Virus World

Transmission of the novel coronavirus is slowly spreading across the country and experts are cautioning about a possible surge in infections in summer. According to reports from about 5,000 prefectorially designated medical institutions nationwide, case numbers have tripled since COVID-19 — a disease caused by the virus — was downgraded to Category 5 under the Infectious Diseases Law. Okinawa Prefecture in particular has seen a sharp spike, registering 28.74 infected patients per medical institution, which is close to the level seen during the 8th wave of the virus at the start of the year. Experts are now expressing concerns about a summer surge and calling on households to prepare test kits and treatments to reduce fever. According to the reports, released Friday by the Health, Labor and Welfare Ministry, the medical institutions each logged 5.60 cases of infection in the week ending June 18, at least three times more than the reference figure of 1.80 per fixed-point medical institution for the week of May 1-7, immediately prior to COVID-19’s reclassification.

By prefecture, Okinawa registered 28.74 cases, approaching the peak figure of 31.85 seen during the 8th wave. As of Wednesday, hospital bed occupancy in the prefecture stood at 59%, with seven key medical institutions placing restrictions on emergency room visits. “Inpatient medical care is being strained in Okinawa,” Japan Hospital Association President Takao Aizawa said at a press conference Wednesday. “There have been cases in which Okinawa has seen a spike in infections, with infections subsequently spreading throughout the country. We’re worried about this happening again.” At a mid-June meeting, an advisory body of the health ministry warned that there could be “a certain level of infection spread during the summer.” Class cancellations have also been on the rise due to the virus. According to the Education, Culture, Sports, Science and Technology Ministry, a total of 105 public and other schools had cancelled classes as of June 1. Some schools in Fukuoka and Saitama prefectures have been shuttered since the start of this month.

Current COVID-19 infections are dominated by the XBB strains. The National Institute of Infectious Diseases estimates that by the end of the month, XBB-1.16 and XBB-1.5 will be responsible for 49% and 12% of new infections, respectively. The XBB strains are said to have a high ability to evade immunological responses obtained through vaccines and other sources. “Even if the effectiveness of the current vaccine is somewhat reduced, elderly people should still receive it to prevent them from developing serious symptoms,” said Tetsuo Nakayama, a specially appointed professor of clinical virology at Kitasato University. Since last month, people aged 65 and older, and others with a pre-existing illness have been vaccinated against BA-5 and other strains.

From September, all generations will be eligible for the BA-5 vaccination, and the health ministry also hopes to introduce a presently under-development vaccine that can also work against the XBB strains. Addressing the optimal way to respond promptly to the spread of infections, Prof. Tetsuya Matsumoto, a professor at the International University of Health and Welfare and scholar in infectious disease medicine, said: “It’s important to keep a close eye on various indicators, such as the weekly numbers for hospitalized patients and bed occupancy. In the event of a rapid spread in infection, medical services could become stretched, so people should lay in test kits and fever-reducing treatments.”

Background

Methods

Findings

Interpretation

Arkansas health officials reported COVID-19 case data during IDWeek that demonstrate the severe toll the delta variant has had on the state’s children.During a July peak, although the number of pediatric COVID-19 cases was lower than the last peak in January, hospitalizations and other indications of severe disease increased significantly, according to Michael Cima, PhD, MPH,state epidemiologist for the Arkansas Department of Health, and colleagues.  Cima conducted the research with Infectious Diseases in Children Editorial Board Member José R. Romero, MD, the state’s secretary of health, and Donald E. Warden, MPH, another epidemiologist in the department. During a presentation, Cima noted that the delta variant became the dominant circulating SARS-CoV-2 virus in Arkansas in June and early July.  “Growing evidence suggests that the delta variant is not only far more infectious than the next most infectious variant of concern, but it's also potentially more virulent, so naturally the question has been asked, How does the delta variant impact the pediatric population? Is a more severe disease being observed?” Cima said.

