Abstract Objectives To characterize the clinical severity of covid-19 associated with the alpha, delta, and omicron SARS-CoV-2 variants among adults admitted to hospital and to compare the effectiveness of mRNA vaccines to prevent hospital admissions related to each variant. Design Case-control study. Setting 21 hospitals across the United States. Participants 11 690 adults (≥18 years) admitted to hospital: 5728 with covid-19 (cases) and 5962 without covid-19 (controls). Patients were classified into SARS-CoV-2 variant groups based on viral whole genome sequencing, and, if sequencing did not reveal a lineage, by the predominant circulating variant at the time of hospital admission: alpha (11 March to 3 July 2021), delta (4 July to 25 December 2021), and omicron (26 December 2021 to 14 January 2022). Main outcome measures Vaccine effectiveness calculated using a test negative design for mRNA vaccines to prevent covid-19 related hospital admissions by each variant (alpha, delta, omicron). Among patients admitted to hospital with covid-19, disease severity on the World Health Organization’s clinical progression scale was compared among variants using proportional odds regression. Results Effectiveness of the mRNA vaccines to prevent covid-19 associated hospital admissions was 85% (95% confidence interval 82% to 88%) for two vaccine doses against the alpha variant, 85% (83% to 87%) for two doses against the delta variant, 94% (92% to 95%) for three doses against the delta variant, 65% (51% to 75%) for two doses against the omicron variant; and 86% (77% to 91%) for three doses against the omicron variant. In-hospital mortality was 7.6% (81/1060) for alpha, 12.2% (461/3788) for delta, and 7.1% (40/565) for omicron. Among unvaccinated patients with covid-19 admitted to hospital, severity on the WHO clinical progression scale was higher for the delta versus alpha variant (adjusted proportional odds ratio 1.28, 95% confidence interval 1.11 to 1.46), and lower for the omicron versus delta variant (0.61, 0.49 to 0.77). Compared with unvaccinated patients, severity was lower for vaccinated patients for each variant, including alpha (adjusted proportional odds ratio 0.33, 0.23 to 0.49), delta (0.44, 0.37 to 0.51), and omicron (0.61, 0.44 to 0.85). Conclusions mRNA vaccines were found to be highly effective in preventing covid-19 associated hospital admissions related to the alpha, delta, and omicron variants, but three vaccine doses were required to achieve protection against omicron similar to the protection that two doses provided against the delta and alpha variants. Among adults admitted to hospital with covid-19, the omicron variant was associated with less severe disease than the delta variant but still resulted in substantial morbidity and mortality. Vaccinated patients admitted to hospital with covid-19 had significantly lower disease severity than unvaccinated patients for all the variants.

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Clinical severity of, and effectiveness of mRNA vaccines against, covid-19 from omicron, delta, and alpha SARS-CoV-2 variants in the United States: prospective observational study

