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Adriano de Bernardi Schneider, MS, PhD Candidate, Contagion® Editorial Advisory Board Member, provides a brief snapshot into some of his work on mapping the evolution of the Zika virus.

Phylogenetically Mapping the Evolution of the Zika Virus as It Spread Across the World

Along with a 1 reported case in Massachusetts, the

New Hampshire Department of Health and Human Services (DHHS) has confirmed a person infected with eastern equine encephalitis (EEE) has died. The public health agency said the person was hospitalized due to severe central nervous system disease. The last reported human EEEV infection in New Hampshire was in 2014, when DHHS identified 3 human infections, including 2 fatalities. In the same statement, DHHS mentions there has been 1 confirmed case in Vermont this summer.

On August 16, the Massachusetts Department of Public Health (MDPH) released a statement discussing the confirmation of the first human case of EEE in the state this year. The confirmed case was discovered in an 80 year old man who was exposed to the vector borne disease in Worcester County. As a result, the risk level in the local communities of Douglas, Oxford, Sutton, and Webster has been raised to critical, and in Dudley, Northbridge, and Uxbridge the risk is increased to high.

Additionally, the neighboring communities of Auburn, Charlton, Grafton, Leicester, Mendon, Millbury, Millville, Southbridge, and Upton are now considered at moderate risk according to MDPH.

“This is the first time we have seen a person infected with EEE in Massachusetts since 2020,” Public Health Commissioner Robbie Goldstein, MD, PhD, said in a statement. “EEE is a rare but serious disease and a public health concern. We want to remind residents of the need to protect themselves from mosquito bites, especially in areas of the state where we are seeing EEE activity.

Though very rare, EEE is serious and a potentially fatal disease that can affect people of all ages. EEE is generally spread to humans through the bite of an infected mosquito. There were 12 human cases of EEE in Massachusetts in 2019 with 6 deaths, and 5 human cases with 1 death in 2020. There were no human cases of EEE in Massachusetts in 2021, 2022, or 2023.

EEE has a fatality rate of 33% to 70%, with most deaths occurring 2–10 days after the onset of symptoms.

In addition to a high mortality rate, long-term physical and mental complications, including permanent neurological deficits have been identified in many people who survive EEE.

Plymouth is approximately 40 miles south of Boston along the coast, and Worcester County is in the middle of the state, so the 2 areas are not in close proximity, but due to the elevated risk locally, the town of Plymouth decided to take action in response to outdoor parks. As of last Friday, all town public parks and fields are close daily from dusk until dawn.

“As Mass DPH has now elevated Plymouth’s EEE risk status to high, it is important to take extra precautions when outdoors and follow state and local health guidelines to avoid unnecessary risk to exposure to EEE. The health and safety of our community, residents, and visitors remain our priority,” Plymouth’s Commissioner of Health and Human Services, Michelle Bratti, said in a statement.

According to the Centers for Disease Control and Prevention (CDC) most people who are infected with the virus do not develop symptoms; however, for those that do, the date from the bite to the onset of the illness is 4 to 10 days. EEE can also result in fever or neurologic disease. The type of illness will depend on the age of the person and other factors. Those who are infected can develop meningitis.

There are no FDA-approved treatments for EEE and for patients who develop severe cases, they can be hospitalized to receive supportive treatment.

Over the weekend, MDPH detailed plans of spraying for mosquitos including aerially in areas of Plymouth County, and truck-mounted spraying in parts of Worcester County. As of Saturday, 10 communities in Massachusetts were raised to high or critical risk for EEE virus.

“The risk from EEE is high in parts of Plymouth County and critical in parts of Worcester County,” State Epidemiologist Catherine M. Brown, DVM, said in a statement. “In addition to recommending that people use mosquito repellent with an EPA-registered active ingredient and clothing to reduce exposed skin, we also recommend that evening outdoor events be rescheduled to avoid the hours between dusk and dawn. The mosquitoes most likely to spread EEE are most active during the dusk to dawn hours.”

