Overview of autoantibodies in COVID-19 convalescents.

Accumulating evidence shows that SARS-CoV-2 can potentially trigger autoimmune processes, which can be responsible for the long-term consequences of COVID-19. Therefore, this paper aims to review the autoantibodies reported in COVID-19 convalescents. Six main groups were distinguished: (i) autoantibodies against components of the immune system, (ii) autoantibodies against components of the cardiovascular system, (iii) thyroid autoantibodies, (iv) autoantibodies specific for rheumatoid diseases, (v) antibodies against G-protein coupled receptors, and (vi) other autoantibodies. The evidence reviewed here clearly highlights that SARS-CoV-2 infection may induce humoral autoimmune responses. However, the available studies share number of limitations, such as: (1) the sole presence of autoantibodies does not necessarily implicate the clinically-relevant risks, (2) functional investigations were rarely performed and it is often unknown whether observed autoantibodies are pathogenic, (3) the control seroprevalence, in healthy, noninfected individuals was often not reported; thus it is sometimes unknown whether the detected autoantibodies are the result of SARS-CoV-2 infection or the accidental post-COVID-19 detection, (4) the presence of autoantibodies was rarely correlated with symptoms of the post-COVID-19 syndrome, (5) the size of the studied groups were often small, (6) the studies focused predominantly on adult populations, (7) age- and sex-related differences in seroprevalence of autoantibodies were rarely explored, (8) genetic predispositions that may be involved in generation of autoantibodies during SARS-CoV-2 infections were not investigated, and (9) the autoimmune reactions following infection with SARS-CoV-2 variants that vary in the clinical course of infection remain unexplored. Further longitudinal studies are advocated to assess the link between identified autoantibodies and particular clinical outcomes in COVID-19 convalescents.

Association between the Seroprevalence of Antibodies against Seasonal Alphacoronaviruses and SARS-CoV-2 Humoral Immune Response, COVID-19 Severity, and Influenza Vaccination

The present study assesses the seroprevalence of antibodies against seasonal human alphacoronaviruses 229E and NL63 among adult patients infected with SARS-CoV-2, and its association with the humoral response to SARS-CoV-2 infection and its severity, and influenza vaccination. A serosurvey was conducted to quantify the presence of IgG antibodies against the nucleocapsid of 229E (anti-229E-N) and NL63 (anti-NL63-N), and anti-SARS-CoV-2 IgG antibodies (against nucleocapsid, receptor-binding domain, S2 domain, envelope, and papain-like protease) for 1313 Polish patients. The seroprevalence of anti-229E-N and anti-NL63 in the studied cohort was 3.3% and 2.4%. Seropositive individuals had a higher prevalence of anti-SARS-CoV-2 IgG antibodies, higher titers of the selected anti-SARS-CoV2 antibodies, and higher odds of an asymptomatic SARS-CoV-2 infection (OR = 2.5 for 229E and OR = 2.7 for NL63). Lastly, the individuals vaccinated against influenza in the 2019/2020 epidemic season had lower odds of seropositivity to 229E (OR = 0.38). The 229E and NL63 seroprevalence was below the expected pre-pandemic levels (up to 10%), likely due to social distancing, increased hygiene, and face masking. The study also suggests that exposure to seasonal alphacoronaviruses may improve humoral responses to SARS-CoV-2 while decreasing the clinical significance of its infection. It also adds to accumulating evidence of the favorable indirect effects of influenza vaccination. However, the findings of the present study are of a correlative nature and thereby do not necessarily imply causation.

Association between the Seroprevalence of Antibodies against Seasonal Alphacoronaviruses and SARS-CoV-2 Humoral Immune Response, COVID-19 Severity, and Influenza Vaccination.

