COVID-19 Critical Illness Research Articles

LONG-TERM OUTCOMES OF CRITICALLY ILL PATIENTS WITH COVID-19: A SYSTEMATIC REVIEW

BackgroundSurvivors of critical illness are susceptible to long-term functional impairments following admission to an intensive care unit (ICU). In the context of the COVID-19 pandemic, there has been a surge in patients admitted to ICU with severe acute respiratory syndrome coronavirus type 2. The long-term consequences of critical illness due to COVID-19 illness remain unclear. Research QuestionTo determine the long-term outcomes of adult patients admitted to ICU for COVID-19. Study Design and MethodsWe searched Ovid MEDLINE and EMBASE using subject heading and free-text terms related to long-term outcomes of critically ill patients with COVID-19. We included all articles that reported original data on outcomes from 90 days onwards for adult patients admitted to ICU for COVID-19. Data extracted included study details, patient characteristics, outcomes reported, measurement tools used and timing of assessment. ResultsA total of 14,882 studies were screened, from which 134 studies fulfilled the selection criteria. Follow-up timepoints ranged from 90 days to 2 years following critical illness. Post-hospital mortality was the most reported outcome (n=60), with the general ICU cohort having an aggregate mortality rate of 35.5% (95% CI 34.7-36.2) at 90 days and 31.6% (95%CI 30.9-32.4) at 6 months. A plethora of other outcomes were assessed, including psychological function/mental health (n=49), persistent symptoms (n=47), quality of life (n=47), physical function (n=33) and cognitive function (n=31). For each outcome, different measurement tools were employed, making data synthesis across studies difficult. InterpretationImportant evidence gaps remain regarding the long-term health outcomes and healthcare needs for survivors of critical COVID-19 illness. This review found that mortality was the most reported long-term outcome. Significant heterogeneity was evident across studies in terms of outcomes assessed, measurement instruments used and the duration of follow-up. Future research requires increased consistency in outcomes assessed and measurement tools to inform clinical practice.

Characterization of postintensive care syndrome in a prospective cohort of survivors of COVID-19 critical illness: a 12-month follow-up study

PurposeStudies integrating an exhaustive longitudinal long-term follow-up of postintensive care syndrome (PICS) in critically ill COVID-19 survivors are scarce. We aimed to 1) describe PICS-related sequelae over a 12-month period after intensive care unit (ICU) discharge, 2) identify relevant demographic and clinical factors related to PICS, and 3) explore how PICS-related sequelae may influence health-related quality of life (HRQoL) in critically ill COVID-19 survivors.MethodsWe conducted a prospective cohort study in adult critically ill survivors of SARS-CoV-2 infection that did or did not need invasive mechanical ventilation (IMV) during the COVID-19 pandemic in Spain (March 2020 to January 2021). We performed a telemedicine follow-up of PICS-related sequelae (physical/functional, cognitive, and mental health) and HRQoL with five data collection points. We retrospectively collected demographic and clinical data. We used multivariable mixed-effects models for data analysis.ResultsWe included 142 study participants in the final analysis, with a median [interquartile range] age of 61 [53–68] yr; 35% were female and 59% needed IMV. Fatigue/dyspnea, pain, impaired muscle function, psychiatric symptomatology and reduced physical HRQoL were prominent sequelae early after ICU discharge. Over the 12-month follow-up, functionality and fatigue/dyspnea improved progressively, while pain remained stable. We observed slight fluctuations in anxiety symptoms and perception of cognitive deficit, whereas posttraumatic stress disorder (PTSD) and depressive symptoms improved, with a mild rebound at the end of the follow-up. Female sex, younger age, and the need for IMV were risk factors for PICS, while having higher cognitive reserve was a potential protective factor. Physical HRQoL scores showed a general improvement over time, whereas mental HRQoL remained stable. Shorter ICU stay, better functionality, and lower scores for fatigue/dyspnea and pain were associated with better physical HRQoL, while lower scores for anxiety, depression, and PTSD were associated with better mental HRQoL.ConclusionsPostintensive care syndrome was common in COVID-19 critical illness survivors and persisted in a significant proportion of patients one year after ICU discharge, impacting HRQoL. The presence of risk factors for PICS may identify patients who are more likely to develop the condition and who would benefit from more specific and closer follow-up after ICU admission.Study registrationClinicalTrials.gov (NCT04422444); first submitted 9 June 2020.

