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COVID-19: Research

Updated May 21, 2020

The CHEST COVID-19 Task Force curates key emerging research deemed to be helpful to clinicians on the front lines. Articles are listed by category in reverse order of publication date, are freely available, and link to the publication site. This list will be maintained regularly. Suggestions for consideration can be sent to COVID-19@chestnet.org.

Clinical Management

Epidemiology

Public Health and Systems Issues

Science

Clinical Management

Contact Tracing Assessment of COVID-19 Transmission Dynamics in Taiwan and Risk at Different Exposure Periods Before and After Symptom Onset
JAMA (May 1, 2020)

  • The objective of this prospective case-ascertained study in Taiwan was to delineate the transmission dynamics of COVID-19.
  • This study of 100 cases of confirmed COVID-19 in Taiwan and 2,761 close contacts found that the overall secondary clinical attack rate was 0.7% and was higher among contacts whose exposure to the index case started within 5 days of symptom onset than those who were exposed later.
  • High transmissibility of COVID-19 before and immediately after symptom onset suggests that finding and isolating symptomatic patients alone may not suffice to contain the epidemic, and more generalized measures may be required, such as social distancing.

Cardiovascular Disease, Drug Therapy, and Mortality in COVID-19
NEJM (May 1, 2020)

  • Coronavirus disease 2019 (COVID-19) may disproportionately affect people with cardiovascular disease.
  • Using an observational database from 169 hospitals in Asia, Europe, and North America, the authors evaluated the relationship of cardiovascular disease and drug therapy with in-hospital death among hospitalized patients with COVID-19.
  • Of the 8,910 patients with COVID-19 for whom discharge status was available at the time of the analysis, a total of 515 died in the hospital (5.8%) and 8,395 survived to discharge.
  • The factors the authors found to be independently associated with an increased risk of in-hospital death were an age greater than 65 years, coronary artery disease, cardiac arrhythmia, chronic obstructive pulmonary disease, and current smoking.

When the Game Changes: Guidance to Adjust Sarcoidosis Management during the COVID-19 Pandemic
CHEST (April 29, 2020)

  • Sarcoidosis patients may have an increased risk of a poor outcome and death from COVID-19 infection because sarcoidosis involves the lung in most patients, and because, although the etiology of sarcoidosis is unknown, it is postulated that immunologic dysfunction and dysregulation play essential roles in the development of the disease.
  • Because of the lethality of COVID-19 infection, there is concern that the risk-benefit ratio of effective immunosuppressive therapies for sarcoidosis may be altered in the current climate.
  • Sarcoidosis management during the current COVID-19 pandemic poses many challenges for treating physicians. A figure in this article (Figure 1) provides a generalized approach to this issue.
  • The risk of a poor outcome from COVID-19 infection must be factored into the clinician’s treatment algorithm and may result in an adjustment of the sarcoidosis patient’s immunosuppressive regimen depending on the stability of their disease and consequences of disease reactivation.

Remdesivir in Adults with Severe COVID-19: a Randomised, Double-Blind, Placebo-Controlled, Multicentre Trial
Lancet (April 29, 2010)

  • This study is an investigator-initiated, individually randomized, placebo-controlled, double-blind trial to assess the effectiveness and safety of intravenous remdesivir in adults (aged ≥18 years) admitted to ten hospitals in Wuhan, Hubei, China; it is registered with ClinicalTrials.gov, NCT04257656.
  • 255 patients were screened; 18 were excluded and 237 were enrolled (158 to the remdesivir group and 79 to the placebo group), a 2:1 ratio.
  • The primary clinical endpoint was time to clinical improvement within 28 days after randomization; clinical improvement was defined as a two-point reduction in patients’ admission status on a six-point ordinal scale, or live discharge from the hospital, whichever came first.
  • No statistically significant benefits were observed for remdesivir treatment beyond those of standard of care treatment.
  • Although not statistically significant, in patients receiving remdesivir or placebo within 10 days of symptom onset in the ITT population, those receiving remdesivir had a numerically faster time to clinical improvement than those receiving placebo and 28-day mortality was similar between the two groups.

Remdesivir for COVID-19: Challenges of Underpowered Studies
The Lancet (April 29, 2020)

  • In the recent article, “Remdesivir in Adults with Severe COVID-19: a Randomised, Double-Blind, Placebo-Controlled, Multicentre Trial,” results of the trial were reported early after enrolling 237 patients out of the intended 453.
  • While well-designed, stopping early gives an underpowered trial, which taken alone, gives inconclusive findings.
  • The study has not shown a statistically significant finding that confirms a remdesivir treatment benefit of at least the minimally clinically important difference, nor has it ruled such a benefit out; likewise, a larger benefit might exist, or remdesivir might actually do harm. It is unknown—more data are needed.

Postmortem Lung Findings in an Asthmatic with Coronavirus Disease 2019 (COVID-19)
CHEST (April 28, 2020)

  • Asthma is increasingly recognized as an underlying risk factor for severe respiratory disease in coronavirus disease 2019 (COVID-19) patients, particularly in the United States.
  • This case report focuses on the postmortem lung findings from a 37-year-old asthmatic man, who met the clinical criteria for severe acute respiratory distress syndrome and died of COVID-19 less than 2 weeks after presentation to the hospital.
  • Treatment included hydroxychloroquine, empiric piperacillin/tazobactam and vancomycin, and corticosteroids.
  • His lungs showed mucus plugging and other histologic changes attributable to asthma as well as early diffuse alveolar damage and a fibrinous pneumonia.

What Policy Makers Need to Know About COVID-19 Protective Immunity
Lancet (April 27, 2010)

  • It is essential that policy makers in all affected countries have the best possible data and understanding to inform any course of action.
  • A study of SARS survivors showed that about 90% had functional, virus-neutralizing antibodies and around 50% had strong T-lymphocyte responses.
  • The best estimate of how long immunity to COVID-19 is likely to last comes from the closely related coronaviruses and suggests that, in people who had an antibody response, immunity might wane, but is detectable beyond 1 year after hospitalization.
  • Reliance on comprehensive seroprevalence data and a solid, research-based grasp of correlates of protection will allow policy to be guided by secure, evidence-based assumptions on herd immunity, rather than optimistic guesses.

