P. Bastard et al.

Autoantibodies against type I IFNs in patients with life-threatening COVID-19

Science, June 2022; doi: 10.1126/science.abd4585

Abstract

Interindividual clinical variability is vast in humans infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), ranging from silent infection to rapid death. Three risk factors for life-threatening coronavirus disease 2019 (COVID-19) pneumonia have been identified— being male, being elderly, or having other medical conditions—but these risk factors cannot explain why critical disease remains relatively rare in any given epidemiological group. Given the rising toll of the COVID-19 pandemic in terms of morbidity and mortality, understanding the causes and mechanisms of life-threatening COVID-19 is crucial.

P. Bastardet al.

Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Science Immunology, June 2022; doi: 10.1126/sciimmunol.abp8966

Abstract

Life-threatening ‘breakthrough’ cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS-CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals (age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto-Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-α2 and IFN-ω, while two neutralized IFN-ω only. No patient neutralized IFN-β. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population.

Vergara-Alertet al.

An anti-SARS-CoV-2 metabolite is reduced in diabetes

Nature Metabolism, May 2022; doi.org/10.1038/s42255-022-00569-x

Abstract

A glucose-like metabolite, which is reduced in the serum of diabetic patients, inhibits the entry of SARS-CoV-2 into key cellular targets. The work led by Cheng and colleagues provides a molecular explanation for the increased risk of severe COVID-19 in patients with diabetes.

From the very beginning of the SARS-CoV-2 pandemic, patients with diabetes and other comorbidities were shown to be more prone to COVID-19 severe progression, probably due to complex and multifactorial complications of their metabolic disease. Since then, understanding which risk factors increase the severity of COVID-19 in patients with diabetes has become a priority for improving their clinical management.

G. D’Alterioet al.

Germline rare variants of lectin pathway genes predispose to asymptomatic SARS-CoV-2 infection in elderly individuals

Genetics in Medicine, May 2022 ; doi.org//10.1016/j.gim.2022.04.007

Abstract

Purpose

Emerging evidence suggest that infection-dependent hyperactivation of complement system (CS) may worsen COVID-19 outcome. We investigated the role of predicted high impact rare variants — referred as qualifying variants (QVs) — of CS genes in predisposing asymptomatic COVID-19 in elderly individuals, known to be more susceptible to severe disease.

Methods

Exploiting exome sequencing data and 56 CS genes, we performed a gene-based collapsing test between 164 asymptomatic subjects (aged ≥60 years) and 56,885 European individuals from the Genome Aggregation Database. We replicated this test comparing the same asymptomatic individuals with 147 hospitalized patients with COVID-19.

Results

We found an enrichment of QVs in 3 genes (MASP1COLEC11, and COLEC10), which belong to the lectin pathway, in the asymptomatic cohort. Analyses of complement activity in serum showed decreased activity of lectin pathway in asymptomatic individuals with QVs. Finally, we found allelic variants associated with asymptomatic COVID-19 phenotype and with a decreased expression of MASP1COLEC11, and COLEC10 in lung tissue.

Conclusion

This study suggests that genetic rare variants can protect from severe COVID-19 by mitigating the activity of lectin pathway and prothrombin. The genetic data obtained through ES of 786 asymptomatic and 147 hospitalized individuals are publicly available at http://espocovid.ceinge.unina.it/

R. Marfellaet al.

Glycaemic control is associated with SARS-CoV-2 breakthrough infections in accinated patients with type 2 diabetes

Nature Communications, April 2022 ;doi.org/10.1038/s41467-022-30068-2

Abstract

Patients with type 2 diabetes (T2D) are characterized by blunted immune responses, which are affected by glycaemic control. Whether glycaemic control influences the response to COVID-19 vaccines and the incidence of SARS-CoV-2 breakthrough infections is unknown. Here we show that poor glycaemic control, assessed as mean HbA1c in the post-vaccination period, is associated with lower immune responses and an increased incidence of SARS-CoV-2 breakthrough infections in T2D patients vaccinated with mRNA-BNT162b2. We report data from a prospective observational study enroling healthcare and educator workers with T2D receiving the mRNA-BNT162b2 vaccine in Campania (Italy) and followed for one year (5 visits, follow-up 346 ± 49 days) after one full vaccination cycle. Considering the 494 subjects completing the study, patients with good glycaemic control (HbA1c one-year mean < 7%) show a higher virus-neutralizing antibody capacity and a better CD4 + T/cytokine response, compared with those with poor control (HbA1c one-year mean ≥ 7%). The one-year mean of HbA1c is linearly associated with the incidence of breakthrough infections (Beta = 0.068; 95% confidence interval [CI], 0.032-0.103; p < 0.001). The comparison of patients with poor and good glycaemic control through Cox regression also show an increased risk for patients with poor control (adjusted hazard ratio [HR], 0.261; 95% CI, 0.097-0.700; p = 0.008). Among other factors, only smoking (HR = 0.290, CI 0.146-0.576 for non-smokers; p < 0.001) and sex (HR = 0.105, CI 0.035-0.317 for females; p < 0.001) are significantly associated with the incidence of breakthrough infections.

Shoaib N et al.

Mol Biol Rep.

Factors associated with cycle threshold values (Ct-values) of SARS-CoV2-rRT-PCR

Mol Biol Rep., https://link.springer.com/content/pdf/10.1007/s11033-022-07360-x.pdf

CONTENUTO E COMMENTO : In questo studio condotto su 6331 individui vengono posti in relazione severità dei sintomi, fattori demografici e storia clinica con i valori di cicli soglia di rRT-PCR (sia per gene Orf1ab, che per N e RdRp). Non è stata riscontrata correlazione fra valore di cicli soglia e età, sesso o storia clinica del paziente. E’ stata riscontrata solo una debole correlazione fra valore di cicli soglia dei geni Orf1ab e N e la presenza di sintomi al momento del test molecolare, ma non è stata riscontrata una correlazione con la severità dei sintomi. Gli autori dello studio concludono che il valore di cicli soglia potrebbe essere poco utile nel predire la severità della COVID-19 e pertanto dovrebbe essere riportato con cautela nei referti.

 Mentre alcuni lavori sembrano suggerire come il valore di cicli soglia possa essere di una certa utilità a scopo diagnostico (ad esempio per differenziare una pregressa infezione da una infezione attiva), probabilmente, anche alla luce di questo lavoro, è di scarsa utilità nella definizione prognostica della COVID-19.

Veyrenche N. et al.

SARS-CoV-2 nucleocapsid urine antigen in hospitalized patients with Covid-19

J Infect Dis., https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8903449/pdf/jiac073.pdf

CONTENUTO E COMMENTO: In questo studio viene valutata la capacità diagnostica di un test per la ricerca dell’antigene nucleocapsidico di SARS-CoV-2 su urine e su sangue e la sua relazione con la severità della malattia. Sono stati testati 82 pazienti ospedalizzati con infezione da SARS-CoV-2 provata tramite test molecolare. E’ stato osservato che nella prima e nella seconda settimana della COVID-19 il test antigenico su urine è risultato positivo rispettivamente nell’81.25% e nel 71.79%, mentre quello su sangue rispettivamente nel 93.75% e nel 94.87%. Elevati livelli di antigene urinario sono stati direttamente correlati all’assenza di anticorpi anti-nucleocapside, ammissione in terapia intensiva, elevati livelli di proteina C reattiva, linfopenia, eosinopenia e elevati livelli di latticodeidrogenasi. Il test su urine si è rivelato più accurato di quello su sangue nel predire la severità della malattia.

I risultati di questo studio rendono questo test per la rilevazione dell’antigene nucleocapsidico urinario estremamente interessante : da un lato infatti potrebbe rappresentare una metodica non invasiva, con buona sensibilità, per la diagnosi dell’infezione, dall’altra, in virtù della sua relazione con la severità della malattia, potrebbe rappresentare un utile elemento per la stratificazione prognostica dei pazienti.

Gretel Sanabria Diaz et al.

Brain cortical changes are related to inflammatory biomarkers in hospitalized SARS-CoV-2 patients with neurological symptoms

Medrxiv.org, https://www.medrxiv.org/content/10.1101/2022.02.13.22270662v1.full.pdf

CONTENUTO E COMMENTO: Studio prospettico multicentrico condotto su 33 pazienti con lo scopo di valutare le alterazioni corticali cerebrali in pazienti affetti da Sars-CoV2 ricoverati e con sintomi neurologici. Sono state evidenziate alterazioni della corteccia orbitofrontale, cingolata e temporale con associate alterazioni liquorali (aumento delle proteine e del rapporto fra proteine liquorali e sieriche), suggerendo che l'infiammazione innescata dal virus provochi danni neurotossici in alcune aree corticali.

Choteau M et al.

Development of SARS-CoV-2 humoral response including neutralizing antibodies is not sufficient to protect patients against fatal infection

Sci Rep., https://www.nature.com/articles/s41598-022-06038-5.pdf

CONTENUTO E COMMENTO : In questo studio condotto su 187 individui affetti da infezione da SARS-CoV-2 in differenti fasi della malattia (asintomatici, malattia lieve, severa, pazienti deceduti per COVID-19 e soggetti guariti dall’infezione) mira a valutare la risposta anticorpale sviluppata da tali individui nei confronti del virus. E’ stato utilizzato un test ELISA “in-house” per misurare il titolo delle IgG, IgM e IgA dirette contro le regioni RBD e N del virus e per analizzare il potere neutralizzante del siero. Sono stati riscontrati titoli di anticorpi più elevati nei pazienti con malattia severa, inclusi pazienti deceduti per COVID-19, rispetto ai pazienti asintomatici o con malattia lieve. Inoltre, la maggior parte dei pazienti guariti dall’infezione virale sembrano continuare a produrre IgG anti-SARS-CoV-2 per oltre 3 mesi dopo l’infezione.

