Rheumatology News

No staff members or patients were diagnosed with COVID-19 after “strict protective measures” for screening and managing patients were implemented at the National Cancer Center/Cancer Hospital, Chinese Academy of Sciences, in Beijing, according to a report published online April 1 in JAMA Oncology.

However, the time period for the analysis, which included nearly 3000 patients, was short — only about 3 weeks (February 12 to March 3). Also, Beijing is more than 1100 kilometers from Wuhan, the center of the Chinese outbreak of COVID-19.

The Beijing cancer hospital implemented a multipronged safety plan in February in order to “avoid COVID-19 related nosocomial cross-infection between patients and medical staff,” explain the authors, led by medical oncologist Zhijie Wang, MD.

Notably, “all of the measures taken in China are actively being implemented and used in major oncology centers in the United States,” Robert Carlson, MD, chief executive officer, National Comprehensive Cancer Network (NCCN), told Medscape Medical News.  

John Greene, MD, section chief, Infectious Disease and Tropical Medicine, Moffitt Cancer Center, Tampa, Florida, pointed out that the Chinese safety plan, which is full of “good measures,” is being largely used at his center. However, he observed that one tool — doing a temperature check at the hospital front door — is not well supported by most of the literature. “It gives good optics and looks like you are doing the most you possibly can, but scientifically it may not be as effective [as other screening measures],” he said.

The Chinese plan consists of four broad elements

First, the above-mentioned on-site temperature tests are performed at the entrances of the hospital, outpatient clinic, and wards. Contact and travel histories related to the Wuhan epidemic area are also established and recorded.

Second, an outpatient appointment scheduling system allows both online scheduling and on-site registration. Online consultation channels are open daily, featuring instruction on medication taking and cancer-related symptom management. These “substantially reduced the flow of people in the hospital,” write the authors. On-site patients must wear a mask and have their own disinfectant.

Third, for patients with cancer preparing to be admitted to hospital, symptoms associated with COVID-19, such as fever and cough, are recorded. Mandatory blood tests and CT scans of the lungs are performed. COVID-19 virus nucleic acid tests are performed for patients with suspected pneumonia on imaging.

Fourth, some anticancer drugs conventionally administered by infusion have been changed to oral administration, such as etoposide and vinorelbine. For adjuvant or maintenance chemotherapy, the infusion intervals were appropriately prolonged depending on patients’ conditions.

Eight out of 2,900 patients had imaging suspicious for infection

The Chinese authors report that a total of 2,944 patients with cancer were seen for clinic consultation and treatment in the wards (2795 outpatients and 149 inpatients).

Patients with cancer are believed to have a higher probability of severe illness and increased mortality compared with the healthy population once infected with COVID-19, point out the authors.

Under the new “strict screening strategy,” 27 patients showed radiologic manifestations of inflammatory changes or multiple-site exudative pneumonia in the lungs, including eight suspected of having COVID-19 infection. “Fortunately, negative results from nucleic acid testing ultimately excluded COVID-19 infection in all these patients,” the authors report.

However, two of these patients “presented with recovered pneumonia after symptomatic treatment.” Commenting on this finding, Moffitt’s Greene said that may mean these two patients were tested and found to be positive but were early in the infection and not yet shedding the virus, or they were infected after the initial negative result.

Greene said his center has implemented some measures not mentioned in the Chinese plan. For example, the Florida center no longer allows inpatient visitation. Also, one third of staff now work from home, resulting in less social interaction. Social distancing in meetings, the cafeteria, and hallways is being observed “aggressively,” and most meetings are now on Zoom, he said.

Moffitt has not been hard hit with COVID-19 and is at level one preparedness, the lowest rung. The center has performed 60 tests to date, with only one positive for the virus (< 2%), Greene told Medscape Medical News.

Currently, in the larger Tampa Bay community setting, about 12% of tests are positive.

The low percentage found among the Moffitt patients “tells you that a lot of cancer patients have fever and respiratory symptoms due to other viruses and, more importantly, other reasons, whether it’s their immunotherapy or chemotherapy or their cancer,” said Greene.

NCCN’s Carlson said the publication of the Chinese data was a good sign in terms of international science.

“This is a strong example of how the global oncology community rapidly shares information and experience whenever it makes a difference in patient care,” he commented.

The authors, as well as Carlson and Greene, have reported no relevant financial relationships.

This article first appeared on Medscape.com.

No staff members or patients were diagnosed with COVID-19 after “strict protective measures” for screening and managing patients were implemented at the National Cancer Center/Cancer Hospital, Chinese Academy of Sciences, in Beijing, according to a report published online April 1 in JAMA Oncology.

However, the time period for the analysis, which included nearly 3000 patients, was short — only about 3 weeks (February 12 to March 3). Also, Beijing is more than 1100 kilometers from Wuhan, the center of the Chinese outbreak of COVID-19.

The Beijing cancer hospital implemented a multipronged safety plan in February in order to “avoid COVID-19 related nosocomial cross-infection between patients and medical staff,” explain the authors, led by medical oncologist Zhijie Wang, MD.

Notably, “all of the measures taken in China are actively being implemented and used in major oncology centers in the United States,” Robert Carlson, MD, chief executive officer, National Comprehensive Cancer Network (NCCN), told Medscape Medical News.  

John Greene, MD, section chief, Infectious Disease and Tropical Medicine, Moffitt Cancer Center, Tampa, Florida, pointed out that the Chinese safety plan, which is full of “good measures,” is being largely used at his center. However, he observed that one tool — doing a temperature check at the hospital front door — is not well supported by most of the literature. “It gives good optics and looks like you are doing the most you possibly can, but scientifically it may not be as effective [as other screening measures],” he said.

The Chinese plan consists of four broad elements

First, the above-mentioned on-site temperature tests are performed at the entrances of the hospital, outpatient clinic, and wards. Contact and travel histories related to the Wuhan epidemic area are also established and recorded.

Second, an outpatient appointment scheduling system allows both online scheduling and on-site registration. Online consultation channels are open daily, featuring instruction on medication taking and cancer-related symptom management. These “substantially reduced the flow of people in the hospital,” write the authors. On-site patients must wear a mask and have their own disinfectant.

Third, for patients with cancer preparing to be admitted to hospital, symptoms associated with COVID-19, such as fever and cough, are recorded. Mandatory blood tests and CT scans of the lungs are performed. COVID-19 virus nucleic acid tests are performed for patients with suspected pneumonia on imaging.

Fourth, some anticancer drugs conventionally administered by infusion have been changed to oral administration, such as etoposide and vinorelbine. For adjuvant or maintenance chemotherapy, the infusion intervals were appropriately prolonged depending on patients’ conditions.

Eight out of 2,900 patients had imaging suspicious for infection

The Chinese authors report that a total of 2,944 patients with cancer were seen for clinic consultation and treatment in the wards (2795 outpatients and 149 inpatients).

Patients with cancer are believed to have a higher probability of severe illness and increased mortality compared with the healthy population once infected with COVID-19, point out the authors.

Under the new “strict screening strategy,” 27 patients showed radiologic manifestations of inflammatory changes or multiple-site exudative pneumonia in the lungs, including eight suspected of having COVID-19 infection. “Fortunately, negative results from nucleic acid testing ultimately excluded COVID-19 infection in all these patients,” the authors report.

However, two of these patients “presented with recovered pneumonia after symptomatic treatment.” Commenting on this finding, Moffitt’s Greene said that may mean these two patients were tested and found to be positive but were early in the infection and not yet shedding the virus, or they were infected after the initial negative result.

Greene said his center has implemented some measures not mentioned in the Chinese plan. For example, the Florida center no longer allows inpatient visitation. Also, one third of staff now work from home, resulting in less social interaction. Social distancing in meetings, the cafeteria, and hallways is being observed “aggressively,” and most meetings are now on Zoom, he said.

Moffitt has not been hard hit with COVID-19 and is at level one preparedness, the lowest rung. The center has performed 60 tests to date, with only one positive for the virus (< 2%), Greene told Medscape Medical News.

Currently, in the larger Tampa Bay community setting, about 12% of tests are positive.

The low percentage found among the Moffitt patients “tells you that a lot of cancer patients have fever and respiratory symptoms due to other viruses and, more importantly, other reasons, whether it’s their immunotherapy or chemotherapy or their cancer,” said Greene.

NCCN’s Carlson said the publication of the Chinese data was a good sign in terms of international science.

“This is a strong example of how the global oncology community rapidly shares information and experience whenever it makes a difference in patient care,” he commented.

The authors, as well as Carlson and Greene, have reported no relevant financial relationships.

This article first appeared on Medscape.com.

No staff members or patients were diagnosed with COVID-19 after “strict protective measures” for screening and managing patients were implemented at the National Cancer Center/Cancer Hospital, Chinese Academy of Sciences, in Beijing, according to a report published online April 1 in JAMA Oncology.

However, the time period for the analysis, which included nearly 3000 patients, was short — only about 3 weeks (February 12 to March 3). Also, Beijing is more than 1100 kilometers from Wuhan, the center of the Chinese outbreak of COVID-19.

The Beijing cancer hospital implemented a multipronged safety plan in February in order to “avoid COVID-19 related nosocomial cross-infection between patients and medical staff,” explain the authors, led by medical oncologist Zhijie Wang, MD.

Notably, “all of the measures taken in China are actively being implemented and used in major oncology centers in the United States,” Robert Carlson, MD, chief executive officer, National Comprehensive Cancer Network (NCCN), told Medscape Medical News.  

John Greene, MD, section chief, Infectious Disease and Tropical Medicine, Moffitt Cancer Center, Tampa, Florida, pointed out that the Chinese safety plan, which is full of “good measures,” is being largely used at his center. However, he observed that one tool — doing a temperature check at the hospital front door — is not well supported by most of the literature. “It gives good optics and looks like you are doing the most you possibly can, but scientifically it may not be as effective [as other screening measures],” he said.

The Chinese plan consists of four broad elements

First, the above-mentioned on-site temperature tests are performed at the entrances of the hospital, outpatient clinic, and wards. Contact and travel histories related to the Wuhan epidemic area are also established and recorded.

Second, an outpatient appointment scheduling system allows both online scheduling and on-site registration. Online consultation channels are open daily, featuring instruction on medication taking and cancer-related symptom management. These “substantially reduced the flow of people in the hospital,” write the authors. On-site patients must wear a mask and have their own disinfectant.

Third, for patients with cancer preparing to be admitted to hospital, symptoms associated with COVID-19, such as fever and cough, are recorded. Mandatory blood tests and CT scans of the lungs are performed. COVID-19 virus nucleic acid tests are performed for patients with suspected pneumonia on imaging.

Fourth, some anticancer drugs conventionally administered by infusion have been changed to oral administration, such as etoposide and vinorelbine. For adjuvant or maintenance chemotherapy, the infusion intervals were appropriately prolonged depending on patients’ conditions.

Eight out of 2,900 patients had imaging suspicious for infection

The Chinese authors report that a total of 2,944 patients with cancer were seen for clinic consultation and treatment in the wards (2795 outpatients and 149 inpatients).

Patients with cancer are believed to have a higher probability of severe illness and increased mortality compared with the healthy population once infected with COVID-19, point out the authors.

Under the new “strict screening strategy,” 27 patients showed radiologic manifestations of inflammatory changes or multiple-site exudative pneumonia in the lungs, including eight suspected of having COVID-19 infection. “Fortunately, negative results from nucleic acid testing ultimately excluded COVID-19 infection in all these patients,” the authors report.

However, two of these patients “presented with recovered pneumonia after symptomatic treatment.” Commenting on this finding, Moffitt’s Greene said that may mean these two patients were tested and found to be positive but were early in the infection and not yet shedding the virus, or they were infected after the initial negative result.

