• 1.

    World Health Organization, 2020. WHO Coronavirus Situation Report- 130. Available at: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports. Accessed May 29, 2020.

    • Search Google Scholar
    • Export Citation
  • 2.

    Plucinski MM 2015. Effect of the Ebola-virus-disease epidemic on malaria case management in Guinea, 2014: a cross-sectional survey of health facilities. Lancet Infect Dis 15: 10171023.

    • Search Google Scholar
    • Export Citation
  • 3.

    WHO, 2020. The Potential Impact of Health Service Disruptions on the Burden of Malaria: A Modelling Analysis for Countries in Sub-Saharan Africa. Available at: https://www.who.int/publications-detail/the-potential-impact-of-health-service-disruptions-on-the-burden-of-malaria. Accessed May 21 2020.

    • Search Google Scholar
    • Export Citation
  • 4.

    Ludvigsson JF, 2020. Systematic review of COVID-19 in children shows milder cases and a better prognosis than adults. Acta Paediatr 109: 10881095.

    • Search Google Scholar
    • Export Citation
  • 5.

    Walker PGT 2020. Report 12: The Global Impact of COVID-19 and Strategies for Mitigation and Suppression. Available at: https://www.imperial.ac.uk/media/imperial-college/medicine/mrc-gida/2020-03-26-COVID19-Report-12.pdf. Accessed May 21, 2020.

    • Search Google Scholar
    • Export Citation
  • 6.

    United Nations Department of Economic and Social Affairs Population Division, 2019. World Population Prospects 2019, Custom Data Acquired via Website. Available at: https://population.un.org/wpp/DataQuery/. Accessed April 20, 2020.

    • Search Google Scholar
    • Export Citation
  • 7.

    Singer M, 2009. Introduction to Syndemics: A Critical Systems Approach to Public and Community Health. San Francisco, CA: John Wiley & Sons.

    • Search Google Scholar
    • Export Citation
  • 8.

    Mulama DH, Bailey JA, Foley J, Chelimo K, Ouma C, Jura WGZO, Otieno J, Vulule J, Moormann AM, 2014. Sickle cell trait is not associated with endemic Burkitt lymphoma: an ethnicity and malaria endemicity-matched case-control study suggests factors controlling EBV may serve as a predictive biomarker for this pediatric cancer. Int J Cancer 134: 645653.

    • Search Google Scholar
    • Export Citation
  • 9.

    Kwenti TE, 2018. Malaria and HIV coinfection in sub-Saharan Africa: prevalence, impact, and treatment strategies. Res Rep Trop Med 9: 123136.

    • Search Google Scholar
    • Export Citation
  • 10.

    Simon GG, 2016. Impacts of neglected tropical disease on incidence and progression of HIV/AIDS, tuberculosis, and malaria: scientific links. Int J Infect Dis 42: 5457.

    • Search Google Scholar
    • Export Citation
  • 11.

    Wall KM 2018. Schistosomiasis is associated with incident HIV transmission and death in Zambia. PLoS Negl Trop Dis 12: e0006902.

  • 12.

    Faure E, 2014. Malarial pathocoenosis: beneficial and deleterious interactions between malaria and other human diseases. Front Physiol 5: 441.

    • Search Google Scholar
    • Export Citation
  • 13.

    World Health Organization, 2019. World Malaria Report 2019. Geneva, Switzerland: WHO.

  • 14.

    World Health Organization, 2020. Ending the Neglect to Attain the Sustainable Development Goals: A Road Map for Neglected Tropical Diseases 2021–2030. Geneva, Switzerland: WHO.

    • Search Google Scholar
    • Export Citation
  • 15.

    CDC, 2020. Parasites. Available at: https://www.cdc.gov/parasites/.

  • 16.

    CDC, 2020. Symptoms of Coronavirus. Available at: https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html. Accessed May 1, 2020.

    • Search Google Scholar
    • Export Citation
  • 17.

    Wu Z, McGoogan JM, 2020. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72314 cases from the Chinese Center for Disease Control and Prevention. JAMA 323: 12391242.

    • Search Google Scholar
    • Export Citation
  • 18.

    Huang C 2020. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 395: 497506.

  • 19.

    Garg S 2020. Hospitalizaiton rates and characteristics of patients hospitalized with laboratory-confirmed conronavirus disease 2019 - COVID-NET, 14 states, March 1–30, 2020. Morb Mortal Wkly Rep 69: 458464.

    • Search Google Scholar
    • Export Citation
  • 20.

    Nishiura H 2020. Estimation of the asymptomatic ratio of novel coronavirus infections (COVID-19). Int J Infect Dis 94: 154155.

