medicina preventiva

#Pathophysiology, Transmission, Diagnosis, and Treatment of #Coronavirus Disease 2019 (COVID-19)A Review W. Joost Wiersin

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Importance  The coronavirus disease 2019 (COVID-19) pandemic, due to the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a worldwide sudden and substantial increase in hospitalizations for pneumonia with multiorgan disease. This review discusses current evidence regarding the pathophysiology, transmission, diagnosis, and management of COVID-19.

Observations  SARS-CoV-2 is spread primarily via respiratory droplets during close face-to-face contact. Infection can be spread by asymptomatic, presymptomatic, and symptomatic carriers. The average time from exposure to symptom onset is 5 days, and 97.5% of people who develop symptoms do so within 11.5 days. The most common symptoms are fever, dry cough, and shortness of breath. Radiographic and laboratory abnormalities, such as lymphopenia and elevated lactate dehydrogenase, are common, but nonspecific. Diagnosis is made by detection of SARS-CoV-2 via reverse transcription polymerase chain reaction testing, although false-negative test results may occur in up to 20% to 67% of patients; however, this is dependent on the quality and timing of testing. Manifestations of COVID-19 include asymptomatic carriers and fulminant disease characterized by sepsis and acute respiratory failure. Approximately 5% of patients with COVID-19, and 20% of those hospitalized, experience severe symptoms necessitating intensive care. More than 75% of patients hospitalized with COVID-19 require supplemental oxygen. Treatment for individuals with COVID-19 includes best practices for supportive management of acute hypoxic respiratory failure. Emerging data indicate that dexamethasone therapy reduces 28-day mortality in patients requiring supplemental oxygen compared with usual care (21.6% vs 24.6%; age-adjusted rate ratio, 0.83 [95% CI, 0.74-0.92]) and that remdesivir improves time to recovery (hospital discharge or no supplemental oxygen requirement) from 15 to 11 days. In a randomized trial of 103 patients with COVID-19, convalescent plasma did not shorten time to recovery. Ongoing trials are testing antiviral therapies, immune modulators, and anticoagulants. The case-fatality rate for COVID-19 varies markedly by age, ranging from 0.3 deaths per 1000 cases among patients aged 5 to 17 years to 304.9 deaths per 1000 cases among patients aged 85 years or older in the US. Among patients hospitalized in the intensive care unit, the case fatality is up to 40%. At least 120 SARS-CoV-2 vaccines are under development. Until an effective vaccine is available, the primary methods to reduce spread are face masks, social distancing, and contact tracing. Monoclonal antibodies and hyperimmune globulin may provide additional preventive strategies.

Conclusions and Relevance  As of July 1, 2020, more than 10 million people worldwide had been infected with SARS-CoV-2. Many aspects of transmission, infection, and treatment remain unclear. Advances in prevention and effective management of COVID-19 will require basic and clinical investigation and public health and clinical interventions.

 

Introduction

 

The coronavirus disease 2019 (COVID-19) pandemic has caused a sudden significant increase in hospitalizations for pneumonia with multiorgan disease. COVID-19 is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 infection may be asymptomatic or it may cause a wide spectrum of symptoms, such as mild symptoms of upper respiratory tract infection and life-threatening sepsis. COVID-19 first emerged in December 2019, when a cluster of patients with pneumonia of unknown cause was recognized in Wuhan, China. As of July 1, 2020, SARS-CoV-2 has affected more than 200 countries, resulting in more than 10 million identified cases with 508 000 confirmed deaths (Figure 1). This review summarizes current evidence regarding pathophysiology, transmission, diagnosis, and management of COVID-19.

 

Methods

 

We searched PubMed, LitCovid, and MedRxiv using the search terms coronavirussevere acute respiratory syndrome coronavirus 22019-nCoVSARS-CoV-2SARS-CoVMERS-CoV, and COVID-19 for studies published from January 1, 2002, to June 15, 2020, and manually searched the references of select articles for additional relevant articles. Ongoing or completed clinical trials were identified using the disease search term coronavirus infection on ClinicalTrials.gov, the Chinese Clinical Trial Registry, and the International Clinical Trials Registry Platform. We selected articles relevant to a general medicine readership, prioritizing randomized clinical trials, systematic reviews, and clinical practice guidelines.

 

Observations

 

Pathophysiology

 

Coronaviruses are large, enveloped, single-stranded RNA viruses found in humans and other mammals, such as dogs, cats, chicken, cattle, pigs, and birds. Coronaviruses cause respiratory, gastrointestinal, and neurological disease. The most common coronaviruses in clinical practice are 229E, OC43, NL63, and HKU1, which typically cause common cold symptoms in immunocompetent individuals. SARS-CoV-2 is the third coronavirus that has caused severe disease in humans to spread globally in the past 2 decades.1 The first coronavirus that caused severe disease was severe acute respiratory syndrome (SARS), which was thought to originate in Foshan, China, and resulted in the 2002-2003 SARS-CoV pandemic.2 The second was the coronavirus-caused Middle East respiratory syndrome (MERS), which originated from the Arabian peninsula in 2012.3

 

SARS-CoV-2 has a diameter of 60 nm to 140 nm and distinctive spikes, ranging from 9 nm to 12 nm, giving the virions the appearance of a solar corona (Figure 2).4 Through genetic recombination and variation, coronaviruses can adapt to and infect new hosts. Bats are thought to be a natural reservoir for SARS-CoV-2, but it has been suggested that humans became infected with SARS-CoV-2 via an intermediate host, such as the pangolin.5,6

 

The Host Defense Against SARS-CoV-2

 

Early in infection, SARS-CoV-2 targets cells, such as nasal and bronchial epithelial cells and pneumocytes, through the viral structural spike (S) protein that binds to the angiotensin-converting enzyme 2 (ACE2) receptor7 (Figure 2). The type 2 transmembrane serine protease (TMPRSS2), present in the host cell, promotes viral uptake by cleaving ACE2 and activating the SARS-CoV-2 S protein, which mediates coronavirus entry into host cells.7 ACE2 and TMPRSS2 are expressed in host target cells, particularly alveolar epithelial type II cells.8,9 Similar to other respiratory viral diseases, such as influenza, profound lymphopenia may occur in individuals with COVID-19 when SARS-CoV-2 infects and kills T lymphocyte cells. In addition, the viral inflammatory response, consisting of both the innate and the adaptive immune response (comprising humoral and cell-mediated immunity), impairs lymphopoiesis and increases lymphocyte apoptosis. Although upregulation of ACE2 receptors from ACE inhibitor and angiotensin receptor blocker medications has been hypothesized to increase susceptibility to SARS-CoV-2 infection, large observational cohorts have not found an association between these medications and risk of infection or hospital mortality due to COVID-19.10,11 For example, in a study 4480 patients with COVID-19 from Denmark, previous treatment with ACE inhibitors or angiotensin receptor blockers was not associated with mortality.11

 

In later stages of infection, when viral replication accelerates, epithelial-endothelial barrier integrity is compromised. In addition to epithelial cells, SARS-CoV-2 infects pulmonary capillary endothelial cells, accentuating the inflammatory response and triggering an influx of monocytes and neutrophils. Autopsy studies have shown diffuse thickening of the alveolar wall with mononuclear cells and macrophages infiltrating airspaces in addition to endothelialitis.12 Interstitial mononuclear inflammatory infiltrates and edema develop and appear as ground-glass opacities on computed tomographic imaging. Pulmonary edema filling the alveolar spaces with hyaline membrane formation follows, compatible with early-phase acute respiratory distress syndrome (ARDS).12 Bradykinin-dependent lung angioedema may contribute to disease.13 Collectively, endothelial barrier disruption, dysfunctional alveolar-capillary oxygen transmission, and impaired oxygen diffusion capacity are characteristic features of COVID-19.

 

In severe COVID-19, fulminant activation of coagulation and consumption of clotting factors occur.14,15 A report from Wuhan, China, indicated that 71% of 183 individuals who died of COVID-19 met criteria for diffuse intravascular coagulation.14 Inflamed lung tissues and pulmonary endothelial cells may result in microthrombi formation and contribute to the high incidence of thrombotic complications, such as deep venous thrombosis, pulmonary embolism, and thrombotic arterial complications (eg, limb ischemia, ischemic stroke, myocardial infarction) in critically ill patients.16 The development of viral sepsis, defined as life-threatening organ dysfunction caused by a dysregulated host response to infection, may further contribute to multiorgan failure.

 

Transmission of SARS-CoV-2 Infection

 

Epidemiologic data suggest that droplets expelled during face-to-face exposure during talking, coughing, or sneezing is the most common mode of transmission (Box 1). Prolonged exposure to an infected person (being within 6 feet for at least 15 minutes) and briefer exposures to individuals who are symptomatic (eg, coughing) are associated with higher risk for transmission, while brief exposures to asymptomatic contacts are less likely to result in transmission.25 Contact surface spread (touching a surface with virus on it) is another possible mode of transmission. Transmission may also occur via aerosols (smaller droplets that remain suspended in air), but it is unclear if this is a significant source of infection in humans outside of a laboratory setting.26,27 The existence of aerosols in physiological states (eg, coughing) or the detection of nucleic acid in the air does not mean that small airborne particles are infectious.28 Maternal COVID-19 is currently believed to be associated with low risk for vertical transmission. In most reported series, the mothers’ infection with SARS-CoV-2 occurred in the third trimester of pregnancy, with no maternal deaths and a favorable clinical course in the neonates.2931

Box 1.

Transmission, Symptoms, and Complications of Coronavirus Disease 2019 (COVID-19)

  • Transmission17 of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occurs primarily via respiratory droplets from face-to-face contact and, to a lesser degree, via contaminated surfaces. Aerosol spread may occur, but the role of aerosol spread in humans remains unclear. An estimated 48% to 62% of transmission may occur via presymptomatic carriers.

  • Common symptoms18 in hospitalized patients include fever (70%-90%), dry cough (60%-86%), shortness of breath (53%-80%), fatigue (38%), myalgias (15%-44%), nausea/vomiting or diarrhea (15%-39%), headache, weakness (25%), and rhinorrhea (7%). Anosmia or ageusia may be the sole presenting symptom in approximately 3% of individuals with COVID-19.

  • Common laboratory abnormalities19 among hospitalized patients include lymphopenia (83%), elevated inflammatory markers (eg, erythrocyte sedimentation rate, C-reactive protein, ferritin, tumor necrosis factor-α, IL-1, IL-6), and abnormal coagulation parameters (eg, prolonged prothrombin time, thrombocytopenia, elevated D-dimer [46% of patients], low fibrinogen).

  • Common radiographic findings of individuals with COVID-19 include bilateral, lower-lobe predominate infiltrates on chest radiographic imaging and bilateral, peripheral, lower-lobe ground-glass opacities and/or consolidation on chest computed tomographic imaging.