The B.1.1.529 (Omicron) variant of SARS-CoV-2, the virus that causes COVID-19, was first clinically identified in the United States on December 1, 2021, and spread rapidly. By late December, it became the predominant strain, and by January 15, 2022, it represented 99.5% of sequenced specimens in the United States* (1). The Omicron variant has been shown to be more transmissible and less virulent than previously circulating variants (2,3). To better understand the severity of disease and health care utilization associated with the emergence of the Omicron variant in the United States, CDC examined data from three surveillance systems and a large health care database to assess multiple indicators across three high-COVID-19 transmission periods: December 1, 2020-February 28, 2021 (winter 2020-21); July 15-October 31, 2021 (SARS-CoV-2 B.1.617.2 [Delta] predominance); and December 19, 2021-January 15, 2022 (Omicron predominance). The highest daily 7-day moving average to date of cases (798,976 daily cases during January 9-15, 2022), emergency department (ED) visits (48,238), and admissions (21,586) were reported during the Omicron period, however, the highest daily 7-day moving average of deaths (1,854) was lower than during previous periods. During the Omicron period, a maximum of 20.6% of staffed inpatient beds were in use for COVID-19 patients, 3.4 and 7.2 percentage points higher than during the winter 2020-21 and Delta periods, respectively. However, intensive care unit (ICU) bed use did not increase to the same degree: 30.4% of staffed ICU beds were in use for COVID-19 patients during the Omicron period, 0.5 percentage points lower than during the winter 2020-21 period and 1.2 percentage points higher than during the Delta period. The ratio of peak ED visits to cases (event-to-case ratios) (87 per 1,000 cases), hospital admissions (27 per 1,000 cases), and deaths (nine per 1,000 cases [lagged by 3 weeks]) during the Omicron period were lower than those observed during the winter 2020-21 (92, 68, and 16 respectively) and Delta (167, 78, and 13, respectively) periods. Further, among hospitalized COVID-19 patients from 199 U.S. hospitals, the mean length of stay and percentages who were admitted to an ICU, received invasive mechanical ventilation (IMV), and died while in the hospital were lower during the Omicron period than during previous periods. COVID-19 disease severity appears to be lower during the Omicron period than during previous periods of high transmission, likely related to higher vaccination coverage,† which reduces disease severity (4), lower virulence of the Omicron variant (3,5,6), and infection-acquired immunity (3,7). Although disease severity appears lower with the Omicron variant, the high volume of ED visits and hospitalizations can strain local health care systems in the United States, and the average daily number of deaths remains substantial.§ This underscores the importance of national emergency preparedness, specifically, hospital surge capacity and the ability to adequately staff local health care systems. In addition, being up to date on vaccination and following other recommended prevention strategies are critical to preventing infections, severe illness, or death from COVID-19.

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Trends in Disease Severity and Health Care Utilization During the Early Omicron Variant Period Compared with Previous SARS-CoV-2 High Transmission Periods — United States, December 2020–January 2022

Abstract Objective To evaluate the impact of vaccine scale-up on population level covid-19 mortality and incidence in the United States. Design Observational study. Setting US county level case surveillance and vaccine administration data reported from 14 December 2020 to 18 December 2021. Participants Residents of 2558 counties from 48 US states. Main outcome measures The primary outcome was county covid-19 mortality rates (deaths/100 000 population/county week). The secondary outcome was incidence of covid-19 (cases/100 000 population/county week). Incidence rate ratios were used to compare rates across vaccination coverage levels. The impact of a 10% improvement in county vaccination coverage (defined as at least one dose of a covid-19 vaccine among adults ≥18 years of age) was estimated During the eras of alpha and delta variant predominance, the impact of very low (0-9%), low (10-39%), medium (40-69%), and high (≥70%) vaccination coverage levels was compared. Results In total, 30 643 878 cases of covid-19 and 439 682 deaths associated with covid-19 occurred over 132 791 county weeks. A 10% improvement in vaccination coverage was associated with an 8% (95% confidence interval 8% to 9%) reduction in mortality rates and a 7% (6% to 8%) reduction in incidence. Higher vaccination coverage levels were associated with reduced mortality and incidence rates during the eras of alpha and delta variant predominance. Conclusions Higher vaccination coverage was associated with lower rates of population level covid-19 mortality and incidence in the US.

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Public health impact of covid-19 vaccines in the US: observational study

