Are women at higher risk of Covid-19 vaccine-related adverse events?

Data to date shows a preponderance of Covid-19 vaccine-related adverse events (AEs) among women compared to men. This finding may be due to the generally more robust immunological response to infections and vaccines among women, increased reporting of AEs by women, genetic factors, microbiome differences as well as other factors.1-3

A CDC study involving mRNA vaccines (Pfizer and Moderna) during the 1st month of vaccination roll out in the US, found that nearly 80% of adverse events were reported by women.  The great majority (>90%) of these AEs were not serious and included symptoms such as headache, dizziness and fatigue.1

A JAMA study involving individuals receiving one of the mRNA vaccines found that 94% (Pfizer) and 100% (Moderna) of anaphylaxis events occurred among women. Of note, the median age was ~40 years  with the majority of anaphylaxis events were reported after the first dose. 2

Higher incidence of AEs following Covid-19 vaccination is not surprising and may be explained biologically. Women typically have a more robust immune response to infections and vaccination, both at the level of innate and adaptive immunity with higher antibody responses.  

These findings may be in part due to hormones such as estrogen which is known to enhance differentiation of dendritic cells and proinflammatory cytokine production. Other proposed mechanisms include differences in microbiome between sexes and sex-based genetic influences on humoral immune profile with the X chromosome expressing 10 times more genes than the Y chromosome, including genes that influence immunity.3

Bonus Pearl: Did you know that anaphylactic reaction to the mRNA Covid-19 vaccines is extremely rare, occurring in only 2-5 cases/ million!2

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References

  1. Gee J, Marquez P, Su J, et al. First month of Covid-19 vaccine safety monitoring—United States, December 14, 2020—January 13, 2021. MMWR 2021;70:283-88. https://www.cdc.gov/mmwr/volumes/70/wr/mm7008e3.htm
  2. Shimabukuro TT, Cole M, Su JR. Reports of anaphylaxis after receipt of mRNA Covid-19 vaccines in the US—December 14, 2020-January 18, 2021. JAMA 20201;325:1101-1102. https://jamanetwork.com/journals/jama/fullarticle/2776557
  3. Fischinger S, Boudreau CM, Butler AL, et al. Sex differences in vaccine-induced humoral immunity. Semin Immunopath 2019;41:239-49. https://pubmed.ncbi.nlm.nih.gov/30547182/

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, Mass General Hospital, Harvard Medical School 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!

Are women at higher risk of Covid-19 vaccine-related adverse events?

How effective are the current Covid-19 vaccines in reducing the risk of asymptomatic infection?

Limited data suggest that not only are the mRNA Covid-19 vaccines effective in reducing the risk of symptomatic disease  by greater than 90% but also reducing the risk of asymptomatic infections by 80-90% after the second dose and by 62-80% after the 1st dose. 1-3

A CDC study of health care personnel, first responders, and other essential and frontline workers who received one of the 2 currently available mRNA vaccines (BNT162b2-Pfizer or mRNA-1273-Moderna) and underwent weekly testing for SARS-CoV-2 infection irrespective of symptoms found 90% efficacy in preventing infection among fully immunized (≥14 days after 2nd dose) and 80% efficacy in preventing infection among the partially immunized (≥14 days after 1st dose).  The majority of SARS-CoV-2 infections were identified by weekly specimens, with 11% remaining without symptoms.1

In a retrospective study of over 39,000 asymptomatic adult patients undergoing pre-procedural SARS-CoV-2 molecular screening tests, an 80% reduction in the risk of a positive test  was observed in those who had received 2 doses of an mRNA vaccine (majority Pfizer) and 72% reduction in those following a single dose of vaccine >10 days prior to their pre-procedure test.2  In the original Moderna trial , a 62% reduction in the risk of asymptomatic infection was seen among participants just before the second dose (ie, partially immunized).3 

Collectively, these reports support the high efficacy of mRNA vaccines in reducing the risk of SARS-CoV-2 in asymptomatic infection.  Whether these findings can be reproduced with other vaccine preparations is not known at this time!

Bonus Pearl: Did you know that according to 1 study, asymptomatic patients with SARS-CoV-2 infection may be more likely to be women, younger and have shorter duration of viral shedding? 4

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References

  1. Thompson MG, Burgess JL, Naleway AL, et al. Interim estimates of vaccine effectiveness of BNT162b2 and mRNA-1273 Covid-19 vaccines in preventing SARS-CoV-2 infection among health care personnel, first responders, and other essential and frontline workers—Eight U.S. locations, December 2020-March 2021. https://www.cdc.gov/mmwr/volumes/70/wr/mm7013e3.htm
  2. Tande AJ, Pollock BD, Shah ND, et al. Impact of the Covid-19 vaccine on asymptomatic infection among patients undergoing pre-procedural Covid-19 molecular screening. Clin Infect Dis 2021. https://pubmed.ncbi.nlm.nih.gov/33704435/
  3. Baden LR, El Sahly HM, Essink B, et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med 2021;384:403-16. https://www.nejm.org/doi/full/10.1056/nejmoa2035389
  4. Yang R, Gui X, Xiong Y. Comparison of clinical characteristics of patients with asymptomatic vs symptomatic coronavirus disease 2019 in Wuhan, China. JAMA Network Open 2020; May 27. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2766237

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, Mass General Hospital, Harvard Medical School 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!

