Neurologic manifestations associated with COVID-19: a multicentre registry

ObjectivesTo provide an overview of the spectrum, characteristics and outcomes of neurologic manifestations associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.MethodsWe conducted a single-centre retrospective study during the French coronavirus disease 2019 (COVID-19) epidemic in March–April 2020. All COVID-19 patients with de novo neurologic manifestations were eligible.ResultsWe included 222 COVID-19 patients with neurologic manifestations from 46 centres in France. Median (interquartile range, IQR) age was 65 (53–72) years and 136 patients (61.3%) were male. COVID-19 was severe or critical in 102 patients (45.2%). The most common neurologic diseases were COVID-19–associated encephalopathy (67/222, 30.2%), acute ischaemic cerebrovascular syndrome (57/222, 25.7%), encephalitis (21/222, 9.5%) and Guillain-Barré syndrome (15/222, 6.8%). Neurologic manifestations appeared after the first COVID-19 symptoms with a median (IQR) delay of 6 (3–8) days in COVID-19–associated encephalopathy, 7 (5–10) days in encephalitis, 12 (7–18) days in acute ischaemic cerebrovascular syndrome and 18 (15–28) days in Guillain-Barré syndrome. Brain imaging was performed in 192 patients (86.5%), including 157 magnetic resonance imaging (70.7%). Among patients with acute ischaemic cerebrovascular syndrome, 13 (22.8%) of 57 had multiterritory ischaemic strokes, with large vessel thrombosis in 16 (28.1%) of 57. Brain magnetic resonance imaging of encephalitis patients showed heterogeneous acute nonvascular lesions in 14 (66.7%) of 21. Cerebrospinal fluid of 97 patients (43.7%) was analysed, with pleocytosis found in 18 patients (18.6%) and a positive SARS-CoV-2 PCR result in two patients with encephalitis. The median (IQR) follow-up was 24 (17–34) days with a high short-term mortality rate (28/222, 12.6%).ConclusionsClinical spectrum and outcomes of neurologic manifestations associated with SARS-CoV-2 infection were broad and heterogeneous, suggesting different underlying pathogenic processes.     

Effectiveness of mRNA-BNT162b2, mRNA-1273, and ChAdOx1 nCoV-19 vaccines against COVID-19 in healthcare workers: an observational study using surveillance data

ObjectivesHealthcare workers (HCWs) at increased risk of coronavirus disease 2019 (COVID-19) were among the primary targets for vaccine campaigns. We aimed to estimate the protective efficacy of the first three COVID-19 vaccines available in Western Europe.MethodsWe merged two prospective databases that systematically recorded, in our institution: (a) HCWs positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by RT-PCR on nasopharyngeal samples, and (b) HCWs who received at least one dose of COVID-19 vaccine. We excluded HCWs with SARS-CoV-2 infection during the 6 months prior to the study. HCWs were categorized as non-vaccinated if they received no vaccine and until the first injection +13 days, partially vaccinated from the first injection +14 days to the second injection +13 days, and fully vaccinated thereafter.ResultsOf the 8165 HCWs employed in our institution, 360 (4.4%) tested positive for SARS-CoV-2 by RT-PCR during the study period (4th January to 17th May 2021). Incidence was 9.1% (8.2–10.0) in non-vaccinated HCWs, 1.2% (0.7–1.9) after one dose of ChAdOx1 nCoV-19, 1.4% (0.6–2.3) and 0.5% (0.1–1.0) after one and two doses of mRNA BNT162b2, 0.7% (0.1–1.9) and 0% after one and two doses of mRNA-1273 (p < 0.0001). Vaccine effectiveness (Cox model) was estimated at, respectively, 86.2% (76.5–91.0), 38.2% (6.3–59.2), and 49.2% (19.1–68.1) 14 days after the first dose for ChAdOx1 nCoV-19, mRNA-1273, and mRNA-BNT162b2, and 100% (ND) and 94.6% (61.0–99.2) 14 days after the second dose for mRNA-1273 and mRNA-BNT162b2.ConclusionsIn this real-world study, the observed effectiveness of COVID-19 vaccines in HCWs was in line with the efficacy reported in pivotal randomized trials.     

