Relationship between leukocyte, neutrophil, lymphocyte, platelet counts, and neutrophil to lymphocyte ratio and polymerase chain reaction positivity.

BACKGROUND: Exposure to viral or bacterial pathogens increases the number of neutrophils with a relative decrease in lymphocytes, leading to elevated neutrophil to lymphocyte ratio (NLR). This study aimed to investigate whether differences in NLR among real-time polymerase chain reaction (PCR)-positive and -negative patients presenting with a prediagnosis of COVID-19 pneumonia could be useful in the differential diagnosis. METHODS: The study included 174 patients admitted because of suspected COVID-19 infection between March and April 2020. Patients were divided into two groups: PCR-negative and PCR-positive. Hemogram, NLR, urea, creatinine, aspartate aminotransferase, alanine aminotransferase, bilirubin, ferritin, D-dimer, C-reactive protein, procalcitonin, troponin, and coagulation parameters were analyzed. RESULTS: On comparison of laboratory parameters between both groups at presentation, PCR-positive patients were significantly more likely to have leukopenia (p < 0.001), thrombocytopenia (p = 0.006), neutropenia (p < 0.001), lymphopenia (p = 0.001), and increased NLR (p = 0.003). Furthermore, PCR-positive patients showed significant elevations of ferritin (p = 0.012) and procalcitonin (p = 0.038) and significant lower potassium levels (p = 0.05). CONCLUSION: COVID-19 pneumonia has become a major global health problem. Early diagnosis and treatment of these patients are crucial, as COVID-19 pneumonia shows a rapid progression in most cases. Thus, leukopenia, thrombocytopenia, elevated NLR, and elevated ferritin may be useful as supplementary diagnostic tests in these patients, which may allow early initiation of treatment and may contribute to preventing progression in patients with abnormal results.

Evidence Regarding Vitamin D and Risk of COVID-19 and Its Severity.

Vitamin D deficiency co-exists in patients with COVID-19. At this time, dark skin color, increased age, the presence of pre-existing illnesses and vitamin D deficiency are features of severe COVID disease. Of these, only vitamin D deficiency is modifiable. Through its interactions with a multitude of cells, vitamin D may have several ways to reduce the risk of acute respiratory tract infections and COVID-19: reducing the survival and replication of viruses, reducing risk of inflammatory cytokine production, increasing angiotensin-converting enzyme 2 concentrations, and maintaining endothelial integrity. Fourteen observational studies offer evidence that serum 25-hydroxyvitamin D concentrations are inversely correlated with the incidence or severity of COVID-19. The evidence to date generally satisfies Hill's criteria for causality in a biological system, namely, strength of association, consistency, temporality, biological gradient, plausibility (e.g., mechanisms), and coherence, although experimental verification is lacking. Thus, the evidence seems strong enough that people and physicians can use or recommend vitamin D supplements to prevent or treat COVID-19 in light of their safety and wide therapeutic window. In view of public health policy, however, results of large-scale vitamin D randomized controlled trials are required and are currently in progress.

Vitamin D Supplementation Associated to Better Survival in Hospitalized Frail Elderly COVID-19 Patients: The GERIA-COVID Quasi-Experimental Study.

BACKGROUND: The objective of this quasi-experimental study was to determine whether bolus vitamin D supplementation taken either regularly over the preceding year or after the diagnosis of COVID-19 was effective in improving survival among hospitalized frail elderly COVID-19 patients. METHODS: Seventy-seven patients consecutively hospitalized for COVID-19 in a geriatric unit were included. Intervention groups were participants regularly supplemented with vitamin D over the preceding year (Group 1), and those supplemented with vitamin D after COVID-19 diagnosis (Group 2). The comparator group involved participants having received no vitamin D supplements (Group 3). Outcomes were 14-day mortality and highest (worst) score on the ordinal scale for clinical improvement (OSCI) measured during COVID-19 acute phase. Potential confounders were age, gender, functional abilities, undernutrition, cancer, hypertension, cardiomyopathy, glycated hemoglobin, number of acute health issues at admission, hospital use of antibiotics, corticosteroids, and pharmacological treatments of respiratory disorders. RESULTS: The three groups (n = 77; mean ± SD, 88 ± 5years; 49% women) were similar at baseline (except for woman proportion, p = 0.02), as were the treatments used for COVID-19. In Group 1 (n = 29), 93.1% of COVID-19 participants survived at day 14, compared to 81.2% survivors in Group 2 (n = 16) (p = 0.33) and 68.7% survivors in Group 3 (n = 32) (p = 0.02). While considering Group 3 as reference (hazard ratio (HR) = 1), the fully-adjusted HR for 14-day mortality was HR = 0.07 (p = 0.017) for Group 1 and HR = 0.37 (p = 0.28) for Group 2. Group 1 had longer survival time than Group 3 (log-rank p = 0.015), although there was no difference between Groups 2 and 3 (log-rank p = 0.32). Group 1, but not Group 2 (p = 0.40), was associated with lower risk of OSCI score ≥5 compared to Group 3 (odds ratio = 0.08, p= 0.03). CONCLUSIONS: Regular bolus vitamin D supplementation was associated with less severe COVID-19 and better survival in frail elderly.

