As a physician assistant, as a nurse practitioner, as a physician, we have to have one source we get our content from. Most people refer to a site called UpToDate, which offers providers up to date medical knowledge. It’s updated all the time and I believe people feel it’s an authoritative reference, because whenever information is updated, it immediately goes to UpToDate. It’s really considered the gold standard for understanding disease processes.
I’ve summarized the information on COVID-19 from UpToDate as of Monday, March 30th. This is the best information I can give based on the data available. This is an informational newsletter, not just for clinicians, but also for laypeople. I’m going to describe what we know about the novel coronavirus, not just in medical language, but also so patients can understand it. In my experience, there’s some very confusing stuff on the news. You hear doom and gloom and then you hear the opposite; it’s hard to know what to believe.
I want to provide the most objective information possible from UpToDate on this problem we’re going through, this pandemic. COVID-19 is now deemed severe acute respiratory distress syndrome coronavirus two. They’re saying this is very similar to SARS. This beta coronavirus is in the same family as severe acute respiratory syndrome, or the SARS virus.
What We Know About COVID-19
The virus has been shown to use the same receptor, the angiotensin-converting enzyme 2 (ACE2), for cell entry. If you’re a layperson, that won’t mean much to you. If you’re a clinician, that makes you think, “Should we cease ACE inhibitors or angiotensin receptor blocking?” The answer is no, but we’ll talk about that later.
In an analysis of 103 strains of COVID-19 from China, two different types were identified. The first is designated as type L, counting for 70% of the strains. The second is type S, which makes up about 30%. It’s unclear how this information is relevant; understand there have been 103 strains, with two different types designated as sinister.
The bottom line is that we don’t completely understand the route of transmission. Person-to-person is the main mode of transmission. It is thought to occur mainly via respiratory droplets, similar to influenza. Droplets typically do not travel more than six feet and do not linger in the air.
However, in one letter to the editor, it was stated that COVID-19 remains viable in aerosolized medium, at least under experimental conditions, for at least three hours. That’s why I’ve been told that in the emergency room they’re avoiding anything that may aerosolize pulmonary secretions, like nebulizers or someone with those puffers. The puffer, I don’t think, is as sinister as a nebulizer, where a patient is hooked up to oxygen and medication runs in. That does give more secretions.
How long is a person infected?
How long are you sick? We don’t know for sure. Anything you see or hear online is speculation. We know that the viral RNA levels appear to be higher soon after symptoms of onset, when compared to levels later in the illness. This suggests transmission is more likely in the earlier stages of infection, but we don’t know that for sure. Now remember, symptoms that we’re going to talk about later are primarily fever and pulmonary symptoms. We’re going to come back to that.
How long does the virus stay around? In one study of 21 patients with mild illness, meaning they weren’t short of breath, they weren’t hypoxic, 90% tested negative 10 days after the start of symptoms. So, with mild symptoms, 90% of the 21 patients, about 18 or 19, were retested at 10 days and the test didn’t find the virus. Tests were positive for longer in patients with more severe disease. In another study of 137 patients who lived, the duration was an average of 20 days, ranging from eight to 37 days. How long is the virus around? It appears anywhere from 10 to 37 days, depending on the severity of the illness.
How contagious is this virus?
If I’m on a bus and there’s someone else on the bus who’s got the virus, what are the chances I’m going to get it, especially if they’re within six feet? Transmission from someone who’s sick varies from person to person. The rate of transmission ranges from 1 to 5% among tens of thousands of close contacts of confirmed patients in China. Among crew members on a cruise ship, 2% developed a confirmed infection.
In the United States, the symptomatic secondary attack rate was about half a percent, 0.45%, among 445 close contacts in 10 confirmed patients. So the bottom line is that the contagious rate is anywhere from about half a percent to 5%.
What is the incubation period?
We believe that it’s about 14 days after exposure, with most cases occurring approximately four to five days after being exposed. Let me make this clear. If I’m in close contact with someone who has COVID-19, my chances of getting it are anywhere from half a percent to 5%. And I could develop symptoms for up to two weeks, even though it’s more likely that if I’m going to get sick, I’m going to get sick at about day five. Those are good general rules.
