Bulgaria is protecting health care workers and outpatients the smart way, as reported here Hydroxychloroquine for prophylaxis and treatment of COVID-19 in health care workers: Bulgaria. Excerpts in italics with my bolds.
Hydroxychloroquine (HCQ) exerts antiviral effects through several mechanisms. Our initial experience suggests that HCQ could be used for prophylaxis of COVID-19 infection in health care workers (HCW) and could help to control the virus in the early disease stages. We suggest a prophylactic strategy with HCQ for autumn-winter-spring 2020-2021.
Providing adequate health care is vitally important during the COVID-19 pandemic to keep morbidity and mortality low. Health care workers (HCW) are key guarantees for this process, and they must feel safe and adequately protected, which includes reliable prophylactic measures (1).
Hydroxychloroquine (HCQ) could exert antiviral effects, essential for prophylaxis and early treatment of COVID-19, through several mechanisms: 1) endosomal pH increase, which inhibits SARS-CoV-2 entry through the host cells’ membranes; 2) inhibition of ACE2 cell receptor glycosylation, which impedes SARS-CoV-2-receptor binding; 3) blocking the transport of SARS-CoV-2 from early endosomes to endolysosomes, which prevents the release of viral genome; 4) immunomodulation; 5) limiting the post-viral cytokine-storm syndrome (2, 3).
We share the experience of the Bulgarian Cardiac Institute (BCI) regarding the use of HCQ for prophylaxis and treatment of COVID-19 in HCW.
BCI comprises seven hospitals and eight medical centers, with around 1200 HCW, covering more than two-thirds of Bulgarian territory.
Since March 2020, many of our employees were in close contact with COVID-19 cases. We offered prophylaxis with HCQ 200 mg qd for 14 days to 204 of them. 76.4% of the group (156 HCW) used HCQ and none of them presented with COVID-19 symptoms. Unfortunately, out of the rest 48 HCW that refused HCQ prophylaxis, three developed symptoms and tested positive for COVID-19.
During the last seven months, 38 HCW at BCI tested positive for COVID-19, half of them symptomatic.
We suggested the following treatment regimen as an early home-based therapy for them: azithromycin 500 mg qd; HCQ 200 mg tid and Zn up to 50 mg qd for 14 days. 33 (86.8%) of them undertook this treatment, with symptoms abolishing between 2nd and 4th day, none of them requiring hospitalization and with a negative PCR on 14th day for all.
In conclusion, our experience at BCI suggests that HCQ could possibly provide protection against infection with SARS-CoV-2 (prophylaxis), and could, if used early, help control the COVID-19 infection (treatment).
Based on this experience, we at BCI adopted a new prophylactic strategy for HCW starting from the 2nd half of October 2020. This includes alternative months of HCQ intake (200 mg qd) and months without therapy. We are planning to continue this prophylaxis regimen throughout the autumn, winter, and spring months.
From previous post:
Article is HCQ is effective for COVID-19 when used early: analysis of 118 studies. Excerpts in italics with my bolds.
HCQ is an effective treatment for COVID-19. The probability that an ineffective treatment generated results as positive as the 118 studies to date is estimated to be 1 in 23 million (p = 0.000000043).
•Early treatment is most successful, with 100% of studies reporting a positive effect and an estimated reduction of 63% in the effect measured (death, hospitalization, etc.) using a random effects meta-analysis, RR 0.37 [0.30-0.47].
•100% of Randomized Controlled Trials (RCTs) for early, PrEP, or PEP treatment report positive effects, the probability of this happening for an ineffective treatment is 0.002.
•There is evidence of bias towards publishing negative results. Significantly more retrospective studies report negative results compared to prospective studies, p = 0.04.
•Significantly more studies in North America report negative results compared to the rest of the world, p = 0.002.
Figure 2 shows stages of possible treatment for COVID-19. Pre-Exposure Prophylaxis (PrEP) refers to regularly taking medication before being infected, in order to prevent or minimize infection. In Post-Exposure Prophylaxis (PEP), medication is taken after exposure but before symptoms appear. Early Treatment refers to treatment immediately or soon after symptoms appear, while Late Treatment refers to more delayed treatment.
