Why is the Delta variant of SARS-CoV-2 increasingly becoming a “variant of concern” in the current Covid-19 pandemic?

The Delta variant (B.1.617.2, formerly India variant) has become an increasingly prevalent strain of SARS-Cov-2 causing Covid-19 in many countries outside of India, including the United States and United Kingdom, particularly affecting younger unvaccinated persons.  Several features of the Delta variant are of particular concern. 1-7

  1. Delta virus appears to be more transmissible when compared to previously emerged variant viruses. Data from new Public Health England (PHE) research suggests that the Delta variant is associated with a 64% increased risk of household transmission compared with the Alpha variant (B.,1.1.7, UK variant) and 40% more transmissibility in outdoors. 1,8  
  2. Delta virus is also associated with a higher rate of severe disease, doubling the risk of hospitalization based on preliminary data from Scotland. In vitro, it replicates more efficiently than the Alpha variant with higher respiratory viral loads.5
  3. Delta virus may also be associated with reduced vaccine effectiveness with increased vaccine breakthroughs. One study found that Delta variant is 6.8-fold more resistant to neutralization by sera from Covid-19 convalescent and mRNA vaccinated individuals.5 Fortunately, a pre-print study released by PHE in May 2021 found that 2 doses of the Pfizer vaccine were still 88% effective against symptomatic infection with Delta variant  (vs 93% for the Alpha variant) and 96% effective against hospitalization; 1 dose was only 33% effective against symptomatic disease (vs 50% for the Alpha variant).  Two doses of Astra Zeneca vaccine were 60% effective against symptomatic disease from the Delta variant.8 
  4. Aside from its somewhat unique epidemiologic features, Covid-19 caused by Delta variant seems to be behaving differently (starting out as a “bad cold” or “off feeling”), with top symptoms of headache, followed by runny nose and sore throat with less frequent fever and cough; loss of sense of smell was not common at all based on reported data to date.1

What the Delta variant reminds us is, again, the importance of vaccination, masks and social distancing. The pandemic is still with us!

Bonus Pearl: Did you know that, on average, a Delta variant-infected person may transmit it to 6 other contacts (Ro~6.0) compared to 3 others (Ro~3) for the original SARS-CoV-2 strains found during the early part of the pandemic?1

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References

  1. https://www.bbc.com/news/health-57467051
  2. Knodell R. Health Advisory: Emergence of Delta variant of coronavirus causing Covid-19 in USA. Missouri Department of Health & Senior Services. 23 June, 2021. https://health.mo.gov/emergencies/ert/alertsadvisories/pdf/update62321.pdf
  3. Kupferschmidt K, Wadman M. Delta variant triggers new phase in the pandemic. Science 25 June 2021; 372:1375-76. https://science.sciencemag.org/content/sci/372/6549/1375.full.pdf
  4. Sheikh A, McMenamin J, Taylor B, et al. SARS-CoV-2 Delta VOC in Scotland: demographics, risk of hospital admission, and vaccine effectiveness. Lancet 2021; 397:2461-2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201647/
  5. Mlcochova P, Kemp S, Dhar MS, et al. Sars-Cov-2 B.1.617.2 Delta variant emergence and vaccine breakthrough. In Review Nature portfolio, posted 22 June, 2021. https://www.researchsquare.com/article/rs-637724/v1
  6. Bernal JL, Andrews N, Gower C, et al. Effectiveness of Covid-19 vaccines against the B.1.617.2 variant. MedRxiv, posted May 24, 2021. https://www.medrxiv.org/content/10.1101/2021.05.22.21257658v1 vaccine efficacy
  7. Allen H, Vusirikala A, Flannagan J, et al. Increased household transmission of Covid-19 cases associatd with SARS-Cov-2 variant of concern B.1.617.2: a national case control study. Public Health England. 2021. https://khub.net/documents/135939561/405676950/Increased+Household+Transmission+of+COVID-19+Cases+-+national+case+study.pdf/7f7764fb-ecb0-da31-77b3-b1a8ef7be9aa  Accessed June 27, 2021.
  8. Callaway E. Delta coronavirus variant: scientists brace for impact. Nature. 22 June 2021. https://www.nature.com/articles/d41586-021-01696-3 

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.

Why is the Delta variant of SARS-CoV-2 increasingly becoming a “variant of concern” in the current Covid-19 pandemic?

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?

Catch these selected key clinical pearls on coronavirus disease (Covid-19)!