Greene said his center has implemented some measures not mentioned in the Chinese plan. For example, the Florida center no longer allows inpatient visitation. Also, one third of staff now work from home, resulting in less social interaction. Social distancing in meetings, the cafeteria, and hallways is being observed “aggressively,” and most meetings are now on Zoom, he said.

Moffitt has not been hard hit with COVID-19 and is at level one preparedness, the lowest rung. The center has performed 60 tests to date, with only one positive for the virus (< 2%), Greene told Medscape Medical News.

Currently, in the larger Tampa Bay community setting, about 12% of tests are positive.

The low percentage found among the Moffitt patients “tells you that a lot of cancer patients have fever and respiratory symptoms due to other viruses and, more importantly, other reasons, whether it’s their immunotherapy or chemotherapy or their cancer,” said Greene.

NCCN’s Carlson said the publication of the Chinese data was a good sign in terms of international science.

“This is a strong example of how the global oncology community rapidly shares information and experience whenever it makes a difference in patient care,” he commented.

The authors, as well as Carlson and Greene, have reported no relevant financial relationships.

This article first appeared on Medscape.com.

Greater prevalence of underlying health conditions such as diabetes and chronic lung disease was seen among nearly 7,200 Americans hospitalized with coronavirus disease 2019 (COVID-19), according to the Centers for Disease Control and Prevention.

Of the 122,653 laboratory-confirmed COVID-19 cases reported to the CDC as of March 28, the COVID-19 Response Team had access to data on the presence or absence of underlying health conditions and other recognized risk factors for severe outcomes from respiratory infections for 7,162 (5.8%) patients.

“Among these patients, higher percentages of patients with underlying conditions were admitted to the hospital and to an ICU than patients without reported underlying conditions. These results are consistent with findings from China and Italy,” Katherine Fleming-Dutra, MD, and associates said in the MMWR.

Individuals with underlying health conditions/risk factors made up 37.6% of all COVID-19 patients in the study but represented a majority of ICU (78%) and non-ICU (71%) hospital admissions. In contrast, 73% of COVID-19 patients who were not hospitalized had no underlying conditions, Dr. Fleming-Dutra and the CDC COVID-19 Response Team reported.

With a prevalence of 10.9%, diabetes mellitus was the most common condition reported among all COVID-19 patients, followed by chronic lung disease (9.2%) and cardiovascular disease (9.0%), the investigators said.

Another look at the data shows that 40.5% of those with underlying conditions were hospitalized, compared with 9.0% of the 4,470 COVID-19 patients without any risk factors.

“Strategies to protect all persons and especially those with underlying health conditions, including social distancing and handwashing, should be implemented by all communities and all persons to help slow the spread of COVID-19,” the response team wrote.

rfranki@mdedge.com

SOURCE: Fleming-Dutra K et al. MMWR. 2020 Mar 31;69 (early release):1-5.

Greater prevalence of underlying health conditions such as diabetes and chronic lung disease was seen among nearly 7,200 Americans hospitalized with coronavirus disease 2019 (COVID-19), according to the Centers for Disease Control and Prevention.

Of the 122,653 laboratory-confirmed COVID-19 cases reported to the CDC as of March 28, the COVID-19 Response Team had access to data on the presence or absence of underlying health conditions and other recognized risk factors for severe outcomes from respiratory infections for 7,162 (5.8%) patients.

“Among these patients, higher percentages of patients with underlying conditions were admitted to the hospital and to an ICU than patients without reported underlying conditions. These results are consistent with findings from China and Italy,” Katherine Fleming-Dutra, MD, and associates said in the MMWR.

Individuals with underlying health conditions/risk factors made up 37.6% of all COVID-19 patients in the study but represented a majority of ICU (78%) and non-ICU (71%) hospital admissions. In contrast, 73% of COVID-19 patients who were not hospitalized had no underlying conditions, Dr. Fleming-Dutra and the CDC COVID-19 Response Team reported.

With a prevalence of 10.9%, diabetes mellitus was the most common condition reported among all COVID-19 patients, followed by chronic lung disease (9.2%) and cardiovascular disease (9.0%), the investigators said.

Another look at the data shows that 40.5% of those with underlying conditions were hospitalized, compared with 9.0% of the 4,470 COVID-19 patients without any risk factors.

“Strategies to protect all persons and especially those with underlying health conditions, including social distancing and handwashing, should be implemented by all communities and all persons to help slow the spread of COVID-19,” the response team wrote.

rfranki@mdedge.com

SOURCE: Fleming-Dutra K et al. MMWR. 2020 Mar 31;69 (early release):1-5.

Greater prevalence of underlying health conditions such as diabetes and chronic lung disease was seen among nearly 7,200 Americans hospitalized with coronavirus disease 2019 (COVID-19), according to the Centers for Disease Control and Prevention.

Of the 122,653 laboratory-confirmed COVID-19 cases reported to the CDC as of March 28, the COVID-19 Response Team had access to data on the presence or absence of underlying health conditions and other recognized risk factors for severe outcomes from respiratory infections for 7,162 (5.8%) patients.

“Among these patients, higher percentages of patients with underlying conditions were admitted to the hospital and to an ICU than patients without reported underlying conditions. These results are consistent with findings from China and Italy,” Katherine Fleming-Dutra, MD, and associates said in the MMWR.

Individuals with underlying health conditions/risk factors made up 37.6% of all COVID-19 patients in the study but represented a majority of ICU (78%) and non-ICU (71%) hospital admissions. In contrast, 73% of COVID-19 patients who were not hospitalized had no underlying conditions, Dr. Fleming-Dutra and the CDC COVID-19 Response Team reported.

With a prevalence of 10.9%, diabetes mellitus was the most common condition reported among all COVID-19 patients, followed by chronic lung disease (9.2%) and cardiovascular disease (9.0%), the investigators said.

Another look at the data shows that 40.5% of those with underlying conditions were hospitalized, compared with 9.0% of the 4,470 COVID-19 patients without any risk factors.

“Strategies to protect all persons and especially those with underlying health conditions, including social distancing and handwashing, should be implemented by all communities and all persons to help slow the spread of COVID-19,” the response team wrote.

rfranki@mdedge.com

SOURCE: Fleming-Dutra K et al. MMWR. 2020 Mar 31;69 (early release):1-5.

A controversial study led by Didier Raoult, MD, PhD, on the combination of hydroxychloroquine and azithromycin in patients with COVID-19 was published March 20. The latest results from the same Marseille team, which involve 80 patients, were reported on March 27.

The investigators report a significant reduction in the viral load (83% patients had negative results on quantitative polymerase chain reaction testing at day 7, and 93% had negative results on day 8). There was a “clinical improvement compared to the natural progression.” One death occurred, and three patients were transferred to intensive care units.

If the data seem encouraging, the lack of a control arm in the study leaves clinicians perplexed, however.

Benjamin Davido, MD, an infectious disease specialist at Raymond-Poincaré Hospital in Garches, Paris, spoke in an interview about the implications of these new results.
 

What do you think about the new results presented by Prof. Raoult’s team? Do they confirm the effectiveness of hydroxychloroquine?

These results are complementary [to the original results] but don’t offer any new information or new statistical evidence. They are absolutely superimposable and say overall that, between 5 and 7 days [of treatment], very few patients shed the virus. But that is not the question that everyone is asking.

Even if we don’t necessarily have to conduct a randomized study, we should at least compare the treatment, either against another therapy – which could be hydroxychloroquine monotherapy, or just standard of care. It needed an authentic control arm.

To recruit 80 patients so quickly, the researchers probably took people with essentially ambulatory forms of the disease (there was a call for screening in the south of France) – therefore, by definition, less severe cases.

But to describe such a population of patients as going home and saying, “There were very few hospitalizations and it is going well,” does not in any way prove that the treatment reduces hospitalizations.
 

The argument for not having a control arm in this study was that it would be unethical. What do you think?

I agree with this argument when it comes to patients presenting with risk factors or who are starting to develop pneumonia.

But I don’t think this is the case at the beginning of the illness. Of course, you don’t want to wait to have severe disease or for the patient to be in intensive care to start treatment. In these cases, it is indeed very difficult to find a control arm.
 

In the ongoing Discovery trial, which involves more than 3,000 patients in Europe, including 800 in France, the patients have severe disease, and there are five treatment arms. Moreover, hydroxychloroquine is given without azithromycin. What do you think of this?

I think it’s a mistake. It will not answer the question of the effectiveness of hydroxychloroquine in COVID-19, especially as they’re not studying azithromycin in a situation where the compound seems necessary for the effectiveness of the treatment.

In addition, Discovery reinforces the notion of studying Kaletra [lopinavir/ritonavir, AbbVie] again, while Chinese researchers have shown that it does not work, the argument being that Kaletra was given too late (N Engl J Med. 2020 Mar 18. doi: 10.1056/NEJMoa2001282). Therefore, if we make the same mistakes from a methodological point of view, we will end up with negative results.
 

What should have been done in the Marseille study?

The question is: Are there more or fewer hospitalizations when we treat a homogeneous population straight away?

The answer could be very clear, as a control already exists! They are the patients that flow into our hospitals every day – ironically, these 80 patients [in the latest results, presented March 27] could be among the 80% who had a form similar to nasopharyngitis and resolved.

In this illness, we know that there are 80% spontaneous recoveries and 20% so-called severe forms. Therefore, with 80 patients, we are very underpowered. The cohort is too small for a disease in which 80% of the evolution is benign.

It would take 1,000 patients, and then, even without a control arm, we would have an answer.

On March 26, Didier Raoult’s team also announced having already treated 700 patients with hydroxychloroquine, with only one death. Therefore, if this cohort increases significantly in Marseille and we see that, on the map, there are fewer issues with patient flow and saturation in Marseille and that there are fewer patients in intensive care, you will have to wonder about the effect of hydroxychloroquine.

We will find out very quickly. If it really works, and they treat all the patients presenting at Timone Hospital, we will soon have the answer. It will be a real-life study.
 

What are the other studies on hydroxychloroquine that could give us answers?

There was a Chinese study that did not show a difference in effectiveness between hydroxychloroquine and placebo, but that was, again, conducted in only around 20 patients (J Zhejiang Univ (Med Sci). 2020. doi: 10.3785/j.issn.1008-9292.2020.03.03). This cohort is too small and tells us nothing; it cannot show anything. We must wait for the results of larger trials being conducted in China.

It surprises me that, today, we still do not have Italian data on the use of chloroquine-type drugs ... perhaps because they have a care pathway that means there is no outpatient treatment and that they arrive already with severe disease. The Italian recommendations nevertheless indicate the use of hydroxychloroquine.

I also wonder about the lack of studies of cohorts where, in retrospect, we could have followed people previously treated with hydroxychloroquine for chronic diseases (e.g., rheumatoid arthritis, lupus, etc.). Or we could identify all those patients on the health insurance system who had prescriptions.

That is how we discovered the AIDS epidemic in San Francisco: There was an increase in the number of prescriptions for trimethoprim/sulfamethoxazole (Bactrim) that corresponded to a population subtype (homosexual), and we realized that it was for a disease that resembled pneumocystosis. We discovered that via the drug!

If hydroxychloroquine is effective, it is enough to look at people who took it before the epidemic and see how they fared. And there, we do not need a control arm. This could give us some direction. The March 26 decree of the new Véran Law states that community pharmacies can dispense to patients with a previous prescription, so we can find these individuals.
 

Do you think that the lack of, or difficulty in setting up, studies on hydroxychloroquine in France is linked to decisions that are more political than scientific?

