Comparison of clinical characteristics between patients with coronavirus disease 2019 (COVID-19) who retested RT-PCR positive versus negative: a retrospective study of data from Nanjing

BackgroundThe epidemiological and clinical characteristics of patients with coronavirus disease 2019 (COVID-19) have been reported. However, the prevalence of retesting positive by RT-PCR for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the associated patient characteristics, remain unclear.MethodsWe included 90 confirmed cases of COVID-19 treated in the Nanjing Public Health Center from January 20, 2020 to February 16, 2020 in this retrospective study. All patients completed treatment for COVID-19 and were retested by RT-PCR for SARS-CoV-2 4–20 days after completion of therapy. The clinical characteristics between patients with who retested positive versus negative by RT-PCR were compared, and the factors predictive of positive retesting were analyzed. Positive retesting was modeled with the area under the receiver operating characteristic curve (AUC).ResultsThe age range of the study population was 0.8–97 years, and all patients were cured or showed improvement. A total of 10 (11%) patients retested positive by RT-PCR 4–20 days after completion of therapy. As compared with patients who retested negative, those who retested positive had a lower percentage of pre-admission fever, a higher percentage of post-admission fever, a lower percentage of bilateral lung infection, higher white blood cell (WBC) count and creatine phosphokinase, and lower hypersensitive c-reactive protein (hs-CRP), interleukin-6 and erythrocyte sedimentation rates (all P<0.05). Logistic regression analysis of the above eight key variables showed that lower hs-CRP and higher WBC were independently associated with positive retesting by RT-PCR. A combination of hs-CRP and WBC were predictive of positive retesting, with an AUC of 0.859.ConclusionsPatients with COVID-19 who retested positive by RT-PCR for SARS-CoV-2 had mild symptoms and better blood testing results. A combination of hs-CRP and WBC may predict positive retesting by RT-PCR; however, the sensitivity and specificity should be studied further.     

Avidity of IgG to SARS-CoV-2 RBD as a Prognostic Factor for the Severity of COVID-19 Reinfection

The avidity index (AI) of IgG to the RBD of SARS-CoV-2 was determined for 71 patients with a mild (outpatient) course of COVID-19, including 39 primarily and 36 secondarily reinfected, and 92 patients with a severe (hospital) course of COVID-19, including 82 primarily and 10 secondarily infected. The AI was shown to correlate with the severity of repeated disease. In the group of outpatients with a mild course, the reinfected patients had significantly higher median AIs than those with primary infections (82.3% vs. 37.1%, p < 0.0001). At the same time, in patients with a severe course of COVID-19, reinfected patients still had low-avidity antibodies (median AI of 28.4% vs. 25% in the primarily infected, difference not significant, p > 0.05). This suggests that the presence of low-avidity IgG to RBD during reinfection is a negative prognostic factor, in which a patient’s risk of developing COVID-19 in a severe form is significantly increased. Thus, patients with IgG of low avidity (AI ≤ 40%) had an 89 ± 20.5% chance of a severe course of recurrent COVID-19, whereas the detection of high-avidity antibodies (AI ≥ 50%) gave a probability of 94 ± 7.9% for a mild course of recurrent disease (p < 0.05).     

COVID-19: A Year Later: Simple mathematical modelling approaches to assessing the transmission risk of SARS-CoV-2 at gatherings

BackgroundGatherings may contribute significantly to the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For this reason, public health interventions have sought to constrain unrepeated or recurrent gatherings to curb the coronavirus disease 2019 (COVID-19) pandemic. Unfortunately, the range of different types of gatherings hinders specific guidance from setting limiting parameters (e.g. total size, number of cohorts, the extent of physical distancing).MethodsWe used a generic modelling framework, based on fundamental probability principles, to derive simple formulas to assess introduction and transmission risks associated with gatherings, as well as the potential efficiency of some testing strategies to mitigate these risks.ResultsIntroduction risk can be broadly assessed with the population prevalence and the size of the gathering, while transmission risk at a gathering is mainly driven by the gathering size. For recurrent gatherings, the cohort structure does not have a significant impact on transmission between cohorts. Testing strategies can mitigate risk, but frequency of testing and test performance are factors in finding a balance between detection and false positives.ConclusionThe generality of the modelling framework used here helps to disentangle the various factors affecting transmission risk at gatherings and may be useful for public health decision-making.     