Publication bias. Publishing is often biased towards positive results, which we would need to adjust for when analyzing the percentage of positive results. Studies that require less effort are considered to be more susceptible to publication bias. Prospective trials that involve significant effort are likely to be published regardless of the result, while retrospective studies are more likely to exhibit bias. For example, researchers may perform preliminary analysis with minimal effort and the results may influence their decision to continue. Retrospective studies also provide more opportunities for the specifics of data extraction and adjustments to influence results.
For HCQ, 87.5% of prospective studies report positive effects, compared to 69.8% of retrospective studies, two-tailed z test 2.07, p = 0.04, indicating a bias toward publishing negative results.
The lack of bias towards positive results is not very surprising. Both negative and positive results are very important given the current use of HCQ for COVID-19 around the world, evidence of which can be found in the studies analyzed here, government protocols, and news reports, for example [AFP, AfricaFeeds, Africanews, Afrik.com, Al Arabia, Al-bab, Anadolu Agency, Anadolu Agency (B), Archyde, Barron’s, Barron’s (B), BBC, Belayneh, A., CBS News, Challenge, Dr. Goldin, Efecto Cocuyo, Expats.cz, Face 2 Face Africa, France 24, France 24 (B), Franceinfo, Global Times, Government of China, Government of India, GulfInsider, Le Nouvel Afrik, LifeSiteNews, Medical World Nigeria, Medical Xpress, Medical Xpress (B), Middle East Eye, Ministerstva Zdravotnictví, Morocco World News, Mosaique Guinee, Nigeria News World, NPR News, Oneindia, Pan African Medical Journal, Parola, Pilot News, Pleno.News, Q Costa Rica, Rathi, Russian Government, Teller Report, The Africa Report, The Australian, The BL, The East African, The Guardian, The Indian Express, The Moscow Times, The North Africa Post, The Tico Times, Ukraine Ministry of Health Care, Ukrinform, Vanguard, Voice of America].
We also note a bias towards publishing negative results by certain journals and press organizations, with scientists reporting difficulty publishing positive results [Boulware, Meneguesso]. Although 88 studies show positive results, The New York Times, for example, has only written articles for studies that claim HCQ is not effective [The New York Times, The New York Times (B), The New York Times (C)]. As of September 10, 2020, The New York Times still claims that there is clear evidence that HCQ is not effective for COVID-19 [The New York Times (D)]. As of October 9, 2020, the United States National Institutes of Health still recommends against HCQ for both hospitalized and non-hospitalized patients [United States National Institutes of Health].
Treatment details. We focus here on the question of whether HCQ is effective or not for COVID-19. Significant differences exist based on treatment stage, with early treatment showing the greatest effectiveness. 100% of early treatment studies report a positive effect, with an estimated reduction of 63% in the effect measured (death, hospitalization, etc.) in the random effects meta-analysis, RR 0.37 [0.30-0.47]. Many factors are likely to influence the degree of effectiveness, including the dosing regimen, concomitant medications such as zinc or azithromycin, precise treatment delay, the initial viral load of patients, and current patient conditions.
News website Panorama.it has launched a petition to get the drug hydroxychloroquine officially reinstated so that Italian doctors can once again use it with patients. If not, some of them will go ahead and use it anyway. The retracted Lancet study and trials using lethal doses(!) of HCQ were enough to get it officially banned in Italy as in other countries. Except the Italian Medicines Agency (AIFA) has not yet reapproved it, despite studies showing its effectiveness. Here are excerpts of the Change.org petition translated from Italian:
At the moment there are no treatments of proven effectiveness to be administered at home. Because the only therapy that AIFA (Italy’s Medicines Agency) had authorized at home, the one based on hydroxychloroquine, has been blocked. It happened on May 26, after the publication of a study in The Lancet, which was withdrawn 13 days later.
Meanwhile, German GPs, who had administered 1,060,000 doses of hydroxychloroquine in March, continued to prescribe it. In the United States, three states lifted the ban on the drug in early August. In China, on August 19, the National Health Commission’s guidelines continued to recommend the active ingredient for Covid 19 patients. And on September 21, The Lancet itself retraced its steps, with a study claiming that hydroxychloroquine reduces mortality.
In order to save lives, we ask AIFA to restore the use of hydroxychloroquine for home patients in the very early stages of the disease, possibly even with an emergency procedure. Otherwise, we invite the Agency to provide shared protocols of treatment practicable in the territory.