Use of Tocilizumab for COVID-19-Induced Cytokine Release Syndrome: A Cautionary Case Report
CHEST (April 25, 2020)

  • This article reports on two cases of patients who received a diagnosis of COVID-19 complicated by cytokine release syndrome (CRS) and were treated with tocilizumab.
  • Both patients progressed to secondary hemophagocytic lymphohistiocytosis despite treatment with tocilizumab, and one developed viral myocarditis, challenging the safety and clinical usefulness of tocilizumab in the treatment of COVID-19-induced CRS.
  • These findings substantiate a report from Wuhan, China, in which four of seven critically ill patients treated with tocilizumab died or experienced disease aggravation despite improvement in C-reactive protein.
  • This report further challenges the clinical usefulness of anti-IL-6 therapy in the treatment of COVID-19-induced CRS.

Regional Planning for Extracorporeal Membrane Oxygenation Allocation During COVID-19
CHEST (April 24, 2020)

  • Health systems confronting the 2019 novel coronavirus (COVID-19) pandemic must plan for surges in ICU demand and equitably distribute resources to maximize benefit for critically ill patients and the public during periods of resource scarcity.
  • For example, morbidity and mortality could be mitigated by a proactive regional plan for the triage of mechanical ventilators.
  • The authors explore underlying assumptions and triage principles that could guide the integration of extracorporeal membrane oxygenation (ECMO) resources into existing disaster planning, drawing from a collaborative framework developed by one US metropolitan area with multiple adult and pediatric extracorporeal life support centers.
  • This article aims to inform decision-making around ECMO use during a pandemic such as COVID-19 and also addresses the ethical and practical aspects of not continuing to offer ECMO during a disaster.

Effect of High vs Low Doses of Chloroquine Diphosphate as Adjunctive Therapy for Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Randomized Clinical Trial
JAMA Network Open (April 24, 2020)

  • There is no specific antiviral therapy recommended for coronavirus disease 2019 (COVID-19).
  • In vitro studies indicate that the antiviral effect of chloroquine diphosphate (CQ) requires a high concentration of the drug.
  • In this phase IIb parallel, double-masked randomized clinical trial of 81 patients with COVID-19, an unplanned interim analysis recommended by an independent data safety and monitoring board found that a higher dosage of chloroquine diphosphate for 10 days was associated with more toxic effects and lethality, particularly affecting QTc interval prolongation.
  • The preliminary findings from the CloroCovid-19 trial suggest that higher dosage of chloroquine should not be recommended for the treatment of severe COVID-19, especially among patients also receiving azithromycin and oseltamivir, because of safety concerns regarding QTc interval prolongation and increased lethality.

How Japan Squandered Its Early Jump on the Pandemic
BMJ (April 24,2020)

  • Japan’s low COVID-19 infection numbers led to a lapse in public vigilance. Now, an explosion of cases has escalated measures that may be too little, too late.
  • Public bath houses have been deemed essential businesses by the government, along with grocery stores, pharmacies, and hospitals. Restaurants and izakaya pubs remain open, albeit with hours limited to daytime. The Tokyo Metropolitan Government also failed in its bid to get barber shops, beauty parlors, and DIY stores to close their doors as part of the national government’s official measures.
  • Japan is not enforcing social distancing rules, partly because by law it cannot enforce closures or fine citizens for breaking the rules. Even under a state of emergency, now extended nationwide, there can be no mandatory lockdown as seen in other countries.
  • Some experts believe that Japanese doctors’ practice of providing tests for the virus only to very sick people with fever or other symptoms led to misleadingly low infection numbers.

Presymptomatic SARS-CoV-2 Infections and Transmission in a Skilled Nursing Facility
NEJM (April 24, 2020)

  • After identification of a case of COVID-19 in a skilled nursing facility, the authors assessed transmission and evaluated the adequacy of symptom-based screening to identify infections in residents.
  • The authors conducted two serial point-prevalence surveys, 1 week apart, in which assenting residents of the facility underwent nasopharyngeal and oropharyngeal testing for SARS-CoV-2, including real-time reverse-transcriptase polymerase chain reaction (rRT-PCR), viral culture, and sequencing.
  • Among 76 residents who participated in point-prevalence surveys, 48 (63%) tested positive. Of these 48 residents, 27 (56%) were asymptomatic at the time of testing; 24 subsequently developed symptoms (median time to onset, 4 days).
  • Rapid and widespread transmission of SARS-CoV-2 was demonstrated in this skilled nursing facility. More than half of residents with positive test results were asymptomatic at the time of testing and most likely contributed to transmission. Infection-control strategies focused solely on symptomatic residents were not sufficient to prevent transmission after SARS-CoV-2 introduction into this facility.

Practical Considerations for the Diagnosis and Treatment of Fibrotic Interstitial Lung Disease During the COVID-19 Pandemic
CHEST (April 23, 2020)

  • This review article summarizes how COVID-19 has impacted key components of the diagnosis and management of fibrotic ILD; provides strategies to mitigate these challenges; reviews major obstacles for researchers; and identifies priority areas for future ILD research related to COVID-19.
  • The authors provide practical considerations to support care of patients with ILD during the COVID-19 pandemic and a road map for clinicians caring for these patients during future infectious disease outbreaks.

Unexpected Blood Pressure Sensitivity to Angiotensin II in COVID-19 Patient With ARDS and Septic Shock
CHEST (April 23, 2020)

  • This case report studies a critically ill 88-year-old man with a history of hypertension, coronary artery disease, and type 2 diabetes mellitus who presented to clinic with a 3-day history of cough and shortness of breath. The patient denied any travel history outside of Minnesota.
  • The patient demonstrated unexpected blood pressure sensitivity to synthetic angiotensin II. This is an interesting observation as SARS-CoV-2 utilizes ACE2 as receptor for cell entry, and ACE2 functions to negatively regulate angiotensin II.
  • The authors hypothesize that sensitivity to Ang-2 might be related to biologic effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
  • This study is suggestive of a potential role for synthetic Ang-2 for patients with COVID-19 and septic shock. Further studies are needed to confirm clinical efficacy.

A Cluster Randomized Trial of Cloth Masks Compared with Medical Masks in Healthcare Workers
BMJ Open (April 22, 2015, with March 30, 2020 update)

  • The aim of this randomized controlled trial was to compare the efficacy of cloth masks with medical masks in hospital healthcare workers.
  • Hospital wards were randomized to medical masks, cloth masks, or a control group (usual practice, which included mask wearing). Participants used the mask on every shift for 4 consecutive weeks. The rates of all infection outcomes were highest in the cloth mask arm, with the rate of influenza-like illness (ILI) statistically significantly higher in the cloth mask arm compared with the medical mask arm. Cloth masks also had significantly higher rates of ILI compared with the control arm.
  • The authors of this article, published in 2015, have written a March 2020 update addressing COVID-19 mask shortages and the use of cloth masks as a last resort; they urge readers to consider the update when reading the article.
  • They recommend that health workers should not work during the COVID-19 pandemic without respiratory protection as a matter of work health and safety.