There are preventative strategies to avoid EEE, and the MDPH has listed such measures 

For those who live in Massachusetts and want more information on EEE, it can be found 

 or by calling the DPH Division of Epidemiology at 617-983-6800.

1.NH DHHS Identifies Person Infected with Eastern Equine Encephalitis Virus in New Hampshire.The New Hampshire Department of Health and Human Services. August 27, 2024. Accessed August 28, 2024.
https://www.dhhs.nh.gov/news-and-media/nh-dhhs-identifies-person-infected-eastern-equine-encephalitis-virus-new-hampshire
2. State health officials announce season’s first human case of Eastern Equine Encephalitis in Massachusetts. MDPH. August 16, 2024. Accessed August 27, 2024.
https://www.mass.gov/news/state-health-officials-announce-seasons-first-human-case-of-eastern-equine-encephalitis-in-massachusetts
3.Plymouth to Close all Public Parks and Fields from Dusk to Dawn. Town of Plymouth. August 23, 2024. Accessed August 27, 2024. PDF.
4. Eastern Equine Encephalitis: Symptoms, Diagnosis, and Treatment. CDC. May 15, 2024. Accessed August 27, 2024.
https://www.cdc.gov/eastern-equine-encephalitis/symptoms-diagnosis-treatment/index.html
5. State officials announce plans to spray for mosquitoes in sections of Worcester and Plymouth counties due to EEE. MDPH. August 24, 2024. Accessed August 27, 2024. 
https://www.mass.gov/news/state-officials-announce-plans-to-spray-for-mosquitoes-in-sections-of-worcester-and-plymouth-counties-due-to-eee



The town of Plymouth decided to prohibit people from using the parks from dusk to dawn due to concerns over eastern equine encephalitis after a man contracted the rare disease in the state.

Concerns Over Mosquito-Borne Illness Causes Massachusetts Town to Create Curfew for Parks, Spraying in Counties

Insights from Robert Bransfield on the immune system’s role in psychiatric disorders

Microbial Infections and Mental Illness: Bridging Psychiatry and Infectious Disease

For more than 50 years, psychiatrist Robert C. Bransfield, MD, has specialized in treating some of the most challenging cases in mental health, patients with treatment-resistant psychiatric conditions. Based in New Jersey, Bransfield’s work has drawn attention to a frequently overlooked factor in psychiatric illness: infectious diseases, especially tick-borne infections such as Lyme disease.

A growing body of evidence is highlighting the role of microbial infections in the development and progression of various mental illnesses, according to a comprehensive review published in 

Bransfield and colleagues. The review identifies a range of pathogens, including 

as being associated with psychiatric conditions such as autism spectrum disorder, schizophrenia, bipolar disorder, depression, and anxiety. These infections have also been linked to suicidality, aggressive behavior, and other behavioral disturbances.

Linking Infections to Psychiatric Disorders

“We did the journal article with microbes and mental illness. That was with two co-authors: Dr. Greenberg and Dr. Mao. Dr. Greenberg is a child psychiatrist. Dr. Mao is a pediatric infectious disease doctor,” said Robert Bransfield, MD, lead author and clinical psychiatrist. “So, we went over the entire literature, and we looked at, first of all, six conditions—well, we looked at three—the conditions that were most associated with disability, and that was autism, schizophrenia, bipolar disorder, depression, anxiety. But then we also looked at suicide and violence.”

The review explores several mechanisms by which infections may influence brain function. These include direct microbial invasion of the central nervous system, immune activation that leads to neuroinflammation, autoimmune responses, and long-term immune dysregulation even after the infection has resolved. “So, you can get developmental impairments. You could get mental illnesses. You could also get behavior problems, such as suicidality or aggressive behavior, substance abuse—you can see increased,” Bransfield explained. “It’s quite a spectrum of psychiatric impairments and cognitive impairments.”

The authors highlight the concept of cumulative pathogen exposure, or total pathogen load, as a possible contributor to persistent neuropsychiatric symptoms in vulnerable individuals. In these cases, the interplay between the immune response and brain function may result in lasting changes in behavior, cognition, and mood. “Think of what the infections can do. They can cause impairments. So, it can be from active infection, or what might be a hit-and-run—a prior infection that causes a permanent impairment, even though the infection is gone—or it could be chronic relapsing infection that can come and go,” Bransfield said.