The researchers examined pediatric records for the 3 months they called “key inflection points” for the COVID-19 pandemic in Arkansas: July 2020, January 2021 and July 2021. They reviewed rates of hospitalization and ICU use, use of mechanical ventilation and, “to a lesser extent,” multisystem inflammatory syndrome in children (MIS-C), Cima said. Data showed that pediatric COVID-19 cases numbered 3,268 in July 2020, 11,735 in January 2021 and 8,031 in July 2021. Despite nearly 32% fewer cases occurring in July 2021 compared with January, there were around 42% more hospitalizations (105 vs. 74), 69% more ICU admissions (18 vs. 11) and a 300% increase in the use of mechanical ventilation, Cima and colleagues reported. Cima said PICU bed availability reached single digits in the entire state. He also noted that the state observed fewer MIS-C cases over the summer but that it was possible that cases would increase because there is usually a delay between infection and the appearance of MIS-C symptoms.

A new study adds to growing evidence suggesting that the Delta coronavirus variant is not only highly transmissible, but also more dangerous.  Covid-19 patients infected with the Delta variant had about double the risk of hospitalization compared to those infected with the Alpha variant, according to the study published Friday in the journal Lancet Infectious Diseases. "The results suggest that patients with the Delta variant had more than two times the risk of hospital admission compared with patients with the Alpha variant," researchers from Public Health England and the University of Cambridge wrote in their new study. "Emergency care attendance combined with hospital admission was also higher for patients with the Delta variant, showing increased use of emergency care services as well as inpatient hospitalization," the researchers wrote.

(HealthDay)—Influenza vaccination may have a protective effect for COVID-19-positive patients, according to a brief report recently published in the Journal of the American Board of Family Medicine. Ming-Jim Yang, M.D., from the University of Florida in Gainesville, and colleagues conducted a retrospective review involving 2,005 patients older than 18 years of age who tested positive for COVID-19. Influenza vaccination status and comorbidities were examined. Severity of disease as reflected by hospitalization and intensive care unit (ICU) admission was examined as the primary outcome. The association between influenza vaccination status and hospitalization was examined. The researchers found that compared with those who were vaccinated, COVID-19-positive patients who had not received the influenza vaccine within the last year had 2.44- and 3.29-fold increased odds of hospitalization and ICU admission, respectively. The results were adjusted for age, race, gender, hypertension, diabetes, chronic obstructive pulmonary disease, obesity, coronary artery disease, and congestive heart failure. "One of the biggest problems we have with any preventive measure is getting people to do it," a coauthor said in a statement. "So, maybe this would be a pretty good push for people to go out and get their flu shot."

Study published in JABFM:

https://www.jabfm.org/sites/default/files/COVID_20-0528.pdf

Fully vaccinating children reduced the risk of hospitalization for complications associated with influenza by 54%, according to a new study by Ben-Gurion University of the Negev (BGU) and University of Michigan researchers. The research, published in the December, 2019 print journal Clinical Infectious Disease, is one of the few studies worldwide that has tested the effectiveness of childhood vaccination against influenza and risk of hospitalization due to the influenza complications. The study was led by Dr. Hannah Segaloff, an epidemiologist at the School of Public Health, University of Michigan and Prof. Mark Katz, M.D., of BGU's Department of Health Management, Faculty of Health Sciences and a senior researcher at the Clalit Institute of General Research. Prof. Katz also teaches in BGU's Medical School for International Health.

The retrospective study reviewed the vaccination data of 3,746 hospitalizations of children ages six months to 8 years old at six hospitals in Israel. They were tested for influenza over three winter seasons 2015-16, 2016-17 and 2017-18. The findings reveal that the flu vaccine reduced hospitalizations associated with the flu by more than half. They also validate guidelines in the United States and Israel that recommend two vaccine doses for children up to age 8 who have never been vaccinated or who previously received one dose. "Children vaccinated according to government guidelines are much better protected from influenza than those who only receive one vaccine," says Dr. Segaloff. "Over half of our study population had underlying conditions that may put them at high risk for severe influenza-related complications, so preventing influenza in this group is critically important.