Upper respiratory tract SARS-CoV-2 RNA loads in symptomatic and asymptomatic children and adults

ObjectivesStudies comparing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA load in the upper respiratory tract (URT) between children and adults—who either presented with coronavirus disease 2019 (COVID-19) or were asymptomatic—have yielded inconsistent results. Here, we conducted a retrospective, single-centre study to address this issue.Patients and methodsIncluded were 1184 consecutive subjects (256 children and 928 adults) testing positive for SARS-CoV-2 RNA in nasopharyngeal exudates (NPs); of these, 424 (121 children and 303 adults) had COVID-19 and 760 (135 children and 625 adults) were asymptomatic close contacts of COVID-19 patients. SARS-CoV-2 RNA testing was carried out using the TaqPath COVID-19 Combo Kit (Thermo Fisher Scientific, MS, USA). The AMPLIRUN® TOTAL SARS-CoV-2 RNA Control (Vircell SA, Granada, Spain) was used for estimating SARS-CoV-2 RNA loads (in copies/mL). SARS-CoV-2 RNA loads at the time of laboratory diagnosis (single specimen/patient) were used for comparison purposes.ResultsMedian initial SARS-CoV-2 RNA load was lower (p 0.094) in children (6.98 log₁₀ copies/mL, range 3.0–11.7) than in adults (7.14 log₁₀ copies/mL, range 2.2–13.4) with COVID-19. As for asymptomatic individuals, median SARS-CoV-2 RNA load was comparable (p 0.97) in children (6.20 log₁₀ copies/mL, range 1.8–11.6) and adults (6.48 log₁₀ copies/mL, range 1.9–11.8). Children with COVID-19 symptoms displayed SARS-CoV-2 RNA loads (6.98 log₁₀ copies/mL, range 3.0–11.7) comparable to those of their asymptomatic counterparts (6.20 log₁₀ copies/mL, range 1.8–11.6) (p 0.61). Meanwhile in adults, median SARS-CoV-2 RNA load was significantly higher in symptomatic (7.14 log₁₀ copies/mL, range 2.2–13.4) than in asymptomatic subjects (6.48 log₁₀ copies/mL, range 1.9–11.8) (p < 0.001). Overall, the observed URT SARS-CoV-2 RNA clearance rate was faster in children than in adults.ConclusionsBased on viral load data at the time of diagnosis, our results suggest that SARS-CoV-2-infected children, with or without COVID-19, may display NP viral loads of comparable magnitude to those found in their adult counterparts. However, children may have shorter viral shedding than adults.     

National surveillance of bacterial and fungal coinfection and secondary infection in COVID-19 patients in England: lessons from the first wave

ObjectivesThe impact of bacterial/fungal infections on the morbidity and mortality of persons with coronavirus disease 2019 (COVID-19) remains unclear. We have investigated the incidence and impact of key bacterial/fungal infections in persons with COVID-19 in England.MethodsWe extracted laboratory-confirmed cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (1st January 2020 to 2nd June 2020) and blood and lower-respiratory specimens positive for 24 genera/species of clinical relevance (1st January 2020 to 30th June 2020) from Public Health England's national laboratory surveillance system. We defined coinfection and secondary infection as a culture-positive key organism isolated within 1 day or 2–27 days, respectively, of the SARS-CoV-2-positive date. We described the incidence and timing of bacterial/fungal infections and compared characteristics of COVID-19 patients with and without bacterial/fungal infection.Results1% of persons with COVID-19 (2279/223413) in England had coinfection/secondary infection, of which >65% were bloodstream infections. The most common causative organisms were Escherichia coli, Staphylococcus aureus and Klebsiella pneumoniae. Cases with coinfection/secondary infections were older than those without (median 70 years (IQR 58–81) versus 55 years (IQR 38–77)), and a higher percentage of cases with secondary infection were of Black or Asian ethnicity than cases without (6.7% versus 4.1%, and 9.9% versus 8.2%, respectively, p < 0.001). Age-sex-adjusted case fatality rates were higher in COVID-19 cases with a coinfection (23.0% (95%CI 18.8–27.6%)) or secondary infection (26.5% (95%CI 14.5–39.4%)) than in those without (7.6% (95%CI 7.5–7.7%)) (p < 0.005).ConclusionsCoinfection/secondary bacterial/fungal infections were rare in non-hospitalized and hospitalized persons with COVID-19, varied by ethnicity and age, and were associated with higher mortality. However, the inclusion of non-hospitalized persons with asymptomatic/mild COVID-19 likely underestimated the rate of secondary bacterial/fungal infections. This should inform diagnostic testing and antibiotic prescribing strategy.     