  • Common complications18,2024 among hospitalized patients with COVID-19 include pneumonia (75%); acute respiratory distress syndrome (15%); acute liver injury, characterized by elevations in aspartate transaminase, alanine transaminase, and bilirubin (19%); cardiac injury, including troponin elevation (7%-17%), acute heart failure, dysrhythmias, and myocarditis; prothrombotic coagulopathy resulting in venous and arterial thromboembolic events (10%-25%); acute kidney injury (9%); neurologic manifestations, including impaired consciousness (8%) and acute cerebrovascular disease (3%); and shock (6%).

  • Rare complications among critically ill patients with COVID-19 include cytokine storm and macrophage activation syndrome (ie, secondary hemophagocytic lymphohistiocytosis).

 

The clinical significance of SARS-CoV-2 transmission from inanimate surfaces is difficult to interpret without knowing the minimum dose of virus particles that can initiate infection. Viral load appears to persist at higher levels on impermeable surfaces, such as stainless steel and plastic, than permeable surfaces, such as cardboard.32 Virus has been identified on impermeable surfaces for up to 3 to 4 days after inoculation.32 Widespread viral contamination of hospital rooms has been documented.28 However, it is thought that the amount of virus detected on surfaces decays rapidly within 48 to 72 hours.32 Although the detection of virus on surfaces reinforces the potential for transmission via fomites (objects such as a doorknob, cutlery, or clothing that may be contaminated with SARS-CoV-2) and the need for adequate environmental hygiene, droplet spread via face-to-face contact remains the primary mode of transmission.

 

Viral load in the upper respiratory tract appears to peak around the time of symptom onset and viral shedding begins approximately 2 to 3 days prior to the onset of symptoms.33 Asymptomatic and presymptomatic carriers can transmit SARS-CoV-2.34,35 In Singapore, presymptomatic transmission has been described in clusters of patients with close contact (eg, through churchgoing or singing class) approximately 1 to 3 days before the source patient developed symptoms.34 Presymptomatic transmission is thought to be a major contributor to the spread of SARS-CoV-2. Modeling studies from China and Singapore estimated the percentage of infections transmitted from a presymptomatic individual as 48% to 62%.17 Pharyngeal shedding is high during the first week of infection at a time in which symptoms are still mild, which might explain the efficient transmission of SARS-CoV-2, because infected individuals can be infectious before they realize they are ill.36 Although studies have described rates of asymptomatic infection, ranging from 4% to 32%, it is unclear whether these reports represent truly asymptomatic infection by individuals who never develop symptoms, transmission by individuals with very mild symptoms, or transmission by individuals who are asymptomatic at the time of transmission but subsequently develop symptoms.3739 A systematic review on this topic suggested that true asymptomatic infection is probably uncommon.38

 

Although viral nucleic acid can be detectable in throat swabs for up to 6 weeks after the onset of illness, several studies suggest that viral cultures are generally negative for SARS-CoV-2 8 days after symptom onset.33,36,40 This is supported by epidemiological studies that have shown that transmission did not occur to contacts whose exposure to the index case started more than 5 days after the onset of symptoms in the index case.41 This suggests that individuals can be released from isolation based on clinical improvement. The Centers for Disease Control and Prevention recommend isolating for at least 10 days after symptom onset and 3 days after improvement of symptoms.42 However, there remains uncertainty about whether serial testing is required for specific subgroups, such as immunosuppressed patients or critically ill patients for whom symptom resolution may be delayed or older adults residing in short- or long-term care facilities.

 

Clinical Presentation

 

The mean (interquartile range) incubation period (the time from exposure to symptom onset) for COVID-19 is approximately 5 (2-7) days.43,44 Approximately 97.5% of individuals who develop symptoms will do so within 11.5 days of infection.43 The median (interquartile range) interval from symptom onset to hospital admission is 7 (3-9) days.45 The median age of hospitalized patients varies between 47 and 73 years, with most cohorts having a male preponderance of approximately 60%.44,46,47 Among patients hospitalized with COVID-19, 74% to 86% are aged at least 50 years.45,47

 

COVID-19 has various clinical manifestations (Box 1 and Box 2). In a study of 44 672 patients with COVID-19 in China, 81% of patients had mild manifestations, 14% had severe manifestations, and 5% had critical manifestations (defined by respiratory failure, septic shock, and/or multiple organ dysfunction).48 A study of 20 133 individuals hospitalized with COVID-19 in the UK reported that 17.1% were admitted to high-dependency or intensive care units (ICUs).47

Box 2.

Commonly Asked Questions About Coronavirus Disease 2019 (COVID-19)

  • How is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) most commonly transmitted?

    • SARS-CoV-2 is most commonly spread via respiratory droplets (eg, from coughing, sneezing, shouting) during face-to-face exposure or by surface contamination.

  • What are the most common symptoms of COVID-19?

    • The 3 most common symptoms are fever, cough, and shortness of breath. Additional symptoms include weakness, fatigue, nausea, vomiting, diarrhea, changes to taste and smell.

  • How is the diagnosis made?

    • Diagnosis of COVID-19 is typically made by polymerase chain reaction testing of a nasopharyngeal swab. However, given the possibility of false-negative test results, clinical, laboratory, and imaging findings may also be used to make a presumptive diagnosis for individuals for whom there is a high index of clinical suspicion of infection.

  • What are current evidence-based treatments for individuals with COVID-19?

    • Supportive care, including supplemental oxygen, is the main treatment for most patients. Recent trials indicate that dexamethasone decreases mortality (subgroup analysis suggests benefit is limited to patients who require supplemental oxygen and who have symptoms for >7 d) and remdesivir improves time to recovery (subgroup analysis suggests benefit is limited to patients not receiving mechanical ventilation).

  • What percentage of people are asymptomatic carriers, and how important are they in transmitting the disease?

    • True asymptomatic infection is believed to be uncommon. The average time from exposure to symptoms onset is 5 days, and up to 62% of transmission may occur prior to the onset of symptoms.

  • Are masks effective at preventing spread?

    • Yes. Face masks reduce the spread of viral respiratory infection. N95 respirators and surgical masks both provide substantial protection (compared with no mask), and surgical masks provide greater protection than cloth masks. However, physical distancing is also associated with substantial reduction of viral transmission, with greater distances providing greater protection. Additional measures such as hand and environmental disinfection are also important.

 

Although only approximately 25% of infected patients have comorbidities, 60% to 90% of hospitalized infected patients have comorbidities.4549 The most common comorbidities in hospitalized patients include hypertension (present in 48%-57% of patients), diabetes (17%-34%), cardiovascular disease (21%-28%), chronic pulmonary disease (4%-10%), chronic kidney disease (3%-13%), malignancy (6%-8%), and chronic liver disease (<5%).45,46,49

 

The most common symptoms in hospitalized patients are fever (up to 90% of patients), dry cough (60%-86%), shortness of breath (53%-80%), fatigue (38%), nausea/vomiting or diarrhea (15%-39%), and myalgia (15%-44%).18,4447,49,50 Patients can also present with nonclassical symptoms, such as isolated gastrointestinal symptoms.18 Olfactory and/or gustatory dysfunctions have been reported in 64% to 80% of patients.5153 Anosmia or ageusia may be the sole presenting symptom in approximately 3% of patients.53

 

Complications of COVID-19 include impaired function of the heart, brain, lung, liver, kidney, and coagulation system. COVID-19 can lead to myocarditis, cardiomyopathy, ventricular arrhythmias, and hemodynamic instability.20,54 Acute cerebrovascular disease and encephalitis are observed with severe illness (in up to 8% of patients).21,52 Venous and arterial thromboembolic events occur in 10% to 25% in hospitalized patients with COVID-19.19,22 In the ICU, venous and arterial thromboembolic events may occur in up to 31% to 59% of patients with COVID-19.16,22

 

Approximately 17% to 35% of hospitalized patients with COVID-19 are treated in an ICU, most commonly due to hypoxemic respiratory failure. Among patients in the ICU with COVID-19, 29% to 91% require invasive mechanical ventilation.47,49,55,56 In addition to respiratory failure, hospitalized patients may develop acute kidney injury (9%), liver dysfunction (19%), bleeding and coagulation dysfunction (10%-25%), and septic shock (6%).18,19,23,49,56

 

Approximately 2% to 5% of individuals with laboratory-confirmed COVID-19 are younger than 18 years, with a median age of 11 years. Children with COVID-19 have milder symptoms that are predominantly limited to the upper respiratory tract, and rarely require hospitalization. It is unclear why children are less susceptible to COVID-19. Potential explanations include that children have less robust immune responses (ie, no cytokine storm), partial immunity from other viral exposures, and lower rates of exposure to SARS-CoV-2. Although most pediatric cases are mild, a small percentage (<7%) of children admitted to the hospital for COVID-19 develop severe disease requiring mechanical ventilation.57 A rare multisystem inflammatory syndrome similar to Kawasaki disease has recently been described in children in Europe and North America with SARS-CoV-2 infection.58,59 This multisystem inflammatory syndrome in children is uncommon (2 in 100 000 persons aged <21 years).60

 

Assessment and Diagnosis

 

Diagnosis of COVID-19 is typically made using polymerase chain reaction testing via nasal swab (Box 2). However, because of false-negative test result rates of SARS-CoV-2 PCR testing of nasal swabs, clinical, laboratory, and imaging findings may also be used to make a presumptive diagnosis.