COVID-19 and splenectomy: Education matters

Whether COVID-19-related morbidity and mortality are increased in splenectomized patients is unknown. The study by Bianchi et al. suggests increased hospitalizations and mortality rates in splenectomized patients, despite observing similar infection rates when compared to the general population. Commentary on: Bianchi et al. Burden of COVID19 disease and vaccine coverages in Apulian splenectomized patients. A retrospective observational study. Br J Haematol 2023;201:1072–1080.     

Medical treatment of 55 patients with COVID-19 from seven cities in northeast China who fully recovered: A single-center,retrospective, observational study

Coronavirus disease 2019 (COVID-19) is an emerging disease caused by severe acute respiratory syndrome coronavirus 2; no specific effective medication to treat the disease has been identified to date. We aimed to investigate the administered medications and intervention times for patients who completely recovered from COVID-19.This single-center, retrospective, observational study included 55 patients with COVID-19 who were transferred to Shenyang Sixth People''s Hospital between January 20 and March 15, 2020. Data on demographics, symptoms, laboratory indicators, treatment processes, and clinical outcomes were collected. Administered drugs and intervention times were compared in 47 and 8 patients with mild and severe symptoms, respectively.All 55 patients recovered. Fifty-three patients (96.36%) received antiviral therapy, including 45 in the mild group (median treatment: 14 days; 17 received umifenovir) and all 8 severe-group patients (median treatment: 17.5 days; 4 received lopinavir/ritonavir). Twenty-nine patients (52.72%) were administered antibiotics, including 21 in the mild group (median treatment: 13.5 days; 15 received moxifloxacin) and all 8 in the severe group (median treatment: 9 days; 2 received linezolid). Moreover, 7 patients (12.72%) were treated with glucocorticoids and 9 (16.36%) with immunomodulators.Given the 100% recovery rate, early administration of antiviral drugs can be considered. Umifenovir may benefit patients with mild symptoms, while lopinavir/ritonavir may benefit those with severe symptoms. Prophylactic administration of common antibiotics may reduce the risk of co-infection. The use of glucocorticoids is usually not necessary. Randomized, double-blind, and controlled trials remain necessary for more accurate conclusions.     

Interventions for Improving Long COVID-19 Symptomatology: A Systematic Review

Introduction: Although the understanding of several aspects of long COVID-19 syndrome is increasing, there is limited literature regarding the treatment of these signs and symptoms. The aim of our systematic review was to understand which therapies have proved effective against the symptoms of long COVID-19. Methods: A systematic search for randomized controlled or clinical trials in several databases was conducted through 15 May 2022. Specific inclusion criteria included: (1) intervention studies, either randomized controlled (RCTs) or clinical trials; (2) diagnosis of long COVID-19, according to the World Health Organization criteria; (3) presence of long COVID-19 for at least 12 weeks after SARS-CoV-2 infection. Results: We initially found 1638 articles to screen. After removing 1602 works based on their title/abstract, we considered 35 full texts, and among them, two intervention studies were finally included. The first RCT focused on the greater improvement of treatment combining olfactory rehabilitation with oral supplementation with Palmitoylethanolamide and Luteolin in patients with olfactory dysfunction after COVID-19. The second study evaluated the positive impact of aromatherapy vs. standard care in adult females affected by fatigue. Conclusion: Our systematic review found only two intervention studies focused on patients affected by long COVID-19. More intervention studies are needed to investigate potentially positive interventions for long COVID-19 symptoms.     

Impaired anti-SARS-CoV-2 antibody response in non-severe COVID-19 patients with diabetes mellitus: A preliminary report