Immune repertoire sequencing reveals an abnormal adaptive immune system in COVID-19 survivors

Accumulating evidence suggests that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) impairs the adaptive immune system during acute infection. Still, it remains largely unclear whether the frequency and functions of T and B cells return to normal after the recovery of Coronavirus Disease 2019 (COVID-19). Here, we analyzed immune repertoires and SARS-CoV-2-specific neutralization antibodies in a prospective cohort of 40 COVID-19 survivors with a 6-month follow-up after hospital discharge. Immune repertoire sequencing revealed abnormal T- and B-cell expression and function with large T cell receptor/B cell receptor clones, decreased diversity, abnormal class-switch recombination, and somatic hypermutation. A decreased number of B cells but an increased proportion of CD19⁺CD138⁺ B cells were found in COVID-19 survivors. The proportion of CD4⁺ T cells, especially circulating follicular helper T (cTfh) cells, was increased, whereas the frequency of CD3⁺CD4⁻ T cells was decreased. SARS-CoV-2-specific neutralization IgG and IgM antibodies were identified in all survivors, especially those recorded with severe COVID-19 who showed a higher inhibition rate of neutralization antibodies. All severe cases complained of more than one COVID-19 sequelae after 6 months of recovery. Overall, our findings indicate that SARS-CoV-2-specific antibodies remain detectable even after 6 months of recovery. Because of their abnormal adaptive immune system with a low number of CD3⁺CD4⁻ T cells and high susceptibility to infections, COVID-19 patients might need more time and medical care to fully recover from immune abnormalities and tissue damage.     

B- and T-cell immune responses elicited by the Comirnaty® COVID-19 vaccine in nursing-home residents

ObjectivesThe immunogenicity of the Comirnaty® vaccine against coronavirus disease 2019 (COVID-19) has not been adequately studied in elderly people with comorbidities. We assessed antibody and T-cell responses targeted to the S protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) following full vaccination in nursing-home residents.MethodsSixty nursing-home residents (44 female, age 53–100 years), of whom ten had previously been diagnosed with COVID-19, and 18 healthy controls (15 female, age 27–54 years) were recruited. Pre- and post-vaccination blood specimens were available for quantification of total antibodies binding the SARS-CoV-2 S protein and for enumeration of SARS-CoV-2 S-reactive IFN-γ CD4⁺ and CD8⁺ T cells by flow cytometry.ResultsThe seroconversion rate in (presumably) SARS-CoV-2-naïve nursing-home residents (41/43, 95.3%) was similar to that in controls (17/18, 94.4%). A booster effect was documented in post-vaccination samples of nursing-home residents with prior COVID-19. Plasma antibody levels were higher (p < 0.01) in recovered nursing-home residents (all 2500 IU/mL) than in individuals across the other two groups (median 1120 IU/mL in naïve nursing-home residents and 2211 IU/ml in controls). A large percentage of nursing-home residents had SARS-CoV-2 S-reactive IFN-γ CD8⁺ (naïve 31/49, 63.2%; recovered 8/10, 80%) or CD4⁺ T cells (naïve 35/49, 71.4%; recovered 7/10, 70%) at baseline, in contrast to healthy controls (3/17, 17.6% and 5/17, 29%, respectively). SARS-CoV-2 IFN-γ CD8⁺ and CD4⁺ T-cell responses were documented in 88% (15/17) and all control subjects after vaccination, respectively, but only in 65.5% (38/58) and 22.4% (13/58) of nursing-home residents. Overall, the median frequency of SARS-CoV-2 IFN-γ CD8⁺ and CD4⁺ T cells in nursing-home residents decreased in post-vaccination specimens, whereas it increased in controls.ConclusionThe Comirnaty COVID-19 vaccine elicits robust SARS-CoV-2 S antibody responses in nursing-home residents. Nevertheless, the rate and frequency of detectable SARS-CoV-2 IFN-γ T-cell responses after vaccination was lower in nursing-home residents than in controls.     

