Henry C. Barry, MD, MS

Recently, my family had a conversation about the volume of news reports on overdose deaths from the illicit use of opioid drugs—a phenomenon that is complex and stems from many factors. We decided, as a family, that we could have a small impact on the problem. How? By carrying naloxone with us and administering it if we encounter a person with potential opioid overdose. Our decision was made possible by the recent US Food and Drug Administration (FDA) approval of naloxone nasal spray for over-the-counter use.¹ At a cost of about $50 for 2 nasal sprays, we decided it would be a reasonable price to pay to potentially save a life.

The CDC encourages clinicians to find a balance of the potential benefits and harms and to avoid inflexibility.

Prescribing opioids in clinical practice is a different side of the problem. The Centers for Disease Control and Prevention (CDC) reports that prescription opioids account for about one-quarter of opioid overdose deaths.² This is not trivial, and much effort has gone into addressing how clinicians can do better by their patients. There are training programs and risk-mitigation strategies for opioid prescribing. States have developed prescribing registries to identify patients who receive controlled substances from multiple prescribers, at higher-than-recommended doses, and too early in the pain management process. These efforts have reduced the number of opioid prescriptions and rates of high-dose prescribing (> 90 morphine milligram equivalents). However, that hasn’t translated into a reduction in the number of deaths.²

The article by Posen et al³ in this issue further reminded me how trends in health care, including opioid prescribing, are like a pendulum—swinging from one extreme to the other before eventually centering. I recall conversations with colleagues about how often we undertreated pain—and then later, how relieved we were when new approaches to pain management, using newer opiates, emerged and were reported to be much safer, even for long-term use. We now know the rest of that story: more prescriptions, higher doses, longer duration, addiction, death, and deception by manufacturers.

In our efforts to prevent addiction and decrease opioid deaths, we tried to get patients off opioids completely, thereby increasing demand for addiction therapy, including medication-assisted recovery. This also drove many of our patients to seek opioids from nefarious suppliers, resulting in even more deaths from fentanyl-laced drugs.

At least one positive has arisen from the “no more opioids” movement: We have re-evaluated their true effect on managing pain. Initially, we were told opioids were safe and highly effective—and, having few tools to help our patients, we were ­Pollyanna-ish in accepting this. But many recent studies have demonstrated that using opioids for pain is no more effective than using other analgesics.^4-9 In addition to overdose deaths and addiction, these studies show significantly higher rates of opioid discontinuation due to adverse effects.

We certainly can manage most patients’ pain effectively with other approaches. For some, though—patients whose pain is not adequately controlled and/or interferes with their ability to function, and those who are terminally ill—opioid nihilism has had unintended consequences. Recognizing these issues, the CDC updated its guideline for prescribing opioids in 2022.¹⁰ Four areas were addressed: whether to initiate opioids; opioid selection and dosing; duration of therapy and need for follow-up; and assessing risk and addressing potential harms of opioid use. The CDC encourages clinicians to find a balance of the potential benefits and harms and to avoid inflexibility. Finally, the CDC encourages clinicians to identify and treat patients with opioid use disorders.

Clearly, opioid overuse and overdose result from complex medical, economic, and societal factors. Individual clinicians are well equipped to manage things “in their own backyards.” However, what we do can be perceived as a bandage for a much larger problem. Our public health system has the potential for greater impact, but the “cure” will require multimodal solutions addressing many facets of society and government.¹¹ At the very least, we should keep some naloxone close by and vote for political candidates who see broader solutions for addressing this life-and-death crisis.

Recently, my family had a conversation about the volume of news reports on overdose deaths from the illicit use of opioid drugs—a phenomenon that is complex and stems from many factors. We decided, as a family, that we could have a small impact on the problem. How? By carrying naloxone with us and administering it if we encounter a person with potential opioid overdose. Our decision was made possible by the recent US Food and Drug Administration (FDA) approval of naloxone nasal spray for over-the-counter use.¹ At a cost of about $50 for 2 nasal sprays, we decided it would be a reasonable price to pay to potentially save a life.

The CDC encourages clinicians to find a balance of the potential benefits and harms and to avoid inflexibility.

Prescribing opioids in clinical practice is a different side of the problem. The Centers for Disease Control and Prevention (CDC) reports that prescription opioids account for about one-quarter of opioid overdose deaths.² This is not trivial, and much effort has gone into addressing how clinicians can do better by their patients. There are training programs and risk-mitigation strategies for opioid prescribing. States have developed prescribing registries to identify patients who receive controlled substances from multiple prescribers, at higher-than-recommended doses, and too early in the pain management process. These efforts have reduced the number of opioid prescriptions and rates of high-dose prescribing (> 90 morphine milligram equivalents). However, that hasn’t translated into a reduction in the number of deaths.²

The article by Posen et al³ in this issue further reminded me how trends in health care, including opioid prescribing, are like a pendulum—swinging from one extreme to the other before eventually centering. I recall conversations with colleagues about how often we undertreated pain—and then later, how relieved we were when new approaches to pain management, using newer opiates, emerged and were reported to be much safer, even for long-term use. We now know the rest of that story: more prescriptions, higher doses, longer duration, addiction, death, and deception by manufacturers.

In our efforts to prevent addiction and decrease opioid deaths, we tried to get patients off opioids completely, thereby increasing demand for addiction therapy, including medication-assisted recovery. This also drove many of our patients to seek opioids from nefarious suppliers, resulting in even more deaths from fentanyl-laced drugs.

At least one positive has arisen from the “no more opioids” movement: We have re-evaluated their true effect on managing pain. Initially, we were told opioids were safe and highly effective—and, having few tools to help our patients, we were ­Pollyanna-ish in accepting this. But many recent studies have demonstrated that using opioids for pain is no more effective than using other analgesics.^4-9 In addition to overdose deaths and addiction, these studies show significantly higher rates of opioid discontinuation due to adverse effects.

We certainly can manage most patients’ pain effectively with other approaches. For some, though—patients whose pain is not adequately controlled and/or interferes with their ability to function, and those who are terminally ill—opioid nihilism has had unintended consequences. Recognizing these issues, the CDC updated its guideline for prescribing opioids in 2022.¹⁰ Four areas were addressed: whether to initiate opioids; opioid selection and dosing; duration of therapy and need for follow-up; and assessing risk and addressing potential harms of opioid use. The CDC encourages clinicians to find a balance of the potential benefits and harms and to avoid inflexibility. Finally, the CDC encourages clinicians to identify and treat patients with opioid use disorders.

Clearly, opioid overuse and overdose result from complex medical, economic, and societal factors. Individual clinicians are well equipped to manage things “in their own backyards.” However, what we do can be perceived as a bandage for a much larger problem. Our public health system has the potential for greater impact, but the “cure” will require multimodal solutions addressing many facets of society and government.¹¹ At the very least, we should keep some naloxone close by and vote for political candidates who see broader solutions for addressing this life-and-death crisis.

Recently, my family had a conversation about the volume of news reports on overdose deaths from the illicit use of opioid drugs—a phenomenon that is complex and stems from many factors. We decided, as a family, that we could have a small impact on the problem. How? By carrying naloxone with us and administering it if we encounter a person with potential opioid overdose. Our decision was made possible by the recent US Food and Drug Administration (FDA) approval of naloxone nasal spray for over-the-counter use.¹ At a cost of about $50 for 2 nasal sprays, we decided it would be a reasonable price to pay to potentially save a life.

The CDC encourages clinicians to find a balance of the potential benefits and harms and to avoid inflexibility.

Prescribing opioids in clinical practice is a different side of the problem. The Centers for Disease Control and Prevention (CDC) reports that prescription opioids account for about one-quarter of opioid overdose deaths.² This is not trivial, and much effort has gone into addressing how clinicians can do better by their patients. There are training programs and risk-mitigation strategies for opioid prescribing. States have developed prescribing registries to identify patients who receive controlled substances from multiple prescribers, at higher-than-recommended doses, and too early in the pain management process. These efforts have reduced the number of opioid prescriptions and rates of high-dose prescribing (> 90 morphine milligram equivalents). However, that hasn’t translated into a reduction in the number of deaths.²

The article by Posen et al³ in this issue further reminded me how trends in health care, including opioid prescribing, are like a pendulum—swinging from one extreme to the other before eventually centering. I recall conversations with colleagues about how often we undertreated pain—and then later, how relieved we were when new approaches to pain management, using newer opiates, emerged and were reported to be much safer, even for long-term use. We now know the rest of that story: more prescriptions, higher doses, longer duration, addiction, death, and deception by manufacturers.

In our efforts to prevent addiction and decrease opioid deaths, we tried to get patients off opioids completely, thereby increasing demand for addiction therapy, including medication-assisted recovery. This also drove many of our patients to seek opioids from nefarious suppliers, resulting in even more deaths from fentanyl-laced drugs.

At least one positive has arisen from the “no more opioids” movement: We have re-evaluated their true effect on managing pain. Initially, we were told opioids were safe and highly effective—and, having few tools to help our patients, we were ­Pollyanna-ish in accepting this. But many recent studies have demonstrated that using opioids for pain is no more effective than using other analgesics.^4-9 In addition to overdose deaths and addiction, these studies show significantly higher rates of opioid discontinuation due to adverse effects.

We certainly can manage most patients’ pain effectively with other approaches. For some, though—patients whose pain is not adequately controlled and/or interferes with their ability to function, and those who are terminally ill—opioid nihilism has had unintended consequences. Recognizing these issues, the CDC updated its guideline for prescribing opioids in 2022.¹⁰ Four areas were addressed: whether to initiate opioids; opioid selection and dosing; duration of therapy and need for follow-up; and assessing risk and addressing potential harms of opioid use. The CDC encourages clinicians to find a balance of the potential benefits and harms and to avoid inflexibility. Finally, the CDC encourages clinicians to identify and treat patients with opioid use disorders.

