As we reach Day 4 of Week 7 of the Covid-19 epidemic, we have all been consumed with the still elevated case rates and death rates in Massachusetts, as well as with our personal safety and our livelihoods. All serious concerns.
Where we are right now in our state
The reported deaths in Massachusetts from the Covid-19 virus have been steadily increasing and are now over 180 daily. By contrast, the average daily death rate from infectious diseases in our state in 2017 was four (4) and the average total daily deaths was 161:
New cases remain at a high level but are no longer increasing daily, but neither are they particularly decreasing through yesterday, not to mention the retroactive addition of several thousand confirmed cases by the state to prior data because of late reporting by Quest.
So we are more or less at a plateau because new cases levels are flat, but the total number of cases (prevalence) will continue to grow because we continue to generate far more new cases than the number of cases from 21 days ago that have completed their course and no longer have active disease. For example, the five-day average of new cases yesterday was 2334. The number of cases dropping out on 4/1 was 1176, almost exactly half the new ones.
We will need to see (and indications have been that we will see) a reduction in the daily number of new cases in order to be able to see a decline in total active cases. Allowing for a 6% daily decrease in current cases (that I have been using for reasonable if a bit simplistic estimation of the rate of decline), we may begin a slow decline in prevalence by the end of April, although we will certainly need till end of May or early June to get down to low levels in the state. I believe this is consistent with most of the more complex models and predictions:
How can we and should we think of risk?
The Covid-19 disease and its distribution and risk to different locales and individuals is immensely complicated to analyze and explain. I will do my best to highlight the underlying themes we need to consider, with emphasis on the inherent uncertainties in all medical tests. I promised myself (for you) that I would also be brief, but I am not sure that I will achieve that goal. We should first review quickly how we diagnose a disease and the role of testing.
How do physicians make a diagnosis?
Physicians make medical diagnoses based on the history or story of the problem as told by the patient or observed from the environment, by physical examination (some of which can be done by video), and by testing, both lab tests and imaging of many sorts. A single lab test is usually only part of the diagnosis, though often an important part. We analyze and organize this data to arrive at a medical conclusion, or diagnosis, as to what the condition is, usually with some understanding as to the known cause, and hopefully with knowledge of some treatment, preferably one that reliably works.
In the case of Covid-19 this process may be difficult and uncertain. We all have heard the “usual” story of onset of cough, shortness of breath, fever and malaise, but hardly everyone gets those symptoms. Fever sometimes doesn’t come till well into the illness. Some people initially have primarily sore throats without cough. Others sometimes mainly intestinal problems including diarrhea. And many other variations. And most important, the CDC (Centers for Disease Control and Prevention) has documented that sizeable numbers of people with documented Covid-19, especially including children, demonstrate no symptoms at all. So the strength of the history in making a Covid-19 diagnosis is really reduced, even when we focus on details of possible exposures.
What are the tests for active Covid-19?
You all have heard of the annoying nasal swab to get a RT PCR test for active infection. RT stands for reverse transcriptase. PCR stands for polymerase chain reaction, a method of amplifying the viral RNA picked up on the nasal swab, to allow confirmation that the virus is present. This is currently the “gold standard” of detection for active cases of Covid-19. You all also know how hard it has been to get such testing for the past two months, with most testing restricted to actively ill patients with suggestive respiratory syndromes. We are still weeks or much more away from getting such a test on anyone who is modestly ill or with no obvious exposure.
The restriction in testing is not because it would be wrong or unhelpful to test more widely, or just because someone was worried (sometimes tests are therapeutic not just diagnostic, by the way), but because we remain shamefully lacking in testing capacity. No other biological test in my memory has ever been unavailable or restricted as the Covid-19 PCR.
How useful is the PCR test?
However, we need ask how good is the PCR test for diagnosing or excluding active disease? The short answer is that, if the test is positive, it likely confirms that you have Covid-19, certainly if you have compatible symptoms. There are not many false positives. If we had the ability to test all the population, this would clearly be the way to ferret out all the infected people who are without symptoms (they exist in real numbers) so they could quarantine themselves. That would be immensely useful, but can’t happen since we lack the testing capacity. Any other method of testing (there are others underway) that reliably located antigens of the active virus (rather than RNA) might serve this screening role for active disease, if such tests were widely available. Keep tuned.
