Covid-19;

What’s the evidence that REGEN-COV (casirivimab and imdevimab) monoclonal antibody cocktail is effective in the post-exposure prophylaxis of Covid-19?

FA Manian MD, MPH, , , , , , , , , , , , , , Leave a comment

The U.S. FDA has issued an Emergency Use Authorization (EUA) for the emergency use of REGEN-COV in adult and pediatric populations (≥12 years of age and older weighing> 40 kg) who are at high risk* of progression to severe COVID-19— including hospitalization or death— and who are not fully vaccinated or are not expected to mount an adequate immune response to the vaccine (eg, immunocompromised state).1  This recommendation is based on a randomized controlled trial involving individuals enrolled within 96 hours of exposure to a known Covid-19 case (Covid-10 Phase 3 Prevention Trial).2

In this trial, the primary efficacy end point was the development of symptomatic SARS-CoV-2 infection through day 28  in participants who did not have SARS-CoV-2 infection  by PCR or serology at the time of enrollment. Symptomatic SARS-CoV-2 infection developed in 1.5% of treatment group (vs 7.8% in placebo group) with 81.4% relative risk reduction (P<0.001); 66% reduction was observed when symptomatic and asymptomatic infections were combined.  Duration of symptoms and the magnitude and duration of detectable RNA were also lower in the REGEN-COV group compared to placebo. Therapy was well tolerated.2

In the same study, in a subgroup analysis of those who were seropositive at the time of enrollment REGEN-COV lowered the risk of symptomatic disease (0.4% vs 2.3% in the placebo group) with relative risk reduction of 81%, though not statistically significant (P=0.14).  This may be why the FDA EUA extended to certain vaccinated groups as well since to date there are no published trials on the use of REGEN-COV as post-exposure prophylaxis in vaccinated individuals.

*High risk group included ≥65 years of age, BMI≥25 kg/m2, diabetes, immunocompromised state, cardiovascular disease or hypertension, chronic lung disease, sickle cell disease and neurodevelopment disorders.

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References

  1. Fact sheet for health care providers emergency use authorization (EUA) of REGEN-COV. https://www.fda.gov/media/145611/download. Accessed September 15, 2021.
  2. O’Brien MP. Forleo-Neto E, Musser BJ et al. Subcutaneous REGEN-COV antibody combination to prevent Covid-19. N Engl J Med 2021, August 4, 2021. https://www.nejm.org/doi/full/10.1056/NEJMoa2109682

 

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, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their 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 evidence that REGEN-COV (casirivimab and imdevimab) monoclonal antibody cocktail is effective in the post-exposure prophylaxis of Covid-19?

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

FA Manian MD, MPH, , , , , , , , , , , Leave a comment

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?

Can I use fist bump when I greet my patients or coworkers in the hospital?

FA Manian MD, MPH, , , , , , Leave a comment

Fist bump may be a safer practice than handshake with respect to transfer of potential pathogens but should not be considered a “safe”’ alternative. Studies to date have demonstrated transfer of bacteria even with fist bump, albeit often at lower counts. 1-3

In an experimental study involving healthcare workers in a hospital,1 fist bump was still associated with bacterial colonization, albeit at levels 4 times less than that of palmar surfaces following handshakes. Smaller contact surface area and reduced total contact time were thought to contribute to lower risk of bacterial transfer via fist bump.

In another experiment involving E. coli, fist bump was associated with ~75% less transfer of bacteria relative to “moderate handshake”.2

Interestingly, in a 2020 study of 50 methicillin-resistant Staphylococcus aureus (MRSA)-colonized patients,3 the rate of MRSA isolated from the fist after a fist bump was not significantly lower than that of the dorsal surface of the hand after a handshake (16% vs 22%, P=0.6).  

In contrast, “cruise tap”, defined as contact between 2 knuckles alone, may be safer than fist bump. In the MRSA study above, cruise tap was associated with significantly lower rate of bacterial transfer compared to handshakes (8% vs 22%, P=0.02).3

Even a safer alternative is to avoid skin-to-skin contact altogether by using elbow bump, or no “bump” at all, particularly in the Covid-19 era!

