What’s the role of small droplets or aerosolized particles in the transmission of Covid-19?

Although transmission of SARS-CoV-2 is often considered to occur through large respiratory droplets by coughing or sneezing, emerging data suggests that smaller respiratory particles (5 microns or less) generated by breathing, speaking or singing also account for a sizeable number of infections. Several lines of evidence make a cogent argument for aerosols serving as an important mode of transmission for SARS-CoV-2. 1-9

 First, there are ample accounts of SARS-CoV-2 spreading by being near an infected individual without symptoms.  Since by definition, those without symptoms do not cough or sneeze transmission must have occurred through other means, including breathing, talking or touching surfaces that might have become secondarily contaminated through aerosol.1,2,5  To make matters worse, the peak of contagion in infected individuals occurs on or before symptoms occur.1

Second, aerosolized SARS-CoV-2 has been shown to remain viable in the air for at least 3 hours and viral RNA (not necessarily viable virus) has been found in the air outside patient rooms and inside patient rooms in the absence of cough.2,9 One study found SARS-CoV-2 in outdoor air at a hospital entrance and in front of a department store.7

Third, contaminated air samples and long-range aerosol transport and transmission have been reported by several studies involving a related coronavirus, SARS-CoV-1, the agent of SARS.2

What’s the ramifications of aerosol transmission of Covid-19? The most obvious is the requirement for universal wearing of masks or face covers in public spaces even when 6 feet apart. This practice is particularly important indoors where the amount of ventilation, number of people, duration of stay in the facility, and airflow direction may impact the risk of exposure to SARS-CoV-2.1

The other potential ramification of aerosolized SARS-CoV-2 is that due to their smaller size, these virus-laden particles may bypass the upper respiratory tract and be inhaled directly into the lungs resulting in more severe disease.4  So it really makes sense to routinely wear a mask when out in public places.

Bonus Pearl: Did you know that 1 minute of loud speaking could generate over 1000 virus-containing aerosols in the air with a “super-emitter” generating over 100,000 virus particles in their droplets during the same time?1

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 References

  1. Prather KA, Wang CC, Schooley RT. Reducing transmission of SARS-CoV-2. Science. May 27, 2020.
  2. Anderson EL, Turnham P, Griffin JR, et al. Consideration of the aerosol transmission for COVID-19 and public health. Risk Analysis 2020;40:902-7.
  3. Hamner L, Dubbel P, Capron I, et al. High SARS-CoV-2 attack rate following exposure at a choir practice-Skagit County, Washington, March 2020. MMWR 2020; 69: 606-10.
  4. Gralton J, Tovey E, McLaws ML, et al. The role of particle size in aerosolized pathogen transmission: a review. J Infect 2011;62:1-13.
  5. Asadi S, Bouvier N, Wexler AS et al. The coronavirus pandemic and aerosols: does COVID-19 transmit via expiratory particles. Aerosol Sci Technol 2020;54:635-38.
  6. Morawska L, Cao J. Airborne transmission of SARS-CoV-2: the world should face the reality. Env International 2020;139:105730.
  7. Liu Y, Ning Z, Chen Y, e al. Aerodynamic analysis of SARS-CoV-2 in two Wuhan hospitals. Nature 2020;582:557-60. https://www.nature.com/articles/s41586-020-2271-3.pdf
  8. Somsen GA, van Rijn C, Kooij S, et al. Small droplet aerosols in poorly ventilated spaces and SARS-CoV-2 transmission. Lancet Respir Med 2020; May 27. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7255254/pdf/main.pdf

9. Santarpia JL, Rivera DN, Herrera V, et al. Transmission potential of SARS-CoV-2 in viral shedding observed at the University of Nebraska Medical Center. 2020 (Preprint) https://www.ehs.ucsb.edu/files/docs/bs/Transmission_potential_of_SARS-CoV-2.pdf

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Massachusetts General Hospital, Harvard Catalyst, Harvard University, its affiliate academic 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!

What’s the role of small droplets or aerosolized particles in the transmission of Covid-19?

How does Covid-19 affect pregnancy?

We still have a long ways to go before fully understanding the potential effects of Covid-19 on pregnant women and their infants but based on data to date the disease severity seems similar to that of non-pregnant people and vertical transmission seems rare.

 
In one of the larger studies involving 158 obstetric patients with Covid-19 from New York City, ~80% had mild or asymptomatic disease with the rest manifesting moderate or severe disease (1). Cough and fever were common symptoms in both groups. Women with moderate/severe disease were more likely to have comorbidities (eg, asthma) and were also more likely to have dyspnea and chest pain/pressure. Other symptoms included muscle aches, sore throat, congestion, headache, diarrhea, nausea and loss of taste or smell. Two women had pre-term delivery because of clinical status deterioration; there were no reported deaths. The generally favorable course of Covid-19 among pregnant women has been supported by other studies (2,3,4).

 
To date, vertical transmission of SARS-CoV-2, the agent of Covid-19 appears rare (2,3,5,6). In one review, only 1 of 75 newborns tested for SARS-CoV-2 infection were positive; this infant did well clinically but had transient lymphocytopenia and abnormal liver function tests (2). A systematic review found no evidence of intrauterine transmission of SARS-CoV-2 (6).

 
Transmission of SARS-CoV-2 during the first trimester may be unlikely because of expression of ACE2 (a receptor for the virus) in the trophoblasts is very low between 6-14 weeks (7). In a small study examining placenta and fetal membranes in Covid-19 women, 3/11 samples were positive for SARS-CoV-2 but none of the infants tested positive on day 1-5 of life or demonstrated symptoms of Covid-19 (8).