Published in Clinical Infectious Diseases:

https://doi.org/10.1093/cid/ciz125

Flu-related hospitalizations nationwide have risen dramatically in recent weeks, reaching levels historically not seen until much later in flu season, according to data released Friday by the Centers for Disease Control and Prevention. "We haven't seen this level of activity this early before," said Lynnette Brammer, team lead of the domestic influenza surveillance team at the CDC. Typical flu seasons usually don't pick up steam until December. Flu hospitalizations are rising across all age groups, especially children. The increase comes as other respiratory viruses, including RSV, or respiratory syncytial virus, are also spiking in kids. According to the Department of Health and Human Services, 76% of pediatric hospital beds nationwide are full. "We realize the potential implications of the co-circulating viruses all at once," Brammer said. "We're taking it very seriously."  Doctors are not required to report each positive flu test to public health officials, so the CDC and others monitor likely flu activity by looking at "influenza-like illnesses": a fever of at least 100 degrees Fahrenheit and a cough and/or sore throat without any other known cause.

Also Friday, the CDC reported the first flu-related death in a child so far this season. The CDC did not provide any details about the child, however KVEO, the NBC affiliate in Brownsville, Texas, recently reported that a 3-year-old girl had died after testing positive for the flu. While the flu and similar viral illnesses are rising nationwide, they're notably high across the Southeast and Eastern Seaboard — from Texas to Georgia, and South Carolina up to Virginia and New Jersey, according to the new report. Doctors also warn that other infections can follow severe cases of the flu, including bacterial infections like pneumococcal pneumonia. Dr. Greg Poland, director of the Mayo Clinic's Vaccine Research Group in Rochester, Minnesota, worries that this season could be bad for these post-viral infections.  Dr. Shannon Martinello, a pediatrician in private practice in New Haven, Connecticut, is already seeing an uptick in post-viral bacterial illness. "The more mucus they have, and the more congested they are, it increases their risk of ear infections," she said. "I always tell parents when their kids have flu, it's going to be a rough week, and they're going to get better," Martinello said. But if a child who has recovered from the flu starts to feel sick again a week or 10 days later, she advises parents to take the child back to the doctor. "I want to re-listen to his lungs and re-check his ears and make sure that something else hasn't happened as a secondary issue." 

There are early signs that this year's flu shot appears to work well at keeping people out of the hospital. A report on Chile's flu season, released Thursday by the CDC, found the vaccine was 49% protective against flu-related hospitalizations. That might seem low, but from 2015 to 2020, flu shot effectiveness in the U.S. ranged from 29% to 48%.  It's unclear whether this year's flu shots in the U.S. will be as effective as was found during Chile's flu season. But the shots used in both countries have one of the same targets: the H3N2 flu strain, which accounts for a majority of flu cases currently detected in the U.S. H3N2 is an influenza A virus and is often associated with increased hospitalizations. Kids under age 5 may be at particular risk. The CDC recommends that everyone 6 months and older get an annual flu shot. Children up through 8 years old may need two shots this year, the agency said, especially if they've never had the flu vaccine. The American Academy of Pediatrics has the same recommendation, adding that kids should get their flu shots by the end of October. But the early start to the flu season has left many Americans vulnerable. Only about half of the population gets an annual flu shot, typically. Many who do often wait until October to get it. "I cannot stress enough how important it is to go ahead and get that vaccine now," Brammer said.

Background: As Omicron became the dominant variant in South Africa, little is known about the severity of its clinical presentation. We describe the clinical severity of patients hospitalised with SARS-CoV-2 infection during the first four weeks of the Omicron-dominated fourth wave and compare this to the first four weeks of the Betadominated second and Delta-dominated third waves in Gauteng Province.

Methods: Polymerase chain reaction and antigen positive SARS-CoV-2 case data were collated daily from laboratory reports. Data on hospital admissions were collected through an active surveillance programme established specifically for COVID-19. In addition to descriptive statistics, post-imputation random effect multivariable logistic regression models were used to compare disease severity in the three wave periods. Severe disease was defined as one or more of acute respiratory distress, supplemental oxygen, mechanical ventilation, high/intensive care or death.

