Rachel Lutz

The Relationship Characteristics of Pediatric Multisystem Inflammatory Disease and COVID-19

,” was originally published on ContagionLive.

-associated multisystem inflammatory syndrome (MIS-C) in children leads to serious and life-threatening illness in otherwise healthy children and teens.

Investigators from the US Centers for Disease Control and Prevention (CDC) and Boston Children’s Hospital prospectively and retrospectively tracked MIS-C and COVID-19 data from March 15 to May 20, 2020 to summarize what is known about the illnesses’ relationship. Their 6 criteria included serious illness leading to hospitalization, age under 21 years, fever that lasted longer than 24 hours, laboratory-confirmed evidence of inflammation, multisystem organ involvement, and evidence of COVID-19 infection based on PCR or antibody testing or exposure to another person with COVID-19 in the past month.

Children with this hyperinflammatory syndrome present similar to 

, the study authors wrote, and it is similar to MIS-C in that it has no diagnostic confirmation tests.

There were 186 cases of MIS-C reported to the Overcoming COVID-19 study and the CDC by clinicians from 26 states, the study authors said. The median age of the patients was about 8 years, there were 115 male patients, and three-quarters of the group had previously been healthy. Additionally, the study authors reported that 19% were white, 25% were Black, 5% were another race, 31% were Hispanic or Latino, and 22% race was unknown.

The majority of those patients were hospitalized in the second half of the study period, from April 16 to May 20, the study authors added, noting the peak incidence of MIS-C occurred when COVID-19 activity was decreasing. Most of the COVID-19 cases were confirmed by PCR testing, antibody testing, or both, and about half could be linked to another person with the infection.

The study authors also identified 14 patients with recorded COVID-19 symptoms prior to the onset of MIS-C. They said the median interval from COVID-19 symptom onset to MIS-C symptom onset was 25 days.

Three-quarters of COVID-19 patients had involvement of at least 4 organ systems, the study authors said, and they were most often the gastrointestinal, cardiovascular, hematologic, mucocutaneous, and respiratory systems. The majority of patients were treated in the ICU and 20% received invasive mechanical ventilation, the investigators reported. At the end of the observation period, the study authors said 130 patients had been discharged alive, 52 remained hospitalized, and 4 patients died. The patients who died were all between ages 10 and 16, and additionally, 2 had underlying conditions, the study authors said.

Of the MIS-C patients, a majority had a fever for more than 5 days, the investigators said, and almost all of them had a fever for more than 4 days. Cardiovascular involvement was common in 4 out of 5 patients and 90 patients received vasoactive support, the study authors wrote. There was respiratory insufficiency or respiratory failure present in 109 patients, of which 85 had no underlying respiratory conditions, they added. From that group, 37 patients received invasive mechanical ventilation and 32 patients received noninvasive mechanical ventilation.

Most patients also had 4 or more laboratory markers that indicated inflammation, the study authors said, including: C-reactive protein level, lymphocytopenia, neutrophilia, elevated ferritin level, hypoalbuminemia, elevated alanine aminotransferase level, anemia, thrombocytopenia and an elevated d-dimer level, prolonged international normalized ratio, or elevated fibrinogen level.

The investigators treated the MIS-C patients with immunomodulatory drugs such as intravenous immune globulin (77%) and systemic glucocorticoids (49%), they wrote.

The study authors suggested that until more is known about long-term cardiac mechanisms behind MIS-C, providers could consider following Kawasaki disease guidelines for follow-up care.

“The clinical and the laboratory features of hyperinflammation, the timing of onset in relation to SARS-CoV-2 infection, and the similarities with the disease pattern in adults with Covid-19 support the hypothesis that MIS-C is a consequence of immune-mediated injury triggered by SARS-CoV-2 infection,” the study authors concluded.

Multisystem Inflammatory Syndrome in U.S. Children and Adolescents

Articles

Until more is known about long-term cardiac mechanisms behind MIS-C, providers could consider following Kawasaki disease guidelines for follow-up care

Pediatric Multisystem Inflammatory Disease and COVID-19

Prior Outbreaks Allude to COVID-19 Psychiatric Manifestation Risks

New study findings suggest outbreaks can cause 

Jonathan Rogers, MRCPsych, and a team of London-based investigators conducted a systematic review and meta-analysis to assess the psychiatric and neuropsychiatric manifestations of prior coronavirus pandemics, including SARS and MERS, to understand the possibility of what might be expected for COVID-19.

They searched the Medline, Embase, PsycINFO, and the Cumulative Index to Nursing and Allied Health Literature databases through April 10, 2020, to find relevant published articles regarding the psychiatric signs or symptoms, symptoms severity, diagnoses, quality of life, and employment.

Ultimately, 65 peer-reviewed studies and 7 pre-prints met inclusion criteria for the analysis. The investigators’ analysis involved 3559 coronavirus cases in international patients aged between 12-68 years.