The good thing is that, based on the best information, about four out of five people who get this are going to have a mild disease. There will be either no pulmonary symptoms or mild pulmonary symptoms in 81% of patients. Severe cases, where your lungs are involved (dyspnea, hypoxia, greater than 50% of lung involvement on a CAT scan), make up about 14% of cases. Critically ill patients are 5% of patients.
Let me back up for a second. Ladies and gentlemen, the infection rate is anywhere from half a percent to 5%. If you’re going to get sick, you get sick at five days. And if you’re going to get sick, 81% of the time it’s going to be mild. This information is a little bit more reassuring to me. Clearly, a lot of bad stuff is going on, but to me, those are reassuring numbers.
The overall case fatality rate so far has been 2.3%. No deaths were reported among patients in noncritical cases.
What are the risk factors for severe disease?
I think this is relatively obvious. If you work in medicine, anytime someone is sick, like with pneumonia, you look at the patient and how sick they were when they presented. Do they have cardiovascular disease or risk factors like diabetes, hypertension, chronic lung disease, chronic kidney disease, or cancer? All of those are linked to worse outcomes.
Now, this is not as much for the layperson. This is more for clinicians. What are some of the signs of poor prognosis? Lymphopenia, low white counts, elevated liver function tests, elevated LDH, elevated inflammatory mediators, such as C-reactive protein and ferritin, elevated D-dimer, elevated prothrombin time.
There is also the impact of age. Adults of middle age and older are most commonly affected, relative to kids. Symptomatic infections in children appear to be uncommon. When it occurs, it’s usually mild, although severe cases have been reported.
Can you have the virus without symptoms?
Can you be an asymptomatic carrier? Yes. Asymptomatic carriers have been described, but we don’t know how often. We just don’t have good data on it. So, you could have no symptoms but carry it to other people. On a cruise ship, most passengers and staff were screened. About 17% tested positive. About half of the 619 confirmed cases had no symptoms at the time of the diagnosis. So absolutely, you can have the virus in you and be a carrier, but have no symptoms.
If the patient has no symptoms, can there still be evidence of disease? Yes. Someone asks me, “John, how do you feel?” I feel good. But then, if you do a CAT scan, the CAT scan might be positive. A study of 24 patients without symptoms who had a chest CT found that 50% had the typical ground-glass opacities or patchy shadowing, and another 20% had some degree of CAT scan abnormalities.
What are some of the clinical manifestations?
How do COVID-19 patients present? The initial presentation is typically pneumonia.
Even a low-grade temperature should be a flag. Let’s make sure we’re really digging into the data on fever. A fever might not be a universal finding. In one study, fever was reported in almost all patients, but about 20% had a very low-grade temp. That means less than 100.4. In another study of about 1100 patients from China, fever defined as an axillary temp above 99.5 was present in only about 44% on admission, but was ultimately noted 89% of the time during hospitalization.
My concern with this is that it was an axillary temp. It was in the armpit, which is notoriously poor. I don’t know how much I can rely on that if it’s not an oral temp, but I understand it. Why wouldn’t they use an oral temp? With an oral temp, you’re getting into secretions.
And then there are pulmonary symptoms. So about 60% of cases had pulmonary symptoms like a dry cough, about 30% had shortness of breath, about 30% coughed up some sputum, and about 30% were overtly short of breath.
Constitutional symptoms include anorexia, meaning they had no appetite, they weren’t hungry, about 40% of the time. You’ll also see muscle pain or myalgias 35% of the time. Overall fatigue is present 70% of the time. Less common symptoms of headache, sore throat, rhinorrhea (a runny nose), and GI symptoms, such as nausea, vomiting or diarrhea have also been reported in some patients, and that may be the presenting complaint.
Anosmia (no sense of smell) has been anecdotally reported. That’s hasn’t been supported in data. A colleague of mine who lives in New York, she said her phone blew up with people calling and saying, “I can’t smell anything.” It was because it just came out that people with COVID-19 could possibly lose their smell.
