April 2020 Hospitalist Journal Club Summary

Respiratory Virus Shedding in Exhaled Breath and Efficacy of Face Masks

Background: There is little information on the efficacy of facemasks in filtering respiratory viruses.  This study aims to determine how effective surgical facemasks are in preventing spread of viral particles?

Study Design and Results:

Study Design

-Note that this study was performed prior to the COVID-19 pandemic and looked at the common viruses influenza, coronavirus, rhinovirus.

-Patients with viral URI symptoms were evaluated with nasal and throat swabs to identify the causative virus.

-They were then randomized to either wearing a facemask or not and exhaled breath was collected for 30 minutes.

Results 

-111 participants

-Viral RNA was identified from 30%, 26%, and 28% of respiratory droplets and 40%, 35%, and 56% of aerosols collected while not wearing a mask for coronavirus, influenza, and rhinovirus respectively.

-For those wearing masks:

o Coronavirus

no virus was detected in respiratory droplets or aerosols

o Influenza

there was a reduction in respiratory droplet virus detected down to 4% but no decrease in virus detected in aerosols

o Rhinovirus,

no significant reduction in virus detected for either droplets or aerosols

Impact on our practice:

The study shows that, in addition to respiratory droplets, aerosol is a potential mode of transmission for coronavirus as well as influenza and rhinovirus in exhaled breath. However, viral load tended to be low in both droplets and aerosols despite 30 min of exhaled breath so prolonged contact may be required for transmission. Although surgical masks did not appear to be effective for rhinovirus or aerosolized influenza, it did appear to be effective for coronavirus suggesting that placing masks on COVID-19 patients may be helpful in reducing transmission.

Reference: Leung N et al. Respiratory virus shedding in exhaled breath and efficacy of face masks. Nature Medicine 2020 Apr 3 [e-pub]

Reviewed by Dan Ruppman

How Effective are Surgical and Cotton Masks in Blocking SARSCoV-2?

Background: With the concern regarding shortages of PPE and the interest in cotton masks, how effective are surgical and cotton masks in filtering COVID-19?

Study Design and Results: 

Study Design

-4 patients with diagnosed COVID-19 were invited to cough 5 times onto a petri dish while wearing the following sequence of masks: no mask, surgical mask, cotton mask, and again with no mask. Separate petri dishes used for each part of the sequence.

-The inner and outer surfaces of both surgical and cotton masks were swabbed

Results

-Median viral loads in log copies/mL were as follows:

o nasopharyngeal  5.66

o saliva  4.00

o without a mask  2.56

o surgical mask  2.42

o cotton mask  1.85

-All outer surfaces of the masks were positive for COVID-19

-3 of 4 patients had no COVID-19 detected on the inner surface of either mask

Impact on our practice:

The findings from this study could be considered limited given only 4 patients were evaluated but the results were somewhat concerning. Neither surgical nor cotton masks effectively filtered COVID-19 during coughs from infected patients. Prior studies have shown that particles 0.04 to 0.2 µm can penetrate surgical masks. The 2002 SARS-CoV particle size was 0.08 to 0.14 µm. If COVID-19 has a similar size, surgical masks may

not effectively filter this virus. However, we don’t know the effectiveness of the masks in non-coughing patients so ongoing use in public may have some usefulness. The finding of virus on the outer but not inner surface of the masks was interesting. The authors suggest the mask’s aerodynamic features may explain this. I also wonder about the make up of the inner surface of the mask compared to the outer surface and it’s ability to hold onto virus. However, this would only explain the finding on the surgical mask, not the cotton mask which should be the same on either side.

Reference: Bae S et al. Effectiveness of Surgical and Cotton Masks in Blocking SARS–CoV-2: A Controlled Comparison in 4 Patients. Ann of Int Med 2020 Apr 6; [e-pub]

Reviewed by Dan Ruppman

Two Hydroxychloroquine Clinical Efficacy In COVID-19 Studies With Disparate Results

Background: An in vitro study showed potential activity of hydroxychloroquine (HCQ) against SARSCoV-2, the COVID-19 culprit virus. Multiple small studies have shown differing results with regards to clinical efficacy of HCQ in treatment of COVID-19. The following is a review of two non-peer reviewed studies reporting positive and negative results respectively with HCQ use in COVID-19.