The present study assesses the seroprevalence of antibodies against seasonal human alphacoronaviruses 229E and NL63 among adult patients infected with SARS-CoV-2, and its association with the humoral response to SARS-CoV-2 infection and its severity, and influenza vaccination. A serosurvey was conducted to quantify the presence of IgG antibodies against the nucleocapsid of 229E (anti-229E-N) and NL63 (anti-NL63-N), and anti-SARS-CoV-2 IgG antibodies (against nucleocapsid, receptor-binding domain, S2 domain, envelope, and papain-like protease) for 1313 Polish patients. The seroprevalence of anti-229E-N and anti-NL63 in the studied cohort was 3.3% and 2.4%. Seropositive individuals had a higher prevalence of anti-SARS-CoV-2 IgG antibodies, higher titers of the selected anti-SARS-CoV2 antibodies, and higher odds of an asymptomatic SARS-CoV-2 infection (OR = 2.5 for 229E and OR = 2.7 for NL63). Lastly, the individuals vaccinated against influenza in the 2019/2020 epidemic season had lower odds of seropositivity to 229E (OR = 0.38). The 229E and NL63 seroprevalence was below the expected pre-pandemic levels (up to 10%), likely due to social distancing, increased hygiene, and face masking. The study also suggests that exposure to seasonal alphacoronaviruses may improve humoral responses to SARS-CoV-2 while decreasing the clinical significance of its infection. It also adds to accumulating evidence of the favorable indirect effects of influenza vaccination. However, the findings of the present study are of a correlative nature and thereby do not necessarily imply causation.

COVID-19 vaccinations and rates of infections, hospitalizations, ICU admissions, and deaths in Europe during SARS-CoV-2 Omicron wave in the first quarter of 2022.

The vaccination campaigns brought hope to minimizing the coronavirus disease 2019 (COVID-19) burden. However, the emergence of novel, highly transmissible Omicron lineage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the waning of neutralizing antibodies a few months after vaccination has brought concerns over the vaccine efficacy. The present work analyzed the relationships between COVID-19 vaccine coverage (completion of primary course and booster dose intake) in the European Economic Area and rates of infection, hospitalizations, admissions to intensive care units (ICU), and deaths during the Omicron wave in the first quarter of 2022 (January-April). As demonstrated, infection rates were not correlated to vaccine coverage in any considered month. For January and February, the rates of hospitalizations, intensive care unit (ICU) admissions, and death due to COVID-19 were strongly negatively correlated (r =- 0.54 to -0.82) with the percentage of individuals who completed initial vaccination protocol and the percentage of those who received a booster dose. However, in March and April, the percentage of the population with primary vaccination course correlated negatively only with ICU admissions (r = -0.77 and -0.46, respectively). The uptake of boosters in March still remained in significant negative correlation with hospitalizations (r = -0.45), ICU admissions (r = -0.70) and deaths due to COVID-19 (r = -0.37), although in April these relationships were no longer observed. The percentage of individuals with confirmed SARS-CoV-2 infection did not correlate with the pandemic indices for any considered month. The study indicates that COVID-19 vaccination, including booster administration, was beneficial in decreasing the overwhelming of healthcare systems during the Omicron wave, but novel vaccine strategies may be required in the long term to enhance the effectiveness and durability of vaccine-induced protection during future waves of SARS-CoV-2 infections.

IgG autoantibodies against ACE2 in SARS-CoV-2 infected patients.

How frequently autoantibodies against angiotensin-converting enzyme 2 (ACE2) occur in patients infected by SARS-CoV-2 is understudied and limited to investigations on a small sample size. The presence of these antibodies may contribute to the long-lasting effects of COVID-19 observed in some individuals, particularly if IgG-class antibodies would emerge in patients. This study assessed the prevalence of IgG autoantibodies against ACE2 in 1139 patients infected with SARS-CoV-2 and examined their relationship with severity, demographic characteristics, and status of vaccination against influenza. The overall prevalence of anti-ACE IgG antibodies in our cohort was 1.5%. Most of these individuals were men (76.5%) and underwent mild COVID-19, but some severe and asymptomatic cases were also observed. Patients with severe infection had twofold higher titers than mild and asymptomatic cases. Age, comorbidities, and influenza vaccination status were not related to antibody prevalence. The prevalence of IgG anti-SARS-CoV-2 antibodies (against nucleocapsid protein and S2 subunit, but not against receptor-binding domain) was higher in the subset with ACE2 autoantibodies. Further research is required to understand the potential spectrum and duration of effects of IgG autoantibodies against ACE2 in patients after SARS-CoV-2 infection, particularly concerning long COVID-19.

The association of airborne particulate matter and benzo[a]pyrene with the clinical course of COVID-19 in patients hospitalized in Poland.