 

Diagnostic Testing: Polymerase Chain Reaction and Serology

 

Reverse transcription polymerase chain reaction–based SARS-CoV-2 RNA detection from respiratory samples (eg, nasopharynx) is the standard for diagnosis. However, the sensitivity of testing varies with timing of testing relative to exposure. One modeling study estimated sensitivity at 33% 4 days after exposure, 62% on the day of symptom onset, and 80% 3 days after symptom onset.6163 Factors contributing to false-negative test results include the adequacy of the specimen collection technique, time from exposure, and specimen source. Lower respiratory samples, such as bronchoalveolar lavage fluid, are more sensitive than upper respiratory samples. Among 1070 specimens collected from 205 patients with COVID-19 in China, bronchoalveolar lavage fluid specimens had the highest positive rates of SARS-CoV-2 PCR testing results (93%), followed by sputum (72%), nasal swabs (63%), and pharyngeal swabs (32%).61 SARS-CoV-2 can also be detected in feces, but not in urine.61 Saliva may be an alternative specimen source that requires less personal protective equipment and fewer swabs, but requires further validation.64

 

Several serological tests can also aid in the diagnosis and measurement of responses to novel vaccines.62,65,66 However, the presence of antibodies may not confer immunity because not all antibodies produced in response to infection are neutralizing. Whether and how frequently second infections with SARS-CoV-2 occur remain unknown. Whether presence of antibody changes susceptibility to subsequent infection or how long antibody protection lasts are unknown. IgM antibodies are detectable within 5 days of infection, with higher IgM levels during weeks 2 to 3 of illness, while an IgG response is first seen approximately 14 days after symptom onset.62,65 Higher antibody titers occur with more severe disease.66 Available serological assays include point-of-care assays and high throughput enzyme immunoassays. However, test performance, accuracy, and validity are variable.67

 

Laboratory Findings

 

A systematic review of 19 studies of 2874 patients who were mostly from China (mean age, 52 years), of whom 88% were hospitalized, reported the typical range of laboratory abnormalities seen in COVID-19, including elevated serum C-reactive protein (increased in >60% of patients), lactate dehydrogenase (increased in approximately 50%-60%), alanine aminotransferase (elevated in approximately 25%), and aspartate aminotransferase (approximately 33%).24 Approximately 75% of patients had low albumin.24 The most common hematological abnormality is lymphopenia (absolute lymphocyte count <1.0 × 109/L), which is present in up to 83% of hospitalized patients with COVID-19.44,50 In conjunction with coagulopathy, modest prolongation of prothrombin times (prolonged in >5% of patients), mild thrombocytopenia (present in approximately 30% of patients) and elevated D-dimer values (present in 43%-60% of patients) are common.14,15,19,44,68 However, most of these laboratory characteristics are nonspecific and are common in pneumonia. More severe laboratory abnormalities have been associated with more severe infection.44,50,69 D-dimer and, to a lesser extent, lymphopenia seem to have the largest prognostic associations.69

 

Imaging

 

The characteristic chest computed tomographic imaging abnormalities for COVID-19 are diffuse, peripheral ground-glass opacities (Figure 3).70 Ground-glass opacities have ill-defined margins, air bronchograms, smooth or irregular interlobular or septal thickening, and thickening of the adjacent pleura.70 Early in the disease, chest computed tomographic imaging findings in approximately 15% of individuals and chest radiograph findings in approximately 40% of individuals can be normal.44 Rapid evolution of abnormalities can occur in the first 2 weeks after symptom onset, after which they subside gradually.70,71

 

Chest computed tomographic imaging findings are nonspecific and overlap with other infections, so the diagnostic value of chest computed tomographic imaging for COVID-19 is limited. Some patients admitted to the hospital with polymerase chain reaction testing–confirmed SARS-CoV-2 infection have normal computed tomographic imaging findings, while abnormal chest computed tomographic imaging findings compatible with COVID-19 occur days before detection of SARS-CoV-2 RNA in other patients.70,71

 

Treatment

 

Supportive Care and Respiratory Support

 

Currently, best practices for supportive management of acute hypoxic respiratory failure and ARDS should be followed.7274 Evidence-based guideline initiatives have been established by many countries and professional societies,7274 including guidelines that are updated regularly by the National Institutes of Health.74

 

More than 75% of patients hospitalized with COVID-19 require supplemental oxygen therapy. For patients who are unresponsive to conventional oxygen therapy, heated high-flow nasal canula oxygen may be administered.72 For patients requiring invasive mechanical ventilation, lung-protective ventilation with low tidal volumes (4-8 mL/kg, predicted body weight) and plateau pressure less than 30 mg Hg is recommended.72 Additionally, prone positioning, a higher positive end-expiratory pressure strategy, and short-term neuromuscular blockade with cisatracurium or other muscle relaxants may facilitate oxygenation. Although some patients with COVID-19–related respiratory failure have high lung compliance,75 they are still likely to benefit from lung-protective ventilation.76 Cohorts of patients with ARDS have displayed similar heterogeneity in lung compliance, and even patients with greater compliance have shown benefit from lower tidal volume strategies.76

 

The threshold for intubation in COVID-19–related respiratory failure is controversial, because many patients have normal work of breathing but severe hypoxemia.77 “Earlier” intubation allows time for a more controlled intubation process, which is important given the logistical challenges of moving patients to an airborne isolation room and donning personal protective equipment prior to intubation. However, hypoxemia in the absence of respiratory distress is well tolerated, and patients may do well without mechanical ventilation. Earlier intubation thresholds may result in treating some patients with mechanical ventilation unnecessarily and exposing them to additional complications. Currently, insufficient evidence exists to make recommendations regarding earlier vs later intubation.

 

In observational studies, approximately 8% of hospitalized patients with COVID-19 experience a bacterial or fungal co-infection, but up to 72% are treated with broad-spectrum antibiotics.78 Awaiting further data, it may be prudent to withhold antibacterial drugs in patients with COVID-19 and reserve them for those who present with radiological findings and/or inflammatory markers compatible with co-infection or who are immunocompromised and/or critically ill.72

 

Targeting the Virus and the Host Response

 

The following classes of drugs are being evaluated or developed for the management of COVID-19: antivirals (eg, remdesivir, favipiravir), antibodies (eg, convalescent plasma, hyperimmune immunoglobulins), anti-inflammatory agents (dexamethasone, statins), targeted immunomodulatory therapies (eg, tocilizumab, sarilumab, anakinra, ruxolitinib), anticoagulants (eg, heparin), and antifibrotics (eg, tyrosine kinase inhibitors). It is likely that different treatment modalities might have different efficacies at different stages of illness and in different manifestations of disease. Viral inhibition would be expected to be most effective early in infection, while, in hospitalized patients, immunomodulatory agents may be useful to prevent disease progression and anticoagulants may be useful to prevent thromboembolic complications.

 

More than 200 trials of chloroquine/hydroxychloroquine, compounds that inhibit viral entry and endocytosis of SARS-CoV-2 in vitro and may have beneficial immunomodulatory effects in vivo,79,80 have been initiated, but early data from clinical trials in hospitalized patients with COVID-19 have not demonstrated clear benefit.8183 A clinical trial of 150 patients in China admitted to the hospital for mild to moderate COVID-19 did not find an effect on negative conversion of SARS-CoV-2 by 28 days (the main outcome measure) when compared with standard of care alone.83 Two retrospective studies found no effect of hydroxychloroquine on risk of intubation or mortality among patients hospitalized for COVID-19.84,85 One of these retrospective multicenter cohort studies compared in-hospital mortality between those treated with hydroxychloroquine plus azithromycin (735 patients), hydroxychloroquine alone (271 patients), azithromycin alone (211 patients), and neither drug (221 patients), but reported no differences across the groups.84 Adverse effects are common, most notably QT prolongation with an increased risk of cardiac complications in an already vulnerable population.82,84 These findings do not support off-label use of (hydroxy)chloroquine either with or without the coadministration of azithromycin. Randomized clinical trials are ongoing and should provide more guidance.

 

Most antiviral drugs undergoing clinical testing in patients with COVID-19 are repurposed antiviral agents originally developed against influenza, HIV, Ebola, or SARS/MERS.79,86 Use of the protease inhibitor lopinavir-ritonavir, which disrupts viral replication in vitro, did not show benefit when compared with standard care in a randomized, controlled, open-label trial of 199 hospitalized adult patients with severe COVID-19.87 Among the RNA-dependent RNA polymerase inhibitors, which halt SARS-CoV-2 replication, being evaluated, including ribavirin, favipiravir, and remdesivir, the latter seems to be the most promising.79,88 The first preliminary results of a double-blind, randomized, placebo-controlled trial of 1063 adults hospitalized with COVID-19 and evidence of lower respiratory tract involvement who were randomly assigned to receive intravenous remdesivir or placebo for up to 10 days demonstrated that patients randomized to receive remdesivir had a shorter time to recovery than patients in the placebo group (11 vs 15 days).88 A separate randomized, open-label trial among 397 hospitalized patients with COVID-19 who did not require mechanical ventilation reported that 5 days of treatment with remdesivir was not different than 10 days in terms of clinical status on day 14.89 The effect of remdesivir on survival remains unknown.

 

Treatment with plasma obtained from patients who have recovered from viral infections was first reported during the 1918 flu pandemic. A first report of 5 critically ill patients with COVID-19 treated with convalescent plasma containing neutralizing antibody showed improvement in clinical status among all participants, defined as a combination of changes of body temperature, Sequential Organ Failure Assessment score, partial pressure of oxygen/fraction of inspired oxygen, viral load, serum antibody titer, routine blood biochemical index, ARDS, and ventilatory and extracorporeal membrane oxygenation supports before and after convalescent plasma transfusion status.90 However, a subsequent multicenter, open-label, randomized clinical trial of 103 patients in China with severe COVID-19 found no statistical difference in time to clinical improvement within 28 days among patients randomized to receive convalescent plasma vs standard treatment alone (51.9% vs 43.1%).91 However, the trial was stopped early because of slowing enrollment, which limited the power to detect a clinically important difference. Alternative approaches being studied include the use of convalescent plasma-derived hyperimmune globulin and monoclonal antibodies targeting SARS-CoV-2.92,93

 

Alternative therapeutic strategies consist of modulating the inflammatory response in patients with COVID-19. Monoclonal antibodies directed against key inflammatory mediators, such as interferon gamma, interleukin 1, interleukin 6, and complement factor 5a, all target the overwhelming inflammatory response following SARS-CoV-2 infection with the goal of preventing organ damage.79,86,94 Of these, the interleukin 6 inhibitors tocilizumab and sarilumab are best studied, with more than a dozen randomized clinical trials underway.94 Tyrosine kinase inhibitors, such as imatinib, are studied for their potential to prevent pulmonary vascular leakage in individuals with COVID-19.

 

Studies of corticosteroids for viral pneumonia and ARDS have yielded mixed results.72,73 However, the Randomized Evaluation of COVID-19 Therapy (RECOVERY) trial, which randomized 2104 patients with COVID-19 to receive 6 mg daily of dexamethasone for up to 10 days and 4321 to receive usual care, found that dexamethasone reduced 28-day all-cause mortality (21.6% vs 24.6%; age-adjusted rate ratio, 0.83 [95% CI, 0.74-0.92]; P < .001).95 The benefit was greatest in patients with symptoms for more than 7 days and patients who required mechanical ventilation. By contrast, there was no benefit (and possibility for harm) among patients with shorter symptom duration and no supplemental oxygen requirement. A retrospective cohort study of 201 patients in Wuhan, China, with confirmed COVID-19 pneumonia and ARDS reported that treatment with methylprednisolone was associated with reduced risk of death (hazard ratio, 0.38 [95% CI, 0.20-0.72]).69

 

Thromboembolic prophylaxis with subcutaneous low molecular weight heparin is recommended for all hospitalized patients with COVID-19.15,19 Studies are ongoing to assess whether certain patients (ie, those with elevated D-dimer) benefit from therapeutic anticoagulation.