A key focus of the article is what the authors term “serious mental illness,” which encompasses autism, schizophrenia, and bipolar disorder. “Now, there’s a condition that we call serious mental illness. And serious mental illness is autism, schizophrenia, and bipolar. This is the group that are very disabled,” Bransfield said. “Now, serious mental illness isn’t just a mental illness. If you look at those three illnesses, it’s a multi-system illness that has a cardiometabolic component also, and it affects other systems.”

In one documented case, Bransfield described a 32-year-old patient with Lyme disease who died by homicide-suicide. “We did an autopsy exam. And autopsies are really the gold standard for this. We found 

 in his pancreas and in his heart, even though he was 32. And we also found a biochemical effect of the infection in his brain, which is quinolinic acid,” he said. “So, there is the triad that we often see where there’s a psychiatric, cardiac, and metabolic component in serious mental illness.”

The review also incorporates insights from emerging disciplines such as psychoimmunology and psychoneuroimmunology, which study how immune signaling within the brain affects mood and cognition. “Part of our brain transmission is neurotransmitters, but part of it is immune transmitters,” said Bransfield. “So, we need to connect the dots and see that connection.”

Rethinking the Biological Model of Mental Illness

This evolving biological model represents a shift from traditional views of psychiatric illness. “Historically, perspectives on the etiology of mental illness have evolved from demonic possession toward multisystem biologically based models that include gene expression, environmental triggers, immune mediators, and infectious diseases,” the authors wrote. Bransfield added, “Genes don’t change that fast, so we can’t blame it on genes. There may be susceptibility genes, but there’s some environmental trigger. There is about 20 different infections there.”

The implications extend beyond psychiatric diagnosis. The authors cite mounting evidence linking microbial agents to neurodegenerative conditions, including dementia. “Now, with something like dementia—and now there’s recent looking at dementia—for instance, the shingles vaccine reduces the risk of dementia. What is the link there?” Bransfield asked. “They find dental spirochetes, they find Lyme, they find other 

, they find microbes that they haven’t even been categorized yet.”

Despite growing recognition of these associations, a significant knowledge gap persists. “A problem is that many psychiatrists don’t know much about infectious disease, and many infectious disease doctors don’t know much about psychiatry,” Bransfield said. “The link between the two is the immune system, and it’s often how the immune system functions within the brain.”

To navigate contentious terminology around persistent infections, Bransfield offers a practical framework: “One way to think of it is infection-associated chronic illness. That’s a way of wording it. People would fight with the word ‘chronic,’ where they argue, ‘Well, is it chronic infection? Is it chronic symptoms?’” He continued, “Infection-associated chronic illness gets around that argument, knowing that there’s probably multiple mechanisms that occur, and some of these are inflammatory-mediated, and some are autoimmune-mediated.”

In conclusion, Bransfield and his colleagues emphasize the importance of interdisciplinary research and clinical strategies to advance prevention, diagnosis, and treatment. “So, when we look at that, we’re really seeing things to treat people in ways we never could before. And that’s a great thing that we can move forward,” he said. Reflecting on the evolving science, Bransfield added, “I’d say the quote of Yogi Berra: ‘I never would have seen it if I didn’t believe it.’ And I think once you start looking for it and paying attention to it, you’ll see this connection, and that can help prevent a lot of these chronic illnesses that are very burdensome to our patients and to our society.”

Bransfield RC, Mao C, Greenberg R. Microbes and Mental Illness: Past, Present, and Future. Healthcare. 2024; 12(1):83. 

https://doi.org/10.3390/healthcare12010083

Part 2 of insights from Robert Bransfield, MD's research on the immune system’s role in psychiatric disorders.

Part 1 of 4: Understanding how infectious diseases may trigger or worsen psychiatric disorders through genetics, immune response, and environmental factors.