La risposta immunitaria nei confronti del virus SARS-CoV-2 è sicuramente estremamente complessa: non è ancora chiaro il ruolo della risposta umorale nella prevenzione dell’infezione o nella modulazione della severità della malattia. Tale studio sembrerebbe comunque smentire l’ipotesi secondo cui nelle forme severe e fatali della malattia esisterebbe un deficit della risposta umorale, dal momento che chi ha forme più severe della malattia sembrerebbe avere addirittura dei titoli anticorpali più elevati, ma sono necessari ulteriori studi per dimostrarlo.

The Severe Covid-19 GWAS Group

Genomewide Association Study of Severe Covid-19 with Respiratory Failure

NEJM, https://www.nejm.org/doi/full/10.1056/NEJMoa2020283

CONTENUTO E COMMENTO : Studio genome-wide (GWAS) su 1980 pazienti con COVID-19, in cui si osserva che un cluster di geni del locus  3p21.31 fra cui quelli determinanti il gruppo sanguigno A sono associati a maggiore gravità di malattia.

Mastboim NS et al

An immune-protein signature combining TRAIL, IP-10 and CRP for accurate prediction of severe COVID-19 outcome

MedRXiv, https://www.semanticscholar.org/paper/An-immune-protein-signature-combining-TRAIL%2C-IP-10-Mastboim-Angel/f5d96efc49e00537794f9e729c8b6f683df4d86b

CONTENUTO E COMMENTO : Creazione di uno score predittivo di outcome avverso (ricovero in Rianimazione, ventilazione meccanica o decesso) per pazienti con COVID-19, a partire dai dati di 394 adulti ricoverati in diversi centri in Israele, Germania e Stati Uniti.

Meyer H et al

Computed tomography-defined body composition as prognostic markers for unfavourable outcomes and in-hospital mortality in coronavirus disease 2019

J Cachexia Sarcopenia Muscle, https://doi.org/10.1002/jcsm.12868

CONTENUTO E COMMENTO : Osservazione di una associazione fra ridotta massa muscolare/elevata massa adiposa viscerale, stimate tramite tomografia computerizzata, e outcome dell’infezione da SARS-CoV-2 : la possibilità di prédire quali pazienti avranno un outcome peggiore è molto utile per una allocazione razionale delle risorse.

Fonseca W et al

COVID-19 Modulates Inflammatory and Renal Markers That May Predict Hospital Outcomes among African American Males

Viruses, https://www.mdpi.com/1999-4915/13/12/2415/htm

CONTENUTO: Studio retrospettivo monocentrico su 56 pazienti maschi afro-americani con più di 50 anni ospedalizzati con COVID 19 confrontati con un gruppo di controllo, con l’obiettivo di valutare la risposta immunitaria e i markers di danno renale. Gli autori hanno osservato una risposta immunitaria nei maschi afro-americani qualitativamente simile a quella riportata in altre popolazioni in letteratura, suggerendo che le differenze di outcome clinico rispetto ad altre popolazioni possano dipendere principalmente da fattori non immunologici.

COMMENTO: Questo studio condotto in afro-americani maschi di oltre 50 anni evidenzia una risposta immunitaria simile a quella riportata per altri gruppi etnici il che suggerisce la necessità di ricercare in altri ambiti (non immunologici) le differenze di tipo prognostico osservate.

Nilles EJ et al

Epidemiological and Immunological Features of Obesity and SARS-CoV-2

Viruses, https://www.mdpi.com/1999-4915/13/11/2235/htm

CONTENUTO: Studio prospettico di coorte con l’obiettivo di valutare se l’obesità influenzi il rischio di infezione da SARS-CoV-2, la tipologia dei sintomi clinici e la risposta immunitaria al virus. I risultati indicano che la sintomatologia, ovvero il numero di sintomi riferiti, è fortemente influenzata dall’obesità nei pazienti giovani ma non nei più anziani. Non è stata invece dimostrata alcuna correlazione tra obesità e rischio di infezione da SARS-CoV-2 e, soprattutto, l’attivazione del sistema immunitario si è dimostrata sostanzialmente la stessa nelle varie categorie di BMI, suggerendo uno stato simile di immunoprotezione tra questi gruppi.

COMMENTO: L’obesità fin da subito è risultata un fattore che influenza negativamente l’infezione da SARS-CoV-2 sia in termini di sintomi che di gravità clinica. Questo studio, indica che la sintomatologia valutata in numero di sintomi riferiti è maggiormente influenzata dalla presenza di obesità nei pazienti più giovani ma non in quelli più anziani. E’ significativa l’osservazione che la presenza di obesità non si correla al rischio di infettarsi con SARS-CoV-2 e che l’attivazione del sistema immunitario è sostanzialmente la stessa dei soggetti non obesi. 

https://bmjopen.bmj.com/content/bmjopen/11/10/e052777.full.pdf

Mahamat-Saleh, Y. et al.

Diabetes, hypertension, body mass index, smoking and COVID-19-related mortality: a systematic review and meta-analysis of observational studies

BMC, https://bmjopen.bmj.com/content/bmjopen/11/10/e052777.full.pdf

CONTENUTO E COMMENTO: Review sistematica e metanalisi su alcuni fattori di rischio per COVID-19.Una revisione della letteratura molto interessante e ben fatta su alcuni fattori di rischio per Covid. Come diabete, ipertensione, fumo di sigaretta etc.

Kim L et al.

Clinical Infectious Diseases

Risk Factors for Intensive Care Unit Admission and In-hospital Mortality Among Hospitalized Adults Identified through the US Coronavirus Disease 2019 (COVID-19)-Associated Hospitalization Surveillance Network (COVID-NET)

Clinical Infectious Diseases, https://academic.oup.com/cid/article/72/9/e206/5872581?searchresult=1

CONTENUTO : Studio retrospettivo coinvolgente 2491 pazienti COVID ricoverati tra marzo e maggio 2020 in 154 ospedali statunitensi. All’analisi dei dati, è risultato che i pazienti con aumentato rischio di mortalità presentavano le seguenti caratteristiche: età superiore a 50 anni, sesso maschile, obesità, immunosoppressione, diabete mellito, insufficienza renale, malattia polmonare cronica, malattia cardiovascolare o neurologica.

COMMENTO: L’età superiore a 50 anni si conferma come il maggiore fattore di rischio per ricovero in ICU e mortalità. I più rilevanti altri fattori di rischio indipendenti per mortalità associata a COVID-19, sono rappresentati dalla presenza di co-morbidità croniche renali, polmonari, cardiovascolari e neurologiche. Lo studio in sostanza conferma quanto già noto e ulteriormente precisando, in un’ampia casistica retrospettiva, il ruolo di vari fattori di rischio prognostici per malattia grave COVID-19 documentati nella prima ondata epidemica fra marzo e maggio 2020.

Chavez-MacGregor M et al

Evaluation of COVID-19 Mortality and Adverse Outcomes in US Patients With or Without Cancer

JAMA Oncology, https://jamanetwork.com/journals/jamaoncology/fullarticle/2785677

CONTENUTO : Studio di coorte su più di 500.000 pazienti con diagnosi di COVID-19 negli Stati Uniti con l’obiettivo di confrontare l’outcome di pazienti con o senza cancro e di identificare i fattori associati a mortalità, ventilazione meccanica, ricovero in terapia intensiva e ospedalizzazione. All’analisi multivariata, i pazienti con cancro che non avevano ricevuto nessun trattamento radioterapico o chemioterapico recente (negli ultimi 30 giorni) hanno presentato outcome clinici simili o addirittura migliori dei pazienti senza neoplasia. Al contrario, nei pazienti con cancro che avevano recentemente ricevuto un trattamento, è stato osservato un rischio più alto di mortalità e di ospedalizzazione. Inoltre i pazienti con neoplasie ematologiche maligne e tumori solidi metastatici presentavano outcome clinici peggiori dei pazienti con tumori solidi non metastatici.

COMMENTO: Fin dagli inizi della pandemia ci si è posti la domanda di quanto le co-morbidità influenzassero la prognosi di COVID-19. Questo importante studio condotto negli USA in oltre 500.000 pazienti oncologici, indica che il trattamento chemioterapico può influenzare in senso negativo la prognosi probabilmente perché riduce le difese immunitarie naturali ed acquisite. Se queste non sono alterate come nei pazienti oncologici non trattati, non si osserva questa situazione.

Mizrahi B et al.

Results of an early second PCR test performed on SARS-CoV-2 positive patients may support risk assessment for severe COVID-19

Sci Rep. , https://www.nature.com/articles/s41598-021-99671-5.pdf

CONTENUTO : Studio retrospettivo su 1683 pazienti che mira a valutare l’associazione fra il risultato di un secondo esame molecolare (effettuato entro 2-7 giorni dopo il primo esame molecolare risultato positivo) e la severità dell’outcome clinico. Gli autori concludono che un secondo esame molecolare con esito negativo, effettuato precocemente dopo il primo risultato positivo, possa associarsi a un minor rischio di deterioramento clinico.