Efficacy of favipiravir in adults with mild COVID-19: a randomized,double-blind,multicentre, placebo-controlled clinical trial

ObjectiveTo evaluate whether favipiravir reduces the time to viral clearance as documented by negative RT-PCR results for severe acute respiratory syndrome coronavirus 2 in mild cases of coronavirus disease 2019 (COVID-19) compared to placebo.MethodsIn this randomized, double-blinded, multicentre, and placebo-controlled trial, adults with PCR-confirmed mild COVID-19 were recruited in an outpatient setting at seven medical facilities across Saudi Arabia. Participants were randomized in a 1:1 ratio to receive either favipiravir 1800 mg by mouth twice daily on day 1 followed by 800 mg twice daily (n = 112) or a matching placebo (n = 119) for a total of 5 to 7 days. The primary outcome was the effect of favipiravir on reducing the time to viral clearance (by PCR test) within 15 days of starting the treatment compared to the placebo group. The trial included the following secondary outcomes: symptom resolution, hospitalization, intensive care unit admissions, adverse events, and 28-day mortality.ResultsTwo hundred thirty-one patients were randomized and began the study (median age, 37 years; interquartile range (IQR): 32–44 years; 155 [67%] male), and 112 (48.5%) were assigned to the treatment group and 119 (51.5%) into the placebo group. The data and safety monitoring board recommended stopping enrolment because of futility at the interim analysis. The median time to viral clearance was 10 days (IQR: 6–12 days) in the favipiravir group and 8 days (IQR: 6–12 days) in the placebo group, with a hazard ratio of 0.87 for the favipiravir group (95% CI 0.571–1.326; p = 0.51). The median time to clinical recovery was 7 days (IQR: 4–11 days) in the favipiravir group and 7 days (IQR: 5–10 days) in the placebo group. There was no difference between the two groups in the secondary outcome of hospital admission. There were no drug-related severe adverse events.ConclusionIn this clinical trial, favipiravir therapy in mild COVID-19 patients did not reduce the time to viral clearance within 15 days of starting the treatment.     

Severity-Adjusted Dexamethasone Dosing and Tocilizumab Combination for Severe COVID-19

PurposeReal-world experience with tocilizumab in combination with dexamethasone in patients with severe coronavirus disease (COVID-19) needs to be investigated.Materials and MethodsA retrospective cohort study was conducted to evaluate the effect of severity-adjusted dosing of dexamethasone in combination with tocilizumab for severe COVID-19 from August 2020 to August 2021. The primary endpoint was 30-day clinical recovery, which was defined as no oxygen requirement or referral after recovery.ResultsA total of 66 patients were evaluated, including 33 patients in the dexamethasone (Dexa) group and 33 patients in the dexamethasone plus tocilizumab (DexaToci) group. The DexaToci group showed a statistically significant benefit in 30-day clinical recovery, compared to the Dexa group (p=0.024). In multivariable analyses, peak FiO₂ within 3 days and tocilizumab combination were consistently significant for 30-day recovery (all p<0.05). The DexaToci group showed a significantly steeper decrease in FiO₂ (-4.2±2.6) than the Dexa group (-2.7±2.6; p=0.021) by hospital day 15. The duration of oxygen requirement was significantly shorter in the DexaToci group than the Dexa group (median, 10.0 days vs. 17.0 days; p=0.006). Infectious complications and cellular and humoral immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the convalescence stage were not different between the two groups.ConclusionA combination of severity-adjusted dexamethasone and tocilizumab for the treatment of severe COVID-19 improved clinical recovery without increasing infectious complications or hindering the immune response against SARS-CoV-2.     