 

Disparities

 

A disproportionate percentage of COVID-19 hospitalizations and deaths occurs in lower-income and minority populations.45,96,97 In a report by the Centers for Disease Control and Prevention of 580 hospitalized patients for whom race data were available, 33% were Black and 45% were White, while 18% of residents in the surrounding community were Black and 59% were White.45 The disproportionate prevalence of COVID-19 among Black patients was separately reported in a retrospective cohort study of 3626 patients with COVID-19 from Louisiana, in which 77% of patients hospitalized with COVID-19 and 71% of patients who died of COVID-19 were Black, but Black individuals comprised only 31% of the area population.97,98 This disproportionate burden may be a reflection of disparities in housing, transportation, employment, and health. Minority populations are more likely to live in densely populated communities or housing, depend on public transportation, or work in jobs for which telework was not possible (eg, bus driver, food service worker). Black individuals also have a higher prevalence of chronic health conditions than White individuals.98,99

 

Prognosis

 

Overall hospital mortality from COVID-19 is approximately 15% to 20%, but up to 40% among patients requiring ICU admission. However, mortality rates vary across cohorts, reflecting differences in the completeness of testing and case identification, variable thresholds for hospitalization, and differences in outcomes. Hospital mortality ranges from less than 5% among patients younger than 40 years to 35% for patients aged 70 to 79 years and greater than 60% for patients aged 80 to 89 years.46 Estimated overall death rates by age group per 1000 confirmed cases are provided in the Table. Because not all people who die during the pandemic are tested for COVID-19, actual numbers of deaths from COVID-19 are higher than reported numbers.

 

Although long-term outcomes from COVID-19 are currently unknown, patients with severe illness are likely to suffer substantial sequelae. Survival from sepsis is associated with increased risk for mortality for at least 2 years, new physical disability, new cognitive impairment, and increased vulnerability to recurrent infection and further health deterioration. Similar sequalae are likely to be seen in survivors of severe COVID-19.100

 

Prevention and Vaccine Development

 

COVID-19 is a potentially preventable disease. The relationship between the intensity of public health action and the control of transmission is clear from the epidemiology of infection around the world.25,101,102 However, because most countries have implemented multiple infection control measures, it is difficult to determine the relative benefit of each.103,104 This question is increasingly important because continued interventions will be required until effective vaccines or treatments become available. In general, these interventions can be divided into those consisting of personal actions (eg, physical distancing, personal hygiene, and use of protective equipment), case and contact identification (eg, test-trace-track-isolate, reactive school or workplace closure), regulatory actions (eg, governmental limits on sizes of gatherings or business capacity; stay-at-home orders; proactive school, workplace, and public transport closure or restriction; cordon sanitaire or internal border closures), and international border measures (eg, border closure or enforced quarantine). A key priority is to identify the combination of measures that minimizes societal and economic disruption while adequately controlling infection. Optimal measures may vary between countries based on resource limitations, geography (eg, island nations and international border measures), population, and political factors (eg, health literacy, trust in government, cultural and linguistic diversity).

 

The evidence underlying these public health interventions has not changed since the 1918 flu pandemic.105 Mathematical modeling studies and empirical evidence support that public health interventions, including home quarantine after infection, restricting mass gatherings, travel restrictions, and social distancing, are associated with reduced rates of transmission.101,102,106 Risk of resurgence follows when these interventions are lifted.

 

A human vaccine is currently not available for SARS-CoV-2, but approximately 120 candidates are under development. Approaches include the use of nucleic acids (DNA or RNA), inactivated or live attenuated virus, viral vectors, and recombinant proteins or virus particles.107,108 Challenges to developing an effective vaccine consist of technical barriers (eg, whether S or receptor-binding domain proteins provoke more protective antibodies, prior exposure to adenovirus serotype 5 [which impairs immunogenicity in the viral vector vaccine], need for adjuvant), feasibility of large-scale production and regulation (eg, ensuring safety and effectiveness), and legal barriers (eg, technology transfer and licensure agreements). The SARS-CoV-2 S protein appears to be a promising immunogen for protection, but whether targeting the full-length protein or only the receptor-binding domain is sufficient to prevent transmission remains unclear.108 Other considerations include the potential duration of immunity and thus the number of vaccine doses needed to confer immunity.62,108 More than a dozen candidate SARS-CoV-2 vaccines are currently being tested in phase 1-3 trials.

 

Other approaches to prevention are likely to emerge in the coming months, including monoclonal antibodies, hyperimmune globulin, and convalscent titer. If proved effective, these approaches could be used in high-risk individuals, including health care workers, other essential workers, and older adults (particularly those in nursing homes or long-term care facilities).

 

Limitations

 

This review has several limitations. First, information regarding SARS CoV-2 is limited. Second, information provided here is based on current evidence, but may be modified as more information becomes available. Third, few randomized trials have been published to guide management of COVID-19.

 

Conclusions

 

As of July 1, 2020, more than 10 million people worldwide had been infected with SARS-CoV-2. Many aspects of transmission, infection, and treatment remain unclear. Advances in prevention and effective management of COVID-19 will require basic and clinical investigation and public health and clinical interventions.

 

Section Editors: Edward Livingston, MD, Deputy Editor, and Mary McGrae McDermott, MD, Deputy Editor.

 

Submissions: We encourage authors to submit papers for consideration as a Review. Please contact Edward Livingston, MD, at Edward.livingston@jamanetwork.org or Mary McGrae McDermott, MD, at mdm608@northwestern.edu.

 

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Article Information

Accepted for Publication: June 30, 2020.

Corresponding Author: W. Joost Wiersinga, MD, PhD, Division of Infectious Diseases, Department of Medicine, Amsterdam UMC, location AMC, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands (w.j.wiersinga@amsterdamumc.nl).

Published Online: July 10, 2020. doi:10.1001/jama.2020.12839

Conflict of Interest Disclosures: Dr Wiersinga is supported by the Netherlands Organisation of Scientific Research outside the submitted work. Dr Prescott reported receiving grants from the US Agency for Healthcare Research and Quality (HCP by R01 HS026725), the National Institutes of Health/National Institute of General Medical Sciences, and the US Department of Veterans Affairs outside the submitted work, being the sepsis physician lead for the Hospital Medicine Safety Continuous Quality Initiative funded by BlueCross/BlueShield of Michigan, and serving on the steering committee for MI-COVID-19, a Michigan statewide registry to improve care for patients with COVID-19 in Michigan. Dr Rhodes reported being the co-chair of the Surviving Sepsis Campaign. Dr Cheng reported being a member of Australian government advisory committees, including those involved in COVID-19. No other disclosures were reported.

Disclaimer: This article does not represent the views of the US Department of Veterans Affairs or the US government. This material is the result of work supported with resources and use of facilities at the Ann Arbor VA Medical Center. The opinions in this article do not necessarily represent those of the Australian government or advisory committees.

 

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#Face Mask Type Matters When #Sterilizing, Study Finds

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When sterilizing face masks, the type of face mask and the method of sterilization have a bearing on subsequent filtration efficiency, according to researchers. The greatest reduction in filtration efficiency after sterilization occurred with surgical face masks.

With plasma vapor hydrogen peroxide (H2O2) sterilization, filtration efficiency of N95 and KN95 masks was maintained at more than 95%, but for surgical face masks, filtration efficiency was reduced to less than 95%. With chlorine dioxide (ClO2) sterilization, on the other hand, filtration efficiency was maintained at above 95% for N95 masks, but for KN95 and surgical face masks, filtration efficiency was reduced to less than 80%.

In a research letter published online June 15 in JAMA Network Open, researchers from the University of Oklahoma Health Sciences Center, Oklahoma City, report the results of a study of the two sterilization techniques on the pressure drop and filtration efficiency of N95, KN95, and surgical face masks.

“The H2O2 treatment showed a small effect on the overall filtration efficiency of the tested masks, but the ClO2 treatment showed marked reduction in the overall filtration efficiency of the KN95s and surgical face masks. All pressure drop changes were within the acceptable range,” the researchers write.

The study did not evaluate the effect of repeated sterilizations on face masks.

Five masks of each type were sterilized with either H2Oor CIO2. Masks were then placed in a test chamber, and a salt aerosol was nebulized to assess both upstream and downstream filtration as well as pressure drop. The researchers used a mobility particle sizer to measure particle number concentration from 16.8 nm to 514 nm. An acceptable pressure drop was defined as a drop of less than 1.38 inches of water (35 mm) for inhalation.

Although pressure drop changes were within the acceptable range for all three mask types following sterlization with either method, H2Osterilization yielded the least reduction in filtration efficacy in all cases. After sterilization with H2O2, filtration efficiencies were 96.6%, 97.1%, and 91.6% for the N95s, KN95s, and the surgical face masks, respectively. In contrast, filtration efficiencies after ClO2 sterilization were 95.1%, 76.2%, and 77.9%, respectively.

The researchers note that although overall filtration efficiency was maintained with ClOsterilization, there was a significant drop in efficiency with respect to particles of approximately 300 nm (0.3 microns) in size. For particles of that size, mean filtration efficiency decreased to 86.2% for N95s, 40.8% for KN95s, and 47.1% for surgical face masks.

The testing described in the report is “quite affordable at $350 per mask type, so it is hard to imagine any healthcare provider cannot set aside a small budget to conduct such an important test,” author Evan Floyd, PhD, told Medscape Medical News.

Given the high demand for effective face masks and the current risk for counterfeit products, Floyd suggested that individual facilities test all masks intended for use by healthcare workers before and after sterilization procedures.

“However, if for some reason testing is not an option, we would recommend sticking to established brands and suppliers, perhaps reach out to your state health department or a local representative of the strategic stockpile of PPE,” he noted.

The authors acknowledge that further studies using a larger sample size and a greater variety of masks, as well as studies to evaluate different sterilization techniques, are required. Further, “measuring the respirator’s filtration efficiency by aerosol size instead of only measuring the overall filtration efficiency” should also be considered. Such an approach would enable researchers to evaluate the degree to which masks protect against specific infectious agents.

 

JAMA Netw Open. Published online June 15, 2020. Full text

#Covid-19: un fármaco “barato y de fácil acceso” reduce el riesgo de muerte en pacientes con #ventilación asistida

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Se trata de la dexametasona, un tratamiento a base de esteroides que, según los investigadores, es “un gran avance”

Este fármaco reduciría en un tercio el riesgo de muerte de aquellos pacientes que se encuentran enchufados a ventiladores.
Este fármaco reduciría en un tercio el riesgo de muerte de aquellos pacientes que se encuentran enchufados a ventiladores.

Un fármaco barato y de fácil acceso en todo el mundo llamado dexametasona puede ayudar a salvar vidas de pacientes que se encuentran graves a causa del coronavirus, según un estudio de la Universidad de Oxford divulgado este martes.

El equipo investigador cree que el tratamiento a base de dosis bajas de esteroides supone un gran avance en la lucha contra la Covid-19, al reducir el riesgo de muerte en un tercio de aquellos pacientes que se encuentran enchufados a ventiladores.