Perhaps the contaminated blood scandal still casts a shadow in France, and there is a great deal of anxiety over the fact that we are already in a crisis, and we do not want a second one. I can understand that.

However, just a week ago, access to this drug (and others with market approval that have been on the market for several years) was blocked in hospital central pharmacies, while we are the medical specialists with the authorization! It was unacceptable.

It was sorted out 48 hours ago: hydroxychloroquine is now available in the hospital, and to my knowledge, we no longer have a problem obtaining it.

It took time to alleviate doubts over the major health risks with this drug. [Officials] seemed almost like amateurs in their hesitation; I think they lacked foresight. We have forgotten that the treatment advocated by Prof. Didier Raoult is not chloroquine but rather hydroxychloroquine, and we know that the adverse effects are less [with hydroxychloroquine] than with chloroquine.
 

You yourself have treated patients with chloroquine, despite the risk for toxicity highlighted by some.

Initially, when we first started treating patients, we thought of chloroquine because we did not have data on hydroxychloroquine, only Chinese data with chloroquine. We therefore prescribed chloroquine several days before prescribing hydroxychloroquine.

The question of the toxicity of chloroquine was not unjustified, but I think we took far too much time to decide on the toxicity of hydroxychloroquine. Is [the latter] political? I don’t know. It was widely publicized, which amazes me for a drug that is already available.

On the other hand, everyone was talking at the same time about the toxicity of NSAIDs. ... One has the impression it was to create a diversion. I think there were double standards at play and a scapegoat was needed to gain some time and ask questions.

What is sure is that it is probably not for financial reasons, as hydroxychloroquine costs nothing. That’s to say there were probably pharmaceutical issues at stake for possible competitors of hydroxychloroquine; I do not want to get into this debate, and it doesn’t matter, as long as we have an answer.

Today, the only thing we have advanced on is the “safety” of hydroxychloroquine, the low risk to the general population. ... On the other hand, we have still not made any progress on the evidence of efficacy, compared with other treatments.

Personally, I really believe in hydroxychloroquine. It would nevertheless be a shame to think we had found the fountain of youth and realize, in 4 weeks, that we have the same number of deaths. That is the problem. I hope that we will soon have solid data so we do not waste time focusing solely on hydroxychloroquine.
 

What are the other avenues of research that grab your attention?

The Discovery trial will probably give an answer on remdesivir [GS-5734, Gilead], which is a direct antiviral and could be interesting. But there are other studies being conducted currently in China.

There is also favipiravir [T-705, Avigan, Toyama Chemical], which is an anti-influenza drug used in Japan, which could explain, in part, the control of the epidemic in that country. There are effects in vitro on coronavirus. But it is not at all studied in France at the moment. Therefore, we should not focus exclusively on hydroxychloroquine; we must keep a close eye on other molecules, in particular the “old” drugs, like this antiviral.

The study was supported by the Institut Hospitalo-Universitaire (IHU) Méditerranée Infection, the National Research Agency, under the Investissements d’avenir program, Région Provence Alpes Côte d’Azur, and European funding FEDER PRIMI. The authors have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

A controversial study led by Didier Raoult, MD, PhD, on the combination of hydroxychloroquine and azithromycin in patients with COVID-19 was published March 20. The latest results from the same Marseille team, which involve 80 patients, were reported on March 27.

The investigators report a significant reduction in the viral load (83% patients had negative results on quantitative polymerase chain reaction testing at day 7, and 93% had negative results on day 8). There was a “clinical improvement compared to the natural progression.” One death occurred, and three patients were transferred to intensive care units.

If the data seem encouraging, the lack of a control arm in the study leaves clinicians perplexed, however.

Benjamin Davido, MD, an infectious disease specialist at Raymond-Poincaré Hospital in Garches, Paris, spoke in an interview about the implications of these new results.
 

What do you think about the new results presented by Prof. Raoult’s team? Do they confirm the effectiveness of hydroxychloroquine?

These results are complementary [to the original results] but don’t offer any new information or new statistical evidence. They are absolutely superimposable and say overall that, between 5 and 7 days [of treatment], very few patients shed the virus. But that is not the question that everyone is asking.

Even if we don’t necessarily have to conduct a randomized study, we should at least compare the treatment, either against another therapy – which could be hydroxychloroquine monotherapy, or just standard of care. It needed an authentic control arm.

To recruit 80 patients so quickly, the researchers probably took people with essentially ambulatory forms of the disease (there was a call for screening in the south of France) – therefore, by definition, less severe cases.

But to describe such a population of patients as going home and saying, “There were very few hospitalizations and it is going well,” does not in any way prove that the treatment reduces hospitalizations.
 

The argument for not having a control arm in this study was that it would be unethical. What do you think?

I agree with this argument when it comes to patients presenting with risk factors or who are starting to develop pneumonia.

But I don’t think this is the case at the beginning of the illness. Of course, you don’t want to wait to have severe disease or for the patient to be in intensive care to start treatment. In these cases, it is indeed very difficult to find a control arm.
 

In the ongoing Discovery trial, which involves more than 3,000 patients in Europe, including 800 in France, the patients have severe disease, and there are five treatment arms. Moreover, hydroxychloroquine is given without azithromycin. What do you think of this?

I think it’s a mistake. It will not answer the question of the effectiveness of hydroxychloroquine in COVID-19, especially as they’re not studying azithromycin in a situation where the compound seems necessary for the effectiveness of the treatment.

In addition, Discovery reinforces the notion of studying Kaletra [lopinavir/ritonavir, AbbVie] again, while Chinese researchers have shown that it does not work, the argument being that Kaletra was given too late (N Engl J Med. 2020 Mar 18. doi: 10.1056/NEJMoa2001282). Therefore, if we make the same mistakes from a methodological point of view, we will end up with negative results.
 

What should have been done in the Marseille study?

The question is: Are there more or fewer hospitalizations when we treat a homogeneous population straight away?

The answer could be very clear, as a control already exists! They are the patients that flow into our hospitals every day – ironically, these 80 patients [in the latest results, presented March 27] could be among the 80% who had a form similar to nasopharyngitis and resolved.

In this illness, we know that there are 80% spontaneous recoveries and 20% so-called severe forms. Therefore, with 80 patients, we are very underpowered. The cohort is too small for a disease in which 80% of the evolution is benign.

It would take 1,000 patients, and then, even without a control arm, we would have an answer.

On March 26, Didier Raoult’s team also announced having already treated 700 patients with hydroxychloroquine, with only one death. Therefore, if this cohort increases significantly in Marseille and we see that, on the map, there are fewer issues with patient flow and saturation in Marseille and that there are fewer patients in intensive care, you will have to wonder about the effect of hydroxychloroquine.

We will find out very quickly. If it really works, and they treat all the patients presenting at Timone Hospital, we will soon have the answer. It will be a real-life study.
 

What are the other studies on hydroxychloroquine that could give us answers?

There was a Chinese study that did not show a difference in effectiveness between hydroxychloroquine and placebo, but that was, again, conducted in only around 20 patients (J Zhejiang Univ (Med Sci). 2020. doi: 10.3785/j.issn.1008-9292.2020.03.03). This cohort is too small and tells us nothing; it cannot show anything. We must wait for the results of larger trials being conducted in China.

It surprises me that, today, we still do not have Italian data on the use of chloroquine-type drugs ... perhaps because they have a care pathway that means there is no outpatient treatment and that they arrive already with severe disease. The Italian recommendations nevertheless indicate the use of hydroxychloroquine.

I also wonder about the lack of studies of cohorts where, in retrospect, we could have followed people previously treated with hydroxychloroquine for chronic diseases (e.g., rheumatoid arthritis, lupus, etc.). Or we could identify all those patients on the health insurance system who had prescriptions.

That is how we discovered the AIDS epidemic in San Francisco: There was an increase in the number of prescriptions for trimethoprim/sulfamethoxazole (Bactrim) that corresponded to a population subtype (homosexual), and we realized that it was for a disease that resembled pneumocystosis. We discovered that via the drug!

If hydroxychloroquine is effective, it is enough to look at people who took it before the epidemic and see how they fared. And there, we do not need a control arm. This could give us some direction. The March 26 decree of the new Véran Law states that community pharmacies can dispense to patients with a previous prescription, so we can find these individuals.
 

Do you think that the lack of, or difficulty in setting up, studies on hydroxychloroquine in France is linked to decisions that are more political than scientific?

Perhaps the contaminated blood scandal still casts a shadow in France, and there is a great deal of anxiety over the fact that we are already in a crisis, and we do not want a second one. I can understand that.

However, just a week ago, access to this drug (and others with market approval that have been on the market for several years) was blocked in hospital central pharmacies, while we are the medical specialists with the authorization! It was unacceptable.

It was sorted out 48 hours ago: hydroxychloroquine is now available in the hospital, and to my knowledge, we no longer have a problem obtaining it.

It took time to alleviate doubts over the major health risks with this drug. [Officials] seemed almost like amateurs in their hesitation; I think they lacked foresight. We have forgotten that the treatment advocated by Prof. Didier Raoult is not chloroquine but rather hydroxychloroquine, and we know that the adverse effects are less [with hydroxychloroquine] than with chloroquine.
 

You yourself have treated patients with chloroquine, despite the risk for toxicity highlighted by some.

Initially, when we first started treating patients, we thought of chloroquine because we did not have data on hydroxychloroquine, only Chinese data with chloroquine. We therefore prescribed chloroquine several days before prescribing hydroxychloroquine.

The question of the toxicity of chloroquine was not unjustified, but I think we took far too much time to decide on the toxicity of hydroxychloroquine. Is [the latter] political? I don’t know. It was widely publicized, which amazes me for a drug that is already available.

On the other hand, everyone was talking at the same time about the toxicity of NSAIDs. ... One has the impression it was to create a diversion. I think there were double standards at play and a scapegoat was needed to gain some time and ask questions.

What is sure is that it is probably not for financial reasons, as hydroxychloroquine costs nothing. That’s to say there were probably pharmaceutical issues at stake for possible competitors of hydroxychloroquine; I do not want to get into this debate, and it doesn’t matter, as long as we have an answer.

Today, the only thing we have advanced on is the “safety” of hydroxychloroquine, the low risk to the general population. ... On the other hand, we have still not made any progress on the evidence of efficacy, compared with other treatments.

Personally, I really believe in hydroxychloroquine. It would nevertheless be a shame to think we had found the fountain of youth and realize, in 4 weeks, that we have the same number of deaths. That is the problem. I hope that we will soon have solid data so we do not waste time focusing solely on hydroxychloroquine.
 

What are the other avenues of research that grab your attention?

The Discovery trial will probably give an answer on remdesivir [GS-5734, Gilead], which is a direct antiviral and could be interesting. But there are other studies being conducted currently in China.

There is also favipiravir [T-705, Avigan, Toyama Chemical], which is an anti-influenza drug used in Japan, which could explain, in part, the control of the epidemic in that country. There are effects in vitro on coronavirus. But it is not at all studied in France at the moment. Therefore, we should not focus exclusively on hydroxychloroquine; we must keep a close eye on other molecules, in particular the “old” drugs, like this antiviral.

The study was supported by the Institut Hospitalo-Universitaire (IHU) Méditerranée Infection, the National Research Agency, under the Investissements d’avenir program, Région Provence Alpes Côte d’Azur, and European funding FEDER PRIMI. The authors have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

A controversial study led by Didier Raoult, MD, PhD, on the combination of hydroxychloroquine and azithromycin in patients with COVID-19 was published March 20. The latest results from the same Marseille team, which involve 80 patients, were reported on March 27.

