Should I treat my patient with Covid-19 with ivermectin?

Despite its potential antiviral activity,1 there is insufficient data at this time to recommend either for or against the use of ivermectin for the treatment of Covid-19, per NIH Covid-19 guidelines.2 This conclusion is based on lack of robust, adequately powered and designed clinical trials.2

Although some studies (published or preprint) have reported benefits of ivermectin (eg, shorter time to resolution of disease or viral clearance, greater reduction in inflammatory markers, and lower mortality rates) in Covid-19, others have found either no benefit or worsening of disease with ivermectin therapy.2-6

Unfortunately, methodological problems have plagued many of these studies.1 For example, a randomized-controlled preprint study from Egypt reported clinical improvement and decreased mortality in Covid-19 patients treated with ivermectin.  Unfortunately, the ivermectin group also received hydroxychloroquine plus a “standard therapy”, defined in the study as azithromycin, vitamin C, zinc, lactoferrin and acetylcysteine.3

A retrospective study from Bangladesh involving hospitalized patients with Covid-19,  reported lower mortality in those receiving only 1 dose of ivermectin (12 mg) within 24 h of admission.  However, 60% of the non-ivermectin group also received antibiotics, often for undefined “secondary infection” (vs 15% of ivermectin group)4, making it difficult to interpret the results.

In contrast, a retrospective preprint study from Peru found significantly higher rates of death and/or ICU transfer among hospitalized patients treated with ivermectin or hydroxychloroquine+azithromycin.4

The plausibility of studies supporting treatment of Covid-19 with ivermectin has been further questioned because, despite its apparent antiviral activity in vitro,1 pharmacokinetic and pharmacodynamic studies suggest that doses up to 100 times higher than those approved for use in humans would be needed to achieve potentially effective plasma concentrations.2,7

Bonus Pearl: Did you know that ivermectin enhances the activity of GABA receptors, resulting in paralysis of somatic muscles, poor pharyngeal function and starvation of parasites and worms? 8 Fortunately, ivermectin’s affinity for parasite is 100 times more than for brain of mammals because of the blood brain barrier.

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References

  1. Lehrer S, Rheinstein PH. Ivermectin docks to the SARS-CoV-2 spike receptor-binding domain attached to ACE2. In vivo 2020;34:3023-6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7652439/pdf/in_vivo-34-3023.pdf
  2. NIH. The Covid-19 treatment guidelines panel’s statement on the use of ivermectin for the treatment of COVID-19. Last updated Jan 14, 2021. https://www.covid19treatmentguidelines.nih.gov/statement-on-ivermectin/. Accessed January 18, 2021.
  3. Elgazzar A, Hany B, Abo Youssef S, et al. Efficacy and safety of ivermectin for treatment and prophylaxis of COVID-19 pandemic. Research Square Preprint 2020. https://assets.researchsquare.com/files/rs-100956/v2/39b225ad-5df4-4da7-9cbd-233bf26a0eb4.pdf
  4. Ahmed S, karim MM, Ross AG, et al. A five-day course of ivermectin for the treatment of COVID-19 may reduce the duration of illness. International J Infect Dis 2021;103:214-16. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7709596/
  5. Soto-Becerra P, Culquichicon C, Hurtado-Roca Y, et al. Real-world effectiveness of hydroxychloroquine, azithromycin, and ivermectin among hospitalized COVID-19 patients: results of a target trial emulation using observational data from a nationwide healthcare system in Peru. MedRxive 2020. https://www.medrxiv.org/content/10.1101/2020.10.06.20208066v3.full.pdf
  6. Chachar AZ, Khan KA, Asif M, et al. Effectiveness of ivermetctin in SARS-CoV-1/COVID-19 patients. International J Sciences 2020; 9:31-35. https://c19ivermectin.com/chachar.html
  7. Chaccour C, hammann F, Ramon-Garcia S, et al. Ivermectin and COVID-19: Keeping rigor in times of urgency. Am J Trop med hyg 2020;102:1156-7. https://pubmed.ncbi.nlm.nih.gov/32314704/  
  8. Kaur H, Shekhar N, Sharma S, et al. Ivermectin as a potential drug for treatment of COVID-19:an in-sync review with clinical and computational attributes. Pharmacological Reports. Published online January 3, 2021. Great review https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7778723/pdf/43440_2020_Article_195.pdf

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis or its affiliate healthcare centers. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

Should I treat my patient with Covid-19 with ivermectin?