Exploring the Hidden Link Between Infection and Mental Illness: An Introduction with Dr. Robert C Bransfield

For half a century, psychiatrist Robert C Bransfield, MD, has practiced psychiatry in New Jersey, dedicating his career to one of the field’s most challenging areas: treatment-resistant psychiatric illness. Over time, his curiosity and clinical observation led him to a striking and often underrecognized contributor to mental illness, infectious disease.

“In doing that,” says Bransfield, “many cases, particularly here in New Jersey, they had an infectious disease component, and when we looked at that infectious disease component, it helped us to get more effective treatment for people who would otherwise be treatment resistant.”

Bransfield has long been fascinated by the complex etiology of mental illness. “I've always been interested in what exactly causes mental illness. That's always been a mystery,” he reflects. “And if you look at it historically, there were old beliefs of demon possession. It was your mother's fault, low serotonin, you had bad genes. And in reality, it's a very complicated formula of what causes it.”

He challenges the notion that mental illness arises spontaneously. “Some people feel that it just comes from nowheres, which doesn't make sense. Everything's caused by something. Nothing's caused by nothing,” he asserts.

While genetics have played a central role in modern psychiatry’s understanding of mental illness, Bransfield urges caution. “Developmental genes alone don't make sense. There's only about half a dozen clear mental illness genes. But in reality, there's susceptibility genes.”

These susceptibility genes, he explains, can be activated by environmental triggers—one of the most compelling being infection. “The environmental trigger can be many things, but infection does come up a lot, and we found 60 different infectious diseases that are associated with different mental illnesses when we did a literature search.”

From an evolutionary standpoint, the prevalence of mental illness remains paradoxical. “If the brain is perfected so well with evolution, why is there so much mental illness?” he asks. His working theory: “You have susceptibility genes that are triggered by certain environmental conditions and that can cause mental illness, either congenitally or early development or fairly recently, and there's often an immune mediator.”

Bransfield emphasizes the importance of mapping disease progression in psychiatric disorders. “If you understand the susceptibility, the early stages, the later stages—think of it like a row of dominoes. And if you intervene at any one of those dominoes, that could prevent disease progression.”

He continues, “Once the disease occurs, then you can look at what perpetuates it, which may be different than what caused it. So it's like a vicious cycle. You're trying to break that, knowing there's many contributors, many deterrents, and sometimes acute triggers.”

The link between infection and mental illness isn't new. “Syphilis drew attention to it. Noguchi, he wrote about that. So that was clear infection in the brain. But then once we had penicillin, there was kind of a shifting away from that.”

He recalls the work of Dr. Henry Cotton in New Jersey’s Trenton State Hospital, who hypothesized infection's role in psychiatric illness and employed a now-infamous method of removing infected organs. “That went over the top, even though there may be some basis to that. It was a radical treatment approach.”

Later, the slow virus theory of the 1960s, along with work from the Stanley Lab at Johns Hopkins, brought renewed attention to infectious contributors—particularly 

. “We would meet in Germany every two years, in Gunzburg, and we would look at the psychoimmunology—the neuropsychoimmunology—which is the intermediate link. You have the infection, then it affects the immune system, and then the immune system contributes to a lot of symptoms.”

In recent decades, tick-borne diseases have emerged as a significant contributor to neuropsychiatric symptoms—especially in New Jersey. “A lot of people have tick-borne disease, and you see a lot of mental illness associated with tick-borne diseases. That happens a lot, often many years after initial infection.”

 as a key pathogen. “The most frequent infection can be Borrelia. Different kinds of Borrelia—it could be relapsing fever Borrelia, it could be Lyme Borrelia. There's a lot of different types of Borrelia.”

, often in tandem with other infections. “Bartonella—think of it almost like with HIV or COVID or Lyme. You see it, one organism. It's a complex, interactive infection, and there may be one organism that may be immunosuppressant, and then that activates other infections that might otherwise be latent.”

Such coinfections complicate diagnosis and treatment. “It's a very complicated formula, it seems, how these infections interact with each other, and we're still trying to understand how that works. It's not a simple postulate, where you get one organism and one clear manifestation.”