Clearly, opioid overuse and overdose result from complex medical, economic, and societal factors. Individual clinicians are well equipped to manage things “in their own backyards.” However, what we do can be perceived as a bandage for a much larger problem. Our public health system has the potential for greater impact, but the “cure” will require multimodal solutions addressing many facets of society and government.¹¹ At the very least, we should keep some naloxone close by and vote for political candidates who see broader solutions for addressing this life-and-death crisis.

Last year, after a long delay due to COVID, my father’s ashes were finally laid to rest at Arlington National Cemetery. Among the loved ones who came was my favorite aunt, Tante Ilse, who was suffering from dementia. While she wasn’t “following” everything that was going on, she did perk up when she heard my father’s name and would comment on how she liked him and how wonderful he had been to her.

After the ceremony, our family of about 30 gathered at a restaurant where we shared stories and old pictures. Tante Ilse seemed to relish the photos and the time with family. She was doing so well that when we went back to my mom’s home after the reception, my cousins decided to bring Tante Ilse there, too. She had a great time, as evidenced by her famous total-body laugh. In the months before her death, we all commented about that day and how happy she seemed.

I would have hoped for something better than merely clearing amyloid for my aunt.

My aunt’s decline comes to mind as I reflect on media reports of 2 Alzheimer drugs— aducanumab and lecanemab—that have been billed by some as “gamechangers.” These new drugs are monoclonal antibodies directed at amyloid, one of several agents thought to cause Alzheimer disease. The details of aducanumab’s approval by the US Food and Drug Administration (FDA) generated a great deal of criticism—with good reason.

Two manufacturer-sponsored studies of aducanumab were halted due to futility of finding a benefit.¹ The FDA’s scientific advisory panel recommended against approval due to a lack of evidence that it did anything more than remove amyloid plaque from the brain. And yet aducanumab received accelerated approval from the FDA. (This author collaborated on an additional analysis using data presented to the FDA, after its approval, which also reported no clinically meaningful effects.²) The other agent, lecanemab, also reduces markers of amyloid and was shown to be only moderately better than placebo in decreasing the rate of decline on various measures of cognition.³ Quite notably, both aducanumab and lecanemab, which are administered parenterally, cost more than $25,000 per year^4,5 and cause amyloid-related imaging abnormalities (brain edema or hemorrhage).

Expensive agents without meaningful benefit. So far, neither of these agents has shown a reduction in things that are truly important to our patients and their families/caregivers: a reduction in caregiver burden and a reduction in the need for placement in long-term care facilities.

This is in contrast to cholinesterase inhibitors, which also slow the rate of cognitive decline.⁶ Among the differences that exist between these agents: Cholinesterase inhibitors are taken orally and are available as generics, which cost less than a thousand dollars per year.⁷ Limited data also suggest that they are associated with a lower risk for nursing home placement.^8,9 (A February 2023 search of clinicaltrials.gov did not reveal any completed or planned head-to-head comparisons of monoclonal antibodies and anticholinergic agents.)

Our patients, their families, and caregivers hold out hope for something that will improve the patient’s cognition and extend the meaningful time they have with their loved ones. So far, the best we have to offer falls far short of these goals. I certainly would have hoped for something better than merely clearing amyloid for my aunt.

It’s time that the FDA adopt more rigorous standards requiring new drugs to, among other things, demonstrate meaningful clinical benefits, provide real cost savings, and be safer than currently available therapies. Other nations seem to be able to do this.^10,11 It is bad enough to provide “hope in a bottle”; it is worse when what is offered is false hope.

Last year, after a long delay due to COVID, my father’s ashes were finally laid to rest at Arlington National Cemetery. Among the loved ones who came was my favorite aunt, Tante Ilse, who was suffering from dementia. While she wasn’t “following” everything that was going on, she did perk up when she heard my father’s name and would comment on how she liked him and how wonderful he had been to her.

After the ceremony, our family of about 30 gathered at a restaurant where we shared stories and old pictures. Tante Ilse seemed to relish the photos and the time with family. She was doing so well that when we went back to my mom’s home after the reception, my cousins decided to bring Tante Ilse there, too. She had a great time, as evidenced by her famous total-body laugh. In the months before her death, we all commented about that day and how happy she seemed.

I would have hoped for something better than merely clearing amyloid for my aunt.

My aunt’s decline comes to mind as I reflect on media reports of 2 Alzheimer drugs— aducanumab and lecanemab—that have been billed by some as “gamechangers.” These new drugs are monoclonal antibodies directed at amyloid, one of several agents thought to cause Alzheimer disease. The details of aducanumab’s approval by the US Food and Drug Administration (FDA) generated a great deal of criticism—with good reason.

Two manufacturer-sponsored studies of aducanumab were halted due to futility of finding a benefit.¹ The FDA’s scientific advisory panel recommended against approval due to a lack of evidence that it did anything more than remove amyloid plaque from the brain. And yet aducanumab received accelerated approval from the FDA. (This author collaborated on an additional analysis using data presented to the FDA, after its approval, which also reported no clinically meaningful effects.²) The other agent, lecanemab, also reduces markers of amyloid and was shown to be only moderately better than placebo in decreasing the rate of decline on various measures of cognition.³ Quite notably, both aducanumab and lecanemab, which are administered parenterally, cost more than $25,000 per year^4,5 and cause amyloid-related imaging abnormalities (brain edema or hemorrhage).

Expensive agents without meaningful benefit. So far, neither of these agents has shown a reduction in things that are truly important to our patients and their families/caregivers: a reduction in caregiver burden and a reduction in the need for placement in long-term care facilities.

This is in contrast to cholinesterase inhibitors, which also slow the rate of cognitive decline.⁶ Among the differences that exist between these agents: Cholinesterase inhibitors are taken orally and are available as generics, which cost less than a thousand dollars per year.⁷ Limited data also suggest that they are associated with a lower risk for nursing home placement.^8,9 (A February 2023 search of clinicaltrials.gov did not reveal any completed or planned head-to-head comparisons of monoclonal antibodies and anticholinergic agents.)

Our patients, their families, and caregivers hold out hope for something that will improve the patient’s cognition and extend the meaningful time they have with their loved ones. So far, the best we have to offer falls far short of these goals. I certainly would have hoped for something better than merely clearing amyloid for my aunt.

It’s time that the FDA adopt more rigorous standards requiring new drugs to, among other things, demonstrate meaningful clinical benefits, provide real cost savings, and be safer than currently available therapies. Other nations seem to be able to do this.^10,11 It is bad enough to provide “hope in a bottle”; it is worse when what is offered is false hope.

Last year, after a long delay due to COVID, my father’s ashes were finally laid to rest at Arlington National Cemetery. Among the loved ones who came was my favorite aunt, Tante Ilse, who was suffering from dementia. While she wasn’t “following” everything that was going on, she did perk up when she heard my father’s name and would comment on how she liked him and how wonderful he had been to her.

After the ceremony, our family of about 30 gathered at a restaurant where we shared stories and old pictures. Tante Ilse seemed to relish the photos and the time with family. She was doing so well that when we went back to my mom’s home after the reception, my cousins decided to bring Tante Ilse there, too. She had a great time, as evidenced by her famous total-body laugh. In the months before her death, we all commented about that day and how happy she seemed.

I would have hoped for something better than merely clearing amyloid for my aunt.

My aunt’s decline comes to mind as I reflect on media reports of 2 Alzheimer drugs— aducanumab and lecanemab—that have been billed by some as “gamechangers.” These new drugs are monoclonal antibodies directed at amyloid, one of several agents thought to cause Alzheimer disease. The details of aducanumab’s approval by the US Food and Drug Administration (FDA) generated a great deal of criticism—with good reason.

Two manufacturer-sponsored studies of aducanumab were halted due to futility of finding a benefit.¹ The FDA’s scientific advisory panel recommended against approval due to a lack of evidence that it did anything more than remove amyloid plaque from the brain. And yet aducanumab received accelerated approval from the FDA. (This author collaborated on an additional analysis using data presented to the FDA, after its approval, which also reported no clinically meaningful effects.²) The other agent, lecanemab, also reduces markers of amyloid and was shown to be only moderately better than placebo in decreasing the rate of decline on various measures of cognition.³ Quite notably, both aducanumab and lecanemab, which are administered parenterally, cost more than $25,000 per year^4,5 and cause amyloid-related imaging abnormalities (brain edema or hemorrhage).

Expensive agents without meaningful benefit. So far, neither of these agents has shown a reduction in things that are truly important to our patients and their families/caregivers: a reduction in caregiver burden and a reduction in the need for placement in long-term care facilities.

This is in contrast to cholinesterase inhibitors, which also slow the rate of cognitive decline.⁶ Among the differences that exist between these agents: Cholinesterase inhibitors are taken orally and are available as generics, which cost less than a thousand dollars per year.⁷ Limited data also suggest that they are associated with a lower risk for nursing home placement.^8,9 (A February 2023 search of clinicaltrials.gov did not reveal any completed or planned head-to-head comparisons of monoclonal antibodies and anticholinergic agents.)

Our patients, their families, and caregivers hold out hope for something that will improve the patient’s cognition and extend the meaningful time they have with their loved ones. So far, the best we have to offer falls far short of these goals. I certainly would have hoped for something better than merely clearing amyloid for my aunt.

It’s time that the FDA adopt more rigorous standards requiring new drugs to, among other things, demonstrate meaningful clinical benefits, provide real cost savings, and be safer than currently available therapies. Other nations seem to be able to do this.^10,11 It is bad enough to provide “hope in a bottle”; it is worse when what is offered is false hope.