En cuanto a los que precisan de una abordaje de la enfermedad con oxígeno, el citado fármaco reduce las muertes en una quinta parte, de acuerdo con estos hallazgos.

Esta medicina es una de las que se están empleando en el considerado mayor ensayo clínico del mundo, donde se experimenta con tratamientos existentes para otros males con el objetivo de ver si también funcionan para combatir el coronavirus.

5.000 vidas

Según estimaciones de los investigadores, si ese fármaco hubiera estado disponible en este país desde el principio de la pandemia, se habrían podido salvar hasta 5.000 vidas.

Además, debido a su bajo coste, consideran que podría ser muy beneficioso en los países pobres que afrontan grandes números de enfermos de COVID-19.

Aproximadamente 19 de cada 20 pacientes que se infectan de coronavirus mejoran sin tener que ser hospitalizados, recuerda el estudio.

De aquellos que han de ser ingresados en un centro médico, la mayoría también experimenta una mejoría, si bien algunos podrían necesitar oxígeno o ventilación mecánica. Estos últimos, según el estudio, son los considerados pacientes de alto riesgo a los que la dexametasona parece ayudar.

Ese fármaco se emplea ya para reducir inflamaciones en el caso de otras condiciones médicas y ayuda, al parecer, a detener parte del daño que se origina cuando el sistema inmunológico se sobreactiva mientras intenta luchar contra el coronavirus.

“Reduce la mortalidad”

En este ensayo clínico participaron unos 2.000 pacientes de hospitales, a los que se administró la medicina y su evolución se comparó con otros 4.000 enfermos a los que no se les prescribió.

Para aquellos pacientes conectados a ventiladores mecánicos, la dexametasona redujo el riesgo de muerte de un 40 a un 28%, al tiempo que en el caso de los enfermos que precisaron de oxígeno, el tratamiento redujo el riesgo mortal de un 25 a un 20%.

“Este es el único fármaco hasta la fecha que ha mostrado que reduce la mortalidad y la reduce de manera significativa. Es un gran avance“, afirmó el investigador principal del estudio, Peter Horby.

Para Martin Landray, otro de los científicos involucrados, los hallazgos sugieren que de cada ocho pacientes tratados que precisan de respiración asistida por ventiladores mecánicos, se podría salvar una vida.

En cuanto a los que necesitan abordaje con oxígeno, se salva una vida de cada 20-25, agregó.

“Hay un claro beneficio. El tratamiento consta de 10 días de dexametasona y cuesta unas 5 libras (5,5 euros/6,2 dólares) por paciente. Así que esencialmente cuesta 35 libras (38 euros/43 dólares) salvar una vida. Es un fármaco que está disponible en todo el globo”, remarcó Landray.

Según el experimento, la dexametasona no parece ayudar a personas que presentan síntomas leves de coronavirus -aquellos que no necesitan asistencia para respirar-.

El ensayo lleva funcionando desde el pasado marzo y en esas pruebas se ha incluido también el producto empleado para tratar la Malaria, la hidroxicloroquina, que ahora ha sido desechado ante el temor de que incremente el número de muertes y dé problemas coronarios.

Otro denominado remdesivir, un tratamiento antiviral que parece acortar el periodo de recuperación en pacientes con Covid-19, ya está disponible en el servicio público de salud de este país.

#Las medidas contra el #SARS-CoV-2 han reducido los casos de #gripe

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El confinamiento y las medidas de precaución han tenido el efecto colateral de frenar la incidencia de la gripe, más en países orientales que occidentales.

Virus de la influenza.
Virus influenza, de los CDC de Atlanta.

“Los esfuerzos para activar la respuesta nacional de alto nivel no solo condujeron a una disminución de casos de Covid-19, sino también a una disminución sustancial en la actividad de la influenza estacional. Las intervenciones aplicadas para controlar el SARS-CoV-2 pueden servir como estrategias útiles para la prevención y el control de la influenza en las próximas temporadas”. Es la conclusión de un estudio dirigido por Hyunju Lee, del Hospital Bundang de la Universidad Nacional de Seúl, en Corea del Sur, que se publica en Clinical Infectious Diseases.

En concreto, las intervenciones de salud pública, como la insistencia en la higiene de manos, la educación sobre cómo toser en público, el uso de mascarillas, el cierre de escuelas, la supresión de actividades sociales no esenciales y la orden de quedarse en casa cuando se tengan problemas respiratorios, han hecho que en Corea del Sur la duración de la epidemia de gripe 2019/2020 disminuyera en 6-12 semanas y el pico de actividad de la influenza cayó a 49,8 por 1.000 visitas frente a tasas de 71,9-86,2 en las siete temporadas anteriores.

Durante el período de distanciamiento físico forzado de la semana 9 a la 17 de 2020, los casos de hospitalización por influenza fueron 11,9-26,9 veces menores en comparación con temporadas anteriores. La influenza B de este año representó solo el 4%, en contraste con el 26,6% al 54,9% de todos los casos en temporadas anteriores. Varios estudios, la mayoría asiáticos, coinciden en este beneficio indirecto de las drásticas medidas tomadas para contener la rápida expansión del nuevo coronavirus.

A finales de abril el equipo de Jing Sun, de la Unidad de Cuidados Intensivos del Hospital de la Cruz Roja de Hangzhou, en China, informaba en Journal of Travel Medicine, con datos de los Centros de Control de Enfermedades de China, que en las primeras seis semanas de 2020 la incidencia de casos de influenza confirmados por laboratorio en hospitales centinelas en todo el país cayó del nivel más alto (47,7%) al más bajo (1,2%) en los últimos años.

Atenuación mundial

Un mes después, en la misma revista, el grupo de Chin Pok Chan, del Centro de Enfermedades Infecciosas Stanley Ho de la Universidad China de Hong Kong, revisaba los datos semanales de influenza confirmada en laboratorio entre 2014/15 y 2019/20 de Hong Kong, Corea del Sur, Taiwán, Estados Unidos y 50 países europeos con sistemas rutinarios de vigilancia de la gripe en la Región Europea de la OMS (https://flunewseurope.org/System). Analizaron el momento de inicio y final de la temporada, los picos, la duración de la temporada y su descenso, amplitud y pendiente.

En comparación con las tasas medias de 2014/15 a 2018/19, las temporadas de influenza invernal 2019/20 se atenuaron notablemente: así, la duración estacional disminuyó de 27,5 a 13 semanas en Hong Kong, de 39 a 25 semanas en Estados Unidos, de 33,2 a 28 semanas en Europa y de 15,3 a 15 semanas en Taiwán. Se observó asimismo un mínimo extremadamente bajo en la postemporada, llegando a cero en Corea del Sur, Europa y Taiwán, y fue del 0,2% en Hong Kong y Estados Unidos. Hallaron además un descenso rápido dentro de las 7-12 semanas en todos los lugares, excepto en Taiwán, en relación con las 8,3-23,4 semanas de 2014 a 2018/2019.

Otros estudios de Singapur, Japón, Australia y Nueva Zelanda confirman ese descenso motivado por las cuarentenas, mascarillas y distanciamientos. Incluso un pequeño estudio de la Universidad Federal de Sao Paulo que se publica en Journal of Infection ha observado tras revisar las infecciones respiratorias agudas de 244 pacientes hospitalizados del 12 de marzo al 16 de abril en el Hospital de Sao Paulo, que 115 tenían SARS-CoV-2, cuatro influenza B, nueve niños presentaban virus respiratorio sincitial (VRS), y ningún caso de influenza A ni de metapneumovirus, lo que supone la reducción a la mitad de los casos esperados en ese periodo de VRS e influenza.

Falta de vigilancia

Es posible de todos modos que la disminución de la gripe se haya notado más en los países orientales, en los que la pandemia empezó antes, que en los occidentales, en los que el SARS-CoV-2 empezó a llegar cuando la influenza estacional estaba en declive. No hay que descartar que algunos casos de influenza hayan quedado enmascarados tras la Covid-19 y que en esta temporada, por culpa de la pandemia, los rastreos y análisis se hayan visto perjudicados.

Como indicaba hace unos días la Organización Mundial de la Salud, “los datos actuales de vigilancia de la influenza deben interpretarse con cautela, ya que la pandemia de Covid-19 podría haber influido en diferentes grados en los comportamientos de búsquedas de salud, en las rutinas en los centros centinela, así como en las prioridades y capacidades de análisis de los países”. Reconocía sin embargo que “las diversas medidas de higiene y distanciamiento físico implantadas para reducir la transmisión del virus SARS-CoV2 también podrían haber desempeñado un papel en la interrupción de la transmisión del virus de la gripe… En la zona templada del hemisferio norte, la actividad de la influenza fue baja en general”.

Y el último informe del Sistema de Vigilancia de la Gripe en España, emitido el 16 de abril, señalaba que “la pandemia de Covid-19 en España podría estar afectando a la información epidemiológica y virológica de la gripe notificada”. Y precisaba que “en la semana 15/2020 (del 6 al 10 de abril), una vez finalizado el periodo epidémico de esta temporada gripal 2019-20, la tasa de incidencia de gripe es de 1,1 casos por 100.000 habitantes, por debajo del umbral establecido para esta temporada, una vez alcanzado el pico de la epidemia de gripe en la semana 05/2020, asociada actualmente a circulación esporádica de virus A(H1N1)pdm09”.

Con todo, la trágica pandemia de Covid-19 sí puede enseñarnos alguna lección válida para contener también a esos primos suyos estacionales que pueden ser tan peligrosos como el nuevo coronavirus.

#Las múltiples implicaciones de la #inflamación en cascada por #Covid-19

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Los ‘efectos’ de la Covid-19 van más allá de la función respiratoria. La inflamación en cascada afecta, y mucho, a la patología cardiovascular, la diabetes y otras enfermedades.

Coronavirus y otras patologías
La infección por Covid-19 agrava el pronóstico en pacientes con patologías crónicas como la diabetes y las enfermedades autoinmunes.

No todas las patologías crónicas hacen necesariamente más vulnerable al paciente frente a la Covid-19, pero sí se puede agravar considerablemente la evolución de la enfermedad infecciosa en función de la patología de base del enfermo. Según los datos del Centro de Coordinación de Alertas y Emergencias Sanitarias del Ministerio de Sanidad, los grupos con mayor riesgo de desarrollar una enfermedad grave por SRAS-Cov-2 son las personas mayores de 60 años, las que padecen enfermedades cardiovasculares, HTA o EPOC, las diabéticas, inmunodeprimidas, embarazadas y enfermos de cáncer. No obstante, el mismo centro expone también otras muchas patologías -algunas de ellas crónicas- que combinadas con la Covid-19 complican el manejo de ambas enfermedades. Es el caso del tabaquismo, la obesidad, algunas patologías neurológicas, reumáticas inmunomediadas, y la enfermedad inflamatoria intestinal, entre otras.