Indeed, two patients with the same infection may present very differently. “Many different people can have the same infection, have many different manifestations of it, depending on their vulnerabilities or genetic vulnerabilities.”

Among the various psychiatric outcomes, depression stands out. “The most common manifestation is really depression—depression particularly with tick-borne disease. With Lyme disease, there have been about 10 different studies on depression.”

But depression is only the tip of the iceberg. “Then there are other, less common manifestations that you see. You can see a broad range of psychiatric illnesses, cognitive impairments, neurological, and general medical impairments.” This series will shed light on new perspectives in understanding and treating complex psychiatric conditions. 

Robert Bransfield, MD, introduces his understanding of how infectious diseases may trigger or worsen psychiatric disorders through genetics, immune response, and environmental factors.

Rethinking Mental Illness: The Overlooked Impact of Infection

This week, the FDA approved a label expansion for glecaprevir/pibrentasvir (Mavyret), an oral pangenotypic direct acting antiviral (DAA) therapy. It is now approved for the treatment of adults and pediatric patients 3 years and older with acute or chronic 

 infection without cirrhosis or with compensated cirrhosis. With this approval, glecaprevir/pibrentasvir is the first and only DAA therapy approved to treat patients with acute HCV in 8 weeks with a 96% cure rate.

"The physical, emotional, and economic burden of a curable condition like hepatitis C is far too great in the United States and around the world," John Ward, MD, director, Coalition for Global Hepatitis Elimination, said in a statement. "If treated early with safe and effective therapies, providers can cure virtually all patients with hepatitis C before it escalates to chronic disease and eventually cirrhosis or liver cancer. The public health community now has a good opportunity to cure nearly all persons to support eliminating the toll of this deadly virus. No one should die of hepatitis C."

The label expansion was supported by data from the phase 3, multicenter, single-arm prospective study evaluating the safety and efficacy of glecaprevir/pibrentasvir 8-week treatment in adults with acute HCV infection.The study results showed the antiviral to be a highly efficacious treatment for people with acute HCV.

The study enrolled 286 treatment-naïve adult patients with acute HCV infection across 70 locations globally. Patients received oral tablets once daily for 8 weeks and were followed for 12 weeks after the end of treatment. The primary endpoint was the percentage of patients with sustained virological response 12 weeks post-treatment (SVR12) in the Intention-to-Treat (ITT) population. Secondary endpoints included the percentage of patients achieving SVR12 in the Modified ITT-Virologic Failure (mITT-VF) population, and the percentage of patients with on-treatment virologic failure and post-treatment relapse in the ITT population.

The majority of the adverse events reported were mild or moderate in severity.

 The most common adverse events were fatigue, asthenia, headache, and diarrhea.

With this approval, providers can now treat HCV patients immediately at the time of diagnosis. American Association for the Study of Liver Diseases and Infectious Diseases Society of America (AASLD/IDSA) have partnered together to create a “screen and treat” algorithm. The algorithm provides guidance for clinicians to show them how to carry out this model and expedite the time needed to get tested and on HCV medication.

The strategy here is to get more people who are infected into the continuum of care right away to not only address their infection, but also prevent other infections.



, Andrew Aronsohn, MD, associate professor of Medicine, University of Chicago Medical Center, and one of the chairs of the AASLD/IDSA HCV panel, discussed the offered further insights into this treatment strategy.

“I think what's really important to think about when caring for people with hep C—both on an individual and a population basis—is that oftentimes, we're really focusing on helping very vulnerable populations,” said Aronsohn. “So these are folks that may be struggling with addiction; these are folks that may have difficulty with transportation or navigating huge health systems, or maybe undomiciled. Every time you set up another step for them to have to follow-up, you risking losing them to follow-up. There's a lot of data in HIV and even in hep C, that if you put this all into 1 visit and you can work on some education and actually give them medication in hand before they go out the door it is beneficial."