The investigators report a significant reduction in the viral load (83% patients had negative results on quantitative polymerase chain reaction testing at day 7, and 93% had negative results on day 8). There was a “clinical improvement compared to the natural progression.” One death occurred, and three patients were transferred to intensive care units.

If the data seem encouraging, the lack of a control arm in the study leaves clinicians perplexed, however.

Benjamin Davido, MD, an infectious disease specialist at Raymond-Poincaré Hospital in Garches, Paris, spoke in an interview about the implications of these new results.
 

What do you think about the new results presented by Prof. Raoult’s team? Do they confirm the effectiveness of hydroxychloroquine?

These results are complementary [to the original results] but don’t offer any new information or new statistical evidence. They are absolutely superimposable and say overall that, between 5 and 7 days [of treatment], very few patients shed the virus. But that is not the question that everyone is asking.

Even if we don’t necessarily have to conduct a randomized study, we should at least compare the treatment, either against another therapy – which could be hydroxychloroquine monotherapy, or just standard of care. It needed an authentic control arm.

To recruit 80 patients so quickly, the researchers probably took people with essentially ambulatory forms of the disease (there was a call for screening in the south of France) – therefore, by definition, less severe cases.

But to describe such a population of patients as going home and saying, “There were very few hospitalizations and it is going well,” does not in any way prove that the treatment reduces hospitalizations.
 

The argument for not having a control arm in this study was that it would be unethical. What do you think?

I agree with this argument when it comes to patients presenting with risk factors or who are starting to develop pneumonia.

But I don’t think this is the case at the beginning of the illness. Of course, you don’t want to wait to have severe disease or for the patient to be in intensive care to start treatment. In these cases, it is indeed very difficult to find a control arm.
 

In the ongoing Discovery trial, which involves more than 3,000 patients in Europe, including 800 in France, the patients have severe disease, and there are five treatment arms. Moreover, hydroxychloroquine is given without azithromycin. What do you think of this?

I think it’s a mistake. It will not answer the question of the effectiveness of hydroxychloroquine in COVID-19, especially as they’re not studying azithromycin in a situation where the compound seems necessary for the effectiveness of the treatment.

In addition, Discovery reinforces the notion of studying Kaletra [lopinavir/ritonavir, AbbVie] again, while Chinese researchers have shown that it does not work, the argument being that Kaletra was given too late (N Engl J Med. 2020 Mar 18. doi: 10.1056/NEJMoa2001282). Therefore, if we make the same mistakes from a methodological point of view, we will end up with negative results.
 

What should have been done in the Marseille study?

The question is: Are there more or fewer hospitalizations when we treat a homogeneous population straight away?

The answer could be very clear, as a control already exists! They are the patients that flow into our hospitals every day – ironically, these 80 patients [in the latest results, presented March 27] could be among the 80% who had a form similar to nasopharyngitis and resolved.

In this illness, we know that there are 80% spontaneous recoveries and 20% so-called severe forms. Therefore, with 80 patients, we are very underpowered. The cohort is too small for a disease in which 80% of the evolution is benign.

It would take 1,000 patients, and then, even without a control arm, we would have an answer.

On March 26, Didier Raoult’s team also announced having already treated 700 patients with hydroxychloroquine, with only one death. Therefore, if this cohort increases significantly in Marseille and we see that, on the map, there are fewer issues with patient flow and saturation in Marseille and that there are fewer patients in intensive care, you will have to wonder about the effect of hydroxychloroquine.

We will find out very quickly. If it really works, and they treat all the patients presenting at Timone Hospital, we will soon have the answer. It will be a real-life study.
 

What are the other studies on hydroxychloroquine that could give us answers?

There was a Chinese study that did not show a difference in effectiveness between hydroxychloroquine and placebo, but that was, again, conducted in only around 20 patients (J Zhejiang Univ (Med Sci). 2020. doi: 10.3785/j.issn.1008-9292.2020.03.03). This cohort is too small and tells us nothing; it cannot show anything. We must wait for the results of larger trials being conducted in China.

It surprises me that, today, we still do not have Italian data on the use of chloroquine-type drugs ... perhaps because they have a care pathway that means there is no outpatient treatment and that they arrive already with severe disease. The Italian recommendations nevertheless indicate the use of hydroxychloroquine.

I also wonder about the lack of studies of cohorts where, in retrospect, we could have followed people previously treated with hydroxychloroquine for chronic diseases (e.g., rheumatoid arthritis, lupus, etc.). Or we could identify all those patients on the health insurance system who had prescriptions.

That is how we discovered the AIDS epidemic in San Francisco: There was an increase in the number of prescriptions for trimethoprim/sulfamethoxazole (Bactrim) that corresponded to a population subtype (homosexual), and we realized that it was for a disease that resembled pneumocystosis. We discovered that via the drug!

If hydroxychloroquine is effective, it is enough to look at people who took it before the epidemic and see how they fared. And there, we do not need a control arm. This could give us some direction. The March 26 decree of the new Véran Law states that community pharmacies can dispense to patients with a previous prescription, so we can find these individuals.
 

Do you think that the lack of, or difficulty in setting up, studies on hydroxychloroquine in France is linked to decisions that are more political than scientific?

Perhaps the contaminated blood scandal still casts a shadow in France, and there is a great deal of anxiety over the fact that we are already in a crisis, and we do not want a second one. I can understand that.

However, just a week ago, access to this drug (and others with market approval that have been on the market for several years) was blocked in hospital central pharmacies, while we are the medical specialists with the authorization! It was unacceptable.

It was sorted out 48 hours ago: hydroxychloroquine is now available in the hospital, and to my knowledge, we no longer have a problem obtaining it.

It took time to alleviate doubts over the major health risks with this drug. [Officials] seemed almost like amateurs in their hesitation; I think they lacked foresight. We have forgotten that the treatment advocated by Prof. Didier Raoult is not chloroquine but rather hydroxychloroquine, and we know that the adverse effects are less [with hydroxychloroquine] than with chloroquine.
 

You yourself have treated patients with chloroquine, despite the risk for toxicity highlighted by some.

Initially, when we first started treating patients, we thought of chloroquine because we did not have data on hydroxychloroquine, only Chinese data with chloroquine. We therefore prescribed chloroquine several days before prescribing hydroxychloroquine.

The question of the toxicity of chloroquine was not unjustified, but I think we took far too much time to decide on the toxicity of hydroxychloroquine. Is [the latter] political? I don’t know. It was widely publicized, which amazes me for a drug that is already available.

On the other hand, everyone was talking at the same time about the toxicity of NSAIDs. ... One has the impression it was to create a diversion. I think there were double standards at play and a scapegoat was needed to gain some time and ask questions.

What is sure is that it is probably not for financial reasons, as hydroxychloroquine costs nothing. That’s to say there were probably pharmaceutical issues at stake for possible competitors of hydroxychloroquine; I do not want to get into this debate, and it doesn’t matter, as long as we have an answer.

Today, the only thing we have advanced on is the “safety” of hydroxychloroquine, the low risk to the general population. ... On the other hand, we have still not made any progress on the evidence of efficacy, compared with other treatments.

Personally, I really believe in hydroxychloroquine. It would nevertheless be a shame to think we had found the fountain of youth and realize, in 4 weeks, that we have the same number of deaths. That is the problem. I hope that we will soon have solid data so we do not waste time focusing solely on hydroxychloroquine.
 

What are the other avenues of research that grab your attention?

The Discovery trial will probably give an answer on remdesivir [GS-5734, Gilead], which is a direct antiviral and could be interesting. But there are other studies being conducted currently in China.

There is also favipiravir [T-705, Avigan, Toyama Chemical], which is an anti-influenza drug used in Japan, which could explain, in part, the control of the epidemic in that country. There are effects in vitro on coronavirus. But it is not at all studied in France at the moment. Therefore, we should not focus exclusively on hydroxychloroquine; we must keep a close eye on other molecules, in particular the “old” drugs, like this antiviral.

The study was supported by the Institut Hospitalo-Universitaire (IHU) Méditerranée Infection, the National Research Agency, under the Investissements d’avenir program, Région Provence Alpes Côte d’Azur, and European funding FEDER PRIMI. The authors have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

In a physician WhatsApp group, a doctor posted he had fever of 101 °F and muscle ache, gently confessing that it felt like his typical “man flu” which heals with rest and scotch. Nevertheless, he worried that he had coronavirus. When the reverse transcription polymerase chain reaction (RT-PCR) for the virus on his nasal swab came back negative, he jubilantly announced his relief.

Like Twitter, in WhatsApp emotions quickly outstrip facts. After he received a flurry of cheerful emojis, I ruined the party, advising that, despite the negative test, he assume he’s infected and quarantine for 2 weeks, with a bottle of scotch.

It’s conventional wisdom that the secret sauce to fighting the pandemic is testing for the virus. To gauge the breadth of the response against the pandemic we must know who and how many are infected. The depth of the response will be different if 25% of the population is infected than 1%. Testing is the third way, rejecting the false choice between death and economic depression. Without testing, strategy is faith based.

Our reliance on testing has clinical precedence – scarcely any decision in medicine is made without laboratory tests or imaging. Testing is as ingrained in medicine as the GPS is in driving. We use it even when we know our way home. But tests impose a question – what’ll you do differently if the test is negative?

That depends on the test’s performance and the consequences of being wrong. Though coronavirus damages the lungs with reckless abandon, it’s oddly a shy virus. In many patients, it takes 3-4 swabs to get a positive RT-PCR. The Chinese ophthalmologist, Li Wenliang, who originally sounded the alarm about coronavirus, had several negative tests. He died from the infection.

In one Chinese study, the sensitivity of RT-PCR – that’s the proportion of the infected who test positive – was around 70%. To put this in perspective, of 1,000 people infected with coronavirus, 700 will test positive but 300 will test negative.

Is this good enough?

Three hundred “false-negative” people may believe they’re not contagious because they got a clean chit and could infect others. False negatives could undo the hard work of containment.

Surely, better an imperfect test than no test. Isn’t flying with partially accurate weather information safer than no information? Here, aviation analogies aren’t helpful. Better to think of a forest fire.

Imagine only 80% of a burning forest is doused because it’s mistakenly believed that 20% of the forest isn’t burning because we can’t see it burning. It must be extinguished before it relights the whole forest, but to douse it you must know it’s burning – a Catch-22. That “20% of the forest” is a false negative – it’s burning but you think it’s not burning.

Because coronavirus isn’t planning to leave in a hurry and long-term lockdown has grave economic consequences, testing may enable precision quarantining of people, communities, and cities. Rather than applying a one-size-fits-all lockdown on the whole nation, testing could tell us who can work and who should stay home. Why should Austin, if it has a low prevalence of infection, shut shop just because of New York City’s high prevalence?

Testing enables us to think globally but act locally. But it’s the asymptomatic people who drive the epidemic. To emphasize – asymptomatics are yet to have symptoms such as cough and fever. They’re feeling well and don’t know they’ve been colonized by the virus. Theoretically, if we test en masse we can find asymptomatics. If only those who test positive are quarantined, the rest can have some breathing space. Will this approach work?

RT-PCR’s sensitivity, which is low in early illness, is even lower in asymptomatics, likely because of lower viral load, which means even more false negatives. The virus’s average incubation time of 5 days is enough time for false negative asymptomatics – remember they resemble the uninfected – to visit Disney World and infect another four.

Whether false negatives behave like tinder or a controllable fire will determine the testing strategy’s success. The net contagiousness of false negatives depends how many there are, which depends on how many are infected. To know how many are infected we need to test. Or, to know whether to believe a negative test in any person we must test widely – another Catch-22.

Maybe we need a bigger test.