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References

  1. Ghareeb PA, Bourlai T, Dutton W, et al. Reducing pathogen transmission in a hospital setting. Handshake verses fist bump: a pilot study. https://pubmed.ncbi.nlm.nih.gov/24144553/
  2. Mela S, Withworth DE. The fist bump: A more hygienic alternative to the handshake. Am J Infect Control 2014;42:916-7. http://www.apic.org/Resource_/TinyMceFileManager/Fist_bump_article_AJIC_August_2014.pdf
  3. Pinto-Herrera NC, Jones LD, Ha W, et al. Transfer of methicillin-resistant Staphylococcus aureus by first bump versus handshake. Infect Control Hospital Epidemiology 2020;41:962-64. https://pubmed.ncbi.nlm.nih.gov/32456719/

 

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!

Can I use fist bump when I greet my patients or coworkers in the hospital?

How often is Covid-19 in hospitalized patients complicated by bacterial infection?

FA Manian MD, MPH, , , , , , , , , , Leave a comment

Despite frequent use of empiric antibiotics in hospitalized patients with Covid-19,1  current data suggests a low rate of documented bacterial co-infection (BCI) in such patients. In fact, the overall reported rate of BCI in hospitalized patients with Covid-19 is generally no greater than 10%.1-3   It’s quite likely that most patients with Covid-19 and chest radiograph changes solely have a coronavirus (SARS-CoV-2) lung infection,4 particularly early in the course of the disease.  

A meta-analysis involving 30 studies (primarily retrospective) found that overall 7% of hospitalized Covid-19 patients had a laboratory-confirmed BCI with higher proportion among ICU patients (14%). 2 Mycoplasma pneumoniae was the most common (42% of BCIs), followed by Pseudomonas aeruginosa and H. influenzae.  Notably, diagnosis of M. pneumoniae infection was based on antibody testing for IgM, which has been associated with false-positive results. Other caveats include lack of a uniform definition of respiratory tract infection among studies and potential impact of concurrent or prior antibiotic therapy on the yield of bacteriologic cultures. 5,6

A low prevalence of BCI was also found in a UK study involving 836 hospitalized Covid-19 patients: 3.2% for early BCI (0-5 days after admission) and 6.1% throughout hospitalization, including hospital-acquired infections.7  Staphylococcus aureus was the most common respiratory isolate among community-acquired cases, while Pseudomonas spp. was the predominant healthcare associated respiratory isolate.  Similarly, S. aureus. and Streptococcus pneumoniae were the most commonly isolated organisms from blind bronchoalveolar lavage of critically ill patients with Covid-19 during their first 5 days of admission, while gram-negative bacilli became dominant later during the hospitalization.8

The discordance between high rates of antibiotic treatment and confirmed bacterial co-infection in Covid-19 patients is likely a reflection of the difficulty in distinguishing Covid-19 pneumonia from bacterial pneumonia based on clinical or radiographic findings alone.

We need better tests to help distinguish bacterial vs Covid-19 pneumonia. Some have suggested using a low serum procalcitonin to help guide the withholding of or early discontinuation of antibiotics, especially in less severe Covid-19 cases. 1  Formal studies of the accuracy of procalcitonin in Covid-19 are needed to test this hypothesis, given its suboptimal sensitivity in bacterial community-acquired pneumonia. 