How effective are the current Covid-19 vaccines in reducing the risk of asymptomatic infection?

How long should my patient recovering from Covid-19 remain on isolation precautions?

For the great majority of patients with Covid-19, the risk of shedding viable SARS-CoV2 diminishes considerably as the time from onset of symptoms nears 10 days or more, with the risk higher among those who have severe (eg, sp02 <94%)  or critical disease (eg, in need of ICU care) or who are immunocompromised. 1-4  

For patients with mild-moderate illness who are not immunocompromised, the CDC recommends isolation for “at least 10 days” from onset of symptoms as long as at least 24 hours have passed since last fever without the use of fever-reducing medications and symptoms  (eg, cough, shortness of breath) have improved.  For patients with severe to critical illness or who are severely immunocompromised, “at least 10 days” and up to 20 days since onset of symptoms—with qualifications as above— is recommended. 1

A 2021 meta-analysis found that although SARS-CoV-2 RNA shedding in respiratory and stool samples may be prolonged, duration of viable virus was relatively short with no study detecting live virus beyond day 9 of illness.2

In contrast, another study involving patients with severe or critical illness (23% immunocompromised, 2/3 on mechanical ventilation) found  that the median time of infectious virus shedding was 8 days (range 0-20) and concluded that detection of infectious virus was common after 8 days or more since onset of symptoms; the probability of isolating infectious SARS-CoV-2 was  ≤5% when the duration of symptoms was 15.2 days (95% CI 13.4-17.2). In the same study, a single patient had infectious particles for up to 20 days following onset of symptoms. 3

The take home point is that although 10 days of isolation since onset of symptoms should be sufficient for mild to moderate Covid-19, for those with severe or critical disease or immunocompromised state, a longer duration up to 20 days may be needed.  The setting and status of the potential contacts (eg, an immunocompromised person in household setting) should also be considered in our decision making. 4

Bonus Pearl: Did you know that infectious particles are unlikely to be isolated from respiratory tract samples once patients develop a serum neutralizing antibody titer of at least 1:80, potentially useful information in deciding when a patient may come off isolation? 3

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References

  1. Discontinuation of transmission-based precautions and disposition of patients with SARS-CoV-2 infection in healthcare settings. https://www.cdc.gov/coronavirus/2019-ncov/hcp/disposition-hospitalized-patients.html#definitions. Accessed March 24, 2021
  2. Cevik M, Tate M, Lloyd O, et al. Sars-Cov-2, SARS-CoV, and MERS-CoV viral load dynamics, duration of viral shedding, and infectiousness: a systematic review and meta-analysis. Lancet Microbe 2021;2:e13-22. https://www.thelancet.com/pdfs/journals/lanmic/PIIS2666-5247(20)30172-5.pdf
  3. Van Kampen JJA, van de Vijver DAMC, Fraaij PLA, et al. Duration and key determinants of infectious virus shedding in hospitalized patients with coronavirus disease-2019 (COVID-19). Nature Communications 2021;12:267. https://www.nature.com/articles/s41467-020-20568-4
  4. Kadire SR, Fabre V, Wenzel RP. Doctor, how long should I isolate? NEJM, March 2021 https://www.nejm.org/doi/pdf/10.1056/NEJMclde2100910?articleTools=true

 

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!

How long should my patient recovering from Covid-19 remain on isolation precautions?

My elderly patient developed a flare-up of her gout few days after receiving Covid-19 vaccine. Is there a connection between immunization and gout flare?

Although the connection between Covid-19 vaccination and gout flare has yet to be established, higher rates of gout/gout flare following the administration of several other vaccines (eg, influenza, tetatnus, recombinant zoster) have been reported.1  Thus, it is conceivable that Covid-19 vaccine may also be associated with gout flare as more and more people are immunized.  

A 2019 prospective study of over 500 patients with gout found that vaccination was associated with 2-fold higher odds of gout flare (aO.R. 1.99; 95% ci 1.01-3.89) during the 2 day period following immunization; no information on the type of vaccines administered was provided, however.1  Similarly,  higher risk of gout (3.6-fold) has been reported in recipients of recombinant zoster vaccine following immunization.1

An intriguing mechanism explaining the association of vaccination and gout flare is the activation of the Nlrp3 inflammasome, a multiprotein complex produced in response to diverse stimuli such as uric acid crystals and ATP released from tissue injury/necrotic cells.2 Of interest, ~25% of patients with asymptomatic hyperuricemia have been found to have evidence of monosodium urate crystals in and around their joints by advanced imaging, such that vaccination may potentially bring out more inflammatory response and gout flare.