Alterations in Smell or Taste in Mildly Symptomatic Outpatients With SARS-CoV-2 Infection
JAMA (April 22, 2020)

  • Altered sense of smell or taste was reported by 130 patients (64.4%, 95% CI, 57.3%-71.0%). Alterations in smell or taste were frequently reported by mildly symptomatic patients with SARS-CoV-2 infection and often were the first apparent symptom.
  • If these results are confirmed, consideration should be given to testing and self-isolation of patients with new onset of altered taste or smell during the COVID-19 pandemic.

Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area
JAMA (April 22, 2019)

  • This case series, which includes 5700 patients hospitalized with COVID-19 in the New York City area, was intended to describe the characteristics and early outcomes of patients hospitalized in the US with COVID-19.
  • The most common comorbidities were hypertension (3026; 56.6%), obesity (1737; 41.7%), and diabetes (1808; 33.8%).
  • Among patients who were discharged or died (n = 2634), 14.2% were treated in the intensive care unit, 12.2% received invasive mechanical ventilation, 3.2% were treated with kidney replacement therapy, and 21% died.
  • The absence of data on patients who remained hospitalized at the final study date, including the high mortality rate of patients older than age 65 years who received mechanical ventilation, may have biased the findings.

Herd Immunity – Estimating the Level Required to Halt the COVID-19 Epidemics in Affected Countries
Journal of Infection (March 21, 2020)

  • There have been serious debates about how to react to the spread of COVID-19, from locking down entire cities and countries or alternatively allowing the causal virus (SARS-CoV-2) to spread to increase the population herd immunity, but at the same time protecting the elderly and those with multiple comorbidities, who are the most vulnerable to this virus.
  • Before initiating either strategy, it is necessary to estimate the basic reproductive number (R0), the number of secondary cases generated by the presence of one infected individual) or to estimate the effective reproductive number (Rt), which uses real-life data (from diagnostic testing and/or clinical surveillance) to estimate the reproductive number for an ongoing epidemic.
  • For this analysis, the authors estimated Rt, by applying the exponential growth method, using data on the daily number of new COVID-19 cases, together with a recent estimate of the serial interval (mean = 4.7 days, standard deviation = 2.9 days) at a 0.05 significance level, with the mathematical software R, from the R Project for Statistical Computing.
  • The results are presented in a table with a calculation of the COVID-19 effective reproduction number (Rt) of 32 study countries and the minimum proportion (Pcrit), as a % of population) needed to have recovered from COVID-19 with subsequent immunity, to halt the epidemic in that population. For the United States, Rt = 3.29 and Pcrit = 69.6% ; for Singapore, Rt = 1.13 and Pcrit = 11.5%.

Building Trust While Influencing Online COVID-19 Content in the Social Media World
The Lancet (April 21, 2020)

  • Unlike historical pandemics such as the 1918 H1N1 pandemic, COVID-19 is spreading across a highly connected world, in which virtually all individuals are linked to each other through the mobile phone in their pockets.
  • The authors discuss ways in which social media have undermined effective responses to COVID-19.
  • Digital social networks have facilitated the spread of misinformation about COVID-19, in which scientific misinformation has been actively propagated to destabilize trust in governments and as a political weapon.
  • Public health practitioner must ensure that measures strike an ethically appropriate balance between protecting speech and preserving and promoting public health.

Viral Load Dynamics and Disease Severity in Patients Infected with SARS-CoV-2 in Zhejiang Province, China, January-March 2020: Retrospective Cohort Study
BMJ (April 21,2020)

  • This retrospective cohort study was designed to evaluate viral loads at different stages of disease progression in patients infected with the 2019 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the first 4 months of the epidemic in Zhejiang province, China.
  • 96 consecutively admitted patients with laboratory confirmed SARS-CoV-2 infection: 22 with mild disease and 74 with severe disease were studied.
  • The study found that the duration of SARS-CoV-2 is significantly longer in stool samples than in respiratory and serum samples, highlighting the need to strengthen the management of stool samples in the prevention and control of the epidemic.
  • The virus persists longer with higher load and peaks later in the respiratory tissue of patients with severe disease.

Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19): A Review
JAMA (April 13, 2020)

  • The pandemic of COVID-19 caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents an unprecedented challenge to identify effective drugs for prevention and treatment.
  • While no proven effective therapies for this virus currently exist, the rapidly expanding knowledge regarding SARS-CoV-2 virology provides a significant number of potential drug targets.
  • The most promising therapy is remdesivir, which has potent in vitro activity against SARS-CoV-2, but it is not US Food and Drug Administration approved and currently is being tested in ongoing randomized trials.
  • The speed and volume of clinical trials launched to investigate potential therapies for COVID-19 highlight both the need and capability to produce high-quality evidence even in the middle of a pandemic.

Compassionate Use of Remdesivir for Patients with Severe COVID-19
JAMA (April 10, 2020)

  • Remdesivir, a nucleotide analogue prodrug that inhibits viral RNA and has shown in vitro activity against SARS-CoV-2, was provided, on a compassionate-use basis, to patients hospitalized with COVID-19, the illness caused by infection with SARS-CoV-2.
  • Patients received a 10-day course of remdesivir, consisting of 200 mg administered intravenously on day 1, followed by 100 mg daily for the remaining 9 days of treatment.
  • In this cohort of patients hospitalized for severe COVID-19 who were treated with compassionate-use remdesivir, clinical improvement was observed in 36 of 53 patients (68%).

Incidence of Thrombotic Complications in Critically Ill ICU Patients with COVID-19
Thrombosis Research (April 10, 2020)

  • COVID-19 may predispose to both venous and arterial thromboembolism due to excessive inflammation, hypoxia, immobilization and diffuse intravascular coagulation, but reports on the incidence of thrombotic complications are not available.
  • The authors evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction, or systemic arterial embolism in all COVID-19 patients admitted to the ICU of 3 Dutch hospital and found that the cumulative incidence was 31%.
  • The 31% incidence of thrombotic complications in ICU patients with COVID-19 infections is remarkably high, reinforcing the recommendation to strictly apply pharmacological thrombosis prophylaxis in all COVID-19 patients admitted to the ICU.
  • The 31% incidence is also strongly suggestive of increasing the prophylaxis towards high-prophylactic doses, even in the absence of randomized evidence.