Un estudio del Centro para el Control de Enfermedades estadounidense (CDC, por sus siglas en inglés), realizado entre 1.482 pacientes de 14 estados diagnosticados de Covid-19 y hospitalizados en el mes de marzo, destaca entre sus conclusiones que las tasas de ingresos aumentan con la edad, y que en la mayoría de los casos los pacientes ingresados en ese mes por Covid tenían patologías previas. En concreto, cerca del 90% de los pacientes ingresados tenían al menos una patología previa, siendo las más comunes obesidad, HTA, EPOC, diabetes y patologías cardiovasculares.

En el caso de las enfermedades cardiovasculares, el SRAS-CoV-2, al igual que el MERS-CoV, produce daño cardiaco agudo e insuficiencia cardiaca. Se observa daño miocárdico en un porcentaje considerable de los pacientes infectados, así como tensión arterial elevada entre los que evolucionan. Así, en una serie de 138 casos en Wuhan, 36 pacientes en estado crítico tenían una mayor elevación de los biomarcadores de daño miocárdico, lo que sugiere que este daño es una complicación frecuente entre los pacientes más graves. Entre los fallecidos en esta serie de Wuhan, el 11,8% de las personas sin antecedentes de enfermedad cardiovascular tenían un daño importante del tejido cardiaco, con elevación de cTnI o parada cardiaca durante el ingreso.

Desregulación de ACE2

La alta incidencia observada de síntomas cardiovasculares parece relacionada con la respuesta inflamatoria sistémica, el efecto de la desregulación de ACE2, y la propia disfunción pulmonar e hipoxia. Todo ello resulta en un daño agudo de las células miocárdicas. Por otra parte, los pacientes con patología cardiovascular tienen ahora miedo de ir al hospital, hasta el punto de que en centros de toda Europa se observa que personas con síntomas de infarto retrasan o evitan las visitas, como lo demuestra la drástica reducción de los ingresos por infartos de miocardio.

Barbra Casadei, presidenta de la Sociedad Europea de Cardiología, ha llegado a pedir que las indicaciones de confinamiento y de evitar acudir a los centros hospitalarios “no se aplicaran a las personas con síntomas de infarto”. Además, estos pacientes están tratando de rehuir o retrasar procedimientos o cirugías programadas, como la sustitución de válvulas cardíacas, por temor a una infección después del procedimiento, con el efecto sobre su salud que esto puede tener. diabetes: factor de riesgo.

Otra de las comorbilidades más frecuentes en pacientes que han desarrollado neumonía grave o han fallecido a causa de la infección es la diabetes. Un informe del citado centro del Ministerio de Sanidad señala que la razón por la que la diabetes supone un factor de riesgo para desarrollar enfermedad grave por Covid-19 no está bien establecida, pero los datos sugieren que la sobreexpresión de ACE2 en pacientes diabéticos puede estar implicada en el proceso. Esta sobreexpresión parece un mecanismo compensatorio para frenar el deterioro de la microvasculatura renal implicada en la nefropatía diabética a largo plazo, así como para limitar el daño cardiovascular a largo plazo en pacientes diabéticos mediante la activación del eje ACE2/Ang-(1–7)/MasR. Por otra parte, el grupo de antidiabéticos orales tiazolidinedionas también se ha relacionado con una mayor expresión de la ACE2.

Inmunosupresión farmacológica

Y aún hay más pacientes vulnerables, como los que padecen enfermedad inflamatoria intestinal (EII), concretamente aquellos que necesitan inmunosupresión farmacológica, que tienen malnutrición o que presentan alta enfermedad inflamatoria, y que constituyen un grupo de alto riesgo frente a la Covid-19 por su predisposición a infecciones. Las personas que padecen alguna enfermedad autoinmune siempre tienen un mayor riesgo de infección, lo que se atribuye a la propia enfermedad, y también a los tratamientos inmunosupresores y a las comorbilidades.

No obstante, y según el citado informe del CDC estadounidense, los datos sobre la relación entre enfermedades autoinmunes y Covid aún son limitados y, de momento, no hay evidencias de que se produzca un incremento de las complicaciones ligadas a infección por Covid-19 en estos pacientes. Además, concluye el trabajo, algunos de los medicamentos más empleados para tratar patologías autoinmunes podrían formar parte del arsenal terapéutico que se emplea frente a la Covid-19.

Impacto ‘indirecto’ en adolescentes

Por último, y entre los muchos posibles impactos indirectos del coronavirus, como consecuencia del confinamiento, se pueden agravar las adicciones entre jóvenes vulnerables. Así, la Fundación de Patología Dual (FPD) señala la importancia de la prevención y la atención de los adolescentes, un colectivo especialmente vulnerable para el desarrollo de trastornos adictivos, dado que su cerebro es inmaduro y tiene menor capacidad de control. El aislamiento social dificulta el abuso de sustancias ilegales e incluso legales debido al control familiar, aunque no impide conectarse a plataformas online a cualquier hora del día, lo que puede agravar los problemas de adicción comportamental en la población adolescente. Por eso, la FPD advierte de que la reclusión en los hogares puede provocar la iniciación de nuevos jugadores a través de plataformas digitales, siempre en personas vulnerables, al tiempo que favorece que las que ya están en tratamiento por trastorno por juego puedan tener recaídas durante el confinamiento.

#Ocho hospitales madrileños investigan la #melatonina en profilaxis frente a la #Covid-19 en sanitarios

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Un ensayo clínico liderado por La Paz en 450 profesionales quiere evaluar si el uso preventivo de ‘Circadin’ podría evitar el contagio entre el personal con alto riesgo de infección.

A la melatonina se le atribuye actividad protectora frente a infecciones bacterianas y virales.
A la melatonina se le atribuye actividad protectora frente a infecciones bacterianas y virales.

El Hospital La Paz de Madrid ha puesto en marcha un ensayo clínico para evaluar la eficacia y seguridad del medicamento melatonina 2 mg de liberación prolongada (Circadinen la profilaxis de la infección por SARS-CoV-2 en personal sanitario en riesgo, con la colaboración de la compañía farmacéutica española Exeltis (perteneciente al grupo Insud Pharma).

En el ensayo también participan otros siete hospitales madrileños: Gómez Ulla, Ramón y Cajal, Infanta Leonor, Clínico San Carlos, La Princesa, Infanta Sofía y 12 de Octubre.

Se trata de un estudio multicéntrico, aleatorizado y controlado con placebo, que contará con la participación de 450 profesionales sanitarios, y cuyo objetivo será comprobar si el uso preventivo de este medicamento podría evitar el contagio entre el personal con alto riesgo de infección. A la melatonina se le atribuye actividad antiinflamatoria, antioxidante y protectora frente a infecciones bacterianas y virales.

Alberto M. Borobia, coordinador del estudio, del Servicio de Farmacología Clínica y de la Unidad Central de Investigación Clínica y Ensayos Clínicos del Hospital La Paz, afirma que es necesaria “la búsqueda de estrategias de prevención de infección por SARS-CoV-2 que permitan reducir su transmisión, especialmente en personal sanitario y asistencial, que presentan un alto riesgo de contagio”.

”La melatonina tiene la ventaja de ser un fármaco ya comercializado, con un buen perfil de seguridad y un precio asequible”

En este contexto, Borobia explica que esta hormona “tiene la ventaja de ser un fármaco ya comercializado, con un buen perfil de seguridad y un precio asequible, y por tanto un buen candidato a estudiar para prevenir la infección por SARS-CoV-2”.

Para el insomnio

Circadin está indicado para el tratamiento del insomnio primario. La melatonina es una hormona natural producida por la glándula pineal. Su secreción aumenta poco después del anochecer, alcanza su pico máximo entre las dos y las cuatro de la madrugada y disminuye durante la segunda mitad de la noche.

La acción de esta hormona asocia al control de los ritmos circadianos y a la adaptación al ciclo de luz-oscuridad. También se asocia a un efecto hipnótico y a una mayor propensión al sueño.

#Al #SRAS-CoV-2 no le gusta tomar el sol

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Las costumbres víricas apuntaban a la estacionalidad del nuevo coronavirus. Varios estudios parecen ir confirmando su repulsión hacia la humedad y las temperaturas elevadas.

Silueta de una playa con el sol al fondo
El nuevo coronavirus parece huir de los rayos solares, al igual que otros virus estacionales.

Una de las dudas, y esperanzas, frente a la pandemia por el SRAS-CoV-2 era si se vería afectado por la temperatura, por la llegada del calor. Varios estudios chinos ya habían alentado esa posibilidad, así como experimentos de laboratorio y experiencias previas con otros coronavirus y virus de la gripe. Así, un ensayo en laboratorio publicado en abril en The Lancet Microbe había comprobado que el SRAS-CoV-2 era muy estable a 4 °C pero sensible al calor. El tiempo de supervivencia del virus fue de 5 minutos a una temperatura de incubación de 70 °C, y a 22 ºC el virus desaparecía a los 14 días y duraba un día a 37 ºC. ¿Tendría por tanto características estacionales? Tres estudios que se acaban de publicar en Science of the Total Environment parecen confirmar esas sospechas.

En el primero de ellos, un equipo de la Universidad Federal de Tocantins, en Brasil, ha analizado la relación entre la temperatura y los casos confirmados recopilados del 27 de febrero al 1 de abril en las 27 capitales de estado de Brasil afectadas por el coronavirus. Los modelos aplicados sugieren una relación lineal negativa entre las temperaturas y los casos diarios acumulados de Covid-19 en el rango de 16,8 °C a 27,4 °C. Cada aumento de temperatura de 1 °C se asoció con una disminución de −4,8% en el número de casos diarios confirmados. En este estudio, que presenta las temperaturas tropicales de Brasil, la variación en las temperaturas promedio anuales osciló entre 16,8 °C y 27,4 °C. Los resultados indican que la curva se aplanó en un umbral de 25,8 °C, si bien no hay evidencia, por falta de datos, que respalde que la curva disminuyera para temperaturas superiores a 25,8 °C.

El segundo estudio, a cargo de Al Asyary y Meita Veruswati, de dos universidades de Indonesia, analiza la correlación entre la exposición a la luz solar y el pronóstico de enfermos de Covid-19 en Yakarta (Indonesia). Examinaron las tasas de incidencia, muerte y recuperación. Solo el número de pacientes recuperados se correlacionó significativamente con la exposición a la luz solar. Los autores matizan que la luz solar no basta para eliminar al virus, por lo que no previene la infección, pero ayuda a mantener el estado de salud de los contagiados. Es sabido que la luz solar estimula el sistema inmunitario, lo que ralentiza el desarrollo de agentes como la influenza, la tuberculosis y el SARS. En este caso, los pacientes de Covid-19 que disfrutaron de luz solar mientras eran atendidos, ya sea en hospitales o en el hogar, tenían más probabilidades de recuperarse de la enfermedad. Puede que a ello contribuya la producción de vitamina D, que potencia la inmunidad.