Air pollution can adversely affect the immune response and increase the severity of the viral disease. The present study aimed to explore the relationship between symptomatology, clinical course, and inflammation markers of adult patients with coronavirus disease 2019 (COVID-19) hospitalized in Poland (n = 4432) and air pollution levels, i.e., mean 24 h and max 24 h level of benzo(a)pyrene (B(a)P) and particulate matter <10 µm (PM10) and <2.5 µm (PM2.5) during a week before their hospitalization. Exposures to PM2.5 and B(a)P exceeding the limits were associated with higher odds of early respiratory symptoms of COVID-19 and hyperinflammatory state: interleukin-6 > 100 pg/mL, procalcitonin >0.25 ng/mL, and white blood cells count >11 × 103/mL. Except for the mean 24 h PM10 level, the exceedance of other air pollution parameters was associated with increased odds for oxygen saturation <90%. Exposure to elevated PM2.5 and B(a)P levels increased the odds of oxygen therapy and death. This study evidences that worse air quality is related to increased severity of COVID-19 and worse outcome in hospitalized patients. Mitigating air pollution shall be an integral part of measures undertaken to decrease the disease burden during a pandemic of viral respiratory illness.

Relationship between Humoral Response in COVID-19 and Seasonal Influenza Vaccination.

There is evidence that vaccination against seasonal influenza can improve innate immune responses to COVID-19 and decrease disease severity. However, less is known about whether it could also impact the humoral immunity in SARS-CoV-2 infected patients. The present study aimed to compare the SARS-CoV-2 specific humoral responses (IgG antibodies against nucleocapsid; anti-N, receptor binding domain; anti-RBD, subunit S2; anti-S2, and envelope protein; anti-E) between non-hospitalized, COVID-19 unvaccinated, and mild COVID-19 convalescent patients who were and were not vaccinated against influenza during the 2019/2020 epidemic season (n = 489 and n = 292, respectively). The influenza-vaccinated group had significantly higher frequency and titers of anti-N antibodies (75 vs. 66%; mean 559 vs. 520 U/mL) and anti-RBD antibodies (85 vs. 76%; mean 580 vs. 540 U/mL). The prevalence and concentrations of anti-S2 and anti-E antibodies did not differ between groups (40-43%; mean 370-375 U/mL and 1.4-1.7%; mean 261-294 U/mL) and were significantly lower compared to those of anti-RBD and anti-N. In both groups, age, comorbidities, and gender did not affect the prevalence and concentrations of studied antibodies. The results indicate that influenza vaccination can improve serum antibody levels produced in response to SARS-CoV-2 infection.

Frequency and Nuisance Level of Adverse Events in Individuals Receiving Homologous and Heterologous COVID-19 Booster Vaccine.

This study aimed to compare the occurrence and nuisance of adverse events following administration of each COVID-19 vaccine dose between two groups: individuals given three doses of mRNA vaccine (homologous group, 3 × mRNA, n = 252) and those given two doses of adenoviral vector vaccine further boosted with mRNA vaccine (heterologous group, 2 × AZ + 1 × mRNA, n = 205). Although the studied groups differed significantly in the frequency and number of side effects after the first and second vaccine dose, no relevant differences were seen following the booster administration. Arm pain and fatigue were the most common effects, regardless of the vaccination group and vaccine dose. In the homologous group, female sex, lower BMI, and no history of regular influenza vaccination were associated with a higher frequency of side effects of a booster dose. In the heterologous group, the history of COVID-19 was associated with an increased number of side effects seen after a booster. In both groups, the number of side effects related to the first and second dose correlated with the number observed after administration of a booster dose. Individuals receiving a homologous booster reported a higher nuisance of side effects than the heterologous group. It was similar to the level reported after the second dose in both groups. The use of pharmaceuticals to counteract the side effects was more frequent after a first dose in the 2 × AZ + 1 × mRNA group, but higher after second dose in individuals receiving the 3 × mRNA vaccination scheme. The frequency of pharmaceutical use after a booster dose was similar in both groups (approx. 60%). Paracetamol was most frequently chosen, regardless of the group and vaccine dose. In addition, the vast majority of participants (93%) declared to accept future doses of the COVID-19 vaccine if their administration would be recommended. This study provides an overview of the response to homologous and heterologous mRNA vaccine booster dose that may be valuable in shaping accurate and honest communication with vaccinated individuals, especially in those regions which are yet to pursue booster strategies.

Air pollution might affect the clinical course of COVID-19 in pediatric patients.