"The label expansion for Mavyret, coupled with the implementation of test and treat models of care, serve as tools to support the public health community in treating more patients and bringing us closer to achieving the global 2030 elimination goal," Roopal Thakkar, MD, executive vice president, research and development, chief scientific officer, AbbVie, said in a statement.



For those interested in downloading the AASLD/IDSA algorithm, readers can go 

Reference
1. US FDA Approves Expanded Indication for AbbVie's MAVYRET® (Glecaprevir/Pibrentasvir) as First and Only Treatment for People with Acute Hepatitis C Virus. Abbvie press release. June 11, 2025. June 13, 2025. https://news.abbvie.com/2025-06-11-U-S-FDA-Approves-Expanded-Indication-for-AbbVies-MAVYRET-R-Glecaprevir-Pibrentasvir-as-First-and-Only-Treatment-for-People-with-Acute-Hepatitis-C-Virus



The antiviral, glecaprevir/pibrentasvir (Mavyet), is the first and only oral 8-week pangenotypic treatment approved for people with acute or chronic hepatitis C. The approval supports global clinical guidelines to advance testing and treatment of HCV regardless of chronicity and supports public health goals for disease elimination.

FDA Expands Indication for AbbVie’s Antiviral as First Treatment for People With Acute Hepatitis C 

An overwhelming majority of newly diagnosed HIV patients who accepted Same-Day ART initiation (SDART) also accepted follow-up telehealth appointments.

Of the 69 patients (93.2%) who accepted SDART, 68 of them agreed to a telehealth session.

International AIDS Society (IAS) AIDS 2020 Virtual Sessions.

This study was performed at the Thai Red Cross Anonymous Clinic in Bangkok, Thailand. Telehealth was added to the clinic to continue taking care of patients while keeping social distancing measures in place during coronavirus (COVID-19). In addition, the subsequent lockdown and local travel restrictions greatly affected access to facilities.

For patients who agree to SDART, they were assessed and if deemed eligible received a 4-week ART supply. Their follow-up telehealth was scheduled for 2 weeks afterwards.

Patients who tolerated ART were referred to long-term ART facilities, and another 6-week ART supply was mailed to ensure ART continuation during the transition.

Of the 47 patients who reached the 2-week follow-up, 37 used telehealth. Among the 10 patients who did an in-clinic follow-up visit, 2 had rashes, 3 needed syphilis injectable treatment, and 5 wanted face-to-face consultations. All patients remained on ART.

Rashes were identified in 4 clients, and 2 were managed through telemedicine. Overall, follow-up visits were successfully conducted in 100% of 47 clients, compared to 97.2% of 105 clients from the same period last year

“Telehealth is a safe and promising differentiated ART service delivery method, even for clients who just started on ART,” the investigators wrote. “Equity, economic, and sustainability aspects of SDART telehealth should be explored beyond its application during the COVID-19 pandemic.”

A small study shows a majority of HIV patients open to both starting ART and follow-up telehealth appointments.

Conferences

Telehealth Seen as Viable Option for Same-Day ART Patients

Although many clinicians may still be processing the collective trauma of COVID-19 , it has been nearly five years since the start of the pandemic.

 According to the World Health Organization (WHO), there have been approximately 777 million cumulative cases of COVID-19 with over 7 million deaths attributed to the disease.

The large spikes of COVID-19 cases seen in the winters of 2021 and 2022 decreased in intensity by winter 2023. Indeed, this year's recent cases reported by the WHO demonstrate an overall trending decline. Obtaining exact numbers of severe and critically ill COVID-19 cases in the United States remains difficult but data from the Centers for Disease Control and Prevention (CDC) demonstrates a decreased weekly death rate attributed to COVID-19.

Yet despite improving numbers, for many clinicians the memory of critically ill COVID-19 patients has yet to wane. 

The news of decreasing vaccination rates (CDC reports that 21.0% of adults > 18 have received 2024-2025 updated vaccine) and the constant possibility of a clinically impactful viral mutation linger as veiled threats for the intensivist. The purpose of the following is to provide a brief review of updates in epidemiology, classification of variants, diagnostic considerations, management, and long term effects of those with critical illness due to COVID-19.