En el tercer estudio, el equipo de Yu Wu, de la Escuela de Salud Pública de la Universidad de Pekín, ha explorado los efectos de la temperatura y humedad en los casos diarios y muertes por Covid-19 en 166 países, excluida China. Basándose en la influencia de los parámetros meteorológicos sobre las infecciones respiratorias, han observado que la temperatura y humedad relativa se relacionaron de modo negativo con la progresión de la infección. Un aumento de 1 ºC se asoció con un 3,08% de reducción en los nuevos casos diarios y con un 1,19% menos de nuevas muertes, mientras que un aumento del 1% de la humedad relativa causaba un 0,85% de reducción de nuevos casos y un 0,51% de reducción en las muertes. La baja humedad parece que facilita que las partículas virales sobrevivan más tiempo en el aire. Además, reduce la capacidad de las células ciliares de las vías respiratorias para eliminar esas partículas virales y secretar moco, exponiendo así al huésped al virus.

De Hokkaido a Okinawa

En la misma línea, el equipo de Mugen Ujiie y Shinya Tsuzuki, del Centro Nacional de Salud Global de Tokio, en Japón, publica en International Journal of Infectious Diseases otro trabajo sobre la temperatura y la infectividad del SRAS-CoV-2. Con datos de las prefecturas (provincias) japonesas, evaluaron la relación entre el número de pacientes acumulado por millón de habitantes y la temperatura media en febrero de 2020 en cada prefectura. Tuvieron en cuenta el número de visitantes llegados de China en enero y la tasa de envejecimiento a fin de reflejar la heterogeneidad de las situaciones. Aunque la estacionalidad del SRAS-CoV-2 no ha sido empíricamente demostrada, es plausible que muestre alta infectividad en el invierno, como otros betacoronavirus. “Nuestros resultados sugieren que la baja temperatura puede acrecentar la infectividad de este virus. Okinawa, por ejemplo, la zona japonesa más meridional, de clima subtropical, solo ha registrado 3 casos. En cambio, Hokkaido, la más septentrional, en la zona subártica, tuvo el mayor número de casos registrados de Japón”.

Los epidemiólogos nipones advierten de que hay que desglosar bien los focos de contagios y sus contactos sociales, así como las aglomeraciones urbanas, factores que lógicamente aumentan los casos. Aun así, observan que en Hokkaido hay una menor densidad de población que en Tokio y se ha visto más afectada que la capital japonesa. Es decir, tras ajustar otros factores, “sí parece que las bajas temperaturas muestran una fuerte relación con un mayor número de casos”.

Quizá esta susceptibilidad al calor explique en parte el menor número de contagios, por ejemplo, en Andalucía. Sin embargo, la existencia de casos en África o en Australia indica que la elevada infectividad del SRAS-CoV-2 puede vencer en ocasiones temperaturas altas, por lo que no hay que confiarse demasiado y, mientras no desaparezca achicharrado por el calor o frenado por una vacuna, haya que seguir defendiéndose de sus garras con mascarillas, higiene, distanciamiento social y rápido control de los contagiados y sus contactos. La llegada del calor puede ser una tregua bienvenida, pero la presunta estacionalidad del nuevo coronavirus es a la vez una amenaza latente para el próximo invierno que se sumaría a la gripe anual y a las otras infecciones respiratorias que huyen del agua y de la luz.

#Plasma de pacientes recuperados para o tratamento da Covid-19?

Postado em

Kathleen Doheny

COVID-19 (coronavirus) update - Royal College of Surgeons in Ireland

 

 

Robert Pace, um padre episcopal norte-americano, está acostumado a colocar os outros em primeiro lugar e a ajudar. Então, quando o pneumologista que o tratou da Covid-19 (sigla do inglês, Coronavirus Disease 2019) perguntou se ele gostaria de doar sangue para ajudar outros pacientes, ele não hesitou.

“Eu disse: ‘Com certeza'”, lembrou Robert, 53 anos. Ele disse que a ideia foi ‘muito interessante’. Quando estava com Covid-19, em março, o padre passou três dias no hospital, isolado, recebendo fluidos por via intravenosa (IV) e oxigênio. Ele teve dispneia e taquicardia. Agora, totalmente recuperado, seu sangue é algo precioso, rico em anticorpos e potencialmente capaz de salvar vidas.

Enquanto os pesquisadores lutam para encontrar medicamentos para combater a Covid-19, outros estão testando um tratamento antigo. Eles estão coletando sangue de pacientes curados para uso em pacientes com infecção grave, um tratamento conhecido como terapia com “plasma convalescente”.

Os médicos disseram que o tratamento provavelmente poderá ser usado até que outros medicamentos e uma vacina estejam disponíveis.

Embora a Food and Drug Administration (FDA) dos Estados Unidos considere o tratamento experimental, no final de março, a agência facilitou o acesso a ele. Os pacientes podem recebê-lo como parte de um ensaio clínico ou por meio de um programa de acesso expandido supervisionado por hospitais ou universidades. Um médico também pode solicitar permissão para tratar um único paciente.

“A justificativa é que se trata de uma necessidade emergente e compassiva”, disse o Dr. John Burk, médico pneumologista do Texas Health Harris Methodist Hospital, nos EUA, que tratou o padre Robert. “É uma maneira de disponibilizá-la na prática clínica”. E a aprovação pode ser rápida. Dr. John disse que recebeu uma aprovação da FDA apenas 20 minutos depois de solicitá-la para um paciente grave.

Como funciona

A premissa de como isso funciona é “bastante simples”, disse o Dr. Michael Joyner, médico e professor de anestesiologia da Mayo Clinic, nos EUA. “Quando alguém se recupera e não é mais sintomático, você pode coletar esses anticorpos do sangue e dá-los para outra pessoa e, espera-se que isso vá mudar a evolução do paciente. “Dr. Michael é o primeiro pesquisador do Expanded Access to Convalescent Plasma for the Treatment of Patients with Covid-19, da FDA, com abrangência nacional e 1.000 locais participantes.

A terapia com “plasma convalescente” foi usada no combate de muitos outros vírus, como o Ebola, a síndrome respiratória aguda grave (SARS, sigla do inglês, Severe Acute Respiratory Syndrome), a gripe “aviária”, a gripe por H1N1 e durante a pandemia de gripe de 1918. O Dr. Michael disse que a evidência mais forte vem da década de 50, quando esta terapia foi usada para tratar uma doença transmitida por roedores chamada febre hemorrágica argentina. O uso de terapia com “plasma convalescente” nesta infecção reduziu a taxa de mortalidade de quase 43%, antes do tratamento se tornar comum no final da década de 50, para cerca de 3% após ser amplamente utilizado, segundo um relatório.

Os dados sobre terapia com “plasma convalescente” especificamente para Covid-19 são limitados. Pesquisadores chineses publicaram um estudo com cinco pacientes graves, todos em ventilação mecânica, tratados com plasma após terem recebido antivirais e anti-inflamatórios. Três pacientes tiveram alta após de 51 a 55 dias, e dois estavam em condição estável no hospital, 37 dias após a transfusão.

Em outro estudo com 10 pacientes graves, os sintomas desapareceram ou melhoraram para todos os 10 até três dias após a transfusão. Dois dos três em ventilação passaram para uso de oxigênio apenas. Nenhum morreu.

Os pesquisadores chineses também relataram três casos de pacientes com Covid-19 que receberam terapia com “plasma convalescente” e tiveram uma recuperação satisfatória.

Pesquisadores que revisaram o histórico desta terapia para outras doenças concluíram recentemente que o tratamento não parece ter efeitos colaterais graves e deve ser estudado para a Covid-19.

Embora as informações sobre os efeitos colaterais específicos deste tratamento estejam evoluindo, o Dr. Michael disse que eles são “muito, muito poucos”.

Segundo a FDA, reações alérgicas podem ocorrer com terapias com plasma. Como o tratamento para Covid-19 é novo, não se sabe se os pacientes podem ter outros tipos de reação.

Quem pode doar?

Representantes dos bancos de sangue e pesquisadores que administram os programas de terapia com plasma convalescente” disseram que o desejo de ajudar é grande, e que receberam inúmeros candidatos para doações. Mas os requisitos são rigorosos.

Os doadores devem ter evidências da infecção por SARS-CoV-2 (sigla do inglês, Severe Acute Respiratory Syndrome Coronavirus 2) documentada de várias formas, como por teste diagnóstico por swab nasal ou exame de sangue mostrando a presença de anticorpos. E eles devem estar sem sintomas por 14 dias, se tiverem o resultado dos testes ou por 28 dias se não.

O tratamento envolve a coleta de plasma, não do sangue. O plasma, a parte líquida do sangue, ajuda na coagulação e na imunidade. Durante a coleta, o sangue de um doador passa por uma máquina que coleta apenas o plasma, e devolve os glóbulos vermelhos e as plaquetas ao doador.

Ensaios clínicos

Os requisitos podem ser mais rigorosos para os doadores participantes de um ensaio clínico formal do que em um programa de acesso expandido. Por exemplo, potenciais doadores em um ensaio clínico randomizado em andamento na Stony Brook University devem ter níveis mais altos de anticorpos do que o exigido pela FDA, disse o líder do estudo Dr. Elliott Bennett-Guerrero, diretor médico de qualidade perioperatória e segurança do paciente e professor da Renaissance School of Medicine.

Ele espera recrutar até 500 pacientes da área de Long Island, NY. Os ensaios clínicos costumam ter uma divisão de 50-50, metade dos indivíduos recebe o tratamento e a outra metade recebe placebo. A distribuição no estudo de Dr. Elliott será de 80% dos pacientes para a terapia com “plasma convalescente” e de 20% para o plasma padrão.

Julia Sabia Motley, 57, de Merrick, Nova York, espera se tornar doadora para o estudo Stony Brook. Ela e o marido, Sean Motley, 59, testaram positivo para Covid-19 no final de março. Ela precisa passar por mais um teste antes de poder participar do estudo. Seu marido também quer doar. “Finalmente, há algo que posso fazer”, disse Julia. Seu filho está no programa de medicina da Stony Brook e contou a ela sobre o estudo.

Ainda há muitas perguntas

O tratamento para Covid-19 ainda está engatinhando. O Dr. John usou o “plasma convalescente” em dois pacientes. Um está se recuperando em casa e o outro está no ventilador, mas está melhorando, disse ele.

Cerca de 200 pacientes em todo o país receberam a terapia, disse o Dr. Michael. Ele espera que o suprimento de sangue aumente à medida que mais pessoas puderem doar.

