Author response for "Effectiveness of two and three mRNA COVID‐19 vaccine doses against Omicron‐ and Delta‐Related outpatient illness among adults, October 2021–February 2022"
Sara KimJessie R. ChungH. Keipp TalbotCarlos G. GrijalvaKaren J. WernliErika KiniryEmily T. MartinArnold S. MontoEdward A. BelongiaHuong Q. McLeanManjusha GaglaniMufaddal MamawalaMary Patricia NowalkKrissy Moehling GeffelSara Y. TartofAna FloreaJustin S. LeeMark W. TenfordeManish M. PatelBrendan FlanneryMeghan L. BentzAlex B. BurginMark BurroughsMorgan L. DavisDakota HowardKristine A. LacekJoseph C. MaddenSarah NoblesJasmine PadillaMili ShethStrain Surveillance and Emerging Variants Team
0
Citation
0
Reference
10
Related Paper
Keywords:
Outpatient clinic
2019-20 coronavirus outbreak
Sars virus
Betacoronavirus
Coronavirus Infections
Cite
Citations (0)
y aparición de variantes del SARS-CoV-
2019-20 coronavirus outbreak
Betacoronavirus
Cite
Citations (1)
The authors declare that there are no conflict of interests.
2019-20 coronavirus outbreak
Sars virus
Value (mathematics)
Cite
Citations (28)
China Cross-sectional 1115 70 ± 12 vs 59 ± 15 49% Death Wu et al 9 China Cross-sectional 201 47 ± 4 vs 59 ± 5 36% Respiratory failure COVID-19 patients developing more severe illness.It is also important to report here the findings of another study, which was omitted from our analysis as the serum prealbumin values were unavailable in COVID-19 patients with or without severe illness.Briefly, Zuo et al 10 prospectively studied 446 COVID-19 elderly patients, followed-up during their hospital stay.In a fully adjusted model, COVID-19 patients in the lowest tertile of serum prealbumin displayed a nearly threefold higher risk of mechanical ventilation (odds ratio, 2.8; 95% CI, 1.2-6.8), a 25-fold higher risk of intensive care (odds ratio, 26.4; 95% CI, 4.0-172.4)and a 19-fold higher risk of death (odds ratio, 20.1; 95% CI, 3.6-111.6)compared with those in the highest serum prealbumin tertile.According to this evidence, we can hence conclude that the progressive decline of serum prealbumin values in COVID-19 reflects a deteriorated clinical status, and may also be considered an additional contributing and predictive factor for enhancing the risk of developing unfavorable disease progression, up to death.
Biomedicine
Cite
Citations (11)
Dyslipidemia
Cite
Citations (3)
Pandemic
Cite
Citations (56)
Repurposing
2019-20 coronavirus outbreak
Coronavirus Infections
Betacoronavirus
Drug repositioning
Cite
Citations (43)
We read with interest the article by Loffredo et al1 [Reference citation was changed on June 17, 2020 after initial publication online.] of conjunctivitis and COVID-19: a meta-analysis. We appreciate the article's suggestions on protection in ophthalmic diagnosis and treatment but believe that the data and conclusions in meta-analysis need further study, the reasons are as follows: First, the original meta-analysis included three studies2-4 one of which the data processing of Wu et al2 may not be consistent with the original text. Wu et al2 found conjunctivitis in 12 of the 38 patients. Among these 12 patients, there were four cases judged as moderate, two cases judged as severe, and six cases judged as critical. Therefore, according to the guideline of PC-NCP,5 the proportion of severe COVID-19 should be 8 of 15 and that of not severe COVID-19 should be 4 of 23. However, the data of this meta-analysis are 2 of 15 and 1 of 23, respectively. Second, in a study by Guan et al,3 [Reference citation was changed on June 17, 2020 after initial publication online.] there is a great difference between the severe and not severe sample sizes, which is larger than that in the other two included studies. The probability of conjunctivitis in patients with ['not' was deleted on June 17, 2020 after initial publication online.] severe COVID-19 was 4 of 173, and the not ['not' was added on June 17, 2020 after initial publication online.] severe COVID-19 is 5 of 926. Although the conclusion remains unchanged after this study is removed, it seems that large sample size differences between studies may lead to publication bias. However, there is no denying that this analysis is still very meaningful, especially when there are few reports on relevant research. [Text 'Although…research' was added on June 17, 2020 after initial publication online.] COVID-19 patients may have conjunctivitis, and even the first symptom of some cases is