What will another professional, who is assessing you for an examination or a job application expect you to know about the current coronavirus, COVID-19 or SARS-COVID-19? I have put down some general knowledge about viruses and the corona viruses in particular. As information about the corona virus which is causing the disease we now recognize as COVID-19 is novel and about which the medical profession is learning even as it is expected to fight the disease, I have put down some studies which we should all be familiar with. Most of these are taken from Journal Watch NEJM.
- What is a virus? It is a non-cellular form of living organism which requires a cellular living organism to replicate and produce the enzymes it needs for survival. The cell the virus enters, dies eventually as its own functions are disrupted by the virus, which takes over it’s DNA either directly or through a reverse transcriptase.
- How are viruses classified? There is extensive classification of viruses. Clinically we recognize them from the diseases they cause or as DNA or RNA viruses from the genetic material they carry and with which they take over the cell nucleus and its synthetic functions. They are also classified according to their shape; helical, or icosahedral or a single or double strand; whether they have an envelope or are naked.
- What does the Corona virus look like? The corona viruses are a spherical or pleomorphic enveloped particles containing single-stranded (positive-sense) RNA associated with a nucleoprotein within a capsid comprising a matrix protein. The envelope bears club-shaped glycoprotein projections. These club shaped structures give it the appearance of a crown hence the name corona. The COVID-19 has an icosahedral shape wrapped in a protein shell with the characteristic club shaped projectiles forming a corona . The genome size of corona viruses ranges from approximately 26 to 32 kilobases, one of the largest among RNA viruses.
- Is there a life form smaller than a virus? Subviral organisms exist.
- What diseases do the coronaviruses cause? Coronaviruses are a group of related RNA viruses that cause diseases in mammals and birds. In humans, these viruses cause respiratory tract infections that can range from mild to lethal. Mild illnesses include some cases of the common cold (which is caused also by certain other viruses, predominantly rhinoviruses), while more lethal varieties can cause SARS, MERS, and COVID-19. Symptoms in other species vary: in chickens, they cause an upper respiratory tract disease, while in cows and pigs they cause diarrhea. There are as yet no vaccines or antiviral drugs to prevent or treat human coronavirus infections.
- Why is the corona virus likely to mutate? RNA viruses lack the the proofreading function. The host exoribonuclease nonstructural protein, provides extra fidelity to replication by providing a proofreading function which the RNA-dependent RNA polymerase lacks. If the host does not form the protein which does the proofreading the virus will mutate.
- What is the effect of mutation of the virus? Vaccines which are in use become ineffective and new vaccines have to be developed according to the current form of the virus as the antibodies in a person no longer recognize the new virus.
- Once infected how long does the acquired immunity last in a subject? The immunity may last for 1 to 2 years. That is why there is a fear of a second wave of COVID-19 infection next year.
- How is the corona virus which causes Covid 19, SARS, MERS spread in humans and animals? Coronaviruses mainly target epithelial cells. They are transmitted from one host to another host, depending on the coronavirus species, by either an aerosol, fomite, or fecal-oral route. Human coronaviruses infect the epithelial cells of the respiratory tract, while animal coronaviruses generally infect the epithelial cells of the digestive tract. Covid 18 and SARS coronaviruses, for example, infect via an aerosol route and fomite route, the human epithelial cells of the lungs by binding to the angiotensin-converting enzyme 2 (ACE2) receptor. ACE2 is a membrane-bound aminopeptidase found ubiquitously in humans and expressed predominantly in heart, intestine, kidney, and pulmonary alveolar (type II) cells. Entry of SARS-CoV-2 into human cells is facilitated by the interaction of a receptor-binding domain in its viral spike glycoprotein ectodomain with the ACE2 receptor.
In an effort to prevent the spread of SARS-CoV-2, the transmission of the corona virus has been studied keeping its similarity to the SARS and MERS virus.
If it acts like the SARS coronavirus, the MERS coronavirus, and other respiratory viruses, SARS-CoV-2 would spread primarily through large droplets and environmental contamination. However, several studies suggest transmission by the aerosol route. An aerosol is a suspension of fine solid or liquid particles in gas smoke, fog, and mist form. Commercially an aerosol is dispensed as a payload propelled through a fine hole from a can containing a propellant gas. In a patient bronchial secretions are propelled through an almost closed mouth by the forceful contraction of the muscles of the chest wall, The mist which emerges from the mouth contains the viral particles. The mist particles are smaller than droplets, propelled further and remain suspended in the air longer hence have a greater capacity to transmit the virus. These particles are deposited on the surface of furniture, counter tops and work surfaces and remain viable and highly infective as fomites. Studies have been published in the reference journals given below and a Chinese study quoted in detail as well.