Beyond masks and hand hygiene, what factors impact transmission of Covid-19 in indoor gatherings?

Aside from factors specific to the source individual (eg, viral load in exhaled air, “superspreader” features, etc…) and host characteristics (eg, older age, obesity, immunocompromised state), transmission of SARS-CoV-2 in indoor settings may be impacted by several factors, including social distancing, ventilation of rooms/ direction of airflow, room occupancy, exposure time and higher risk activities, such as eating, talking loud, heavy breathing during exercise, laughing, coughing and sneezing. 1-4

  1. Physical distance from infected individuals. Although a “safe” distance of 6 feet has often been cited, increasing evidence suggests that SARS-CoV-2 may be spread not only by larger droplets but also by airborne route (ie, beyond 6 feet or shortly after an infected person leaves the area). In fact, 8 of 10 studies on horizontal droplet distance have reported droplets traveling more than 6 feet (2 meters), some cases up to 26 feet (8 meters), and 1 study documented virus at 13 feet (4 meters). Transmission beyond 6 feet is not surprising since even as early as 1948 beta streptococci were found 9.5 feet from 10% of people who were infected!1
  2. Quality of ventilation and direction of airflow in the room. Poorly ventilated rooms would be expected to have more potentially infectious droplets in the air for longer periods of time, even after an infected person leaves the area.
  3. Room occupancy. The higher the occupancy the more likely to have exhaled contaminated air from 1 or more infected persons (symptomatic or asymptomatic) with exposure of susceptible hosts.
  4. Exposure time. Exposure to contaminated air in the room even for a relatively short period of time (ie, >5-15 minutes) is likely to increase the risk of transmission.
  5. Activity of infected individual. Many activities such as singing, speaking loudly, eating, laughing, breathing heavily during exercise, coughing and sneezing may increase risk of Covid-19 transmission in indoor settings.

Recall that over one-half of Covid-19 transmissions are due to asymptomatic individuals.5 In this setting and in the presence of factors discussed above, it’s easy to see how transmission of Covid-19 in indoor settings can occur readily, possibly explaining cases without apparent source.

Bonus Pearl: Did you know that the odds of Covid-19 transmission may be 18.7 times greater indoors compared to open-air environment and the odds of superspreading event in closed environments may be 32.6 times higher?4

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References

  1. Bahl P, Doolan C, de Silva C, et al. Airborne or droplet precautions for health workers treating coronavirus disease 2019? J Infect Dis 2020. Published online April 16, 2020. https://pubmed.ncbi.nlm.nih.gov/32301491/
  2. Jones NR, Quereshi Z, Temple RJ, et al. Two metres or one: what is the evidence for physical distancing in covid-19? BMJ 2020;370:m3223. https://www.bmj.com/content/370/bmj.m3223/rr-18
  3. Johansson MA, Quandelacy TM, Kada S, et al. SARS-CoV-2 transmission from people without COVID-19 symptoms. JAMA Network open. 2021;4():e2035057. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2774707?utm_source=For_The_Media&utm_medium=referral&utm_campaign=ftm_links&utm_term=010721
  4. Nishiura H, Oshitani H, Kobayashi T, et al. Closed environments facilitate secondary transmission of coronavirus disease 2019 (COVID-19). MedRxiv 2020. https://www.medrxiv.org/content/10.1101/2020.02.28.20029272v2.full.pdf
  5. Leclerc QJ, Fuller NM, Knight LE,e tal. What settings have been linked to SARS-CoV-2 transmission clusters? Wellcome Open Research October, 2020. https://wellcomeopenresearch.org/articles/5-83    

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis or its affiliate healthcare centers. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

Beyond masks and hand hygiene, what factors impact transmission of Covid-19 in indoor gatherings?

Can race affect the accuracy of pulse oximetry measurement?

It can! In persons with darkly pigmented skin, pulse oximeters may overestimate arterial oxygen saturation, such that some individuals with oxygen saturation within an acceptable range by pulse oximetry may actually be hypoxemic by arterial blood measurement.1-3

A 2020 study involving 2 large patient populations with oxygen saturations of 92-96% by pulse oximetry, found occult hypoxemia (<88% arterial oxygen saturation) in ~12% of patients who were Black vs ~4% of those who were White. Black individuals were 3 times more likely to have occult hypoxemia than White patients.1

Overestimation of oxygen saturation—particularly at low arterial oxygen saturation— by pulse oximetry in dark-skinned individuals has been previously reported by several studies, although some have not found significant differences at normal saturations, and the degree of discordance may vary among various pulse oximeters.2,3

The reason for the apparent discrepancy between oxygen saturation measured by pulse oximetry vs arterial blood sample in those with dark skin is unclear. Some have suggested “pulse oximeter optical factors” and theorized that provision of correction factors, tables, or even built-in user -optional adjustments may be necessary.2

Given the frequent use of pulse oximetry for medical decision making in Covid-19, these studies should serve as a cautionary note when interpreting oxygen saturation by pulse oximeter in dark-skinned patients with Covid-19.