Chest CT is an alternative. It’s rapid – takes less than an hour whereas RT-PCR can take over a day to report. In one study CT had a sensitivity of 97% in symptomatic patients and was often positive before RT-PCR. But there are caveats.

The real sensitivity of CT is likely much lower than 97% because the study has biases which inflate performance. CT, like RT-PCR, has a low sensitivity in early illness and even lower sensitivity in asymptomatic carriers for the same reason – lower viral load. Furthermore, CT has to be disinfected to prevent spread, which limits its access for other patients.

Coronavirus’s signature on CT – white patches in lungs, known as ground glass opacities – doesn’t have the uniqueness of the Mark of Zorro, and looks like lung injury from other rogue actors, which means we can mistake other serious conditions for coronavirus. Imagine hyenas in wolf’s clothing.

No test is perfect. We still use imaging despite its imperfections. But, let’s ask: What would you do differently if the test is negative and you have mild symptoms of cough and fever? Should you not self-isolate? What if you’re falsely negative and still contagious? If the advice dispensed whether the test is positive or negative is the same – i.e. quarantine for 2 weeks – what’s the test’s value?

Perhaps people will more likely comply with voluntary quarantine if they know they’re infected. Information can nudge behavior. But the logical corollary is that to comply with social distancing you need to be tested. People flocking to CT scans to affirm they’re not infected could infect those hitherto uninfected. A pandemic is no time to test nudge theories.

Does that mean testing has no value? Testing is valuable in managing populations. To individuals, the results must be framed wisely, such as by advising those who test positive to quarantine because “you’re infected” and those who test negative to keep social distancing because “you could still be infected.”

Even when policy goals are uniform, messaging can be oppositional. “Get yourself tested now” contradicts “you must hunker down now.” When messages contradict, one must choose which message to amplify.

The calculus of testing can change with new tests such as antibodies. The value of testing depends also on what isolation entails. A couple of weeks watching Netflix on your couch isn’t a big ask. If quarantine means being detained in an isolation center fenced by barbed wires, the cost of frivolous quarantining is higher and testing becomes more valuable.

I knew the doctor with the negative RT-PCR well. He’s heroically nonchalant about his wellbeing, an endearing quality that’s a liability in a contagion. In no time he’d be back in the hospital; or helping his elderly parents with grocery. Not all false negatives are equal. False-negative doctors could infect not just their patients but their colleagues, leaving fewer firefighters to fight fires.

It is better to mistake the man flu for coronavirus than coronavirus for the man flu. All he has to do is hunker down, which is what we should all be doing as much as we can.

Dr. Jha is a contributing editor to The Health Care Blog, where this article first appeared. He can be reached @RogueRad.

This article appeared on Medscape.com.

In a physician WhatsApp group, a doctor posted he had fever of 101 °F and muscle ache, gently confessing that it felt like his typical “man flu” which heals with rest and scotch. Nevertheless, he worried that he had coronavirus. When the reverse transcription polymerase chain reaction (RT-PCR) for the virus on his nasal swab came back negative, he jubilantly announced his relief.

Like Twitter, in WhatsApp emotions quickly outstrip facts. After he received a flurry of cheerful emojis, I ruined the party, advising that, despite the negative test, he assume he’s infected and quarantine for 2 weeks, with a bottle of scotch.

It’s conventional wisdom that the secret sauce to fighting the pandemic is testing for the virus. To gauge the breadth of the response against the pandemic we must know who and how many are infected. The depth of the response will be different if 25% of the population is infected than 1%. Testing is the third way, rejecting the false choice between death and economic depression. Without testing, strategy is faith based.

Our reliance on testing has clinical precedence – scarcely any decision in medicine is made without laboratory tests or imaging. Testing is as ingrained in medicine as the GPS is in driving. We use it even when we know our way home. But tests impose a question – what’ll you do differently if the test is negative?

That depends on the test’s performance and the consequences of being wrong. Though coronavirus damages the lungs with reckless abandon, it’s oddly a shy virus. In many patients, it takes 3-4 swabs to get a positive RT-PCR. The Chinese ophthalmologist, Li Wenliang, who originally sounded the alarm about coronavirus, had several negative tests. He died from the infection.

In one Chinese study, the sensitivity of RT-PCR – that’s the proportion of the infected who test positive – was around 70%. To put this in perspective, of 1,000 people infected with coronavirus, 700 will test positive but 300 will test negative.

Is this good enough?

Three hundred “false-negative” people may believe they’re not contagious because they got a clean chit and could infect others. False negatives could undo the hard work of containment.

Surely, better an imperfect test than no test. Isn’t flying with partially accurate weather information safer than no information? Here, aviation analogies aren’t helpful. Better to think of a forest fire.

Imagine only 80% of a burning forest is doused because it’s mistakenly believed that 20% of the forest isn’t burning because we can’t see it burning. It must be extinguished before it relights the whole forest, but to douse it you must know it’s burning – a Catch-22. That “20% of the forest” is a false negative – it’s burning but you think it’s not burning.

Because coronavirus isn’t planning to leave in a hurry and long-term lockdown has grave economic consequences, testing may enable precision quarantining of people, communities, and cities. Rather than applying a one-size-fits-all lockdown on the whole nation, testing could tell us who can work and who should stay home. Why should Austin, if it has a low prevalence of infection, shut shop just because of New York City’s high prevalence?

Testing enables us to think globally but act locally. But it’s the asymptomatic people who drive the epidemic. To emphasize – asymptomatics are yet to have symptoms such as cough and fever. They’re feeling well and don’t know they’ve been colonized by the virus. Theoretically, if we test en masse we can find asymptomatics. If only those who test positive are quarantined, the rest can have some breathing space. Will this approach work?

RT-PCR’s sensitivity, which is low in early illness, is even lower in asymptomatics, likely because of lower viral load, which means even more false negatives. The virus’s average incubation time of 5 days is enough time for false negative asymptomatics – remember they resemble the uninfected – to visit Disney World and infect another four.

Whether false negatives behave like tinder or a controllable fire will determine the testing strategy’s success. The net contagiousness of false negatives depends how many there are, which depends on how many are infected. To know how many are infected we need to test. Or, to know whether to believe a negative test in any person we must test widely – another Catch-22.

Maybe we need a bigger test.

Chest CT is an alternative. It’s rapid – takes less than an hour whereas RT-PCR can take over a day to report. In one study CT had a sensitivity of 97% in symptomatic patients and was often positive before RT-PCR. But there are caveats.

The real sensitivity of CT is likely much lower than 97% because the study has biases which inflate performance. CT, like RT-PCR, has a low sensitivity in early illness and even lower sensitivity in asymptomatic carriers for the same reason – lower viral load. Furthermore, CT has to be disinfected to prevent spread, which limits its access for other patients.

Coronavirus’s signature on CT – white patches in lungs, known as ground glass opacities – doesn’t have the uniqueness of the Mark of Zorro, and looks like lung injury from other rogue actors, which means we can mistake other serious conditions for coronavirus. Imagine hyenas in wolf’s clothing.

No test is perfect. We still use imaging despite its imperfections. But, let’s ask: What would you do differently if the test is negative and you have mild symptoms of cough and fever? Should you not self-isolate? What if you’re falsely negative and still contagious? If the advice dispensed whether the test is positive or negative is the same – i.e. quarantine for 2 weeks – what’s the test’s value?

Perhaps people will more likely comply with voluntary quarantine if they know they’re infected. Information can nudge behavior. But the logical corollary is that to comply with social distancing you need to be tested. People flocking to CT scans to affirm they’re not infected could infect those hitherto uninfected. A pandemic is no time to test nudge theories.

Does that mean testing has no value? Testing is valuable in managing populations. To individuals, the results must be framed wisely, such as by advising those who test positive to quarantine because “you’re infected” and those who test negative to keep social distancing because “you could still be infected.”

Even when policy goals are uniform, messaging can be oppositional. “Get yourself tested now” contradicts “you must hunker down now.” When messages contradict, one must choose which message to amplify.

The calculus of testing can change with new tests such as antibodies. The value of testing depends also on what isolation entails. A couple of weeks watching Netflix on your couch isn’t a big ask. If quarantine means being detained in an isolation center fenced by barbed wires, the cost of frivolous quarantining is higher and testing becomes more valuable.

I knew the doctor with the negative RT-PCR well. He’s heroically nonchalant about his wellbeing, an endearing quality that’s a liability in a contagion. In no time he’d be back in the hospital; or helping his elderly parents with grocery. Not all false negatives are equal. False-negative doctors could infect not just their patients but their colleagues, leaving fewer firefighters to fight fires.

It is better to mistake the man flu for coronavirus than coronavirus for the man flu. All he has to do is hunker down, which is what we should all be doing as much as we can.

Dr. Jha is a contributing editor to The Health Care Blog, where this article first appeared. He can be reached @RogueRad.

This article appeared on Medscape.com.

In a physician WhatsApp group, a doctor posted he had fever of 101 °F and muscle ache, gently confessing that it felt like his typical “man flu” which heals with rest and scotch. Nevertheless, he worried that he had coronavirus. When the reverse transcription polymerase chain reaction (RT-PCR) for the virus on his nasal swab came back negative, he jubilantly announced his relief.

Like Twitter, in WhatsApp emotions quickly outstrip facts. After he received a flurry of cheerful emojis, I ruined the party, advising that, despite the negative test, he assume he’s infected and quarantine for 2 weeks, with a bottle of scotch.

It’s conventional wisdom that the secret sauce to fighting the pandemic is testing for the virus. To gauge the breadth of the response against the pandemic we must know who and how many are infected. The depth of the response will be different if 25% of the population is infected than 1%. Testing is the third way, rejecting the false choice between death and economic depression. Without testing, strategy is faith based.

Our reliance on testing has clinical precedence – scarcely any decision in medicine is made without laboratory tests or imaging. Testing is as ingrained in medicine as the GPS is in driving. We use it even when we know our way home. But tests impose a question – what’ll you do differently if the test is negative?

That depends on the test’s performance and the consequences of being wrong. Though coronavirus damages the lungs with reckless abandon, it’s oddly a shy virus. In many patients, it takes 3-4 swabs to get a positive RT-PCR. The Chinese ophthalmologist, Li Wenliang, who originally sounded the alarm about coronavirus, had several negative tests. He died from the infection.

In one Chinese study, the sensitivity of RT-PCR – that’s the proportion of the infected who test positive – was around 70%. To put this in perspective, of 1,000 people infected with coronavirus, 700 will test positive but 300 will test negative.

Is this good enough?

Three hundred “false-negative” people may believe they’re not contagious because they got a clean chit and could infect others. False negatives could undo the hard work of containment.

Surely, better an imperfect test than no test. Isn’t flying with partially accurate weather information safer than no information? Here, aviation analogies aren’t helpful. Better to think of a forest fire.

Imagine only 80% of a burning forest is doused because it’s mistakenly believed that 20% of the forest isn’t burning because we can’t see it burning. It must be extinguished before it relights the whole forest, but to douse it you must know it’s burning – a Catch-22. That “20% of the forest” is a false negative – it’s burning but you think it’s not burning.

Because coronavirus isn’t planning to leave in a hurry and long-term lockdown has grave economic consequences, testing may enable precision quarantining of people, communities, and cities. Rather than applying a one-size-fits-all lockdown on the whole nation, testing could tell us who can work and who should stay home. Why should Austin, if it has a low prevalence of infection, shut shop just because of New York City’s high prevalence?

Testing enables us to think globally but act locally. But it’s the asymptomatic people who drive the epidemic. To emphasize – asymptomatics are yet to have symptoms such as cough and fever. They’re feeling well and don’t know they’ve been colonized by the virus. Theoretically, if we test en masse we can find asymptomatics. If only those who test positive are quarantined, the rest can have some breathing space. Will this approach work?