Study Design and Results:

Positive Study:

Between 2/4/20-2/28/20, 62 COVID-19 patients (median age 45 yrs, 47% male, 53% female) at one hospital in Wuhan, China were randomized (31 pts to 5-days of 400 mg/ day HCQ; 31 pts to standard treatment). Time to clinical recovery (fever resolution, cough relief) analyzed after 5 days and Chest CT changes analyzed on day 6. Exclusion criteria such that patients studied had very mild illness (SaO2/SPO2 ratio >93% or PaO2/FIO2 ratio > 300 mmHg).  Patients on HCQ became afebrile in 2.2 days vs 3.2 days in control group. Cough resolved in 2.0 days compared to 3.1 days in control group. Chest CT on day 6 compared to day 0 in HCQ patients showed pneumonia improvement in 81% of patients compared to 55% in control group. Two patients had mild HCQ adverse events (rash & headache).

Negative Study:

Between 3/17/20 – 3/31/20, 181 COVID-19 patients (median age 60 years, 71% male, 29% female) requiring oxygen ≥ 2 LPM at four French hospitals, were treated with 600 mg/day HCQ within 48 hrs of admission (84 pts) while 97 pts did not get HCQ.  Retrospectively analyzed and statistical adjustments made for confounding factors to “emulate” randomization. Primary endpoint was transfer to ICU and/or death within 7 days. 20.2% (16) of patients treated with HCQ transferred to ICU or died vs. 22.1% (21) in the non-HCQ group (RR 0.91; 95% CI 0.47-1.80). 2.8% (3) of patients on HCQ died within 7 days compared to 4.6% (4) in non-HCQ patients (RR 0.61; 95% CI 0.13-2.89). 27.4% (24) in HCQ group developed ARDS within 7 days compared to 24.1% (23) in non-HCQ groups (RR 1.14; 95% CI 0.65-2.00). 8 pts on HCQ had ECG changes necessitating discontinuation of HCQ.

Impact on our practice: The single center smaller Chinese study showed clinical improvement with HCQ in mildly ill patients while the larger, multicenter French study of sicker patients showed no clinical improvement with use of HCQ in hypoxic COVID-19 patients. In our current practice, patients with mild symptoms such as those in the positive study likely would not be treated with HCQ. We usually reserve that for sicker patients but the above French study suggests that HCQ does not benefit the population of patients we currently treat with HCQ. It is possible that HCQ may be more effective when symptoms mild – or very early in disease course. So the jury is still out on HCQ effectiveness pending larger randomized controlled trials. However, without much else to offer, will likely continue treating COVID-19 patients with HCQ even though efficacy is very much in question – unless studies suggest harm outweigh potential benefits.

Reference: Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial. Zhaowei Chen et al. Preprint on medrxiv.org No evidence of clinical efficacy of hydroxychloroquine in patients hospitalized for COVID-19 infection and requiring oxygen: results of a study using routinely collected data to emulate a target trial. Matthieu Mahevas et al. Preprint on medrxiv.org

Reviewed by Brian French

Risk Of Coagulopathy In COVID-19 With Guidance On Management

Background:

COVID-19 is creating DIC in severe cases that has been shown by labs and autopsy findings. There is rising concern COVID patients are at increased risk of

thromboembolism even when they are ambulatory due to endothelial damage. At this point there are labs that can potentially guide on prognosis or risk of worsening (CRP, ferritin, d-dimer) but can some labs point towards risk of developing DIC? Is there anything we can do to reduce the risk?