Deployment of Convalescent Plasma for the Prevention and Treatment of COVID-19
J Clin Invest (April 7, 2020)

  • To date, there are neither proven prophylaxis options for those who have been exposed to COVID-19, nor therapy for those who develop COVID-19.
  • Immune (“convalescent”) plasma refers to plasma that is collected from individuals following resolution of infection and development of antibodies.
  • Passive antibody administration through transfusion of convalescent plasma may offer the only short-term strategy to confer immediate immunity to susceptible individuals.
  • Data from rigorously controlled clinical trials of convalescent plasma are few, underscoring the need to evaluate its use objectively for a range of indications (eg, prevention vs treatment) and patient populations (eg, age, comorbidities).

Locally Informed Simulation to Predict Hospital Capacity Needs During the COVID-19 Pandemic
Annals of Internal Medicine (April 7, 2020)

  • The COVID-19 Hospital Impact Model (CHIME) (http://penn-chime.phl.io) SIR model was used to estimate the time from March 23, 2020, until hospital capacity would probably be exceeded, and the intensity of the surge, including for ICU beds and ventilators.
  • Using patients with COVID-19 alone, CHIME estimated that it would be 31 to 53 days before demand exceeds existing hospital capacity. In best- and worst-case scenarios of surges in the number of patients with COVID-19, the needed total capacity for hospital beds would reach 3,131 to 12,650 across the three hospitals, including 338 to 1,608 ICU beds and 118 to 599 ventilators.
  • The authors concluded that this publicly available modeling tool, designed for hospital operations leaders, can inform preparations for capacity strain during the early days of a pandemic.

Prediction Models for Diagnosis and Prognosis of COVID-19 Infection: Systematic Review and Critical Appraisal
BMJ (April 7, 2020)

  • The focus of this systematic review and critical appraisal was published and preprint reports of prediction models for diagnosing coronavirus disease 2019 (COVID-19) in patients with suspected infection; for prognosis of patients with COVID-19; and for detecting people in the general population at risk of being admitted to hospital for COVID-19 pneumonia.
  • The data sources were PubMed and Embase through Ovid, Arxiv, medRxiv, and bioRxiv up to 24 March 2020.
  • At least two of the authors independently extracted data using the CHARMS (critical appraisal and data extraction for systematic reviews of prediction modelling studies) checklist and risk of bias was assessed using PROBAST (prediction model risk of bias assessment tool).
  • This review indicated that proposed models are poorly reported, at high risk of bias, and their reported performance is probably optimistic.

Effectiveness of Convalescent Plasma Therapy in Severe COVID-19 Patients
PNAS (April 6, 2020)

  • This study explores the feasibility of convalescent plasma (CP) transfusion to rescue patients with severe disease.
  • The results from 10 severe adult cases showed that one dose (200 mL) of CP was well tolerated and could significantly increase or maintain the neutralizing antibodies at a high level, leading to disappearance of viremia in 7 days.
  • The studied patients’ clinical symptoms were significantly improved with increase of oxyhemoglobin saturation, increased lymphocyte counts, decreased C-reactive protein, varying degrees of absorption of lung lesions, and undetectable viral load in seven patients who had previous viremia, with no observed severe adverse effects.
  • The optimal dose and time point, as well as the clinical benefit of CP therapy, needs further investigation in larger well-controlled trials.

Baseline Characteristics and Outcomes of 1591 Patients Infected With SARS-CoV-2 Admitted to ICUs of the Lombardy Region, Italy
JAMA (April 6, 2020)

  • This study retroactively examined the clinical characteristics of 1,591 consecutive patients admitted to the ICU with confirmed SARS-CoV-2.
  • The majority of patients were men (82%), had at least one comorbidity (69%), and had hypertension (49%).
  • A large proportion of patients required ventilator support, and ICU mortality was 26%.

Respiratory virus shedding in exhaled breath and efficacy of face masks
Nature Medicine (April 3, 2020)

  • There is little information on the efficacy of face masks in filtering respiratory viruses and reducing viral release from an individual with respiratory infections; most research has focused on influenza.
  • Most of the existing evidence on the filtering efficacy of face masks and respirators comes from in vitro experiments with nonbiological particles, which may not be generalizable to infectious respiratory virus droplets.
  • This study focused on 246 individuals randomized into two groups (wearing and not wearing a face mask during the first exhaled breath).
  • Surgical face masks significantly reduced detection of influenza virus RNA in respiratory droplets and coronavirus RNA in aerosols, with a trend toward reduced detection of coronavirus RNA in respiratory droplets.
  • The results indicate that surgical face masks could prevent transmission of human coronaviruses and influenza viruses from symptomatic individuals.

Comment from the COVID Task Force

What does this paper mean? While this study did not specifically address SARS-CoV-2, it does demonstrate that transmission of seasonal coronaviruses could be reduced by use of surgical face masks. Adoption of widespread use of masks may be beneficial for prevention of COVID-19 given the prolonged incubation period of the virus, the potential for viral shedding in asymptomatic individuals, and the current limitations on testing.


Preliminary Findings of Control of Dispersion of Aerosols and Droplets during High Velocity Nasal Insufflation Therapy Using a Simple Surgical Mask: Implications for High Flow Nasal Cannula
CHEST (April 2, 2020)

  • The primary mode of transmission of COVID-19 pneumonia appears to be droplet-borne.
  • The study used computational fluid dynamics (CFD) modeling to evaluate (1) effect of the addition of a surgical mask over the face on the velocity of the gas outflow into the room (2) what is the consequence of leakage around the mask (3) what effect does the addition of a mask have on the ability of high-velocity nasal insufflation (HVNI) to flush the upper airway dead space. Two models were used to answer these questions.
  • The preliminary findings suggest the addition of a simple type I surgical mask may provide an effective tool to further reduce droplet deposition due to exhaled gas flow.

Effect of Intermittent or Continuous Feed on Muscle Wasting in Critical Illness: A Phase II Clinical Trial
CHEST (April 2, 2020)

  • Acute skeletal muscle wasting in critical illness is associated with excess morbidity and mortality.
  • Continuous feeding may suppress muscle protein synthesis as a result of the muscle-full effect, unlike intermittent feeding which may ameliorate it.
  • In this single-blinded, randomized, controlled trial 121 mechanically ventilated adult patients were divided into the intervention group (intermittent enteral feeding from six 4-hourly feeds per 24 hours) and control group (standard continuous enteral feeding). The primary outcome was 10-day loss of rectus femoris muscle cross-sectional area determined by ultrasound.
  • Intermittent feeding in early critical illness is not shown to preserve muscle mass despite resulting in a greater achievement of nutritional targets than continuous feeding. However, it is feasible and safe.