In this issue, Mayo and colleagues¹ summarize what we know about patients with long COVID. The report made me pause and realize that it has been 3 years since we heard the very first reports of patients infected with SARS-CoV-2, which would eventually cause the COVID-19 pandemic. I suspect that I am not alone in having been fascinated by the rapid communication of information (of variable quality and veracity) via peer-reviewed papers, pre-print servers, the media, and social media.

The early studies were largely descriptive, focusing on symptom constellations and outbreak data. Much of what we had by way of treatment was supportive and “let’s try anything”—whether reasonable or, in some cases, not. In relatively short order, though, we developed effective vaccines to help protect people from getting seriously ill, being hospitalized, and dying; we also identified targeted therapies for those who became ill.² But variants continued—or rather, continue—to emerge, and we remain committed to meeting the demands of the day.

The Centers for Disease Control and Prevention reports that more than 98 million Americans have contracted COVID, and more than 1 million have died.³ Besides the astonishingly high total mortality, the ravages of COVID-19 include new-onset respiratory, cardiovascular, neurologic, and psychiatric illnesses.^4,5 As many as half of adults hospitalized for COVID report having persistent symptoms.⁶

As described in this issue, what we know about long COVID appears to be following the early course of its parent illness. As was true then, we are learning about the symptoms, etiology, and best ways to manage our patients. As in the early days of the pandemic, treatment is supportive, and we await definitive therapies.

I am optimistic, though. Why? Because shortly after the first reports of ­COVID-19, the virus’ DNA sequence was shared online. Based on that information, diagnostic assays were developed. Within 2 years of the outbreak, we had effective vaccines and specific therapies.

Another call to action. If 5% of patients contracting COVID (a very low estimate) develop long COVID, that would translate to 4.9 million people with long ­COVID in the United States. That is an astounding burden of suffering that I have no doubt will motivate innovation.

Innovation is a strength of the US health care system. I believe we will rise to the next challenge that COVID-19 has put before us. We have reason to be hopeful.

In this issue, Mayo and colleagues¹ summarize what we know about patients with long COVID. The report made me pause and realize that it has been 3 years since we heard the very first reports of patients infected with SARS-CoV-2, which would eventually cause the COVID-19 pandemic. I suspect that I am not alone in having been fascinated by the rapid communication of information (of variable quality and veracity) via peer-reviewed papers, pre-print servers, the media, and social media.

The early studies were largely descriptive, focusing on symptom constellations and outbreak data. Much of what we had by way of treatment was supportive and “let’s try anything”—whether reasonable or, in some cases, not. In relatively short order, though, we developed effective vaccines to help protect people from getting seriously ill, being hospitalized, and dying; we also identified targeted therapies for those who became ill.² But variants continued—or rather, continue—to emerge, and we remain committed to meeting the demands of the day.

The Centers for Disease Control and Prevention reports that more than 98 million Americans have contracted COVID, and more than 1 million have died.³ Besides the astonishingly high total mortality, the ravages of COVID-19 include new-onset respiratory, cardiovascular, neurologic, and psychiatric illnesses.^4,5 As many as half of adults hospitalized for COVID report having persistent symptoms.⁶

As described in this issue, what we know about long COVID appears to be following the early course of its parent illness. As was true then, we are learning about the symptoms, etiology, and best ways to manage our patients. As in the early days of the pandemic, treatment is supportive, and we await definitive therapies.

I am optimistic, though. Why? Because shortly after the first reports of ­COVID-19, the virus’ DNA sequence was shared online. Based on that information, diagnostic assays were developed. Within 2 years of the outbreak, we had effective vaccines and specific therapies.

Another call to action. If 5% of patients contracting COVID (a very low estimate) develop long COVID, that would translate to 4.9 million people with long ­COVID in the United States. That is an astounding burden of suffering that I have no doubt will motivate innovation.

Innovation is a strength of the US health care system. I believe we will rise to the next challenge that COVID-19 has put before us. We have reason to be hopeful.

In this issue, Mayo and colleagues¹ summarize what we know about patients with long COVID. The report made me pause and realize that it has been 3 years since we heard the very first reports of patients infected with SARS-CoV-2, which would eventually cause the COVID-19 pandemic. I suspect that I am not alone in having been fascinated by the rapid communication of information (of variable quality and veracity) via peer-reviewed papers, pre-print servers, the media, and social media.

The early studies were largely descriptive, focusing on symptom constellations and outbreak data. Much of what we had by way of treatment was supportive and “let’s try anything”—whether reasonable or, in some cases, not. In relatively short order, though, we developed effective vaccines to help protect people from getting seriously ill, being hospitalized, and dying; we also identified targeted therapies for those who became ill.² But variants continued—or rather, continue—to emerge, and we remain committed to meeting the demands of the day.

The Centers for Disease Control and Prevention reports that more than 98 million Americans have contracted COVID, and more than 1 million have died.³ Besides the astonishingly high total mortality, the ravages of COVID-19 include new-onset respiratory, cardiovascular, neurologic, and psychiatric illnesses.^4,5 As many as half of adults hospitalized for COVID report having persistent symptoms.⁶

As described in this issue, what we know about long COVID appears to be following the early course of its parent illness. As was true then, we are learning about the symptoms, etiology, and best ways to manage our patients. As in the early days of the pandemic, treatment is supportive, and we await definitive therapies.

I am optimistic, though. Why? Because shortly after the first reports of ­COVID-19, the virus’ DNA sequence was shared online. Based on that information, diagnostic assays were developed. Within 2 years of the outbreak, we had effective vaccines and specific therapies.

Another call to action. If 5% of patients contracting COVID (a very low estimate) develop long COVID, that would translate to 4.9 million people with long ­COVID in the United States. That is an astounding burden of suffering that I have no doubt will motivate innovation.

Innovation is a strength of the US health care system. I believe we will rise to the next challenge that COVID-19 has put before us. We have reason to be hopeful.

Many years ago, I had a patient I’ll call “Hannah,” who was well into her 80s and always came into the office with her daughter. She was a heavy smoker and had hypertension and type 2 diabetes.

At each visit, I would ask her if she still smoked and if she was interested in talking about quitting. At every visit, she would say that she was still smoking and didn’t want to quit. My response was always something along the lines of: “When you’re ready, we can talk more. But I think it is the most important thing you can do to improve your health.” From there, we would discuss any concerns she or her daughter had.

It is our longitudinal relationships with patients that allow us to plant seeds and reap the benefits over time.

A few years shy of her 100th birthday, Hannah told me she had quit smoking. I was amazed and asked her why, after all these years, she’d done it.

“I quit,” she said, “because I was tired of you nagging me, sonny!” And we both had a good laugh about that.

Hannah’s story reminds me that, as family physicians, we often have an impact on our patients in ways we don’t see in the short term. It is our longitudinal relationships with patients that allow us to plant seeds and reap the benefits over time.

It is these relationships that we can draw upon when counseling our patients with type 2 diabetes to address lifestyle issues such as exercise and a healthy diet. In this issue, McMullan et al¹ provide us with a rather hopeful review of the evidence in support of lifestyle changes. For our patients with type 2 diabetes, lifestyle changes can decrease A1C levels by 0.5% (with environmental changes related to diet)² and 0.7% (with moderate aerobic exercise).³ This is comparable to what is reported for the starting doses of most medications.⁴ In fact, a meta-analysis showed that a low-carbohydrate diet induced remission at 6 months in 32% of patients.⁵ (Caveat: The result was not controlled for weight loss as a possible confounding factor and an A1C cutoff of 6.5% was used.)

And yet, we often focus more on the various medications we can prescribe, with professional guidelines pointing the way.

Continue to: The National Institute for Health and Care Excellence

The National Institute for Health and Care Excellence,⁶ American Diabetes Association,⁷ American College of Physicians,⁸ and American Academy of Family Physicians⁸ have followed the accumulating evidence that various medications improve outcomes—especially in patients at high risk or with established atherosclerotic cardiovascular disease. They have endorsed a stepwise pharmacologic approach beginning with metformin and recommend assessing each patient’s comorbidities to guide whether to add a sodium glucose co-transporter 2 (SGLT2) inhibitor or another agent. Where the groups diverge is what that second agent should be (glucagon-like peptide 1 receptor agonist, SGLT2 inhibitor, or dipeptidyl peptidase-4 inhibitor).

But what about lifestyle? Each organization’s guidelines address lifestyle changes as a foundation for managing patients with type 2 diabetes. But is that call loud enough? Do we heed it well enough?

Implementing lifestyle changes in office practice can be time consuming. Many clinicians lack adequate training or experience to gain any traction with it. Also, there is skepticism about success and sustainability.

I believe change starts when we recognize that while we have a priority list for each patient encounter, so do our patients. But they may not share that list with us unless we open the door by asking questions, such as:

• Of all the things you have heard about caring for your diabetes, what would you like to work on?
• What are you currently doing and what prevents you from meeting your goals?
• How would you like me to help you?

From there, we can start small and build on successes over time. We can go the distance with our patients. In the case of Hannah, I had the honor of caring for her until she died at age 104.

Many years ago, I had a patient I’ll call “Hannah,” who was well into her 80s and always came into the office with her daughter. She was a heavy smoker and had hypertension and type 2 diabetes.

At each visit, I would ask her if she still smoked and if she was interested in talking about quitting. At every visit, she would say that she was still smoking and didn’t want to quit. My response was always something along the lines of: “When you’re ready, we can talk more. But I think it is the most important thing you can do to improve your health.” From there, we would discuss any concerns she or her daughter had.

