COVID-19, caused by SARS-CoV-2 infection, is mild to moderate in the majority of previously healthy individuals, but can cause life-threatening disease or persistent debilitating symptoms in some cases. The most important determinant of disease severity is age, with individuals over 65 years having the greatest risk of requiring intensive care, and men are more susceptible than women. In contrast to other respiratory viral infections, young children seem to be less severely affected. It is now clear that mild to severe acute infection is not the only outcome of COVID-19, and long-lasting symptoms are also possible. In contrast to severe acute COVID-19, such 'long COVID' is seemingly more likely in women than in men. Also, postinfectious hyperinflammatory disease has been described as an additional outcome after SARS-CoV-2 infection. Here I discuss our current understanding of the immunological determinants of COVID-19 disease presentation and severity and relate this to known immune-system differences between young and old people and between men and women, and other factors associated with different disease presentations and severity.

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Immune determinants of COVID-19 disease presentation and severity.

The emergence of SARS-CoV-2 variants harboring mutations in the spike (S) protein has raised concern about potential immune escape. Here, we studied humoral and cellular immune responses to wild type SARS-CoV-2 and the B.1.1.7 and B.1.351 variants of concern in a cohort of 121 BNT162b2 mRNA-vaccinated health care workers (HCW). Twenty-three HCW recovered from mild COVID-19 disease and exhibited a recall response with high levels of SARS-CoV-2-specific functional antibodies and virus-specific T cells after a single vaccination. Specific immune responses were also detected in seronegative HCW after one vaccination, but a second dose was required to reach high levels of functional antibodies and cellular immune responses in all individuals. Vaccination-induced antibodies cross-neutralized the variants B.1.1.7 and B.1.351, but the neutralizing capacity and Fc-mediated functionality against B.1.351 was consistently 2- to 4-fold lower than to the homologous virus. In addition, peripheral blood mononuclear cells were stimulated with peptide pools spanning the mutated S regions of B.1.1.7 and B.1.351 to detect cross-reactivity of SARS-CoV-2-specific T cells with variants. Importantly, we observed no differences in CD4+ T-cell activation in response to variant antigens, indicating that the B.1.1.7 and B.1.351 S proteins do not escape T-cell-mediated immunity elicited by the wild type S protein. In conclusion, this study shows that some variants can partially escape humoral immunity induced by SARS-CoV-2 infection or BNT162b2 vaccination, but S-specific CD4+ T-cell activation is not affected by the mutations in the B.1.1.7 and B.1.351 variants.

SARS-CoV-2 variants of concern partially escape humoral but not T-cell responses in COVID-19 convalescent donors and vaccinees.

Importance The coronavirus disease 2019 (COVID-19) pandemic has placed unprecedented strain on patients and health care professionals and institutions, but the association of the pandemic with use of preventive, elective, and nonelective care, as well as potential disparities in use of health care, remain unknown. Objective To examine changes in health care use during the first 2 months of the COVID-19 pandemic in March and April of 2020 relative to March and April of 2019 and 2018, and to examine whether changes in use differ by patient’s zip code–level race/ethnicity or income. Design, Setting, and Participants This cross-sectional study analyzed health insurance claims for patients from all 50 US states who receive health insurance through their employers. Changes in use of preventive services, nonelective care, elective procedures, prescription drugs, in-person office visits, and telemedicine visits were examined during the first 2 months of the COVID-19 pandemic in 2020 relative to existing trends in 2019 and 2018. Disparities in the association of the pandemic with health care use based on patient’s zip code–level race and income were also examined. Results Data from 5.6, 6.4, and 6.8 million US individuals with employer-sponsored insurance in 2018, 2019, and 2020, respectively, were analyzed. Patient demographics were similar in all 3 years (mean [SD] age, 34.3 [18.6] years in 2018, 34.3 [18.5] years in 2019, and 34.5 [18.5] years in 2020); 50.0% women in 2018, 49.5% women in 2019, and 49.5% women in 2020). In March and April 2020, regression-adjusted use rate per 10 000 persons changed by −28.2 (95% CI, −30.5 to −25.9) and −64.5 (95% CI, −66.8 to −62.2) for colonoscopies; −149.1 (95% CI, −162.0 to −16.2) and −342.1 (95% CI, −355.0 to −329.2) for mammograms; −60.0 (95% CI, −63.3 to −54.7) and −118.1 (95% CI, −112.4 to −113.9) for hemoglobin A1ctests; −300.5 (95% CI, −346.5 to −254.5) and −369.0 (95% CI, −414.7 to −323.4) for child vaccines; −4.6 (95% CI, −5.3 to −3.9) and −10.9 (95% CI, −11.6 to −10.2) for musculoskeletal surgery; −1.1 (95% CI, −1.4 to −0.7) and −3.4 (95% CI, −3.8 to −3.0) for cataract surgery; −13.4 (95% CI, −14.6 to −12.2) and −31.4 (95% CI, −32.6 to −30.2) for magnetic resonance imaging; and −581.1 (95% CI, −612.9 to −549.3) and −1465 (95% CI, −1496 to −1433) for in-person office visits. Use of telemedicine services increased by 227.9 (95% CI, 221.7 to 234.1) per 10 000 persons and 641.6 (95% CI, 635.5 to 647.8) per 10 000 persons. Patients living in zip codes with lower-income or majority racial/ethnic minority populations experienced smaller reductions in in-person visits (≥80% racial/ethnic minority zip code: 200.0 per 10 000 [95% CI, 128.9-270.1]; 79%-21% racial/ethnic minority zip code: 54.2 per 10 000 [95% CI, 33.6-74.9]) but also had lower rates of adoption of telemedicine (≥80% racial/ethnic minority zip code: −71.6 per 10 000 [95% CI, −87.6 to −55.5]; 79%-21% racial/ethnic minority zip code: −15.1 per 10 000 [95% CI, −19.8 to −10.4]). Conclusions and Relevance In this cross-sectional study of a large US population with employer-sponsored insurance, the first 2 months of the COVID-19 pandemic were associated with dramatic reductions in the use of preventive and elective care. Use of telemedicine increased rapidly but not enough to account for reductions in in-person primary care visits. Race and income disparities at the zip code level exist in use of telemedicine.