Air pollution, to which children are more susceptible than adults, can promote airway inflammation, potentially exaggerating the effects of respiratory viral infection. This study examined the association between the clinical manifestation of COVID-19 in unvaccinated pediatric patients hospitalized in Poland (n = 766) and levels of particulate matter 2.5 (PM2.5) and benzo(a)pyrene (B(a)P) within a week before hospitalization. Children aged ≤ 12 years exposed to mean and max 24 h B(a)P levels > 1 ng/m3 revealed higher odds of cough, dyspnea, fever, and increased concentrations of inflammatory markers (C-reactive protein, interleukin-6, procalcitonin, white blood cell count). In older patients (13-17 years), elevated mean 24 h B(a)P levels increased odds of dyspnea, fever, and diarrhea, and higher concentrations of C-reactive protein and procalcitonin. Exposure to max 24 h PM2.5 levels > 20 µg/m3 was associated with higher odds of cough, increased concentrations of C-reactive protein (group ≤12 years), and increased procalcitonin concentration (groups ≤12 years and 13-17 years). In both age groups, length of stay was extended in patients exposed to elevated levels of max 24 h PM2.5, mean and max 24 h B(a)P. This study suggests that worse air quality, particularly reflected in increased B(a)P levels, might affect the clinical course of COVID-19 in pediatric patients and adds to the disease burden during a pandemic.

COVID-19 Vaccine Boosters: The Good, the Bad, and the Ugly.

Pursuing vaccinations against COVID-19 brings hope to limit the spread of SARS-CoV-2 and remains the most rational decision under pandemic conditions. However, it does not come without challenges, including temporary shortages in vaccine doses, significant vaccine inequity, and questions regarding the durability of vaccine-induced immunity that remain unanswered. Moreover, SARS-CoV-2 has undergone evolution with the emergence of its novel variants, characterized by enhanced transmissibility and ability to at least partially evade neutralizing antibodies. At the same time, serum antibody levels start to wane within a few months after vaccination, ultimately increasing the risk of breakthrough infections. This article discusses whether the administration of booster doses of COVID-19 vaccines is urgently needed to control the pandemic. We conclude that, at present, optimizing the immunity level of wealthy populations cannot come at the expense of low-income regions that suffer from vaccine unavailability. Although the efficiency of vaccination in protecting from infection may decrease over time, current data show that efficacy against severe disease, hospitalization, and death remains at a high level. If vaccine coverage continues at extremely low levels in various regions, including African countries, SARS-CoV-2 may sooner or later evolve into variants better adapted to evade natural and vaccine-induced immunity, ultimately bringing a global threat that, of course, includes wealthy populations. We offer key recommendations to increase vaccination rates in low-income countries. The pandemic is, by definition, a major epidemiological event and requires looking beyond one's immediate self-interest; otherwise, efforts to contain it will be futile.

Willingness to Receive the Booster COVID-19 Vaccine Dose in Poland.

COVID-19 vaccinations are essential to mitigate the pandemic and prevent severe SARS-CoV-2 infections. However, the serum antibody levels in vaccinated individuals gradually decrease over time, while SARS-CoV-2 is undergoing an evolution toward more transmissible variants, such as B.1.617.2, ultimately increasing the risk of breakthrough infections and further virus spread. This cross-sectional online study of adult Poles (n = 2427) was conducted in September 2021 (before a general recommendation to administer a booster COVID-19 vaccine dose in Poland was issued) to assess the attitude of individuals who completed the current vaccination regime toward a potential booster dose of the COVID-19 vaccine and identify potential factors that may influence it. Overall, 71% of participants declared willingness to receive a booster COVID-19 dose, with a low median level of fear of receiving it of 1.0 (measured by the 10-point Likert-type scale), which was increased particularly in those having a worse experience (in terms of severity of side effects and associated fear) with past COVID-19 vaccination. The lowest frequency of willingness to receive a booster dose (26.7%) was seen in the group previously vaccinated with Ad26.COV2.S. The majority of individuals vaccinated previously with mRNA vaccines wished to receive the same vaccine, while in the case of AZD1222, such accordance was observed only in 9.1%. The main reasons against accepting a booster COVID-19 dose included the side effects experienced after previous doses, the opinion that further vaccination is unnecessary, and safety uncertainties. Women, older individuals (≥50 years), subjects with obesity, chronic diseases, and pre-vaccination and post-vaccination SARS-CoV-2 infections, and those with a history of vaccination against influenza were significantly more frequently willing to receive a booster COVID-19 dose. Moreover, the majority of immunosuppressed individuals (88%) were willing to receive an additional dose. The results emphasize some hesitancy toward potential further COVID-19 vaccination in the studied group of Poles and indicate the main groups to be targeted with effective science communication regarding the booster doses.