COVID 19: Therapeutics and clinical management

HPIO is collecting the latest research so that Ohio policymakers and other stakeholders can make informed decisions on the rapidly evolving COVID-19 pandemic. Regular research updates are mailed to HPIO’s email contact list (click here to join our mailing list and if you are already signed up for our mailing list and do not see the updates, please check your spam folder).

May 11

Potential treatment for mild and moderate cases of COVID-19

A study of a potential treatment of COVID-19 (The Lancet, May 8) found that a combination of three drugs showed promising results for reducing the duration of the virus. The study’s authors found that early treatment with the triple combination of antiviral therapy with interferon beta-1b, lopinavir–ritonavir and ribavirin is safe and highly effective in shortening the duration of virus shedding, decreasing cytokine responses, alleviating symptoms and facilitating the discharge of patients with mild to moderate COVID-19. Furthermore, the triple antiviral therapy rapidly rendered viral load negative in all specimens, thereby reducing infectiousness of the patient.

May 4

Effectiveness of therapeutic interventions

A cohort study of hydroxychloroquine use to treat COVID-19 (JAMA Cardiology, May 1) found that patients at a Boston hospital who received hydroxychloroquine for the treatment of pneumonia associated with COVID-19 were at high risk of serious heart arrythmia, and concurrent treatment with azithromycin was associated with greater changes in heart rhythms. In addition, the study included a reported case of other abnormal heart rates with administration of hydroxychloroquine and azithromycin, which to the authors’ knowledge, has yet to be reported here in the literature. Given these findings, clinicians should carefully weigh risks and benefits if considering hydroxychloroquine and azithromycin, with close monitoring of patient heart rhythms.

A randomized, double-blind, placebo-controlled trial of remdesivir (The Lancet, April 29) at ten hospitals in Hubei, China found that the drug was not associated with statistically significant clinical benefits. Although not statistically significant, patients receiving remdesivir had a numerically faster time to clinical improvement than those receiving placebo among patients with symptom duration of 10 days or less. Adverse events were reported in 102 (66%) of 155 remdesivir recipients versus 50 (64%) of 78 placebo recipients.

Symptoms and outcomes in children

A study of 100 Italian children with COVID-19 in 17 pediatric emergency department (NEJM, May 1) found that 55% of the cases involved exposure to SARS-CoV-2, the virus that causes COVID-19, from an unknown source or from a source outside the family. The study found that 21% of the patients were asymptomatic, 58% had mild disease, 19% had moderate disease, 1% had severe disease and 1% were in critical condition. Common symptoms were cough (44%) and no feeding or difficulty feeding (23%). No deaths were reported.

A study of children tested in a hospital in Wuhan, China (NEJM, April 23) found that of 1,391 children tested, a total of 171 (12.3%) were confirmed to have SARS-CoV-2. Fever was present in 41.5% of the children. Other common symptoms included cough and sore throat. As of March 8, there was one death in a 10-month-old child, 21 patients were in stable condition in the general ward and 149 were discharged. Asymptomatic infections (15.8%) were not uncommon. Determination of the transmission potential of these asymptomatic patients is important for guiding the development of measures to control the ongoing pandemic.

A systematic review of 18 studies of pediatric patients with COVID-19 (JAMA Pediatrics, April 22) found that most pediatric patients with SARS-CoV-2 infection presented with fever, dry cough and fatigue or were asymptomatic. Most children with COVID-19 presented with mild symptoms, if any, and generally required supportive care only. Typically, children had a good prognosis and recovered within 1 to 2 weeks.

April 30

Racial and ethnic disparities in COVID-19 patients

A study of the demographic characteristics, underlying medical conditions and clinical outcomes of hospitalized COVID-19 patients (CDC MMWR, April 29) found the proportion of hospitalized patients who were black was higher than expected based on overall hospital admissions. Black patients were not more likely than were nonblack patients to receive invasive mechanical ventilation or to die during hospitalization. Among the 305 hospitalized patients studied, the median duration of hospitalization was 8.5 days and duration increased with age. ICU admission occurred among 119 (39.0%) patients and increased significantly with age group. Among 281 (92.1%) patients who were no longer hospitalized at the time of data abstraction, 48 (17.1%) died. The authors found that given the overrepresentation of black patients within this hospitalized cohort, it is important for public health officials to ensure that prevention activities prioritize communities and racial/ethnic groups most affected by COVID-19. Community mitigation recommendations (e.g., social distancing) should be widely instituted, not only to protect older adults and those with underlying medical conditions, but also to prevent the spread of SARS-CoV-2 among persons in the general population who might not consider themselves to be at risk for severe illness.