Rogers and the team said COVID-19 may have psychiatric consequences in those infected as well as those not infected, due to “widespread anxiety, social isolation, stress in health care workers and other essential workers, and unemployment and financial difficulties,” they wrote.

However, those with the illness may experience “concern about the outcome of their illness, stigma, and amnesia or traumatic memories of severe illness.”

During the acute SARS or MERS illness, common patient symptoms for patients admitted to the hospital included depressed mood, anxiety, impaired memory, impaired concentration or attention, and insomnia, the investigators determined. Confusion was also reported by 36 of 129 patients—despite mean ages of 37 and 42 years in 1 study.

In assessing another study, investigators wrote that 1744 patients with SARS in Hong Kong were diagnosed with steroid-induced psychotic disorders. A pair of studies reported cases of depression, anxiety disorder, acute stress reaction, psychotic depression, and deterioration of dementia among patients.

There were 5 studies that examined the experiences of SARS and MERS patients, which found that loneliness, boredom, and frustration due to isolation were prominent. These individuals were often concerned with family members who were infected, spreading the virus to others, and death; however, 2 of those studies noted “enormous gratitude felt by patients for the support they received,” investigators wrote.

Once infection resolved, investigators found a depressed mood, euphoria, pressured speech, insomnia, anxiety, irritability, memory impairment, fatigue, emotional liability, traumatic memories, and sleep disorder were frequently reported.

There were 2 studies that looked into positive psychological outcomes, finding that patients gained a better perspective on life and valued their relationships, health, and every day existence more, investigators noted.

After a mean follow up of nearly 1 year, the point prevalence of anxiety disorder cases was 14.8%, investigators found. After about 22 months, the point prevalence for depression was 14.9%. After about 33 months, the point prevalence for PTSD was 32.2%.

Health-related quality of life was lower in patients after SARS infection, according to 3 studies included in the meta-analysis. After a mean follow-up time of 35.3 months, 446 of 580 patients in 6 studies had returned to work, investigators wrote.

The COVID-19 data showed evidence for delirium and altered consciousness, and after discharge, dysexecutive syndrome. Investigators also discovered 2 reports of hypoxic encephalopathy and 1 report of encephalitis.

“Although there are many ways in which mental health might be adversely affected by a pandemic, this review suggests, first, that most people do not suffer from a psychiatric disorder following coronavirus infection, and second, that so far there is little to suggest that common neuropsychiatric complications beyond short-term delirium are a feature,” Rogers and the investigators concluded. “Clinicians must be aware of the possibility of depression, anxiety, fatigue, post-traumatic stress disorder, and rarer neuropsychiatric syndromes in the aftermath.”

Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the COVID-19 pandemic

Prior coronavirus outbreaks help assess the possible psychiatric dangers related to COVID-19.

Past Outbreaks Shed Light on COVID-19 Psychiatric Risks

Why Comparing Flu and COVID-19 Severity Is Not Equivalent

 mortality rates cannot be compared to the mortality rate of 

In fact, doing such is a threat to public health and demonstrates the lack of understanding about how the data are collected for each infection by varying agencies.

Authors from Brigham and Women’s Hospital and Emory University School of Medicine outlined why the apparent equivalence of deaths from COVID-19 and seasonal flu are not capturing the entirety of the situation.

They said that public officials continually draw comparisons between the 2 infections, “often in an attempt to minimize the effects of the unfolding pandemic.”

The number of deaths from COVID-19 was estimated in early May to be approximately 65,000, which the authors agreed appeared similar to the estimated number of seasonal influenza deaths reported every year by the US Centers for Disease Control and Prevention (CDC).

However, that represents a fundamental misunderstanding of the way the CDC reports seasonal influenza morbidity and mortality.

From 2013-14 to 2018-19, the CDC reported yearly estimates of influenza deaths ranging from 23,000-61,000. However, the number of counted influenza deaths during those 2 seasons was 3448 and 15,620, respectively.

It would be more accurate to compare weekly counts of COVID-19 deaths to weekly counts of seasonal influenza deaths, the authors said, due to COVID-19 fatalities being counted and reported directly instead of estimated.

There were 15,455 COVID-19 deaths reported in the US during the week ending April 21, 2020.

There were 14,478 COVID-19 deaths reported in the US during the week prior.

There were 351 flu deaths during the peak week (week 11 of 2016) of the flu season in 201516.

There were 1626 flu deaths during the peak week (week 3 of 2018) of the flu season in 201819.

“These statistics on counted deaths suggest that the number of COVID-19 deaths for the week ending April 21 was 9.5-fold to 44.1-fold greater than the peak week of counted influenza deaths during the past 7 influenza seasons in the US, with a 20.5-fold mean increase,” the authors wrote.