Results: There were 41,046, 33,423, and 133,551 SARS-CoV-2 cases in the second, third and fourth waves respectively. About 4.9% of cases were admitted to hospital during the fourth wave compared to 18.9% and 13.7% during the second and third waves (p<0.001). During the fourth wave, 28.8% of admissions were severe disease compared to 60.1% and 66.9% in the second and third waves (p<0.001). Admitted patients in the omicron-dominated fourth wave were 73% less likely to have severe disease than patients admitted during the delta-dominated third wave (adjusted odds ratio [aOR] 0.27, 95% confidence interval [CI] 0.25-0.31).

Conclusion: The proportion of cases admitted was lower and those admitted were less severe during the first four weeks of the Omicron-dominated fourth wave in Gauteng province of South Africa. Since any combination of a less-virulent virus, comorbidities, high immunity from prior infection(s) or vaccination may be important contributors to this clinical presentation, care should be taken in extrapolating this to other populations with different co-morbidity profiles, prevalence of prior infection and vaccination coverage.

Preprint to be published in The Lancet available (Dec. 29, 2021):

https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3996320

The new results, which were issued in a press release, could help shore up the perception that the medicine is effective. Gilead’s Covid-19 drug remdesivir appeared to reduce hospitalizations by 87% in high-risk patients diagnosed early in the disease in a new study, the company said Wednesday. The new results, which were issued in a press release, could help shore up the perception that the medicine is effective. They also could boost hopes for the use of oral antiviral drugs being developed by drug companies including Pfizer and Merck to treat people in the early stages of Covid-19. The administration of remdesivir remains challenging. It must be given intravenously, and in the study it was given in three infusions over three days — a logistical hurdle for patients who are not hospitalized. Remdesivir, under the brand name Veklury, has full approval from the Food and Drug Administration to treat Covid-19 and is widely used, but there has still been controversy about its effectiveness. A study conducted by Gilead and the National Institutes of Health showed that it helped patients recover faster. But a second large trial, conducted by the World Health Organization, failed to show any benefit for the drug in reducing Covid deaths. One challenge of using antiviral drugs like remdesivir is that they tend to work better early in the course of the disease. Currently, in part because it is an IV drug, remdesivir is used to treat patients who are already in the hospital.

The study was meant to test whether giving remdesivir earlier could have a bigger effect on Covid-19. But Gilead stopped it in April 2021 when it had only enrolled about half of the expected number of patients. The company said that this was because of the “changing epidemiology” of Covid-19 and “additional treatment options of the time,” likely meaning data about monoclonal antibody cocktails from Regeneron and Eli Lilly that could be given to outpatients in a single infusion. But Gilead continued to analyze the data from the 562 patients who were enrolled in the study and who were randomly assigned to receive either remdesivir or placebo. The company said there was an 87% reduction in hospitalization. This means that two patients were hospitalized or died in the remdesivir group, compared to 15 in the placebo group. There was also an 81% reduction in medical visits due to Covid-19. (Twenty-one patients in the placebo group sought a medical visit compared to four in the remdesivir group.) Gilead said there was one death in the study, in the placebo group, but that it occurred after the day 28 cutoff for the main analysis. Full results of the study will be presented at IDWeek, a medical conference. Gilead did not immediately provide information on the demographics of the patients in the trial. The company said side effects were similar to those seen in previous studies. The most common side effects were nausea and headache. A Gilead spokesman said that the company had shared the results with the FDA.