What about the course and complications?
What does UpToDate say? Well, dyspnea presents approximately five days after onset of symptoms and hospital admission occurs typically about seven days after symptoms appear. Acute respiratory distress syndrome is the major complication. That’s where your lungs just freak out and shut down. In a study of 138 patients described with acute respiratory distress syndrome, it developed in about 20% approximately eight days after the onset of symptoms. In another study, 41% of patients developed ARDS. What does the acute respiratory distress syndrome literature tell me? About 20% will get it. If you have risk factors, the chances go up. Age greater than 65, diabetes, and hypertension were each associated with ARDS.
Other complications include arrhythmia (abnormal heartbeat) and acute cardiac injury, which means your heart took a beating. Not necessarily that you’ve had a heart attack, but your heart got sick from an infection. Or there’s been overt shock, that’s where you lose your blood pressure and that doesn’t perfuse your body well.
In a series of 21 severely ill patients admitted to the ICU in the United States, about one-third of them developed cardiomyopathy. If you have cardiomyopathy that means that the heart gets sick, it can’t pump blood well, and the patient goes into a kind of congestive heart failure.
Recovery time appears to be around two weeks for mild infections and about three to six weeks for severe infections. In laboratory findings, the white blood cell count can vary, so it could be high or low, as well as a lymphocyte count. The lymphocytes typically fight viruses and that’s been shown to be low. Elevated lactate dehydrogenase, LDH, and ferritin levels are common, and elevated AST and ALTs are also common. CAT scans demonstrate this ground-glass opacification that’s consistent with viral pneumonia.
When should we test?
When should we even consider testing? Consider this diagnosis in patients with a new onset of pulmonary symptoms and/or fever. Increases rate relative to exposure: if you traveled within the prior 14 days to a risk location or had close contact with a confirmed or suspected case. And if you think you have COVID-19 and do not need emergency care, call prior to presenting to an emergency room.
A positive test generally confirms the diagnosis, although false-positive tests are possible. That’s the best UpToDate can say. If initial testing is negative, but the suspicion for COVID remains, the World Health Organization (WHO) recommends re-sampling and testing from multiple respiratory tract sites. We just don’t know how accurate those tests are.
Let’s say you have mild disease and you’re going to stay at home. Stay at home and be smart. Try to separate yourself from other people and animals within the household. You should wear face masks when you’re in close contact with others. Disinfect frequently.
How long should we home isolate? When a patient has a positive test, and the patient may discontinue home isolation when there is:
- A complete resolution of fever without using medication to lower your fever. And remember, right now we’re recommending only acetaminophen or Tylenol. We are not recommending ibuprofen, Motrin or Advil.
- Improvement in your lung symptoms, so you don’t have the cough. All your lung symptoms go away.
- Two negative specimens done 24 hours apart.
Now, testing is limited so that seems incredibly unrealistic. If you’re going to be at home, we’re really looking for decreasing of the fever and betterment of your pulmonary symptoms. You want to talk to your primary care provider about how you’re going to get testing done and if that’s even an option for you.
So what about if there’s no test done? If you have mild symptoms, they’re not recommending testing. So if you have no testing done, when could you discontinue home isolation? Patients may discontinue home isolation when the following criteria are met:
- At least seven days have passed since the symptoms first appeared.
- At least three days or 72 hours have passed since recovery from the symptoms.
Again, resolution of symptoms is defined as reduction of the fever without the use of fever-reducing medications, and improvement of the pulmonary symptoms, including cough or shortness of breath.
For example, a person came down with a fever and a cough on Monday and they felt like crap for another two days (Wednesday and Thursday) and felt better on Thursday. By Thursday there was no cough, no fever, no shortness of breath. Then, if they remain symptom-free Friday, Saturday and Sunday, they could go back in the public on Monday. That’s what I believe they’re saying.