A point-of-care selenium nanoparticle-based test for the combined detection of anti-SARS-CoV-2 IgM and IgG in human serum and blood.

COVID-19 is a widespread and highly contagious disease in the human population. COVID-19 is caused by SARS-CoV-2 infection. There is still a great demand for point-of-care tests for detection, epidemic prevention and epidemiological investigation, both now and after the epidemic. We present a lateral flow immunoassay kit based on a selenium nanoparticle-modified SARS-CoV-2 nucleoprotein, which detects anti-SARS-CoV-2 IgM and anti-SARS-CoV-2 IgG in human serum, and the results can be read by the naked eye in 10 minutes. We expressed and purified the SARS-CoV-2 nucleoprotein in HEK293 cells, with a purity of 98.14% and a concentration of 5 mg mL-1. Selenium nanoparticles were synthesized by l-ascorbic acid reduction of seleninic acid at room temperature. After conjugation with the nucleoprotein, a lateral flow kit was successfully prepared. The IgM and IgG detection limits of the lateral flow kit reached 20 ng mL-1 and 5 ng mL-1, respectively, in human serum. A clinical study sample comprising 90 COVID-19-diagnosed patients and 263 non-infected controls was used to demonstrate a sensitivity and specificity of 93.33% and 97.34%, respectively, based on RT-PCR and clinical results. No cross-reactions with rheumatoid factor and positive serum for anti-nuclear antibodies, influenza A, and influenza B were observed. Moreover, the lateral flow kit remained stable after storage for 30 days at 37 °C. Our results demonstrate that the selenium nanoparticle lateral flow kit can conveniently, rapidly, and sensitively detect anti-SARS-CoV-2 IgM and IgG in human serum and blood; it can also be suitable for the epidemiological investigation of COVID-19.

Is vitamin D deficiency a risk factor for COVID-19 in children?

OBJECTIVE: Coronavirus disease 2019 (COVID-19) is a global health problem that can result in serious complications. The aim of this study was to investigate the prevalence and clinical importance of vitamin D deficiency in children with COVID-19. MATERIAL AND METHODS: This study includes 40 patients who were diagnosed to have COVID-19 and hospitalized with the real-time reverse transcription polymerase chain reaction method, 45 healthy matched control subjects with vitamin D levels. The age of admission, clinical and laboratory data, and 25-hydroxycholecalciferol (25-OHD) levels were recorded. Those with vitamin D levels which are below 20 ng/ml were determined as Group 1 and those with ≥20 ng/ml as Group 2. RESULTS: Patients with COVID-19 had significantly lower vitamin D levels 13.14 µg/L (4.19-69.28) than did the controls 34.81 (3.8-77.42) µg/L (p < .001). Patients with COVID-19 also had significantly lower serum phosphorus (4.09 ± 0.73 vs. 5.06 ± 0.93 vs. (U/L) (p < .001)) values compared with the controls. The symptom of fever was significantly higher in COVID- 19 patients who had deficient and insufficient vitamin D levels than in patients who had sufficient vitamin D levels (p = .038). There was a negative correlation found between fever symptom and vitamin D level (r = -0.358, p = .023). CONCLUSION: This is the first to evaluate vitamin D levels and its relationship with clinical findings in pediatric patients with COVID-19. Our results suggest that vitamin D values may be associated with the occurrence and management of the COVID-19 disease by modulating the immunological mechanism to the virus in the pediatric population.