Impact of prior statin use on clinical outcomes in COVID-19 patients: data from tertiary referral hospitals during COVID-19 pandemic in Italy

BackgroundEpidemiological evidence suggests that anti-inflammatory and immunomodulatory properties of statins may reduce the risk of infections and infection-related complications.ObjectiveWe aimed to assess the impact of prior statin use on coronavirus disease (COVID-19) severity and mortality.MethodsIn this observational multicenter study, consecutive patients hospitalized for COVID-19 were enrolled. In-hospital mortality and severity of COVID-19 assessed with National Early Warning Score (NEWS) were deemed primary and secondary outcomes, respectively. Propensity score (PS) matching was used to obtain balanced cohorts.ResultsAmong 842 patients enrolled, 179 (21%) were treated with statins before admission. Statin patients showed more comorbidities and more severe COVID-19 (NEWS 4 [IQR 2–6] vs 3 [IQR 2–5], p < 0.001). Despite having similar rates of intensive care unit admission, noninvasive ventilation, and mechanical ventilation, statin users appeared to show higher mortality rates. After balancing pre-existing relevant clinical conditions that could affect COVID-19 prognosis with PS matching, statin therapy confirmed its association with a more severe disease (NEWS ≥5 61% vs. 48%, p = 0.025) but not with in-hospital mortality (26% vs. 28%, p = 0.185). At univariate logistic regression analysis, statin use was confirmed not to be associated with mortality (OR 0.901; 95% CI: 0.537 to 1.51; p = 0.692) and to be associated with a more severe disease (NEWS≥5 OR 1.7; 95% CI 1.067–2.71; p = 0.026).ConclusionsOur results did not confirm the supposed favorable effects of statin therapy on COVID-19 outcomes. Conversely, they suggest that statin use should be considered as a proxy of underlying comorbidities, which indeed expose to increased risks of more severe COVID-19.     

Effect of hydroxychloroquine pre-exposure on infection with SARS-CoV-2 in rheumatic disease patients: a population-based cohort study

ObjectivesEarly in vitro studies have suggested that hydroxychloroquine (HCQ) is a potentially useful drug against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. This study was conducted to determine whether HCQ had a preventive effect on coronavirus disease 2019 (COVID-19) in rheumatic disease patients who were taking HCQ.MethodsWe conducted a population-based retrospective cohort study using the records of the Korean Health Insurance Review and Assessment (HIRA) claim records. The clinical data of patients with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) who were tested for SARS-CoV-2 were investigated. We compared the attack rate of COVID-19 between those who underwent HCQ therapy within 14 days before the test for SARS-CoV-2 (HCQ users) and HCQ non-users. Data were analysed using logistic regression models, χ², and Student's t-tests.ResultsAs of 15th May 2020, 2066 patients with RA or SLE were tested for COVID-19. Among them, 31.4% (649/2066) were treated with HCQ. Most HCQ users (93.7%, 608/649) were taking 200–400 mg/day recommended for the treatment of rheumatic diseases. The attack rate of COVID-19 in the HCQ users (2.3%, 15/649) did not differ from that in the HCQ non-users (2.2%, 31/1417) (p 0.86).ConclusionsHCQ prophylactic use at a usual dose did not prevent COVID-19 in patients with rheumatic disease.     