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Changes in Health Services Use Among Commercially Insured US Populations During the COVID-19 Pandemic.

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The Lancet Commission on lessons for the future from the COVID-19 pandemic

http://www.thelancet.com/article/S0140673622015859/pdf

https://digitalcommons.unl.edu/cgi/viewcontent.cgi?article=1477&context=virologypub

High prevalence of pre-existing serological cross-reactivity against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in sub-Saharan Africa.

Background Neutralizing-antibody (nAb) is the major focus of most ongoing COVID-19 vaccine trials. However, nAb response against SARS-CoV-2, when present, decays rapidly. Given the myriad roles of antibodies in immune responses, it is possible that antibodies could also mediate protection against SARS-CoV-2 via effector mechanisms such as antibody-dependent cellular cytotoxicity (ADCC), which we sought to explore here. Methods Plasma of 3 uninfected controls and 20 subjects exposed to, or recovering from, SARS-CoV-2 infection were collected from U.S. and sub-Saharan Africa. Immunofluorescence assay was used to detect the presence of SARS-CoV-2 specific IgG antibodies in the plasma samples. SARS-CoV-2 specific neutralizing capability of these plasmas was assessed with SARS-CoV-2 spike pseudotyped virus. ADCC activity was assessed with a calcein release assay. Results SARS-CoV-2 specific IgG antibodies were detected in all COVID-19 subjects studied. All but three COVID-19 subjects contained nAb at high potency (>80% neutralization). Plasma from 19/20 of COVID-19 subjects also demonstrated strong ADCC activity against SARS-CoV-2 spike glycoprotein, including two individuals without nAb against SARS-CoV-2. Conclusion Both neutralizing and non-neutralizing COVID-19 plasmas can mediate ADCC. Our findings argue that evaluation of potential vaccines against SARS-CoV-2 should include investigation of the magnitude and durability of ADCC, in addition to nAb.

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Presence of antibody-dependent cellular cytotoxicity (ADCC) against SARS-CoV-2 in COVID-19 plasma.

Background: Despite the high COVID-19 morbidity and mortality rates across the world, the reported rates in sub-Saharan Africa (SSA), which has a higher burden of other infectious diseases and overwhelmed healthcare systems, remain relatively low. This study aims to better understand the potential factors that contribute to this phenomenon, especially among cancer patients who are considered as a high-risk group for developing severe COVID-19. Methods: Plasma samples collected during the COVID-19 pandemic from SARS-CoV-2 unvaccinated cancer and potential blood donor populations were analyzed for SARS-CoV-2 (spike and nucleocapsid proteins) antibodies by an immunofluorescence assay. The relationships between SARS-CoV-2 seroprevalences and study variables were determined using a logistic regression analysis. Results: High seroprevalence against the SARS-CoV-2 spike and nucleocapsid proteins were found among the SARS-CoV-2 unvaccinated COVID-19 pandemic populations in SSA. However, the cancer patients demonstrated a lower seroprevalence compared to potential blood donors. There was also an association between mild COVID-19 symptoms with prior tuberculosis vaccination among cancer patients. Conclusion: Cancer patients in SSA tend to have a relatively lower SARS-CoV-2 seroprevalence compared to potential blood donors recruited from the same geographic locations during the COVID-19 pandemic. More study is required to determine its cause and potential impact on SARS-CoV-2 vaccination among cancer patients.

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Phoebe B. Peña

Papers

High prevalence of pre-existing serological cross-reactivity against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in sub-Saharan Africa.

Presence of antibody-dependent cellular cytotoxicity (ADCC) against SARS-CoV-2 in COVID-19 plasma.

Lower SARS-CoV-2 Seroprevalence among Cancer Patients in Sub-Saharan Africa