Background and aimsPatients with diabetes mellitus (DM) often demonstrate impaired antibody response to influenza/hepatitis B vaccines. Hence, we compared anti-SARS-CoV-2 antibody response in non-severe COVID-19 patients with and without type 2 diabetes mellitus (T2DM).MethodsRecords of non-severe COVID-19 patients admitted at our institution between April 10, 2020 and May 20, 2020 were retrieved. Qualitative detection of total (IgG + IgM) anti-SARS-CoV-2 antibody was performed using electrochemiluminescence immunoassay in plasma samples collected at least 14 days post-polymerase chain reaction (PCR) confirmation of diagnosis.ResultsThirty-one non-severe COVID-19 patients were included. Nine patients (29%) had T2DM with mean HbA_1c at admission of 8.3 ± 1.0%. Anti-SARS-CoV-2 antibody was estimated at a median of 16 (14–17) days post-PCR confirmation of COVID-19 diagnosis. Only three patients (10%) were seronegative, and all had T2DM. Patients with T2DM were more likely to have non-detectable anti-SARS-CoV-2 antibodies than those without DM (p = 0.019).ConclusionsCOVID-19 patients with T2DM may not undergo seroconversion even after two weeks of diagnosis. Impaired seroconversion could theoretically increase the risk of reinfections in patients with DM. However, the finding requires validation in large-scale studies involving serial estimations of anti-SARS-CoV-2 antibodies in patients with and without DM.     

Monoclonal antibody for COVID-19: Unveiling the recipe of a new cocktail

The coronavirus disease 2019 (COVID-19) pandemic has had a tremendous adverse impact on the global health system, public sector, and social aspects. It is unarguably the worst pandemic of the century. However, COVID-19 management is a mystery in front of us, and an authentic treatment is urgently needed. Various repurposed drugs, like ivermectin, remdesivir, tocilizumab, baricitinib, etc., have been used to treat COVID-19, but none are promising. Antibody therapy and their combinations are emerging modalities for treating moderate COVID-19, and they have shown the potential to reduce hospitalisations. One antibody monotherapy, bamlanivimab, and two cocktails, casirivimab/imdevimab and bamlanivimab/ esterivimab, have received authorization for emergency use by the United States Food and Drug Administration for the treatment of mild COVID-19 in high risk individuals. The European Emergency has made similar recommendations for use of the drug in COVID-19 patients without oxygen therapy. This brief review will focus on monoclonal antibodies and their combination cocktail therapy in managing COVID-19 infection.     

Steroid resistance and rebound phenomena in patients with COVID-19

BackgroundIn patients with coronavirus disease (COVID-19) pneumonia, corticosteroids reduce progression to respiratory failure and death. Some patients, however, remain unresponsive to this treatment, or experience a rebound after termination.MethodsThis retrospective cohort study included COVID-19 patients treated with systemic corticosteroids in a Japanese hospital between June 1, 2020, and January 17, 2021. Patients were categorized into three groups: success, rebound, and refractory, and clinical characteristics and outcomes were compared.ResultsA total of 319 COVID-19 patients were admitted to our hospital and 113 patients met inclusion criteria. The success group had 83 patients (73.5%), the rebound group had nine patients (8.0%), and the refractory group had 21 patients (18.6%). Compared with the success group, the rebound group received corticosteroids earlier, for a shorter duration, and stopped them sooner. The median time from symptom onset to rebound was 12 days. There was no rebound after 20 days. Compared with the success group, the hazard ratio for the number of days from corticosteroid onset to an improvement of two points on a seven-point ordinal scale was 0.29 (95% confidence interval [CI], 0.14–0.60, P < .001) for the rebound group versus 0.13 (95% CI, 0.07–0.25, P < .001) for the refractory group.ConclusionsCOVID-19 patients treated with corticosteroids were classified into three response groups: success, rebound, and refractory, between which recovery time and prognosis differed. It was found that corticosteroid administration may prevent rebound phenomena if administered at least two weeks from symptom onset.     

Anti-SARS CoV-2 IgG in COVID-19 Patients with Hematological Diseases: A Single-center,Retrospective Study in Japan

Objective Coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread globally. Although the relationship between anti-SARS-CoV-2 immunoglobulin G (IgG) antibodies and COVID-19 severity has been reported, information is lacking regarding the seropositivity of patients with particular types of diseases, including hematological diseases. Methods In this single-center, retrospective study, we compared SARS-CoV-2 IgG positivity between patients with hematological diseases and those with non-hematological diseases. Results In total, 77 adult COVID-19 patients were enrolled. Of these, 30 had hematological disorders, and 47 had non-hematological disorders. The IgG antibody against the receptor-binding domain of the spike protein was detected less frequently in patients with hematological diseases (60.0%) than in those with non-hematological diseases (91.5%; p=0.029). Rituximab use was significantly associated with seronegativity (p=0.010). Conclusion Patients with hematological diseases are less likely to develop anti-SARS-CoV-2 antibodies than those with non-hematological diseases, which may explain the poor outcomes of COVID-19 patients in this high-risk group.     