Since the initial onset of the 2019 novel coronavirus, numerous variants have been identified. In an attempt to classify clinically significant variants, the WHO developed updated definitions for variant subclasses in 2023. These subclasses include the terms 

Variant Under Monitoring (VUM), Variant of Interest (VOI), and Variant of Concern (VOC).

 VUM and VOI are categorized by scientific nomenclature systems (eg JN118) with VOIs representing variants with genetic changes that affect viral characteristics (eg transmissibility, virulence) and have growth advantages over other variants. 

In addition to meeting the definition of VOI, VOC must be associated with either a detrimental change in clinical disease severity, a change in COVID-19 epidemiology causing substantial impact on health systems, or a significant decrease in the effectiveness of available vaccines. Additionally, VOCs are the only variant identified with Greek letters. To date there have been a total of 5 VOCs: Alpha, Beta, Gamma, Delta, and Omicron. As of December 2, 2024 no VOCs are listed on the WHO website although there is one VOI (JN1) and several VUMs.

Microbiologic work up of COVID-19 should include at a minimum the collection of respiratory specimens for nucleic amplification testing (NAAT). The WHO recommends consideration of fecal specimens and postmortem samples in the deceased. Antibody testing is not recommended in acute illness but testing for other potential etiologies based on local epidemiology such as influenza is encouraged. For severe or critical illness, blood cultures should also be obtained prior to initiation of antimicrobial therapy if able.

The definition of severe COVID-19 differs slightly between guidelines but generally requires hypoxemia at room air (≤90% per WHO,

), tachypnea (respiratory rate > 30), and signs of pneumonia including cough and lung infiltrates on chest imaging. Criteria for critically ill patients is less nuanced and includes those with associated acute organ dysfunction, shock, or need for respiratory support with either non-invasive or invasive ventilation. One of the hallmarks of patients with critical illness from COVID-19 is acute respiratory distress syndrome (ARDS). 

Current guidelines focus on previously established protocols for ARDS with use of high-flow nasal cannula, a trial of non-invasive ventilation, judicious use of intravenous fluids, support for low tidal volume ventilation once mechanical ventilation is required, and prone positioning for intubated patients with a PaO2/FiO2 ratio of < 150.

The WHO currently conditionally recommends awake prone positioning not requiring mechanical ventilation although high quality evidence supporting its use is limited. A trial of higher positive end expiratory pressure (PEEP) is suggested with a focus on patient individualization and monitoring of driving pressures. Routine use of continuous infusions of neuromuscular blocking agents is no longer recommended,

 however can be considered in certain patients such as those with ventilator dyssynchrony. ECMO referral is recommended for capable centers in patients who have refractory hypoxemia (PaO2:FiO2 < 80 mmHg for > 6 hours) despite optimization of a lung protective strategy.

Decreasing rates of COVID-19 and the available pharmaceutical armamentarium against COVID-19 led to the dissolution of the NIH Treatments Guideline Panel in August of 2024. Nevertheless the panel’s work provided a robust foundation for other society guidelines. The Infectious Disease Society of America (IDSA), American College of Physicians (ACP) and WHO provide the basis of high quality clinical recommendations for COVID-19 in 2024.

 The following summarizes currently widely accepted therapeutic options for hospitalized patients with COVID-19. Remdesivir remains recommended as first-line antiviral therapy for hospitalized patients requiring oxygen therapy after demonstrating decreased time to recovery for this population  but is not recommended for patients requiring mechanical ventilation.

 Other recommended antiviral therapies generally focus on management of nonhospitalized individuals and include nirmatrelvir and ritonavir. Immunomodulation therapy consists of steroids which demonstrated decreased mortality in hospitalized patients requiring oxygen who received dexamethasone in the pivotal RECOVERY trial.

Although COVID-19 has receded quite a bit from the minds of many, it still remains a virus that can present serious morbidity and mortality. Here is a review of clinical treatment strategies by an intensivist when seeing patients with severe COVID-19. 

Adriano de Bernardi Schneider, MS

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