Immunity after COVID-19 vaccination in people with higher risk of compromised immune status: a scoping review.

BACKGROUND: High efficacy in terms of protection from severe COVID-19 has been demonstrated for several SARS-CoV-2 vaccines. However, patients with compromised immune status develop a weaker and less stable immune response to vaccination. Strong immune response may not always translate into clinical benefit, therefore it is important to synthesise evidence on modified schemes and types of vaccination in these population subgroups for guiding health decisions. As the literature on COVID-19 vaccines continues to expand, we aimed to scope the literature on multiple subgroups to subsequently decide on the most relevant research questions to be answered by systematic reviews. OBJECTIVES: To provide an overview of the availability of existing literature on immune response and long-term clinical outcomes after COVID-19 vaccination, and to map this evidence according to the examined populations, specific vaccines, immunity parameters, and their way of determining relevant long-term outcomes and the availability of mapping between immune reactivity and relevant outcomes. SEARCH METHODS: We searched the Cochrane COVID-19 Study Register, the Web of Science Core Collection, and the World Health Organization COVID-19 Global literature on coronavirus disease on 6 December 2021.  SELECTION CRITERIA: We included studies that published results on immunity outcomes after vaccination with BNT162b2, mRNA-1273, AZD1222, Ad26.COV2.S, Sputnik V or Sputnik Light, BBIBP-CorV, or CoronaVac on predefined vulnerable subgroups such as people with malignancies, transplant recipients, people undergoing renal replacement therapy, and people with immune disorders, as well as pregnant and breastfeeding women, and children. We included studies if they had at least 100 participants (not considering healthy control groups); we excluded case studies and case series. DATA COLLECTION AND ANALYSIS: We extracted data independently and in duplicate onto an online data extraction form. Data were represented as tables and as online maps to show the frequency of studies for each item. We mapped the data according to study design, country of participant origin, patient comorbidity subgroup, intervention, outcome domains (clinical, safety, immunogenicity), and outcomes.  MAIN RESULTS: Out of 25,452 identified records, 318 studies with a total of more than 5 million participants met our eligibility criteria and were included in the review. Participants were recruited mainly from high-income countries between January 2020 and 31 October 2021 (282/318); the majority of studies included adult participants (297/318).  Haematological malignancies were the most commonly examined comorbidity group (N = 54), followed by solid tumours (N = 47), dialysis (N = 48), kidney transplant (N = 43), and rheumatic diseases (N = 28, 17, and 15 for mixed diseases, multiple sclerosis, and inflammatory bowel disease, respectively). Thirty-one studies included pregnant or breastfeeding women. The most commonly administered vaccine was BNT162b2 (N = 283), followed by mRNA-1273 (N = 153), AZD1222 (N = 66), Ad26.COV2.S (N = 42), BBIBP-CorV (N = 15), CoronaVac (N = 14), and Sputnik V (N = 5; no studies were identified for Sputnik Light). Most studies reported outcomes after regular vaccination scheme.  The majority of studies focused on immunogenicity outcomes, especially seroconversion based on binding antibody measurements and immunoglobulin G (IgG) titres (N = 179 and 175, respectively). Adverse events and serious adverse events were reported in 126 and 54 studies, whilst SARS-CoV-2 infection irrespective of severity was reported in 80 studies. Mortality due to SARS-CoV-2 infection was reported in 36 studies. Please refer to our evidence gap maps for more detailed information. AUTHORS' CONCLUSIONS: Up to 6 December 2021, the majority of studies examined data on mRNA vaccines administered as standard vaccination schemes (two doses approximately four to eight weeks apart) that report on immunogenicity parameters or adverse events. Clinical outcomes were less commonly reported, and if so, were often reported as a secondary outcome observed in seroconversion or immunoglobulin titre studies. As informed by this scoping review, two effectiveness reviews (on haematological malignancies and kidney transplant recipients) are currently being conducted.

Effectiveness, immunogenicity, and safety of COVID-19 vaccines for individuals with hematological malignancies: a systematic review.

The efficacy of SARS-CoV-2 vaccination in patients with hematological malignancies (HM) appears limited due to disease and treatment-associated immune impairment. We conducted a systematic review of prospective studies published from 10/12/2021 onwards in medical databases to assess clinical efficacy parameters, humoral and cellular immunogenicity and adverse events (AE) following two doses of COVID-19 approved vaccines. In 57 eligible studies reporting 7393 patients, clinical outcomes were rarely reported and rates of SARS-CoV-2 infection (range 0-11.9%), symptomatic disease (0-2.7%), hospital admission (0-2.8%), or death (0-0.5%) were low. Seroconversion rates ranged from 38.1-99.1% across studies with the highest response rate in myeloproliferative diseases and the lowest in patients with chronic lymphocytic leukemia. Patients with B-cell depleting treatment had lower seroconversion rates as compared to other targeted treatments or chemotherapy. The vaccine-induced T-cell response was rarely and heterogeneously reported (26.5-85.9%). Similarly, AEs were rarely reported (0-50.9% ≥1 AE, 0-7.5% ≥1 serious AE). In conclusion, HM patients present impaired humoral and cellular immune response to COVID-19 vaccination with disease and treatment specific response patterns. In light of the ongoing pandemic with the easing of mitigation strategies, new approaches to avert severe infection are urgently needed for this vulnerable patient population that responds poorly to current COVID-19 vaccine regimens.

Case Report: Clinical Management of a Patient With Metastatic Non-Small Cell Lung Cancer Newly Receiving Immune Checkpoint Inhibition During Symptomatic COVID-19.

Effects of initiation of programmed-death-protein 1 (PD1) blockade during active SARS-CoV-2 infection on antiviral immunity, COVID-19 course, and underlying malignancy are unclear. We report on the management of a male in his early 40s presenting with highly symptomatic metastatic lung cancer and active COVID-19 pneumonia. After treatment initiation with pembrolizumab, carboplatin, and pemetrexed, the respiratory situation initially worsened and high-dose corticosteroids were initiated due to suspected pneumonitis. After improvement and SARS-CoV-2 clearance, anti-cancer treatment was resumed without pembrolizumab. Immunological analyses with comparison to otherwise healthy SARS-CoV-2-infected ambulatory patients revealed a strong humoral immune response with higher levels of SARS-CoV-2-reactive IgG and neutralizing serum activity. Additionally, sustained increase of Tfh as well as activated CD4+ and CD8+ T cells was observed. Sequential CT scans showed regression of tumor lesions and marked improvement of the pulmonary situation, with no signs of pneumonitis after pembrolizumab re-challenge as maintenance. At the latest follow-up, the patient is ambulatory and in ongoing partial remission on pembrolizumab. In conclusion, anti-PD1 initiation during active COVID-19 pneumonia was feasible and cellular and humoral immune responses to SARS-CoV-2 appeared enhanced in our hospitalized patient. However, distinguishing COVID-19-associated changes from anti-PD1-associated immune-related pneumonitis posed a considerable clinical, radiographic, and immunologic challenge.