COMMENTO: Lo studio suggerisce una nuova applicazione del cosiddetto tampone molecolare.  Al momento esso viene utilizzato sostanzialmente per rilevare l’infezione da SARS-CoV-2 e indirizzare quindi la prosecuzione delle indagini cliniche di routine oltre che le misure di contenimento. Gli autori suggeriscono che la ripetizione del tampone entro 2-7 gg dal tampone iniziale può rappresentare uno strumento complementare per la valutazione del rischio di progressione. In effetti la persistenza della positività nel secondo tampone sembra essere predittiva del peggioramento della situazione clinica. Anche se l’interpretazione della persistenza del virus nelle alte vie respiratorie richiede ulteriori approfondimenti, tale procedura, se confermata, potrebbe facilmente essere adottata nei soggetti ospedalizzati in modo da dedicare preventivamente maggiore attenzione ai pazienti caratterizzati da un decorso grave della malattia.

Vishal PS, et al.

Association Between SARS-CoV-2 Cycle Threshold Values and Clinical Outcomes in Patients With COVID-19: A Systematic Review and Meta-analysis

Open Forum in Infect Dis ,https://academic.oup.com/ofid/article/8/9/ofab453/6360381                                            

CONTENUTO: Il numero di cicli di replicazione rappresenta un surrogato della “carica virale” rilevato nel contesto di un tampone naso-faringeo molecolare per la ricerca di SARS-CoV2. In questa metanalisi, i pazienti con un numero di cicli <25, quindi con più alta carica virale, hanno dimostrato un rischio significativamente aumentato di manifestare forme di malattia più severa, nonché una più elevata mortalità rispetto ai pazienti con numero di cicli di replicazione maggiori.

COMMENTO: In questo studio vengono individuati due cut-off di significato prognostico: CT <25, che comporta un rischio significativamente maggiore di malattia grave e di mortalità rispetto a un CT >30. Esiste una “zona grigia” fra questi valori in cui il rischio non è ben definibile. Comunque gli Autori sottolineano come il significato degli stessi valori di CT vadano interpretati con cautela nei loro riflessi sul piano clinico.

Mendez R et al

Acute and sustained increase in endothelial biomarkers in COVID-19

Thorax, https://thorax.bmj.com/content/early/2021/10/03/thoraxjnl-2020-216797

CONTENUTO : Studio longitudinale prospettico su pazienti con COVID-19 con l’obiettivo di valutare l’associazione tra danno endoteliale (misurato attraverso la proadrenomedullina –proADM-  e la proendotelina, due biomarkers surrogati sistemici di danno endoteliale) ed outcome clinico. Alti livelli di proADM e/o proendotelina al baseline sono risultati associati ad un aumentato rischio di mortalità intra-ospedaliera e ad un più alto rischio di malattia grave e di ricovero in terapia intensiva. La persistenza di alti livelli di questi biomarcatori dopo la dimissione risultava invece associata ad una ridotta capacità di diffusione alveolo-capillare (DLCO).

COMMENTO: Il danno endoteliale gioca un ruolo rilevante nella patogenesi della malattia COVID-19. Vi sono già diversi studi che si sono ficalizzati su alterazioni dell’endotelio e la malattia. Questo studio indica che due diversi marcatori del danno endoteliale possono indicare una malattia più grave ed un rischio di morte maggiore. Inoltre quando questi risultano elevati, testimoniano di un difetto degli scambi gas sangue a livello del polmone. Le autopsie, specie condotte nel caso della prima ondata, hanno indicato la presenza di lesioni riconducibili al danno endoteliale ed hanno sottolineato l’importanza di somministrare anti-infiammatori ed anticoagulanti per migliorare la prognosi.

Espejo-Paeres C et al

Predictors of poor prognosis in healthy, young, individuals with SARS-CoV-2 infections

Clinical Microbiology and Infection, https://www.clinicalmicrobiologyandinfection.com/action/showPdf?pii=S1198-743X%2821%2900545-0

CONTENUTO: Studio retrospettivo di coorte su 773 pazienti giovani (<65 anni) senza comorbidità ricoverati per COVID-19. È stata osservata una mortalità del 3,6% ed un raggiungimento dell’outcome clinico composito (che includeva eventi clinici avversi maggiori quali mortalità, ventilazione meccanica, terapia con ossigeno ad alti flussi, pronazione, sepsi, SIRS ed eventi embolici) nel 29% dei pazienti, una percentuale sorprendentemente alta considerando le caratteristiche cliniche di base. La presenza di compromissione respiratoria al momento del ricovero ed il genere maschile risultano essere gli unici fattori predittivi di prognosi sfavorevole in pazienti giovani e senza comorbidità ricoverati per COVID-19.

COMMENTO: E’ ben noto che le persone >65 anni hanno un rischio maggiore di soffrire di forme gravi anche mortali. Questo studio condotto in oltre 700 soggetti sani, giovani, senza malattie sottostanti, cerca di chiarire i fattori prognostici negativi in questa popolazione. Interessante osservare che la mortalità è comunque significativa (3,6%) e che anche gli altri parametri che definiscono una forma grave, si osservavano in una percentuale sorprendentemente alta. I maschi erano più frequentemente associati a queste forme gravi. Si può concludere che non esistono fasce di età o condizioni cliniche dibasebuone, che si possono considerare indenni da forme gravi di COVID-19. Da qui la necessità di vaccinare il più possibile tutti.

Papamanoli A et al

Association of Serum Ferritin Levels and Methylprednisolone Treatment With Outcomes in Nonintubated Patients With Severe COVID-19 Pneumonia

JAMA, https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2784632

CONTENUTO : Studio retrospettivo monocentrico di coorte su pazienti ospedalizzati con COVID-19 grave in ossigeno-terapia ad alti flussi (FiO2 >50%) non intubati, con l’obiettivo di esaminare l’associazione tra livelli di ferritina sierica (marker infiammatorio di fase acuta) ed efficacia del trattamento con metilprednisolone in termini di mortalità (outcome primario) e di mortalità o necessità di ventilazione meccanica a 28 giorni (outcome composito secondario). Il metilprednisolone si è dimostrato essere associato a migliori outcome clinici soltanto nel gruppo di pazienti con livelli di ferritina nel terzile più alto (1322-13 418 ng/mL).

COMMENTO: Nell’interessante tentativo di identificare un biomarcatore predittivo di risposta al trattamento, i ricercatori di un centro universitario newyorkese hanno effettuato la revisione sistematica delle cartelle cliniche dei loro pazienti associando la terapia con metilprednisolone ad un vantaggio clinico anche in termini di sopravvivenza nei soggetti adulti affetti da polmonite grave da SARS-CoV-2 non sottoposti a intubazione orotracheale ma solo in coloro che presentavano i livelli più elevati di ferritina sierica.

In questi termini, la ferritina rappresenta un candidato interessante in quanto è già utilizzata come biomarcatore in alcune patologie infiammatorie. Infatti, essa viene rilasciata in grandi quantità dal fegato in diverse infezioni allo scopo di ridurre la biodisponibilità di ferro, metallo essenziale per la crescita e lo sviluppo di molti microrganismi patogeni (plausibilità biologica).

Purtroppo, poiché in questo studio nessuno dei pazienti della coorte riceveva desametasone, non è possibile concludere formalmente che vi sia la stessa associazione tra gli elevati livelli di ferritina sierica e la risposta clinica anche per questo farmaco che è attualmente lo standard di cura. Tuttavia, è noto come, anche per desametasone, il massimo beneficio si riscontri in pazienti che necessitano di supporto d’ossigeno, una condizione in cui lo stato di iper-infiammazione dei pazienti è maggiore.

Lo stato di iper-infiammazione viene identificato in base ai valori di ferritina sierica (≥900 ng/ml) ma anche in accordo ai valori anormali di lattato deidrogenasi, PCR (≥100 mg/L), IL-6 (≥40 pg/ml) e XDP (>20 mcg/ml). Sarà quindi interessante valutare la predittività dei valori di ferritina in confronto a quella di altri bio-marcatori, da soli o in associazione tra loro.

In effetti, la ricerca di nuovi biomarcatori e score prognostici e predittivi della risposta terapeutica è di sicuro interesse. In tal senso, sebbene l’analisi sia stata condotta utilizzando una metodologia statistica appropriata nell’intento di minimizzare eventuali distorsioni nei risultati (propensity score, inverse probability of treatment weights), lo studio rimane retrospettivo e basato su un numero limitato di pazienti.

Nello studio in oggetto, l’impatto del biomarcatore di interesse si è riscontrato nei pazienti più gravi in cui il numero di eventi (morte/ricorso a ventilazione meccanica) è un rischio maggiore e, quindi, la significatività statistica si può raggiungere con un più ridotto numero di pazienti in studio. Non è tuttavia da escludere come, aumentando il numero di pazienti con livelli di biomarcatore meno elevati, anche tra quest’ultimi si possa individuare un sottogruppo di pazienti in cui risulti evidente l’impatto clinico dello steroide grazie a un aumento del power dello studio. Peraltro, grazie a un incremento della numerosità casistica si potrà validare il reale cut-off di ferritina sierica associato ad un significativo beneficio clinico (nello studio in oggetto la stratificazione dei livelli del parametro è attuata in base alla sua distribuzione in terzili e questo rappresenta una mera convenzione statistica).