(NEJM JW Infect Dis May 2020 and N Engl J Med 2020; 382:1564; NEJM JW Infect Dis Jun 2020 and Nat Med 2020 Apr 2; [e-pub], and Ann Intern Med 2020 Apr 6; [e-pub]).
Investigators from Wuhan, China, now report the results of air sampling in and around two hospitals designated for COVID-19 patients.
Relatively little viral RNA was found in air samples from negative-pressure isolation rooms, intensive care unit (ICU) rooms, or ward rooms in a tertiary-care COVID-19 designated hospital. Deposition of 31 and 113 copies per meter2 per hour was found on two surfaces in ICU rooms. In contrast, in a temporary field hospital, low levels of viral RNA were found in air samples from general patient care areas and from a portable toilet unit. Three air samples from protective apparel removal rooms in the field hospital had from 16 to 42 viral RNA copies per meter3; most particles were 0.25 to 1 μm in size. After intense sanitization in the field hospital, air samples had no viral RNA. Most air samples from public areas near the two hospitals were negative; one from a crowd-gathering site near a department store entrance by the tertiary-care hospital had 11 copies per meter3, and one just outside the hospital entrance had 7 copies per meter3. This report provides real-world evidence of SARS-CoV-2 RNA suspended in submicrometer particles in the air and deposited on surfaces in two hospitals. The investigators did not test whether the sample viruses were infectious or provide direct evidence of airborne transmission. Still, the findings raise further concern that airborne transmission might be contributing to the rapid spread of COVID-19 and support intensive disinfection of bathrooms and areas where protective apparel is doffed; they also support wearing face masks in public areas.
9. What symptoms does the virus cause?
The COVID-19 virus may cause mild to moderately severe flu like symptoms but with a tendency to cause high fever. Because of its proclivity for the ACE-2 in the lungs it causes acute inflammatory pulmonary edema, the Severe Acute Respiratory Syndrome, requiring the use of an invasive ventilator. It also has has a tendency to attack people with previous heart disease with severe consequences. About 20% of patients have an acute decline in the renal functions and may require the attention of a nephrologist. A patient may present with vomiting and diarrhoea from having contracted Covid 19 without respiratory symptoms. In patients with Covid 19 there is a tendency for strokes to occur especially in younger patients because of platelet dysfunction and tendency to clot. In older patients a wide variety of neurological symptoms occur which cannot be directly linked to the virus itself.
Are outpatient physicians susceptible to acquiring COVID-19 from their patients?
More studies will come in later but I quote one survey from Italy where the disease was widely rampant. Office-based physicians have not been as visible in COVID-19 news coverage as hospital staff, although outpatient clinicians clearly are affected by similar safety and volume issues, all without the support structure a hospital provides. How are they faring? A survey that was sent in February and March 2020 to 450 Italian primary care physicians affiliated with a single hospital in Lombardy (the hardest hit region of Italy) provides a glimpse.
Of 272 respondents (60% response rate) who were providing care to an estimated 400,000 patients, about half reported at least one known contact with a SARS-CoV-2 patient. Almost all had tried to prevent overcrowding in the office, and about 90% had modified their practice to include phone-based care or telemedicine. Most had purchased their own personal protective equipment (PPE), less than half had received PPE from the Ministry of Health (the employer of Italian physicians), and less than 20% had provided PPE for use by waiting patients.
About 40% reported that they themselves had experienced cough, fever, or gastrointestinal symptoms during the preceding 4 weeks; symptoms lasted for longer than 1 week in about half who were ill. Only 18 respondents were tested for SARS-CoV-2; only 2 tests were positive. These data (skewed, of course, to a set of primary care doctors with the time and, presumably, the health to respond to a survey) are notable for high rates of preparation and very low rates of testing, despite a sizable prevalence of suggestive symptoms. The authors note that, when they wrote this report, 20 primary care physicians in the region had died of COVID-19.
11. Do the ACE-I or ARBs make the prognosis worse if the patient has COVID-19?
Mancia and colleagues studied 6272 people (age, ≥40) with SARS-CoV-2 infection from the Lombardy region of Italy and 30,759 uninfected controls matched by age, sex, and residence. Infected patients more commonly used ACE inhibitors and ARBs than controls. However, after multivariable adjustment, these medications were not associated with infection or severe disease.