Convalescent Plasma as a Potential Therapy for COVID-19
The Lancet (April 1, 2020)

  • Convalescent plasma or immunoglobulins have been used as a last resort to improve the survival rate of patients with SARS whose condition continued to deteriorate despite treatment with pulsed methylprednisolone.
  • Several prior studies showed a shorter hospital stay and lower mortality in patients treated with convalescent plasma than those who were not treated with convalescent plasma.
  • One possible explanation for the efficacy of convalescent plasma therapy is that the antibodies from convalescent plasma might suppress viremia.
  • Evidence shows that convalescent plasma from patients who have recovered from viral infections can be used as a treatment without the severe adverse events.
  • It might be worthwhile to test the safety and efficacy of convalescent plasma transfusion in COVID-19-infected patients.

Use of Hydroxychloroquine and Chloroquine During the COVID-19 Pandemic: What Every Clinician Should Know
Annals of Internal Medicine (March 31, 2020)

  • The antimalarials hydroxychloroquine (HCQ) and chloroquine (CQ) have demonstrated antiviral activity against severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) in vitro and in small, poorly controlled or uncontrolled clinical studies.
  • Normally, such research would be deemed hypothesis-generating at best; however, a tweet by President Trump claiming that the combination of HCQ and azithromycin “ha[s] a real chance to be one of the biggest game changers in the history of medicine” accelerated a worldwide run on the drugs, with pharmacies reporting shortages within 24 hours.
  • Additional trials are needed to determine benefit.

Safety of Ibuprofen in Patients with COVID-19: Causal or Confounded?
CHEST (March 31, 2020)

  • The mainstay therapy for those with mild to moderate symptoms of COVID-19 remains supportive therapy, which includes use of analgesics such as ibuprofen.
  • Recent reports of a potential harm with ibuprofen in patients with COVID-19 have received significant international media coverage. The news started when an infectious disease specialist in France anecdotally reported four cases of children who took ibuprofen and experienced worsening symptoms of COVID-19 infection in her clinic. This opinion was soon endorsed by the French Health Minister and the World Health Organization.
  • Clinicians need to have a picture of both the strength and quality of the evidence before they can make informed decisions regarding use of ibuprofen for COVID-19. The current epidemiological evidence is not strong enough to infer a causal link of a harmful effect of ibuprofen in patients with COVID-19 and is not sufficient to advise against coadministration of ibuprofen with acetaminophen, although risk of adding ibuprofen should still be assessed against its benefits.

Treatment With Convalescent Plasma for Critically Ill Patients With SARS-CoV-2 Infection
CHEST (March 30, 2020)

  • Immunotherapy with virus-specific antibodies in convalescent plasma had been used as a last resort to improve survival rate of patients with serious infectious diseases.
  • To date, no therapeutics have yet been proven effective for the treatment of critical illness except for supportive care, including treatment with antiviral drugs, corticosteroids, immunoglobulins, and noninvasive or invasive mechanical ventilation.
  • The results of this four-patient study indicated that convalescent plasma might be a potential therapy for critically ill patients infected with SARS-CoV-2.
  • No serious adverse reactions associated with the transfusion of convalescent plasma were noticed. However, the relative contributions of supportive care, investigational therapies, and patient’s immune response on survival could not be determined.

COVID-19 in Critically Ill Patients in the Seattle Region — Case Series
NEJM (March 30, 2020)

  • Twenty-four patients were admitted to the ICU for hypoxemic respiratory failure with confirmed COVID-19, and 18 required mechanical ventilation.
  • Initial symptoms included shortness of breath and cough beginning 4-7 days prior to admission.
  • Most patients had fever (50%) and hypotension (70%) requiring vasopressors on admission and comorbidities of diabetes (58%).
  • Half of the patients died between ICU day 1 and 18.

Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma
JAMA (March 27, 2020)

  • This uncontrolled case series of five critically ill patients with COVID-19 and ARDS addressed the following question: Could administration of convalescent plasma transfusion be beneficial in the treatment of critically ill patients with coronavirus disease 2019 (COVID-19)?
  • Administration of convalescent plasma containing neutralizing antibody was followed by an improvement in clinical status.
  • These preliminary findings raise the possibility that convalescent plasma transfusion may be helpful in the treatment of critically ill patients with COVID-19 and ADRS, but this approach requires evaluation in randomized clinical trials.

The Effect of Control Strategies to Reduce Social Mixing on Outcomes of the COVID-19 Epidemic in Wuhan, China: A Modelling Study
The Lancet Public Health (March 25, 2020)

  • The authors of this paper aimed to estimate the effects of physical distancing measures on the progression of the COVID-19 epidemic, hoping to provide some insights for the rest of the world.
  • They simulated the ongoing trajectory of an outbreak in Wuhan using an age-structured susceptible-exposed-infected-removed (SEIR) model for several physical distancing measures.
  • The authors’ projections showed that physical distancing measures were most effective if the staggered return to work was at the beginning of April.
  • There are benefits to sustaining these measures until April in terms of delaying and reducing the height of the peak, median epidemic size at end-2020, and affording health-care systems more time to expand and respond.

Management of Pregnant Women Infected with COVID-19
The Lancet Infectious Diseases (March 24, 2020)

  • With immunocompromised status and physiological adaptive changes during pregnancy, pregnant women could be more susceptible to COVID-19 infection than the general population, but there is scarce information of assessment and management of pregnant women infected with COVID-19, and the potential risk of vertical transmission is unclear.
  • Seven pregnant women with COVID-19 pneumonia were assessed in this study, all of whom had caesarean section. The outcomes of the pregnant women and neonates were good.
  • Three neonates were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and one was found to be infected with COVID-19 36 h after birth.
  • More evidence is needed to establish when to deliver and when caesarean sections should be recommended. Previous treatment experience has been inconclusive about which delivery method is safer in this patient population.

Coronavirus Disease 2019 (COVID-19) and Cardiovascular Disease
Circulation (March 21, 2020)

  • Among those with COVID-19, there is a higher prevalence of cardiovascular disease and more than 7% of patients suffer myocardial injury from the infection (22% of the critically ill).
  • COVID-19 poses a challenge for heart transplantation, impacting donor selection, immunosuppression, and posttransplant management.
  • The exact mechanism of cardiac involvement in COVID-19 remains under investigation.
  • There are many promising treatments under investigation, but none with proven clinical efficacy to date.