In conclusione, studi di più ampie dimensioni potranno meglio chiarire la natura e la forza della associazione tra impiego degli steroidi e outcome terapeutico in tutte le categorie di pazienti stratificati per gravità in base alla clinica e/o a uno o più marcatori -inclusa ferritina sierica- (eventualmente combinati in score compositi) per una terapia di COVID-19 sempre più “di precisione”.

Daix T et al

Journal of Intensive Care

Immature granulocytes can help the diagnosis of pulmonary bacterial infections in patients with severe COVID-19 pneumonia

Journal of Intensive Care, https://jintensivecare.biomedcentral.com/track/pdf/10.1186/s40560-021-00575-3.pdf

COMMENTO E CONTENUTO : Studio osservazionale prospettico su una piccola popolazione di 19 persone sottoposte a ventilazione meccanica per insufficienza respiratoria da COVID-19, di cui 7 hanno sviluppato, come complicanza delle cure intensive, anche una polmonite batterica. Viene studiata in questi pazienti una popolazione di globuli bianchi, i granulociti immaturi, identificandone un valore soglia che consente di riconoscere chi sviluppa la polmonite batterica.

Perez-Garcia F et al

Age-Adjusted Endothelial Activation and Stress Index for Coronavirus Disease 2019 at Admission Is a Reliable Predictor for 28-Day Mortality in Hospitalized Patients With Coronavirus Disease 2019

Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2021.736028/full

CONTENUTO : Studio retrospettivo su pazienti affetti da COVID-19, con l’obiettivo di valutare l’efficacia predittiva in termini di mortalità dell’ Endothelial Activation and Stress Index (EASIX), un indice già utilizzato come predittore di mortalità nei pazienti trapiantati di midollo osseo che sviluppano danno endoteliale, e dell’EASIX-COVID (stesso indice corretto per età). Entrambi gli indici sono risultati significativamente associati alla mortalità a 28 giorni nei pazienti ricoverati con COVID-19, anche se l’EASIX-COVID ha mostrato un miglior valore predittivo negativo, ovvero una migliore capacità di individuare i pazienti che non andranno incontro all’evento morte. L’EASIX-COVID potrebbe pertanto risultare di utilità nella gestione dei pazienti con COVID-19.

COMMENTO: questo studio che valutaEASIX applicato a COVID-19, così come altri studi che utilizzano metodologie diverse, hanno l’obiettivo di identificare parametri sicuri che indicano il rischio di sviluppare forme gravi in soggetti osservati precocemente. Oggi l’affidabilità di questi metodi riveste ancor più valore poiché esistono gli anticorpi monoclonali e sempre più esisteranno farmaci (antivirali) in grado di favorevolmente influenzare la prognosi.

Sulaiman I et al

Microbial signatures in the lower airways of mechanically ventilated COVID-19 patients associated with poor clinical outcome

Nature Microbiology, https://www.nature.com/articles/s41564-021-00961-5

CONTENUTO: Studio osservazionale prospettico su una coorte di 589 adulti trattati con ventilazione meccanica per COVID-19, di cui 142 sottoposti a broncoscopia : associazione della mortalità con una alta carica di SARS-CoV-2 nel BAL, una ridotta risposta anticorpale contro SARS-CoV-2 e un trascrittoma mostrante down-regolazione di meccanismi antinfiammatori e pro-apoptotici; non si dimostra invece una associazione con l’isolamento da BAL di patogeni nosocomiali. 

COMMENTO: Lo studio tende a chiarire il ruolo delle infezioni polmonari secondarie in pazienti COVID 19 ventilati meccanicamente. Interessante il rilievo nei 142 pazienti sui 589 studiati e sottoposti a prelievo di materiale broncoscopico, di una downregolazione dei meccanismi antiinfiammatori  e apoptotici. Lo studio conclude dando priorità alla replicazione virale e al potenziamento della risposta dell’ospite, negando un ruolo determinate delle infezioni secondarie respiratoprie in termini di mortalità.

Ren-qi Y et al

Development of septic shock and prognostic assessment in critically ill patients with coronavirus disease outside Wuhan, China

World Journal of Emergency Medicine, https://www.proquest.com/openview/59832b56913f5ce23d94c1349c11436f/1?pq-origsite=gscholar&cbl=2050688

CONTENUTO: Su 35 pazienti ricoverati in Rianimazione all’inizio della pandemia di COVID-19 (gennaio-febbraio 2020) in Cina, oltre un quarto ha presentato shock settico con prognosi peggiore in termini di disfuzione d’organo e mortalità rispetto agli altri.

COMMENTO: Lo studio pone l’accento su come anche il COVID 19 possa esitare nelllo shock settico che è uno dei quadri più pericoloso e devastante nei pazienti ricoverati in terapia intensiva. Il campione è limitato ma il segnale in parte confermato da altri studi internazionali è forte e preoccupante.

Reiterer M et al

Hyperglycemia in Acute COVID-19 is Characterized by Insulin Resistance and Adipose Tissue Infectivity by SARS-CoV-2

Cell Metabolism, https://www.cell.com/action/showPdf?pii=S1550-4131%2821%2900428-9

CONTENUTO: In questo studio retrospettivo su 3854 pazienti ricoverati con diagnosi di COVID-19, di cui 823 con ARDS, gli autori dimostrano una forte correlazione tra iperglicemia e rischio di ARDS, rischio di mortalità e aumento di durata di degenza. I pazienti con ARDS e COVID-19 vengono poi confrontati con 4748 pazienti negativi per COVID-19 e ricoverati in ICU, di cui 3558 senza ARDS e 1190 con ARDS. La prevalenza di iperglicemia è simile nei due gruppi di pazienti con ARDS, indipendentemente dalla diagnosi di COVID-19. Tuttavia nei pazienti con ARDS e COVID-19 il principale meccanismo alla base dell’iperglicemia è rappresentato dall’insulino-resistenza e sembra essere indipendente dal concomitante trattamento con glucocorticoidi, mentre nei pazienti con ARDS ma senza COVID-19 il meccanismo prevalente sembra essere l’insufficienza delle cellule beta-pancreatiche. Questi dati suggeriscono che l’infezione da SARS-CoV-2 possa essere alla base di una disfunzione del tessuto adiposo che è causa di insulino-resistenza e iperglicemia, da cui potrebbe derivare un potenziale beneficio nell’utilizzo di farmaci insulino-sensibilizzanti, come la metformina, nel trattamento dell’iperglicemia nei pazienti con COVID-19 grave. 

COMMENTO: L’iperglicemia rappresenta un marker di gravità presente sia nell’ARDS correlata a COVID-19 che in quella non correlata. Va sottolineato che questo studio retrospettivo (elemento questo da non trascurare) condotto su una non piccola casistica, indica in maniera chiara che la patogenesi dell’iperglicemia differisce in queste due forme morbose. Per ARDS+Sars-CoV-2 l’iperglicemia è conseguenza dell’insulino-resistenza (e non del trattamento steroideo che determina l’insufficienza delle cellule beta pancreatiche) e potrebbe coinvolgere la disfunzione del tessuto adiposo. Questo ruolo del tessuto  adiposo potrebbe spiegare come l’obesità sia un fattore di rischio per forme gravi/morte dei pazienti con COVID-19. Interessante, ma tutta da dimostrare, l’eventuale ruolo terapeutico di metformina.

Bailly L et al

Obesity, diabetes, hypertension and severe outcomes among inpatients with COVID-19: a nationwide study

Clinical Microbiology and Infection, https://www.clinicalmicrobiologyandinfection.com/action/showPdf?pii=S1198-743X%2821%2900503-6

CONTENUTO: Studio retrospettivo di coorte condotto in Francia durante la prima ondata epidemica (febbraio-settembre 2020) su 134.209 pazienti adulti affetti da COVID-19, con l’obiettivo di studiare l’associazione tra comorbidità (in particolare obesità, diabete ed ipertensione arteriosa) e morte o necessità di ventilazione meccanica invasiva (IMV), tenendo in considerazione età, genere e Charlson’s comorbidity index score. Gli autori dimostrano un maggior rischio di mortalità nei pazienti con obesità e diabete, ed un maggior rischio di IMV nei pazienti con obesità, diabete ed ipertensione. Questi gruppi di pazienti dovrebbero ricevere un attento monitoraggio clinico qualora affetti da COVID-19 ed essere inclusi nelle categorie ad alta priorità in corso di campagna vaccinale.

COMMENTO: Questo studio retrospettivo francese di coorte condotto su una molto ampia casistica, dimostra che giocano un ruolo rilevante i fattori di rischio: obesità, diabete per la mortalità e obesità , diabete e ipertensione per la necessità di ventilazione meccanica. Il dato, ancorchè ottenuto su una vasta casistica, non è nuovo, anche se permette una volta di più di ribadire la necessità di vaccinare questi soggetti e, nel caso, di considerarli prioritari per la 3° dose.

Jones A et al

External validation of the 4C mortality score among COVID‑19 patients admitted to hospital in Ontario, Canada: a retrospective study

Scientifc Reports, https://www.nature.com/articles/s41598-021-97332-1.pdf

CONTENUTO : Studio di validazione esterna del 4C mortality score, originariamente sviluppato in Gran Bretagna, su una popolazione di 959 pazienti ricoverati per COVID-19 in Canada. Il 4C score include età, sesso, comorbidità, frequenza respiratoria, saturazione periferica di ossigeno, GCS, azotemia e proteina-C-reattiva. Con una AUC di 0.77 (95% IC 0.79-0.87), il 4C score risulta essere un valido strumento prognostico di mortalità da COVID-19 negli ospedali canadesi, e potrebbe essere utilizzato per dare priorità di cura ai pazienti a maggior rischio di exitus.

