SARS-CoV-2 と COVID-19 に関する備忘録 Vol.17――オミクロンによる深刻な障害は改善しない割合が高い…etc.

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SARS-CoV-2 と COVID-19 に関するメモ・備忘録


◆Abnormal Surge of Brain Abscesses in American Children, CDC Reports【science alert：Michelle Starr　2023年10月30日】

Following the easing of pandemic restrictions in the US, cases of brain abscess in children under 18 rose to new heights, according to a pair of CDC reports released earlier in the year.

December 2022 saw a peak of 102 cases across the country. Since then, cases have fallen again but remained over the baseline maximum of 61 cases per month, up to and including March 2023.

These abscesses usually follow a respiratory infection – including COVID-19, the flu, or sinusitis – underscoring the importance that children remain up-to-date with their vaccinations, the CDC said.

Brain abscesses – even at these elevated numbers – are relatively rare, but they are also quite dangerous. They’re an infection in your brain caused by bacteria or fungi that enter the brain, usually either via the bloodstream from an infection in another part of the body, like pneumonia, or through an infection in the head, such as the ears, teeth, or sinuses.

These pus-filled pockets can exert pressure on the brain tissue around it and even cut off blood flow. The abscesses can cause brain damage and, in severe cases, be fatal, so they need to be treated fairly quickly with antibiotics and, in some cases, surgery.

According to a June report led by epidemiologist Emma Accorsi of the CDC, there were 34 cases a month of brain abscess as a baseline median from 2016 to 2019, based on hospitalization data. During this time, the baseline maximum was 61 cases in a month.

Then, the global COVID-19 pandemic hit the world in March 2020, and countries around the world began introducing measures to try to reduce the spread of infection, including wearing masks, using respirators to curtail aerosol transmission, and lockdowns, in which entire regions were confined to their homes to reduce person-to-person contact.

During the following months, many illnesses declined. Influenza cases, for example, dropped dramatically, as did respiratory syncytial virus (RSV) cases. It seems like cases of brain abscess caused by Streptococcus were another. This bacterium is commonly found in patients with RSV or influenza.

From May 2020, monthly cases dropped well below the baseline and remained that way until May 2021, the CDC reported. After this, however, cases started to climb to numbers significantly higher than those counted pre-pandemic.

“Although some variability between US Census Bureau regions was observed, overall patterns were generally similar: consistently low case counts after the onset of the pandemic, then a period of increase beginning in mid- to late-2021 followed by a large peak during winter 2022–2023,” Accorsi and her team explained.

Cases of brain abscess in children are recognized as a severe complication of viral respiratory infection in children. Following the easing of pandemic restrictions in 2022, respiratory viruses rose worldwide. In particular, cases of influenza and RSV surged to new heights, joining COVID-19 in a phenomenon that came to be known as the “tripledemic”.

The cause of this, according to infectious disease expert Christopher Gill of Boston University, was a sort of rebound effect from the low infection rates during the height of pandemic restrictions.

“Due to the COVID-19 restrictions, in the past several years, we saw major declines in the incidence and impact of RSV and influenza. That was good, but also meant that the population was NOT acquiring as much herd immunity to those other viruses,” he said in December 2022.

“At the same time, infants were still being born and adding to the population of susceptible individuals. The result was a bit like winding a clock spring too tightly, because now the rebound has been much more severe than in typical years. While this is a bit of a simplification of a very complex process, our best guess is that we are now in the midst of a planet-wide rebound of viral transmission.”

After that record peak of 102 cases last December, more than triple the baseline median, cases of pediatric brain abscess began to fall. However, they remained above the baseline maximum of 61 monthly cases until March 2023. Data after this time was not included in the report.

Although the report makes no speculations about the cause of the rise in cases, a second report, also published in June, specifically considered cases in Nevada, and did make a tentative correlation. The researchers, led by Jessica Penney of the CDC, suggested that there might be a link between the rise in cases of brain abscess and the lifting of mask mandates in that state in February 2022.

Cases do remain rare, even at that peak number in December 2022, but the CDC will continue to monitor the phenomenon and suggest that doctors remain vigilant for the signs of brain abscess in children presenting with respiratory symptoms.

“CDC continues to track trends in pediatric intracranial infections,” Accorsi and her team said, “and recommends that all persons aged ≤18 years remain current with recommended vaccinations, including influenza and COVID-19.”

There’s currently no RSV vaccine available for people under 60. But you can familiarize yourself with the symptoms of brain abscess on the Johns Hopkins Medicine website.

 

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◆SARS-CoV-2 spike protein S1 activates Cx43 hemichannels and disturbs intracellular Ca2+ dynamics【Biological Research　2023年10月25日】

Abstract

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the ongoing coronavirus disease 2019 (COVID-19). An aspect of high uncertainty is whether the SARS-CoV-2 per se or the systemic inflammation induced by viral infection directly affects cellular function and survival in different tissues. It has been postulated that tissue dysfunction and damage observed in COVID-19 patients may rely on the direct effects of SARS-CoV-2 viral proteins. Previous evidence indicates that the human immunodeficiency virus and its envelope protein gp120 increase the activity of connexin 43 (Cx43) hemichannels with negative repercussions for cellular function and survival. Here, we evaluated whether the spike protein S1 of SARS-CoV-2 could impact the activity of Cx43 hemichannels.