Study Design and Results:

Expert opinion based on available data. Data is very minimal and mostly retrospective extrapolation. Following D-dimer, Prothrombin time and platelet count may help in predicting development of DIC. One study compared high coagulopathy score patients, those who received prophylactic dose low molecular weight heparin (lovenox) had improved mortality.

Impact on our practice:

Allina wide COVID clinical content group (CCCG) recommends pharmacological prophylaxis (strong preference to lovenox) in all COVID patients (unless contraindicated).  To promote it we have added a guiding sentence in the general admission order set. Reference document is available on provider resources under COVID-19 resources on AKN.

Reference: Thachil J et al. ISTH interim guidance on recognition and management of coagulopathy in COVID-19. J Thromb Haemost 2020 Mar 25; [e-pub].  

Reviewed by Love Patel

What is the Rate of Undocumented COVID-19 Infections?

Background: The novel coronavirus that emerged in Wuhan, China (SARS-CoV2) at the end of 2019 quickly spread to all Chinese provinces and at the time of the publication of this article has spread to 58 countries. Estimation of the prevalence and contagiousness of undocumented novel coronavirus (SARS-CoV2) infections is critical for understanding the overall prevalence and pandemic potential of this disease. The fraction of undocumented but infectious cases is a critical epidemiological characteristic that modulates the pandemic potential of an emergent respiratory virus.

Study Design and Results:

Study Design

-To assess the full epidemic potential of SARS-CoV2, a model-inference framework (Bayesian inference) to estimate the contagiousness and proportion of undocumented infections in China during the weeks before (Jan 10 to 23) and after (Jan 24-Feb 8) the shutdown of travel in and out of Wuhan.

-A mathematical model that simulates the spatiotemporal dynamics of infections among 375 Chinese cities. In the model, infections divided into into two classes: (i) documented infected individuals with symptoms severe enough to be confirmed, i.e., observed infections; and (ii) undocumented infected individuals.

-Spatial spread of SARS-CoV2 across cities is captured by the daily number of people traveling among 375 cities (during the Spring Festival) and a multiplicative factor. Human mobility data collected by the Tencent Location-based Service.

-To infer SARS-CoV2 transmission dynamics during the early stage of the outbreak, they simulated observations during 10–23 January 2020  using an iterated filterensemble adjustment Kalman filter (IF-EAKF) framework.

-With this combined model-inference system, they estimated the trajectories of four model state variables (the susceptible, exposed, documented infected, and undocumented infected sub-populations in city) for each of the 375 cities

-Simultaneously inferring six model parameters (the average latent period, the average duration of infection, the transmission reduction factor for undocumented infections, the transmission rate for documented infections; the fraction of documented infections, and the travel multiplicative factor).

Results

-86% of all infections were undocumented (95% CI: [82%–90%]) prior to 23 January 2020 travel restrictions (This finding is independently corroborated by the infection rate among foreign nationals evacuated from Wuhan).

-Per person, the transmission rate of undocumented infections was 55% of documented infections ([46%–62%]), yet, due to their greater numbers, undocumented infections were the infection source for 79% of documented cases.

-The median estimates for the latent and infectious periods are approximately 3.69 and 3.48 days, respectively.

Impact on our practice:

Radical increase in the identification and isolation of currently undocumented infections would be needed to avoid infectious spread in the hospital (crucial for reopening elective procedures/surgeries). Universal masking is necessary to prevent spread among healthcare workers and reciprocally between patients and health care workers.

These findings underscore the seriousness and pandemic potential of SARS-CoV2. The 2009 H1N1 pandemic influenza virus also caused many mild cases, quickly spread globally, and eventually became endemic. Presently, there are four, endemic, coronavirus strains currently circulating in human populations (229E, HKU1, NL63, OC43). If the novel coronavirus follows the pattern of 2009 H1N1 pandemic influenza, it will also spread globally and become a fifth endemic coronavirus within the human population and becomes a huge challenge without vaccine or treatment.

