Ivermectin for COVID-19: real-time meta analysis of 63 studies

Authors: Covid AnalysisAug 12, 2021Version 109 — twitter personality response, added Together Trial (V1 Nov 26, 2020)

•Meta analysis using the most serious outcome reported shows 73% and 86% improvement for early treatment and prophylaxis (RR 0.27 [0.16-0.44] and 0.14 [0.08-0.25]), with similar results after exclusion based sensitivity analysis, restriction to peer-reviewed studies, restriction to serious outcomes, and restriction to Randomized Controlled Trials.•61% and 96% lower mortality is observed for early treatment and prophylaxis (RR 0.39 [0.17-0.90] and 0.04 [0.00-0.59]). Statistically significant improvements are seen for mortalityhospitalizationrecoverycases, and viral clearance. 27 studies show statistically significant improvements in isolation.

StudiesProphylaxisEarly treatmentLate treatmentPatientsAuthors
All studies6386% [75‑92%]73% [56‑84%]40% [24‑52%]26,422613
With exclusions5188% [76‑94%]76% [66‑83%]50% [28‑65%]18,907525
Peer-reviewed4286% [73‑93%]75% [61‑84%]43% [21‑59%]16,455436
Randomized Controlled Trials3184% [25‑96%]67% [54‑76%]30% [2‑50%]6,561359
Mortality results2596% [41‑100%]61% [10‑83%]53% [32‑67%]13,911263
Percentage improvement with ivermectin treatment
Meta-Analysis of Studies for Ivermectin Effectiveness Against COVID-19

•The probability that an ineffective treatment generated results as positive as the 63 studies to date is estimated to be 1 in 1 trillion (p = 0.00000000000083).

Heterogeneity arises from many factors including treatment delay, population, dose, and effect measured, and is low in specific cases, e.g., early treatment mortality.

•While many treatments have some level of efficacy, they do not replace vaccines and other measures to avoid infection. Only 29% of ivermectin studies show zero events in the treatment arm.

•Elimination of COVID-19 is a race against viral evolution. No treatment, vaccine, or intervention is 100% available and effective for all current and future variants. All practical, effective, and safe means should be used. Those denying the efficacy of treatments share responsibility for the increased risk of COVID-19 becoming endemic; and the increased mortality, morbidity, and collateral damage.

•The evidence base is much larger and has much lower conflict of interest than typically used to approve drugs.•All data to reproduce this paper and sources are in the appendix.

See [BryantHariyantoHillKoryLawrieNardelli] for other meta analyses with similar results confirming effectiveness. 00.250.50.7511.251.51.752+Kory et al.69%0.31 [0.20-0.47]Improvement, RR [CI]Hill et al.75%0.25 [0.12-0.52]Bryant et al.62%0.38 [0.19-0.73]Lawrie et al.83%0.17 [0.08-0.35]Nardelli et al.79%0.21 [0.11-0.36]Hariyanto et al.69%0.31 [0.15-0.62]WHO (OR)81%0.19 [0.09-0.36]ivmmeta61%0.39 [0.28-0.56]Ivermectin meta analysis mortality resultsivmmeta.com 8/14/21Lower RiskIncreased Risk

Global adoption: 30%
Evidence base used for other COVID-19 approvals
MedicationStudiesPatientsImprovement
Budesonide (UK)11,77917%
Remdesivir (USA)11,06331%
Casiri/imdevimab (USA)179966%
Ivermectin evidence6326,39869% [60‑75%]
Effectiveness of Other Medications Against COVID-19

For More Information: https://ivmmeta.com/

Fighting post-COVID fatigue: Here’s what doctors suggest

Authors: Rajeswari Parasa 

When TNM spoke to doctors about the post-recovery phase, they say it takes anywhere between four to twelve weeks for a patient to recover from the symptoms of COVID-19.

Doctors suggest that people should limit themselves to doing only mild muscle strengthening and breathing exercises. And that anything beyond mild exercises would only lead to tiredness and fatigue at least for the first two months after testing negative.

“Muscle weakness and fatigue are common in the post-recovery phase of COVID-19. There are two reasons for this, one being lack of nutrition and the other being drop in the oxygen levels, which affects the tissues during the infection. In order to improve the condition, one should properly hydrate themselves and see that electrolytes are maintained. Sodium, potassium, and other such microelements should be balanced with proper nutrition to the body,” says Dr. Raj Kumar Korra, a consultant pulmonologist.

He further suggests that basic muscle strengthening basic exercises such as walking, climbing stairs should be done along with breathing exercises to increase the capacity of the lungs.

Doctors also indicate that the presence of cough-like symptoms also hints at the presence of mild viral load in the body.

