Maternal and Cord Anti-SARS-CoV-2-Spike IgG following COVID-19 Vaccination versus Infection during Pregnancy: A Prospective Study, Israel October 2021-March 2022.

OBJECTIVE: Defining how pregnant women respond to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination is critical to optimize vaccination strategies that protect mother and infant at the epidemic. This study aimed to compare anti-SARS-CoV-2-spike immunoglobulin G (IgG) of vaccinated versus infected women and to determine the optimal timing of maternal vaccination during pregnancy at the time of epidemic. STUDY DESIGN: We collected maternal/cord blood at delivery (October 2021-March 2022) and measured anti-SARS-CoV-2-spike IgG geometric mean concentrations (IgG-GMCs) using a quantitative immunoassay. We compared groups according to timing and number of doses and correlated maternal and fetal IgG levels. We described the proportion of women with IgG levels above the 150 AU/mL positivity threshold according to the timing of infection/vaccination and performed a subanalysis for maternal IgG-GMC levels pre- and during the Omicron wave. RESULTS: We included 238 vaccinated women, 125 who received two doses and 113 three doses, and 48 unvaccinated infected women. All groups infected/vaccinated in the second or third trimester had an IgG-GMC above the positivity threshold. Third-trimester vaccination (second/third dose) resulted in higher maternal and cord-blood IgG-GMC compared to the second trimester (maternal-IgG: 102,32 vs. 4,325 AU/mL, p < 0.001; cord-IgG: 12,113 vs. 8,112 AU/mL, p < 0.001). Compared with infected-only women, a higher proportion of vaccinated women with ≥2 doses and their newborns had IgG levels above the positivity threshold at all time points. In vaccinated women, there were higher maternal IgG-GMC levels during the Omicron wave than pre-Omicron. CONCLUSION: At the time of epidemic, receiving an additional COVID-19 vaccine dose in the third trimester resulted in a higher IgG-GMC compared to the second trimester. Relatively higher levels of maternal and cord IgG-GMC were achieved following vaccination than infection. Women infected during or before the first trimester might benefit from an additional third-trimester dose to prevent peripartum infection and to passively immunize their newborn. The higher levels of maternal IgG-GMC in the Omicron period are suggestive of hybrid immunity. KEY POINTS: · Higher maternal anti-SARS-IgGs in vaccinated → infected.. · Higher cord anti-SARS-IgGs in vaccinated → infected.. · Third-trimester vaccine resulted in high-cord IgG levels..

Baseline moderate-range albuminuria is associated with protection against severe COVID-19 pneumonia.

BACKGROUND: Diabetes mellitus is considered a leading contributor to severe coronavirus disease 2019 (COVID-19). AIM: To characterize differences between hospitalized diabetic patients with vs without COVID-19, and parameters associated with COVID-19 severity for prediction. METHODS: This case-control study included 209 patients with type 2 diabetic mellitus hospitalized at the Galilee Medical Center (Nahariya, Israel) and recruited between September 2020 and May 2021, 65 patients with COVID-19 infection in dedicated wards and 144 COVID-19-negative patients in internal medicine wards hospitalized due to other reasons. Clinical parameters - including age, type of antiglycemic medications, presence of retinopathy, smoking history, body mass index (BMI), glycosylated hemoglobin, maximum neutrophil:lymphocyte ratio (NLRmax), C-reactive protein (CRP), estimated glomerular filtration rate (eGFR), and albumin (blood and urine) - were compared between the two primary patient groups, and then between COVID-19-negative patients hospitalized due to infectious vs non-infectious disease. Finally, we explored which parameters were associated with severe COVID-19 pneumonia. RESULTS: COVID-19-negative patients were older (63.9 ± 9.9 vs 59.8 ± 9.2, P = 0.005), and had longer duration of diabetes (P = 0.031), lower eGFR (P = 0.033), higher albumin (P = 0.026), lower CRP (P < 0.001), greater smoking prevalence (P < 0.001), and more baseline albuminuria (54.9% vs 30.8%, P = 0.005) at admission; 70% of COVID-19 patients with albuminuria had moderate-range albuminuria (albumin:creatinine 30-300 mg/g). Most of the patients with albuminuria had chronic kidney disease stage II (CKD II). Oral antiglycemic therapies were not significantly different between the two groups. Multivariable logistic regression showed that higher BMI was significantly associated with severe COVID-19 (OR 1.24, 95%CI: 1.01-1.53, P = 0.04), as was higher NLRmax (OR 1.2, 95%CI: 1.06-1.37, P = 0.005). Surprisingly, pre-hospitalization albuminuria, mostly moderate-range, was associated with reduced risk (OR 0.09, 95%CI: 0.01-0.62, P = 0.015). Moderate-range albuminuria was not associated with bacterial infections. CONCLUSION: Moderate-range albuminuria in COVID-19-positive diabetic patients with CKD II is associated with less severe COVID-19. Further studies should explore this potential biomarker for risk of COVID-19-related deterioration and early interventions.