COVID-19 in Nursing Homes: Calming the Perfect Storm

The pandemic of viral infection with the severe acute respiratory syndrome coronavirus-2 that causes COVID-19 disease has put the nursing home industry in crisis. The combination of a vulnerable population that manifests nonspecific and atypical presentations of COVID-19, staffing shortages due to viral infection, inadequate resources for and availability of rapid, accurate testing and personal protective equipment, and lack of effective treatments for COVID-19 among nursing home residents have created a “perfect storm” in our countryʼs nursing homes. This perfect storm will continue as society begins to reopen, resulting in more infections among nursing home staff and clinicians who acquire the virus outside of work, remain asymptomatic, and unknowingly perpetuate the spread of the virus in their workplaces. Because of the elements of the perfect storm, nursing homes are like a tinderbox, and it only takes one person to start a fire that could cause many deaths in a single facility. Several public health interventions and health policy strategies, adequate resources, and focused clinical quality improvement initiatives can help calm the storm. The saddest part of this perfect storm is that many years of inaction on the part of policy makers contributed to its impact. We now have an opportunity to improve nursing homes to protect residents and their caregivers ahead of the next storm. It is time to reimagine how we pay for and regulate nursing home care to achieve this goal. J Am Geriatr Soc 68:2153–2162, 2020.     

Plasma metabolome and cytokine profile reveal glycylproline modulating antibody fading in convalescent COVID-19 patients

The COVID-19 pandemic has incurred tremendous costs worldwide and is still threatening public health in the “new normal.” The association between neutralizing antibody levels and metabolic alterations in convalescent patients with COVID-19 is still poorly understood. In the present work, we conducted absolutely quantitative profiling to compare the plasma cytokines and metabolome of ordinary convalescent patients with antibodies (CA), convalescents with rapidly faded antibodies (CO), and healthy subjects. As a result, we identified that cytokines such as M-CSF and IL-12p40 and plasma metabolites such as glycylproline (gly-pro) and long-chain acylcarnitines could be associated with antibody fading in COVID-19 convalescent patients. Following feature selection, we built machine-learning–based classification models using 17 features (six cytokines and 11 metabolites). Overall accuracies of more than 90% were attained in at least six machine-learning models. Of note, the dipeptide gly-pro, a product of enzymatic peptide cleavage catalyzed by dipeptidyl peptidase 4 (DPP4), strongly accumulated in CO individuals compared with the CA group. Furthermore, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination experiments in healthy mice demonstrated that supplementation of gly-pro down-regulates SARS-CoV-2–specific receptor-binding domain antibody levels and suppresses immune responses, whereas the DPP4 inhibitor sitagliptin can counteract the inhibitory effects of gly-pro upon SARS-CoV-2 vaccination. Our findings not only reveal the important role of gly-pro in the immune responses to SARS-CoV-2 infection but also indicate a possible mechanism underlying the beneficial outcomes of treatment with DPP4 inhibitors in convalescent COVID-19 patients, shedding light on therapeutic and vaccination strategies against COVID-19.