We tested whether COVID-19 incidence and hospitalization rates were inversely related to vaccination coverage among the 112 most populous counties in the United States, each with a population exceeding 600,000, and together with a combined total population of 147 million persons. We measured vaccination coverage as the percent of the total population fully vaccinated as of July 15, 2021, with the exception of 11 Texas counties, where the cutoff date was July 14, 2021. We measured COVID-19 incidence as the number of confirmed cases per 100,000 population during the 14-day period ending August 12, 2021. We measured hospitalization rates as the number of confirmed COVID-19 admissions per 100,000 population during the same 14-day period. COVID-19 incidence was significantly higher among counties in the lower half of the distribution of vaccination coverage (incidence 543.8 per 100,000 among 56 counties with mean coverage 42.61%) than among counties in the upper half of the distribution of coverage (incidence 280.7 per 100,000 among 56 counties with mean coverage 57.37%, p < 0.0001). Hospital admissions were also significantly higher among counties in the lower half of the distribution (55.37 per 100,000) than in the upper half of the distribution (20.48 per 100,000, p < 0.0001). In log-linear regression models, a 10-percentage-point increase in vaccination coverage was associated with a 28.3% decrease in COVID-19 incidence (95% confidence interval, 16.8 - 39.7%), a 44.9 percent decrease in the rate of COVID-19 hospitalization (95% CI, 28.8 - 61.0%), and a 16.6% decrease in COVID-19 hospitalizations per 100 cases (95% CI, 8.4 - 24.8%). Higher vaccination coverage is associated not only with significantly lower COVID-19 incidence, but also significantly less severe cases of the disease.

Available as preprint (August 20, 2021):

https://doi.org/10.1101/2021.08.17.21262195 

In a single-center experience, no patients hospitalized with COVID-19 who developed cardiac arrest survived to discharge after receiving CPR, researchers found.“ These outcomes warrant further investigation into the risks and benefits of performing prolonged CPR in this subset of patients, especially because the resuscitation process generates aerosols that may place health care personnel at a higher risk of contracting the virus,” Shrinjaya B. Thapa, MD, internist at William Beaumont Hospital in Royal Oak, Michigan, and colleagues wrote.  In this single-center study, researchers analyzed data from 1,309 patients with COVID-19 admitted to the hospital between March 15 and April 3. These data were used to identify patients who underwent CPR for cardiac arrest. Primary outcomes included the initial cardiac arrest rhythm, overall survival to discharge and time to return of spontaneous circulation.

Among the cohort, 4.6% (n = 60) had in-hospital cardiac arrest and underwent CPR. The sample size was reduced to 54 patients (mean age, 62 years; 61% men; 67% Black) after some lacked CPR documentation. The time to cardiac arrest from admission was a median of 8 days. The median duration of CPR was 10 minutes. None of the patients who received CPR survived to discharge (95% CI, 0-6.6). The initial rhythm was nonshockable in 96.3% of patients, 14.8% had asystole and 81.5% had pulseless electrical activity. Although no patients developed ventricular fibrillation, 3.7% of patients had pulseless ventricular tachycardia. More than half of patients (53.7%) achieved return of spontaneous circulation during a median time of 8 minutes. Of these patients, 51.7% changed their code status to do not resuscitate and 48.3% were recoded, underwent further CPR and died. “The high mortality following CPR is likely multifactorial,” Thapa and colleagues wrote. “Given that most of the patients in this study developed a nonshockable rhythm, the outcome was likely to be poor. Additionally, at the time of cardiac arrest, many patients were either receiving mechanical ventilation, kidney replacement therapy or vasopressor support, all factors previously shown to be associated with a poor outcome following [in-hospital cardiac arrest].”

In a related editorial, Matthew E. Modes, MD, MPP, MS, fellow in the division of pulmonary, critical care and sleep medicine at University of Washington in Seattle, and colleagues wrote: “These small case series reporting hospital survival after in-hospital cardiac arrest among patients with COVID-19 must be interpreted with caution, as only one or two additional survivors would make important differences in the observed estimates. Outcomes in the setting of COVID-19 may not actually differ from pre-COVID-19 outcomes of in-hospital cardiac arrest for patients with nonshockable rhythms, for whom hospital survival is often less than 15%. Nonetheless, this article represents important early evidence suggesting outcomes for in-hospital cardiac arrest in patients with COVID-19 pneumonia are likely poor, particularly among patients with respiratory failure. Improving outcomes for patients with severe illness with COVID-19 and in-hospital cardiac arrest will be challenging, as few of the likely drivers of poor outcomes (eg, nonshockable rhythms, respiratory etiologies of arrest and underlying critical illness) are modifiable.”