Bonus Pearl: Did you know that falsely-LOW oxygen saturation has been reported with blue and green nail polish but not red?4

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References

  1. Sjoding MW, Dickson RP, Valley TS. Racial bias in pulse oximetry measurement. N Engl J Med 2020;383:2477-78. https://pubmed.ncbi.nlm.nih.gov/33326721/
  2. Bickler PE, Feiner JR, Severinghaus JW. Effects of skin pigmentation on pulse oximeter accuracy at low saturation. Anesthesiology 2005;102:715-9. https://pubs.asahq.org/anesthesiology/article/102/4/715/7364/Effects-of-Skin-Pigmentation-on-Pulse-Oximeter
  3. Zeballos RJ, Weisman. Reliability of noninvasive oximetry in Black subjects during exercise and hypoxia. Am Rev Resp Dis 1991;144:1240-4. https://www.atsjournals.org/doi/pdf/10.1164/ajrccm/144.6.1240
  4. Cote CJ, Goldstein EA, Fuchsman WH. The effect of nail polish on pulse oximetry. Anesth Analg 1988;75:683-6. https://pubmed.ncbi.nlm.nih.gov/3382042/

 

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis or its affiliate healthcare centers. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

Can race affect the accuracy of pulse oximetry measurement?

Is the discovery of new variants of SARS-CoV-2 expected to impact the transmissibility, clinical course or vaccine efficacy in Covid-19?

To date, the discovery of new variants of SARS-CoV-2 has raised concerns primarily around their association with higher than expected transmission rates, not increased severity, risk of death or impairment in vaccine efficacy. 1-5

The new variants of SARS-CoV-2—first recognized in the U.K (strain B.1.1.7), then South Africa (B.1.351), and now many parts of the world, including US and Canada—seem to be associated with higher rates of transmission without any evidence for more severe disease or hospitalization.3 Based on mathematical models, it is suggested that the new variant may be up to 70% more transmissible than the original virus.1 However, it is important to point out that, to date, there are no published studies that corroborates this finding in laboratory animals and some have questioned whether these new strains are truly more transmissible.1

The B.1.1.7 strain has several mutations involving the spike protein (the surface  protein that attaches to host cells) at least 1 of which (N501Y) seems to improve the virus’s ability to bind to cells.1 Preliminary laboratory studies have also found higher viral replication rates in upper respiratory tract of hamsters when challenged with another SARS-CoV-2 variant with spike protein mutation (D614G) compared to the lungs.4  Both “stickiness” to cells and high replication rates in upper respiratory tract alone may explain more rapid spread of the virus without increased severity of disease.

Preliminary reports also suggest that that antibodies against the original strain  neutralize the B.1.1.7 strain, supporting the efficacy of the current Covid-19 vaccine in protecting against this strain.1

A theoretical concern, however, based on a preprint publication, is the suboptimal binding and neutralization of new strains by commercially available monoclonal antibodies.2

The potential increased transmissibility of new SARS-CoV-2 variants only underscores the importance of public health measure such as masks, social distancing and hand hygiene, now more than ever before!

Bonus Pearl: Did you know that despite lack of clear increase in the severity of disease associated with new variants of SARS-CoV-2, increased rate of transmission will lead to more people getting infected and therefore die from its complications. That’s why, more than ever before, we should double down our efforts to stick to public health measures to mask, social distance and exercise hand hygiene during this critical period of the pandemic. Please spread the word, again!