  • 21.

    Mizumoto K, Kagaya K, Zarebski A, Chowell G, 2020. Estimating the asymptomatic proportion of coronavirus disease 2019 (COVID-19) cases on board the Diamond Princess Cruise ship, Yokohama, Japan, 2020. Euro Surveill 25: 2000180.

    • Search Google Scholar
    • Export Citation
  • 22.

    Kimball A 2020. Asymptomatic and presymptomatic SARS-CoV-2 infections in residents of a long-term care skilled nursing facility–King County, Washington, March 2020. MMWR Morb Mortal Wkly Rep 69: 377381.

    • Search Google Scholar
    • Export Citation
  • 23.

    Ye Q, Wang B, Mao J, 2020. The pathogenesis and treatment of the ‘Cytokine Storm’ in COVID-19. J Infect 80: 607613.

  • 24.

    Liao YC, Liang WG, Chen FW, Hsu JH, Yang JJ, Chang MS, 2020. IL-19 induces production of IL-6 and TNF-alpha and results in cell apoptosis through TNF-alpha. J Immunol 169: 42884297.

    • Search Google Scholar
    • Export Citation
  • 25.

    Onder G, Rezza G, Brusaferro S, 2020. Case-fatality rate and characteristics of patients dying in relation to COVID-19 in Italy. JAMA doi:10.1001/jama.2020.4683.

    • Search Google Scholar
    • Export Citation
  • 26.

    Lighter J, Phillips M, Hochman S, Sterling S, Johnson D, Francois F, Stachel A, 2020. Obesity in patients younger than 60 years is a risk factor for COVID-19 hospital admission. Clin Infect Dis doi:10.1093/cid/ciaa415.

    • Search Google Scholar
    • Export Citation
  • 27.

    Yang J, Zheng Y, Gou X, Pu K, Chen Z, Guo Q, Ji R, Wang H, Wang Y, Zhou Y, 2020.Prevalence of comorbidities in the novel Wuhan coronavirus (COVID-19) infection: a systematic review and meta-analysis. Int J Infect Dis 94: 9195.

    • Search Google Scholar
    • Export Citation
  • 28.

    Bucsan AN, Williamson KC, 2020. Setting the stage: the initial immune response to blood-stage parasites. Virulence 11: 88103.

  • 29.

    Othoro C, Lal AA, Nahlen B, Koech D, Orago AS, Udhayakumar V, 1999. A low interleukin-10 tumor necrosis factor-alpha ratio is associated with malaria anemia in children residing in a holoendemic malaria region in western Kenya. J Infect Dis 179: 279282.

    • Search Google Scholar
    • Export Citation
  • 30.

    Akanmori BD, Kurtzhals JA, Goka BQ, Adabayeri V, Ofori MF, Nkrumah FK, Behr C, Hviid L, 2000. Distinct patterns of cytokine regulation in discrete clinical forms of Plasmodium falciparum malaria. Eur Cytokine Netw 11: 113118.

    • Search Google Scholar
    • Export Citation
  • 31.

    Lokken KL, Stull-Lane AR, Poels K, Tsolis RM, 2018. Malaria parasite-mediated alteration of macrophage function and increased iron availability predispose to disseminated nontyphoidal Salmonella infection. Infect Immun 86: e0030118.

    • Search Google Scholar
    • Export Citation
  • 32.

    Mooney JP 2014. The mucosal inflammatory response to non-typhoidal Salmonella in the intestine is blunted by IL-10 during concurrent malaria parasite infection. Mucosal Immunol 7: 13021311.

    • Search Google Scholar
    • Export Citation
  • 33.

    Thompson MG 2012. Influenza and malaria coinfection among young children in western Kenya, 2009–2011. J Infect Dis 206: 16741684.

  • 34.

    Edwards CL 2015. Coinfection with blood-stage Plasmodium promotes systemic type I interferon production during pneumovirus infection but impairs inflammation and viral control in the lung. Clin Vaccine Immunol 22: 477483.

    • Search Google Scholar
    • Export Citation
  • 35.

    Saghazadeh A, Rezaei N, 2020. Immune-epidemiological parameters of the novel coronavirus - a perspective. Expert Rev Clin Immunol doi:10.1080/1744666X.2020.1750954.

    • Search Google Scholar
    • Export Citation
  • 36.

    Lindblade KA, Steinhardt L, Samuels A, Kachur SP, Slutsker L, 2013. The silent threat: asymptomatic parasitemia and malaria transmission. Expert Rev Anti Infect Ther 11: 623639.

    • Search Google Scholar
    • Export Citation
  • 37.