The WHO suggests home isolation in patients with documented COVID-19 should continue at least two weeks after symptom resolution. These patients often need oxygen. If they need oxygen, we have to be very careful about aerosolizing secretions because we don’t know the risks.
How do we treat COVID-19 patients?
What about steroids, glucocorticoids, things like prednisone, dexamethasone or Solu-Medrol? The WHO and the Centers for Disease Control and Prevention (CDC) recommended glucocorticoids not be used on COVID-19 patients unless it’s needed for another indication, such as COPD or asthma. Glucocorticoids have been associated with an increased risk in some viral infected patients.
What about NSAIDs (ibuprofen, Motrin, Advil, Aleve, Naprosyn)? We’re uncertain. These concerns are based on anecdotal reports from a few young patients who received NSAIDs early in the course of infection and then experienced severe disease.
Just so you know, when they say anecdotal, it’s not evidence-based. It just means some people said, “Hey, these people got pretty sick when they used Motrin.” There could be no correlation, there could be a correlation. We don’t know for sure. In light of these concerns, some providers are using acetaminophen in place of NSAIDs for reduction of fever. However, there’s been no clinical or population-based data that directly addresses the risk of NSAIDs.
What do the European Medicines Agency and the WHO say about using Motrin? Well, the European Medical Agencies and the World Health Organization do not recommend that NSAIDs are avoided when clinically indicated. So it seems we’re holding back on it, but just know that around the world they’re saying, if you need them, go ahead and use them. If they’re indicated, don’t worry about it.
What about ACE inhibitors and ARBs? Patients receiving angiotensin-converting enzyme inhibitors or angiotensin receptor blockers should continue treatment with these agents. There’s been no recommendation to stop them.
Screening is a good thing. If someone has symptoms, they recommended possibly screening by phone or video conferencing. In the healthcare setting, the WHO and CDC recommendations for infection control for suspected or confirmed cases of infection differ only slightly. So basically, everybody’s pretty much saying the same thing. The World Health Organization recommends standard contact and droplet precautions: gloves, gown, mask, and eye protection or face protection. The addition of airborne precautions, such as respirators, is warranted during aerosolized-generating procedures.
The CDC recommends that patients with confirmed or suspected COVID-19 be placed in a single occupying room with a closed door and dedicated bathroom. The patient should wear a face mask if being transported out of the room. An airborne infection isolated room, i.e., a single-patient negative pressure room, should be reserved for patients undergoing aerosolized generating procedures. Any personnel entering the room of a patient with a suspected infection should wear the appropriate personal protective equipment: gloves, gown, eye protection, and a respirator – an N95 respirator, not just a mask.
We have limited resources, right? So if respirator supply is limited, the CDC acknowledges that face masks are an acceptable alternative, in addition to contact precautions and eye precautions; respirators should be worn during aerosolized-producing procedures. Aerosolized-generating procedures include tracheal intubation; noninvasive ventilation, so that’s BiPAP or CPAP; a tracheostomy; CPR; manual ventilation before intubation, so that’s Ambu bagging; upper endoscopy; and bronchoscopy.
The CDC does not consider nasal pharyngeal oropharyngeal specimen collection an aerosolized generating procedure that warrants an airborne isolation room, but it should be performed in a single occupied room with a closed door, and any personnel in the room should wear a respirator, or if unavailable, a face mask. In Washington State, suboptimal use of infection control procedures contributed to the spread of the infection. So there’s some evidence that this is clearly really important – it sounds intuitive, but there’s also some evidence behind it.
So, we have a shortage of personal protective equipment (PPE). What’s recommended? We’re in a battle zone right now; we have to do what we have to do. Strategies include canceling non-urgent procedures or visits that would warrant the use of PPE, prioritizing the use of certain PPE for high-risk situations, and cautious extension or limited reuse of PPE.
What about decontamination with ultraviolet light for reuse, particularly of N95 respirators? It has been shown to be helpful with other viruses like H1N1, so it’s an option.