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References

  1. Reardon S. The U.K. coronavirus mutation is worrying but not terrifying. Scientific American. December 24, 2020. https://www.scientificamerican.com/article/the-u-k-coronavirus-mutation-is-worrying-but-not-terrifying/
  2. Starr TN, Greaney AJ, Addetia A, et al. Prospective mapping of viral mutations that escape antibodies used to treat COVID-19. Bio Rxiv 2020. https://www.biorxiv.org/content/10.1101/2020.11.30.405472v1
  3. CDC. Interim: Implications of the emerging SARS-CoV-2 variant VOC 202012/01. Accessed Jan 12, 2020. https://www.cdc.gov/coronavirus/2019-ncov/more/scientific-brief-emerging-variant.html
  4. Plante JA, Liu Y, Liu J, et al. Spike mutation D614G alters SARS-CoV-2 fitness. Nature. Published online 26, 2020. https://pubmed.ncbi.nlm.nih.gov/33106671/
  5. Baric RS. Emergence of a highly fit SARS-CoV-2 variant. N Engl J Med 2020; 383;2684-2686. https://www.nejm.org/doi/full/10.1056/NEJMcibr2032888

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis or its affiliate healthcare centers. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

Is the discovery of new variants of SARS-CoV-2 expected to impact the transmissibility, clinical course or vaccine efficacy in Covid-19?

What’s the connection between Covid-19 and persistent fatigue?

Fatigue is one of the most common symptoms in patients with Covid-19, both during the acute illness as well during the weeks or months that follows it. Depending on the study, fatigue has been reported in around 30%-80% of patients at 2-3 weeks to 6 months or longer after the onset of illness (1-4).

In a study of hospitalized patients with Covid-19, ~80% of patients complained of fatigue during the acute illness, with ~50% having persistent fatigue at a mean follow-up of 60 days following onset of illness (1). Persistent fatigue was the most common symptom during the post-Covid-19 period, followed by dyspnea, joint pain, chest pain and cough.

In another study, 52.3% of patients with Covid-19 complained of persistent debilitating fatigue at a median of 10 weeks after initial onset of symptoms, despite a negative test for the virus (2). Of interest, there was no association between severity of Covid-19 illness/need for hospitalization and post-covid fatigue.  No association was found between routine laboratory markers of inflammation, WBC profile, LDH, C-reactive protein or interleukin-6 levels and persistent fatigue.

A CDC survey of outpatients with Covid-19 patients at 14-21 days from test date found persistent fatigue in one-third of patients (3).   

A MedRxive study (pending peer review) of over 3700 patients with definite (27%) or probable diagnosis of Covid-19 from 56 countries (>90% not hospitalized) reported fatigue in 78% of patients after 6 months (4).

Although the true nature or course of persistent fatigue following Covid-19 has yet to be clearly defined, In some respects, it’s reminiscent of chronic fatigue syndrome associated with many acute viral infections, such as SARS, EBV, and enteroviruses (5-7).

Bonus pearl: Did you know that persistent fatigue following Covid-19 may be more frequent than that following influenza in which >90% of outpatients recover within about 2 weeks (3)?

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References

  1. Carfi A, Bernabei R, Landi. Persistent symptoms in patients after acute COVID-19.JAMA 2020;324:603-605. https://pubmed.ncbi.nlm.nih.gov/32644129/
  2. Townsend L, Dyer AH, Jones K, et al. Persistent fatigue following SARS-CoV-2 infection is common and independent of severity of initial infection. PLOS ONE 2020. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0240784   
  3. Tenforde MW, Kim SS, Lindsell CJ, et al. Duration and risk factors for delayed return to usual health among outpatients with COVID-19 in a multistate health care systems network—United States, March—June 2020. MMWR 2020;69:993-98. https://www.cdc.gov/mmwr/volumes/69/wr/mm6930e1.htm
  4. Davis HE, Assaf GS, MCorkell L, et al. Characterizing long COVID in an international cohort:7 months of symptoms and their impact. MedRxive 2020. https://www.medrxiv.org/content/10.1101/2020.12.24.20248802v2.full.pdf
  5. Chia JKS, Chia AY. Chronic fatigue syndrome is associated with chronic infection of the stomach. Clin Pathol 2008;61:43-48. https://jcp.bmj.com/content/61/1/43
  6. Moldofsky H, Patcai J. Chronic widespread musculoskeletal pain, fatigue, depression and disordered sleep in chronic post-SARS syndrome; a case control study. BMC Neurol 2011;11:37. https://pubmed.ncbi.nlm.nih.gov/21435231/
  7. Hickie I, Davenport T, Whitfield D, et al. Post-infective and chronic fatigue syndrome precipitated by pathogens: prospective cohort study. BMJ 2006;333:575. https://jcp.bmj.com/content/61/1/43

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital or its affiliated institutions. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

What’s the connection between Covid-19 and persistent fatigue?