It is our longitudinal relationships with patients that allow us to plant seeds and reap the benefits over time.

A few years shy of her 100th birthday, Hannah told me she had quit smoking. I was amazed and asked her why, after all these years, she’d done it.

“I quit,” she said, “because I was tired of you nagging me, sonny!” And we both had a good laugh about that.

Hannah’s story reminds me that, as family physicians, we often have an impact on our patients in ways we don’t see in the short term. It is our longitudinal relationships with patients that allow us to plant seeds and reap the benefits over time.

It is these relationships that we can draw upon when counseling our patients with type 2 diabetes to address lifestyle issues such as exercise and a healthy diet. In this issue, McMullan et al¹ provide us with a rather hopeful review of the evidence in support of lifestyle changes. For our patients with type 2 diabetes, lifestyle changes can decrease A1C levels by 0.5% (with environmental changes related to diet)² and 0.7% (with moderate aerobic exercise).³ This is comparable to what is reported for the starting doses of most medications.⁴ In fact, a meta-analysis showed that a low-carbohydrate diet induced remission at 6 months in 32% of patients.⁵ (Caveat: The result was not controlled for weight loss as a possible confounding factor and an A1C cutoff of 6.5% was used.)

And yet, we often focus more on the various medications we can prescribe, with professional guidelines pointing the way.

Continue to: The National Institute for Health and Care Excellence

The National Institute for Health and Care Excellence,⁶ American Diabetes Association,⁷ American College of Physicians,⁸ and American Academy of Family Physicians⁸ have followed the accumulating evidence that various medications improve outcomes—especially in patients at high risk or with established atherosclerotic cardiovascular disease. They have endorsed a stepwise pharmacologic approach beginning with metformin and recommend assessing each patient’s comorbidities to guide whether to add a sodium glucose co-transporter 2 (SGLT2) inhibitor or another agent. Where the groups diverge is what that second agent should be (glucagon-like peptide 1 receptor agonist, SGLT2 inhibitor, or dipeptidyl peptidase-4 inhibitor).

But what about lifestyle? Each organization’s guidelines address lifestyle changes as a foundation for managing patients with type 2 diabetes. But is that call loud enough? Do we heed it well enough?

Implementing lifestyle changes in office practice can be time consuming. Many clinicians lack adequate training or experience to gain any traction with it. Also, there is skepticism about success and sustainability.

I believe change starts when we recognize that while we have a priority list for each patient encounter, so do our patients. But they may not share that list with us unless we open the door by asking questions, such as:

• Of all the things you have heard about caring for your diabetes, what would you like to work on?
• What are you currently doing and what prevents you from meeting your goals?
• How would you like me to help you?

From there, we can start small and build on successes over time. We can go the distance with our patients. In the case of Hannah, I had the honor of caring for her until she died at age 104.

Many years ago, I had a patient I’ll call “Hannah,” who was well into her 80s and always came into the office with her daughter. She was a heavy smoker and had hypertension and type 2 diabetes.

At each visit, I would ask her if she still smoked and if she was interested in talking about quitting. At every visit, she would say that she was still smoking and didn’t want to quit. My response was always something along the lines of: “When you’re ready, we can talk more. But I think it is the most important thing you can do to improve your health.” From there, we would discuss any concerns she or her daughter had.

It is our longitudinal relationships with patients that allow us to plant seeds and reap the benefits over time.

A few years shy of her 100th birthday, Hannah told me she had quit smoking. I was amazed and asked her why, after all these years, she’d done it.

“I quit,” she said, “because I was tired of you nagging me, sonny!” And we both had a good laugh about that.

Hannah’s story reminds me that, as family physicians, we often have an impact on our patients in ways we don’t see in the short term. It is our longitudinal relationships with patients that allow us to plant seeds and reap the benefits over time.

It is these relationships that we can draw upon when counseling our patients with type 2 diabetes to address lifestyle issues such as exercise and a healthy diet. In this issue, McMullan et al¹ provide us with a rather hopeful review of the evidence in support of lifestyle changes. For our patients with type 2 diabetes, lifestyle changes can decrease A1C levels by 0.5% (with environmental changes related to diet)² and 0.7% (with moderate aerobic exercise).³ This is comparable to what is reported for the starting doses of most medications.⁴ In fact, a meta-analysis showed that a low-carbohydrate diet induced remission at 6 months in 32% of patients.⁵ (Caveat: The result was not controlled for weight loss as a possible confounding factor and an A1C cutoff of 6.5% was used.)

And yet, we often focus more on the various medications we can prescribe, with professional guidelines pointing the way.

Continue to: The National Institute for Health and Care Excellence

The National Institute for Health and Care Excellence,⁶ American Diabetes Association,⁷ American College of Physicians,⁸ and American Academy of Family Physicians⁸ have followed the accumulating evidence that various medications improve outcomes—especially in patients at high risk or with established atherosclerotic cardiovascular disease. They have endorsed a stepwise pharmacologic approach beginning with metformin and recommend assessing each patient’s comorbidities to guide whether to add a sodium glucose co-transporter 2 (SGLT2) inhibitor or another agent. Where the groups diverge is what that second agent should be (glucagon-like peptide 1 receptor agonist, SGLT2 inhibitor, or dipeptidyl peptidase-4 inhibitor).

But what about lifestyle? Each organization’s guidelines address lifestyle changes as a foundation for managing patients with type 2 diabetes. But is that call loud enough? Do we heed it well enough?

Implementing lifestyle changes in office practice can be time consuming. Many clinicians lack adequate training or experience to gain any traction with it. Also, there is skepticism about success and sustainability.

I believe change starts when we recognize that while we have a priority list for each patient encounter, so do our patients. But they may not share that list with us unless we open the door by asking questions, such as:

• Of all the things you have heard about caring for your diabetes, what would you like to work on?
• What are you currently doing and what prevents you from meeting your goals?
• How would you like me to help you?

From there, we can start small and build on successes over time. We can go the distance with our patients. In the case of Hannah, I had the honor of caring for her until she died at age 104.

The ongoing COVID-19 pandemic has caused more than 1 million deaths in the United States and continues to be a major public health challenge. Cases can be asymptomatic, or symptoms can range from a mild respiratory tract infection to acute respiratory distress and multiorgan failure.

Three strategies can successfully contain the pandemic and its consequences:

• Public health measures, such as masking and social distancing
• Prophylactic vaccines to reduce transmission
• Safe and effective drugs for reducing morbidity and mortality among infected patients.

Optimal treatment strategies for patients in ambulatory and hospital settings continue to evolve as new studies are reported and new strains of the virus arise. Many medical and scientific organizations, including the National Institutes of Health (NIH) COVID-19 treatment panel,¹ Infectious Diseases Society of America (IDSA),² World Health Organization (WHO),³ and Centers for Disease Control and Prevention,⁴ provide recommendations for managing patients with ­COVID-19. Their guidance is based on the strongest research available and is updated intermittently; nevertheless, a plethora of new data emerges weekly and controversies surround several treatments.

In this article, we summarize evidence for the efficacy of treatments for COVID-19. We present data based on the severity of illness, and review special considerations for some patient populations, including pregnant women and children. We focus on practical therapeutic information for primary care providers practicing in a variety of settings, including outpatient and inpatient care.

We encourage clinicians, in planning treatment, to consider:

• The availability of medications (ie, use the COVID-19 Public Therapeutic Locator^a)
• The local COVID-19 situation
• Patient factors and preferences
• Evolving evidence regarding new and existing treatments.

When planning treatment, consider the availability of medications; the local COVID-19 situation; patient factors and preferences; and evolving evidence about treatments.

Most evidence about the treatment of COVID-19 comes from studies conducted when the Omicron variant of SARS-CoV-2 was not the dominant variant, as it is today in the United States. As such, drugs authorized or approved by the US Food and Drug Administration (FDA) to treat COVID-19 or used off-label for that purpose might not be as efficacious today as they were almost a year ago. Furthermore, many trials of potential therapies against new viral variants are ongoing; if your patient is interested in enrolling in a clinical trial of an investigational COVID-19 treatment, refer them to www.clinicaltrials.gov.

General managementof COVID-19

Patients with COVID-19 experience a range of illness severity—from asymptomatic to mild symptoms, such as fever and myalgia, to critical illness requiring intensive care (TABLE 1^1,2). Patients with COVID-19 should therefore be monitored for progression, remotely or in person, until full recovery is achieved. Key concepts of general management include:

Assess and monitor patients’ oxygenation status by pulse oximetry; identify those with low or declining oxygen saturation before further clinical deterioration.

Continue to: Consider the patient's age and general health

Consider the patient’s age and general health. Patients are at higher risk of severe disease if they are > 65 years or have an underlying comorbidity.⁴

Emphasize self-isolation and supportive care, including rest, hydration, and over-the-counter medications to relieve cough, reduce fever, and alleviate other symptoms.

Drugs: Few approved, some under study

The antiviral remdesivir is the only drug fully approved for clinical use by the FDA to treat COVID-19 in patients > 12 years.^5,6

In addition, the FDA has issued an emergency use authorization (EUA) for several monoclonal antibodies as prophylaxis and treatment: tixagevimab packaged with cilgavimab (Evusheld) is the first antibody combination for pre-exposure prophylaxis (PrEP) against COVID-19; the separately packaged injectables are recommended for patients who have a history of severe allergy that prevents them from being vaccinated or those with moderate or severe immune-compromising disorders.⁷

In the pipeline. Several treatments are being tested in clinical trials to evaluate their effectiveness and safety in combating COVID-19, including:

• Antivirals, which prevent viruses from multiplying
• Immunomodulators, which reduce the body’s immune reaction to the virus
• Antibody therapies, which are manufactured antibodies against the virus
• Anti-inflammatory drugs, which reduce systemic inflammation and prevent organ dysfunction
• Cell therapies and gene therapies, which alter the expression of cells and genes.