What about pregnant and breastfeeding women? In a review of 38 pregnant women with COVID-19, no cases of intrauterine transmission and no maternal deaths have been documented. The approach to prevention, evaluation, diagnosis, and treatment of pregnant women with suspected COVID-19 should be similar to that of a non-pregnant individual. It is unknown whether the virus can be transmitted through breast milk. The only report of testing found no virus in the maternal milk of six patients. Hand hygiene and use of a face mask are recommended if breastfeeding.
Preventing Community Exposure
We need diligent hand washing, particularly after touching surfaces in public. The use of hand sanitizer that contains at least 60% alcohol is a reasonable alternative if hands are not visibly dirty. Respiratory hygiene, covering your cough or sneeze, is important. Avoiding touching your face and in particular your eyes, nose, and mouth – mucus membranes. Avoid crowds, particularly in poorly ventilated spaces. If possible, avoid close contact with ill individuals. Clean and disinfect objects and surfaces that are frequently touched.
If COVID-19 is prevalent in the community, residents should practice social distancing by staying at home as much as possible. Individuals who develop an acute respiratory illness, i.e., fever and/or respiratory symptoms, should be encouraged to stay home from school or work for the duration of the illness.
In situations involving asymptomatic individuals with potential exposure, it’s recommended that we practice social distancing and be monitored for the development of consistent signs and symptoms (cough, fever, dyspnea). In some cases, quarantine may be warranted. Clinical manifestations should prompt self-isolation at home and should be dictating medical evaluation. In the United States, the CDC currently recommends that individuals avoid all nonessential travel to high infection rates areas.
UpToDate says we should consider the diagnosis primarily in patients with fever and/or respiratory tract symptoms who reside in or have had traveled to areas with community transmission, or who have had recent close contact with a confirmed or suspected case. We’re looking at two factors: fever and pulmonary symptoms, and risk. Have you been exposed?
Limitations in testing capacity may preclude testing in all patients. We just don’t have enough tests for everybody. The CDC recommends a single occupying room for patients with gloves, gown, eye protection, and respirator (or face mask as an alternative) to healthcare practitioners.
Management consists of supportive care. And we must reduce the risk of transmission. So folks, wash your hands, practice respiratory hygiene, cover your cough, avoid crowds and close contact with individuals. Social distancing is advised.
A John-ism for You
This is a John-ism; it’s me just talking to you. This is not from UpToDate. Remember that viral bronchitis is still real. Allergies are still very real. You can still get pneumonia. You want to look at yourself and say, “Do I have a fever? Do I have pulmonary symptoms? Have I been exposed?” I’m here at a condo development in St. Petersburg, Florida. I have very little contact. I’m by myself all day and I go out on the boat. I’m not around people, so I’m a really low-risk guy. So if I got pulmonary symptoms, I’m not jumping to the conclusion that I have COVID-19.
If you have pulmonary symptoms and a fever and you have not been around people, that still puts you in a low-risk category. Be very hesitant just popping up in an emergency room, because you don’t want to get sick in the emergency room. And if you do have COVID-19 and you have mild symptoms, you don’t want to bring it into the ED.
We have to be smart about this, okay? We have to be reasonable about this; maybe that’s the best way to put it. Because I don’t even know what smart is anymore. I grossly under predicted this. Two or three weeks ago, I was going, “Oh, come on guys, this is nothing. We’re making a big deal out of nothing.” And clearly, I was grossly mistaken, so I say it with humility. I want to be reasonable. And that’s why I want to share the best information that clinicians have right now, based on UpToDate.
Colleagues, Daniel Kahneman wrote a book called Thinking, Fast and Slow. In it, he says something that was very powerful for me. He said that the cornerstone of rationality is an unbiased appreciation for uncertainty. The cornerstone of rationality is an unbiased appreciation for what’s going on right now.
All we can do is take the best data that we have, which is being updated all the time. I’m going to keep making these newsletters and putting them out. It’s the best that I feel I can do to help my colleagues and my friends out there, people who need information. If you are like me and you’re struggling with the information on the news, I believe UpToDate is very accurate and unbiased, and that’s what I’m going to keep presenting on.