RT-PCR’s sensitivity, which is low in early illness, is even lower in asymptomatics, likely because of lower viral load, which means even more false negatives. The virus’s average incubation time of 5 days is enough time for false negative asymptomatics – remember they resemble the uninfected – to visit Disney World and infect another four.

Whether false negatives behave like tinder or a controllable fire will determine the testing strategy’s success. The net contagiousness of false negatives depends how many there are, which depends on how many are infected. To know how many are infected we need to test. Or, to know whether to believe a negative test in any person we must test widely – another Catch-22.

Maybe we need a bigger test.

Chest CT is an alternative. It’s rapid – takes less than an hour whereas RT-PCR can take over a day to report. In one study CT had a sensitivity of 97% in symptomatic patients and was often positive before RT-PCR. But there are caveats.

The real sensitivity of CT is likely much lower than 97% because the study has biases which inflate performance. CT, like RT-PCR, has a low sensitivity in early illness and even lower sensitivity in asymptomatic carriers for the same reason – lower viral load. Furthermore, CT has to be disinfected to prevent spread, which limits its access for other patients.

Coronavirus’s signature on CT – white patches in lungs, known as ground glass opacities – doesn’t have the uniqueness of the Mark of Zorro, and looks like lung injury from other rogue actors, which means we can mistake other serious conditions for coronavirus. Imagine hyenas in wolf’s clothing.

No test is perfect. We still use imaging despite its imperfections. But, let’s ask: What would you do differently if the test is negative and you have mild symptoms of cough and fever? Should you not self-isolate? What if you’re falsely negative and still contagious? If the advice dispensed whether the test is positive or negative is the same – i.e. quarantine for 2 weeks – what’s the test’s value?

Perhaps people will more likely comply with voluntary quarantine if they know they’re infected. Information can nudge behavior. But the logical corollary is that to comply with social distancing you need to be tested. People flocking to CT scans to affirm they’re not infected could infect those hitherto uninfected. A pandemic is no time to test nudge theories.

Does that mean testing has no value? Testing is valuable in managing populations. To individuals, the results must be framed wisely, such as by advising those who test positive to quarantine because “you’re infected” and those who test negative to keep social distancing because “you could still be infected.”

Even when policy goals are uniform, messaging can be oppositional. “Get yourself tested now” contradicts “you must hunker down now.” When messages contradict, one must choose which message to amplify.

The calculus of testing can change with new tests such as antibodies. The value of testing depends also on what isolation entails. A couple of weeks watching Netflix on your couch isn’t a big ask. If quarantine means being detained in an isolation center fenced by barbed wires, the cost of frivolous quarantining is higher and testing becomes more valuable.

I knew the doctor with the negative RT-PCR well. He’s heroically nonchalant about his wellbeing, an endearing quality that’s a liability in a contagion. In no time he’d be back in the hospital; or helping his elderly parents with grocery. Not all false negatives are equal. False-negative doctors could infect not just their patients but their colleagues, leaving fewer firefighters to fight fires.

It is better to mistake the man flu for coronavirus than coronavirus for the man flu. All he has to do is hunker down, which is what we should all be doing as much as we can.

Dr. Jha is a contributing editor to The Health Care Blog, where this article first appeared. He can be reached @RogueRad.

This article appeared on Medscape.com.

SAN DIEGO – On the days family physician Nick Yphantides, MD, announces updates on the COVID-19 epidemic to San Diego County residents, he can’t help but think about his late father.

In June of 2009, 75-year-old George Yphantides, a Steinway-trained piano technician who lived in Escondido, Calif., became the third person in the United States to die from complications of the pandemic H1N1 swine flu – just days before a vaccine became available.

“I loved my dad,” Dr. Yphantides, who has been San Diego County’s Chief Medical Officer since the year of his father’s death, said in an interview. “So, when you take a step back and take into consideration my sense of purpose in serving the 3.3 million residents of San Diego County, my passion based on my personal Christian faith, and my activation in terms of what happened to my dad, I have such a storm of internal sense of urgency right now.”

San Diego County and public health officials got experience with COVID-19 in advance of the country’s widely documented cases of community-based transmission. Around 9 pm on Jan. 31, 2020 – the Friday of Super Bowl weekend – Dr. Yphantides answered a phone call from Eric C. McDonald, MD, the county’s medical director of epidemiology. Dr. McDonald informed him that in a few days, a plane full of American citizens traveling from Wuhan, China, would be landing at Marine Corp Air Station Miramar in San Diego for a 2-week quarantine and that the task of providing medical support to any affected individuals fell on county officials.

“I will never forget that phone call,” he said. “We did have two positive cases. What we experienced with those evacuees was amazing surge preparation, and without exaggeration, I have worked 18-20 hours a day since that day.”

Fast forward to March 31, 2020, the county’s confirmed COVID-19 caseload had grown to 734, up 131 from the day before. As of the final day of March, nine people have died, with an age range between 25 and 87 years. Of confirmed cases, 61% are between the ages of 20 and 49, 43% are female, 19% have required hospitalization, 7% have required admission to intensive care, and the mortality rate has been 1.2%. Data currently show optimal proactive hospital capacity.

In the opinion of Dr. Yphantides, the 734 COVID-19 cases represent a tip of the iceberg. “How big is that iceberg? I can’t tell you yet,” he said.

Courtesy Tim McClain

Instead of being fearful or apprehensive about this uncertainty, Dr. Yphantides said he is “energized.”

"I see this as the Super Bowl of public health,” he exclaimed.

At least some of Dr. Yphantides’ vigor seems to be fueled by his pride in his team of professionals who have been helping him respond to the surge of COVID-19 cases.

As the county’s CMO, Dr. Yphantides serves as the liaison for the entire Emergency Medical System, the entire local health care delivery system, the entire physician and medical society network, the payor system, and the proportion of the area population using Medi-Cal.

Dr. Yphantides, who attended medical school at the University of California, San Diego, said that, compared with other regions of the country, San Diego County has made “tremendous progress” in overcoming many chronic lifestyle illnesses. For example, cardiovascular disease is no longer the number one cause of death in the county; it’s bookended by cancer and Alzheimer’s disease.

“In the context of the COVID-19 response, [the county’s health care team established] an entire incident command system in our emergency operations center. Our emergency operations center is activated to the top level,” he said.

Dr. Yphantides shares public communication efforts with Dr. McDonald and Wilma J. Wooten, MD, the county’s public health officer. The San Diego County CMO also engages with policymakers, including the board of supervisors, local mayors, state legislators, and national legislators.

“Because of the relational trust capital that I have in this community, I get pulled into unexpected rooms of discussion,” he said. This included meeting with top executives from the San Diego Padres in early March, putting them on notice that the 2020 Major League Baseball season would likely be postponed. (This was officially announced on March 16.)

“We have made some decisions that have devastated some people economically. Talk about flipping the switch. We are living and making history every day. It is unbelievable,” he said.

“San Diego is a more aged population compared to many other parts of the country. ... [Part] of the reason why I’m so frantically doing everything I can to prepare, to batten down the hatches, and to optimize our health care delivery system is because we have a population that collectively is more at risk [for more serious complications from COVID-19]. A lot of what drives me is advocacy,” Dr. Yphantides noted.
 

A colleague’s perspective

Kristi L. Koenig, MD, medical director of emergency medical services for the County of San Diego, characterized Dr. Yphantides’ management style as collaborative. “Under his leadership, we have the perspective of ‘just focus on patient care, get it done, be creative, work together as a team,’ ” said Dr. Koenig, who coedited the textbook, “Koenig and Schultz’s Disaster Medicine: Comprehensive Principles and Practices” (Cambridge University Press, 2016). “He’s decisive and he’s responsive. You don’t have to wait a long time to get a decision, which is very important right now because this is so fast moving.”

Dr. Koenig, who has worked with Dr. Yphantides for 3 years, said that she routinely feeds him information that might help the team navigate its response to COVID-19. “For example, if I see an idea for how to get more [personal protective equipment] and feed it to him, he might have a contact somewhere in a factory that could make the PPE,” she said. “We work together by my reminding him to keep it within the incident command system structure, so that we can coordinate all the resources and not duplicate efforts.”

He uses his personal connections in a way to implement ideas that are beneficial to the overall goal of decreasing morbidity and mortality,” Dr. Koenig added.
 

Predictions for San Diego County

Dr. Yphantides said he considers San Diego to still be in the calm before the storm and that he is working hard to “board up his community.” The county CMO is also trying to prepare the health care delivery system to optimize its capacity, of doing interventions with hopes of lowering the curve and enhancing the capacity, he said.

When the storm hits, “it’s going be brutal, because we’re going to lose life,” Dr. Yphantides said.

“I am praying that maybe by some of our efforts, instead of a Category 5 storm, it’ll be a Category 3 storm,” he remarked.
 

The future of health care

Dr. Yphantides views the COVID-19 pandemic as “an absolute game-changer” in terms of what the future of health care delivery will look like in the United States. “Whether the right word is the ‘Amazonification’ of health care, or the ‘Uberization’ of health care, I don’t know, but the essence of how we deliver care is radically being transformed literally before our eyes,” he said. “I would encourage my colleagues to embrace that” and take care of their people by doing whatever it takes under this unprecedented paradigm.

Meanwhile, Dr. Yphantides braces for a potential surge of COVID-19 cases in San Diego County in the coming weeks. He honors the memory of his dad, and he expresses thanks for his mom, who cares for his two teenaged daughters while he helps steward the region’s response to the pandemic.

“Without my mom I could not function in the way that I’m currently functioning,” he said. “So, when you add all of those factors up, and wrap it with a bowtie of sincere love and passion for my community, there’s a fire that’s burning inside of me right now.”
 

dbrunk@mdedge.com

SAN DIEGO – On the days family physician Nick Yphantides, MD, announces updates on the COVID-19 epidemic to San Diego County residents, he can’t help but think about his late father.

In June of 2009, 75-year-old George Yphantides, a Steinway-trained piano technician who lived in Escondido, Calif., became the third person in the United States to die from complications of the pandemic H1N1 swine flu – just days before a vaccine became available.

“I loved my dad,” Dr. Yphantides, who has been San Diego County’s Chief Medical Officer since the year of his father’s death, said in an interview. “So, when you take a step back and take into consideration my sense of purpose in serving the 3.3 million residents of San Diego County, my passion based on my personal Christian faith, and my activation in terms of what happened to my dad, I have such a storm of internal sense of urgency right now.”

San Diego County and public health officials got experience with COVID-19 in advance of the country’s widely documented cases of community-based transmission. Around 9 pm on Jan. 31, 2020 – the Friday of Super Bowl weekend – Dr. Yphantides answered a phone call from Eric C. McDonald, MD, the county’s medical director of epidemiology. Dr. McDonald informed him that in a few days, a plane full of American citizens traveling from Wuhan, China, would be landing at Marine Corp Air Station Miramar in San Diego for a 2-week quarantine and that the task of providing medical support to any affected individuals fell on county officials.

“I will never forget that phone call,” he said. “We did have two positive cases. What we experienced with those evacuees was amazing surge preparation, and without exaggeration, I have worked 18-20 hours a day since that day.”

Fast forward to March 31, 2020, the county’s confirmed COVID-19 caseload had grown to 734, up 131 from the day before. As of the final day of March, nine people have died, with an age range between 25 and 87 years. Of confirmed cases, 61% are between the ages of 20 and 49, 43% are female, 19% have required hospitalization, 7% have required admission to intensive care, and the mortality rate has been 1.2%. Data currently show optimal proactive hospital capacity.