If, however, you test negative by PCR, then the answer is much fuzzier. Reports from China and elsewhere worry that up to 30% of people who have the Covid-19 syndrome and appear ill may falsely test negative by PCR. The diagnosis of Covid-19 may still be made, however, based on history and physical findings and chest CT and so forth, since the lab test is only part of the information.
What about those PCR false negatives?
The false negative rate really comes into play if you desire to clear people as free of active disease so they can return to work, or for you to socialize with them in small groups, or visit grandma, and so forth. Being certified free of active disease is immensely useful. It is also difficult to achieve. Why?
If the PCR specificity (ability to accurately identify currently infected and contagious people) is well less than 100%, what do you do? You can test repeatedly in a short period. If the specificity is 70%, then 30% of the time an infected person could test negative. If you repeat the same test, the likelihood of two successive false negative tests is 0.3 x 0.3 or 9% (o.09). Is that acceptable, a 9% chance of infection in someone said to be clear? Probably not. It takes two more or a total of 4 sequential PCR tests at 70% specificity to get the risk of being wrong below 1% (0.3*0.3*0.3*0.3=0.008 or 0.8%). If you are happy with that level of risk (1% chance of being wrong), then you are okay. But even if the false negative rate is only 10%, single negative PCR tests are unlikely to assure people that they are reliably free of disease, especially not when the stakes are high (such as interacting with highly vulnerable older relatives), without considering the overall exposure context.
For the record, medical staff are being cleared to return to work at most hospitals after two (not four) PCR tests. That would suggest a specificity of 90% for the PCR tests to hit a 1% risk of false negative after two tests. It is hardly clear that the tests are that good.
This exercise was to explain why PCR tests are not our saviors, even though their lack of availability remains an embarrassing debility. Currently single negative PCR tests, devoid of context, are weak data, although positive results offer solid confirmation in the context of apparent disease.
What about antibody testing?
Antibody testing will eventually be useful but how and when is fuzzy, like the PCR data. After exposure to a viral disease, our bodies develop early antibodies of a specific class, called IgM, that appear in perhaps 10 days and last 3-6 months, and later give way to long-acting IgG antibodies, that may start as early as 6 weeks or so and can last a lifetime. Knowing the presence of IgG or IgM antibodies to Covid-19 certainly could be immensely useful. But, again, there are still issues.
First, the accuracy of the current crop of antibody tests, which we have all just begun to hear about, is questionable. The New York Times just reported 3 days ago on an independent scientific analysis of 14 different antibody lab tests, none as yet approved by the FDA but allowed on the market by an emergency exception. The disappointing result was that 11 of the 14 were grossly inaccurate and unusable. These did not include a newly announced Quest Diagnostics test, but the same concerns have to apply to that as well until further validation data by experts is available. An unreliable antibody test, whether positive or negative, is worse than nothing.
Second, even if we had accurate results of IgG testing, it is still not known whether IgG antibody is actually protective against reinfection. This is the crucial issue. The World Health Organization and our CDC continue to identify that as the critical issue to be resolved in order to deploy IgG testing for epidemiological purposes and for decision-making. The obvious import of having protective IgG antibody would be the ability to go out, circulate and work and socialize without worry. In reality, though, most people are expected to test negative since epidemiologists think that a relatively small proportion (? 5-10%) of the whole population has been affected so far.
Third, if it were accurate, IgG testing would be intellectually satisfying to confirm that a prior case had in fact been Covid-19, even if antibodies prove not to be preventive. But the tests still have be to known reliable, and they are not yet. When antibody tests are reliable, we certainly will recommend that most patients get them to learn where they stand, perhaps even before it is definite as to the protection they provide.
Opportunity to help validate an antibody test
If you want to help in the validation process of a new, quantitative IgG/IgM antibody test, specifically by providing a fingerstick blood test, your help would be welcome. An Orchard Health Care member, Andrew E. Levin, Ph.D., is the president and scientific director of Kephera Diagnostics LLC, which is working to complete the validation of their ELISA antibody test, which has preliminary approvals. While they are primarily looking for people with PCR confirmed Covid-19 (who are exceedingly few in our practice), they may soon be interested as well in testing people who clinically appeared to have Covid-19 but could not get PCR tests. There are a number of members like that. A flyer attached explains what they are doing and how to contact them.
Managing your risk in face of uncertainty
Enough of all the uncertainties of exposure, testing and so forth. Life is uncertain. This disease is uncertain but clearly worrisome. Next week will be different. What do we do now?
