key: cord-1047486-5x7w9w0q
authors: Chahla, Rossana E.; Medina Ruiz, Luis; Ortega, Eugenia S.; Morales, RN, Marcelo F.; Barreiro, Francisco; George, Alexia; Mancilla, RN, Cesar; D' Amato, RN, Sylvia; Barrenechea, Guillermo; Goroso, Daniel G.; Peral de Bruno, Maria
title: Intensive Treatment With Ivermectin and Iota-Carrageenan as Pre-exposure Prophylaxis for COVID-19 in Health Care Workers From Tucuman, Argentina
date: 2021-08-16
journal: Am J Ther
DOI: 10.1097/mjt.0000000000001433
sha: 1afd27c1f599b82a206584b29bb9dca0156c2c2f
doc_id: 1047486
cord_uid: 5x7w9w0q

nan

To the Editor: After COVID-19 emerged, a multitude of both novel and repurposed therapeutic agents were used empirically and studied in controlled clinical trials. [1] [2] [3] Ivermectin is a broad spectrum antiparasitic agent that has shown to have antiviral activity against a wide range of viruses. 4, 5 On March 31, the World Health Organization (WHO) stated that evidence about ivermectin use for COVID-19 treatment is not conclusive. However, it encouraged its utilization in controlled clinical trials. At June 2021, there were 65 studies registered at https://www.ClinicalTrials.gov and 45 studies listed at https://ClinicalTrials.gov/ct2/who_table about the safety and effectiveness of ivermectin in subjects with COVID-19, of which 16 studies have been completed (for COVID-19 treatment). Most of these studies on ivermectin repositioning came from developing countries like ours, Argentina, with limited access to vaccines. These emergent economies have the need to find supportive therapies that are synergistic or alternatives to contain the spread of the disease and deter the health systems' collapse.

Kory's meta-analysis (2021) reported that ivermectin has antiviral and anti-inflammatory mechanisms with statistically significant positive outcome. 6 However, most of these studies were not published in peerreviewed journals; nevertheless, several expert groups including the WHO have undertaken a global effort to contact all active clinical trials to rapidly gather the data needed to perform a systematic review and meta-analyses. In Kory's publication, 6 ivermectin showed ability to prevent transmission and improvement in the treatment in both observational 9,10 and randomized trials. 7, 8, 11, 12, 13 Our work was included in this systematic review. This letter to the editor aims to provide more details of our findings, presenting experimental evidence for the prophylactic use of ivermectin associated with iota-carrageenan in health workers. 12 We conducted a randomized controlled 1-1 clinical trial (registry number NCT04701710 www.ClinicalTrial.gov) in 234 adults. The subjects were divided into the experimental group (EG), n 5 117, median age5 40 years [interquartile range (IQR), 32-46], and 65 F (55.56%) and the control group (CG) n 5 117, 37 years (IQR, 33-44), and 69 F (58.97%). All subjects completed the study; 134 were female (57.3%) and 100 were men (42.7%), and 77.4% were health care workers ( Table 1 ). The experimental group received ivermectin orally 2 tablets of 6 mg every 7 days and iota-carrageenan 6 sprays per day for 4 weeks. All participants were evaluated by physical examination and COVID-19 diagnosed with negative reverse transcription polymerase chain reaction at the protocol baseline. We calculated odds ratio (OR) and created a logistic regression using comorbidity, sex, age, and job designation as covariables. A P value , 0.05 was considered significant.

The number of subjects who were diagnosed with COVID-19 in the EG was lower than subjects in the CG (P value 5 0.0001), Figure 1A . Overall, 19 patients had mild symptoms, 4 were in the EG whereas 15 were in the CG (P value 5 0.001), Figure 1B . The probability of becoming ill with COVID-19 was significantly lower in the EG [OR 0.13, 95% confidence interval (CI) 0.03-0.40; P value 5 0.0001]. We also found that increasing age decreases the risk of contagion (OR 5 0.93, 95% CI 0.88-0.98, P value 5 0.02). The probability of contracting COVID-19 was dependent on the subject's pre-existing comorbidity (OR 3.45, 95% CI 1.55-7.67, P value 5 0.002). The other variables (sex and job designation) did not have influence on COVID-19 infection.

Health personnel are one of the most exposed groups to COVID-19 because of their steady contact with infected patients. In this study, treatment with IVER/IOTACRC for pre-exposure prophylaxis to COVID-19 has shown a protective effect over the control group. People infected with COVID-19 at the end of the follow-up was significantly higher in the CG compared with the EG ( Figure 1B) .