conjunctivitis.6-8 However, it is not clear whether the onset of conjunctivitis is different for COVID-19 patients with different severe conditions. Based on the above thinking, we searched PubMed and CNKI for articles on COVID-19 and conjunctivitis with the words of COVID-19, 2019-CoV, SARS-CoV-2, and conjunctivitis. The severity of COVID-19 was distinguished according to PC-NCP guidelines, the incidence of conjunctivitis in patients with severe and not severe COVID-19 was included. A total of 62 studies were searched, 37 studies were read in full after duplication, and 4 studies were included (Figure 1).2, 4, 9, 10 Meta-analysis showed that the probability of conjunctivitis (log odds ratio [It was changed on June 17, 2020 after initial publication online.] = −0.84; 95% confidence interval, [− 1.66, − 0.01]; P = .05) between severe patients and not severe patients was statistically significant, ['not' was delete from here on June 17, 2020 after initial publication online.] severe COVID-19 patients seem to be more likely to develop conjunctivitis. It can be seen that the results of our meta-analysis are consistent with those of the original meta-analysis. To a certain extent, we have confirmed the great possibility of the original analysis results. [Text 'To a…results' was added on June 17, 2020 after initial publication online.] Inevitably, our meta-analysis also has certain limitations, such as too few documents and factors of the reporting population. Therefore, whether the patient has conjunctivitis or not is not necessarily related to the severity of COVID-19, this controversial issue may require further study. But when it is unknown whether conjunctival infection exists and whether it has an early warning effect on some systemic diseases, it is necessary to improve prevention and is also an important measure to facilitate treatment and avoid further spread.
2019-20 coronavirus outbreak
Coronavirus Infections
Cite
Citations (15)
Medical microbiology
Parasitology
Medical science
Cite
Citations (1)
In a rapidly evolving pandemic such as COVID-19, theories which help unify disparate pre-clinical and clinical observations would be useful. The current pandemic and its pleotropic effects can be explained in part by interaction between SARS-CoV-2 spike protein S, the ACE2/L-SIGN/CD209 receptor on the type II alveolar cell of the lung, and the DC-SIGN receptor on the respiratory dendritic cell (DC) and associated endothelial cells. Infection of the DC by SARS-CoV-2 can potentially explain the exuberant distal immunopathology seen in COVID-19. In a mouse model of severe acute respiratory distress syndrome (SARS), the human disease most related to coronavirus disease 2019 (COVID-19) in clinical course, severe disease is correlated with slow kinetics of SARS coronavirus (CoV) viral clearance.1 This is accompanied by delayed activation and transit of respiratory dendritic cells (DCs) to the draining lymph nodes with a deficient virus-specific T-cell response.1 In the SARS-CoV-2 infection, there is initial lymphopenia, and the lymphocyte count is predictive of disease severity and mortality.2 Lymphocyte counts recover with viral clearance and disease resolution, with adaptive immune cells (CD3+ T-cells) being especially important.2 Such immune deficiency can in part be explained by viral infection and T-cell interaction with the respiratory DC. Early and central infection of tissue-resident DC by the SARS-CoV-2 coronavirus explain some of the immunopathology of the COVID-19 pandemic. DC are richly abundant in the lung and responsive to viral infection.3 RNA expression profiling studies demonstrate that human DC express the angiotensin-converting enzyme 2 (ACE2) receptor for SARS-CoV-2.4 In COVID-19, T-cell receptor (TCR) repertoires are dramatically reduced during the early onset of severe SARS-CoV-2 infection but recover during the convalescent stage.5 Such reduction of T-cells suggest acute wholesale apoptotic death with engagement of the TCR in the absence of costimulatory molecules, normally provided by DC.6 DC also express DC-SIGN. Dendritic cell-specific ICAM-3-grabbing non-integrin (DC-SIGN) is a membrane receptor of a C-type lectin family expressed on DCs with a primary function of recognizing high mannose glycans present on other cellular receptors or pathogens.7 With L-SIGN (CD209L, DC-SIGNR, or liver/lymph specific SIGN) expression, the other SIGN found in humans,8 these