_Journal) June 20, 2023
Review | Breathing difficulties after covid-19: a guide for primary care
29 Jun, 2023 | 14:04h | UTCBreathing difficulties after covid-19: a guide for primary care – The BMJ
Opinion | Strategic masking to protect patients from all respiratory viral infections
20 Jun, 2023 | 12:50h | UTCStrategic Masking to Protect Patients from All Respiratory Viral Infections – New England Journal of Medicine (link to abstract – $ for full-text)
Perspective | Observational studies must be reformed before the next pandemic
15 Jun, 2023 | 15:12h | UTCObservational studies must be reformed before the next pandemic – Nature Medicine
Review | Wastewater monitoring can anchor global disease surveillance systems
13 Jun, 2023 | 14:07h | UTCWastewater monitoring can anchor global disease surveillance systems – The Lancet Global Health
Related:
Use of Wastewater for Mpox Outbreak Surveillance in California – New England Journal of Medicine
Opinion: Wastewater analysis can be a powerful public health tool—if it’s done sensibly.
CDC unveils its latest weapon in Covid-19 detection: wastewater.
[Preprint] Wastewater genomic testing can effectively track COVID-19 variants of concern.
Human Waste Could Be The Next Big Weapon in Controlling COVID-19 – TIME
Next steps for wastewater testing to help end this pandemic — and prevent the next one – STAT
The myriad ways sewage surveillance is helping fight COVID around the world – Nature
It’s time to begin a national wastewater testing program for Covid-19 – STAT
Coronavirus: Testing sewage an ‘easy win’ – BBC
2ry Analysis of a RCT | Metformin linked to 41% reduction in long COVID incidence in outpatient treatment
12 Jun, 2023 | 13:55h | UTCNews Release: Study shows metformin lowers the risk of getting long COVID – University of Minnesota Medical School
Commentary on Twitter
These data not persuasive. There are 6 different arms. 3 drugs. This is not the primary endpoint. No adjustment for multiple testing.
Even USFDA would not accept these data for regulatory approval, and they are basically working for Pharma at this pthttps://t.co/FZoxo9shtG
— Vinay Prasad MD MPH (@VPrasadMDMPH) June 9, 2023
RCT | P2Y12 inhibitors don’t improve outcomes in critically ill COVID-19 patients
31 May, 2023 | 14:13h | UTCSee also: Visual Abstract
RCT | Rivaroxaban doesn’t reduce thrombotic events, hospitalization, or death in outpatients with COVID-19
15 May, 2023 | 13:19h | UTCSummary: The PREVENT-HD trial, a double-blind, placebo-controlled randomized study, was conducted to evaluate the effectiveness of prophylactic anticoagulation in reducing venous and arterial thrombosis, hospitalization, and death in nonhospitalized patients with symptomatic COVID-19 and at least one thrombosis risk factor. The trial took place between August 2020 and April 2022 across 14 US integrated healthcare delivery networks, with 1,284 patients enrolled and randomly assigned to receive either 10 mg of oral rivaroxaban or placebo daily for 35 days.
However, the study was terminated prematurely due to enrollment challenges and lower-than-expected event rates. The primary efficacy outcome, a composite of various hazardous events, occurred in 3.4% of the rivaroxaban group and 3.0% of the placebo group, with no significant difference between the two groups (hazard ratio, 1.16 [95% CI, 0.63–2.15]; P=0.63). No critical-site or fatal bleeding was observed, and only one patient in the rivaroxaban group experienced a major bleed.
In conclusion, rivaroxaban prescribed for 35 days in nonhospitalized patients with symptomatic COVID-19 at risk for thrombosis does not appear to reduce the composite end point of venous and arterial thrombotic events, hospitalization, and death. The study’s premature termination and lower-than-expected event rates may limit the generalizability of these findings.
Commentary on Twitter
#OriginalArticle: In this #RCT, Rivaroxaban did not appear to reduce a composite endpoint of venous and arterial thrombotic events, hospitalization, and death among non‐hospitalized patients with symptomatic COVID‐19 #AHAJournals https://t.co/PhdXnTJ0V9 pic.twitter.com/f04uYu2M5f
— Circulation (@CircAHA) May 10, 2023
RCT | Cognitive behavioral therapy proves effective for severe post-COVID-19 fatigue
15 May, 2023 | 13:16h | UTCNews Release: Cognitive behavioral therapy lessens post-viral fatigue after COVID-19 – Amsterdam UMC
Commentary on Twitter
Efficacy of Cognitive Behavioral Therapy Targeting Severe Fatigue Following COVID-19: Results of a Randomized Controlled Trial
✅ Just Accepted
🔓 Open Access@amsterdamUMChttps://t.co/P1jwLOcfvw— Clinical Infectious Diseases (@CIDJournal) May 13, 2023
M-A | Association of SARS-CoV-2 vaccination or infection with Bell palsy
10 May, 2023 | 16:03h | UTC
Review | Therapeutics for COVID-19
9 May, 2023 | 14:53h | UTCTherapeutics for COVID-19 – Nature Microbiology
Commentary on Twitter
📢New Perspective out now:
Therapeutics for COVID-19
By Sima Toussi, Jennifer Hammond, Brian Gerstenberger & Annaliesa Andersonhttps://t.co/WNJzkFMFuF
— Nature Microbiology (@NatureMicrobiol) May 5, 2023
Cohort Study | Limited evidence linking COVID-19 vaccines to menstrual disturbance or postmenopausal bleeding
9 May, 2023 | 14:52h | UTCNews Release: New study finds no increased risk of menstrual changes after covid-19 vaccination – BMJ Newsroom
Commentary: Large study shows no changes to menstrual cycles after COVID vaccination – CIDRAP
Related:
Editorial: Menstruation and Covid-19 vaccination.
Commentary on Twitter
The findings of this new study do not provide substantial support for a causal association between SARS-CoV-2 vaccination and healthcare contacts related to menstrual or bleeding disordershttps://t.co/Tsw2hjIiIz
— The BMJ (@bmj_latest) May 4, 2023
WHO declares end to COVID-19 global health emergency
8 May, 2023 | 13:26h | UTCWHO Declares End to COVID-19 Global Health Emergency – Health Policy Watch