COMMENTO: Questo studio, come altri che utilizzano diverse metodologie basate sul punteggio (score) derivato da diversi parametri clinici e di laboratorio, ha come obiettivo quello di fornire un mezzo semplice (dal momento che  valuta parametri comuni) al fine di precocemente identificare i soggetti che più facilmente potrebbero necessitare di interventi il più precoci possibili (es. anticorpi monoclonali specifici) per significativamente ridurre il rischio forme gravi/ morte.

Recalde M et al

Body mass index and risk of COVID-19 diagnosis, hospitalisation, and death: a cohort study of 2 524 926 Catalans

Journal of Clinical Endocrinology and Metabolism, July 2021; doi.org/10.1210/clinem/dgab546

COMMENTO : Context : A comprehensive understanding of the association between body mass index (BMI) and COVID-19 is still lacking.

Objective : To investigate associations between BMI and risk of COVID-19 diagnosis, hospitalisation with COVID-19, and death after a COVID-19 diagnosis or hospitalisation (subsequent death), accounting for potential effect modification by age and sex.

Design : Population-based cohort study.

Setting : Primary care records covering >80% of the Catalan population, linked to region-wide testing, hospital, and mortality records from March to May 2020.

Participants : Adults (≥18 years) with at least one measurement of weight and height.

Main outcome measures : Hazard ratios (HR) for each outcome.

Results : We included 2 524 926 participants. After 67 days of follow-up, 57 443 individuals were diagnosed with COVID-19, 10 862 were hospitalised with COVID-19, and 2467 had a subsequent death. BMI was positively associated with being diagnosed and hospitalised with COVID-19. Compared to a BMI of 22kg/m 2, the HR (95%CI) of a BMI of 31kg/m 2 was 1.22 (1.19-1.24) for diagnosis, and 1.88 (1.75-2.03) and 2.01 (1.86-2.18) for hospitalisation without and with a prior outpatient diagnosis, respectively. The association between BMI and subsequent death was J-shaped, with a modestly higher risk of death among individuals with BMIs ≤19kg/m 2 and a more pronounced increasing risk for BMIs ≥40kg/m 2. The increase in risk for COVID-19 outcomes was particularly pronounced among younger patients.

Conclusions : There is a monotonic association between BMI and COVID-19 diagnosis and hospitalisation risks, but a J-shaped one with mortality. More research is needed to unravel the mechanisms underlying these relationships.

Harrison SL et al

Cardiovascular risk factors, cardiovascular disease, and COVID-19: an umbrella review of systematic reviews

European Heart Journal, July 2021;   DOI: 10.1093/ehjqcco/qcab029

COMMENTO: Aims To consolidate evidence to determine (i) the association  between cardiovascular risk factors and health outcomes with coronavirus 2019 (COVID-19); and (ii) the impact of COVID-19 on cardiovascular health.

Methods and results An umbrella review of systematic reviews was conducted. Fourteen medical databases and pre-print servers were searched from 1 January 2020 to 5 November 2020. The review focused on reviews rated as moderate or high- quality using the AMSTAR 2 tool. Eighty-four reviews were identified; 31 reviews were assessed as moderate quality and one was high-quality. The following risk factors were associated with higher mortality and severe COVID-19: renal disease [odds ratio (OR) (95% confidence interval) for mortality 3.07 (2.43–3.88)], diabetes mellitus [OR 2.09 (1.80–2.42)], hypertension [OR 2.50 (2.02–3.11)], smoking history [risk ratio (RR) 1.26 (1.20–1.32)],cerebrovascular dise ase [RR 2.75 (1.54–4.89)], and cardiovascular disease [OR 2.65 (1.86–3.78)]. Liver disease was associated with higher odds of mortality [OR 2.81 (1.31–6.01)], but not severe COVID-19. Current smoking was associated with a higher risk of severe COVID-19 [RR 1.80 (1.14–2.85)], but not mortality. Obesity associated with higher odds of mortality [OR 2.18 (1.10–4.34)], but there was an absence of evidence for severe COVID-19. In patients hospitalized with COVID-19, the following incident cardiovascular complications were identified: acute heart failure (2%), myocardial infarction (4%), deep vein thrombosis (7%), myocardial injury (10%), angina (10%),

arrhythmias (18%), pulmonary embolism (19%), and venous thromboembolism (25%).

Conclusion Many of the risk factors identified as associated with adverse outcomes with COVID-19 are potentially modifiable.

Primary and secondary prevention strategies that target cardiovascular risk factors may improve outcomes for people following COVID-19.

Lim ZJ et al

A Systematic Review of the Incidence and Outcomes of In-Hospital Cardiac Arrests in Patients With Coronavirus Disease 2019

Critical Care Medicine, March 2021 ; DOI: 10.1097/CCM.0000000000004950

COMMENTO : OBJECTIVES: To investigate the incidence, characteristics, and outcomes of in-hospital cardiac arrest in patients with coronavirus disease 2019 and to describe the characteristics and outcomes for patients with in-hospital cardiac arrest within the ICU, compared with non-ICU patients with in-hospital cardiac arrest. Finally, we evaluated outcomes stratified by age.

DATA SOURCES: A systematic review of PubMed, EMBASE, and preprint websites was conducted between January 1, 2020, and December 10, 2020. Prospective Register of Systematic Reviews identification: CRD42020203369.

STUDY SELECTION: Studies reporting on consecutive in-hospital cardiac arrest with a resuscitation attempt among patients with coronavirus disease 2019.

DATA EXTRACTION: Two authors independently performed study selection and data extraction. Study quality was assessed with the Newcastle-Ottawa Scale. Data were synthesized according to the Preferred Reporting Items for Systematic Reviews guidelines. Discrepancies were resolved by consensus or through an independent third reviewer.

DATA SYNTHESIS: Eight studies reporting on 847 in-hospital cardiac arrest were included. In-hospital cardiac arrest incidence varied between 1.5% and 5.8% among hospitalized patients and 8.0–11.4% among patients in ICU. In-hospital cardiac arrest occurred more commonly in older male patients. Most initial rhythms were nonshockable (83.9%, [asystole = 36.4% and pulseless electrical activity = 47.6%]). Return of spontaneous circulation occurred in 33.3%, with a 91.7% in-hospital mortality. In-hospital cardiac arrest events in ICU had higher incidence of return of spontaneous circulation (36.6% vs 18.7%; p < 0.001) and relatively lower mortality (88.7% vs 98.1%; p < 0.001) compared with in-hospital cardiac arrest in non-ICU locations. Patients greater than or equal to 60 years old had significantly higher in-hospital mortality than those less than 60 years (93.1% vs 87.9%; p = 0.019).

CONCLUSIONS: Approximately, one in 20 patients hospitalized with coronavirus disease 2019 received resuscitation for an in-hospital cardiac arrest. Hospital survival after in-hospital cardiac arrest within the ICU was higher than non-ICU locations and seems comparable with prepandemic survival for nonshockable rhythms. Although the data provide guidance surrounding prognosis after in-hospital cardiac arrest, it should be interpreted cautiously given the paucity of information surrounding treatment limitations and resource constraints during the pandemic. Further research is into actual causative mechanisms is needed.

Sprung C et al

Reassessing Cardiopulmonary Resuscitation in Hospitalized Patients With Coronavirus Disease 2019

Critical Care Medicine, June 2021; DOI: 10.1097/CCM.0000000000004962

COMMENTO:  The coronavirus disease 2019 (COVID-19) pandemic has caused morbidity, mortality, and an economic crisis worldwide. Necessity has required adjustments in the provision of medical care including, for the first-time in developed countries, triaging of scarce resources and considerable increased use of telemedicine as examples. Changes in procedures due to the pandemic offer an opportunity to reevaluate policies that may not be the most medically beneficial or efficient even under normal circumstances. Although cardiopulmonary resuscitation (CPR) was developed for sudden cardiac arrhythmias leading to cardiac arrest (patients too healthy to die rather than those too sick to keep living), CPR is typically performed on most dying hospitalized patients who do not have a “do-not-resuscitate” order.

Landes SD et al

Risk Factors Associated With COVID-19 Outcomes Among People With Intellectual and Developmental Disabilities Receiving Residential Services

JAMA, June 2021; DOI: 10.1001/jamanetworkopen.2021.12862

COMMENTO: Importance  Although there is evidence of more severe COVID-19 outcomes, there is no information describing the risk factors for COVID-19 diagnosis and/or mortality among people with intellectual and developmental disabilities (IDD) receiving residential support services in the US.

Objective  To identify associations between demographic characteristics, residential characteristics, and/or preexisting health conditions and COVID-19 diagnosis and mortality for people with IDD receiving residential support services.

Design, Setting, and Participants  This cohort study tracked COVID-19 outcomes for 543 individuals with IDD. Participants were receiving support services from a single organization providing residential services in the 5 boroughs of New York City from March 1 to October 1, 2020. Statistical analysis was performed from December 2020 to February 2021.

Exposures  Resident-level characteristics, including age, sex, race/ethnicity, disability status, residential characteristics, and preexisting medical conditions.

Main Outcomes and Measures  COVID-19 diagnosis was confirmed by laboratory test. COVID-19 mortality indicated that the individual died from COVID-19 during the course of the study. Logistic regression models were used to evaluate associations between demographic characteristics, residential characteristics, and preexisting health conditions and COVID-19 diagnosis and mortality.