Pathway-Based Mendelian Randomization for Pre-Infection IL-6 Levels Highlights Its Role in Coronavirus Disease.

Interleukin 6 (IL-6) levels at hospital admission have been suggested for disease prognosis, and IL-6 antagonists have been suggested for the treatment of patients with severe COVID-19. However, less is known about the relationship between pre-COVID-19 IL-6 levels and the risk of severe COVID-19. To fill in this gap, here we extensively investigated the association of genetically instrumented IL-6 pathway components with the risk of severe COVID-19. We used a two-sample Mendelian randomization study design and retrieved genetic instruments for blood biomarkers of IL-6 activation, including IL-6, soluble IL-6 receptor, IL-6 signal transducer, and CRP, from respective large available GWASs. To establish associations of these instruments with COVID-19 outcomes, we used data from the Host Genetics Initiative and GenOMICC studies. Our analyses revealed inverse associations of genetically instrumented levels of IL-6 and its soluble receptor with the risk of developing severe disease (OR = 0.60 and 0.94, respectively). They also demonstrated a positive association of severe disease with the soluble signal transducer level (OR = 1.13). Only IL-6 associations with severe COVID-19 outcomes reached the significance threshold corrected for multiple testing (p < 0.003; with COVID-19 hospitalization and critical illness). These potential causal relationships for pre-COVID-19 IL-6 levels with the risk of developing severe symptoms provide opportunities for further evaluation of these factors as prognostic/preventive markers of severe COVID-19. Further studies will need to clarify whether the higher risk for a severe disease course with lower baseline IL-6 levels may also extend to other infectious diseases.

Occurrence, co-occurrence and persistence of symptoms of depression and post-traumatic stress disorder in survivors of COVID-19 critical illness

ABSTRACT Background: Intensive care unit (ICU) admission and invasive mechanical ventilation (IMV) are associated with psychological distress and trauma. The COVID-19 pandemic brought with it a series of additional long-lasting stressful and traumatic experiences. However, little is known about comorbid depression and post-traumatic stress disorder (PTSD). Objective: To examine the occurrence, co-occurrence, and persistence of clinically significant symptoms of depression and PTSD, and their predictive factors, in COVID-19 critical illness survivors. Method: Single-centre prospective observational study in adult survivors of COVID-19 with ≥24 h of ICU admission. Patients were assessed one and 12 months after ICU discharge using the depression subscale of the Hospital Anxiety and Depression Scale and the Davidson Trauma Scale. Differences in isolated and comorbid symptoms of depression and PTSD between patients with and without IMV and predictors of the occurrence and persistence of symptoms of these mental disorders were analysed. Results: Eighty-nine patients (42 with IMV) completed the 1-month follow-up and 71 (34 with IMV) completed the 12-month follow-up. One month after discharge, 29.2% of patients had symptoms of depression and 36% had symptoms of PTSD; after one year, the respective figures were 32.4% and 31%. Coexistence of depressive and PTSD symptoms accounted for approximately half of all symptomatic cases. Isolated PTSD symptoms were more frequent in patients with IMV (p≤.014). The need for IMV was associated with the occurrence at one month (OR = 6.098, p = .005) and persistence at 12 months (OR = 3.271, p = .030) of symptoms of either of these two mental disorders. Conclusions: Comorbid depressive and PTSD symptoms were highly frequent in our cohort of COVID-19 critical illness survivors. The need for IMV predicted short-term occurrence and long-term persistence of symptoms of these mental disorders, especially PTSD symptoms. The specific role of dyspnea in the association between IMV and post-ICU mental disorders deserves further investigation. Trial registration: ClinicalTrials.gov identifier: NCT04422444.