Field evaluation of a rapid antigen test (Panbio™ COVID-19 Ag Rapid Test Device) for COVID-19 diagnosis in primary healthcare centres

ObjectivesTo our knowledge no previous study has assessed the performance of a rapid antigen diagnostic immunoassay (RAD) conducted at the point of care (POC). We evaluated the Panbio? COVID-19 Ag Rapid Test Device for diagnosis of coronavirus 2019 disease (COVID-19) in symptomatic patients (n = 412) attending primary healthcare centres.MethodsRAD was performed immediately after sampling following the manufacturer's instructions (reading at 15 min). RT-PCRs were carried out within 24 h of specimen collection. Samples displaying discordant results were processed for culture in Vero E6 cells. Presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in cell cultures was confirmed by RT-PCR.ResultsOut of 412 patients, 43 (10.4%) tested positive by RT-PCR and RAD, and 358 (86.9%) tested negative by both methods; discordant results (RT-PCR+/RAD–) were obtained in 11 patients (2.7%). Overall specificity and sensitivity of rapid antigen detection (RAD) was 100% (95%CI 98.7–100%) and 79.6% (95%CI 67.0–88.8%), respectively, taking RT-PCR as the reference. Overall RAD negative predictive value for an estimated prevalence of 5% and 10% was 99% (95%CI 97.4–99.6%) and 97.9% (95%CI 95.9–98.9), respectively. SARS-CoV-2 could not be cultured from specimens yielding RT-PCR+/RAD– results (n = 11).ConclusionThe Panbio? COVID-19 Ag Rapid Test Device performed well as a POC test for early diagnosis of COVID-19 in primary healthcare centres. More crucially, the data suggested that patients with RT-PCR-proven COVID-19 testing negative by RAD are unlikely to be infectious.     

Immunological response against SARS-CoV-2 following full-dose administration of Comirnaty® COVID-19 vaccine in nursing home residents

ObjectivesThe current study was aimed at examining SARS-CoV-2 immune responses following two doses of Comirnaty® COVID-19 vaccine among elderly people in nursing homes.MethodsA prospective cohort study in a representative sample from nursing homes in Valencia (n = 881; males: 271, females 610; median age, 86 years) recruited residents using a random one-stage cluster sampling approach. A lateral flow immunochromatography device (LFIC) (OnSite COVID-19 IgG/IgM Rapid Test; CTK BIOTECH, Poway, CA, USA) was used as the front-line test for detecting SARS-CoV-2-Spike (S)-specific antibodies in whole blood obtained using a fingerstick. Residents returning negative LFIC results underwent venipuncture and testing for presence of SARS-CoV-2-S-reactive antibodies and T cells using the Roche Elecsys® Anti-SARS-CoV-2 S (Roche Diagnostics, Pleasanton, CA, USA), the LIAISON® SARS-CoV-2 TrimericS IgG assay (Diasorin S.p.A, Saluggia, Italy) and by flow cytometry, respectively.ResultsThe SARS-CoV-2-S antibody detection rate in nursing home residents was 99.6% (283/284) and 98.3% (587/597) for SARS-CoV-2 recovered and naïve residents, respectively, within a median of 99 days (range 17–125 days) after full vaccination. Three out of five residents lacking SARS-CoV-2-S antibodies had detectable S-reactive CD8⁺ and/or CD4⁺ T cells. In addition, 50/50 and 40/50 participants with detectable SARS-CoV-2 antibodies also had SARS-CoV-2-S-reactive interferon-γ-producing CD4⁺ and CD8⁺ T cells, respectively.DiscussionThe Comirnaty® COVID-19 vaccine is highly immunogenic in nursing home residents.     