Results  Among the 543 individuals with IDD in the study, the median (interquartile range) age was 57.0 (45-65) years; 217 (40.0%) were female, and 274 (50.5%) were Black, Asian/Pacific Islander, American Indian or Alaskan Native, or Hispanic. The case rate was 16 759 (95% CI, 13 853-20 131) per 100 000; the mortality rate was 6446 (95% CI, 4671-8832) per 100 000; and the case-fatality rate was 38.5% (95% CI, 29.1%-48.7%). Increased age (odds ratio [OR], 1.04; 95% CI, 1.02-1.06), Down syndrome (OR, 2.91; 95% CI, 1.49-5.69), an increased number of residents (OR, 1.07; 95% CI, 1.00-1.14), and chronic kidney disease (OR, 4.17; 95% CI, 1.90-9.15) were associated with COVID-19 diagnosis. Heart disease (OR, 10.60; 95% CI, 2.68-41.90) was associated with COVID-19 mortality.

Conclusions and Relevance  This study found that, similar to the general population, increased age and preexisting health conditions were associated with COVID-19 outcomes for people with IDD receiving residential support services in New York City. As with older adults living in nursing homes, number of residents was also associated with more severe COVID-19 outcomes. Unique to people with IDD was an increased risk of COVID-19 diagnosis for people with Down syndrome.

The African COVID-19 Critical Care Outcomes Study (ACCCOS) Investigators

Patient care and clinical outcomes for patients with COVID-19 infection admitted to African high-care or intensive care units (ACCCOS): a multicentre, prospective, observational cohort study

The Lancet, May 2021; doi.org/10.1016/S0140-6736(21)00441-4

COMMENTO : Background : There have been insufficient data for African patients with COVID-19 who are critically ill. The African COVID-19 Critical Care Outcomes Study (ACCCOS) aimed to determine which resources, comorbidities, and critical care interventions are associated with mortality in this patient population.

Methods : The ACCCOS study was a multicentre, prospective, observational cohort study in adults (aged 18 years or older) with suspected or confirmed COVID-19 infection who were referred to intensive care or high-care units in 64 hospitals in ten African countries (ie, Egypt, Ethiopia, Ghana, Kenya, Libya, Malawi, Mozambique, Niger, Nigeria, and South Africa). The primary outcome was in-hospital mortality censored at 30 days. We studied the factors (ie, human and facility resources, patient comorbidities, and critical care interventions) that were associated with mortality in these adult patients. This study is registered on ClinicalTrials.gov, NCT04367207.

Findings : From May to December, 2020, 6779 patients were referred to critical care. Of these, 3752 (55·3%) patients were admitted and 3140 (83·7%) patients from 64 hospitals in ten countries participated (mean age 55·6 years; 1890 [60·6%] of 3118 participants were male). The hospitals had a median of two intensivists (IQR 1–4) and pulse oximetry was available to all patients in 49 (86%) of 57 sites. In-hospital mortality within 30 days of admission was 48·2% (95% CI 46·4–50·0; 1483 of 3077 patients). Factors that were independently associated with mortality were increasing age per year (odds ratio 1·03; 1·02–1·04); HIV/AIDS (1·91; 1·31–2·79); diabetes (1·25; 1·01–1·56); chronic liver disease (3·48; 1·48–8·18); chronic kidney disease (1·89; 1·28–2·78); delay in admission due to a shortage of resources (2·14; 1·42–3·22); quick sequential organ failure assessment score at admission (for one factor [1·44; 1·01–2·04], for two factors [2·0; 1·33–2·99], and for three factors [3·66, 2·12–6·33]); respiratory support (high flow oxygenation [2·72; 1·46–5·08]; continuous positive airway pressure [3·93; 2·13–7·26]; invasive mechanical ventilation [15·27; 8·51–27·37]); cardiorespiratory arrest within 24 h of admission (4·43; 2·25–8·73); and vasopressor requirements (3·67; 2·77–4·86). Steroid therapy was associated with survival (0·55; 0·37–0·81). There was no difference in outcome associated with female sex (0·86; 0·69–1·06).

Interpretation : Mortality in critically ill patients with COVID-19 is higher in African countries than reported from studies done in Asia, Europe, North America, and South America. Increased mortality was associated with insufficient critical care resources, as well as the comorbidities of HIV/AIDS, diabetes, chronic liver disease, and kidney disease, and severity of organ dysfunction at admission.

De Havenon A et al

Characteristics and Outcomes Among US Patients Hospitalized for Ischemic Stroke Before vs During the COVID-19 Pandemic

JAMA, May 2021; doi:10.1001/jamanetworkopen.2021.10314

COMMENTO: Importance  After the emergence of COVID-19, studies reported a decrease in hospitalizations of patients with ischemic stroke (IS), but there are little to no data regarding hospitalizations for the remainder of 2020, including outcome data from a large cohort of patients with IS and comorbid COVID-19.

Objective  To assess hospital discharge rates, demographic factors, and outcomes of hospitalization associated with the COVID-19 pandemic among US patients with IS before vs during the COVID-19 pandemic.

Design, Setting, and Participants  This retrospective cohort study used data from the Vizient Clinical Data Base on 324 013 patients with IS at 478 nonfederal hospitals in 43 US states between January 1, 2019, and December 31, 2020. Patients were eligible if theywereadmitted to the hospital on a nonelective basis and were not receiving hospice care at the time of admission. A total of 41 166 dischargedbetweenJanuary and March 2020 wereexcludedfrom the analysis because they hadunreliable data on COVID-19 status, leaving 282 847 patients for the study.

Exposure  Ischemic stroke and laboratory-confirmed COVID-19.

Main Outcomes and Measures  Monthly counts of discharges among patients with IS in 2020. Demographic characteristics and outcomes, including in-hospital death, among patients with IS who were dischargedin 2019 (control group) were compared with those of patients with IS with or without comorbid COVID-19 (COVID-19 and non–COVID-19 groups, respectively) who were discharged between April and December 2020.

Results  Of the 282 847 patients included in the study, 165 912 (50.7% male; 63.4% White; 26.3% aged ≥80 years) were allocated to the control group; 111 418 of 116 935 patients (95.3%; 51.9% male; 62.8% White; 24.6% aged ≥80 years) were allocated to the non–COVID-19 group and 5517 of 116 935 patients (4.7%; 58.0% male; 42.5% White; 21.3% aged ≥80 years) to the COVID-19 group. A mean (SD) of 13 846 (553) discharges per month among patients with IS was reported in 2019. Discharges began decreasing in February 2020, reaching a low of 10 846 patients in April 2020 before returning to a prepandemic level of 13 639 patients by July 2020. A mean (SD) of 13 492 (554) discharges per month was recorded for the remainder of 2020. Black and Hispanic patients accounted for 21.4% and 7.0% of IS discharges in 2019, respectively, but accounted for 27.5% and 16.0% of those discharged with IS and comorbid COVID-19 in 2020. Compared with patients in the control and non–COVID-19 groups, those in the COVID-19 group were less likely to smoke (16.0% vs 17.2% vs 6.4%, respectively) and to have hypertension (73.0% vs 73.1% vs 68.2%) or dyslipidemia (61.2% vs 63.2% vs 56.6%) but were more likely to have diabetes (39.8% vs 40.5% vs 53.0%), obesity (16.2% vs 18.4% vs 24.5%), acute coronary syndrome (8.0% vs 9.2% vs 15.8%), or pulmonary embolus (1.9% vs 2.4% vs 6.8%) and to require intubation (11.3% vs 12.3% vs 37.6%). After adjusting for baseline factors, patients with IS and COVID-19 were more likely to die in the hospital than were patients with IS in 2019 (adjusted odds ratio, 5.17; 95% CI, 4.83-5.53; National Institutes of Health Stroke Scale adjusted odds ratio, 3.57; 95% CI, 3.15-4.05).

Conclusions and Relevance  In this cohort study, after the emergence of COVID-19, hospital discharges of patients with IS decreased in the US but returned to prepandemic  levels by July 2020. Among patients with IS between April and December 2020, comorbid COVID-19 was relatively common, particularly among Black and Hispanic populations, and morbiditywas high.

Chou SH et al

Factors Associated With Risk for Care Escalation Among Patients With COVID-19 Receiving Home-Based Hospital Care

Annals of Internal Medicine, May 2021; doi.org/10.7326/M21-0409

COMMENTO : Background: The COVID-19 pandemic, which has resulted in more than 142 million cases globally, has challenged health care systems to rapidly transform care to address complex and dynamic resource demands. Early in the pandemic, our large integrated health system implemented the Atrium Health Hospital at Home (AH-HaH) program to deliver home-based, hospital-level care to patients with COVID-19 and increase the healthsystem'sbedcapacity.

Objective: To determine which AH-HaH patients were at increased risk for care escalation to traditional brick-and-mortar facilities.

Bertuzzi AF et al

Impact of active cancer on COVID-19 survival: a matched-analysis on 557 consecutive patients at an Academic Hospital in Lombardy, Italy

British Journal of Cancer – Nature, April 2021; doi.org/10.1038/s41416-021-01396-9

COMMENTO: Background : The impact of active cancer in COVID-19 patients is poorly defined; however, most studies showed a poorer outcome in cancer patients compared to the general population.