For More Information: https://www.thenewsminute.com/article/fighting-post-covid-fatigue-here-s-what-doctors-suggest-149119

Cytokine Storm in COVID-19: The Current Evidence and Treatment Strategies

Authors: Yujun Tang, Jiajia Liu, Dingyi ZhangZhenghao XuJinjun Ji,* and Chengping Wen*

Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) is the pathogen that causes coronavirus disease 2019 (COVID-19). As of 25 May 2020, the outbreak of COVID-19 has caused 347,192 deaths around the world. The current evidence showed that severely ill patients tend to have a high concentration of pro-inflammatory cytokines, such as interleukin (IL)-6, compared to those who are moderately ill. The high level of cytokines also indicates a poor prognosis in COVID-19. Besides, excessive infiltration of pro-inflammatory cells, mainly involving macrophages and T-helper 17 cells, has been found in lung tissues of patients with COVID-19 by postmortem examination. Recently, increasing studies indicate that the “cytokine storm” may contribute to the mortality of COVID-19. Here, we summarize the clinical and pathologic features of the cytokine storm in COVID-19. Our review shows that SARS-Cov-2 selectively induces a high level of IL-6 and results in the exhaustion of lymphocytes. The current evidence indicates that tocilizumab, an IL-6 inhibitor, is relatively effective and safe. Besides, corticosteroids, programmed cell death protein (PD)-1/PD-L1 checkpoint inhibition, cytokine-adsorption devices, intravenous immunoglobulin, and antimalarial agents could be potentially useful and reliable approaches to counteract cytokine storm in COVID-19 patients.

For More Information: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7365923/

Cytokine storm in COVID-19: pathogenesis and overview of anti-inflammatory agents used in treatment

Authors: Mehmet Soy 1Gökhan Keser 2Pamir Atagündüz 3Fehmi Tabak 4Işık Atagündüz 5Servet Kayhan

COVID-19 infection has a heterogenous disease course; it may be asymptomatic or causes only mild symptoms in the majority of the cases, while immunologic complications such as macrophage activation syndrome also known as secondary hemophagocytic lymphohistiocytosis, resulting in cytokine storm syndrome and acute respiratory distress syndrome, may also occur in some patients. According to current literature, impairment of SARS-CoV-2 clearance due to genetic and viral features, lower levels of interferons, increased neutrophil extracellular traps, and increased pyroptosis and probable other unknown mechanisms create a background for severe disease course complicated by macrophage activation syndrome and cytokine storm. Various genetic mutations may also constitute a risk factor for severe disease course and occurrence of cytokine storm in COVID-19. Once, immunologic complications like cytokine storm occur, anti-viral treatment alone is not enough and should be combined with appropriate anti-inflammatory treatment. Anti-rheumatic drugs, which are tried for managing immunologic complications of COVID-19 infection, will also be discussed including chloroquine, hydroxychloroquine, JAK inhibitors, IL-6 inhibitors, IL-1 inhibitors, anti-TNF-α agents, corticosteroids, intravenous immunoglobulin (IVIG), and colchicine. Early recognition and appropriate treatment of immunologic complications will decrease the morbidity and mortality in COVID-19 infection, which requires the collaboration of infectious disease, lung, and intensive care unit specialists with other experts such as immunologists, rheumatologists, and hematologists.

For More Information: https://pubmed.ncbi.nlm.nih.gov/32474885/

Accumulating evidence suggests anti-TNF therapy needs to be given trial priority in COVID-19 treatment

Authors: Philip C Robinson, Duncan Richards, Helen L Tanner, Marc Feldmann

The COVID-19 pandemic continues to wreak havoc on global health-care systems and to claim an increasing number of lives. Although some treatments have shown promise, including dexamethasone and remdesivir, problems remain with access to medication and high mortality despite treatment. Patient selection also appears to be critical, with some patient groups benefitting from treatment, but not others. One potential treatment that deserves higher priority in COVID-19 trials, based on the documented evidence of its effects, is the biological agent anti-TNF.Feldmann and colleagues1 described the rationale for trialling anti-TNF therapies in COVID-19. These therapies neutralise TNF, a major component of the cytokine response that is part of the damaging excess inflammatory phase of COVID-19, which is termed hyperinflammation or cytokine release syndrome. This hyperinflammatory response in COVID-19 is characterised by elevated concentrations of serum TNF, interleukin (IL)-6, and IL-8, but relatively little IL-1.2 However, IL-1 has a short serum half-life, and mononuclear transcriptome data show that genes and pathways upregulated by TNF, IL-1β, and type I interferon predominate.3 A major component of deteriorating lung function in patients with COVID-19 is capillary leak, a result of inflammation driven by key inflammatory cytokines: TNF, IL-1, IL-6, and vascular endothelial growth factor. Administration of anti-TNF to patients for treatment of autoimmune disease leads to reductions in all of these key inflammatory cytokines.45 It is therefore conceivable that anti-TNF therapy could reduce inflammation-driven capillary leak in COVID-19 and have a major impact on the need for ventilation and mortality.