Post–COVID-19 syndrome and humoral response association after 1 year in vaccinated and unvaccinated patients

ObjectivesThis study aimed to describe the impact of vaccination and the role of humoral responses on post–COVID-19 syndrome 1 year after the onset of SARS coronavirus type 2 (CoV-2).MethodsThis prospective study was conducted through interviews to investigate post–COVID-19 syndrome 6 and 12 months after disease onset in all adult in- and outpatients with COVID-19 at Udine Hospital (March–May 2020). Vaccination status and two different serological assays to distinguish between response to vaccination (receptor-binding domain (RBD) SARS-CoV-2 IgG) and/or natural infection (non-RBD-SARS-CoV-2 IgG) were also assessed.ResultsA total of 479 patients (52.6% female; mean age: 53 years) were interviewed 13.5 months (standard deviation: 0.6 months) after acute infection. Post–COVID-19 syndrome was observed in 47.2% of patients (n = 226) after 1 year. There were no significant differences in the worsening of post–COVID-19 symptoms (22.7% vs. 15.8%; p = 0.209) among vaccinated (n = 132) and unvaccinated (n = 347) patients. The presence of non-RBD SARS-CoV-2 IgG induced by natural infection showed a significant association with post–COVID-19 syndrome (OR: 1.35; 95% CI, 1.11–1.64; p = 0.003), and median non-RBD SARS-CoV-2 IgG titres were significantly higher in long haulers than in patients without symptoms (22 kAU/L (interquartile range, 9.7–37.2 kAU/L) vs. 14.1 kAU/L (interquartile range, 5.4–31.3 kAU/L); p = 0.009) after 1 year. In contrast, the presence of RBD SARS-CoV-2 IgG was not associated with the occurrence of post–COVID-19 syndrome (>2500 U/mL vs. 0.9–2500 U/mL; OR: 1.36; 95% CI, 0.62–3.00; p = 0.441), and RBD SARS-CoV-2 IgG titres were similar in long haulers as in patients without symptoms (50% values > 2500 U/mL vs. 55.6% values > 2500 U/mL; p = 0.451).DiscussionThe SARS-CoV-2 vaccination is not associated with the emergence of post–COVID-19 symptoms more than 1 year after acute infection. The persistence of high serological titre response induced by natural infection, but not vaccination, may play a role in long-haul COVID-19.     

COVID-19 associated with pulmonary aspergillosis: A literature review

Bacterial or virus co-infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported in many studies, however, the knowledge on Aspergillus co-infection among patients with coronavirus disease 2019 (COVID-19) was limited. This literature review aims to explore and describe the updated information about COVID-19 associated with pulmonary aspergillosis. We found that Aspergillus spp. can cause co-infections in patients with COVID-19, especially in severe/critical illness. The incidence of IPA in COVID-19 ranged from 19.6% to 33.3%. Acute respiratory distress syndrome requiring mechanical ventilation was the common complications, and the overall mortality was high, which could be up to 64.7% (n = 22) in the pooled analysis of 34 reported cases. The conventional risk factors of invasive aspergillosis were not common among these specific populations. Fungus culture and galactomannan test, especially from respiratory specimens could help early diagnosis. Aspergillus fumigatus was the most common species causing co-infection in COVID-19 patients, followed by Aspergillus flavus. Although voriconazole is the recommended anti-Aspergillus agent and also the most commonly used antifungal agent, aspergillosis caused by azole-resistant Aspergillus is also possible. Additionally, voriconazole should be used carefully in the concern of complicated drug–drug interaction and enhancing cardiovascular toxicity on anti-SARS-CoV-2 agents. Finally, this review suggests that clinicians should keep alerting the possible occurrence of pulmonary aspergillosis in severe/critical COVID-19 patients, and aggressively microbiologic study in addition to SARS-CoV-2 via respiratory specimens should be indicated.     