Methods : We analysed clinical data from 557 consecutive COVID-19 patients. Uni-multivariable analysis was performed to identify prognostic factors of COVID-19 survival; propensity score matching was used to estimate the impact of cancer.

Results : Of 557 consecutive COVID-19 patients, 46 had active cancer (8%). Comorbidities included diabetes (n = 137, 25%), hypertension (n = 284, 51%), coronary artery disease (n = 114, 20%) and dyslipidaemia (n = 122, 22%). Oncologic patients were older (mean age 71 vs 65, p = 0.012), more often smokers (20% vs 8%, p = 0.009), with higher neutrophil-to-lymphocyte ratio (13.3 vs 8.2, p = 0.046). Fatality rate was 50% (CI 95%: 34.9;65.1) in cancer patients and 20.2% (CI 95%: 16.8;23.9) in the non-oncologic population. Multivariable analysis showed active cancer (HRactive: 2.26, p = 0.001), age (HRage>65years: 1.08, p < 0.001), as well as lactate dehydrogenase (HRLDH>248mU/mL: 2.42, p = 0.007), PaO2/FiO2 (HRcontinuous: 1.00, p < 0.001), procalcitonin (HRPCT>0.5ng/mL: 2.21, p < 0.001), coronary artery disease (HRyes: 1.67, p = 0.010), cigarette smoking (HRyes: 1.65, p = 0.041) to be independent statistically significant predictors of outcome. Propensity score matchingshowed a 1.92× risk of death in active cancer patients compared to non-oncologic patients (p = 0.013), adjusted for ICU-relatedbias. Weobserved a median OS of 14 days for cancer patients vs 35 days for other patients.

Conclusion : A near-doubleddeath rate between cancer and non-cancer COVID-19 patients was reported. Active cancer has a negative impact on clinica loutcome regard less of pre-existing clinical comorbidities.

Sharov KS

8806 Russian patients demonstrate T cell count as better marker of COVID-19 clinical course severity than SARS-CoV-2 viral load

Scientific Reports, May 2021; DOI: 10.1038/s41598-021-88714-6

COMMENTO: The article presents a comparative analysis of SARS-CoV-2 viral load (VL), T lymphocyte count and respiratory index PaO2:FiO2 ratio as prospective markers of COVID-19 course severity and prognosis. 8806 patients and asymptomatic carriers were investigated in time interval 15 March–19 December 2020. T cell count demonstrated better applicability as a marker of aggravating COVID-19 clinical course and unfavourable disease prognosis than SARS-CoV-2 VL or PaO2:FiO2 ratio taken alone. Using T cell count in clinical practice may provide an opportunity of early prediction of deteriorating a patient’s state.

Wu T et al

Asthma does not influence the severity of COVID-19: a Meta-analysis

Journal of Asthma, April 2021; doi.org/10.1080/02770903.2021.1917603

COMMENTO : OBJECTIVE: Previous studies have reported a correlation between coronavirus disease-2019 (COVID-19) and asthma. However, data on whether asthma constitutes a risk factor for COVID-19 and the prevalence of asthma in COVID-19 cases still remains scant. Here, we interrogated and analysed the association between COVID-19 and asthma. METHODS: In this study, we systematically searched PubMed, Embase, and Web of Science databases for studies published between January 1, to August 28, 2020. We included studies that reported the epidemiological and clinical features of COVID-19 and its prevalence in asthma patients. We excluded reviews, animal trails, single case reports, small case series and studies evaluating other coronavirus-related illnesses. Raw data from the studies were pooled into a meta-analysis. RESULTS: We analysed findings from 18 studies, including asthma patients with COVID-19. The pooled prevalence of asthma in COVID-19 cases was 0.08 (95% CI, 0.06-0.11), with an overall I(2) of 99.07%, p < 0.005 . The data indicated that asthma did not increase the risk of developing severe COVID-19 (odds ratio [OR] 1.04 (95% CI, 0.75-1.46) p = 0.28; I(2)=20%). In addition, there was no significant difference in the incidence of asthma with analyse age in COVID-19 infections [OR] 0.7795% CI, 0.59-1.00) p = 0.24; I(2)=29%). CONCLUSION: Taken together, our data suggested that asthma is not a significant risk factor for the development of severe COVID-19.

Anderson JL et al

Association of Sociodemographic Factors and Blood Group Type With Risk of COVID-19 in a US Population

JAMA, April 2021; doi:10.1001/jamanetworkopen.2021.7429

COMMENTO : The observedvariability in susceptibility to SARS-CoV-2 and severity of the ensuing COVID-19 have raised intense interest in theirenvironmental and geneticriskfactors. An early report from China1 suggestedthatblood group A wasassociatedwithincreasedsusceptibility and blood group O wasassociatedwithreducedsusceptibility to SARS-CoV-2 infection. These reports motivatedwidespreadinterest in examining ABO blood groups as potential COVID-19 riskfactors. SubsequentstudiesfromItaly and Spain2 reportedthatblood group A wasassociatedwith an increasedrisk of severe COVID-19 and blood group O wasassociatedwith a reducedrisk. In contrast, a large Danish study3 implicateddiseasesusceptibility but not severity. However, observations from Boston, Massachussets,4 and New York, New York,5 did not confirmanyspecific associations between ABO blood group and disease. The controversyraised by thesecontrasting reports led to this case-control study.

Mehta HB et al

Risk Factors Associated With SARS-CoV-2 Infections, Hospitalization, and Mortality Among US Nursing Home Residents

JAMA, March 2021; doi:10.1001/jamanetworkopen.2021.6315

COMMENTO: Importance  Nursing home residents account for approximately 40% of deaths from SARS-CoV-2.

Objective  To identify risk factors for SARS-CoV-2 incidence, hospitalization, and mortality among nursing home residents in the US.

Design, Setting, and Participants  This retrospective longitudinal cohort study was conducted in long-stay residents aged 65 years or older with fee-for-service Medicare residing in 15 038 US nursing homes from April 1, 2020, to September 30, 2020. Data were analyzed from November 22, 2020, to February 10, 2021.

Main Outcomes and Measures  The main outcome was risk of diagnosis with SARS-CoV-2 (per International Statistical Classification of Diseases, Tenth Revision, Clinical Modification [ICD-10-CM] codes) by September 30 and hospitalization or death within 30 days after diagnosis. Three-level (resident, facility, and county) logistic regression models and competing risk models conditioned on nursing home facility were used to determine association of patient characteristics with outcomes.

Results  Among 482 323 long-stay residents included, the mean (SD) age was 82.7 (9.2) years, with 326 861 (67.8%) women, and 383 838 residents (79.6%) identifying as White. Among 137 119 residents (28.4%) diagnosed with SARS-CoV-2 during follow up, 29 204 residents (21.3%) were hospitalized, and 26 384 residents (19.2%) died within 30 days. Nursing homes explained 37.2% of the variation in risk of infection, while county explained 23.4%. Risk of infection increased with increasing body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) (eg, BMI>45 vs BMI 18.5-25: adjusted hazard ratio [aHR], 1.19; 95% CI, 1.15-1.24) but varied little by other resident characteristics. Risk of hospitalization after SARS-CoV-2 increased with increasing BMI (eg, BMI>45 vs BMI 18.5-25: aHR, 1.40; 95% CI, 1.28-1.52); male sex (aHR, 1.32; 95% CI, 1.29-1.35); Black (aHR, 1.28; 95% CI, 1.24-1.32), Hispanic (aHR, 1.20; 95% CI, 1.15-1.26), or Asian (aHR, 1.46; 95% CI, 1.36-1.57) race/ethnicity; impaired functional status (eg, severely impaired vs not impaired: aHR, 1.15; 95% CI, 1.10-1.22); and increasing comorbidities, such as renal disease (aHR, 1.21; 95% CI, 1.18-1.24) and diabetes (aHR, 1.16; 95% CI, 1.13-1.18). Risk of mortality increased with age (eg, age >90 years vs 65-70 years: aHR, 2.55; 95% CI, 2.44-2.67), impaired cognition (eg, severely impaired vs not impaired: aHR, 1.79; 95% CI, 1.71-1.86), and functional impairment (eg, severely impaired vs not impaired: aHR, 1.94; 1.83-2.05).

Conclusions and Relevance  These findings suggest that among long-stay nursing home residents, risk of SARS-CoV-2 infection was associated with county and facility of residence, while risk of hospitalization and death after SARS-CoV-2 infection was associated with facility and individual resident characteristics. For many resident characteristics, there were substantial differences in risk of hospitalization vs mortality. This may represent resident preferences, triaging decisions, or inadequate recognition of risk of death.

Frasca D et al

Influence of obesity on serum levels of SARS-CoV-2-specific antibodies in COVID-19 patients

PLoS One, March 2021; doi.org/10.1371/journal.pone.0245424

COMMENTO: SARS-CoV-2 (Severe Acute Respiratory Syndrome Corona Virus-2), cause of COVID-19 (Coronavirus Disease of 2019), represents a significant risk to people living with pre-existing conditions associated with exacerbated inflammatory responses and consequent dysfunctional immunity. In this paper, we have evaluated the influence of obesity, a condition associated with chronic systemic inflammation, on the secretion of SARS-CoV-2-specific IgG antibodies in the blood of COVID-19 patients. Our hypothesis is that obesity is associated with reduced amounts of specific IgG antibodies. Results have confirmed our hypothesis and have shown that SARS-CoV-2 IgG antibodies are negatively associated with Body Mass Index (BMI) in COVID-19 obese patients, as expected based on the known influence of obesity on humoral immunity. Antibodies in COVID-19 obese patients are also negatively associated with serum levels of pro-inflammatory and metabolic markers of inflammaging and pulmonary inflammation, such as SAA (serum amyloid A protein), CRP (C-reactive protein), and ferritin, but positively associated with NEFA (nonesterified fatty acids). These results altogether could help to identify an inflammatory signature with strong predictive value for immune dysfunction. Inflammatory markers identified may subsequently be targeted to improve humoral immunity in individuals with obesity and in individuals with other chronic inflammatory conditions.