In the opinion of Dr. Yphantides, the 734 COVID-19 cases represent a tip of the iceberg. “How big is that iceberg? I can’t tell you yet,” he said.

Courtesy Tim McClain

Instead of being fearful or apprehensive about this uncertainty, Dr. Yphantides said he is “energized.”

"I see this as the Super Bowl of public health,” he exclaimed.

At least some of Dr. Yphantides’ vigor seems to be fueled by his pride in his team of professionals who have been helping him respond to the surge of COVID-19 cases.

As the county’s CMO, Dr. Yphantides serves as the liaison for the entire Emergency Medical System, the entire local health care delivery system, the entire physician and medical society network, the payor system, and the proportion of the area population using Medi-Cal.

Dr. Yphantides, who attended medical school at the University of California, San Diego, said that, compared with other regions of the country, San Diego County has made “tremendous progress” in overcoming many chronic lifestyle illnesses. For example, cardiovascular disease is no longer the number one cause of death in the county; it’s bookended by cancer and Alzheimer’s disease.

“In the context of the COVID-19 response, [the county’s health care team established] an entire incident command system in our emergency operations center. Our emergency operations center is activated to the top level,” he said.

Dr. Yphantides shares public communication efforts with Dr. McDonald and Wilma J. Wooten, MD, the county’s public health officer. The San Diego County CMO also engages with policymakers, including the board of supervisors, local mayors, state legislators, and national legislators.

“Because of the relational trust capital that I have in this community, I get pulled into unexpected rooms of discussion,” he said. This included meeting with top executives from the San Diego Padres in early March, putting them on notice that the 2020 Major League Baseball season would likely be postponed. (This was officially announced on March 16.)

“We have made some decisions that have devastated some people economically. Talk about flipping the switch. We are living and making history every day. It is unbelievable,” he said.

“San Diego is a more aged population compared to many other parts of the country. ... [Part] of the reason why I’m so frantically doing everything I can to prepare, to batten down the hatches, and to optimize our health care delivery system is because we have a population that collectively is more at risk [for more serious complications from COVID-19]. A lot of what drives me is advocacy,” Dr. Yphantides noted.
 

A colleague’s perspective

Kristi L. Koenig, MD, medical director of emergency medical services for the County of San Diego, characterized Dr. Yphantides’ management style as collaborative. “Under his leadership, we have the perspective of ‘just focus on patient care, get it done, be creative, work together as a team,’ ” said Dr. Koenig, who coedited the textbook, “Koenig and Schultz’s Disaster Medicine: Comprehensive Principles and Practices” (Cambridge University Press, 2016). “He’s decisive and he’s responsive. You don’t have to wait a long time to get a decision, which is very important right now because this is so fast moving.”

Dr. Koenig, who has worked with Dr. Yphantides for 3 years, said that she routinely feeds him information that might help the team navigate its response to COVID-19. “For example, if I see an idea for how to get more [personal protective equipment] and feed it to him, he might have a contact somewhere in a factory that could make the PPE,” she said. “We work together by my reminding him to keep it within the incident command system structure, so that we can coordinate all the resources and not duplicate efforts.”

He uses his personal connections in a way to implement ideas that are beneficial to the overall goal of decreasing morbidity and mortality,” Dr. Koenig added.
 

Predictions for San Diego County

Dr. Yphantides said he considers San Diego to still be in the calm before the storm and that he is working hard to “board up his community.” The county CMO is also trying to prepare the health care delivery system to optimize its capacity, of doing interventions with hopes of lowering the curve and enhancing the capacity, he said.

When the storm hits, “it’s going be brutal, because we’re going to lose life,” Dr. Yphantides said.

“I am praying that maybe by some of our efforts, instead of a Category 5 storm, it’ll be a Category 3 storm,” he remarked.
 

The future of health care

Dr. Yphantides views the COVID-19 pandemic as “an absolute game-changer” in terms of what the future of health care delivery will look like in the United States. “Whether the right word is the ‘Amazonification’ of health care, or the ‘Uberization’ of health care, I don’t know, but the essence of how we deliver care is radically being transformed literally before our eyes,” he said. “I would encourage my colleagues to embrace that” and take care of their people by doing whatever it takes under this unprecedented paradigm.

Meanwhile, Dr. Yphantides braces for a potential surge of COVID-19 cases in San Diego County in the coming weeks. He honors the memory of his dad, and he expresses thanks for his mom, who cares for his two teenaged daughters while he helps steward the region’s response to the pandemic.

“Without my mom I could not function in the way that I’m currently functioning,” he said. “So, when you add all of those factors up, and wrap it with a bowtie of sincere love and passion for my community, there’s a fire that’s burning inside of me right now.”
 

dbrunk@mdedge.com

SAN DIEGO – On the days family physician Nick Yphantides, MD, announces updates on the COVID-19 epidemic to San Diego County residents, he can’t help but think about his late father.

In June of 2009, 75-year-old George Yphantides, a Steinway-trained piano technician who lived in Escondido, Calif., became the third person in the United States to die from complications of the pandemic H1N1 swine flu – just days before a vaccine became available.

“I loved my dad,” Dr. Yphantides, who has been San Diego County’s Chief Medical Officer since the year of his father’s death, said in an interview. “So, when you take a step back and take into consideration my sense of purpose in serving the 3.3 million residents of San Diego County, my passion based on my personal Christian faith, and my activation in terms of what happened to my dad, I have such a storm of internal sense of urgency right now.”

San Diego County and public health officials got experience with COVID-19 in advance of the country’s widely documented cases of community-based transmission. Around 9 pm on Jan. 31, 2020 – the Friday of Super Bowl weekend – Dr. Yphantides answered a phone call from Eric C. McDonald, MD, the county’s medical director of epidemiology. Dr. McDonald informed him that in a few days, a plane full of American citizens traveling from Wuhan, China, would be landing at Marine Corp Air Station Miramar in San Diego for a 2-week quarantine and that the task of providing medical support to any affected individuals fell on county officials.

“I will never forget that phone call,” he said. “We did have two positive cases. What we experienced with those evacuees was amazing surge preparation, and without exaggeration, I have worked 18-20 hours a day since that day.”

Fast forward to March 31, 2020, the county’s confirmed COVID-19 caseload had grown to 734, up 131 from the day before. As of the final day of March, nine people have died, with an age range between 25 and 87 years. Of confirmed cases, 61% are between the ages of 20 and 49, 43% are female, 19% have required hospitalization, 7% have required admission to intensive care, and the mortality rate has been 1.2%. Data currently show optimal proactive hospital capacity.

In the opinion of Dr. Yphantides, the 734 COVID-19 cases represent a tip of the iceberg. “How big is that iceberg? I can’t tell you yet,” he said.

Courtesy Tim McClain

Instead of being fearful or apprehensive about this uncertainty, Dr. Yphantides said he is “energized.”

"I see this as the Super Bowl of public health,” he exclaimed.

At least some of Dr. Yphantides’ vigor seems to be fueled by his pride in his team of professionals who have been helping him respond to the surge of COVID-19 cases.

As the county’s CMO, Dr. Yphantides serves as the liaison for the entire Emergency Medical System, the entire local health care delivery system, the entire physician and medical society network, the payor system, and the proportion of the area population using Medi-Cal.

Dr. Yphantides, who attended medical school at the University of California, San Diego, said that, compared with other regions of the country, San Diego County has made “tremendous progress” in overcoming many chronic lifestyle illnesses. For example, cardiovascular disease is no longer the number one cause of death in the county; it’s bookended by cancer and Alzheimer’s disease.

“In the context of the COVID-19 response, [the county’s health care team established] an entire incident command system in our emergency operations center. Our emergency operations center is activated to the top level,” he said.

Dr. Yphantides shares public communication efforts with Dr. McDonald and Wilma J. Wooten, MD, the county’s public health officer. The San Diego County CMO also engages with policymakers, including the board of supervisors, local mayors, state legislators, and national legislators.

“Because of the relational trust capital that I have in this community, I get pulled into unexpected rooms of discussion,” he said. This included meeting with top executives from the San Diego Padres in early March, putting them on notice that the 2020 Major League Baseball season would likely be postponed. (This was officially announced on March 16.)

“We have made some decisions that have devastated some people economically. Talk about flipping the switch. We are living and making history every day. It is unbelievable,” he said.

“San Diego is a more aged population compared to many other parts of the country. ... [Part] of the reason why I’m so frantically doing everything I can to prepare, to batten down the hatches, and to optimize our health care delivery system is because we have a population that collectively is more at risk [for more serious complications from COVID-19]. A lot of what drives me is advocacy,” Dr. Yphantides noted.
 

A colleague’s perspective

Kristi L. Koenig, MD, medical director of emergency medical services for the County of San Diego, characterized Dr. Yphantides’ management style as collaborative. “Under his leadership, we have the perspective of ‘just focus on patient care, get it done, be creative, work together as a team,’ ” said Dr. Koenig, who coedited the textbook, “Koenig and Schultz’s Disaster Medicine: Comprehensive Principles and Practices” (Cambridge University Press, 2016). “He’s decisive and he’s responsive. You don’t have to wait a long time to get a decision, which is very important right now because this is so fast moving.”

Dr. Koenig, who has worked with Dr. Yphantides for 3 years, said that she routinely feeds him information that might help the team navigate its response to COVID-19. “For example, if I see an idea for how to get more [personal protective equipment] and feed it to him, he might have a contact somewhere in a factory that could make the PPE,” she said. “We work together by my reminding him to keep it within the incident command system structure, so that we can coordinate all the resources and not duplicate efforts.”

He uses his personal connections in a way to implement ideas that are beneficial to the overall goal of decreasing morbidity and mortality,” Dr. Koenig added.
 

Predictions for San Diego County

Dr. Yphantides said he considers San Diego to still be in the calm before the storm and that he is working hard to “board up his community.” The county CMO is also trying to prepare the health care delivery system to optimize its capacity, of doing interventions with hopes of lowering the curve and enhancing the capacity, he said.

When the storm hits, “it’s going be brutal, because we’re going to lose life,” Dr. Yphantides said.

“I am praying that maybe by some of our efforts, instead of a Category 5 storm, it’ll be a Category 3 storm,” he remarked.
 

The future of health care

Dr. Yphantides views the COVID-19 pandemic as “an absolute game-changer” in terms of what the future of health care delivery will look like in the United States. “Whether the right word is the ‘Amazonification’ of health care, or the ‘Uberization’ of health care, I don’t know, but the essence of how we deliver care is radically being transformed literally before our eyes,” he said. “I would encourage my colleagues to embrace that” and take care of their people by doing whatever it takes under this unprecedented paradigm.

Meanwhile, Dr. Yphantides braces for a potential surge of COVID-19 cases in San Diego County in the coming weeks. He honors the memory of his dad, and he expresses thanks for his mom, who cares for his two teenaged daughters while he helps steward the region’s response to the pandemic.

“Without my mom I could not function in the way that I’m currently functioning,” he said. “So, when you add all of those factors up, and wrap it with a bowtie of sincere love and passion for my community, there’s a fire that’s burning inside of me right now.”
 

dbrunk@mdedge.com

The risk for death from COVID-19 is 1.38% overall, according to a new study. However, the fatality rate rises with age, from well below 1% among children aged 9 years or younger to nearly 8% for seniors aged 80 years or older, the latest statistics show.

“These early estimates give an indication of the fatality ratio across the spectrum of COVID-19 disease and show a strong age gradient in risk of death,” Robert Verity, PhD, of University College London, and colleagues, wrote in a study published online in the Lancet Infectious Diseases.

