Background Patients with cancer may be at high risk of adverse outcomes from SARS-CoV-2 infection. We analyzed a cohort of patients with cancer and COVID-19 reported to the COVID-19 and Cancer Consortium (CCC19) to identify prognostic clinical factors, including laboratory measurements and anti-cancer therapies. Patients and Methods Patients with active or historical cancer and a laboratory-confirmed SARS-CoV-2 diagnosis recorded between March 17-November 18, 2020 were included. The primary outcome was COVID-19 severity measured on an ordinal scale (uncomplicated, hospitalized, admitted to intensive care unit, mechanically ventilated, died within 30 days). Multivariable regression models included demographics, cancer status, anti-cancer therapy and timing, COVID-19-directed therapies, and laboratory measurements (among hospitalized patients). Results 4,966 patients were included (median age 66 years, 51% female, 50% non-Hispanic white); 2,872 (58%) were hospitalized and 695 (14%) died; 61% had cancer that was present, diagnosed, or treated within the year prior to COVID-19 diagnosis. Older age, male sex, obesity, cardiovascular and pulmonary comorbidities, renal disease, diabetes mellitus, non-Hispanic Black race, Hispanic ethnicity, worse ECOG performance status, recent cytotoxic chemotherapy, and hematologic malignancy were associated with higher COVID-19 severity. Among hospitalized patients, low or high absolute lymphocyte count, high absolute neutrophil count, low platelet count, abnormal creatinine, troponin, LDH, and CRP were associated with higher COVID-19 severity. Patients diagnosed early in the COVID-19 pandemic (January-April 2020) had worse outcomes than those diagnosed later. Specific anti-cancer therapies (e.g. R-CHOP, platinum combined with etoposide, and DNA methyltransferase inhibitors) were associated with high 30-day all-cause mortality. Conclusions Clinical factors (e.g. older age, hematological malignancy, recent chemotherapy) and laboratory measurements were associated with poor outcomes among patients with cancer and COVID-19. Although further studies are needed, caution may be required in utilizing particular anti-cancer therapies.

Maternal anemia and low birth weight (LBW) may complicate malaria in pregnancy, and placental monocyte infiltrates have been associated with LBW, and anecdotally with anemia. We examined placental pathology from 357 Malawian women. Intervillous monocyte infiltrates were frequent in placental malaria and were not seen in uninfected placentas. Histology was grouped according to a 5-point scale. Dense monocyte infiltrates and presence of intramonocytic malaria pigment were associated with anemia and LBW. Of factors associated with LBW and/or anemia in univariate analysis, gravidity (P ‫ס‬ 0.002), number of antenatal clinic (ANC) visits (P < 0.001), malaria pigment in fibrin (P ‫ס‬ 0.03), and monocyte malaria pigment (P ‫ס‬ 0.0001) remained associated with lower birth weight by multivariate analysis. Associated with maternal anemia were HIV infection (P < 0.0001), intervillous monocyte numbers (P < 0.0001), number of ANC visits (P ‫ס‬ 0.002), and recent febrile symptoms (P ‫ס‬ 0.0001). Pigment-containing placental monocytes are associated with anemia and LBW due to malaria, and may have a causative role in their development.

Malaria during pregnancy is associated with poor birth outcomes, particularly low birth weight. Recently, monocyte infiltration into the placental intervillous space has been identified as a key risk factor for low birth weight. However, the malaria-induced chemokines involved in recruiting and activating placental monocytes have not been identified. In this study, we determined which chemokines are elevated during placental malaria infection and the association between chemokine expression and placental monocyte infiltration. Placental malaria infection was associated with elevations in mRNA expression of three beta chemokines, macrophage-inflammatory protein 1 (MIP-1) alpha (CCL3), monocyte chemoattractant protein 1 (MCP-1; CCL2), and I-309 (CCL1), and one alpha chemokine, IL-8 (CXCL8); all correlated with monocyte density in the placental intervillous space. Placental plasma concentrations of MIP-1 alpha and IL-8 were increased in women with placental malaria and were associated with placental monocyte infiltration. By immunohistochemistry, we localized placental chemokine production in malaria-infected placentas: some but not all hemozoin-laden maternal macrophages produced MIP-1 beta and MCP-1, and fetal stromal cells produced MCP-1. In sum, local placental production of chemokines is increased in malaria, and may be an important trigger for monocyte accumulation in the placenta.

Malaria in pregnancy predisposes to maternal anemia and low birth weight (LBW). We examined the possible roles of the cytokines tumor necrosis factor alpha (TNF-␣) and gamma interferon (IFN-␥) in these adverse outcomes. We measured cytokine concentrations in placental, peripheral, and cord blood plasma in relation to malaria parasitemia and placental monocyte accumulation in 276 Malawian women. Maternal hemoglobin concentration, human immunodeficiency virus status, and infant birth weight were determined. Concentrations of TNF-␣ in placental blood were correlated with densities of Plasmodium falciparum-infected erythrocytes (P < 0.0001) and of intervillous monocyte infiltrates (P < 0.0001) on placental histology. Peripheral blood TNF-␣ concentrations were relatively low and were weakly associated with malaria. TNF-␣ concentrations were higher in placental blood, where they were strongly associated with malaria. Placental plasma TNF-␣ levels were higher in women who had LBW babies (P ‫؍‬ 0.0027), women with febrile symptoms (P < 0.0001), and teenage mothers (P ‫؍‬ 0.04) than in other women. The presence of TNF-␣ in cord blood was not associated with malaria infection. IFN-␥ levels were infrequently elevated, and elevated IFN-␥ levels were not associated with poor pregnancy outcomes. Placental production of TNF-␣, but not of IFN-␥, may be implicated in impaired fetal growth in Malawian women.

We measured antibodies to chondroitin sulfate A (CSA)-binding and placental Plasmodium falciparum-infected red blood cells (PRBCs) among pregnant women with or without placental malaria. Immunoglobulin G to PRBC surface antigens was rare in uninfected primigravidae (3.7%), more prevalent in infected primigravidae (70%; P<.001), and common in infected (77%) and uninfected (83%) multigravidae. Similar patterns were seen for agglutinating antibodies, and antibodies were similar among women with past or active placental infection. PRBC adhesion to CSA was inhibited 60% by serum from infected primigravidae but 24% by serum from uninfected primigravidae (P=.025), whereas infection did not alter adhesion inhibition by multigravidae (77% inhibition)[corrected]. There was substantial heterogeneity in antibody type and levels. Antibodies did not correlate with parasite density or pregnancy outcome. Comparisons between antibodies suggest that adhesion-inhibitory antibodies and those to PRBC variant antigens have distinct and overlapping epitopes, may be acquired independently, and have different roles in immunity.