Pulmonary long-term consequences of COVID-19 infections after hospital discharge

ObjectivesCoronavirus disease 2019 (COVID-19) survivors are reporting residual abnormalities after discharge from hospital. Limited information is available about this stage of recovery or the lingering effects of the virus on pulmonary function and inflammation. This study aimed to describe lung function in patients recovering from COVID-19 hospitalization and to identify biomarkers in serum and induced sputum samples from these patients.MethodsPatients admitted to Spanish hospitals with laboratory-confirmed COVID-19 infection by a real-time PCR (RT-PCR) assay for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were recruited for this study. Each hospital screened their lists of discharged patients at least 45 days after symptom onset. SARS-CoV-2-infected patients were divided into mild/moderate and severe disease groups according to the severity of their symptoms during hospitalization. Patients’ epidemiological and medical histories, comorbidities, chronic treatments, and laboratory parameters were evaluated. Pulmonary function tests, the standardized 6-minute walk test (6MWT) and chest computed tomography (CT) were also performed. The levels of proteases, their inhibitors, and shed receptors were measured in serum and induced sputum samples.ResultsA total of 100 patients with respiratory function tests were included in this study. The median number of days after the onset of symptoms was 104 (IQR 89.25, 126.75). COVID-19 was severe in 47% of patients (47/100). CT was normal in 48% of patients (48/100). Lung function was normal forced expiratory volume in one second (FEV1) ≥80%, forced vital capacity (FVC) ≥80%, FEV1/FVC ≥0.7, and diffusing capacity for carbon monoxide (DLCO) ≥80% in 92% (92/100), 94% (94/100), 100% (100/100) and 48% (48/100) of patients, respectively. Multivariate analysis showed that a DLCO <80% (OR 5.92; 95%CI 2.28–15.37; p < 0.0001) and a lower serum lactate dehydrogenase level (OR 0.98; 95%CI 0.97–0.99) were associated with the severe disease group of SARS-CoV-2 cases during hospital stay.ConclusionsA diffusion deficit (DLCO <80%) was still present after hospital discharge and was associated with the most severe SARS-CoV-2 cases.     

Antibody response induced by the BNT162b2 mRNA COVID-19 vaccine in a cohort of health-care workers,with or without prior SARS-CoV-2 infection: a prospective study

ObjectivesTo assess the antibody response to BNT162b2 mRNA COVID-19 vaccine in a cohort of health-care workers (HCW), comparing individuals with previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and SARS-CoV-2-naive individuals.MethodsHCW were tested at T0 (day of first dose), T1 (day of second dose) and T2 (2–3 weeks after second dose) for IgG anti-nucleocapsid protein, IgM anti-spike protein and IgG anti-receptor binding domain (IgG-RBD-S). The antibody response was compared between four main groups: group A, individuals with previous infection and positive antibodies at baseline; group B, individuals with the same history but negative antibodies; group C, individuals with no infection history but positive antibodies; group D, naive individuals. Repeated measures analysis was used to compare results over time-points.ResultsA total of 1935 HCW were included. Median IgG-RBD-S titre was significantly higher for group A (232 individuals) than for group B (56 individuals) both at T1 (A: 22 763 AU/mL, interquartile range (IQR) 14 222–37 204 AU/mL; B: 1373 AU/mL, IQR 783–3078 AU/mL, p 0.0003) and T2 (A: 30 765 AU/mL, IQR 19 841–42 813 AU/mL; B: 13 171 AU/mL, IQR 2324–22 688 AU/mL, p 0.0038) and for group D (1563 individuals; 796 AU/mL, IQR 379–1510 AU/mL at T1; 15 494 AU/mL, IQR 9122–23 916 AU/mL at T2, p < 0.0001 for both time-points). T1 values of group A were also significantly higher than T2 values of group D (p < 0.0001). Presence of symptoms, younger age and being female were associated with stronger antibody response. HCW infected in March showed a significantly stronger response (T1: 35 324 AU/mL, IQR 22 003–44 531 AU/mL; T2: 37 648 AU/mL, IQR 27 088–50 451 AU/mL) than those infected in November (T1: 18 499 AU/mL, IQR 11 492–27 283 AU/mL; T2: 23 210 AU/mL, IQR 18 074–36 086 AU/mL, p < 0.0001 for both time-points.ConclusionsIndividuals with past SARS-CoV-2 infection had a strong antibody response after one single vaccine shot. A single dose might be sufficient for this group, regardless of the time elapsed since infection; however, the clinical correlation with antibody response needs to be studied.