Reference: Leung J. Munster, M. Koopmans, N. van Doremalen, D. van Riel, E. de Wit, A novel coronavirus emerging in China - Key questions for impact assessment. N. Engl. J. Med. 382, 692–694 (2020).doi:10.1056/NEJMp2000929pmid:31978293 et al. Respiratory virus shedding in exhaled breath and efficacy of face masks. Nature Medicine 2020 Apr 3 [e-pub]

Reviewed by Rajesh Kethireddy

Cardiovascular Implications of Fatal Outcomes of Patients With Coronavirus Disease 2019 (COVID-19)

Background: Increasing numbers of confirmed cases and mortality rates of COVID-19 are occurring in several countries and continents. Information regarding the impact of cardiovascular complication on fatal outcome is scarce.

Study Design and Results:

Study Design 

-A retrospective single-center case series analyzed patients with COVID-19 at the Seventh Hospital of Wuhan City, China from 1/23/20 to 2/23/20. This included 187 patients. 144 (77%) were discharged and 43 died (23%).

-There was no difference in therapy used between those with elevated TnT and those with no elevation. Those with elevated TnT had a higher rate of glucocorticoid treatment as well as mechanical ventilation

Results

-66 (35.3%) had underlying CVD and 52 (27.8%) exhibited myocardial injury as indicated by elevated TnT levels

-Those with elevated TnT were older with higher rates of hypertension, CAD, cardiomyopathy, diabetes, COPD and CKD. They were more likely to develop ARDS, malignant arrhythmias, acute coagulopathy and AKI

-Mortality:

o  No underlying CVD and normal TnT levels – 7.62%

o  Underlying CVD with normal TnT levels – 13.33%

o  No underlying CVD with elevated TnT – 37.50%

o  Underlying CVD with elevated TnT – 69.44%

-TnT and BNP increased significantly in those who died, no such changes were seen in survivors. No echocardiogram data is available due to the circumstances of the treatment period.

-TnT levels were significantly positively linear correlated with CRP levels.

-No significant difference in outcome for those on ACEI/ARB treatment

Impact on our practice:

Limitations of this study include the small sample size, a lack of availability of echocardiogram data and the difficulty in attributing death to MI in the setting of multiple organ dysfunction. Those with no troponin elevation, whether they had preexisting CAD or not, showed similar mortality rates. It appears that elevated troponin could act as a marker for severity of illness similar to other tests such as ferritin, D-dimer and CRP. The authors suggest possibly pursuing more aggressive treatment for those with an elevated troponin, though it is uncertain what that would be outside the current guidelines for care. The linear correlation with elevated CRP could suggest an inflammatory pathogenesis leading to direct damage to cardiomyocytes by the virus for cardiac injury.

Reference: Guo T et al. Cardiovascular implications of fatal outcomes of patients with coronavirus disease 2019 (COVID-19). JAMA Cardiol 2020 Mar 27

Reviewed by Chris Maier

Treatment of COVID-19 with Convalescent Plasma

Background: There is no specific treatment for critically ill COVID 19 and as a pandemic with substantial mortality, there is an impetus to explore/identify new treatments. Is convalescent plasma transfusion (CPT) beneficial for critically ill COVID patients?

 -Use of convalescent plasma recommended as empirical tx for Ebola in 2014 and MERS in 2015

-Felt to be effective SARS, H5N1 avian flu, and H1N1 flu

-Prev SARS study showed CPT had significantly higher discharge rate by day 22

-Influenza study showed stat significant fewer deaths

Study Design and Results:

Study Design 

-Case series of 5 critically ill (ventilated, shock, or organ failure requiring ICU) patients with COVID infection with ARDS conducted at ID dept in Shenzhen Hospital from 1/20/20. Age 36-65 yo, 2 women – all vented and received anti-viral meds and Solumedrol. Final date of follow up 3/25/20. Clinical outcomes compared before and after CPT. Patients given CPT with IgG binding titer of > 1:1000 obtained from 5 patients who recovered from COVID. Administered to patients 10-22 days after admission to hospital. Approved by Ethics Committee from Shenzhen Hospital.