April 27

Risk factors and comorbidities

review of early data examining the effects of body mass index (BMI) on COVID-19 patients (Nature Reviews Endocrinology, April 23) concluded that, while it is widely recognized that the presence of comorbidities such as hypertension, diabetes and cardiovascular disease are associated with more severe cases COVID-19, obesity has not been sufficiently investigated. Obesity is a main risk factor for these comorbidities and more generally for impaired metabolic health (such as dyslipidemia and insulin resistance) and is also linked to an increased risk of pneumonia. However, authors also note an “obesity paradox,” where despite the increased risk of pneumonia and difficulties associated with intubation and mask ventilation, the risk of death in patients with obesity and pneumonia might be decreased. Preliminary data suggest that people with obesity are at increased risk of severe COVID-19. However, data is limited.
Astudy of risk of COVID-19 complications (CDC, Emerging Infectious Diseases, April 23) estimated that 45.4% of U.S. adults are at increased risk for complications from COVID-19 because of cardiovascular disease, diabetes, respiratory disease, hypertension or cancer. The percentage of adults with any of the chronic conditions increased by age, from 19.8% for persons 18-29 years of age to 80.7% for persons older than 80. The rate of chronic conditions also varied by state, race/ethnicity, health insurance status and employment. The authors found that 48.3% of Ohioans surveyed had at least 1 of 6 chronic conditions that increase risk for coronavirus disease complications. They estimated that, in total, 4,268,748 Ohioans have increased risk for complications due to these chronic conditions.

April 23

New guidelines, research on treating COVID-19 patients

new set of COVID-19 treatment guidelines (National Institutes of Health, April 21) have been developed to inform clinicians on how to care for patients with COVID-19. The guidelines state that, at present, no drug has been proven to be safe and effective for treating COVID-19. There are insufficient data to recommend either for or against the use of any drug therapy in patients with COVID-19 who have mild, moderate, severe or critical illness. Because clinical information about the optimal management of COVID-19 is evolving quickly, these guidelines will be updated frequently as published data and other authoritative information becomes available.
review of 73 studies of acute viral respiratory infections or conditions commonly caused by respiratory viruses (WHO, April 19) found that there is no evidence of severe adverse events in patients with respiratory conditions as a result of the use of non-steroidal anti-inflammatory drugs (NSAIDs), which had previously been reported as potentially dangerous for COVID-19 patients. This analysis can inform the practices and recommendations of healthcare providers related to NSAID use and COVID-19. The authors note, however, that the research provides no direct evidence from patients with COVID-19, SARS or MERS. Therefore, all evidence included should be considered indirect evidence with respect to the use of NSAIDs and COVID-19.

Alternative ventilation strategies

literature review of current guidance treating COVID-19 patients with ventilators (American Journal of Tropical Medicine and Hygiene, April 21) finds that supplemental oxygen is a first essential step for the treatment of severe COVID-19 patients with low oxygen levels and should be a primary focus in resource-limited settings where capacity for invasive ventilation is limited. The presence of only low oxygen levels should in general not trigger intubation, the authors conclude. The authors suggest that this ventilation strategy, which reduces the use of ventilators among COVID-19 patients, might reduce the currently very high case fatality rate (more than 50%) in invasively ventilated COVID-19 patients.
commentary on COVID treatment (Lancet Respiratory Medicine, April 20) argues that healthcare workers should continue using less invasive treatments to treat COVID-19, including continuous positive airway pressure (CPAP) or non-invasive ventilation (NIV), when appropriate. Early intubation of every patient suspected to have COVID-19 could result in the unnecessary use of an invasive procedure and lead to equipment shortages for patients that need mechanical ventilation. The author states that the use of NIV during the SARS epidemic was not associated with an increased risk of transmission of the virus to healthcare workers, whereas, intubation was associated with an increased risk of aerosolization and infection of health-care workers. There is also evidence that, in a series of 20 patients with SARS, endotracheal intubation was avoided in 14 (70%) patients with the use of NIV.