For More Information: https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(20)30309-X/fulltext

TNF Biologics and COVID-19: What Autoimmune Patients Need to Know

Authors:

If you’re taking a type of medication known as tumor necrosis factor inhibitors, also called anti-TNF or TNFis, you may be wondering how these drugs could impact your chances of contracting COVID-19, or having more severe complications from it. After all, the common cold or other upper respiratory tract infections can be more common in people taking anti-TNF inhibitors.

On the other hand, some rheumatologists are pointing out that TNF biologics may actually be protective against COVID-19 inflammation — and they are calling for more clinical trials to study these drugs as a potential COVID treatment.

No wonder there is confusion and anxiety among the people who take these medications to manage conditions like rheumatoid arthritis, psoriasis, and Crohn’s disease.

While more research is needed to fully understand the impact of these medications on COVID-19, at least there is some preliminary data from the first few months of the pandemic, which is helping doctors and researchers make decisions help keep you healthy and safe.

We talked with top rheumatologist to help quell your fears and answer your questions. Read on to learn about how anti-TNF biologics work in the body, what the latest coronavirus research says, and how to best manage your inflammatory condition and minimize your risk of COVID-19.

For More Information: https://web.archive.org/web/20210530063127/https://creakyjoints.org/living-with-arthritis/coronavirus/treatments/tumor-necrosis-factor-biologics-covid-19/

COVID-19 One Year Later

Authors: Giuseppe NovelliMichela BiancolellaRuty Mehrian-ShaiVito Luigi ColonaAnderson F. BritoNathan D. GrubaughVasilis VasiliouLucio Luzzatto & Juergen K. V. Reichardt 

COVID-19 has engulfed the world and it will accompany us all for some time to come. Here, we review the current state at the milestone of 1 year into the pandemic, as declared by the WHO (World Health Organization). We review several aspects of the on-going pandemic, focusing first on two major topics: viral variants and the human genetic susceptibility to disease severity. We then consider recent and exciting new developments in therapeutics, such as monoclonal antibodies, and in prevention strategies, such as vaccines. We also briefly discuss how advances in basic science and in biotechnology, under the threat of a worldwide emergency, have accelerated to an unprecedented degree of the transition from the laboratory to clinical applications. While every day we acquire more and more tools to deal with the on-going pandemic, we are aware that the path will be arduous and it will require all of us being community-minded. In this respect, we lament past delays in timely full investigations, and we call for bypassing local politics in the interest of humankind on all continents.

For More Information: https://humgenomics.biomedcentral.com/articles/10.1186/s40246-021-00326-3

Early High-Titer Plasma Therapy to Prevent Severe Covid-19 in Older Adults

Authors: Romina Libster, M.D., Gonzalo Pérez Marc, M.D., Diego Wappner, M.D., Silvina Coviello, M.S., Alejandra Bianchi, Virginia Braem, Ignacio Esteban, M.D., Mauricio T. Caballero, M.D., Cristian Wood, M.D., Mabel Berrueta, M.D., Aníbal Rondan, M.D., Gabriela Lescano, M.D., et al., for the Fundación INFANT–COVID-19 Group*

Therapies to interrupt the progression of early coronavirus disease 2019 (Covid-19) remain elusive. Among them, convalescent plasma administered to hospitalized patients has been unsuccessful, perhaps because antibodies should be administered earlier in the course of illness.

For More Information: https://www.nejm.org/doi/full/10.1056/NEJMoa2033700

Coronavirus 2019 (COVID-19)- Using Ascorbic Acid and Zinc Supplementation (COVIDAtoZ)

Authors: Milind Desai, M. D, Suma Thomas Principal Investigators: The Cleveland Clinic

A Clinical Trail to see whether ascorbic acid and zinc gluconate which has limited side effect profile and is readily available over the counter can decrease the duration of symptoms seen in patients with new diagnosis of COVID-2019. A secondary purpose is to see whether Zinc and/or Ascorbic acid supplementation can prevent progression of the severe manifestations of the disease including development of dyspnea and acute respiratory distress syndrome which may require hospitalization, mechanical ventilation, and or lead to death.

For More Information: https://clinicaltrials.gov/ct2/show/NCT04342728

Considerations for Certain Concomitant Medications in Patients With COVID-19

Authors: NIH

  • Patients with COVID-19 who are receiving concomitant medications (e.g., angiotensin-converting enzyme [ACE] inhibitors, angiotensin receptor blockers [ARBs], statins, systemic or inhaled corticosteroids, nonsteroidal anti-inflammatory drugs, acid-suppressive therapy) for underlying medical conditions should not discontinue these medications during acute management of COVID-19 unless discontinuation is otherwise warranted by their clinical condition (AIIa for ACE inhibitors and ARBs; (AIII) for other medications).
  • The COVID-19 Treatment Guidelines Panel recommends against using medications off-label to treat COVID-19 if they have not demonstrated safety and efficacy in patients with COVID-19, except in a clinical trial.

For More Information: https://www.covid19treatmentguidelines.nih.gov/therapies/concomitant-medications/