Although aluminum adjuvants intended to increase the immunogenicity of one-half of all routine adult vaccines (eg, tetanus, diphteria, pertussis) have been shown to activate the Nlrp3 inflammasome in vitro, neither currently available mRNA vaccines (Pfizer, Moderna) nor the Johnson&Johnson vaccine contains aluminum as an adjuvant. 4  

Despite the potential for gout flare following adult vaccination, it should be emphasized that the absolute risk is still low and pales compared to the overwhelming benefits of vaccination in general.1

Bonus Pearl: Did you know that, in addition to the usual uric acid lowering drugs, losartan, fenofibrate and some non-steroidal anti-inflammatory drugs, such as indomethacin, also lower serum uric acid levels? 5,6

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References

  1. Yokose C, McCormick N, Chen C, et al. Risk of gout flares after vaccination: a prospective case-crossoverstudy. Ann Rheum Dis 2019;78:1601-1604. https://ard.bmj.com/content/early/2019/07/31/annrheumdis-2019-215724.info?versioned=true
  2. Lyer SS, Pulskens WP, Sadler JJ, et al. Necrotic cells trigger a sterile inflammatory response throught the Nlrp3 inflammasome. PNAS 2009;106:20388-20393. https://pubmed.ncbi.nlm.nih.gov/19918053/
  3. Yokose C, Choi H. Response to “Clarification regarding the statement of the association between the recombinant zoster vaccine (RZV) and gout flares’ by Didierlaurent etal. Ann Rheum Dis Month, December 2019. https://ard.bmj.com/content/annrheumdis/early/2019/12/18/annrheumdis-2019-216670.full.pdf
  4. Covid-19 vaccine information. https://covidvaccine.mo.gov/ Accessed March 16, 2021.
  5. Daskalopoulou SS, Tzovaras V, Mikhailidis DP, et al. Effect on serum uric acid levels of drugs prescribed for indications other than treating hyperuricaemia. Current Pharmaceutical Design 2005;11:4161-75. https://www.eurekaselect.com/60510/article
  6. Tiitinen S, Nissila M, Ruutsalo HM, et al. Effect of nonsteroidal anti-inflammatory drugs on the renal excretion of uric acid. Clin Rheumatol 1983;2:233-6. https://pubmed.ncbi.nlm.nih.gov/6678696/#:~:text=The%20effect%20of%209%20nonsteroidal,studied%20had%20no%20significant%20influence.

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!

My elderly patient developed a flare-up of her gout few days after receiving Covid-19 vaccine. Is there a connection between immunization and gout flare?

Is Covid-19 vaccine effective in immunocompromised patients?

The short answer is that we don’t have any solid data on the performance of Covid-19 among immunocompromised (IC) patients at this time because the large trials used to clear the available vaccines for FDA Emergency Use Authorization essentially excluded IC subjects (1,2). 

However, despite a potentially blunted response, the immunogenicity of the Covid-19 vaccine may be sufficient to reduce the risk of serious disease. The CDC and the American Society of Clinical Oncologists support Covid-19 vaccination of IC patients as long as there are no contraindications and patients are counseled about the uncertainty in vaccine efficacy and safety in this particular population (3,4).

 For patients undergoing treatment for cancer, the ASCO believes that Covid-19 vaccine may be offered in the absence of any contraindications.  To reduce the risk of Covid-19 while retaining vaccine efficacy, it recommends that the vaccine be given between cycles of therapy and after “appropriate waiting periods” for those receiving stem cell transplants and immunoglobulin therapy (4).

Previous experience with pneumococcal and influenza vaccine in IC patients have reported frequent suboptimal immunological response (2). Concomitant treatment with infliximab or other immunomodulatory drugs have had a negative impact on seroconversion after influenza vaccination. Similarly, in patients with Crohn’s on immunosuppressives, immune response to polysaccharide pneumococcal vaccine has been blunted (2). 

Nevertheless, the benefits of vaccination may still outweigh any risks of adverse events in this population. In fact, the CDC routine vaccination schedule for adults includes immunocompromised patients (5).  

At this time, given the seriousness of the Covid-19 pandemic and higher risk of severe disease among many IC patients, offering Covid-19 vaccine to these patients (with aforementioned caveats) seems prudent. 

 

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References

  1. Kumar A, Quraishi MN, Segal JP, et al. Covid-19 vaccinations in patients with inflammatory bowel disease. Lancet 2020;4:965-6. https://www.thelancet.com/journals/langas/article/PIIS2468-1253(20)30295-8/fulltext
  2. Polack FP, Thomas SJ, Ktichin N, et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med 2020;383:2603-15. https://www.nejm.org/doi/full/10.1056/NEJMoa2034577
  3. Interim clinical considerations for use of mRNA COVID-19 vaccines currently authorized in the United States. https://www.cdc.gov/vaccines/covid-19/info-by-product/clinical-considerations.html. Accessed Feb 14, 2021.
  4. American Society of Clinical Oncologists. Covid-19 vaccine and patients with cancer.. https://www.asco.org/asco-coronavirus-resources/covid-19-patient-care-information/covid-19-vaccine-patients-cancer Accessed Feb 14, 2021
  5. CDC. Immunization schedules. https://www.cdc.gov/vaccines/schedules/hcp/imz/adult.html Accessed Feb 14, 2021.  

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy healthcare centers, or its contributors. 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 Covid-19 vaccine effective in immunocompromised patients?

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?