 
Although another source of perinatal infection is exposure to mother’s secretions during vaginal delivery, so far presence of SARS-CoV-2 in vaginal secretions has not been reported (8). Also encouraging is a study of 18 infants born of women testing positive for SARS-CoV-2, all of whom had normal APGAR scores, with the majority (>80%) testing negative (3).

 
So overall, the major threat of Covid-19 to the fetus appears to be the severity of illness in the mother. Pregnant women should be familiar with the early symptoms of Covid-19 and seek medical care as soon as possible.

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References
1. Andrikopoulou M, Madden N, Wen T, et al. Symptoms and critical illness among obstetric patients with coronavirus disease 2019 (COVID-19) infection. OB GYN 2020 https://pubmed.ncbi.nlm.nih.gov/32459701/
2. Zaigham M, Andersson O. Maternal and perinatal outcomes with COVID-19: a systematic review of 108 pregnancies. Acta Obstet Gynecol Scand 2020;00:1-7. https://pubmed.ncbi.nlm.nih.gov/32259279/
3. Breslin N, Baptiste C, Gyamfi-Bannerman C, et al. Coronavirus disease 2019 infection among asymptomatic and symptomatic pregnant women: two weeks of confirmed presentations to an affiliated pair of New York City hospitals. Am J Obstet Gynecol MFM 2020;100118. https://www.sciencedirect.com/science/article/pii/S2589933320300483
4. Chen L, Li Q, Zheng D, et al. Clinical characteristics of pregnant women with Covid-19 in Wuhan, China. N Engl J Med 2020, April 17. https://www.nejm.org/doi/full/10.1056/NEJMc2009226?af=R&rss=currentIssue
5. Di Mascio D, Khalil A, Saccone G, et al. Outcome of coronavirus spectrum infections (SARS, MERS, COVID-19) during pregnancy: a systematic review and meta-analysis. Am J OB GYN 2020. https://www.sciencedirect.com/science/article/pii/S0002937820305585
6. Yang Z, Liu Y. Vertical transmission of severe acute respiratory syndrome coronavirus 2: A systematic review. Am J Perinatol 2020;10.1055/s-0040-1712161. https://pubmed.ncbi.nlm.nih.gov/32403141/
7. Amouroux A, Attie-Bitach, Martinovic J, et al. Evidence for and against vertical transmission for SARS-CoV-2 (COVID-19). Am J OB GYN 2020. https://www.sciencedirect.com/science/article/pii/S000293782030524X
8. Penfield CA, Brubaker SG, Lighter J. Detection of severe acute respiratory syndrome coronavirus 2 in placental and fetal membrane samples. Am J OB GYN MFM 2020. https://pubmed.ncbi.nlm.nih.gov/32391518/

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Massachusetts General Hospital, Harvard Catalyst, Harvard University, its affiliate academic 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!

How does Covid-19 affect pregnancy?

What’s the connection between elevated troponins and Covid-19?

Elevated cardiac troponins or myocardial injury (defined as troponin levels above the 99th percentile upper reference range) are not uncommon in Covid-19, having been reported in ~10-30% of hospitalized patient and usually observed in the absence of acute coronary syndrome (ACS) (1-4).

 
Elevated troponins have been associated with increased risk of in-hospital mortality in Covid-19. The prevalence of elevated troponins among patients who died was 76% compared to 10% among survivors in 1 Chinese study (3). Another study from China found increasing troponin levels over a 22 day period among those who died while troponin levels remained low in those who survived (5).

 
Risk factors for elevated troponins in Covid-19 include older age, cardiovascular comorbidities (eg, hypertension, coronary heart disease, heart failure), diabetes, chronic obstructive pulmonary disease, chronic renal failure, and the presence of a high inflammatory state, as indicated by elevated inflammatory markers such as C-reactive protein (CRP) (3).

 
Several mechanisms have been proposed to explain elevated troponins in Covid-19, including cytokine-induced myocardial injury, microangiopathy due to prothrombotic state, myocardial infarction (type I due to plaque rupture or type II due to oxygen supply/demand imbalance), and myocarditis either due to direct viral invasion or indirectly through immune-mediated mechanisms (1,2).

 
Patients with Covid-19 and modest troponin elevation with rapid fall in the absence of signs or symptoms of ACS, may have type II myocardial infarction due to demand ischemia, particularly in the setting of coronary disease. In contrast, more protracted elevation of troponins associated with high inflammatory markers such as CRP is suggestive of hyperinflammatory myocardial injury (1).

 

It will be interesting to see if trials of anti-inflammatory agents, such as colchicine and anti-interleukin-I, will have an impact on the troponin levels in Covid-19 patients (1).

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References
1. Cremer PC. SARS-CoV-2 and myocardial injury: few answers, many questions. Clev Clin J Med. Posted April 8, 2020. Doi:10.3949/ccjm.87a.ccc001 https://www.ccjm.org/content/early/2020/05/12/ccjm.87a.ccc001
2. Tersalvi G, Vicenzi M, Calabretta D, et al. Elevated troponin in patients with coronavirus disease 2019:possible mechanisms. J Card Failure 2020; https://pubmed.ncbi.nlm.nih.gov/32315733/
3. Shi S, Qin M, Cai Y, et al. Characteristics and clinical significance of myocardial injury in patients with severe coronavirus disease 2019. Eur Heart J 2020. https://pubmed.ncbi.nlm.nih.gov/32391877/
4. Richardson S, Hirsch JS, Narasimhan M, et al. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area. JAMA 2020;323:2052-59. https://jamanetwork.com/journals/jama/fullarticle/2765184
5. Zhou F, YU T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020;395:1054-62. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30566-3/fulltext

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Massachusetts General Hospital, Harvard Catalyst, Harvard University, its affiliate academic 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!

 

What’s the connection between elevated troponins and Covid-19?