bims-covirf Biomed News
on COVID19 risk factors
Issue of 2021–04–04
four papers selected by
Catherine Rycroft, BresMed



  1. Arch Virol. 2021 Apr 02.
      Coronavirus disease 2019 (COVID-19), defined by the World Health Organization (WHO), has affected more than 50 million patients worldwide and caused a global public health emergency. Therefore, there is a recognized need to identify risk factors for COVID-19 severity and mortality. A systematic search of electronic databases (PubMed, Embase and Cochrane Library) for studies published before September 29, 2020, was performed. Studies that investigated risk factors for progression and mortality in COVID-19 patients were included. A total 344,431 participants from 34 studies were included in this meta-analysis. Regarding comorbidities, cerebrovascular disease (CVD), chronic kidney disease (CKD), coronary heart disease (CHD), and malignancy were associated with an increased risk of progression and mortality in COVID-19 patients. Regarding clinical manifestations, sputum production was associated with a dramatically increased risk of progression and mortality. Hemoptysis was a risk factor for death in COVID-19 patients. In laboratory examinations, increased neutrophil count, decreased lymphocyte count, decreased platelet count, increased C-reactive protein (CRP), coinfection with bacteria or fungi, increased alanine aminotransferase (ALT) and creatine kinase (CK), increased N-terminal pronatriuretic peptide (NT-proBNP), and bilateral pneumonia in CT/X-ray were significantly more frequent in the severe group compared with the non-severe group. Moreover, the proportion of patients with increased CRP and total bilirubin (TBIL) was also significantly higher in the deceased group than in the survival group. CVD, CKD, sputum production, increased neutrophil count, decreased lymphocyte count, decreased platelet count, increased CRP, coinfection with bacteria or fungi, increased ALT and CK, increased NT-proBNP, and bilateral pneumonia in CT/X-ray were associated with an increased risk of progression in COVID-19 patients. Moreover, the proportion of patients with increased sputum production, hemoptysis, CRP and TBIL was also significantly higher in the deceased group.
    DOI:  https://doi.org/10.1007/s00705-021-05012-2
  2. J Clin Med. 2021 Mar 12. pii: 1194. [Epub ahead of print]10(6):
      The independent role of hypertension for COVID-19 outcomes in the population remains unclear. We aimed to estimate the independent effect of hypertension and hypertension-related conditions, i.e., cardiovascular, cerebrovascular and chronic kidney diseases, as potential risk factors for COVID-19 hospitalization and severe COVID-19 (i.e., intensive care unit admission or death) in the population. The risk for severe COVID-19 among hospitalized patients was also evaluated. A Spanish population-based cohort of people aged 25-79 years was prospectively followed from March to May 2020 to identify hospitalizations for laboratory-confirmed COVID-19. Poisson regression was used to estimate the adjusted relative risk (aRR) for COVID-19 hospitalization and severe COVID-19 among the whole cohort, and for severe COVID-19 among hospitalized patients. Of 424,784 people followed, 1106 were hospitalized by COVID-19 and 176 were severe cases. Hypertension was not independently associated with a higher risk of hospitalization (aRR 0.96, 95% CI 0.83-1.12) nor severe COVID-19 (aRR 1.12, 95% CI 0.80-1.56) in the population. Persons with cardiovascular, cerebrovascular and chronic kidney diseases were at higher risk for COVID-19 hospitalization (aRR 1.33, 95% CI 1.13-1.58; aRR 1.41, 95% CI 1.04-1.92; and aRR 1.52, 95% CI 1.21-1.91; respectively) and severe COVID-19 (aRR 1.61, 95% CI 1.13-2.30; aRR 1.91, 95% CI 1.13-3.25; and aRR 1.78, 95% CI 1.14-2.76; respectively). COVID-19 hospitalized patients with cerebrovascular diseases were at higher risk of mortality (aRR 1.80, 95% CI 1.00-3.23). The current study shows that, in the general population, persons with cardiovascular, cerebrovascular and chronic kidney diseases, but not those with hypertension only, should be considered as high-risk groups for COVID-19 hospitalization and severe COVID-19.
    Keywords:  COVID-19 hospitalization; COVID-19 mortality; SARS-CoV-2; cardiovascular disease; cerebrovascular disease; chronic kidney disease; hypertension
    DOI:  https://doi.org/10.3390/jcm10061194
  3. JAMA Netw Open. 2021 03 01. 4(3): e216315
       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.
    DOI:  https://doi.org/10.1001/jamanetworkopen.2021.6315
  4. Metabolism. 2021 Mar 24. pii: S0026-0495(21)00053-6. [Epub ahead of print] 154753
       BACKGROUND: Disease severity and mortality rates due to COVID-19 infection are greater in the elderly and chronically ill patients, populations at high risk for vitamin D deficiency. Vitamin D plays an important role in immune function and inflammation. This systematic review and meta-analysis assesses the impact of vitamin D status and supplementation on COVID-19 related mortality and health outcomes.
    METHODS: We searched four databases until December 18th 2020, and trial registries until January 20th 2021. Two reviewers screened the studies, collected data, assessed the risk of bias, and graded the evidence for each outcome across studies, independently and in duplicate. Pre-specified outcomes of interest were mortality, ICU admission, invasive and non-invasive ventilation, hospitalization, time of hospital stay, disease severity and SARS-CoV-2 positivity. We only included data from peer-reviewed articles in our primary analyses.
    RESULTS: We identified 31 peer-reviewed observational studies. In our primary analysis, there was a positive trend between serum 25(OH)D level < 20 ng/ml and an increased risk of mortality, ICU admission, invasive ventilation, non-invasive ventilation or SARS-CoV-2 positivity. However, these associations were not statistically significant. Mean 25(OH)D levels was 5.9 ng/ml (95%CI [-9.5, -2.3]) significantly lower in COVID-19 positive, compared to negative patients. The certainty of the evidence was very low. We identified 32 clinical trial protocols, but only three have published results to-date. The trials administer vitamin D doses of 357 to 60,000 IU/d, from one week to 12 months. Eight megatrials investigate the efficacy of vitamin D in outpatient populations. A pilot trial revealed a significant decrease in ICU admission with calcifediol, compared to placebo (OR = 0.003), but the certainty of the evidence was unclear. Another small trial showed that supplementation with cholecalciferol, 60,000 IU/d, decreased fibrinogen levels, but did not have an effect on D-dimer, procalcitonin and CRP levels, compared to placebo. The third trial did not find any effect of vitamin D supplementation on COVID-19 related health outcomes.
    CONCLUSION: While the available evidence to-date, from largely poor-quality observational studies, may be viewed as showing a trend for an association between low serum 25(OH)D levels and COVID-19 related health outcomes, this relationship was not found to be statistically significant. Calcifediol supplementation may have a protective effect on COVID-19 related ICU admissions. The current use of high doses of vitamin D in COVID-19 patients is not based on solid evidence. It awaits results from ongoing trials to determine the efficacy, desirable doses, and safety, of vitamin D supplementation to prevent and treat COVID-19 related health outcomes.
    Keywords:  COVID-19; Hospitalization; ICU admission; Mortality; Vitamin D
    DOI:  https://doi.org/10.1016/j.metabol.2021.154753