April 14

No treatment yet proven effective for COVID-19

A summary of proposed treatments for COVID-19 (JAMA, April 13) found that, to date, no therapies have been proven effective to treat the virus. Some repurposed and experimental agents have shown promise in case reports and more robust clinical trials are ongoing. The article provides a summary of research to date, links to clinical treatment guidance and an FAQ on COVID-19 clinical management.

April 13

Tobacco use, other risk factors associated with COVID-19

commentary on the link between smoking and COVID-19 (Journal of Clinical Medicine, March 20) reports that people who smoke are more vulnerable to respiratory viruses and outbreaks in countries such as China, Italy, Iran and South Korea likely include an overrepresentation of smokers among COVID-19 fatalities. Research has found that smoking can increase the production of the angiotensin-converting enzyme-2 (ACE2) receptor, which is the receptor where COVID-19 infections begin. The link between tobacco use and COVID-19 is of particular interest in Ohio. The 2019 Health Value Dashboardfinds that Ohio ranks in the bottom quartile on metrics related to tobacco use, including adult smoking and children living in a household with a smoker. Ohioians may be more susceptible to severe cases of COVID-19 because Ohioans smoke more than people in most other states.
A literature review of COVID-19 patient studies(Archives of Academic Emergency Medicine, March 23) found that hypertension, cardiovascular diseases, diabetes, smoking, chronic obstructive pulmonary disease (COPD), cancer and chronic kidney disease were among the most prevalent underlying diseases among hospitalized COVID-19 patients, respectively.

April 8

Intensive care management and outcomes

Studies of COVID-19 patients in China and Italy give insights that could be useful for Ohio healthcare providers.
An in-depth review(Lancet, April 6) of intensive care treatment of COVID-19 patients in China provides an overview of the challenges facing ICUs and recommendations for addressing these challenges.
Key messages highlighted in the journal are:
  • Clinical features of coronavirus disease 2019 (COVID-19) are non-specific and do not easily distinguish it from other causes of severe community-acquired pneumonia
  • As the pandemic worsens, ICU practitioners should increasingly have a high index of suspicion and a low threshold for diagnostic testing for COVID-19
  • Many questions on clinical management remain unanswered, including the significance of myocardial dysfunction, and the role of non-invasive ventilation, high-flow nasal cannula, corticosteroids, and various repurposed and experimental therapies
A study of COVID-19 patients in ICUs in Lombardy, Italy (JAMA, April 6) found that 82% were male; 18% were female. Median age was 63 but there were multiple cases of people who were below this age with no comorbidities. Most of these patients required some type of respiratory support and the ICU mortality rate was 26% as of March 25, 2020. Prevalence of hypertension was higher for those who died in the ICU than for those who were discharged. The authors note that the need for invasive ventilation in this patient population was higher than that reported in Washington state and Wuhan.

April 7

Child outcomes for COVID-19

A preliminary description of pediatric U.S. COVID-19 cases (CDC, April 6) finds that relatively few children with the disease are hospitalized, and hospitalization was most common among pediatric patients less than a year old and those with underlying conditions. The analysis found that nearly one third of reported pediatric cases occurred in children aged 15-17 years, followed by cases in children aged 10-14 years. It is important to note that severe outcomes have been reported in children, including three deaths. Social distancing and everyday preventive behaviors remain important for all age groups because patients with less serious illness and those without symptoms likely play an important role in disease transmission.

