Previous studies have found a correlation between malnutrition and prognosis in respiratory infections. Our objectives were to determine (i) the percentage of malnutrition, and (ii) its prognosis in patients admitted for coronavirus disease 2019 (COVID-19). In this monocentric retrospective study, we consecutively included all adult patients presenting with acute COVID-19 between 9 April and 29 May 2020. Malnutrition was diagnosed on low body mass index (BMI) and weight loss ≥ 5% in the previous month and/or ≥ 10% in the previous six months. The Nutritional Risk Index (NRI) defined nutritional risk. Severe COVID-19 was defined as a need for nasal oxygen ≥ 6 L/min. We enrolled 108 patients (64 men, 62 ± 16 years, BMI 28.8 ± 6.2 kg/m2), including 34 (31.5%) with severe COVID-19. Malnutrition was found in 42 (38.9%) patients, and moderate or severe nutritional risk in 83 (84.7%) patients. Malnutrition was not associated with COVID-19 severity. Nutritional risk was associated with severe COVID-19 (p < 0.01; p < 0.01 after adjustment for C reactive protein), as were lower plasma proteins, albumin, prealbumin, and zinc levels (p < 0.01). The main cause of malnutrition was inflammation. The high percentage of malnutrition and the association between nutritional risk and COVID-19 prognosis supports international guidelines advising regular screening and nutritional support when necessary.

Objectives: Coronavirus disease 2019 (COVID-19) vaccination is reportedly efficient in people with HIV (PWH) but vaccine trials included participants with normal CD4 þ Tcell counts. We analyzed seroconversion rates and antibody titers following two-dose vaccination in PWH with impaired CD4 þ T-cell counts. Methods:We collected retrospective postvaccination SARS-COV-2 serology results available in a university hospital for PWH vaccinated between March and September, 2021 who were tested for antispike antibodies from 8 to 150 days following dose 2. Antibody titers were compared in PWH with CD4 þ T-cell count less than 200 cells/ml, 200 < CD4 þ T-cell counts < 500 cells/ml and CD4 þ T-cell count greater than 500 cells/ml at vaccination.Results: One hundred and five PWH were included: n ¼ 54 in the CD4 þ T-cell count less than 500 cells/ml group (n ¼ 18 with CD4 þ <200 cells/ml, n ¼ 36 with 200 < CD4 þ < 500 cells/ml) and 51 in the CD4 þ T-cell count greater than 500 cells/ml group. They received two doses of BNT162b2 (75%), mRNA-1273 (8.5%), or ChAdOx1 nCoV-19 (16.5%). The median time from vaccine dose 2 to serology was consistent across all groups (73 days, interquartile range [29-97], P ¼ 0.14). Seroconversion rates were 100% in the CD4 þ T-cell count greater than 500 cells/ml group but 89% in participants with CD4 þ T-cell counts less than 500 cells/ml (22 and 5.5% seronegative in the CD4 þ T-cell counts <200 cells/ml and 200 < CD4 þ < 500 cells/ml groups, respectively). Median antibody titers were 623.8 BAU/ml [262.2-2288] in the CD4 þ greater than 500 cells/ml group versus 334.3 BAU/ml [69.9-933.9] in the CD4 þ less than 500 cells/ml group (P ¼ 0.003). They were lowest in the CD4 þ less than 200 cells/ml group: 247.9 BAU/ml [5.88-434.9] (P ¼ 0.0017) with only 44% achieving antibody titers above the putative protection threshold of 260 BAU/ml. Conclusion:PWH with CD4 þ T-cell counts less than 500 cells/ml and notably less than 200 cells/ml had significantly lower seroconversion rates and antispike antibody titers compared with PWH with CD4 þ T-cell counts greater than 500 cells/ml, warranting the consideration of targeted vaccine strategies in this fragile population.

Background We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. Methods We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5–528.7, P = 1.1 × 10−4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3–8.2], P = 2.1 × 10−4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1–2635.4], P = 3.4 × 10−3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3–8.4], P = 7.7 × 10−8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10−5). Conclusions Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old.