Hypertension, Medications, and COVID-19 Risks
Harlan M. Krumholz, MD, SM reviewing Mehra MR et al. N Engl J Med 2020 May 1 Reynolds HR et al. N Engl J Med 2020 May 1 Mancia G et al. N Engl J Med 2020 May 1
Are children more susceptible to COVID-19?
A review of published pediatric cases of confirmed SARS-CoV-2 infection shows largely mild disease.
Most COVID-19 cases are in adults, but we are gaining data on the clinical effects of the virus in children (NEJM JW Pediatr and Adolesc Med Apr 2020 and MMWR Morb Mortal Wkly Rep 2020 Apr 10; 69:422). These investigators conducted a systematic review of articles published between December 1, 2019, and March 3, 2020, that included children ≤19 years of age with confirmed SARS-CoV-2 infection. They identified 17 studies from China and 1 from Singapore, which included 1065 cases. Findings include:
444 children were aged <10 years and 553 were aged 10 to 19 years (age was not provided for some). Most children acquired infection after close contact with infected family members.
Clinical presentation was mild in all cases, with the exception of one infant who had a severe presentation and required intensive care. Fever, dry cough, and fatigue, as well as nasal congestion and rhinorrhea, were the most commonly reported symptoms; gastrointestinal symptoms were noted in infants. Similar to findings in adults, radiographic findings included bronchial thickening, ground-glass opacity, and evidence of pneumonia. Although limited information on therapeutic interventions was available, only one patient required respiratory support, including oxygen therapy. One death was reported in a child in the age range 10 to 19 years, but the children otherwise recovered uneventfully.
This review suggests that infected children have mild symptoms and are not likely to require hospitalization or intensive care. We do not know the role infected children play in community spread of the virus. With new information emerging about a possible connection between SARS-CoV-2 infection and a condition that resembles Kawasaki toxic shock syndrome, it is clear there is still much more to learn about this virus.
(COVID-19 in Children and Adolescents in China and Singapore
Deborah Lehman, MD reviewing Castagnoli R et al. JAMA Pediatr 2020 Apr 22)
Does C0VID-19 affect the sense of smell and taste?
Two thirds of patients with mild COVID-19 reported alterations in their sense of smell or taste. A phone survey was completed by 202 out of 283 patients who were contacted, in Lombardy Italy. The patients’ median age was 56 years, and 52% were women. Any alteration in the sense of smell or taste was reported by 64.4% of the patients, with median score of 4. The alteration in the sense of smell or taste occurred before the onset of typical COVID-19 symptoms in 11.9% of the patients, and it was the only symptom in 3.0% of patients. Women were significantly more likely than men to report alterations in the sense of smell or taste (72.4% vs. 55.7%).
This cross-sectional survey suffers from lack of control patients — for example contemporaneous patients with respiratory symptoms who tested negative for SARS-CoV-2, or those with known infections with other respiratory viruses. Nonetheless, the Centers for Disease Control and Prevention added altered sense of smell or taste to the list of COVID-19 manifestations that would trigger priority testing. The inclusion of this symptom as a trigger for testing will likely generate data that help us define the sensitivity and specificity of this symptom when comparing COVID-19 manifestations to those of other respiratory illnesses.
Does self proning help in patients with respiratory symptoms in Covid 19?
In this observational study, oxygen saturations in patients with COVID-19 increased after self-proning for 5 minutes.
Patients with severe COVID-19 often present with profound hypoxemia. Initial recommendations for their management included early intubation, but this was not predicated on evidence. Recently, many hospitals have initiated awake or self-proning protocols early in patients’ hospital courses, in an attempt to improve oxygenation and stave off intubation. Unlike the labor-intensive and risky proning procedure in patients with acute respiratory distress syndrome (in which patients are paralyzed, sedated, and rotated onto their stomachs), with self-proning, alert patients roll onto their stomachs or sides by themselves.
In this observational study, researchers in a New York City emergency department measured the change in oxygen saturation 5 minutes after self-proning in 50 patients with hypoxia and suspected (subsequently confirmed) Covid19. Median oxygen saturation was 80% on arrival and increased to 84% after patients were placed on supplemental oxygen. After 5 minutes of proning, median oxygen saturation increased to 94%. Ultimately, 36% of patients were intubated within 72 hours and, of these, 38% (7) were intubated within the first hour.