Critically-ill COVID-19 susceptibility gene CCR3 shows natural selection in sub-Saharan Africans

The prevalence of COVID-19 critical illness varies across ethnicities, with recent studies suggesting that genetic factors may contribute to this variation. The aim of this study was to investigate natural selection signals of genes associated with critically-ill COVID-19 in sub-Saharan Africans. Severe COVID-19 SNPs were obtained from the HGI website. Selection signals were assessed in 661 sub-Sahara Africans from 1000 Genomes Project using integrated haplotype score (iHS), cross-population extended haplotype homozygosity (XP-EHH), and fixation index (Fst). Allele frequency trajectory analysis of ancient DNA samples were used to validate the existing of selection in sub-Sahara Africans. We also used Mendelian randomization to decipher the correlation between natural selection and critically-ill COVID-19. We identified that CCR3 exhibited significant natural selection signals in sub-Sahara Africans. Within the CCR3 gene, rs17217831-A showed both high iHS (Standardized iHS = 2) and high XP-EHH (Standardized XP-EHH = 2.5) in sub-Sahara Africans. Allele frequency trajectory of CCR3 rs17217831-A revealed natural selection occurring in the recent 1,500 years. Natural selection resulted in increased CCR3 expression in sub-Sahara Africans. Mendelian Randomization provided evidence that increased blood CCR3 expression and eosinophil counts lowered the risk of critically ill COVID-19. Our findings suggest that sub-Saharan Africans are resistant to critically ill COVID-19 due to natural selection and identify CCR3 as a potential novel therapeutic target.

Risk factors for critical COVID-19 illness during Delta- and Omicron-predominant period in Korea; using K-COV-N cohort in the National health insurance service.

This study evaluated the clinical characteristics of patients with COVID-19 in Korea, and examined the relationship between severe COVID-19 cases and underlying health conditions during the Delta (September 20, 2021 to December 4, 2021) and the Omicron (February 20, 2022 to March 31, 2022) predominant period. This study assessed the association between critical COVID-19 illness and various risk factors, including a variety of underlying health conditions, using multiple logistic regression models based on the K-COV-N cohort, a nationwide data of confirmed COVID-19 cases linked with COVID-19 vaccination status and the National Health Insurance claim information. We analyzed 137,532 and 8,294,249 cases of COVID-19 infection during the Delta and the Omicron variant dominant periods, respectively. During the Delta as well as the Omicron period, old age (≥80 years) showed the largest effect size among risk factors for critical COVID-19 illness (aOR = 18.08; 95% confidence interval [CI] = 14.71-22.23 for the Delta; aOR = 24.07; 95% CI = 19.03-30.44 for the Omicron period). We found that patients with solid organ transplant (SOT) recipients, unvaccinated, and interstitial lung disease had more than a two-fold increased risk of critical COVID-19 outcomes between the Delta and Omicron periods. However, risk factors such as urban residence, underweight, and underlying medical conditions, including chronic cardiac diseases, immunodeficiency, and mental disorders, had different effects on the development of critical COVID-19 illness between the Delta and Omicron periods. We found that the severity of COVID-19 infection was much higher for the Delta variant than for the Omicron. Although the Delta and the Omicron variant shared many risk factors for critical illness, several risk factors were found to have different effects on the development of critical COVID-19 illness between those two variants. Close monitoring of a wide range of risk factors for critical illness is warranted as new variants continue to emerge during the pandemic.

New perspectives on tracheal resection for COVID-19–related stenosis: A propensity score matching analysis

ObjectiveThe large number of patients with COVID-19 subjected to prolonged invasive mechanical ventilation has been expected to result in a significant increase in tracheal stenosis in the next years. The aim of this study was to evaluate and compare postoperative outcomes of patients who survived COVID-19 critical illness and underwent tracheal resection for postintubation/posttracheostomy tracheal stenosis with those of non–COVID-19 patients. MethodsIt was single-center, retrospective study. All consecutive patients with post-intubation/posttracheostomy tracheal stenosis who underwent tracheal resection from February 2020 to March 2022 were enrolled. A total of 147 tracheal resections were performed: 24 were in post–COVID-19 patients and 123 were in non–COVID-19 patients. A 1:1 propensity score matching analysis was performed, considering age, gender, body mass index, and length of stenosis. After matching, 2 groups of 24 patients each were identified: a post–COVID-19 group and a non–COVID group. ResultsNo mortality after surgery was registered. Posttracheostomy etiology of stenosis resulted more frequently in post–COVID-19 patients (n = 20 in the post–COVID-19 group vs n = 11 in the non–COVID-19 group; P = .03), as well as intensive care unit admissions during the postoperative period (16 vs 9 patients; P = .04). Need for postoperative reintubation for glottic edema and respiratory failure was higher in the post–COVID-19 group (7 vs 2 postoperative reintubation procedures; P = .04). Postoperative dysphonia was observed in 11 (46%) patients in the post–COVID-19 group versus 4 (16%) patients in the non–COVID-19 group (P = .03). ConclusionsTracheal resection continues to be safe and effective in COVID-19–related tracheal stenosis scenarios. Intensive care unit admission rates and postoperative complications seem to be higher in post–COVID-19 patients who underwent tracheal resection compared with non–COVID-19 patients.