Let’s summarize the environmental risks, the biological risks, what personal defenses we can invoke, and then what our personal safety strategies might be.
First, I want to list important components of the environmental risk framework:
- Densely populated areas near Boston and elsewhere are generally more affected than western Mass. rural areas, and Massachusetts has higher overall infection rates than most states
- Dense living conditions (nursing homes, assisted living, rest homes) and downtowns are much more affected than suburban and rural areas. Nursing homes and related eldercare facilities account for around half of all cases and deaths
- Infection rates appear highest in prolonged close social contact with others especially indoors (think conference rooms, auditoriums, also restaurants, churches and family gatherings). Distance matters, hence the 6 ft standard.
- Brief passing contact and outdoor contacts have little risk of spreading the virus (duration of contact matters)
- CDC recently confirmed that infected people can be contagious for at least 48 hours before they are symptomatic, and people can also be contagious and never be symptomatic. While the numbers may be small, it is clear that the lack of a cough or fever does not mean another person is free of disease. The hidden illness makes assessing the risk much more difficult.
- Inanimate objects such as mail, cartons, or your groceries all have low risk of passing the virus, although hard surfaces in public places are suspect
- Currently there is no effective therapy for Covid-19, though countless companies are working to find one (it is not hydroxychloroquine or bleach)
- Currently there is no vaccine for Covid-19, though an Oxford University group apparently is close to a human trial (light speed in terms of vaccine development)
Second, the biological risk is not uniform. CDC as well as world data are clear on this. As of yesterday 958,000 Americans were confirmed with the disease:
- Children are rarely seriously affected
- All age groups are affected, most recently of the total cases so far, 2% were under 18, 35% were 18-44, 35% were 44-65, 11% were 65-74, and 12% 75 or older (CDC data)
- Severity increases with age, with greater hospitalizations, ICU need, and deaths with increasing age especially after age 65-70.
- Significant underlying diseases make for greater severity and death at any age. These include active heart and kidney disease, insulin-dependent or poorly controlled diabetes, chronic obstructive lung disease and obesity, but do not clearly include well controlled high blood pressure or preventive drug programs to prevent heart disease.
- Immunosuppression with Enbrel or comparable biologicals for rheumatoid arthritis, psoriasis, Crohn’s disease or multiple sclerosis likely are a risk for more severe Covid-19 disease, but that is not necessarily an indication to forgo such treatment.
- In addition, anyone at any age can potentially have a severe and overwhelming case of Covid-19, where the exact susceptibility is as yet not known.
- CDC recently confirmed that people who are infected can be contagious for at least 48 hours before they are symptomatic, and people can also be contagious and never be symptomatic. While the numbers may be small, it is clear that the lack of a cough or fever does not mean another person is free of disease.
Third, what personal safety measures can we take in the absence of a vaccine or preventive medication? These issues have been much discussed:
- Staying at home in quarantine, more or less, avoids external contact with any Covid-19 risk of an infected or unknowingly infected person. But we don’t want to do this forever. It is getting pretty long already.
- Frequent and careful handwashing works well against the virus. Purell is an acceptable substitute if soap and water not available or convenient.
- Careful social distancing of at least 6 ft indoors or out, preferably a bit more indoors, should be effective. It is not completely clear that simple distancing is truly protective for prolonged lingering in an indoor space, even with a standard surgical mask.
- Wearing masks when encountering others is likely to be mandatory for some time, but which mask matters, and our mask supply is limited.
- Surgical or procedure masks protect others from you but are not really secure against incoming air streams in close contact. These are still in short supply though some people have been able to get them. They are probably the best available for the moment.
- N95 “respirator” masks provide the most secure protection against infection, and are now worn by all medical personnel working with Covid patients, but they have been and remain exceedingly hard to obtain. We are still trying to get an adequate supply for our office after two months. I think this should be the target mask for everyone once they finally become available.
- Cloth face masks may offer some protection for others, and perhaps some for you for low-threat encounters (a quick run into the pharmacy to pick up something), but they are a thin reed on which to base your safety in any close contact situation. As soon as supplies of surgical masks or N95 improve, the hand-made masks should be retired.
- Eye shields are worn by medical staff in any close encounter with a patient with Covid-19. These are little talked about, but the virus can infect (according to CDC and other data) by landing on the cornea and eventually finding its way to the nasal passage through the tear drainage system. Close contacts with infected people do carry risk of infection through the eyes.