April 6

Studies highlight COVID-related mental health challenges for children, healthcare workers

Recent research literature has examined the mental health impact of COVID-19, particularly on groups such as children and healthcare workers.
A new commentary(Lancet, March 27) highlights that children’s mental health should be considered when designing and implementing strategies to combat COVID-19. When children are quarantined or separated from parents due to COVID-19, policymakers should consider: (1) establishing evidence-based guidelines and strategies to cope with COVID-19 pandemic-related mental health problems in children; (2) improving children’s access to mental health services through nationwide networks of psychiatrists, psychotherapists, researchers and community volunteers; (3) conducting post-pandemic surveillance of mental disorders among children.
A study of healthcare workers in China during the COVID-19 outbreak (JAMA, March 23) found that people working in hospitals and other healthcare settings may experience increased symptoms of psychological distress and need additional support. The study measured symptoms of depression, anxiety, insomnia and distress among workers. Participants reported experiencing psychological burden, especially nurses, women and frontline health care workers directly engaged in the diagnosis, treatment and care of patients with COVID-19.

March 31

COVID-19 may worsen or induce cardiovascular problems, studies find

A review (JAMA Cardiology, March 27) of the potential effects of coronaviruses on the cardiovascular system concluded that COVID-19 can cause cardiovascular complications, which put patients at increased risk for severe disease and mortality. Until specific treatments for COVID-19 are developed, cardiovascular complications should be treated using guideline-based therapies, the authors found. According to the Heart Failure Society of America, American College of Cardiology and American Heart Association, ACE inhibitors, ARBs or renin-angiotensin-aldosterone system antagonists, “can be continued in patients with COVID-19 without interruption in compliance with available clinical guidelines.”
Another study(JAMA Cardiology, March 27) of COVID-19 patients in China found that those with cardiovascular disease and myocardial injury were at elevated risk for mortality from COVID-19. People with underlying cardiovascular disease and no myocardial injury experience relatively favorable outcomes. Triaging for cardiovascular disease and myocardial injury can help providers to make treatment decisions.

March 30

Analysis shows severe COVID-19 impacting Americans of all ages

An early analysis of U.S. cases by the CDC(March 26) between Feb. 12 and March 16 found that not all severe cases of COVID-19 involve older adults. Of the cases reported during that early time period, 31% were people age 65 and older. Older Americans comprised 45% of hospitalizations, 53% of ICU admissions and 80% of deaths. While the virus appears to be affecting older adults in higher numbers, the analysis found that 20% of hospitalizations were adults age 20-44. The CDC continues to recommend social distancing to slow the spread of the virus and protect the healthcare system. They also recommend that older adults maintain supplies of nonperishable foods and prescription medications.

Chinese studies shed light on outcomes for pregnant women with COVID-19 and newborns

Several early studies from China examine the impact on children who are born to a mother who has tested positive for COVID-19.
case report(Lancet, March 24)of seven full-term pregnant women who tested positive for COVID-19 in Wuhan, China, found that people infected with COVID-19 late in pregnancy experienced “very good” maternal, fetal and neonatal outcomes, which were achieved with “intensive, active management.” The report provides information for healthcare providers with patients who are pregnant and positive for COVID-19. However, it is important to note that the report includes a small sample and there has been no assessment of long-term outcomes and/or mother-to-child transmission.
Another study (Journal of the American Medical Association, March 26) of six moms in Wuhan, China, infected with confirmed COVID-19 found that the virus was not detected in any of the newborns and all of the infants had positive birth outcomes. The study measured antibodies from infant throat swabs and blood samples. All six infants had antibodies for COVID-19 detected in their serum, although information about the mode of transmission is not conclusive. This early research indicates that infants born to women with COVID-19 pneumonia have positive birth outcomes and have antibodies for COVID-19. Like the other study of pregnant women in Wuhan, this study is limited by a small sample size, lack of cord blood, amniotic fluid and breast milk studies and by incomplete information on the outcome of the infants.

March 25

Work continues on finding therapeutic drugs

Efforts to identify a drug or drug combination that can treat COVID-19 have gained a lot of attention, but no drug has yet to be proven effective.

Nearly 70 drugs and experimental compounds may be effective in treating the coronavirus, a team of researchers reported (bioRxiv, March 22, 2020) this week. Some of the medications are already used to treat other diseases, and repurposing them to treat COVID-19, the illness caused by the coronavirus, may be faster than trying to invent a new antiviral from scratch, the scientists said.

review of early efforts (Open Forum Infectious Diseases, March 23, 2020) to identify medications to treat COVID-19 concluded that evidence of effectiveness has been elusive.