Among those infected with SARS-CoV-2, the virus that causes COVID-19, the risk for hospitalization also increases with age. Specifically, 11.8% of people in their 60s require admission, as do 16.6% of people in their 70s and 18.4% for those in their 80s or older.

The case fatality estimates are based on data regarding individual patients who died from COVID-19 in Hubei, China, through Feb. 8, as well as those who died in Hong Kong, Macau, and 37 countries outside China through Feb. 25.

“It is clear from the data that have emerged from China that case fatality ratio increases substantially with age. Our results suggest a very low fatality ratio in those under the age of 20 years. As there are very few cases in this age group, it remains unclear whether this reflects a low risk of death or a difference in susceptibility, although early results indicate young people are not at lower risk of infection than adults,” Dr. Verity and colleagues wrote.

The authors emphasized that serologic testing of adolescents and children will be vital to understanding how individuals younger than 20 years may be driving viral transmission.

In an accompanying editorial Shigui Ruan, PhD, of the department of mathematics at the University of Miami in Coral Gables, Fla., wrote that early detection, diagnosis, isolation, and treatment, as practiced in China, may help to prevent more deaths

“Even though the fatality rate is low for younger people, it is very clear that any suggestion of COVID-19 being just like influenza is false: Even for those aged 20-29 years, once infected with SARS-CoV-2, the mortality rate is 33 times higher than that from seasonal influenza,” he noted.

Dr. Ruan, who uses applied mathematics to model disease transmission, noted that otherwise healthy people stand a good chance – approximately 95% – of surviving COVID-19, but the odds of survival for people with comorbidities will be “considerably decreased.”

Time to death or discharge

Dr. Verity and colleagues first used data on deaths of 24 patients in mainland China and on 165 persons who recovered from infection outside of China to estimate the time between onset of symptoms and either death or discharge from the hospital. They estimated that the mean duration from symptom onset to death is 17.8 days, and the mean duration to discharge is 24.7 days.

They then estimated age-stratified case fatality ratios among all clinically diagnosed and laboratory-confirmed cases in mainland China to the end of the study period (70,117 cases).

The estimated crude case fatality ratio, adjusted for censoring, was 3.67%. With further adjustment for demographic characteristics and under-ascertainment, the authors’ best estimate of a case fatality ratio in China is 1.38%.

The following figure shows adjusted fatality infection rates by age group.

Hospitalizations rise with age

The investigators also estimated the proportion of infected patients who require hospitalization. Their estimation was based on data from a subset of cases reported in mainland China. The hospitalization estimates range from zero among the youngest patients to 18% among the oldest.

A version of this article originally appeared on Medscape.com.

The risk for death from COVID-19 is 1.38% overall, according to a new study. However, the fatality rate rises with age, from well below 1% among children aged 9 years or younger to nearly 8% for seniors aged 80 years or older, the latest statistics show.

“These early estimates give an indication of the fatality ratio across the spectrum of COVID-19 disease and show a strong age gradient in risk of death,” Robert Verity, PhD, of University College London, and colleagues, wrote in a study published online in the Lancet Infectious Diseases.

Among those infected with SARS-CoV-2, the virus that causes COVID-19, the risk for hospitalization also increases with age. Specifically, 11.8% of people in their 60s require admission, as do 16.6% of people in their 70s and 18.4% for those in their 80s or older.

The case fatality estimates are based on data regarding individual patients who died from COVID-19 in Hubei, China, through Feb. 8, as well as those who died in Hong Kong, Macau, and 37 countries outside China through Feb. 25.

“It is clear from the data that have emerged from China that case fatality ratio increases substantially with age. Our results suggest a very low fatality ratio in those under the age of 20 years. As there are very few cases in this age group, it remains unclear whether this reflects a low risk of death or a difference in susceptibility, although early results indicate young people are not at lower risk of infection than adults,” Dr. Verity and colleagues wrote.

The authors emphasized that serologic testing of adolescents and children will be vital to understanding how individuals younger than 20 years may be driving viral transmission.

In an accompanying editorial Shigui Ruan, PhD, of the department of mathematics at the University of Miami in Coral Gables, Fla., wrote that early detection, diagnosis, isolation, and treatment, as practiced in China, may help to prevent more deaths

“Even though the fatality rate is low for younger people, it is very clear that any suggestion of COVID-19 being just like influenza is false: Even for those aged 20-29 years, once infected with SARS-CoV-2, the mortality rate is 33 times higher than that from seasonal influenza,” he noted.

Dr. Ruan, who uses applied mathematics to model disease transmission, noted that otherwise healthy people stand a good chance – approximately 95% – of surviving COVID-19, but the odds of survival for people with comorbidities will be “considerably decreased.”

Time to death or discharge

Dr. Verity and colleagues first used data on deaths of 24 patients in mainland China and on 165 persons who recovered from infection outside of China to estimate the time between onset of symptoms and either death or discharge from the hospital. They estimated that the mean duration from symptom onset to death is 17.8 days, and the mean duration to discharge is 24.7 days.

They then estimated age-stratified case fatality ratios among all clinically diagnosed and laboratory-confirmed cases in mainland China to the end of the study period (70,117 cases).

The estimated crude case fatality ratio, adjusted for censoring, was 3.67%. With further adjustment for demographic characteristics and under-ascertainment, the authors’ best estimate of a case fatality ratio in China is 1.38%.

The following figure shows adjusted fatality infection rates by age group.

Hospitalizations rise with age

The investigators also estimated the proportion of infected patients who require hospitalization. Their estimation was based on data from a subset of cases reported in mainland China. The hospitalization estimates range from zero among the youngest patients to 18% among the oldest.

A version of this article originally appeared on Medscape.com.

The risk for death from COVID-19 is 1.38% overall, according to a new study. However, the fatality rate rises with age, from well below 1% among children aged 9 years or younger to nearly 8% for seniors aged 80 years or older, the latest statistics show.

“These early estimates give an indication of the fatality ratio across the spectrum of COVID-19 disease and show a strong age gradient in risk of death,” Robert Verity, PhD, of University College London, and colleagues, wrote in a study published online in the Lancet Infectious Diseases.

Among those infected with SARS-CoV-2, the virus that causes COVID-19, the risk for hospitalization also increases with age. Specifically, 11.8% of people in their 60s require admission, as do 16.6% of people in their 70s and 18.4% for those in their 80s or older.

The case fatality estimates are based on data regarding individual patients who died from COVID-19 in Hubei, China, through Feb. 8, as well as those who died in Hong Kong, Macau, and 37 countries outside China through Feb. 25.

“It is clear from the data that have emerged from China that case fatality ratio increases substantially with age. Our results suggest a very low fatality ratio in those under the age of 20 years. As there are very few cases in this age group, it remains unclear whether this reflects a low risk of death or a difference in susceptibility, although early results indicate young people are not at lower risk of infection than adults,” Dr. Verity and colleagues wrote.

The authors emphasized that serologic testing of adolescents and children will be vital to understanding how individuals younger than 20 years may be driving viral transmission.

In an accompanying editorial Shigui Ruan, PhD, of the department of mathematics at the University of Miami in Coral Gables, Fla., wrote that early detection, diagnosis, isolation, and treatment, as practiced in China, may help to prevent more deaths

“Even though the fatality rate is low for younger people, it is very clear that any suggestion of COVID-19 being just like influenza is false: Even for those aged 20-29 years, once infected with SARS-CoV-2, the mortality rate is 33 times higher than that from seasonal influenza,” he noted.

Dr. Ruan, who uses applied mathematics to model disease transmission, noted that otherwise healthy people stand a good chance – approximately 95% – of surviving COVID-19, but the odds of survival for people with comorbidities will be “considerably decreased.”

Time to death or discharge

Dr. Verity and colleagues first used data on deaths of 24 patients in mainland China and on 165 persons who recovered from infection outside of China to estimate the time between onset of symptoms and either death or discharge from the hospital. They estimated that the mean duration from symptom onset to death is 17.8 days, and the mean duration to discharge is 24.7 days.

They then estimated age-stratified case fatality ratios among all clinically diagnosed and laboratory-confirmed cases in mainland China to the end of the study period (70,117 cases).

The estimated crude case fatality ratio, adjusted for censoring, was 3.67%. With further adjustment for demographic characteristics and under-ascertainment, the authors’ best estimate of a case fatality ratio in China is 1.38%.

The following figure shows adjusted fatality infection rates by age group.

Hospitalizations rise with age

The investigators also estimated the proportion of infected patients who require hospitalization. Their estimation was based on data from a subset of cases reported in mainland China. The hospitalization estimates range from zero among the youngest patients to 18% among the oldest.

A version of this article originally appeared on Medscape.com.

As the COVID-19 pandemic continues to spread across the United States, several members of the Ob.Gyn. News Editorial Advisory Board shared their experiences.

• One person will cover labor and delivery.
• One person will cover triage and help on labor and delivery.
• One person will be assigned to the resident office.
• One person will be assigned to cover the team of the post call attending (Sunday through Thursday call).
• One person will be assigned to gynecology coverage, consults, and postpartum rounds.

To further minimize the patient interactions, when possible, each patient should be seen by the attending physician with the resident. This is a change from usual practice, where the patient is first seen by the resident, who reports back to the attending, and then both physicians see the patient together.

The network’s offices now open from 9 a.m. (many offices had been offering early-morning hours starting at 7 a.m.), and the physicians and advanced practice providers will work through the last scheduled patient appointment, Dr. Jaspan explained. “The office-based team will preferentially see in-person visits.”

Several offices have been closed so that ob.gyns. and staff can be reassigned to telehealth. The remaining five offices generally have one attending physician and one advanced practice provider.

The remaining team of ob.gyns. provides telehealth with the help of staff members. This involves an initial call to the patient by staff letting them know the doctor will be calling, checking them in, verifying insurance, and collecting payment, followed by the actual telehealth visit. If follow-up is needed, the staff member schedules the follow-up.

Dr. Jaspan called the new approach to prenatal care because of COVID-19 a “cataclysmic change in how we care for our patients. We have decided to further limit our obstetrical in-person visits. It is our feeling that these changes will enable patients to remain outside of the office and in the safety of their homes, provide appropriate social distancing, and diminish potential exposures to the office staff providers and patients.”

In-person visits will occur at: the initial visit, between 24 and 28 weeks, at 32 weeks, and at 36 or 37 weeks; if the patient at 36/37 has a blood pressure cuff, they will not have additional scheduled in-patient visits. We have partnered with the insurance companies to provide more than 88% of obstetrical patients with home blood pressure cuffs.

Obstetrical visits via telehealth will continue at our standard intervals: monthly until 26 weeks; twice monthly during 26-36 weeks; and weekly from 37 weeks to delivery. These visits should use a video component such as Zoom, Doxy.me, or FaceTime.

“If the patient has concerns or problems, we will see them at any time. However, the new standard will be telehealth visits and the exception will be the in-person visit,” Dr. Jaspan said.

In addition, we have worked our division of maternal-fetal medicine to adjust the antenatal testing schedules, and we have curtailed the frequency of ultrasound, he noted.

He emphasized the importance of documenting telehealth interactions with obstetrical patients, in addition to “providing adequate teaching and education for patients regarding kick counts to ensure fetal well-being.” It also is key to “properly document conversations with patients regarding bleeding, rupture of membranes, fetal movement, headache, visual changes, fevers, cough, nausea and vomiting, diarrhea, fatigue, muscle aches, etc.”

The residents’ schedule also has been modified to diminish their exposure. Within our new paradigm, we have scheduled video conferences to enable our program to maintain our commitment to academics.

It is imperative that we keep our patients safe, and it is critical to protect our staff members. Those who provide women’s health cannot be replaced by other nurses or physicians.