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Reference

  1. Stevens RW, Jensen K, O’Horo JC, et al. Antimicrobial prescribing practices at a tertiary-care center in patients diagnosed with COVID-19 across the continuum of care. Infect Control Hosp Epidemiology 2020. https://reference.medscape.com/medline/abstract/32703323
  2. Lansbury L, Lim B, Baskaran V, et al. Co-infections in people with COVID-19: a systematic review and meta-analysis. J Infect 2020;81:266-75. https://pubmed.ncbi.nlm.nih.gov/32473235/
  3. Rawson TM, Moore LSP, Zhu N. Bacterial and fungal co-infection in individuals with coronavirus: A rapid review to support COVID-19 antimicrobial prescribing. Clin Infect Dis 2020 (Manuscrpit published online ahead of print 2 June ). Doi:10.1093/cid/ciaa530.https://pubmed.ncbi.nlm.nih.gov/32358954/
  4. Metlay JP, Waterer GW. Treatment of community-acquired pneumonia during the coronavirus 2019 (COVID-19) pandemic. Ann Intern Med 2020; 173:304-305. https://pubmed.ncbi.nlm.nih.gov/32379883/
  5. Chang CY, Chan KG. Underestimation of co-infections in COVID-19 due to non-discriminatory use of antibiotics. J Infect 2020;81:e29-30. https://pubmed.ncbi.nlm.nih.gov/32628960/
  6. Rawson TM, Moore LSP, Zhu N, et al. Bacterial pneumonia in COVID-19 critically ill patients: A case series. Reply letter. Clin Infect Dis 2020. https://academic.oup.com/cid/advance-
  7. Hughes S, Troise O, Donaldson H, et al. Bacterial and fungal coinfection among hospitalized patients with COVID-19: a retrospective cohort study in a UK secondary-care setting. Clin Microbiol Infect 2020. https://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(20)30369-4/fulltext
  8. Dudoignon E, Camelena F, Deniau B, et al. Bacterial pneumonia in COVID-19 critically ill patients: A case series. Clin Infect Dis 2020. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7337703/

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 often is Covid-19 in hospitalized patients complicated by bacterial infection?

How might categorizing severity of illness help in the management of my patient with Covid-19?

FA Manian MD, MPH, , , , , , , , , , , , , , , , , , , , , , , , , , , , Leave a comment

Although the criteria for Covid-19 severity of illness categories may overlap at times or vary across guidelines and clinical trials, I have found those published in the National Institute of Health (USA) Covid-19 Treatment Guidelines most useful and uptodate.1  Keep in mind that the primary basis for severity categories in Covid-19 is the degree by which it alters pulmonary anatomy and physiology and respiratory function (see my table below).

The first question to ask when dealing with Covid-19 patients is whether they have any signs or symptoms that can be attributed to the disease (eg, fever, cough, sore throat, malaise, headache, muscle pain, lack of sense of smell). In the absence of any attributable symptoms, your patient falls into “Asymptomatic” or “Presymptomatic” category.  These patients should be monitored for any new signs or symptoms of Covid-19 and should not require additional laboratory testing or treatment.

If symptoms of Covid-19 are present (see above), the next question to ask is whether the patient has any shortness of breath or abnormal chest imaging. If neither is present, the illness can be classified as “Mild” with no specific laboratory tests or treatment indicated in otherwise healthy patients. These patients may be safely managed in ambulatory settings or at home through telemedicine or remote visits. Those with risk factors for severe disease (eg, older age, obesity, cancer, immunocompromised state), 2 however, should be closely monitored as rapid clinical deterioration may occur.

Once lower respiratory tract disease based on clinical assessment or imaging develops, the illness is no longer considered mild. This is a good time to check a spot 02 on room air and if it’s 94% or greater at sea level, the illness qualifies for “Moderate” severity. In addition to close monitoring for signs of progression, treatment for possible bacterial pneumonia or sepsis should be considered when suspected. Corticosteroids are not recommended here and there are insufficient data to recommend either for or against the use of remdesivir in patients with mild/moderate Covid-19.

Once spot 02 on room air drops below 94%, Covid-19 illness is considered “Severe”; other parameters include respiratory rate >30, Pa02/Fi02 < 300 mmHg or lung infiltrates >50%. Here, patients require further evaluation, including pulmonary imaging, ECG, CBC with differential and a metabolic profile, including liver and renal function tests. C-reactive protein (CRP), D-dimer and ferritin are also often obtained for their prognostic value. These patients need close monitoring, preferably in a facility with airborne infection isolation rooms.  In addition to treatment of bacterial pneumonia or sepsis when suspected, consideration should also be given to treatment with corticosteroids. Remdesivir is recommended for patients who require supplemental oxygen but whether it’s effective in those with more severe hypoxemia (eg, those who require oxygen through a high-flow device, noninvasive or invasive mechanical ventilation or extracorporeal membrane oxygenation-ECMO) is unclear. Prone ventilation may be helpful here in patients with refractory hypoxemia as long as it is not used to avoid intubation in those who otherwise require mechanical ventilation.