Clinical Characteristics of Severe Acute Respiratory Syndrome Coronavirus 2 Reactivation
Journal of Infection (March 20, 2020)

  • While only limited data were available for COVID-19 reactivation, this study aimed to evaluate the clinical characteristics of the SARS-CoV-2 reactivation.
  • The authors retrospectively recruited 55 patients who were diagnosed with COVID-19 pneumonia at the Zhongnan Hospital of Wuhan University from Jan 8, 2020 to Feb 10, 2020 to evaluate the clinical characteristics of the SARS-CoV-2 reactivation because only limited reactivation data was available.
  • In a significant proportion of COVID-19 patients, SARS-CoV-2 reactivation developed after discharging from hospital (9%). The clinical characteristics of the patients with SARS-CoV-2 reactivation were similar to those of non-reactivated patients with COVID-19 infection.
  • This evidence suggests that a proportion of recovered COVID-19 patients could reactivate, posing a major public health burden in terms of global morbidity and possibly mortality.

Hydroxychloroquine and Azithromycin as a Treatment of COVID-19: Results of an Open-Label Non-Randomized Clinical Trial
International Journal of Antimicrobial Agents (March 20, 2020)

  • Chloroquine and hydroxychloroquine have been found to be efficient on SARS-CoV-2 and reported to be efficient in Chinese patients with COVID-19.
  • Azithromycin added to hydroxychloroquine was significantly more efficient for virus elimination.
  • The authors concluded that despite its small sample size their survey shows that hydroxychloroquine treatment is significantly associated with viral load reduction/disappearance in COVID-19 patients and its effect is reinforced by azithromycin.

A Trial of Lopinavir–Ritonavir in Adults Hospitalized With Severe COVID-19
NEJM (March 18, 2020)

  • This randomized, controlled, open-label trial studied 199 hospitalized adult patients with confirmed SARS-CoV-2 infection.
  • No benefit was observed with lopinavir–ritonavir treatment beyond standard care.

COVID-19 — The Search for Effective Therapy
NEJM (March 18, 2020)

  • This study reports the results of an urgent open-label randomized clinical trial of the efficacy of lopinavir–ritonavir in patients with COVID-19 in Wuhan, China, the epicenter of the outbreak.
  • No benefit was observed in the primary end point of time to clinical improvement: both groups.

Severe Outcomes Among Patients With Coronavirus Disease 2019 (COVID-19) — United States, February 12–March 16, 2020
Mortality and Morbidity Weekly Report (March 18, 2020)

  • This report by the CDC COVID-19 Response Team describes the then-current current epidemiology of COVID-19 in the United States, using preliminary data.
  • During the period, 80% of deaths occurred among adults aged ≥65 years with the highest percentage of severe outcomes among persons aged ≥85 years.
  • These findings are similar to data from China, which indicated >80% of deaths occurred among persons aged ≥60 years.

Interrupting Transmission of COVID-19: Lessons From Containment Efforts in Singapore
Journal of Travel Medicine (March 13, 2020)

  • Singapore was one of the first countries to be affected by COVID-19 and is the country with the highest COVID-19 numbers outside of China from February 5, 2020 to February 18, 2020.
  • Due to Singapore being impacted so greatly by the 2003 SARS outbreak, Singapore has steadily built up its outbreak preparedness, including developing a national pandemic preparedness plan based on risk assessment and calibration of response measures that are proportionate to the risk.
  • Despite multiple importations resulting in local chains of transmission, Singapore has been able to control the COVID-19 outbreak without major disruption to daily living.

Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China
JAMA (March 13, 2020)

  • This cohort study, involving 201 patients with confirmed COVID-19 pneumonia, addresses the question of what clinical characteristics are associated with the development of acute respiratory distress syndrome (ARDS) and the progression from ARDS to death.
  • Pneumonia risk factors included older age, neutrophilia, and organ and coagulation dysfunction.
  • Treatment with methylprednisolone may be beneficial for patients who develop ARDS.

Detection of SARS-CoV-2 in Different Types of Clinical Specimens
JAMA (March 11, 2020)

  • Whether the SARS-COV-2 virus can be detected in specimens from other sites, and therefore potentially transmitted in other ways than by respiratory droplets, is unknown.
  • In this study, SARS-CoV-2 was detected in specimens from multiple sites of 205 patients with COVID-19, with lower respiratory tract samples most often testing positive for the virus.
  • Importantly, the live virus was detected in feces, implying that SARS-CoV-2 may be transmitted by the fecal route.

The Incubation Period of Coronavirus Disease 2019 (COVID-19) From Publicly Reported Confirmed Cases: Estimation and Application
Annals of Internal Medicine (March 10, 2020)

  • The objective of this study was to estimate the length of the incubation period of COVID-19 and describe its public health implications.
  • There were 181 confirmed cases with identifiable exposure and symptom onset windows used to estimate the incubation period of COVID-19.
  • The median incubation period was estimated to be 5.1 days (95% CI, 4.5 to 5.8 days), and 97.5% of those who develop symptoms will do so within 11.5 days (CI, 8.2 to 15.6 days) of infection.

In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)
Clinical Infectious Disease (March 9, 2020)

  • Chloroquine has been sporadically used in treating SARS-CoV-2 infection.
  • Hydroxychloroquine shares the same mechanism of action as chloroquine, but its more tolerable safety profile makes it the preferred drug to treat malaria and autoimmune conditions.
  • The pharmacological activity of chloroquine and hydroxychloroquine was tested using SARS-CoV-2 infected Vero cells.
  • Hydroxychloroquine was found to be more potent than chloroquine in inhibiting SARS-CoV-2 in vitro.

Can We Contain the COVID-19 Outbreak with the Same Measures as SARS?
The Lancet Infectious Diseases (March 5, 2020)

  • This “personal view” addresses the fact that there are many similarities between severe acute respiratory syndrome (SARS) and coronavirus disease 2019 (COVID-19) from the virus homology to the origin and transmission
  • COVID-19 has a higher transmissibility than SARS, and many more patients with COVID-19 rather than SARS have mild symptoms that contribute to spread because these patients are often missed and not isolated.
  • Because of the extent of community spread, traditional public health measures might not be able to halt all human-to-human transmission, and we need to consider moving from containment to mitigation.

COVID-19 and the Cardiovascular System
Nature Reviews Cardiology (March 5, 2020)

  • Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells through ACE2 receptors, leading to coronavirus disease (COVID-19)-related pneumonia, while also causing acute myocardial injury and chronic damage to the cardiovascular system.
  • Particular attention should be given to cardiovascular protection during treatment for COVID-19.

Chloroquine and Hydroxychloroquine as Available Weapons to Fight COVID-19
International Journal of Microbial Agents (March 4, 2020)

  • Repositioning of drugs for use as antiviral treatments is a critical need. There is a strong rationality for the use of chloroquine to treat infections with intracellular micro-organisms. Malaria has been treated for several decades with this molecule.
  • Twenty clinical studies were launched in several Chinese hospitals.
  • The first results obtained from more than 100 patients showed the superiority of chloroquine compared with treatment of the control group in terms of reduction of exacerbation of pneumonia, duration of symptoms and delay of viral clearance, all in the absence of severe side effects.

Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review
Journal of Clinical Medicine (February 26, 2020)

  • This study systematically reviews the potential of rapid diagnostics, vaccines, and therapeutics, including those for Middle East respiratory syndrome-Coronavirus (MERS-CoV) and severe acute respiratory syndrome (SARS)-CoV, to guide policymakers globally on their prioritization of resources for research and development.
  • A systematic search was carried out in three major electronic databases to identify published studies in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
  • The analysis shows that as the US tries to move beyond its months-long coronavirus testing debacle — faulty tests, shortages of tests, and guidelines that excluded many people who should have been tested to mitigate the outbreak — it is at risk of fumbling the next challenge: testing enough people to determine which cities and states can safely reopen and stay open.
  • Several vaccine candidates are in the pipeline, but there are currently no effective specific antivirals or drug combinations supported by high-level evidence.

Clinical Course and Outcomes of Critically Ill Patients With SARS-CoV-2 Pneumonia in Wuhan, China: A Single-Centered, Retrospective, Observational Study
Lancet Respiratory (February 24, 2020)

  • The mortality of critically ill patients with SARS-CoV-2 pneumonia is high. The survival term of the nonsurvivors is likely to be within 1-2 weeks after ICU admission.
  • Older patients (>65 years) with comorbidities and ARDS are at increased risk of death.
  • The severity of SARS-CoV-2 pneumonia poses great strain to hospital critical care resources, especially if they are not adequately staffed or resourced.

Preparing for the Most Critically Ill COVID-19 Patients: The Potential Role of ECMO
JAMA (February 19, 2020)

  • Extracorporeal membrane oxygenation (ECMO) is a resource-intensive, highly specialized, and expensive form of life support.
  • The role of ECMO in the management of COVID-19 is unclear at this point.

Epidemiology

Risk factors of fatal outcome in hospitalized subjects with coronavirus disease 2019 from a nationwide analysis in China
CHEST (April 15, 2020)

  • While the cumulative number of new confirmed COVID-19 cases and death are still increasing in China, the independent predicted factors associated with the fatal outcome remain uncertain.
  • A retrospective cohort of 1,590 hospitalized subjects with COVID-19 throughout China was established for this study.
  • The prognostic effects of variables, including clinical features and laboratory findings, were analyzed, and a prognostic nomogram was formulated to predict the survival of a patient with COVID-19 based on risk factors associated with fatal outcomes.
  • In this nationwide cohort, non-survivors showed higher incidence in elderly people and subjects with co-existing chronic illness, dyspnea, and laboratory abnormalities on admission, compared with survivors.
  • A nomogram was established based on the results of multivariate analysis. Internal bootstrap resampling suggested that the nomogram has sufficient discriminatory power. Calibration plots also demonstrated good consistency between the prediction and the observation.

A call to action: the need for autopsies to determine the full extent of organ involvement associated with COVID-19 infections
CHEST (April 10, 2020)

  • There have been several reports in the Chinese medical literature and Lancet describing large case series of patients who have had COVID-19 infections, a subset of which have died as a result of their infections.
  • A number of these decedents clinically had involvement of organ systems in addition to the lungs. To the best of the authors’ knowledge, there is only one report describing pathologic findings in a single decedent who had a “complete” autopsy.
  • As an example, the authors describe a report in the Journal of Forensic Medicine of an 85-year-old Chinese man who died following COVID-19 infection. Briefly summarized, the gross autopsy revealed heavy lungs with copious amounts of gray-white viscous fluid, but otherwise the heart, liver and kidneys were unremarkable. However, no pathologic diagnoses were made, and no histopathologic examination was reported. Therefore, it is difficult to make any more specific diagnoses beyond the gross findings.
  • Even though fewer and fewer autopsies are being done throughout the world, they are a powerful tool to better understand the full scope of new and emerging diseases such as COVID-19.
  • The authors’ purpose in submitting this Call to Action letter is to recommend detailed autopsies of patients who have succumbed to COVID-19 infections.

Epidemiology of COVID-19 in a Long-Term Care Facility in King County, Washington
NEJM (March 27, 2020)

  • Long-term care facilities are high-risk settings for severe outcomes from outbreaks of COVID-19, owing to both the advanced age and frequent chronic underlying health conditions of the residents and the movement of health-care personnel among facilities in a region.
  • After identification on February 28, 2020, of a confirmed case of COVID-19 in a skilled nursing facility in King County, Washington, with approximately 130 facility residents and 170 staff, authorities launched a case investigation, contact tracing, quarantine of exposed persons, isolation of confirmed and suspected cases, and on-site enhancement of infection prevention and control.
  • As of March 18, a total of 167 confirmed cases of COVID-19 affecting 101 residents, 50 health-care personnel, and 16 visitors were found to be epidemiologically linked to the facility.
  • Proactive steps by long-term care facilities to identify and exclude potentially infected staff and visitors, actively monitor for potentially infected patients, and implement appropriate infection prevention and control measures are needed to prevent the introduction of COVID-19.

Clinical Characteristics of Coronavirus Disease 2019 in China
NEJM (February 28, 2020)

  • The authors extracted data regarding 1,099 patients with laboratory-confirmed COVID-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020.
  • Approximately 2% of the patients had a history of direct contact with wildlife, whereas more than three quarters were either residents of Wuhan, had visited the city, or had contact with city residents.
  • The median duration of hospitalization was 12.0 days (mean, 12.8). During hospital admission, most of the patients received a diagnosis of pneumonia from a physician (91.1%), followed by ARDS (3.4%) and shock (1.1%).
  • Despite the number of deaths associated with COVID-19, SARS-CoV-2 appears to have a lower case fatality rate than either SARS-CoV or Middle East respiratory syndrome-related coronavirus (MERS-CoV).

A Novel Coronavirus (COVID-19) Outbreak: A Call for Action
CHEST (February 19, 2020)

  • This review article traces the history of the novel Coronavirus (COVID-19) outbreak from the Huanan Seafood Market in December 2019, and the sharing of the initial genome sequence with the World Health Organization on January 12, 2020, and the late January epidemic update and risk assessment from the Chinese Center for Disease Control and Prevention.
  • It focuses on molecular characterization and clinical features, and the treatment of coronaviruses.