Preexisting renal graft dysfunction as a major risk factor for SARS-CoV-2 Omicron variant pneumonia: A postinfection cross-sectional study of 312 immunosuppressed renal transplant recipients

ObjectivesSARS-CoV-2 pneumonia poses significant challenges to health systems worldwide, particularly, in severe and critical cases. Immunosuppressed renal transplant recipients appear to be at a particularly high risk for severe or critical COVID-19 illness. However, few studies elucidated the risk factors of SARS-CoV-2 pneumonia in renal transplant recipients with COVID-19. MethodsA postinfection cross-sectional survey was conducted in 312 renal transplant recipients and 503 age- and sex-matched controls to explore risk factors for SARS-CoV-2 pneumonia in immunosuppressed renal transplant recipients. ResultsThe results showed that renal transplant recipients had a much higher incidence of SARS-CoV-2 pneumonia (48.1%) after infection with the SARS-CoV-2 Omicron variant than controls (5.6%). The multivariate binary logistic regression analysis identified older age, lower creatinine clearance before infection, and higher dose of prednisone before infection as risk factors for SARS-CoV-2 pneumonia in renal transplant recipients. Preexisting renal dysfunction was a major risk factor for SARS-CoV-2 pneumonia, with an odds ratio of 3.27 (1.01-10.61). ConclusionsPreexisting renal graft dysfunction was a major risk factor for SARS-CoV-2 Omicron variant pneumonia. It is suggested that high-risk renal transplant recipients should undergo computed tomography scanning within 14 days after infection with SARS-CoV-2.

The Influence of Autoimmune Thyroid Diseases on Viral Pneumonia Development, Including COVID-19: A Two-Sample Mendelian Randomization Study.

The association between thyroid function and viral pneumonia has undergone extensive examination, yet the presence of a causal link remains uncertain. The objective of this paper was to employ Two-Sample Mendelian Randomization (MR) analysis to investigate the connections between three thyroid diseases and thyroid hormone indicators with viral pneumonia and COVID-19. We obtained summary statistics datasets from seven genome-wide association studies (GWASs). The primary method used for estimating relationships was inverse-variance weighting (IVW). In addition, we employed weighted median, weighted mode, MR-Egger, and MR-PRESSO as supplementary analytical tools. Sensitivity analyses encompassed Cochran's Q test, MR-Egger intercept test, and MR-PRESSO. Our study revealed significant causal relationships between having a genetic predisposition to autoimmune thyroid disease (AITD) and an increased susceptibility to viral pneumonia (odds ratio [OR]: 1.096; 95% confidence interval [CI]: 1.022-1.176). Moreover, it demonstrated a heightened susceptibility and severity of COVID-19 (OR for COVID-19 susceptibility, COVID-19 hospitalization, and COVID-19 critical illness, with 95% CIs of 1.016, 1.001-1.032; 1.058, 1.003-1.116; 1.045, 1.010-1.081). However, no statistically significant associations were found between TSH, FT4, subclinical hypo- or hyperthyroidism, and the risk of viral pneumonia incidence, or the susceptibility and severity of COVID-19 (all p > 0.05). This study establishes a cause-and-effect relationship between AITD and the development of viral pneumonia, as well as the susceptibility and severity of COVID-19.

Prior physical illness predicts death better than acute physiological derangement on intensive care unit admission in COVID-19: A Swedish registry study.