Original study published in JAMA (Sept. 28, 2020):

https://doi.org/10.1001/jamainternmed.2020.4779

The influenza (flu) vaccine can not only prevent illness that may cause a week or more of misery, it can reduce the likelihood of hospitalization in children and death in adults, according to two analyses of Centers for Disease Control and Prevention (CDC)-supported U.S. influenza surveillance data being presented at IDWeek 2019.  The first study supports the benefit of flu vaccination in preventing severe outcomes in children. Children who received the influenza vaccine were half as likely to be hospitalized with flu as those who didn’t get vaccinated, according to the study, which followed more than 3,600 children over two seasons. The second study looked at more than 43,000 older adults hospitalized with flu over five seasons and found that vaccination reduced the risk of severe outcomes – including death, pneumonia, intensive care admission and mechanical ventilation – by more than one-third.

“These studies add to the evidence that influenza vaccines prevent serious complications from flu,” said Angela P. Campbell, MD, MPH, FIDSA, FPIDS, lead author of the study in children and medical officer in the Epidemiology and Prevention Branch of the Influenza Division at the CDC, Atlanta. “They show just how important it is that everyone six months and older who is eligible to get a flu vaccine does so every year.”

Flu vaccination in children reduces risk of hospitalization

In the first study, conducted by seven pediatric medical centers comprising the New Vaccine Surveillance Network, researchers analyzed flu test results from 3,630 children, aged 6 months to 17 years old, who were hospitalized with acute respiratory illness over two flu seasons in which influenza A(H3N2) viruses were the predominantly circulating virus. Patients were tested for influenza using molecular diagnostic tests: 163 out of 1,714 (10%) during the 2016-2017 season and 218 out of 1,916 (11%) during the 2017-2018 season tested positive for flu, including A(H3N2), A(H1N1) and B viruses. Researchers estimated how well the flu vaccine worked to reduce hospitalizations due to laboratory-confirmed influenza by comparing the frequency of flu vaccination among children who tested positive for flu to vaccination among children without flu, adjusting for age, race/ethnicity, enrollment month, study site and underlying medical conditions. Based on this information, the vaccine effectiveness against influenza-associated hospitalizations was 50% over the two seasons (49% for the first season and 51% the second), meaning that vaccination reduced the risk of hospitalization with flu by about half. “This is encouraging given that flu vaccines often work better against H1N1 and B flu viruses than against H3N2 viruses,” said Dr. Campbell. “Our findings support the use of vaccination to prevent severe flu illness in children during every flu season, regardless of which viruses are predominant.”

Flu vaccination in adults reduces risk of death

In the second study, researchers looked at five flu seasons using the U.S. Influenza Hospitalization Surveillance Network and identified 43,608 adults (18 and older) hospitalized with laboratory-confirmed flu. Overall, 38% of those 18 to 64 years old and 65% of those 65 or older had received a flu vaccine. Researchers assessed vaccination status among hospitalized patients to determine the reduction in the odds of severe outcomes among vaccinated patients compared to those who were unvaccinated. The findings showed that in patients diagnosed with influenza A(H1N1), flu vaccination reduced their odds of severe outcomes, including death, by 36%. Severe outcomes included death, pneumonia, admission to the intensive care unit and mechanical ventilation.

Flu vaccination in adults 18-64 with A/(H1N1) influenza was associated with reduced risk of the following: 36% death, 17% pneumonia, 19% intensive care unit (ICU) admission and 34% mechanical ventilation. Vaccination also was associated with a shorter ICU length of stay. Flu vaccination in those 65 years or older was associated with reduced risk of the following: 28% ICU admission, 46% mechanical ventilation. It was also associated with a shorter hospital length of stay.....