Beginning the week of December 19-25, 2021, the B.1.1.529 (Omicron) variant of SARS-CoV-2 (the virus that causes COVID-19) became the predominant circulating variant in the United States (i.e., accounted for >50% of sequenced isolates).* Information on the impact that booster or additional doses of COVID-19 vaccines have on preventing hospitalizations during Omicron predominance is limited. Data from the COVID-19-Associated Hospitalization Surveillance Network (COVID-NET)† were analyzed to compare COVID-19-associated hospitalization rates among adults aged ≥18 years during B.1.617.2 (Delta; July 1-December 18, 2021) and Omicron (December 19, 2021-January 31, 2022) variant predominance, overall and by race/ethnicity and vaccination status. During the Omicron-predominant period, weekly COVID-19-associated hospitalization rates (hospitalizations per 100,000 adults) peaked at 38.4, compared with 15.5 during Delta predominance. Hospitalizations rates increased among all adults irrespective of vaccination status (unvaccinated, primary series only, or primary series plus a booster or additional dose). Hospitalization rates during peak Omicron circulation (January 2022) among unvaccinated adults remained 12 times the rates among vaccinated adults who received booster or additional doses and four times the rates among adults who received a primary series, but no booster or additional dose. The rate among adults who received a primary series, but no booster or additional dose, was three times the rate among adults who received a booster or additional dose. During the Omicron-predominant period, peak hospitalization rates among non-Hispanic Black (Black) adults were nearly four times the rate of non-Hispanic White (White) adults and was the highest rate observed among any racial and ethnic group during the pandemic. Compared with the Delta-predominant period, the proportion of unvaccinated hospitalized Black adults increased during the Omicron-predominant period. All adults should stay up to date (1) with COVID-19 vaccination to reduce their risk for COVID-19-associated hospitalization. Implementing strategies that result in the equitable receipt of COVID-19 vaccinations, through building vaccine confidence, raising awareness of the benefits of vaccination, and removing barriers to vaccination access among persons with disproportionately higher hospitalizations rates from COVID-19, including Black adults, is an urgent public health priority.

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COVID-19–Associated Hospitalizations Among Adults During SARS-CoV-2 Delta and Omicron Variant Predominance, by Race/Ethnicity and Vaccination Status — COVID-NET, 14 States, July 2021–January 2022

http://www.cell.com/article/S2666634022001386/pdf

Rapid emergence of SARS-CoV-2 Omicron variant is associated with an infection advantage over Delta in vaccinated persons

Previous reports of COVID-19 case, hospitalization, and death rates by vaccination status† indicate that vaccine protection against infection, as well as serious COVID-19 illness for some groups, declined with the emergence of the B.1.617.2 (Delta) variant of SARS-CoV-2, the virus that causes COVID-19, and waning of vaccine-induced immunity (1-4). During August-November 2021, CDC recommended§ additional primary COVID-19 vaccine doses among immunocompromised persons and booster doses among persons aged ≥18 years (5). The SARS-CoV-2 B.1.1.529 (Omicron) variant emerged in the United States during December 2021 (6) and by December 25 accounted for 72% of sequenced lineages (7). To assess the impact of full vaccination with additional and booster doses (booster doses),¶ case and death rates and incidence rate ratios (IRRs) were estimated among unvaccinated and fully vaccinated adults by receipt of booster doses during pre-Delta (April-May 2021), Delta emergence (June 2021), Delta predominance (July-November 2021), and Omicron emergence (December 2021) periods in the United States. During 2021, averaged weekly, age-standardized case IRRs among unvaccinated persons compared with fully vaccinated persons decreased from 13.9 pre-Delta to 8.7 as Delta emerged, and to 5.1 during the period of Delta predominance. During October-November, unvaccinated persons had 13.9 and 53.2 times the risks for infection and COVID-19-associated death, respectively, compared with fully vaccinated persons who received booster doses, and 4.0 and 12.7 times the risks compared with fully vaccinated persons without booster doses. When the Omicron variant emerged during December 2021, case IRRs decreased to 4.9 for fully vaccinated persons with booster doses and 2.8 for those without booster doses, relative to October-November 2021. The highest impact of booster doses against infection and death compared with full vaccination without booster doses was recorded among persons aged 50-64 and ≥65 years. Eligible persons should stay up to date with COVID-19 vaccinations.