“Critical” illness category is the severest forms of Covid-19 and includes acute respiratory distress syndrome (ARDS), septic shock, cardiac dysfunction and cytokine storm. In addition to treatment for possible bacterial pneumonia or sepsis when suspected, corticosteroids and supportive treatment for hemodynamic instability and ARDS, including prone ventilation, are often required. The effectiveness of remdesivir in patients with severe hypoxemia (see above) is unclear at this time.

 

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 References

  1. NIH COVID-19 Treatment Guidelines. https://www.covid19treatmentguidelines.nih.gov/. Accessed Aug 27, 2020.
  2. CDC. Covid-19.  https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-with-medical-conditions.html/. Accessed Aug 27, 2020.  

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 might categorizing severity of illness help in the management of my patient with Covid-19?

When should I consider systemic corticosteroids in my patient with Covid-19?

FA Manian MD, MPH, , , , , , , Leave a comment

As of July 30, 2020, The National Institute of Health (NIH) Coronavirus Disease 2019 (COVID-19) Guidelines Panel recommends using dexamethasone 6 mg per day for up to 10 days for the treatment of Covid-19 in patients who are mechanically ventilated (“Strong” recommendation based on 1 or more randomized trials) with a a less strong recommendation (“Moderate”) in those who require supplemental oxygen but who are not mechanically ventilated.1

These recommendations appear to primarily stem from a multicenter, open label randomized controlled trial of dexamethasone vs standard of care in hospitalized patients in United Kingdom, 2 with treated group receiving dexamethasone 6 mg IV or orally daily for 10 days or until hospital discharge (whichever came first).  Mortality at 28 days was significantly lower among patients on mechanical ventilation who received dexamethasone (29.3% vs 41.4%, rate ratio 0.64, 95% CI, 0.51-0.81) and in those receiving supplemental oxygen without mechanical ventilation (23.3% vs 26.2%). The risk of progression to invasive mechanical ventilation was also lower in the dexamethasone group. No significant difference in mortality was found in patients who did not require supplemental oxygen. 

Retrospective and case series studies have reported conflicting results on the efficacy of corticosteroid for the treatment of covid-19. 3-10 That’s why despite its limitations (open label, wide range of 02 supplementation, few patients receiving remdesvir), the randomized controlled trial discussed above should guide our decision making on the use of corticosteroids in patients with Covid-19.

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References

  1. NIH. The Coronavirus Disease 2019 (COVID-19) Guidelines. https://www.covid19treatmentguidelines.nih.gov/immune-based-therapy/immunomodulators/corticosteroids/ Accessed August 6, 2020.
  2. Horby P, Lim WS, Emberson JR, et al. Dexamethasone in hospitalized patients with Covid-19—Preliminary report. N Engl J Med 2020; July 17, 2020. https://www.nejm.org/doi/full/10.1056/NEJMoa2021436
  3. Keller MJ, Kitsis EA, Arora S, et al. Effect of systemic glucocorticoids on mortality or mechanical ventilation in patients with COVID-19. J Hosp Med 2020;15(8):489-493. https://www.journalofhospitalmedicine.com/jhospmed/article/225402/hospital-medicine/effect-systemic-glucocorticoidsmortalityor-mechanical
  4. Wang Y, Jiang W, He Q, et al. A retrospective cohort study of methylprednisolone therapy in severe patients with COVID-19 pneumonia. Signal Transduct Target Ther. 2020;5(1):57. https://www.ncbi.nlm.nih.gov/pubmed/32341331
  5. Wu C, Chen X, Cai Y, et al. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern Med. 2020. https://www.ncbi.nlm.nih.gov/pubmed/32167524
  6. Corral L, Bahamonde A, Arnaiz delas Revillas F, et al. GLUCOCOVID: A controlled trial of methylprednisolone in adults hospitalized with COVID-19 pneumonia. medRxiv. 2020. https://www.medrxiv.org/content/10.1101/2020.06.17.20133579v1
  7. Fadel R, Morrison AR, Vahia A, et al. Early short course corticosteroids in hospitalized patients with COVID-19. Clin Infect Dis. 2020. https://www.ncbi.nlm.nih.gov/pubmed/32427279
  8. Fernandez Cruz A, Ruiz-Antoran B, Munoz Gomez A, et al. Impact of glucocorticoid treatment in SARS-CoV-2 infection mortality: a retrospective controlled cohort study. Antimicrob Agents Chemother 2020. https://www.ncbi.nlm.nih.gov/pubmed/32571831
  9. Yang Z, Liu J, Zhou Y, Zhao X, Zhao Q, Liu J. The effect of corticosteroid treatment on patients with coronavirus infection: a systematic review and meta-analysis. J Infect. 2020;81(1):e13-e20. https://www.ncbi.nlm.nih.gov/pubmed/32283144