Pre-infection 25-hydroxyvitamin D3 levels and association with severity of COVID-19 illness.

OBJECTIVE: Studies have demonstrated a potential correlation between low vitamin D status and both an increased risk of infection with SARS-CoV-2 and poorer clinical outcomes. This retrospective study examines if, and to what degree, a relationship exists between pre-infection serum 25-hydroxyvitamin D (25(OH)D) level and disease severity and mortality due to SARS-CoV-2. PARTICIPANTS: The records of individuals admitted between April 7th, 2020 and February 4th, 2021 to the Galilee Medical Center (GMC) in Nahariya, Israel, with positive polymerase chain reaction (PCR) tests for SARS-CoV-2 (COVID-19) were searched for historical 25(OH)D levels measured 14 to 730 days prior to the positive PCR test. DESIGN: Patients admitted to GMC with COVID-19 were categorized according to disease severity and level of 25(OH)D. An association between pre-infection 25(OH)D levels, divided between four categories (deficient, insufficient, adequate, and high-normal), and COVID-19 severity was ascertained utilizing a multivariable regression analysis. To isolate the possible influence of the sinusoidal pattern of seasonal 25(OH)D changes throughout the year, a cosinor model was used. RESULTS: Of 1176 patients admitted, 253 had records of a 25(OH)D level prior to COVID-19 infection. A lower vitamin D status was more common in patients with the severe or critical disease (<20 ng/mL [87.4%]) than in individuals with mild or moderate disease (<20 ng/mL [34.3%] p < 0.001). Patients with vitamin D deficiency (<20 ng/mL) were 14 times more likely to have severe or critical disease than patients with 25(OH)D ≥40 ng/mL (odds ratio [OR], 14; 95% confidence interval [CI], 4 to 51; p < 0.001). CONCLUSIONS: Among hospitalized COVID-19 patients, pre-infection deficiency of vitamin D was associated with increased disease severity and mortality.

Pre-infection 25-hydroxyvitamin D3 levels and association with severity of COVID-19 illness (preprint)

Objective: Studies have demonstrated a potential link between low vitamin D levels and both an increased risk of infection with SARS-CoV-2 and poorer clinical outcomes but have not established temporality. This retrospective study examined if, and to what degree, a relationship exists between pre-infection serum vitamin D levels and disease severity and mortality of SARS-CoV-19. Design and patients: The records of individuals admitted between April 7th, 2020 and February 4th, 2021 to the Galilee Medical Center (GMC) in Nahariya, Israel with positive polymerase chain reaction (PCR) tests for SARS-CoV-2 were searched for vitamin D (VitD) levels measured 14 to 730 days prior to the positive PCR test. Measurements: Patients admitted to GMC with COVID-19 were categorized according to disease severity and VitD level. Association between pre-infection VitD levels and COVID-19 severity was ascertained utilizing a multivariate regression analysis. Results: Of 1176 patients admitted, 253 had VitD levels prior to COVID-19 infection. Compared with mildly or moderately diseased patients, those with severe or critical COVID-19 disease were more likely to have pre-infection vitamin D deficiency of less than 20 ng/mL (OR=14.30, 95%, 4.01-50.9; p < .001); be older (OR=1.039 for each year, 95% CI for OR, 1.017-1.061; p< .01), and have diabetes (OR=2.031, 95% CI for OR, 1.04-3.36; p= 0.038). Vitamin D deficiency was associated with higher rates of mortality (p<0.001) and comorbidities including COPD (p=0.006), diabetes (p=0.026), and hypertension (p =0.016). Conclusions: Among hospitalized COVID-19 patients, pre-infection deficiency of vitamin D was associated with increased disease severity and mortality.