COVID-19 is associated with prolonged intensive care unit (ICU) stay and considerable mortality. The onset of persistent critical illness, defined as when prior illness predicts death better than acute physiological derangement, has not been studied in COVID-19. This national cohort study based on the Swedish Intensive Care Registry (SIR) included all patients admitted to a Swedish ICU due to COVID-19 from 6 March 2020 to 9 November 2021. Simplified Acute Physiology Score-3 (SAPS3) Box 1 was used as a measure of prior illness and Box 3 as a measure of acute derangement to evaluate the onset and importance of persistent critical illness in COVID-19. To compare predictive capacity, the area under receiver operating characteristic (AUC) of SAPS3 and its constituent Box 1 and 3 was calculated for 30-day mortality. In 7 969 patients, of which 1 878 (23.6%) died within 30 days of ICU admission, the complete SAPS3 score had acceptable discrimination: AUC 0.75 (95% CI 0.74 to 0.76) but showed under prediction in low-risk patients and over prediction in high-risk patients. SAPS3 Box 1 showed markedly better discrimination than Box 3 (AUC 0.74 vs 0.65, P<0,0001). Using custom logistic models, the difference in predictive performance of prior and acute illness was validated, AUC 0.76 vs AUC 0.69, p<0.0001. Prior physical illness predicts death in COVID-19 better than acute physiological derangement during ICU stay, and the whole SAPS3 score is not significantly better than just prior illness. The results suggests that COVID-19 may exhibit similarities to persistent critical illness immediately from ICU admission, potentially because of long median ICU length-of-stay. Alternatively, the variables in the acute physiological derangement model may not adequately capture the severity of illness in COVID-19.

Association of IFNAR2 rs2236757 and OAS3 rs10735079 Polymorphisms with Susceptibility to COVID-19 Infection and Severity in Palestine.

The clinical course and severity of COVID-19 vary among patients. This study aimed to investigate the potential correlation between the gene polymorphisms of the interferon receptor (IFNAR2) rs2236757 and oligoadenylate synthetase 3 (OAS3) rs10735079 with the risk of COVID-19 infection and its severity among Palestinian patients. The study was conducted between April and May 2021 on 154 participants who were divided into three groups: the control group (RT-PCR-negative, n = 52), the community cases group (RT-PCR-positive, n = 70), and the critically ill cases (ICU group; n = 32). The genotyping of the investigated polymorphisms was performed using amplicon-based next-generation sequencing. The genotypes distribution for the IFNAR2 rs2236757 was significantly different among the study groups (P = 0.001), while no statistically significant differences were found in the distribution of genotypes for the OAS3 rs10735079 (P = 0.091). Logistic regression analysis adjusted for possible confounding factors revealed a significant association between the risk allele rs2236757A and critical COVID-19 illness (P < 0.025). Among all patients, those who carried the rs2236757GA were more likely to have a sore throat (OR, 2.52 (95% CI 1.02-6.24); P = 0.011); the presence of the risk allele rs2236757A was associated with an increased risk to dyspnea (OR, 4.70 (95% CI 1.80-12.27); P < 0.001), while the rs10735079A carriers were less likely to develop muscle aches (OR, 0.34 (95% CI 0.13-0.88); P = 0.0248) and sore throat (OR, 0.17 (95% CI 0.05-0.55); P < 0.001). In conclusion, our results revealed that the rs2236757A variant was associated with critical COVID-19 illness and dyspnea, whereas the rs10735079A variant was protective for muscle aches and sore throat.

Validation of reference gene stability for miRNA quantification by reverse transcription quantitative PCR in the peripheral blood of patients with COVID-19 critical illness.

The COVID-19 pandemic has created an urgency to study the host gene response that leads to variable clinical presentations of the disease, particularly the critical illness response. miRNAs have been implicated in the mechanism of host immune dysregulation and thus hold potential as biomarkers and/or therapeutic agents with clinical application. Hence, further analyses of their altered expression in COVID-19 is warranted. An important basis for this is identifying appropriate reference genes for high quality expression analysis studies. In the current report, NanoString technology was used to study the expression of 798 miRNAs in the peripheral blood of 24 critically ill patients, 12 had COVID-19 and 12 were COVID-19 negative. A list of potentially stable candidate reference genes was generated that included ten miRNAs. The top six were analyzed using reverse transcription quantitative polymerase chain reaction (RT-qPCR) in a total of 41 patients so as to apply standard computational algorithms for validating reference genes, namely geNorm, NormFinder, BestKeeper and RefFinder. There was general agreement among all four algorithms in the ranking of four stable miRNAs: miR-186-5p, miR-148b-3p, miR-194-5p and miR-448. A detailed analysis of their output rankings led to the conclusion that miR-186-5p and miR-148b-3p are appropriate reference genes for miRNA expression studies using PaxGene tubes in the peripheral blood of patients critically ill with COVID-19 disease.