Clinical analysis of 132 cases COVID-19 from Wuhan.

Numerous cases of pneumonia from a novel coronavirus (SARS-CoV-2) emerged in Wuhan, China during December 2019.We determined the correlations of patient parameters with disease severity in patients with COVID-19.A total of 132 patients from Wuhan Fourth Hospital who had COVID-19 from February 1 to February 29 in 2020 were retrospectively analyzed.Ninety patients had mild disease, 32 had severe disease, and 10 had critical disease. The severe/critical group was older (P < .05), had a higher proportion of males (P < .05), and had a greater mortality rate (0% vs 61.9%, P < .05). The main symptoms were fever (n = 112, 84.8%) and cough (n = 96, 72.7%). Patients were treated with antiviral agents (n = 94, 71.2%), antibiotics (n = 92, 69.7%), glucocorticoids (n = 46, 34.8%), intravenous immunoglobulin (n = 38, 27.3%), and/or traditional Chinese medicine (n = 40, 30.3%). Patients in the severe/critical group received mechanical ventilation (n = 22, 16.7%) or high-flow nasal can-nula oxygen therapy (n = 6, 4.5%). Chest computed tomography (CT) indicated bilateral pneumonia in all patients. Relative to the mild group, the severe/critical group had higher levels of leukocytes, C-reactive protein (CRP), procalcitonin (PCT), D-dimer, B-type natriuretic peptide (BNP), liver enzymes, and myocardial enzymes (P < .05), and decreased levels of lymphocytes and blood oxygen partial pressure (P < .05).The main clinical symptoms of patients from Wuhan who had COVID-19 were fever and cough. Patients with severe/critical disease were more likely to be male and elderly. Disease severity correlated with increased leukocytes, CRP, PCT, BNP, D-dimer, liver enzymes, and myocardial enzymes, and with decreased lymphocytes and blood oxygen partial pressure.

Relationships between hyperinsulinaemia, magnesium, vitamin D, thrombosis and COVID-19: rationale for clinical management.

Risk factors for COVID-19 patients with poorer outcomes include pre-existing conditions: obesity, type 2 diabetes mellitus, cardiovascular disease (CVD), heart failure, hypertension, low oxygen saturation capacity, cancer, elevated: ferritin, C reactive protein (CRP) and D-dimer. A common denominator, hyperinsulinaemia, provides a plausible mechanism of action, underlying CVD, hypertension and strokes, all conditions typified with thrombi. The underlying science provides a theoretical management algorithm for the frontline practitioners.Vitamin D activation requires magnesium. Hyperinsulinaemia promotes: magnesium depletion via increased renal excretion, reduced intracellular levels, lowers vitamin D status via sequestration into adipocytes and hydroxylation activation inhibition. Hyperinsulinaemia mediates thrombi development via: fibrinolysis inhibition, anticoagulation production dysregulation, increasing reactive oxygen species, decreased antioxidant capacity via nicotinamide adenine dinucleotide depletion, haem oxidation and catabolism, producing carbon monoxide, increasing deep vein thrombosis risk and pulmonary emboli. Increased haem-synthesis demand upregulates carbon dioxide production, decreasing oxygen saturation capacity. Hyperinsulinaemia decreases cholesterol sulfurylation to cholesterol sulfate, as low vitamin D regulation due to magnesium depletion and/or vitamin D sequestration and/or diminished activation capacity decreases sulfotransferase enzyme SULT2B1b activity, consequently decreasing plasma membrane negative charge between red blood cells, platelets and endothelial cells, thus increasing agglutination and thrombosis.Patients with COVID-19 admitted with hyperglycaemia and/or hyperinsulinaemia should be placed on a restricted refined carbohydrate diet, with limited use of intravenous dextrose solutions. Degree/level of restriction is determined by serial testing of blood glucose, insulin and ketones. Supplemental magnesium, vitamin D and zinc should be administered. By implementing refined carbohydrate restriction, three primary risk factors, hyperinsulinaemia, hyperglycaemia and hypertension, that increase inflammation, coagulation and thrombosis risk are rapidly managed.

Vitamin D Deficiency and Outcome of COVID-19 Patients.

Infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) poses an enormous challenge to health care systems throughout the world. Without causal treatment, identification of modifiable prognostic factors may help to improve outcomes. To explore possible associations of vitamin D (VitD) status with disease severity and survival, we studied 185 patients diagnosed with coronavirus disease 2019 (COVID-19) and treated at our center. VitD status at first presentation was assessed retrospectively using accredited laboratory methods. VitD deficiency was defined as serum total 25-hydroxyvitamin D level < 12 ng/mL (<30 nM). Primary endpoint was severe course of disease (i.e., need for invasive mechanical ventilation and/or death, IMV/D). Within a median observation period of 66 days (range 2-92), 23 patients required IMV. A total of 28 patients had IMV/D, including 16 deaths. Ninety-three (50%) patients required hospitalization (inpatient subgroup). A total of 41 (22%) patients were VitD deficient. When adjusted for age, gender, and comorbidities, VitD deficiency was associated with higher risk of IMV/D and death (HR 6.12, 95% CI 2.79-13.42, p < 0.001 and HR 14.73, 95% CI 4.16-52.19, p < 0.001, respectively). Similar correlations were observed in the inpatient subgroup. Our study demonstrates an association between VitD deficiency and severity/mortality of COVID-19, highlighting the need for interventional studies on VitD supplementation in SARS-CoV-2 infected individuals.

SARS-CoV-2 positivity rates associated with circulating 25-hydroxyvitamin D levels.

Until treatment and vaccine for coronavirus disease-2019 (COVID-19) becomes widely available, other methods of reducing infection rates should be explored. This study used a retrospective, observational analysis of deidentified tests performed at a national clinical laboratory to determine if circulating 25-hydroxyvitamin D (25(OH)D) levels are associated with severe acute respiratory disease coronavirus 2 (SARS-CoV-2) positivity rates. Over 190,000 patients from all 50 states with SARS-CoV-2 results performed mid-March through mid-June, 2020 and matching 25(OH)D results from the preceding 12 months were included. Residential zip code data was required to match with US Census data and perform analyses of race/ethnicity proportions and latitude. A total of 191,779 patients were included (median age, 54 years [interquartile range 40.4-64.7]; 68% female. The SARS-CoV-2 positivity rate was 9.3% (95% C.I. 9.2-9.5%) and the mean seasonally adjusted 25(OH)D was 31.7 (SD 11.7). The SARS-CoV-2 positivity rate was higher in the 39,190 patients with "deficient" 25(OH)D values (<20 ng/mL) (12.5%, 95% C.I. 12.2-12.8%) than in the 27,870 patients with "adequate" values (30-34 ng/mL) (8.1%, 95% C.I. 7.8-8.4%) and the 12,321 patients with values ≥55 ng/mL (5.9%, 95% C.I. 5.5-6.4%). The association between 25(OH)D levels and SARS-CoV-2 positivity was best fitted by the weighted second-order polynomial regression, which indicated strong correlation in the total population (R2 = 0.96) and in analyses stratified by all studied demographic factors. The association between lower SARS-CoV-2 positivity rates and higher circulating 25(OH)D levels remained significant in a multivariable logistic model adjusting for all included demographic factors (adjusted odds ratio 0.984 per ng/mL increment, 95% C.I. 0.983-0.986; p<0.001). SARS-CoV-2 positivity is strongly and inversely associated with circulating 25(OH)D levels, a relationship that persists across latitudes, races/ethnicities, both sexes, and age ranges. Our findings provide impetus to explore the role of vitamin D supplementation in reducing the risk for SARS-CoV-2 infection and COVID-19 disease.

Are Adequate Vitamin D Levels Helpful in Fighting COVID-19? A Look at the Evidence.

COVID-19 is a global pandemic with high mortality in vulnerable groups. Given the current lack of definitive treatment or vaccine that significantly reduces mortality rate, governments, researchers and healthcare providers are racing to find possible solutions to the crisis. Vitamin D and its analogues have been previously studied for their non-skeletal benefits. In particular, questions regarding their role in the modulation of immunity have re-surfaced, in view of possible epidemiological links observed between COVID-19 and vitamin D levels in selected populations. In this review, we highlight potential mechanisms and summarise the evidence for and against the potential role of vitamin D supplementation in our fight against COVID-19.

Point of view: Should COVID-19 patients be supplemented with vitamin D?