Continue to: Outpatient treatment

Several assessment tools that take into account patients’ age, respiratory status, and comorbidities are available for triage of patients infected with COVID-19.⁸

Most (> 80%) patients with COVID-19 have mild infection and are safely managed as outpatients or at home.^9,10 For patients at high risk of severe disease, a few options are recommended for patients who do not require hospitalization or supplemental oxygen; guidelines on treatment of COVID-19 in outpatient settings that have been developed by various organizations are summarized in TABLE 2.^7,11-25

Antiviral drugs target different stages of the SARS-CoV-2 replication cycle. They should be used early in the course of infection, particularly in patients at high risk of severe disease.

IDSA recommends antiviral therapy with molnupiravir, nirmatrelvir + ritonavir packaged together (Paxlovid), or remdesivir.^11,12,26,27 Remdesivir requires intravenous (IV) infusion on 3 consecutive days, which can be difficult in some clinic settings.^13,28 Nirmatrelvir + ritonavir should be initiated within 5 days after symptom onset. Overall, for most patients, nirmatrelvir + ritonavir is preferred because of oral dosing and higher efficacy in comparison to other antivirals. With nirmatrelvir + ritonavir, carefully consider drug–drug interactions and the need to adjust dosing in the presence of renal disease.^28,29 There are no data on the efficacy of any combination treatments with these agents (other than co-packaged Paxlovid).

Monoclonal antibodies for COVID-19 are given primarily intravenously. They bind to the viral spike protein, thus preventing SARS-CoV-2 from attaching to and entering cells. Bamlanivimab + etesevimab and bebtelovimab are available under an EUA for outpatient treatment.^14b Treatment should be initiated as early as possible in the course of infection—ideally, within 7 to 10 days after onset of symptoms.

Continue to: Bebtelovimab was recently given...

Bebtelovimab was recently given an EUA. It is a next-generation antibody that neutralizes all currently known variants and is the most potent monoclonal antibody against the Omicron variant, including its BA.2 subvariant.³¹ However, data about its activity against the BA.2 subvariant are based on laboratory testing and have not been confirmed in clinical trials. Clinical data were similar for this agent alone and for its use in combination with other monoclonal antibodies, but those trials were conducted before the emergence of Omicron.

In your decision-making about the most appropriate therapy, consider (1) the requirement that monoclonal antibodies be administered parenterally and (2) the susceptibility of the locally predominating viral variant.

Other monoclonal antibody agents are in the investigative pipeline; however, data about them have been largely presented through press releases or selectively reported in applications to the FDA for EUA. For example, preliminary reports show cilgavimab coverage against the Omicron variant¹⁴; so far, cilgavimab is not approved for treatment but is used in combination with tixagevimab for PreP—reportedly providing as long as 12 months of protection for patients who are less likely to respond to a vaccine.³²

Corticosteroids. Guidelines recommend against dexamethasone and other systemic corticosteroids in outpatient settings. For patients with moderate-to-severe symptoms but for whom hospitalization is not possible (eg, beds are unavailable), the NIH panel recommends dexamethasone, 6 mg/d, for the duration of supplemental oxygen, not to exceed 10 days of treatment.¹

Patients who were recently discharged after COVID-19 hospitalization should not continue remdesivir, dexamethasone, or baricitinib at home, even if they still require supplemental oxygen.

Continue to: Some treatments should not be in your COVID-19 toolbox

Some treatments should not be in your COVID-19 toolbox

High-quality studies are lacking for several other potential COVID-19 treatments. Some of these drugs are under investigation, with unclear benefit and with the potential risk of toxicity—and therefore should not be prescribed or used outside a clinical trial. See “Treatments not recommended for COVID-19,” page E14. ^{1-4,15-19,33-41}

Treatment during hospitalization

The NIH COVID-19 treatment panel recommends hospitalization for patients who have any of the following findings¹:

• Oxygen saturation < 94% while breathing room air
• Respiratory rate > 30 breaths/min
• A ratio of partial pressure of arterial O₂ to fraction of inspired O₂ (PaO₂/FiO₂) < 300 mm Hg
• Lung infiltrates > 50%.

General guidance for the care of hospitalized patients:

• Treatments that target the virus have the greatest efficacy when given early in the course of disease.
• Anti-inflammatory and immunosuppressive agents help prevent tissue damage from a dysregulated immune system. (See TABLE 3^26,42-46)
• The NIH panel,¹ IDSA,² and WHO³ recommend against dexamethasone and other corticosteroids for hospitalized patients who do not require supplemental oxygen.
• Prone positioning distributes oxygen more evenly in the lungs and improves overall oxygenation, thus reducing the need for mechanical ventilation.

Remdesivir. Once a hospitalized patient does require supplemental oxygen, the NIH panel,¹ IDSA,² and WHO³ recommend remdesivir; however, remdesivir is not recommended in many other countries because WHO has noted its limited efficacy.⁴² Dexamethasone is recommended alone, or in combination with remdesivir for patients who require increasing supplemental oxygen and those on mechanical ventilation.

Baricitinib. For patients with rapidly increasing oxygen requirements, invasive mechanical ventilation, and systemic inflammation, baricitinib, a Janus kinase inhibitor, can be administered, in addition to dexamethasone, with or without remdesivir.⁴⁷

Continue to: Tocilizumab

Tocilizumab. A monoclonal antibody and interleukin (IL)-6 inhibitor, tocilizumab is also recommended in addition to dexamethasone, with or without remdesivir.⁴⁸ Tocilizumab should be given only in combination with dexamethasone.⁴⁹ Patients should receive baricitinib or tocilizumab—not both. IDSA recommends tofacitinib, with a prophylactic dose of an anticoagulant, for patients who are hospitalized with severe COVID-19 but who are not on any form of ventilation.⁵⁰

Care of special populations

Special patient populations often seek primary care. Although many questions remain regarding the appropriate care of these populations, it is useful to summarize existing evidence and recommendations from current guidelines. 

Children. COVID-19 is generally milder in children than in adults; many infected children are asymptomatic. However, infants and children who have an underlying medical condition are at risk of severe disease, including multisystem inflammatory syndrome.⁵¹

Because patients with COVID-19 experience a range of illness severity, they should be monitored for progression, remotely or in person, until fully recovered.

The NIH panel recommends supportive care alone for most children with mild-to-moderate disease.¹ Remdesivir is recommended for hospitalized children ≥ 12 years who weigh ≥ 40 kg, have risk factors for severe disease, and have an emergent or increasing need for supplemental oxygen. Dexamethasone is recommended for hospitalized children requiring high-flow oxygen, noninvasive ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation. Molnupiravir is not authorized for patients < 18 years because it can impede bone and cartilage growth.

There is insufficient evidence for or against the use of monoclonal antibody products for children with COVID-19 in an ambulatory setting. For hospitalized children, there is insufficient evidence for or against use of baricitinib and tocilizumab. 

Continue to: Patients who are pregnant

Patients who are pregnant are at increased risk of severe COVID-19.^52,53 The NIH states that, in general, treatment and vaccination of pregnant patients with COVID-19 should be the same as for nonpregnant patients.¹

Pregnant subjects were excluded from several trials of COVID-19 treatments.⁵⁴ Because Janus kinase inhibitors, such as baricitinib, are associated with an increased risk of thromboembolism, they are not recommended in pregnant patients who are already at risk of thromboembolic complications. Molnupiravir is not recommended for pregnant patients because of its potential for teratogenic effects.

The Society for Maternal-Fetal Medicine states that there are no absolute contraindications to the use of monoclonal antibodies in appropriate pregnant patients with COVID-19.⁵⁵ Remdesivir has no known fetal toxicity and is recommended as a treatment that can be offered to pregnant patients. Dexamethasone can also be administered to pregnant patients who require oxygen; however, if dexamethasone is also being used to accelerate fetal lung maturity, more frequent initial dosing is needed.

Older people. COVID-19 treatments for older patients are the same as for the general adult population. However, because older people are more likely to have impaired renal function, renal function should be monitored when an older patient is being treated with COVID-19 medications that are eliminated renally (eg, remdesivir, baricitinib). Furthermore, drug–drug interactions have been reported in older patients treated with nirmatrelvir + ritonavir, primarily because of the effects of ritonavir. Review all of a patient’s medications, including over-the-counter drugs and herbal supplements, when prescribing treatment for COVID-19, and adjust the dosage by following guidance in FDA-approved prescribing information—ideally, in consultation with a pharmacist.

Immunocompromised patients. The combination product tixagevimab + cilgavimab [Evusheld] is FDA approved for COVID-19 PrEP, under an EUA, in patients who are not infected with SARS-CoV-2 who have an immune-compromising condition, who are unlikely to mount an adequate immune response to the COVID-19 vaccine, or those in whom vaccination is not recommended because of their history of a severe adverse reaction to a COVID-19 vaccine or one of its components.⁷

Continue to: Summing up

Summing up

With a growing need for effective and readily available COVID-19 treatments, there are an unprecedented number of clinical trials in process. Besides antivirals, immunomodulators, and antibody therapies, some novel mechanisms being tested include Janus kinase inhibitors, IL-6-receptor blockers, and drugs that target adult respiratory distress syndrome and cytokine release.

Guidelines recommend against using dexamethasone and other systemic corticosteroids in COVID-19 outpatient settings.