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COVID-19 Incidence and Death Rates Among Unvaccinated and Fully Vaccinated Adults with and Without Booster Doses During Periods of Delta and Omicron Variant Emergence — 25 U.S. Jurisdictions, April 4–December 25, 2021

Background: In the midst of the COVID-19 pandemic, there has been an information overload of health data (both accurate and inaccurate) available to the public. With vitamins and supplements being readily accessible, many have turned to using them in an effort to combat the virus. The purpose of this review was to analyse clinical trials regarding vitamins and supplements for the treatment of COVID-19 infections. Methods: Articles were identified through a literature search utilizing online databases and bibliographic review. Results: A total of seven articles were identified for review. All articles evaluated the use of vitamins and supplements for the treatment of COVID-19. Drug therapies included oral vitamin D, intravenous and oral vitamin C, oral vitamin D/magnesium/ vitamin B12, oral zinc, oral combination zinc/ascorbic acid, and intravenous alpha-lipoic acid. The end points of each study varied, including the Sequential Organ Failure Assessment score, mortality, rate of intensive care unit (ICU) admissions, negativity of COVID-19 tests, oxygen requirements, and symptom burden. Conclusion: Of the vitamins and supplements that were studied, vitamin D presented the most promising data demonstrating significant decreases in oxygen requirements, need for ICU treatment, SARS-CoV-2 RNA test positivity, and mortality. All of these benefits were exhibited in hospitalized patients. Other vitamins and supplements that were evaluated in studies did not demonstrate any statistically significant benefits. Common shortcomings of the articles included generally small sample sizes, varying sites of study (which could determine the virus variant), a lack of standard of care as background therapy, and utilization of doses that were higher than standard. , The severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) disease (COVID‑19) pandemic has caused millions of deaths worldwide. Genome‑wide association studies identified the 3p21.31 region as conferring a twofold increased risk of respiratory failure. Here, using a combined multiomics and machine learning approach, we identify the gain‑of‑function risk A allele of an SNP, rs17713054G > A, as a probable causative variant. We show with chromosome conformation capture and gene‑expression analysis that the rs17713054‑affected enhancer upregulates the interacting gene, leucine zipper transcrip‑ tion factor like 1 ( LZTFL1 ). Selective spatial transcriptomic analysis of lung biopsies from patients with COVID‑19 shows the presence of signals associated with epithelial–mesenchymal transition (EMT), a viral response pathway that is regulated by LZTFL1 . We conclude that pulmonary epithelial cells undergoing EMT, rather than immune cells, are likely responsible for the 3p21.31‑associated risk. Since the 3p21.31 effect is conferred by a gain‑of‑function, LZTFL1 may represent a therapeutic target. he COVID-19 pandemic is estimated to have caused over 4.6 million deaths so far 1,2 . The predominant cause of mor- tality is pneumonia and severe acute respiratory distress syndrome 3 . However, Aging, obesity, and diabetes are major risk factors for the severe progression and outcome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (coro-navirus disease 2019 [COVID-19]), but the underlying mechanism is not yet fully understood. In this study, we found that the SARS-CoV-2 spike protein physically inter-acts with cell surface GRP78, which promotes the binding to and accumulation in ACE2-expressing cells. GRP78 was highly expressed in adipose tissue and increased in humans and mice that were older, obese, and had diabetes. The overexpression of GRP78 was attributed to hyperinsulinemia in adipocytes, which was in part mediated by the stress-responsive transcription factor XBP-1s. Management of hyperinsulinemia by pharmacological approaches, including metformin, sodium – glucose cotransporter 2 inhibitor, or b 3-adrenergic receptor agonist, decreased GRP78 gene expression in adipose tissue. Environmental interventions, including exercise, calorie restriction, fasting, or cold expo-sure, reduced the gene expression of GRP78 in adipose tissue. This study provides scienti ﬁ c evidence for the role of GRP78 as a binding partner of the SARS-CoV-2 spike protein and ACE2, which might be related to the severe progression and outcome of COVID-19 in older and obese patients with diabetes. The management of hyperinsulinemia and the related GRP78 expression

Sarah Kangas

Papers

COVID-19 Incidence and Death Rates Among Unvaccinated and Fully Vaccinated Adults with and Without Booster Doses During Periods of Delta and Omicron Variant Emergence — 25 U.S. Jurisdictions, April 4–December 25, 2021

Boosting COVID-19 Vaccine Confidence: An Educational Toolkit for Providers