Using Hill's methodology for exploring causality, we aimed to determine in early May 2020 whether evidence supports vitamin D as a biological determinant of COVID-19 outcomes. Vitamin D is a secosteroid hormone theoretically able to reduce COVID-19 risk through regulation of (i) the renin-angiotensin system, (ii) cellular innate and adaptive immunity, and (iii) physical barriers. Inverse associations were found between 25-hydroxyvitamin D concentrations and COVID-19 incidence and mortality. Randomized controlled trials testing vitamin D supplementation in the treatment of COVID-19 are in progress. Positive results in such studies would encourage the use of vitamin D supplements as an adjuvant treatment in COVID-19.

Immune Modulatory Effects of Vitamin D on Viral Infections.

Viral infections have been a cause of mortality for several centuries and continue to endanger the lives of many, specifically of the younger population. Vitamin D has long been recognized as a crucial element to the skeletal system in the human body. Recent evidence has indicated that vitamin D also plays an essential role in the immune response against viral infections and suggested that vitamin D deficiency increases susceptibility to viral infections as well as the risk of recurrent infections. For instance, low serum vitamin D levels were linked to increased occurrence of high burdens viral diseases such as hepatitis, influenza, Covid-19, and AIDS. As immune cells in infected patients are responsive to the ameliorative effects of vitamin D, the beneficial effects of supplementing vitamin D-deficient individuals with an infectious disease may extend beyond the impact on bone and calcium homeostasis. Even though numerous studies have highlighted the effect of vitamin D on the immune cells, vitamin D's antiviral mechanism has not been fully established. This paper reviews the recent mechanisms by which vitamin D regulates the immune system, both innate and adaptive systems, and reflects on the link between serum vitamin D levels and viral infections.

Impact of Vitamin D Deficiency on COVID-19-A Prospective Analysis from the CovILD Registry.

The novel Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is a global health concern. Vitamin D (VITD) deficiency has been suggested to alter SARS-CoV-2 susceptibility and the course of disease. Thus, we aimed to investigate associations of VITD status to disease presentation within the CovILD registry. This prospective, multicenter, observational study on long-term sequelae includes patients with COVID-19 after hospitalization or outpatients with persistent symptoms. Eight weeks after PCR confirmed diagnosis, a detailed questionnaire, a clinical examination, and laboratory testing, including VITD status, were evaluated. Furthermore, available laboratory specimens close to hospital admission were used to retrospectively analyze 25-hydroxyvitamin D levels at disease onset. A total of 109 patients were included in the analysis (60% males, 40% females), aged 58 ± 14 years. Eight weeks after the onset of COVID-19, a high proportion of patients presented with impaired VITD metabolism and elevated parathyroid hormone (PTH) levels. PTH concentrations were increased in patients who needed intensive care unit (ICU) treatment, while VITD levels were not significantly different between disease severity groups. Low VITD levels at disease onset or at eight-week follow-up were not related to persistent symptom burden, lung function impairment, ongoing inflammation, or more severe CT abnormalities. VITD deficiency is frequent among COVID-19 patients but not associated with disease outcomes. However, individuals with severe disease display a disturbed parathyroid-vitamin-D axis within their recovery phase. The proposed significance of VITD supplementation in the clinical management of COVID-19 remains elusive.

Vitamin D Supplementation in COVID-19 Patients: A Clinical Case Series.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has infected more than 4.4 million people and caused more than 300,000 deaths partly through acute respiratory distress syndrome with propensity to affect African American and Hispanic communities disproportionately. Patients with worse outcomes have exhibited higher blood plasma levels of proinflammatory cytokines. Activation of the vitamin D receptor expressed on immune cells has been shown to directly reduce the secretion of inflammatory cytokines, such as interleukin-6, and indirectly affect C-reactive protein. AREAS OF UNCERTAINTY: The significance of the vitamin D pathway in patients diagnosed with COVID-19. THERAPEUTIC INNOVATION: Vitamin D supplementation in patients after diagnosis of COVID-19. PATIENTS AND PHARMACOLOGICAL INTERVENTIONS: We report 4 vitamin D deficient patients diagnosed with COVID-19 in April 2020 who were provided with either cholecalciferol of 1000 IU daily (standard dose) or ergocalciferol 50,000 IU daily for 5 days (high dose) as part of supplementation. CLINICAL OUTCOMES: Patients that received a high dose of vitamin D supplementation achieved normalization of vitamin D levels and improved clinical recovery evidenced by shorter lengths of stay, lower oxygen requirements, and a reduction in inflammatory marker status. CONCLUSIONS: Vitamin D supplementation may serve as a viable alternative for curtailing acute respiratory distress syndrome in patients in underserved communities where resources to expensive and sought-after medications may be scarce. Randomized clinical trials will serve as an appropriate vessel to validate the efficacy of the therapeutic regimen and dissection of the pathway.