 10. Lu X, Chen T, Wang Y, Wang J, Yan F. Adjuvant corticosteroid therapy for critically ill patients with COVID-19. Crit Care. 2020;24(1):241. https://www.ncbi.nlm.nih.gov/pubmed/32430057

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!

 

When should I consider systemic corticosteroids in my patient with Covid-19?

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

FA Manian MD, MPH, , , , , , , , , , , 2 Comments

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?

FA Manian MD, MPH, , , , , , , Leave a comment

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?

FA Manian MD, MPH, , , , , , , , , , , , Leave a comment

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?

What role does obesity play in severe Covid-19?

FA Manian MD, MPH, , , , , , , , , , Leave a comment

Obesity has been shown to be a strong independent predictor of not only Covid-19-related hospitalization but also critical illness requiring invasive mechanical ventilation (IMV) or ICU support (1-3).

 
A large New York City study involving over 4,000 Covid-19 patients found obesity ( BMI≥30 kg/m2) to be an independent risk factor for hospitalization; BMI 30-40 kg/m2 was associated with ~4-fold and >40 kg/m2 with ~6-fold increased risk. Obesity was also strongly associated with increased risk of critical illness, stronger than other common preexisting conditions such as heart disease, hypertension or diabetes (1, preprint).

 
Another New York City study found that among Covid-19 patients younger than 60 years of age, obese patients were twice as likely to be hospitalized or have critical illness (2). Similarly, a French study found severe obesity (BMI >35 kg/m2) to be strongly associated with IMV compared to those with BMI <25 kg/m2 (O.R. 7.4, 1.7-33) (3).

 
Many factors likely play a role in making obese patients particularly susceptive to severe Covid-19. Obesity is a well-recognized inflammatory state and is associated with abnormal secretion of cytokines and adipokines which may have an effect on lung parenchyma and bronchi (1,3,4). Somewhat paradoxically, obese patients may also have an impaired adaptive immune response to certain infections, including influenza (4). Abdominal obesity is also associated with impaired ventilation of the base of the lungs resulting in reduced oxygenation (1).

 

 

Bonus Pearl: Did you know among pre-existing conditions commonly found in the population (eg, hypertension, diabetes, COPD), obesity has been found to be the only condition independently associated with pulmonary embolism in Covid-19 (O.R. 2.7, 1.3-5.5) (5).

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References
1. Petrilli CM, Jones SA, Yang J, et al. Factors associated with hospitalization and critical illness among 4, 103 patients with Covid-19 disease in New York City. MedRxiv preprint doi: https://doi.org/10.1101/2020.04.0820057794
2. Lighter J, Phillips M, Hochman S, et al. Obesity in patients younger than 60 years is a risk factor for COVID-19 hospital admission. Clin Infect Dis 2020. https://pubmed.ncbi.nlm.nih.gov/32271368/
3. Simonnet A, Chetboun M, Poissy J, et al. High prevalence of obesity in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) requiring invasive mechanical ventilation. https://pubmed.ncbi.nlm.nih.gov/32271993/
4. Sattar N, BcInnes IB, McMurray JJV. Obesity a risk factor for severe COVID-19 infection:multiple potential mechanisms. Circulation 2020. https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.120.047659
5. Poyiadji N, Cormier P, Patel PY, et al. Acute pulmonary embolism and COVID-19. Radiology 2020; https://pubmed.ncbi.nlm.nih.gov/32407256/

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 role does obesity play in severe Covid-19?