A large-scale genome-wide cross-trait analysis for the effect of COVID-19 on female-specific cancers

Little is known regarding the long-term adverse effects of COVID-19 on female-specific cancers, nor the shared genetic influences underlying these conditions. We performed a comprehensive genome-wide cross-trait analysis to investigate the shared genetic architecture between COVID-19 (infection, hospitalization, and critical illness) with three female-specific cancers (breast cancer (BC), epithelial ovarian cancer (EOC), and endometrial cancer (EC)). We identified significant genome-wide genetic correlations with EC for both hospitalization (= 0.19, p= 0.01) and critical illness (= 0.29, p= 3.00×10-4). Mendelian randomization demonstrated no valid association of COVID-19 with any cancer of interest, except for suggestive associations of genetically predicted hospitalization (ORIVW= 1.09, p= 0.04) and critical illness (ORIVW= 1.06, p= 0.04) with EC risk, none withstanding multiple correction. Cross-trait meta-analysis identified 20 SNPs shared between COVID-19 with BC, 15 with EOC, and 5 with EC; and transcriptome-wide association studies revealed multiple shared genes. Findings support intrinsic links underlying these complex traits, highlighting shared mechanisms rather than causal associations.

VOC-Based Probes, a New Set of Analytical Tools to Monitor Patient Health from Blood Sample. Proof of Concept on Tracking COVID-19 Infection.

Induced volatolomics is an emerging field that holds promise for many biomedical applications including disease detection and prognosis. In this pilot study, we report the first use of a cocktail of volatile organic compounds (VOCs)-based probes to highlight new metabolic markers allowing disease prognosis. In this pilot study, we specifically targeted a set of circulating glycosidases whose activities could be associated with critical COVID-19 illness. Starting from blood sample collection, our approach relies on the incubation of VOC-based probes in plasma samples. Once activated, the probes released a set of VOCs in the sample headspace. The dynamic monitoring of the signals of VOC tracers enabled the identification of three dysregulated glycosidases in the initial phase after infection, for which preliminary machine learning analyses suggested an ability to anticipate critical disease development. This study demonstrates that our VOC-based probes are a new set of analytical tools that can provide access to biological signals until now unavailable to biologists and clinicians and which could be included in biomedical research to properly construct multifactorial therapy algorithms, necessary for personalized medicine.

Profile of Critical COVID-19 Illness in Children During the Second and Third Wave of the Pandemic: A Single Center Study from South India

Profile of Critical COVID-19 Illness in Children During the Second and Third Wave of the Pandemic: A Single Center Study from South India

Evaluating Adult Idiopathic Scoliosis as an Independent Risk Factor for Critical Illness in SARS-CoV-2 Infection

Thoracic spinal deformities may reduce chest wall compliance, leading to respiratory complications. The first SARS-CoV-2 (L-variant) strain caused critical respiratory illness, especially in vulnerable patients. This study investigates the association between scoliosis and SARS-CoV-2 (COVID-19) disease course severity. Clinical data of 129 patients treated between March 2020 to June 2021 who received a positive COVID-19 polymerase chain reaction result from Mount Sinai and had a scoliosis ICD-10 code (M41.0-M41.9) was retrospectively analyzed. Degree of coronal plane scoliosis on imaging was confirmed by 2 independent measurers and grouped into no scoliosis (Cobb angle <10°), mild (10°-24°), moderate (25°-39°), and severe (>40°) cohorts. Baseline characteristics were compared, and a multivariable logistic regression controlling for clinically significant comorbidities examined the significance of scoliosis as an independent risk factor for hospitalization, intensive care unit (ICU) admission, acute respiratory distress syndrome (ARDS), mechanical ventilation, and mortality. The no (n= 42), mild (n=14), moderate (n=44), and severe scoliosis (n= 29) cohorts differed significantly only in age (P= 0.026). The percentage ofpatients hospitalized (P= 0.59), admitted to the ICU(P= 0.33), developing ARDS (P= 0.77), requiring mechanical ventilation (P= 1.0), or who expired (P=0.77) did not significantly differ between cohorts. The scoliosis cohorts did not have a significantly higher likelihood of hospital admission (mild P= 0.19, moderate P= 0.67, severe P= 0.98), ICU admission (P= 0.97, P= 0.94, P= 0.22), ARDS (P= 0.87, P= 0.74, P= 0.94), mechanical ventilation (P= 0.73, P= 0.69, P= 0.70), or mortality (P=0.74, P= 0.87, P= 0.66) than the no scoliosis cohort. Scoliosis was not an independent risk factor for critical COVID-19 illness. No trends indicated any consistent effect of degree of scoliosis on increased adverse outcome likelihood.