mannose receptors are involved in virus capture and entry into cells.9 L-SIGN is expressed on human type II alveolar cells, is associated with ACE2,10 and can enhance ACE2 mediated binding and cellular entry of viral pseudotypes expressing the spike protein S of SARS-CoV.9 Lentiviral pseudotyped viruses expressing SARS-CoV S protein require acidification of the endosome for viral entry.11 DC-SIGN mediates binding of these pseudotyped vectors to human DC with uptake into the endosome, followed by polarization of the endosome and delivery of the virus in an "infectious synapse."11 This appears similar to an infectious synapse between infected DC and T cells that facilitates HIV infection mediated by DC-SIGN.12 Deglycosylation reduces infectivity of viral pseudotypes expressing SARS-CoV spike protein13 and specific asparagine glycosylation sites in three clusters within the SARS-CoV S protein appear critical for DC/L-SIGN mediated, but not ACE2 mediated, SARS Co-V pseudotype entry into cells.13 Infectivity mediated through DC/L-SIGN is reduced in proportion to the number of mutated glycosylated sites, suggesting that the number of glycosylated sites, and not just specific mutation, is important.13 Comparison of amino acid sequences of the S protein in SARS-like coronavirus in civets as well as in several human SARS-CoV isolates demonstrates progressive mutation of additional NXS/T amino acid canonical glycosylated sites in the human strains.13 This suggests a mechanism for increase in viral virulence through progressive glycosylation of the SARS-CoV-2 spike. This may explain a recently reported observation where a stable nonsynonymous D614G mutation in the spike glycoprotein of SARS-CoV-2 appears to arise from an ancestral aspartic acid (D) residue early in the course of the pandemic.14 This ancestral D appears to be more common in the West Coast of the United States, and the glycine (G) residue is more common in the East Coast, where substantial differences in mortality and transmission are observed. The D614G mutation is predicted to be present in a highly glycosylated portion of the viral spike two amino acids N-terminal to a predicted NXS/T glycosylated asparagine at residue 616.15 Statistical analysis of the protein environment of N-glycosylation sites16 suggests that replacement of a polar D by an aliphatic G at residue 614 should increase the probability of glycosylation of the asparagine NXS/T site at residue 616. This is predicted to increase virulence of SARS-CoV-2 through increased glycosylation at that site. Increased binding of this G variant to either DC- or L-SIGN in both type II alveolar cells, as well as DCs, could explain in part the observed mortality and transmissibility differences. Several reports17, 18 now suggest that there are multiple SARS-CoV-2 isolates with stable mutations in the spike S protein. SARS-CoV-2 mutations described one of these recent reports17 (Table 1) demonstrates that these are either predicted to increase or decrease glycosylation at various sites in the in the spike S protein, and these may possibly account for differences in virulence. A stable mutation in the SARS-CoV-2 spike protein found in one report is predicted to bind ACE2 less tightly, predicting a decrease in virulence. SARS-CoV-2 strains with various mutations in the viral spike can vary as much as 270-fold in virulence in Vero E6 culture.18 Viral evolutionary theory suggests that one option for a viral strain introduced to a novel host is to maintain fitness through reduction in virulence,19 and these various glycosylation mutations in the spike protein can plausibly provide one such mechanism for attenuation. A single-nucleotide polymorphism in the promoter region of the DC-SIGN gene is associated with disease severity in SARS.20 This underscores the likely involvement of DC/L-SIGN family members in the pathogenesis, virulence, and attenuation of the pathogen responsible for SARS and most likely COVID-19. Strategies designed to limit T-cell apoptosis through DC modulation, limiting expression or glycosylation of SARS-CoV-2 spike protein, or possibly driving intracellular degradation of viral proteins, should be considered. The authors would like to thank Richard Steinman, MD, PhD for helpful suggestions, and Eliza Brufsky for assistance with manuscript preparation. The authors declare that there are no conflict of interests.
Coronavirus
Pandemic
Cite
Citations (50)