Ainda não se conhece a efetividade da terapia com “plasma convalescente”. Embora os especialistas saibam que os anticorpos contra o SARS-CoV-2 “podem ser úteis no combate ao vírus”, eles não sabem “quanto tempo os anticorpos permanecem no plasma”, disse o Dr. Elliott.

Os médicos também não sabem para quem a terapia pode ser útil, além das pessoas com doença grave ou com risco de morte. Quando é usada para outras infecções, geralmente é administrada nos estágios iniciais, ao início dos sintomas, disse o Dr. Michael.

O Dr. Michael disse que vê o tratamento como uma medida paliativa, “até que os anticorpos concentrados estejam disponíveis”. Várias empresas farmacêuticas estão atuando na coleta de anticorpos de doadores e na produção de medicamentos com anticorpos concentrados.

“Normalmente, consideraríamos o “plasma convalescente” como um tratamento a ser usado até que terapias seguras, efetivas e que possam ser produzidas em massa estejam disponíveis, como uma vacina ou um medicamento”, disse o Dr. Elliott.

Mesmo assim, ele disse que não acha que terá problemas para atrair doadores e que terá doadores recorrentes, que querem muito ajudar.

Mais informações para potenciais doadores

Bancos de sangue, a Cruz Vermelha norte-americana e outros envolvidos com a terapia com “plasma convalescente” publicaram informações on-line para potenciais doadores. As pessoas que não atendem aos requisitos para doação de plasma para Covid-19 ainda podem doar sangue nos bancos de sangue comuns se atenderem a esses critérios.

Segundo a FDA, uma doação pode salvar a vida de até quatro pacientes com Covid-19.

O padre Robert já está planejando outra visita ao banco de sangue. Para passar o tempo da última vez que doou, ele disse que orou pela pessoa que eventualmente receberia seu sangue.

# Medscape

#Tests sérologiques : les indications ont été précisées

Postado em

France— Qui pourra faire un test sérologique (de détection des anticorps) pour savoir s’il est ou s’il a été infecté par le SARS-CoV-2 ? La HAS a dévoilé sa liste d’indications, lors d’une e-conférence de presse le samedi 2 mai [1]. Les recommandations ont été élaborées par un groupe de travail de la HAS dont le rapport est disponible ici.

Pas de dépistage général de la population

Première information délivrée par le Pr Dominique Le Guludec (Présidente de la HAS) : « Il y a encore beaucoup d’inconnues sur la réponse immunitaire de l’organisme à ce virus. On ne sait pas quelle protection elle confère aux personnes qui ont contracté le virus. C’est ce qui a amené le groupe de travail à ne pas préconiser le dépistage général de la population ».

Toutefois, les recommandations seront susceptibles d’évoluer avec le temps. « Il s’agit de recommandations basées sur les connaissances scientifiques que l’on a aujourd’hui mais elles seront actualisées au fil de l’eau chaque fois que des connaissances importantes apparaitront, en particulier sur le caractère protecteur de la réponse immunitaire », a souligné le Pr Le Guludec.

La présidente de la HAS a également précisé que ces recommandations ne concernaient que les tests ELISA de laboratoire et non les tests rapides (TROD ou autotests) qui feront l’objet d’un autre rapport qui sera rendu publique d’ici 8 à 10 jours.

Les indications retenues par le groupe de travail de la HAS

A ce stade, les tests sérologiques sont indiqués pour confirmer un diagnostic de COVID-19 et dans le cadre d’études épidémiologiques.

Chez les personnes symptômatiques graves hospitalisés :

– les tests sont recommandés en cas de résultats discordants : si le tableau clinique ou scanographique est évocateur et que la RT-PCR est négative.

-Ils sont aussi recommandés, en rattrapage, chez les personnes n’ayant pas été en mesure de réaliser un test de RT-PCR avant 7 jours.

Dans ces deux cas, les tests sont recommandés à partir du 7ème jour en raison du fait que dans les formes graves, les titrages d’anticorps sont probablement plus élevés et que l’on ne peut pas attendre le moment optimum (J14) pour tester.

Chez les personnes symptômatiques sans gravité suivis en ville :

-Les tests sont recommandés en cas de résultats discordants : si le tableau clinique ou scanographique est évocateur et que la RT-PCR est négative.

-Ils sont aussi recommandés en rattrapage, chez les personnes n’ayant pas été en mesure de réaliser un test de RT-PCR avant 7 jours

-Ils sont aussi préconisés pour un diagnostic étiologique à distance. Lorsque le patient a eu un diagnostic clinique mais n’a pas bénéficié d’une RT-PCR ou d’un scanner, il lui sera possible de demander à son médecin une ordonnance pour réaliser un test.

Dans ces trois cas, les tests sont recommandés à partir du 14ème jour.

Chez les personnes asymptômatiques

– Les tests sont recommandés chez les professionnels soignants non symptômatiques lors de dépistage et détection de personne-contact par RT-PCR selon les recommandations en vigueur après une RT-PCR négative, uniquement à titre individuel sur prescription médicale.

– Les tests sont recommandés chez les personnes d’hébergement collectif non symptomatiques lors de dépistage et détection de personne-contact par RT-PCR selon les recommandations en vigueur après une RT-PCR négative, uniquement à titre individuel sur prescription médicale (EHPAD, foyers d’hébergements pour adultes et enfants en situation de handicap, centres d’accueil de migrants, prisons, casernes militaires et des pompiers, porte-avion, résidences universitaires, internats…).

Enfin, les tests sérologiques sont aussi recommandés pour la surveillance épidémiologique « pour mieux comprendre l’épidémie au niveau local et national, guider les décisions, pouvoir dire quelle part de la population a été contaminée », a souligné Cédric Carbonneil qui a piloté le projet (Chef du Service d’Evaluation des Actes Professionnel, HAS).

N’ont donc pas été retenues comme indications : le test des personnes-contacts d’un patient confirmé ou suspecté, la sortie hospitalière, le dépistage chez les patients à risque de forme grave de COVID-19, le dépistage des patients en vue d’une hospitalisation ou encore le dépistage des groupes socio-professionnels confinés ou non confinés. Les tests sérologiques ne sont donc pas recommandés à ce stade dans les entreprises ou chez les professionnels particulièrement exposés comme les caissiers, livreurs, professeurs des écoles ou gendarmes (en dehors des indications pré-citées).

Quand les tests seront-ils disponibles ?

« Les médecins pourront commencer à prescrire ces tests dès que le remboursement aura été ratifié par le ministère. La HAS donnera un avis rapidement, probablement en début de semaine prochaine », a indiqué le Pr Le Guludec à Medscape édition française.

Seront-ils disponibles en quantité suffisante par rapport aux indications sélectionnées ? « Les différents tests sont en train d’être évalués par le Centre National de Référence (CNR). Au fur et à mesure, il y en aura de plus en plus », a précisé la présidente de la HAS.

En pratique

Tous les médecins pourront prescrire ces tests ELISA. Ces derniers devront mesurer à la fois les IgG et les IgM ou les Ig totaux. Les résultats seront obtenus en 4 heures et devraient être délivrés en 24 heures maximum.

#Uso universal de #mascarillas: para la OMS, aún falta evidencia científica

Postado em

La Organización Mundial de la Salud (OMS) recuerda que el beneficio del empleo de las mascarillas en la comunidad aún se desconoce.

Viajeros con mascarilla para evitar contagios por coronavirus chino, en el aeropuerto Hong Kong.
Viajeros con mascarilla para evitar contagios por coronavirus chino, en el aeropuerto Hong Kong.

El máximo organismo sanitario mundial no despeja las dudas sobre la conveniencia de utilizar mascarillas de forma generalizada.

El director general de la OMS, Tedros Adhanom Ghebreyesus, ha afirmado que sí está recomendado su uso en sanitarios y cuidadores de enfermos; también lo aconseja de forma generalizada en las comunidades que no pueden acceder a otras medidas de protección -como el lavado de manos, por falta de agua-.

Pero, como tantas otras cosas con este nuevo patógeno, algunas cuestiones se mueven en un territorio gris. Ese es el caso del uso generalizado de las mascarillas en sociedades que sí pueden seguir las consabidas medidas de protección, incluida la de la higiene de manos.

El doctor Tedros ha expuesto hoy, en rueda de prensa telemática, sobre el uso universal de mascarillas que la investigación en este terreno es “limitada” y la OMS aún está elaborando un consenso sobre ello.

Por eso, “animamos a los países que consideren el uso de las mascarillas para toda la población que estudien la eficacia de la medida, para que todos podamos aprender“, ha dicho.

Y ha recordado que en cualquier caso, las mascarillas “por sí solas, no pueden detener la pandemia”. Los países, ha insistido, deben continuar encontrando casos, diagnosticando, aislando y tratando cada infectado y rastreando sus contactos.

“Con máscara o sin ella, hay otras cosas que han demostrado que nos pueden proteger: mantener la distancia con otros, lavarse las manos, estornudar en el hueco del codo y evitar tocarse la cara”.

La controversia sobre las mascarillas ha surgido al hilo de observaciones en países asiáticos donde la población ha asimilado su uso, en especial desde las últimas pandemias víricas.

Algunos epidemiólogos y preventivistas consideran que ese uso generalizado ha podido ayudar a atajar los contagios, en especial entre los asintomáticos.

Estudios recientes, como el llevado a cabo por investigadores de Múnich publicado en Nature, también han sugerido que el contagio por el SARS-CoV-2 puede producirse durante los primeros días de la infección, cuando el enfermo aún no es consciente de que tiene el virus.

Otro trabajo, publicado hace unos días en Nature Medicine, también indicaba que las mascarillas quirúrgicas parecen reducir la transmisión de los coronavirus estacionales, rinovirus o el de la propia gripe.

A este goteo de evidencias científicas, se suman otros factores que también pueden influir en la recomendación de un uso generalizado de las mascarillas. Entre ellos, el hecho de que ver a los demás llevarlas ayuda a recordar las medidas de distanciamiento físico y otras en relación al riesgo de la infección. Así se recordaba en un artículo sobre la conveniencia o no de llevar mascarilla publicado esta semana en NEJM.

Por el contrario, aducía este artículo, un uso inadecuado puede dar una falsa sensación de seguridad entre los usuarios.

Y en este debate científico, no hay que olvidar el principal argumento esgrimido por la OMS, desde el principio de esta emergencia sanitaria: en una situación de escasez de material protector, son las personas que están en primera línea de lucha quienes deben estar protegidos.

“Nos preocupa que el uso masivo de mascarillas por parte de la población general pueda agravar la escasez para las personas que más las necesitan. En algunos lugares, esa escasez está poniendo a los sanitarios en un verdadero peligro”, ha vuelto a recordar el doctor Tedros esta tarde.