Outcomes associated with SARS-CoV-2 reinfection in individuals with natural and hybrid immunity

BackgroundStudies comparing SARS-CoV-2 reinfection outcomes among individuals with previous infection (natural immunity) and previous infection plus vaccination (hybrid immunity) are limited. MethodsRetrospective cohort study comparing SARS-CoV-2 reinfection among patients with hybrid immunity (cases) and natural immunity (controls) from March 2020 to February 2022. Reinfection was defined as positive PCR> 90 days after initial laboratory-confirmed SARS-CoV-2 infection. Outcomes included time to reinfection, symptom severity, COVID-19-related hospitalization, critical COVID-19 illness (need for intensive care unit, invasive mechanical ventilation, or death), length of stay (LOS). ResultsA total of 773 (42%) vaccinated and 1073 (58%) unvaccinated patients with reinfection were included. Most patients (62.7%) were asymptomatic. Median time to reinfection was longer with hybrid immunity (391 [311−440] vs 294 [229−406] days, p < 0.001). Cases were less likely to be symptomatic (34.1% vs 39.6%, p = 0.001) or develop critical COVID-19 (2.3% vs 4.3%, p = 0.023). However, there was no significant difference in rates of COVID-19-related hospitalization (2.6% vs 3.8%, p = 0.142) or LOS (5 [2–9] vs 5 [3–10] days, p = 0.446). Boosted patients had longer time to reinfection (439 [IQR 372–467] vs 324 [IQR 256–414] days, p < 0.001) and were less likely to be symptomatic (26.8% vs 38%, p = 0.002) compared to unboosted patients. Rates of hospitalization, progression to critical illness and LOS were not significantly different between the two groups. ConclusionsNatural and hybrid immunity provided protection against SARS-CoV-2 reinfection and hospitalization. However, hybrid immunity conferred stronger protection against symptomatic disease and progression to critical illness and was associated with longer time to reinfection. The stronger protection conferred by hybrid immunity against severe outcomes due to COVID-19 should be emphasized with the public to further the vaccination effort, especially in high-risk individuals.

GWAS and meta-analysis identifies 49 genetic variants underlying critical COVID-19

Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown1 to be highly efficient for discovery of genetic associations2. Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group3. Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Coping in times of disruption and deprivation-Experiences of family members during COVID-19 patients' critical illness: A qualitative study.

To explore the experiences and needs of family members during the course of COVID-19 critical illness from onset to rehabilitation. An exploratory qualitative study. Twelve family members of surviving critically ill COVID-19 patients and restricted from visiting the patients, were interviewed digitally. Reflexive thematic analysis was used. Three themes were generated from the data; 'Experiencing a double burden', 'Becoming an insignificant other' and 'Regaining significance'. Family members were often ill themselves, which represented an extra burden when the patient deteriorated. From admission, the family members became bystanders, deprived of most contact with the patients, as communication and information from the intensive care unit appeared unstructured and haphazard. However, when patients were discharged, great responsibility was placed on the family members.

Neurorecovery after Critical COVID-19 Illness

With the hundreds of millions of people worldwide who have been, and continue to be, affected by pandemic coronavirus disease (COVID-19) and its chronic sequelae, strategies to improve recovery and rehabilitation from COVID-19 are critical global public health priorities. Neurologic complications have been associated with acute COVID-19 infection, usually in the setting of critical COVID-19 illness. Neurologic complications are also a core feature of the symptom constellation of long COVID and portend poor outcomes. In this article, we review neurologic complications and their mechanisms in critical COVID-19 illness and long COVID. We focus on parallels with neurologic disease associated with non-COVID critical systemic illness. We conclude with a discussion of how recent findings can guide both neurologists working in post-acute neurologic rehabilitation facilities and policy makers who influence neurologic resource allocation.