Pranata R et al

Delirium and Mortality in Coronavirus Disease 2019 (COVID-19) - A Systematic Review and Meta-analysis

Archives in Gerontology and Geriatrics, March 2021; DOI: 10.1016/j.archger.2021.104388

COMMENTO: INTRODUCTION: Older adults are indisputably struck hard by the coronavirus disease 2019 (COVID-19) pandemic. The main objective of this meta-analysis is to establish the association between delirium and mortality in older adults with COVID-19. METHODS: Systematic literature searches of PubMed, Embase, and Scopus databases were performed up until 28 November 2020. The exposure in this study was the diagnosis of delirium using clinically validated criteria. Delirium might be in-hospital, at admission, or both. The main outcome was mortality defined as clinically validated non-survivor/death. The effect estimates were reported as odds ratios (ORs) and adjusted odds ratios (aORs). RESULTS: A total of 3,868 patients from 9 studies were included in this systematic review and meta-analysis. The percentage of patients with delirium was 27% [20%, 34%]. Every 1 mg/L increase in CRP was significantly associated with 1% increased delirium risk (OR 1.01 [1.00. 1.02], p=0.033). Delirium was associated with mortality (OR 2.39 [1.64, 3.49], p<0.001; I(2): 82.88%). Subgroup analysis on delirium assessed at admission indicate independent association (OR 2.12 [1.39, 3.25], p<0.001; I(2): 82.67%). Pooled adjusted analysis indicated that delirium was independently associated with mortality (aOR 1.50 [1.16, 1.94], p=0.002; I(2): 31.02%). Subgroup analysis on delirium assessed at admission indicate independent association (OR 1.40 [1.03, 1.90], p=0.030; I(2): 35.19%). Meta-regression indicates that the association between delirium and mortality were not significantly influenced by study-level variations in age, sex [reference: male], hypertension, diabetes, and dementia. CONCLUSION: The presence of delirium is associated with increased risk of mortality in hospitalized older adults with COVID-19.

Saibin W et al

Association between peripheral lymphocyte count and the mortality risk of COVID-19 inpatients

BMC Pulmonary Medicine, February 2021; DOI: 10.1186/s12890-021-01422-9

COMMENTO : BACKGROUND: To explore the relationship between peripheral lymphocyte counts (PLCs) and the mortality risk of coronavirus disease 2019 (COVID-19), as well as the potential of PLC for predicting COVID-19 hospitalized patients death. METHODS: Baseline characteristics, laboratory tests, imaging examinations, and outcomes of 134 consecutive COVID-19 hospitalized patients were collected from a tertiary hospital in Wuhan city from January 25 to February 24, 2020. Multiple regression analysis was used to analyze the relationship between the PLC at admission and mortality risk in COVID-19 patients and to establish a model for predicting death in COVID-19 hospitalized patients based on PLC. RESULTS: Afteradjusting for potentialconfoundingfactors, wefound a non-linearrelationship and threshold saturation effectbetween PLC and mortalityrisk in COVID-19 patients (infection point of PLC: 0.95 x 10(9)/L). Multiple regression analysis showed that when PLCs of COVID-19 patients were lower than 0.95 x 10(9)/L, the patients had a significantly higher mortality risk as compared to COVID-19 patient with PLCs > 0.95 x 10(9)/L (OR 7.27; 95% CI 1.10-48.25). The predictive power of PLC for death in COVID-19 patients (presented as area under the curve) was 0.78. The decision curve analysis showed that PLC had clinical utility for the prediction of death in COVID-19 inpatients. CONCLUSIONS: PLC had a non-linear relationship with mortality risk in COVID-19 inpatients. Reduced PLCs (< 0.95 x 10(9)/L) were associated with an increased mortality risk in COVID-19 inpatients. PLCsalsohad a potentialpredictive value for the death of COVID-19 inpatients.

Raschke RA et al

Discriminant Accuracy of the SOFA Score for Determining the Probable Mortality of Patients With COVID-19 Pneumonia Requiring Mechanical Ventilation

JAMA, February 2021; doi:10.1001/jama.2021.1545

COMMENTO : The coronavirus disease 2019 (COVID-19) pandemic has raisedconcernregarding the capacity to provide care for a surge of criticallyill patients thatmightrequireexcluding patients with a lowprobability of short-termsurvivalfromreceivingmechanical ventilation. A surveyidentified 26 unique COVID-19 triage policies, of which 20 usedsomeform of the SequentialOrgan Failure Assessment (SOFA) score.

However, studiesperformedin 2016 and 2017 have shown only moderate discriminant accuracy of the SOFA score for predicting survival in intensive care unit (ICU) patients with sepsis and an area under the receiver operating characteristiccurve (AUROC) of 0.74 to 0.75.3,4 Wehypothesizedthat the SOFA score mightbelessaccurate in patients requiringmechanical ventilation for COVID-19 pneumonia because such patients generally have severe single-organdys function and less variation in SOFA scores.

Benard A et al

Interleukin-3 is a predictive marker for severity and outcome during SARS-CoV-2 infections

Nature, July 2020; doi.org/10.1101/2020.07.02.184093

COMMENTO : Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a world wid ehealththreat. In a prospective multicentricstudy, weidentify IL-3 as an independent prognostic marker for the outcomeduring SARS-CoV-2 infections. Specifically, low plasma IL-3 levelsisassociatedwithincreasedseverity, viral load, and mortalityduring SARS-CoV-2 infections. Patients withsevere COVID-19 exhibitalsoreduced circulating plasma cytoid dendritic cells (pDCs) and low plasma IFNalpha and IFNlambdalevelswhencompared to non-severe COVID-19 patients. In a mouse model of pulmonary HSV-1 infection, treatmentwith recombinant IL-3 reduces viral load and mortality. Mechanistically, IL-3 increases innate antiviral immunity by promoting the recruitment of circulatingpDCsinto the airways by stimulating CXCL12 secretionfrompulmonary CD123(+) epithelialcells, both, in mice and in COVID-19 negative patients exhibiting pulmonary diseases. This study identifies IL-3 as a predictive disease marker for SARS-CoV-2 infections and as a potentia ltherapeutic target for pulmunory viral infections.

Gorges RJ et al

Factors Associated With Racial Differences in Deaths Among Nursing Home Residents With COVID-19 Infection in the US

JAMA, Febraury 2021 ; doi:10.1001/jamanetworkopen.2020.37431

COMMENTO: Importance  It is important to understand differences in coronavirus disease 2019 (COVID-19) deaths by nursing home racial composition and the potential reasons for these differences so that limited resources can be distributed equitably.

Objective  To describe differences in the number of COVID-19 deaths by nursing home racial composition and examine the factors associated with these differences.

Design, Setting, and Participants  This cross-sectional study of 13 312 nursing homes in the US used the Nursing Home COVID-19 Public File from the Centers for Medicare and Medicaid Services, which contains COVID-19 cases and deaths among nursing home residents as self-reported by nursing homes beginning between January 1, 2020, and May 24, 2020, and ending on September 13, 2020. Data were analyzed from July 28 to December 18, 2020.

Exposures  Confirmed or suspected COVID-19 infection. Confirmed cases were defined as COVID-19 infection confirmed by a diagnostic laboratory test. Suspected cases were defined as signs and/or symptoms of COVID-19 infection or patient-specific transmission-based precautions for COVID-19 infection.

Main Outcomes and Measures  Deaths associated with COVID-19 among nursing home residents. Death counts were compared by nursing home racial composition, which was measured as the proportion of White residents.

Results  Among 13 312 nursing homes included in the study, the overall mean (SD) age of residents was 79.5 (6.7) years. A total of 51 606 COVID-19–associated deaths among residents were reported, with a mean (SD) of 3.9 (8.0) deaths per facility. The mean (SD) number of deaths in nursing homes with the lowest proportion of White residents (quintile 1) vs nursing homes with the highest proportions of White residents (quintile 5) were 5.6 (9.2) and 1.7 (4.8), respectively. Facilities in quintile 1 experienced a mean (SE) of 3.9 (0.2) more deaths than those in quintile 5, representing a 3.3-fold higher number of deaths in quintile 1 compared with quintile 5. Adjustment for the number of certified beds reduced the mean (SE) difference between these 2 nursing home groups to 2.2 (0.2) deaths. Controlling for case mix measures and other nursing home characteristics did not modify this association. Adjustment for county-level COVID-19 prevalence further reduced the mean (SE) difference to 1.0 (0.2) death.

Conclusions and Relevance  In this study, nursing homes with the highest proportions of non-White residents experienced COVID-19 death counts that were 3.3-fold higher than those of facilities with the highest proportions of White residents. These differences were associated with factors such as larger nursing home size and higher infection burden in counties in which nursing homes with high proportions of non-White residents were located. Focusing limited available resources on facilities with high proportions of non-White residents is needed to support nursing homes during potential future outbreaks.

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