Epidemiological and Clinical Characteristics of 99 Cases of 2019 Novel Coronavirus Pneumonia in Wuhan, China: A Descriptive Study.
Lancet (February 15, 2020)

  • In this retrospective, single-center study, all confirmed cases of 2019-nCoV in Wuhan Jinyintan Hospital from January 1 to January 20, 2020 were reviewed.
  • Cases were confirmed by real-time Reverse Transcription Polymerase Chain Reaction (RT-PCR) and were analyzed for epidemiological, demographic, clinical, and radiological features and laboratory data.
  • In total, 49 (49%) patients were clustered and had a history of exposure to the Huanan seafood market. By the end of January 25, 31 (31%) patients had been discharged and 11 (11%) patients had died; all other patients were still in hospital.
  • In conclusion, the infection of 2019-nCoV was of clustering onset, is more likely to infect older men with comorbidities, and can result in severe and even fatal respiratory diseases such as ARDS.

Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus–Infected Pneumonia
NEJM (January 29, 2020)

  • The authors analyzed data on the first 425 confirmed cases in Wuhan to determine the epidemiologic characteristics of NCIP; and collected information on demographic characteristics, exposure history, and illness timelines of laboratory-confirmed cases of NCIP that had been reported by January 22, 2020.
  • On the basis of this information, there is evidence that human-to-human transmission occurred among close contacts since the middle of December 2019.
  • Considerable efforts to reduce transmission will be required to control outbreaks if similar dynamics apply elsewhere. Measures to prevent or reduce transmission should be implemented in populations at risk.

Public Health and Systems Issues

The Ethics of COVID-19 Immunity-Based Licenses (“Immunity Passports”)
JAMA (May 6, 2020)

  • Chile, Germany, and the United Kingdom, among others, have indicated they will implement certifications that a person has contracted and recovered from COVID-19 or, in the future, has received a COVID-19 vaccine.
  • This option been discussed, but not implemented, in the United States, but if other countries require these certifications for entrance, the United States may adopt them to enable travel.
  • Certifications of immunity are sometimes called “immunity passports” but are better conceptualized as immunity-based licenses because periodic testing and renewal of immunity licenses at designated intervals based on specific criteria may be necessary, similar to the renewal process for driver’s licenses.
  • Such policies raise important questions about fairness, stigma, and counterproductive incentives but could also further individual freedom and improve public health; the authors present a framework for analyzing the ethics of immunity licenses.

Occurrence, prevention, and management of the psychological effects of emerging virus outbreaks on healthcare workers: rapid review and meta-analysis
BMJ (May 5, 2020)

  • This rapid review and meta-analysis of 59 papers examines the psychological effects on clinicians who are working to manage COVID-19 outbreaks and describes successful measures to manage stress and psychological distress.
  • The authors’ conclusions were that effective interventions are available to help mitigate the psychological distress experienced by staff caring for patients in an emerging disease outbreak.
  • Although psychological distress is to be expected in situations where staff are under pressure to look after a large number of potentially infectious patients, employers can help to mitigate this by immediate implementation of several effective interventions.
  • Further research is required into the effectiveness of these interventions, particularly during the COVID-19 pandemic.

Staff Safety During Emergency Airway Management for COVID-19 in Hong Kong
The Lancet Respiratory Medicine (April 1, 2020)

  • Medical professionals caring for patients with coronavirus disease 2019 (COVID-19) are at high risk of contracting the infection.
  • Aerosol-generating procedures, such as non-invasive ventilation (NIV), high-flow nasal cannula (HFNC), bag-mask ventilation, and intubation are of particularly high risk.
  • All medical personnel involved in the management of patients with suspected COVID-19 must adhere to airborne precautions, hand hygiene, and donning of personal protective equipment. All aerosol-generating procedures should be done in an airborne infection isolation room.
  • Double-gloving, as a standard practice might provide extra protection and minimize spreading via fomite contamination to the surrounding equipment after intubation.

Coronavirus Disease (COVID-19): A Primer for Emergency Physicians
American Journal of Emergency Medicine (March 24, 2020)

  • This review article provides emergency physicians with an overview of the most current recommendations on the evaluation and management of patients with suspected COVID-19.
  • Risk factors for severe COVID-19 disease include advanced age, chronic medical conditions, immunocompromise, and cancer.

Fair Allocation of Scarce Medical Resources in the Time of COVID-19
NEJM (March 23, 2020)

  • The rapidly growing imbalance between supply and demand for medical resources in many countries presents an inherently normative question: How can medical resources be allocated fairly during a COVID-19 pandemic?
  • The authors make six specific recommendations for allocating medical resources in the COVID-19 pandemic: maximize benefits; prioritize health workers; do not allocate on a first-come, first-served basis; be responsive to evidence; recognize research participation; and apply the same principles to all COVID-19 and non–COVID-19 patients.

Critical Care Utilization for the COVID-19 Outbreak in Lombardy, Italy: Early Experience and Forecast During an Emergency Response
JAMA (March 13, 2020)

  • Within 24 hours, the number of reported positive cases in Codogno Hospital (Lodi, Lombardy, Italy) increased from 1 to 36.
  • The recognition that this outbreak likely occurred via community spread suggested that a large number of COVID-19–positive patients were already present in the region.
  • This experience would suggest that only an ICU network can provide the initial immediate surge response to allow every patient in need for an ICU bed to receive one.
  • Health-care systems not organized in collaborative emergency networks should work toward one now.

Science

Probable Pangolin Origin of SARS-CoV-2 Associated with the COVID-19 Outbreak
Current Biology (April 6, 2020)

  • Since it is vital to explore potential intermediate hosts of SARS-CoV-2 to control COVID-19 spread, the authors reinvestigated published data from pangolin lung samples from which SARS-CoV-like CoVs were detected.
  • They found genomic and evolutionary evidence of the occurrence of a SARS-CoV-2-like CoV (named Pangolin-CoV) in dead Malayan pangolins.
  • Pangolin-CoV is 91.02% identical to SARS-CoV-2 at the whole-genome level and is the second closest relative of SARS-CoV-2behind RaTG13d. Five key amino acids are consistent between Pangolin-CoV and SARS-CoV-2d.
  • This study suggests that pangolin species are a natural reservoir of SARS-CoV-2-like CoVs. This finding might help to find the intermediate host of SARS-CoV-2 for blocking a global coronavirus pandemic.

SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor
Cell (March 5, 2020)

  • In this study the authors demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming.
  • A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option.
  • The results reveal important commonalities between SARS-CoV-2 and SARS-CoV infection and identify a potential target for antiviral intervention.
  • Although confirmation with infectious virus is pending, the results indicate that neutralizing antibody responses raised against SARS-S could offer some protection against SARS-CoV-2 infection, which may have implications for outbreak control.