Neurologic Symptoms and Findings Among Patients with Severe SARS-CoV-2 Infection
John C. Probasco, MD reviewing Helms J et al. N Engl J Med 2020 Apr 15
Encephalopathy, corticospinal tract signs, and frontotemporal hypoperfusion by MRI were commonly observed in the absence of detectable virus in the cerebrospinal fluid.
Researchers in France detail neurologic observations of a cohort of 58 consecutive patients admitted to two intensive care units for management of SARS-CoV-2 infection. All were positive for SARS-CoV-2 by RT-PCR assay of nasopharyngeal samples. Median age was 63 years; seven patients had a history of a neurologic disorder.
Neurologic findings were recorded on admission or when sedation and neuromuscular blockade were discontinued. Agitation was observed in 69% of patients, and 26 (65%) of 40 patients assessed met criteria for confusion. Diffuse corticospinal tract signs were present in 67% of patients. At discharge, 33% of 45 patients displayed a dysexecutive syndrome characterized by inattention, disorganization, or poorly organized movements to command.
Thirteen patients underwent brain MRI (11 with perfusion imaging) for evaluation of unexplained encephalopathy. Eight patients had leptomeningeal enhancement. Of the 11 patients with perfusion imaging, all demonstrated bilateral frontotemporal hypoperfusion. One patient had a subacute ischemic stroke. Eight patients underwent electroencephalography, which produced nonspecific findings. Of seven patients who underwent cerebrospinal fluid (CSF) analysis, none demonstrated a CSF pleocytosis and all were negative for SARS-CoV-2 in CSF by RT-PCR.
As the authors note, it is unclear to what extent these neurologic observations can be attributed directly to SARS-CoV-2 infection as opposed to encephalopathy due to critical illness, the systemic response to infection, or the effects of medications. The frequent observation of corticospinal tract signs is notable. The lack of virus or other notable findings in CSF assays could result from either absence of central nervous system infection or poor RT-PCR assay sensitivity. The asymptomatic stroke raises concern for increased stroke risk in the setting of systemic inflammation. Dysexecutive syndrome in one third of discharged patients indicates a need for close post-hospitalization follow-up. We anticipate that future studies will clarify the pathogenesis of SARS-CoV-2 neurologic syndromes and guide preventive, acute, and longitudinal treatment.
Is there a definite treatment available for COVID-19?
Since the first cases were reported in December 2019, infection with the severe acute respiratory coronavirus 2 (SARS-CoV-2) has become a worldwide pandemic. COVID-19 — the illness caused by SARS-CoV-2 — is overwhelming health care systems globally. The symptoms of SARS-CoV-2 infection vary widely, from asymptomatic disease to pneumonia and life-threatening complications, including acute respiratory distress syndrome, multisystem organ failure, and ultimately, death. Older patients and those with preexisting respiratory or cardiovascular conditions appear to be at the greatest risk for severe complications. In the absence of a proven effective therapy, current management consists of supportive care, including invasive and noninvasive oxygen support and treatment with antibiotics.8,9 In addition, many patients have received off-label or compassionate-use therapies, including antiretrovirals, antiparasitic agents, anti-inflammatory compounds, and convalescent plasma.
Remdesivir is a prodrug of a nucleotide analogue that is intracellularly metabolized to an analogue of adenosine triphosphate that inhibits viral RNA polymerases. Remdesivir has broad-spectrum activity against members of several virus families, including filoviruses (e.g., Ebola) and coronaviruses (e.g., SARS-CoV and Middle East respiratory syndrome coronavirus [MERS-CoV]) and has shown prophylactic and therapeutic efficacy in nonclinical models of these coronaviruses. In vitro testing has also shown that remdesivir has activity against SARS-CoV-2. Remdesivir appears to have a favorable clinical safety profile, as reported on the basis of experience in approximately 500 persons, including healthy volunteers and patients treated for acute Ebola virus infection
In this cohort of patients hospitalized for severe COVID-19 who were treated with compassionate-use remdesivir, clinical improvement was observed in 36 of 53 patients (68%). Measurement of efficacy will require ongoing randomized, placebo-controlled trials of remdesivir therapy. (Funded by Gilead Sciences.). Hence the compassionate use of remdimovir is being practiced even though all the studies are not completed and FDA approval not given as yet,