-Main outcomes and metrics: change in body temp, SOFA score (sequential organ failure assessment), PAO2/FIO2, viral load, serum antibody titer, routine blood biochemical index, ARDS, vent requirement, ECMO.

Results

-Following CPT, body temp normalized within 3 days in 4/5 pts, SOFA score decreased, PAO2/FIO2 increased within 12 days, viral loads decreased and converted to negative within 12 days of CPT, and neutralizing antibody (IgG) increased. ARDS resolved in 4 patients at 12 days, 3 patients weaned form ventilator within 2 wks. 3 patients discharged from hospital eventually (51-55 days).

-Limitations/Considerations

o1/5 patient also had pre-existing chronic comorbidities prior to COVID, also had fungal and bacterial pneumonia superimposed infection while the other 4 did not

Implications: hard to extrapolate given small sample size (n=1) that another patient with these conditions will respond similarly

o5/5 patients also received antiviral lopinavir/ritonavir

Implication: CPT might best be utilized w/concurrent anti-virals but that was not explored specifically with this case study

Impact on our practice: Used of convalescent plasma transfusion for critically ill COVID patients did not demonstrate significant harm. This was case study, not controlled study, and also low sample size so hard to generalize results, but at least use of CPT as later line supportive therapy can and maybe should be considered for critically ill patients.

Reference: Shen C et al. Treatment of 5 critically ill patients with COVID-19 with convalescent plasma. JAMA 2020 Mar 27; [e-pub].

Reviewed by Jimmy Haung

Surgical Comanagement by Hospitalists

Background: Surgical comanagement by hospitalists has been an attractive arrangement for many years as it allows surgeons the ability to focus on surgical recovery alongside hospitalists who prevent and manage medical conditions.

Study Design and Results:

Study Design 

The study was performed at Stanford University Hospital using a regression analysis of 26,380 discharges from 9/1/12 - 6/30/18 with patients on orthopedics and neurosurgery.

SCM Team Description: Dedicated hospitalist staff who only see orthopedic and neurosurgery patients. Weekdays 8A-5P: 2 on orthopedics, 1 on neurosurgery Sees both services on weekends. After hours call by 1 hospitalist for both services  First calls go to the surgeon on call who reaches out to the hospitalist on call for any medical issues in which they need assistance. Hospitalists communicate directly with the surgeon and not through students or residents. There are no mid-level providers on the SCM service. Hospitalist screens all patients on the service and will only see those patients with preventable or active medical conditions or new unexpected complications.

Measures:

Primary outcome measure was the proportion of patients with =>1 medical complication (sepsis, pneumonia, UTI, delirium, AKI, afib, or ileus).

Secondary outcome measures were mean LOS, proportion of patients with =>2 medical consultations, RRT calls, codes, and top-box patient satisfaction scores. Cost savings were estimated indirectly via LOS and compared to pre SCM data.                

Comparison of pre-SCM unadjusted rates reported in prior study 2009

Results

-Patients with =>1 medical complication decreased by 3.8% per year, odds of RRT calls decreased by 12.2% per year.

-Odds of patients with =>medical consultations, codes, or top-box satisfaction score were not statistically significant.

-Estimated average, direct cost savings of $3,424 per discharge between 2012 and 2018

Impact on our practice: None, I believe hospitalist programs with "geographic rounding" practices have already demonstrated their value to administration. The primary benefit of this study appears to be proving their value to administration and serving as an example to others who are trying to start up the same program at their institution. UHS does not use the same dedicated hospitalist on these kinds of services as our physicians' value maintaining their clinical skills across a wider variety of patients. It would be interesting to see if that would result in a statistically significant difference.

Reference: Rohatgi N et al. Surgical comanagement by hospitalists: Continued improvement over 5 years. J Hosp Med 2020 Apr; 15:232.

Reviewed by Scott Tongen