The Role of Chest Radiograph, Procalcitonin and Moxifloxacin in Diagnosis and Management of Breast Cancer Patients with COVID-19.

Global widespread of current coronavirus disease 2019 (COVID-19) pandemic has emerged huge predicament to healthcare systems globally. This disease caused by a new beta-type coronavirus, known as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), may lead to systemic multiorgan dysfunction syndrome and subsequently cause death due to abundant angiotensin converting enzyme 2 as its functional receptors throughout body. Oncology patients even have a worse prognosis with greater infection susceptibility because they are in a state of suppression of the systemic immune system due to malignancy and anticancer therapy. This problem makes adequate and appropriate treatment urgently needed. Through randomized clinical trials, various drugs were known to have good responses in COVID-19 patients. Here, we reported a-49-year-old-woman that was confirmed for COVID-19 by clinical manifestation, radiology profile, high procalcitonin concentration, and positive polymerase chain reaction (PCR) test. The patient also had breast and thyroid cancers history and had undergone various therapeutic modalities such as chemotherapy, thyroid surgery, and breast surgery. She was undergoing hormone therapy but experiencing disease progression after achieving complete remission based on PET-CT scan 4 months before. The patient was treated with various antibiotics but showed a significant clinical improvement by administering moxifloxacin.

Ankaferd hemostat (ABS) as a potential mucosal topical agent for the management of COVID-19 syndrome based on its PAR-1 inhibitory effect and oestrogen content.

COVID-19 due to the SARS-CoV-2 infection is a multi-systemic immune syndrome affecting mainly the lungs, oropharyngeal region, and other vascular endothelial beds. There are tremendous ongoing efforts for the aim of developing drugs against the COVID-19 syndrome-associated inflammation. However, currently no specific medicine is present for the absolute pharmacological cure of COVID-19 mucositis. The re-purposing/re-positioning of already existing drugs is a very important strategy for the management of ongoing pandemy since the development of a new drug needs decades. Apart from altering angiotensin signaling pathways, novel drug candidates for re-purposing comprise medications shall target COVID-19 pathobiology, including pharmaceutical formulations that antagonize proteinase-activated receptors (PARs), mainly PAR-1. Activation of the PAR-1, mediators and hormones impact on the hemostasis, endothelial activation, alveolar epithelial cells and mucosal inflammatory responses which are the essentials of the COVID-19 pathophysiology. In this context, Ankaferd hemostat (Ankaferd Blood Stopper, ABS) which is an already approved hemostatic agent affecting via vital erythroid aggregation and fibrinogen gamma could be a potential topical remedy for the mucosal management of COVID-19. ABS is a clinically safe and effective topical hemostatic agent of plant origin capable of exerting pleiotropic effects on the endothelial cells, angiogenesis, cell proliferation and vascular dynamics. ABS had been approved as a topically applied hemostatic agent for the management of post-surgical/dental bleedings and healing of infected inflammatory mucosal wounds. The anti-inflammatory and proteinase-activated receptor axis properties of ABS with a considerable amount of oestrogenic hormone presence highlight this unique topical hemostatic drug regarding the clinical re-positioning for COVID-19-associated mucositis. Topical ABS as a biological response modifier may lessen SARS-CoV-2 associated microthrombosis, endothelial dysfunction, oropharyngeal inflammation and mucosal lung damage. Moreover, PAR-1 inhibition ability of ABS might be helpful for reducing the initial virus propagation and mocasal spread of COVID-19.

Vitamin D Insufficiency and Deficiency and Mortality from Respiratory Diseases in a Cohort of Older Adults: Potential for Limiting the Death Toll during and beyond the COVID-19 Pandemic?