Once larger trials are completed, we can expect stronger evidence of potential treatment options and of safety and efficacy in children, pregnant women, and vulnerable populations. During the pandemic, the FDA’s EUA program has brought emerging treatments rapidly to clinicians; nevertheless, high-quality evidence, with thorough peer review, remains critical to inform COVID-19 treatment guidelines.

^ahttps://healthdata.gov/Health/COVID-19-PublicTherapeutic-Locator/rxn6-qnx8/data

^b Sotrovimab was effective against the Omicron variant of SARS-CoV-2—the dominant variant in early 2022— but is currently not FDA authorized in any region of the United States because of the prevalence of the Omicron BA.2 subvariant.30

CORRESPONDENCE
Ambar Kulshreshtha, MD, PhD, Department of Epidemiology, Emory Rollins School of Public Health, 4500 North Shallowford Road, Suite 134, Atlanta, GA 30338; [email protected]

The ongoing COVID-19 pandemic has caused more than 1 million deaths in the United States and continues to be a major public health challenge. Cases can be asymptomatic, or symptoms can range from a mild respiratory tract infection to acute respiratory distress and multiorgan failure.

Three strategies can successfully contain the pandemic and its consequences:

• Public health measures, such as masking and social distancing
• Prophylactic vaccines to reduce transmission
• Safe and effective drugs for reducing morbidity and mortality among infected patients.

Optimal treatment strategies for patients in ambulatory and hospital settings continue to evolve as new studies are reported and new strains of the virus arise. Many medical and scientific organizations, including the National Institutes of Health (NIH) COVID-19 treatment panel,¹ Infectious Diseases Society of America (IDSA),² World Health Organization (WHO),³ and Centers for Disease Control and Prevention,⁴ provide recommendations for managing patients with ­COVID-19. Their guidance is based on the strongest research available and is updated intermittently; nevertheless, a plethora of new data emerges weekly and controversies surround several treatments.

In this article, we summarize evidence for the efficacy of treatments for COVID-19. We present data based on the severity of illness, and review special considerations for some patient populations, including pregnant women and children. We focus on practical therapeutic information for primary care providers practicing in a variety of settings, including outpatient and inpatient care.

We encourage clinicians, in planning treatment, to consider:

• The availability of medications (ie, use the COVID-19 Public Therapeutic Locator^a)
• The local COVID-19 situation
• Patient factors and preferences
• Evolving evidence regarding new and existing treatments.

When planning treatment, consider the availability of medications; the local COVID-19 situation; patient factors and preferences; and evolving evidence about treatments.

Most evidence about the treatment of COVID-19 comes from studies conducted when the Omicron variant of SARS-CoV-2 was not the dominant variant, as it is today in the United States. As such, drugs authorized or approved by the US Food and Drug Administration (FDA) to treat COVID-19 or used off-label for that purpose might not be as efficacious today as they were almost a year ago. Furthermore, many trials of potential therapies against new viral variants are ongoing; if your patient is interested in enrolling in a clinical trial of an investigational COVID-19 treatment, refer them to www.clinicaltrials.gov.

General managementof COVID-19

Patients with COVID-19 experience a range of illness severity—from asymptomatic to mild symptoms, such as fever and myalgia, to critical illness requiring intensive care (TABLE 1^1,2). Patients with COVID-19 should therefore be monitored for progression, remotely or in person, until full recovery is achieved. Key concepts of general management include:

Assess and monitor patients’ oxygenation status by pulse oximetry; identify those with low or declining oxygen saturation before further clinical deterioration.

Continue to: Consider the patient's age and general health

Consider the patient’s age and general health. Patients are at higher risk of severe disease if they are > 65 years or have an underlying comorbidity.⁴

Emphasize self-isolation and supportive care, including rest, hydration, and over-the-counter medications to relieve cough, reduce fever, and alleviate other symptoms.

Drugs: Few approved, some under study

The antiviral remdesivir is the only drug fully approved for clinical use by the FDA to treat COVID-19 in patients > 12 years.^5,6

In addition, the FDA has issued an emergency use authorization (EUA) for several monoclonal antibodies as prophylaxis and treatment: tixagevimab packaged with cilgavimab (Evusheld) is the first antibody combination for pre-exposure prophylaxis (PrEP) against COVID-19; the separately packaged injectables are recommended for patients who have a history of severe allergy that prevents them from being vaccinated or those with moderate or severe immune-compromising disorders.⁷

In the pipeline. Several treatments are being tested in clinical trials to evaluate their effectiveness and safety in combating COVID-19, including:

• Antivirals, which prevent viruses from multiplying
• Immunomodulators, which reduce the body’s immune reaction to the virus
• Antibody therapies, which are manufactured antibodies against the virus
• Anti-inflammatory drugs, which reduce systemic inflammation and prevent organ dysfunction
• Cell therapies and gene therapies, which alter the expression of cells and genes.

Continue to: Outpatient treatment

Several assessment tools that take into account patients’ age, respiratory status, and comorbidities are available for triage of patients infected with COVID-19.⁸

Most (> 80%) patients with COVID-19 have mild infection and are safely managed as outpatients or at home.^9,10 For patients at high risk of severe disease, a few options are recommended for patients who do not require hospitalization or supplemental oxygen; guidelines on treatment of COVID-19 in outpatient settings that have been developed by various organizations are summarized in TABLE 2.^7,11-25

Antiviral drugs target different stages of the SARS-CoV-2 replication cycle. They should be used early in the course of infection, particularly in patients at high risk of severe disease.

IDSA recommends antiviral therapy with molnupiravir, nirmatrelvir + ritonavir packaged together (Paxlovid), or remdesivir.^11,12,26,27 Remdesivir requires intravenous (IV) infusion on 3 consecutive days, which can be difficult in some clinic settings.^13,28 Nirmatrelvir + ritonavir should be initiated within 5 days after symptom onset. Overall, for most patients, nirmatrelvir + ritonavir is preferred because of oral dosing and higher efficacy in comparison to other antivirals. With nirmatrelvir + ritonavir, carefully consider drug–drug interactions and the need to adjust dosing in the presence of renal disease.^28,29 There are no data on the efficacy of any combination treatments with these agents (other than co-packaged Paxlovid).

Monoclonal antibodies for COVID-19 are given primarily intravenously. They bind to the viral spike protein, thus preventing SARS-CoV-2 from attaching to and entering cells. Bamlanivimab + etesevimab and bebtelovimab are available under an EUA for outpatient treatment.^14b Treatment should be initiated as early as possible in the course of infection—ideally, within 7 to 10 days after onset of symptoms.

Continue to: Bebtelovimab was recently given...

Bebtelovimab was recently given an EUA. It is a next-generation antibody that neutralizes all currently known variants and is the most potent monoclonal antibody against the Omicron variant, including its BA.2 subvariant.³¹ However, data about its activity against the BA.2 subvariant are based on laboratory testing and have not been confirmed in clinical trials. Clinical data were similar for this agent alone and for its use in combination with other monoclonal antibodies, but those trials were conducted before the emergence of Omicron.

In your decision-making about the most appropriate therapy, consider (1) the requirement that monoclonal antibodies be administered parenterally and (2) the susceptibility of the locally predominating viral variant.

Other monoclonal antibody agents are in the investigative pipeline; however, data about them have been largely presented through press releases or selectively reported in applications to the FDA for EUA. For example, preliminary reports show cilgavimab coverage against the Omicron variant¹⁴; so far, cilgavimab is not approved for treatment but is used in combination with tixagevimab for PreP—reportedly providing as long as 12 months of protection for patients who are less likely to respond to a vaccine.³²

Corticosteroids. Guidelines recommend against dexamethasone and other systemic corticosteroids in outpatient settings. For patients with moderate-to-severe symptoms but for whom hospitalization is not possible (eg, beds are unavailable), the NIH panel recommends dexamethasone, 6 mg/d, for the duration of supplemental oxygen, not to exceed 10 days of treatment.¹

Patients who were recently discharged after COVID-19 hospitalization should not continue remdesivir, dexamethasone, or baricitinib at home, even if they still require supplemental oxygen.

Continue to: Some treatments should not be in your COVID-19 toolbox

Some treatments should not be in your COVID-19 toolbox

High-quality studies are lacking for several other potential COVID-19 treatments. Some of these drugs are under investigation, with unclear benefit and with the potential risk of toxicity—and therefore should not be prescribed or used outside a clinical trial. See “Treatments not recommended for COVID-19,” page E14. ^{1-4,15-19,33-41}

Treatment during hospitalization

The NIH COVID-19 treatment panel recommends hospitalization for patients who have any of the following findings¹:

• Oxygen saturation < 94% while breathing room air
• Respiratory rate > 30 breaths/min
• A ratio of partial pressure of arterial O₂ to fraction of inspired O₂ (PaO₂/FiO₂) < 300 mm Hg
• Lung infiltrates > 50%.

General guidance for the care of hospitalized patients:

• Treatments that target the virus have the greatest efficacy when given early in the course of disease.
• Anti-inflammatory and immunosuppressive agents help prevent tissue damage from a dysregulated immune system. (See TABLE 3^26,42-46)
• The NIH panel,¹ IDSA,² and WHO³ recommend against dexamethasone and other corticosteroids for hospitalized patients who do not require supplemental oxygen.
• Prone positioning distributes oxygen more evenly in the lungs and improves overall oxygenation, thus reducing the need for mechanical ventilation.

Remdesivir. Once a hospitalized patient does require supplemental oxygen, the NIH panel,¹ IDSA,² and WHO³ recommend remdesivir; however, remdesivir is not recommended in many other countries because WHO has noted its limited efficacy.⁴² Dexamethasone is recommended alone, or in combination with remdesivir for patients who require increasing supplemental oxygen and those on mechanical ventilation.