Our findings are supported by several recent prevention trials such as Alam et al 10 (also cited by Kory's metaanalysis), who conducted an observational prophylactic study in 118 health care workers and found significant less contagious infection in subjects who received ivermectin. 6, 10 Our findings, similarly to Carvallo et al and Abd-Elsalam et al, confirm the hypothesis that IVER/ IOTACRC decreases the possibility of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and possibly acts synergistically. 9, 14, 15 We hypothesize that a double viral barrier is formed, enhancing its action in the following ways: (1) The first barrier for viral protection would be at the entry of the virus into the nasal cavity where the carrageenan would behave as a mucolytic agent in the barrier of sulfated polysaccharides with negative charge 9 ; (2) ivermectin decreases the viral load based on its systemic cellular action. 5, 16 Ivermectin has shown viral clearance in other clinical trials which evaluate its use to treat COVID-19. Kolewieski et al found that a 5-day intensive treatment of ivermectin resulted in earlier clearance of the virus compared with the control group. 8 Ivermectin can prevent the entry into the cell nucleus of the viral RNA by blocking importin alpha/beta, thereby preventing replication because SARS-CoV-2 does not have the nuclear mechanisms and enzymatic actions for the transcription of new viral replicates. 4 Our study is supported by findings which demonstrated the effect of ivermectin as a drug for inhibiting viral replication in vitro and places the drug as a new therapeutic candidate against SARS-CoV-2. 16,17 In a meta-analysis published in June 2021, Bryant et al after analyzing different clinical trials showed that ivermectin may have beneficial effects in both prophylaxis and treatment of Covid-19. 18 Our study shows agreement with other research groups regarding positive findings in the use of ivermectin for the treatment of COVID-19 that deserves further studies about repurposing ivermectin. To the Editor: Immune thrombocytopenia (ITP) is an acquired coagulopathy caused by antibody-mediated platelet destruction. Patients may be asymptomatic or may present with mucocutaneous to life-threatening bleeding. 1 Vaccines such as influenza, MMR, hepatitis B, and diphtheria-tetanus-pertussis have been reported to cause ITP. 2 Approximately 40 cases of ITP were reported to the Vaccine Adverse Event Reporting System after receiving the Pfizer and Moderna COVID-19 vaccines by the end of January 2021. 3 It is unknown whether these cases include those with pre-existing thrombocytopenia. Here, we present a case report of an elderly woman presenting with life-threatening thrombocytopenia after receiving the Ad26.COV2.S (Janssen; Johnson & Johnson, New Brunswick, NJ) vaccine. To the best of our knowledge, this is the first publication of isolated severe thrombocytopenia in a patient with no pre-existing risk factors after receiving the Ad26.COV2.S vaccine.

A 63-year-old woman with a medical history of cervical cancer status after total hysterectomy, presented to the hospital with complaints of bleeding from her gums for the past 3 days. Seventeen days before presentation, the patient had received the Ad26.COV2.S (Janssen; Johnson & Johnson) vaccine. She did not experience any major side effects after her vaccination except for muscle soreness at the administration site. She did not have fever, chills, shortness of breath, or recent infections. A week later, she went for a routine dental checkup which was unremarkable. She started experiencing bleeding in her gums 3 days before presentation. She later had sudden onset nose bleeds which prompted her to go to the emergency department.

On presentation to the emergency department, the patient was hemodynamically stable and afebrile. Her bleeding had resolved. Complete blood count showed hemoglobin 12.2 g/dL, hematocrit 36.3%, white blood cell count 10.9 3 10 3 cells/uL, and significant severe thrombocytopenia 2 3 10 9 /L. Her international normalized ratio was 1.02, with a prothrombin time of 13.5 seconds and a partial thromboplastin time of 27.0 seconds. Hemolytic workup was completed with lactate dehydrogenase 150 U/L, haptoglobin 192 mg/dL, and D-dimer 0.76.

On admission, she received 2 units of platelets. She was also given a one-time dose of prednisone 60 mg orally. Her repeat platelet count posttransfusion improved to 14 3 10 9 /L. Hematology was consulted and recommended starting the patient on immune globulin (human) infusion intravenously and dexamethasone 20 mg daily.

Throughout admission, the patient's platelet count steadily increased. She did not have further bleeding episodes and did not require additional platelet transfusions. Testing for HIV and hepatitis B and C was negative. Heparin-induced platelet IgG antibody was negative. Imaging including ultrasound Doppler of the abdomen/pelvis, ultrasound Doppler of upper and lower extremities, magnetic resonance venogram of the head, and computed tomography angiography of the thorax showed no evidence of thrombosis. The patient remained hemodynamically stable throughout admission with no signs of active bleeding. She was ultimately deemed stable for discharge 5 days after admission, with a platelet count of 252 3 10 9 /L. Immune thrombocytopenia purpura (ITP) is a diagnosis of exclusion characterized by a decrease in platelet count and prolonged bleeding time secondary to impaired platelet production or destruction of circulating platelets. Patients are commonly asymptomatic; however, based on the severity of thrombocytopenia, clinical features include easy bruising, petechiae, bleeding gums, hematuria, or melena. ITP is often triggered idiopathically; however, other triggers include previous viral or bacterial infections, lymphoma or

New uses for old drugs

In silico drug repositioning: what we need to know

Drug repositioning: identifying and developing new uses for existing drugs

Nuclear trafficking of proteins from RNA viruses: potential target for antivirals?

Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect , the company' s public news and information

Review of the emerging evidence demonstrating the efficacy of ivermectin in the prophylaxis and treatment of COVID-19

The effect of early treatment with ivermectin on viral load, symptoms and humoral response in patients with nonsevere COVID-19: a pilot, double-blind, placebocontrolled

Antiviral effect of high-dose ivermectin in adults with COVID-19: A proof-of-concept randomized trial

Study of the efficacy and safety of topical ivermectin + iota-carrageenan in the prophylaxis against COVID-19 in health personnel

Ivermectin as pre-exposure prophylaxis for COVID-19 among healthcare providers in a selected tertiary hospital in dhakaan observational study

Use of ivermectin as a potential chemoprophylaxis for COVID-19 in Egypt: a randomized clinical trial

Prophylaxis covid-19 in health workers through intensive treatment with ivermectin and iotacarrageenan (Ivercar-Tuc)

The sars-cov-2 ivermectin navarra-isglobal trial (saint) to evaluate the potential of ivermectin to reduce covid-19 transmission in low risk, non-severe covid-19 patients in the first 48 hours after symptoms onset: a structured summary of a study protocol

Covid 19 and ivermectin prevention and treatment update

Clinical study evaluating the efficacy of ivermectin in COVID-19 treatment: A randomized controlled study