The COVID-19 pandemic goes along with increased mortality from acute respiratory disease. It has been suggested that vitamin D3 supplementation might help to reduce respiratory disease mortality. We assessed the prevalence of vitamin D insufficiency and deficiency, defined by 25-hydroxyvitamin D (25(OH)D) blood levels of 30-50 and <30 nmol/L, respectively, and their association with mortality from respiratory diseases during 15 years of follow-up in a cohort of 9548 adults aged 50-75 years from Saarland, Germany. Vitamin D insufficiency and deficiency were common (44% and 15%, respectively). Compared to those with sufficient vitamin D status, participants with vitamin D insufficiency and deficiency had strongly increased respiratory mortality, with adjusted hazard ratios (95% confidence intervals) of 2.1 (1.3-3.2) and 3.0 (1.8-5.2) overall, 4.3 (1.3-14.4) and 8.5 (2.4-30.1) among women, and 1.9 (1.1-3.2) and 2.3 (1.1-4.4) among men. Overall, 41% (95% confidence interval: 20-58%) of respiratory disease mortality was statistically attributable to vitamin D insufficiency or deficiency. Vitamin D insufficiency and deficiency are common and account for a large proportion of respiratory disease mortality in older adults, supporting the hypothesis that vitamin D3 supplementation could be helpful to limit the burden of the COVID-19 pandemic, particularly among women.

Viral Coagulopathy in Patients With COVID-19: Treatment and Care.

COVID-19 has proven to be particularly challenging given the complex pathogenesis of SARS-CoV-2. Early data have demonstrated how the host response to this novel coronavirus leads to the proliferation of pro-inflammatory cytokines, massive endothelial damage, and generalized vascular manifestations. While SARS-CoV-2 primarily targets the upper and lower respiratory tract, other organ systems are also affected. SARS-CoV-2 relies on 2 host cell receptors for successful attachment: angiotensin-converting enzyme 2 and transmembrane protease serine 2. Clinicopathologic reports have demonstrated associations between severe COVID-19 and viral coagulopathy, resulting in pulmonary embolism; venous, arterial, and microvascular thrombosis; lung endothelial injury; and associated thrombotic complications leading to acute respiratory distress syndrome. Viral coagulopathy is not novel given similar observations with SARS classic, including the consumption of platelets, generation of thrombin, and increased fibrin degradation product exhibiting overt disseminated intravascular coagulation-like syndrome. The specific mechanism(s) behind the thrombotic complications in COVID-19 patients has yet to be fully understood. Parenteral anticoagulants, such as heparin and low-molecular-weights heparins, are widely used in the management of COVID-19 patients. Beyond the primary (anticoagulant) effects of these agents, they may exhibit antiviral, anti-inflammatory, and cytoprotective effects. Direct oral anticoagulants and antiplatelet agents are also useful in the management of these patients. Tissue plasminogen activator and other fibrinolytic modalities may also be helpful in the overall management. Catheter-directed thrombolysis can be used in patients developing pulmonary embolism. Further investigations are required to understand the molecular and cellular mechanisms involved in the pathogenesis of COVID-19-associated thrombotic complications.

Immunologic Effects of Vitamin D on Human Health and Disease.

Vitamin D is responsible for regulation of calcium and phosphate metabolism and maintaining a healthy mineralized skeleton. It is also known as an immunomodulatory hormone. Experimental studies have shown that 1,25-dihydroxyvitamin D, the active form of vitamin D, exerts immunologic activities on multiple components of the innate and adaptive immune system as well as endothelial membrane stability. Association between low levels of serum 25-hydroxyvitamin D and increased risk of developing several immune-related diseases and disorders, including psoriasis, type 1 diabetes, multiple sclerosis, rheumatoid arthritis, tuberculosis, sepsis, respiratory infection, and COVID-19, has been observed. Accordingly, a number of clinical trials aiming to determine the efficacy of administration of vitamin D and its metabolites for treatment of these diseases have been conducted with variable outcomes. Interestingly, recent evidence suggests that some individuals might benefit from vitamin D more or less than others as high inter-individual difference in broad gene expression in human peripheral blood mononuclear cells in response to vitamin D supplementation has been observed. Although it is still debatable what level of serum 25-hydroxyvitamin D is optimal, it is advisable to increase vitamin D intake and have sensible sunlight exposure to maintain serum 25-hydroxyvitamin D at least 30 ng/mL (75 nmol/L), and preferably at 40-60 ng/mL (100-150 nmol/L) to achieve the optimal overall health benefits of vitamin D.