Baricitinib. For patients with rapidly increasing oxygen requirements, invasive mechanical ventilation, and systemic inflammation, baricitinib, a Janus kinase inhibitor, can be administered, in addition to dexamethasone, with or without remdesivir.⁴⁷

Continue to: Tocilizumab

Tocilizumab. A monoclonal antibody and interleukin (IL)-6 inhibitor, tocilizumab is also recommended in addition to dexamethasone, with or without remdesivir.⁴⁸ Tocilizumab should be given only in combination with dexamethasone.⁴⁹ Patients should receive baricitinib or tocilizumab—not both. IDSA recommends tofacitinib, with a prophylactic dose of an anticoagulant, for patients who are hospitalized with severe COVID-19 but who are not on any form of ventilation.⁵⁰

Care of special populations

Special patient populations often seek primary care. Although many questions remain regarding the appropriate care of these populations, it is useful to summarize existing evidence and recommendations from current guidelines. 

Children. COVID-19 is generally milder in children than in adults; many infected children are asymptomatic. However, infants and children who have an underlying medical condition are at risk of severe disease, including multisystem inflammatory syndrome.⁵¹

Because patients with COVID-19 experience a range of illness severity, they should be monitored for progression, remotely or in person, until fully recovered.

The NIH panel recommends supportive care alone for most children with mild-to-moderate disease.¹ Remdesivir is recommended for hospitalized children ≥ 12 years who weigh ≥ 40 kg, have risk factors for severe disease, and have an emergent or increasing need for supplemental oxygen. Dexamethasone is recommended for hospitalized children requiring high-flow oxygen, noninvasive ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation. Molnupiravir is not authorized for patients < 18 years because it can impede bone and cartilage growth.

There is insufficient evidence for or against the use of monoclonal antibody products for children with COVID-19 in an ambulatory setting. For hospitalized children, there is insufficient evidence for or against use of baricitinib and tocilizumab. 

Continue to: Patients who are pregnant

Patients who are pregnant are at increased risk of severe COVID-19.^52,53 The NIH states that, in general, treatment and vaccination of pregnant patients with COVID-19 should be the same as for nonpregnant patients.¹

Pregnant subjects were excluded from several trials of COVID-19 treatments.⁵⁴ Because Janus kinase inhibitors, such as baricitinib, are associated with an increased risk of thromboembolism, they are not recommended in pregnant patients who are already at risk of thromboembolic complications. Molnupiravir is not recommended for pregnant patients because of its potential for teratogenic effects.

The Society for Maternal-Fetal Medicine states that there are no absolute contraindications to the use of monoclonal antibodies in appropriate pregnant patients with COVID-19.⁵⁵ Remdesivir has no known fetal toxicity and is recommended as a treatment that can be offered to pregnant patients. Dexamethasone can also be administered to pregnant patients who require oxygen; however, if dexamethasone is also being used to accelerate fetal lung maturity, more frequent initial dosing is needed.

Older people. COVID-19 treatments for older patients are the same as for the general adult population. However, because older people are more likely to have impaired renal function, renal function should be monitored when an older patient is being treated with COVID-19 medications that are eliminated renally (eg, remdesivir, baricitinib). Furthermore, drug–drug interactions have been reported in older patients treated with nirmatrelvir + ritonavir, primarily because of the effects of ritonavir. Review all of a patient’s medications, including over-the-counter drugs and herbal supplements, when prescribing treatment for COVID-19, and adjust the dosage by following guidance in FDA-approved prescribing information—ideally, in consultation with a pharmacist.

Immunocompromised patients. The combination product tixagevimab + cilgavimab [Evusheld] is FDA approved for COVID-19 PrEP, under an EUA, in patients who are not infected with SARS-CoV-2 who have an immune-compromising condition, who are unlikely to mount an adequate immune response to the COVID-19 vaccine, or those in whom vaccination is not recommended because of their history of a severe adverse reaction to a COVID-19 vaccine or one of its components.⁷

Continue to: Summing up

Summing up

With a growing need for effective and readily available COVID-19 treatments, there are an unprecedented number of clinical trials in process. Besides antivirals, immunomodulators, and antibody therapies, some novel mechanisms being tested include Janus kinase inhibitors, IL-6-receptor blockers, and drugs that target adult respiratory distress syndrome and cytokine release.

Guidelines recommend against using dexamethasone and other systemic corticosteroids in COVID-19 outpatient settings.

Once larger trials are completed, we can expect stronger evidence of potential treatment options and of safety and efficacy in children, pregnant women, and vulnerable populations. During the pandemic, the FDA’s EUA program has brought emerging treatments rapidly to clinicians; nevertheless, high-quality evidence, with thorough peer review, remains critical to inform COVID-19 treatment guidelines.

^ahttps://healthdata.gov/Health/COVID-19-PublicTherapeutic-Locator/rxn6-qnx8/data

^b Sotrovimab was effective against the Omicron variant of SARS-CoV-2—the dominant variant in early 2022— but is currently not FDA authorized in any region of the United States because of the prevalence of the Omicron BA.2 subvariant.30

CORRESPONDENCE
Ambar Kulshreshtha, MD, PhD, Department of Epidemiology, Emory Rollins School of Public Health, 4500 North Shallowford Road, Suite 134, Atlanta, GA 30338; [email protected]

The ongoing COVID-19 pandemic has caused more than 1 million deaths in the United States and continues to be a major public health challenge. Cases can be asymptomatic, or symptoms can range from a mild respiratory tract infection to acute respiratory distress and multiorgan failure.

Three strategies can successfully contain the pandemic and its consequences:

• Public health measures, such as masking and social distancing
• Prophylactic vaccines to reduce transmission
• Safe and effective drugs for reducing morbidity and mortality among infected patients.

Optimal treatment strategies for patients in ambulatory and hospital settings continue to evolve as new studies are reported and new strains of the virus arise. Many medical and scientific organizations, including the National Institutes of Health (NIH) COVID-19 treatment panel,¹ Infectious Diseases Society of America (IDSA),² World Health Organization (WHO),³ and Centers for Disease Control and Prevention,⁴ provide recommendations for managing patients with ­COVID-19. Their guidance is based on the strongest research available and is updated intermittently; nevertheless, a plethora of new data emerges weekly and controversies surround several treatments.

In this article, we summarize evidence for the efficacy of treatments for COVID-19. We present data based on the severity of illness, and review special considerations for some patient populations, including pregnant women and children. We focus on practical therapeutic information for primary care providers practicing in a variety of settings, including outpatient and inpatient care.

We encourage clinicians, in planning treatment, to consider:

• The availability of medications (ie, use the COVID-19 Public Therapeutic Locator^a)
• The local COVID-19 situation
• Patient factors and preferences
• Evolving evidence regarding new and existing treatments.

When planning treatment, consider the availability of medications; the local COVID-19 situation; patient factors and preferences; and evolving evidence about treatments.

Most evidence about the treatment of COVID-19 comes from studies conducted when the Omicron variant of SARS-CoV-2 was not the dominant variant, as it is today in the United States. As such, drugs authorized or approved by the US Food and Drug Administration (FDA) to treat COVID-19 or used off-label for that purpose might not be as efficacious today as they were almost a year ago. Furthermore, many trials of potential therapies against new viral variants are ongoing; if your patient is interested in enrolling in a clinical trial of an investigational COVID-19 treatment, refer them to www.clinicaltrials.gov.

General managementof COVID-19

Patients with COVID-19 experience a range of illness severity—from asymptomatic to mild symptoms, such as fever and myalgia, to critical illness requiring intensive care (TABLE 1^1,2). Patients with COVID-19 should therefore be monitored for progression, remotely or in person, until full recovery is achieved. Key concepts of general management include:

Assess and monitor patients’ oxygenation status by pulse oximetry; identify those with low or declining oxygen saturation before further clinical deterioration.

Continue to: Consider the patient's age and general health

Consider the patient’s age and general health. Patients are at higher risk of severe disease if they are > 65 years or have an underlying comorbidity.⁴

Emphasize self-isolation and supportive care, including rest, hydration, and over-the-counter medications to relieve cough, reduce fever, and alleviate other symptoms.

Drugs: Few approved, some under study

The antiviral remdesivir is the only drug fully approved for clinical use by the FDA to treat COVID-19 in patients > 12 years.^5,6

In addition, the FDA has issued an emergency use authorization (EUA) for several monoclonal antibodies as prophylaxis and treatment: tixagevimab packaged with cilgavimab (Evusheld) is the first antibody combination for pre-exposure prophylaxis (PrEP) against COVID-19; the separately packaged injectables are recommended for patients who have a history of severe allergy that prevents them from being vaccinated or those with moderate or severe immune-compromising disorders.⁷

In the pipeline. Several treatments are being tested in clinical trials to evaluate their effectiveness and safety in combating COVID-19, including:

• Antivirals, which prevent viruses from multiplying
• Immunomodulators, which reduce the body’s immune reaction to the virus
• Antibody therapies, which are manufactured antibodies against the virus
• Anti-inflammatory drugs, which reduce systemic inflammation and prevent organ dysfunction
• Cell therapies and gene therapies, which alter the expression of cells and genes.

Continue to: Outpatient treatment

Several assessment tools that take into account patients’ age, respiratory status, and comorbidities are available for triage of patients infected with COVID-19.⁸

Most (> 80%) patients with COVID-19 have mild infection and are safely managed as outpatients or at home.^9,10 For patients at high risk of severe disease, a few options are recommended for patients who do not require hospitalization or supplemental oxygen; guidelines on treatment of COVID-19 in outpatient settings that have been developed by various organizations are summarized in TABLE 2.^7,11-25

Antiviral drugs target different stages of the SARS-CoV-2 replication cycle. They should be used early in the course of infection, particularly in patients at high risk of severe disease.