Although the Covid-19 pandemic is continuing to evolve and our knowledge of its epidemiology and pathophysiology is still far from complete, you may find the following pearls based on published literature to date useful when discussing this disease with your colleagues or the public. 1-11

  • Age group: Primarily an adult disease. Children (< 15-year-old) account for only a minority of symptomatic patients (<1%); ~50% of patients are between 15-49 years of age with 15% in the ≥ 65 year group. 1
  • Incubation period: A bit longer than seasonal flu. Median 4.0 days (IQR 2.0-7.0 days); an upper range up to 24 days has also been reported. In contrast, for seasonal flu the median incubation period is shorter (median 2.0 days, 1.0-7.0 days. 1,4,11
  • Transmission: Contact, droplet, and possibly airborne. On average each person may transmit Covid-19 virus to 2-3 other persons (vs <2 people for seasonal flu). Unlike SARS or MERS, but more akin to the seasonal flu, asymptomatic persons may also be able to transmit the disease. 4,5,11
  • Comorbid conditions (eg, diabetes, hypertension, COPD…): Present in about 1/3 of reported patients. 1
  • Symptoms 1,5
    • ~80% of patients may be either asymptomatic or have mild disease
    • Fever may be absent in ~50% of patients on presentation but will eventually develop in ~90% of hospitalized patients
    • Cough (2/3 dry) is present in majority (~80%) of cases
    • Rhinorrhea is uncommon (<10%), in contrast to the seasonal influenza
    • GI symptoms (nausea/vomiting/diarrhea) are uncommon by some reports(<10%), but not by others (>30.0%). 12
    • May take 9-12 days from onset of symptoms to severe disease
  • Labs 1
    • Lymphopenia is common (up to ~80%)
    • Abnormal liver function (AST and ALT) is found in about 1/3 of patients
    • C-reactive protein (CRP) is usually elevated (~80% of severe cases)
    • Procalcitonin is usually normal
  • Treatment: Supportive for now. Candidate drugs include remdesivir, lopinavir/ritonavir, chloroquine phosphate, ribavirin and several others.4
  • Mortality: Reported mortality among mostly symptomatic hospitalized cases is ~2.0% (0.9% without comorbidities, 5-10% in those with comorbidities, 50% among critically ill). Overall mortality rates will likely drop as more patients without symptoms or with mild disease are tested. In contrast, 2 other coronavirus diseases, SARS and MERS, have mortality rates of ~9.0% and 36.0%, respectively. 1,4,5

 

Bonus pearl: Did you know that, Covid-19-infected patients shed the virus in their nasopharyngeal secretions on the average for 12 days, some as long as 24 days?3

 

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References

  1. Guan W, Ni Z, Hu Y, et al. Clinical characteristics of Coronavirus disease 2019 in China. N Engl J Med 2020. First published Feb 28, 220, last updated March 6, 2020. https://www.nejm.org/doi/10.1056/NEJMoa2002032
  2. Holshue ML, DeBolt C, Lindquist S, et al. First case of 2019 novel Coronavirus in the United States. N Engl J Med 2020; 382:929-36. https://www.nejm.org/doi/full/10.1056/NEJMoa2001191
  3. Young BE, Ong SWX, Kalimuddin S, et al. Epidemiologic features and clinical course of patients infected with SARS-CoV-2 in Singapore. JAMA. Doi:10.1001/jama.2020.3204. Published online March 3, 2020. https://jamanetwork.com/journals/jama/fullarticle/2762688
  4. Wang Y, Wang Y, Chen Y, et al. Unique epidemiological and clinical features of the emerging 2019 novel coronavirus pneumonia (COVID-19) implicate special control measures. J Med Virol 2020. Doi: 10.1002/jmv.25748. https://www.ncbi.nlm.nih.gov/pubmed/32134116
  5. Fauci AS, Lane HC, Redfield RR. Covid-19—Navigating the uncharted. N Eng J Med 2020. DOI:10.1056/NEJMe2002387. https://www.nejm.org/doi/full/10.1056/NEJMe2002387
  6. Del Rio C, Malani PN. 2019 novel coronavirus—important information for clinicians. JAMA 2020, Feb 5. https://www.ncbi.nlm.nih.gov/pubmed/32022836
  7. Lipsitch M, Swerdlow DL, Finelli L. Defining the epidemiology of Covid-19—studies needed. N Engl J Med 2020. Feb 19. DOI:10.1056/NEJMp2002125. https://www.ncbi.nlm.nih.gov/pubmed/32074416/
  8. Morens DM, Daszak P, Taubenberger JK. Escaping Pandora’s box—another novel coronavirus. N Eng J Med 2020. Feb 26. DOI:10.1056/NEJMp2002106. https://www.nejm.org/doi/full/10.1056/NEJMp2002106
  9. She J, Jiang J, Ye L, et al. 2019 novel coronavirus of pneumonia in Wuhan, China: merging attack and management strategies. Clin Trans Med 2020;9:19. https://clintransmed.springeropen.com/articles/10.1186/s40169-020-00271-z
  10. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395: 497-506. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30183-5/fulltext
  11. Bai Y, Yao L, Wei T, et al. Presumed asymptomatic carrier transmission of COVID-19. JAMA 2020. Feb 21. https://jamanetwork.com/journals/jama/fullarticle/2762028
  12. Pan L, Mu M, Yang P, et al. Clinical characteristics of COVID-19 patients with digestive symptoms in Hubei, China: a descriptive, cross-sectional, multicenter study. Am j Gastroenterol 2020. https://journals.lww.com/ajg/Documents/COVID_Digestive_Symptoms_AJG_Preproof.pdf
Catch these selected key clinical pearls on coronavirus disease (Covid-19)!