The CDC also recognizes that their COVID-19 death counts are continually revised due to delays in reporting. The authors believed that the ratio of counted COVID-19 deaths to flu deaths will rise. Additionally, they said their ratios are more clinically consistent with the experiences of health care workers on the front lines.

“We infer that either the CDC’s annual estimates substantially overstate the actual number of deaths caused by influenza or that the current number of COVID-19 counted deaths substantially understates the actual number of deaths caused by SARS-CoV-2, or both,” they wrote.

The authors allowed for several considerations, including that testing capacity is limited for COVID-19 and there could be false-negative results. They also said that flu deaths are not reportable to public health authorities—while COVID-19 deaths are, which could lead to potential underreporting.

Drawing direct comparisons between 2 diseases, despite mortality statistics being collected by different methods, provides inaccurate information. The failure to consider these differences by experts “threatens public health,” the authors wrote, especially as they rely on the comparisons “to reopen the economy and deescalate mitigation strategies.”

“Although officials may say that SARS-CoV-2 is ‘just another flu,’ this is not true,” the authors concluded. “Our analysis suggests that comparisons between SARS-CoV-2 mortality and seasonal influenza mortality must be made using an apples-to-apples comparison, not an apples-to-oranges comparison. Doing so better demonstrates the true threat to public health from COVID-19.”

Authors say comparing mortality rates between the 2 conditions is a threat to public health.

Comparing Severity of Flu and COVID-19 Is Not the Same

Lopinavir-Ritonavir Not Better than Standard Care for COVID-19 Patients

Recent study findings showed that there were no observable benefits of lopinavir-ritonavir treatment for patients with severe 

Currently, no therapeutics have proven effective against severe COVID-19, leading a team investigators from China conducted a randomized, controlled trial involving 199 patients with laboratory-confirmed coronavirus. Lopinavir is an HIV drug which has shown in vitro inhibitory activity against SARS-CoV-2. Ritonavir can be combined with lopinavir to increase its plasma half-life, Bin Cao, MD, and colleagues wrote.

There were 99 patients randomized to receive lopinavir-ritonavir 400 mg/100 mg twice daily for 14 days plus standard care. However, 5 patients in this group did not receive any doses of lopinavir-ritonavir because of 3 early deaths within 24 hours after randomization and 2 others whose attending physician refused to prescribe lopinavir-ritonavir following randomization.

The 100 other patients in the study received standard care alone. The investigators aimed to measure time to clinical improvement and hospital discharge, whichever came first.

The investigators found that the median interval time between symptom onset and randomization was 13 days. They added that there were no major differences between the two groups. The median age of the patients was 58 years and 60% of the patients were men.

Patients that received lopinavir-ritonavir did not have a time to clinical improvement different from the patients who received standard care only, the investigators found. Those treated with lopinavir-ritonavir had a 15-day median time to clinical improvement, compared to 16 days in the standard care group.

Investigators observed no differences between the groups on the time to clinical deterioration, which they defined as a one-category increase on a seven-category scale.

However, the Cao and the team did find that the 28-day mortality was numerically lower in the lopinavir-ritonavir-treated group compared to the standard care-only group (19% vs 25%).

The patients treated with lopinavir-ritonavir were also found to have a shorter stay in the intensive care unit compared to standard care patients (6 days vs 11 days). The intervention group also had shorter duration from randomization to hospital discharge compared to the standard care cohort (12 days vs 14 days), investigators found.

Additionally, the team found that on day 14, a higher percentage of lopinavir-ritonavir-treated patients showed clinical improvement compared to the standard care group (45% vs 30%). But duration of oxygen therapy, duration of hospitalization, and time from randomization to death measures showed no differences between the groups, the study authors added.

Half of the lopinavir-ritonavir patients and half of the standard care patients reported adverse events in the time between randomization and day 28 including nausea, vomiting, and diarrhea. These gastrointestinal events were more common in the lopinavir-ritonavir patients, investigators noted.

Four gastrointestinal events were observed in the lopinavir-ritonavir patients but none in the standard care group. Cao and the investigators judged all of these serious adverse events to be related to the lopinavir-ritonavir treatment. The deaths that occurred within the study period were all COVID-19-related.

“We found that lopinavir-ritonavir treatment did not significantly accelerate clinical improvement, reduce mortality, or diminish throat viral RNA detectability in patients with serious Covid-19,” Cao and the team concluded. “These early data should inform future studies to assess this and other medication in the treatment of infection with SARS-CoV-2.”

A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19

The treatment was no better than standard care.

Author | Rachel Lutz

Articles

Pediatric Multisystem Inflammatory Disease and COVID-19

Past Outbreaks Shed Light on COVID-19 Psychiatric Risks

Comparing Severity of Flu and COVID-19 Is Not the Same

No Observable Benefits of Lopinavir-Ritonavir for Severe COVID-19