IDSA recommends antiviral therapy with molnupiravir, nirmatrelvir + ritonavir packaged together (Paxlovid), or remdesivir.^11,12,26,27 Remdesivir requires intravenous (IV) infusion on 3 consecutive days, which can be difficult in some clinic settings.^13,28 Nirmatrelvir + ritonavir should be initiated within 5 days after symptom onset. Overall, for most patients, nirmatrelvir + ritonavir is preferred because of oral dosing and higher efficacy in comparison to other antivirals. With nirmatrelvir + ritonavir, carefully consider drug–drug interactions and the need to adjust dosing in the presence of renal disease.^28,29 There are no data on the efficacy of any combination treatments with these agents (other than co-packaged Paxlovid).

Monoclonal antibodies for COVID-19 are given primarily intravenously. They bind to the viral spike protein, thus preventing SARS-CoV-2 from attaching to and entering cells. Bamlanivimab + etesevimab and bebtelovimab are available under an EUA for outpatient treatment.^14b Treatment should be initiated as early as possible in the course of infection—ideally, within 7 to 10 days after onset of symptoms.

Continue to: Bebtelovimab was recently given...

Bebtelovimab was recently given an EUA. It is a next-generation antibody that neutralizes all currently known variants and is the most potent monoclonal antibody against the Omicron variant, including its BA.2 subvariant.³¹ However, data about its activity against the BA.2 subvariant are based on laboratory testing and have not been confirmed in clinical trials. Clinical data were similar for this agent alone and for its use in combination with other monoclonal antibodies, but those trials were conducted before the emergence of Omicron.

In your decision-making about the most appropriate therapy, consider (1) the requirement that monoclonal antibodies be administered parenterally and (2) the susceptibility of the locally predominating viral variant.

Other monoclonal antibody agents are in the investigative pipeline; however, data about them have been largely presented through press releases or selectively reported in applications to the FDA for EUA. For example, preliminary reports show cilgavimab coverage against the Omicron variant¹⁴; so far, cilgavimab is not approved for treatment but is used in combination with tixagevimab for PreP—reportedly providing as long as 12 months of protection for patients who are less likely to respond to a vaccine.³²

Corticosteroids. Guidelines recommend against dexamethasone and other systemic corticosteroids in outpatient settings. For patients with moderate-to-severe symptoms but for whom hospitalization is not possible (eg, beds are unavailable), the NIH panel recommends dexamethasone, 6 mg/d, for the duration of supplemental oxygen, not to exceed 10 days of treatment.¹

Patients who were recently discharged after COVID-19 hospitalization should not continue remdesivir, dexamethasone, or baricitinib at home, even if they still require supplemental oxygen.

Continue to: Some treatments should not be in your COVID-19 toolbox

Some treatments should not be in your COVID-19 toolbox

High-quality studies are lacking for several other potential COVID-19 treatments. Some of these drugs are under investigation, with unclear benefit and with the potential risk of toxicity—and therefore should not be prescribed or used outside a clinical trial. See “Treatments not recommended for COVID-19,” page E14. ^{1-4,15-19,33-41}

Treatment during hospitalization

The NIH COVID-19 treatment panel recommends hospitalization for patients who have any of the following findings¹:

• Oxygen saturation < 94% while breathing room air
• Respiratory rate > 30 breaths/min
• A ratio of partial pressure of arterial O₂ to fraction of inspired O₂ (PaO₂/FiO₂) < 300 mm Hg
• Lung infiltrates > 50%.

General guidance for the care of hospitalized patients:

• Treatments that target the virus have the greatest efficacy when given early in the course of disease.
• Anti-inflammatory and immunosuppressive agents help prevent tissue damage from a dysregulated immune system. (See TABLE 3^26,42-46)
• The NIH panel,¹ IDSA,² and WHO³ recommend against dexamethasone and other corticosteroids for hospitalized patients who do not require supplemental oxygen.
• Prone positioning distributes oxygen more evenly in the lungs and improves overall oxygenation, thus reducing the need for mechanical ventilation.

Remdesivir. Once a hospitalized patient does require supplemental oxygen, the NIH panel,¹ IDSA,² and WHO³ recommend remdesivir; however, remdesivir is not recommended in many other countries because WHO has noted its limited efficacy.⁴² Dexamethasone is recommended alone, or in combination with remdesivir for patients who require increasing supplemental oxygen and those on mechanical ventilation.

Baricitinib. For patients with rapidly increasing oxygen requirements, invasive mechanical ventilation, and systemic inflammation, baricitinib, a Janus kinase inhibitor, can be administered, in addition to dexamethasone, with or without remdesivir.⁴⁷

Continue to: Tocilizumab

Tocilizumab. A monoclonal antibody and interleukin (IL)-6 inhibitor, tocilizumab is also recommended in addition to dexamethasone, with or without remdesivir.⁴⁸ Tocilizumab should be given only in combination with dexamethasone.⁴⁹ Patients should receive baricitinib or tocilizumab—not both. IDSA recommends tofacitinib, with a prophylactic dose of an anticoagulant, for patients who are hospitalized with severe COVID-19 but who are not on any form of ventilation.⁵⁰

Care of special populations

Special patient populations often seek primary care. Although many questions remain regarding the appropriate care of these populations, it is useful to summarize existing evidence and recommendations from current guidelines. 

Children. COVID-19 is generally milder in children than in adults; many infected children are asymptomatic. However, infants and children who have an underlying medical condition are at risk of severe disease, including multisystem inflammatory syndrome.⁵¹

Because patients with COVID-19 experience a range of illness severity, they should be monitored for progression, remotely or in person, until fully recovered.

The NIH panel recommends supportive care alone for most children with mild-to-moderate disease.¹ Remdesivir is recommended for hospitalized children ≥ 12 years who weigh ≥ 40 kg, have risk factors for severe disease, and have an emergent or increasing need for supplemental oxygen. Dexamethasone is recommended for hospitalized children requiring high-flow oxygen, noninvasive ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation. Molnupiravir is not authorized for patients < 18 years because it can impede bone and cartilage growth.

There is insufficient evidence for or against the use of monoclonal antibody products for children with COVID-19 in an ambulatory setting. For hospitalized children, there is insufficient evidence for or against use of baricitinib and tocilizumab. 

Continue to: Patients who are pregnant

Patients who are pregnant are at increased risk of severe COVID-19.^52,53 The NIH states that, in general, treatment and vaccination of pregnant patients with COVID-19 should be the same as for nonpregnant patients.¹

Pregnant subjects were excluded from several trials of COVID-19 treatments.⁵⁴ Because Janus kinase inhibitors, such as baricitinib, are associated with an increased risk of thromboembolism, they are not recommended in pregnant patients who are already at risk of thromboembolic complications. Molnupiravir is not recommended for pregnant patients because of its potential for teratogenic effects.

The Society for Maternal-Fetal Medicine states that there are no absolute contraindications to the use of monoclonal antibodies in appropriate pregnant patients with COVID-19.⁵⁵ Remdesivir has no known fetal toxicity and is recommended as a treatment that can be offered to pregnant patients. Dexamethasone can also be administered to pregnant patients who require oxygen; however, if dexamethasone is also being used to accelerate fetal lung maturity, more frequent initial dosing is needed.

Older people. COVID-19 treatments for older patients are the same as for the general adult population. However, because older people are more likely to have impaired renal function, renal function should be monitored when an older patient is being treated with COVID-19 medications that are eliminated renally (eg, remdesivir, baricitinib). Furthermore, drug–drug interactions have been reported in older patients treated with nirmatrelvir + ritonavir, primarily because of the effects of ritonavir. Review all of a patient’s medications, including over-the-counter drugs and herbal supplements, when prescribing treatment for COVID-19, and adjust the dosage by following guidance in FDA-approved prescribing information—ideally, in consultation with a pharmacist.

Immunocompromised patients. The combination product tixagevimab + cilgavimab [Evusheld] is FDA approved for COVID-19 PrEP, under an EUA, in patients who are not infected with SARS-CoV-2 who have an immune-compromising condition, who are unlikely to mount an adequate immune response to the COVID-19 vaccine, or those in whom vaccination is not recommended because of their history of a severe adverse reaction to a COVID-19 vaccine or one of its components.⁷

Continue to: Summing up

Summing up

With a growing need for effective and readily available COVID-19 treatments, there are an unprecedented number of clinical trials in process. Besides antivirals, immunomodulators, and antibody therapies, some novel mechanisms being tested include Janus kinase inhibitors, IL-6-receptor blockers, and drugs that target adult respiratory distress syndrome and cytokine release.

Guidelines recommend against using dexamethasone and other systemic corticosteroids in COVID-19 outpatient settings.

Once larger trials are completed, we can expect stronger evidence of potential treatment options and of safety and efficacy in children, pregnant women, and vulnerable populations. During the pandemic, the FDA’s EUA program has brought emerging treatments rapidly to clinicians; nevertheless, high-quality evidence, with thorough peer review, remains critical to inform COVID-19 treatment guidelines.

^ahttps://healthdata.gov/Health/COVID-19-PublicTherapeutic-Locator/rxn6-qnx8/data

^b Sotrovimab was effective against the Omicron variant of SARS-CoV-2—the dominant variant in early 2022— but is currently not FDA authorized in any region of the United States because of the prevalence of the Omicron BA.2 subvariant.30

CORRESPONDENCE
Ambar Kulshreshtha, MD, PhD, Department of Epidemiology, Emory Rollins School of Public Health, 4500 North Shallowford Road, Suite 134, Atlanta, GA 30338; [email protected]