Results

We found that spike S1 time and dose-dependently increased the activity of Cx43 hemichannels in HeLa-Cx43 cells, as measured by dye uptake experiments. These responses were potentiated when the angiotensin-converting enzyme 2 (ACE2) was expressed in HeLa-Cx43 cells. Patch clamp experiments revealed that spike S1 increased unitary current events with conductances compatible with Cx43 hemichannels. In addition, Cx43 hemichannel opening evoked by spike S1 triggered the release of ATP and increased the [Ca2+]i dynamics elicited by ATP.

Conclusions

We hypothesize that Cx43 hemichannels could represent potential pharmacological targets for developing therapies to counteract SARS-CoV-2 infection and their long-term consequences.

 


◆Long-term prognosis at 1.5 years after infection with wild-type strain of SARS-CoV-2 and Alpha, Delta, as well as Omicron variants【International Journal of Infectious Diseases　2023年10月29日】

Highlights

  • Trajectory of long COVID in SARS-CoV-2 wild-type, Alpha, Delta, and Omicron.
  • Similar patterns of symptoms and severity of long COVID across all four variants.
  • No clinically significant decline in median severity up to 1.5 years after infection.
  • More than 50% of long COVID patients failed to improve using any outcome measure.
  • Patients infected with Omicron may experience severe non-improving long COVID.

Abstract

Objectives

Knowledge is limited on how changing SARS-CoV-2 variants may translate into different characteristics and affect the prognosis of patients with long COVID, especially following Omicron variants. We compared long-term prognosis of patients in a Danish Post-COVID Clinic infected with wild-type strain, Alpha, Delta, or Omicron variants as well as the pre-Omicron compared to the Omicron period.

Methods

At enrollment, a Post-COVID symptom Questionnaire (PCQ), and standard health scores, were registered and repeated four times until 1.5 years after infection. PCQ was the primary outcome to assess the severity of long COVID, and Delta PCQ to assess failure to improve.

Results

A total of 806 patients were enrolled. Patients infected with Omicron and Delta variants presented with more severe long COVID (median PCQ 43 in Delta vs 38 in wild-type, P = 0.003) and health scores (EuroQol five-dimension five-level-index was 0.70 in Omicron vs 0.76 in wild-type, P = 0.009 and 0.78 pre-Omicron, P = 0.006). At 1.5 years after infection, patients had no clinically meaningful decline in severity of long COVID, and 57% (245/429) of patients failed to improve 1.5 years after infection, with no differences between variants.

Conclusion

More than half of patients referred to a Post-COVID Clinic failed to improve in long COVID severity 1.5 years after infection regardless of variants of SARS-CoV-2.

 


◆Effectiveness of Nirmatrelvir–Ritonavir Against the Development of Post–COVID-19 Conditions Among U.S. Veterans【ACP Journals：Annals of Internal Medicine　2023年10月31日】

Abstract

Background:

COVID-19 has been linked to the development of many post–COVID-19 conditions (PCCs) after acute infection. Limited information is available on the effectiveness of oral antivirals used to treat acute COVID-19 in preventing the development of PCCs.

Objective:

To measure the effectiveness of outpatient treatment of COVID-19 with nirmatrelvir–ritonavir in preventing PCCs.

Design:

Retrospective target trial emulation study comparing matched cohorts receiving nirmatrelvir–ritonavir versus no treatment.

Setting:

Veterans Health Administration (VHA).

Participants:

Nonhospitalized veterans in VHA care who were at risk for severe COVID-19 and tested positive for SARS-CoV-2 during January through July 2022.

Intervention:

Nirmatrelvir–ritonavir treatment for acute COVID-19.

Measurements:

Cumulative incidence of 31 potential PCCs at 31 to 180 days after treatment or a matched index date, including cardiac, pulmonary, renal, thromboembolic, gastrointestinal, neurologic, mental health, musculoskeletal, endocrine, and general conditions and symptoms.

Results:

Eighty-six percent of the participants were male, with a median age of 66 years, and 17.5% were unvaccinated. Baseline characteristics were well balanced between participants treated with nirmatrelvir–ritonavir and matched untreated comparators. No differences were observed between participants treated with nirmatrelvir–ritonavir (n = 9593) and their matched untreated comparators in the incidence of most PCCs examined individually or grouped by organ system, except for lower combined risk for venous thromboembolism and pulmonary embolism (subhazard ratio, 0.65 [95% CI, 0.44 to 0.97]; cumulative incidence difference, −0.29 percentage points [CI, −0.52 to −0.05 percentage points]).

Limitations:

Ascertainment of PCCs using International Classification of Diseases, 10th Revision, codes may be inaccurate. Evaluation of many outcomes could have resulted in spurious associations with combined thromboembolic events by chance.

Conclusion:

Out of 31 potential PCCs, only combined thromboembolic events seemed to be reduced by nirmatrelvir–ritonavir.