Importance of better PPE to mitigate enhanced risk
I want to emphasize the potential importance of seriously effective face and eye protection as part of an eventual repertoire for our own self-protection as we consider our emergence from hibernation later this spring. The CDC emphasizes both face and eye protection for front-line health care workers, but unlike N95 respirator masks, eye protection has received little public comment.
In a CDC guidance this month directed toward health care personnel working with Covid-19 patients, the document (Interim U.S. Guidance for Risk Assessment and Public Health Management of Healthcare Personnel with Potential Exposure in a Healthcare Setting to Patients with Coronavirus Disease 2019 (COVID-19)) made clear that N-95 masks were clearly better protection in close quarters with an infected person than was a plain surgical mask, and also that eye protections (shields or goggles) had independent benefit of protection.
In fact, their table of exposure risks fact elevates the seriousness of any close exposure to an infected patient (direct contact, aerosol-producing procedures) by one level, from low to medium risk (requiring 14 days quarantine) for wearing a surgical mask and not an N95 respirator, and establishes a medium level risk in close physical patient contacts (think massage parlor workers) who don’t have an eye shield.
While these risk evaluations and PPE advice related to health professionals dealing directly with Covid-19 patients, the issue relates to everyone. The CDC recommends elevating the level of personal protection equipment in response to a higher risk of exposure, in order to reduce the combined risk of a Covid-19 infection and adverse personal outcome for the average healthy health care professional.
Similar analysis promptly suggests that one could and should elevate one’s level of personal protection at any given level of exposure if one is either at higher risk of infection or of suffering a worse outcome if infected. The CDC advisory specifically points to better masks and eye protection as key tools of greater self-protection.
My suggestions to thinking about your own risk profile
Everyone must remember that, ultimately, anyone you meet for many months could be an asymptomatic carrier or presymptomatic victim of Covid-19. The only questions is how widespread this asymptomatic disease is, which we hope to learn by community test sampling over the next few months. This is why “universal precautions” for everyone’s protection are what is needed, implemented through social distancing and masks.
- Everyone should plan to practice careful social distancing for the foreseeable future. Six feet is minimum. Outdoors is less risky. Masks must be worn in any close encounter, however brief, as part of social distancing. Of course careful handwashing. Gloves do not appear to be essential if you wash your hands carefully after any exposure.
- Additionally, everyone should also give careful thought before lingering in any inside space with any group, even if separated and wearing standard surgical masks. While separation and a plain surgical mask appear to work well for healthy people in short encounters (like going through super markets), I am personally skeptical that the same is true of long stationary stays in a room. I can’t imagine, therefore, how dining in restaurants can safely return in coming months. Fortunately the summer months will enable safer outdoor social contact.
For younger and middle-aged healthy people, the effective safety from social distancing and plain surgical masks (and in some brief circumstances, a cloth mask) may be sufficient protection to lower your risk level compatible with your lower risk of developing serious disease from Covid-19. Similarly, eye protection may not be needed for you in general, because of the lower risk of severe outcome from a Covid-19 infection.
For older members (over 65 even if vigorous, as most of you are) and for anyone on any immunosuppression, you should carefully think about your risk profile. Data show that you are more likely to have a severe course with a Covid-19 infection should it occur, and those who are immunosuppressed are also more likely to contract the infection. So your defensive posture should be higher to mitigate your enhanced risks. The goal is to keep everyone out of hospital or the ICU.
To me this means that older or immunosuppressed members should use stronger PPE when out, specifically trying to obtain N95 masks (like medical workers) as your protection norm. And you should strongly consider some sort of face shield, which could be worker’s goggles from Home Depot, for any prolonged encounters even with social distancing and the N95. I would also be reluctant to engage in closed room social gatherings with any lingering, even with that protection. I am essentially suggesting you adopt these higher protective barriers (like general medical staff) to protect you against the unknown but still present Covid-19 exposures since you are more susceptible and since the outcome of infection is likely to be more serious.
I have tried to walk you through multiple, some rather complex issues with the Covid-19 epidemic, starting with where we are in the infection epidemiology and then exploring the types and efficacy of biological tests, and winding up with discussion of differential personal risk and differential possible responses in behavior and personal protective ingredients. My apology for the length of this discussion. I tried to keep it short, but ultimately chose clarity over brevity. I hope you see it that way as well.
Comment and questions are welcome.