To date more than 400 million people have caught COVID-19 and the death toll is around 6 million around the world. COVID-19 is caused by a β-coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), due to its nearly 80% genomic similarity to SARS-CoV (1), the pathogen causing the severe acute respiratory syndrome (SARS) outbreak in 2002. The worldwide epidemic of the disease necessitated the immediate and global dedication of a massive amount of resources and intelligence. After over 2 y, although most of the COVID-19 patients have recovered from the disease and billions of citizens have been vaccinated, the pandemic is still raging across the world. Deeper insights into the response and recovery processes of this disease are of value for risk prediction and for the most important follow-up issues such as vaccination strategies and herd immunity.The rapidly accumulated data of patients and convalescents with COVID-19 have been characterized by heterogeneity in susceptibility and severity. The COVID-19 patients ranged from asymptomatic infections to ones with multiorgan failure. The interindividual variability of the disease has been associated with age, biological sex, ethnicity, and the presence of preconditions (2). One of the important heterogeneities is the interindividual biological difference in the production of antibodies against invading viruses and vaccines. The convalescents with low levels of anti–SARS-CoV-2 antibodies have drawn clinical concern since early on (3, 4). A study of the patients in Wanzhou District, Chongqing City, China reported that approximately a sixth of the infected were seronegative in SARS-CoV-2–specific immunoglobulin G (IgG) in their acute phase; in 12.9% symptomatic and 40% asymptomatic IgG-positive individuals, the virus-specific IgG antibodies have faded 8 wk after they were discharged from the hospital (5). The race of vaccine development against SARS-CoV-2 started immediately after the unprecedented breakout of the pandemic and billions of people have been vaccinated worldwide. However, it has been observed since the early phase of vaccine development that vaccine recipients showed variability up to three orders of magnitude in antibody production (6–9). It has also been reported that a small proportion of participants have not successfully seroconverted postvaccination, and the virus-specific antibodies in some seropositive individuals faded in a few months even after two doses of SARS-CoV-2 vaccination (10). The levels of neutralizing antibodies are highly associated with immune protection from SARS-CoV-2 infection (11). How many individuals can produce enough antibodies is crucial for herd immunity against this infectious disease. An autopsy study revealed that the fatal COVID-19 patients lacked germinal centers in their lymph nodes, which might impair their production of antibodies against SARS-CoV-2 (12). However, the underlying etiology of these interindividual variations in SARS-CoV-2–induced immune responses, especially the fast fading of SARS-CoV-2–specific antibodies in some patients, is still unclear.Similar to many other infectious respiratory diseases, SARS-CoV-2 causes changes in plasma molecules. The alterations of cytokines are essential in host immune responses to SARS-CoV-2 infection. The plasma cytokines of severe COVID-19 patients were significantly higher (13, 14). Rapid cytokine release could cause acute respiratory distress syndrome and respiratory failure, which is called the cytokine storm, considered the main cause of mortality in COVID-19 patients (14, 15). Consistently, lower levels of cytokines, as well as virus-specific antibodies, characterized the weak immune response of asymptomatic COVID-19 patients, who had a longer duration of viral spreading than symptomatic ones (5). Clinical reports have demonstrated that the sera of COVID-19 patients have elevated levels of proinflammatory cytokines such as interleukin-6 (IL-6), IL-1β, interferon γ (IFNγ), C-X-C motif chemokine ligand 10 (CXCL10), and monocyte chemoattractant protein-1 (MCP1), similar to the cases of SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV) infections (14). The changes in plasma metabolome have also been tightly associated with viral infections. With the accumulation of COVID-19 cases, more and more studies have profiled the metabolomic changes in the sera of COVID-19 patients and convalescents (16–19). These studies demonstrated dramatic alterations in the pathways of macrophage function, platelet degranulation, complement system, and energy metabolism. In addition, integrative analysis of cytokines and metabolites in COVID-19 patients found that the changes in amino acids and purine metabolism might be correlated with proinflammatory cytokines (18). However, little is known about the traits of cytokines and metabolites associated with the receptor-binding domain (RBD)-specific antibody levels in convalescent COVID-19 patients.Herein, we conducted absolute quantification of cytokines and circulating metabolites to profile the molecular alterations associated with two subgroups of convalescent COVID-19 patients, including convalescent patients with antibodies (normal convalescent patients; CA group) and antibody-faded convalescent patients (CO group). Our findings uncovered some COVID-19–associated alterations of host cytokines and metabolites in two different types of convalescent patients. Among these changed molecules, our data showed that aberrant metabolisms of gly-pro (glycylproline) and its producing enzyme dipeptidyl peptidase 4 (DPP4), also known as CD26 or glycylproline dipeptidyl aminopeptidase (GPDA), may contribute to the fast fading of SARS-CoV-2 antibodies in the CO group of convalescent COVID-19 patients. Importantly, we demonstrate that changes in circulating gly-pro and the activities of DPP4 altered the production of antibodies against the RBD of SARS-CoV-2 in immunized mice. This result demonstrates a possible reason for the beneficial effects of DPP4 inhibitors on COVID-19 patients clinically (20–22). Therefore, our study reveals the physiological changes in metabolism in different types of convalescent COVID-19 patients, and the findings here could help mechanistically understand how the inhibition of DPP4 can benefit COVID-19 patients.