    Taylor WRJ, Hanson J, Turner GDH, White NJ, Dondorp AM, 2012. Respiratory manifestations of malaria. Chest 142: 492505.

  • 38.

    Jin Y, Yang H, Ji W, Wu W, Chen S, Zhang W, Duan G, 2020. Virology, epidemiology, pathogenesis, and control of COVID-19. Viruses 12: 372.

  • 39.

    Van den Steen PE, Deroost K, Deckers J, Van Herck E, Struyf S, Opdenakker G, 2013. Pathogenesis of malaria-associated acute respiratory distress syndrome. Trends Parasitol 29: 346358.

    • Search Google Scholar
    • Export Citation
  • 40.

    Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ, 2020. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet 395: 10331034.

    • Search Google Scholar
    • Export Citation
  • 41.

    Taylor T 2006. Standardized data collection for multi-center clinical studies of severe malaria in African children: establishing the SMAC network. Trans R Soc Trop Med Hyg 100: 615622.

    • Search Google Scholar
    • Export Citation
  • 42.

    Lippi G, Mattiuzzi C, 2020. Hemoglobin value may be decreased in patients with severe coronavirus disease 2019. Hematol Transfus Cell Ther S2531–1379: 3002930028.

    • Search Google Scholar
    • Export Citation
  • 43.

    Visseren F, Bouwman JJ, Bouter KP, Diepersloot RJ, de Groot PH, Erkelens DW, 2000. Procoagulant activity of endothelial cells after infection with respiratory viruses. Thromb Haemost 84: 319324.

    • Search Google Scholar
    • Export Citation
  • 44.

    Giannis D, Ziogas IA, Gianni P, 2020. Coagulation disorders in coronavirus infected patients: COVID-19, SARS-CoV-1, MERS-CoV and lessons from the past. J Clin Virol 127: 104362.

    • Search Google Scholar
    • Export Citation
  • 45.

    Tang N, Li D, Wang X, Sun Z, 2020. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost 18: 844847.

    • Search Google Scholar
    • Export Citation
  • 46.

    Klok FA 2020. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res doi:10.1016/j.thromres.2020.04.013.

    • Search Google Scholar
    • Export Citation
  • 47.

    Oxley TJ 2020. Large-vessel stroke as a presenting feature of COVID-19 in the young. N Engl J Med 382: e60.

  • 48.

    Guan W-J 2020. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 382: 17081720.

  • 49.

    Fox SE, Akmatbekov A, Harbert JL, Li G, Brown JQ, Vander Heide RS, 2020. Pulmonary and cardiac pathology in African American patients with COVID-19: an autopsy series from New Orleans. Lancet doi:10.1016/S2213-2600(20)30243-5.

    • Search Google Scholar
    • Export Citation
  • 50.

    Lippi G, Plebani M, Henry BM, 2020. Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: a meta-analysis. Clinica Chim Acta 506: 145148.

    • Search Google Scholar
    • Export Citation
  • 51.

    Angchaisuksiri P, 2014. Coagulopathy in malaria. Thromb Res 133: 59.

  • 52.

    Krishnan A, Karnad DR, Limaye U, Siddharth W, 2004. Cerebral venous and dural sinus thrombosis in severe falciparum malaria. J Infect 48: 8690.

  • 53.

    Musoke C, Ssendikadiwa C, Babua C, Schwartz JI, 2014. Severe falciparum malaria associated with massive pulmonary embolism. Ann Afr Med 13: 4749.

    • Search Google Scholar
    • Export Citation
  • 54.

    Srichaikul T, 1993. Hemostatic alterations in malaria. Southeast Asian J Trop Med Public Health 24 (Suppl 1): 8691.

  • 55.

    Bashi T, Bizzaro G, Ben-Ami Shor D, Blank M, Shoenfeld Y, 2015. The mechanisms behind helminth’s immunomodulation in autoimmunity. Autoimmun Rev 14: 98104.

    • Search Google Scholar
    • Export Citation
  • 56.

    Maizels RM, McSorley HJ, 2016. Regulation of the host immune system by helminth parasites. J Allergy Clin Immunol 138: 666675.

  • 57.

    Cox FE, 2001. Concomitant infections, parasites and immune responses. Parasitology 122 (Suppl): S23S38.

  • 58.

    Supali T 2010. Polyparasitism and its impact on the immune system. Int J Parasitol 40: 11711176.

  • 59.

    Perez-Molina JA, Molina I, 2018. Chagas disease. Lancet 391: 8294.

  • 60.

    Campbell SJ 2016. Complexities and perplexities: a critical appraisal of the evidence for soil-transmitted helminth infection-related morbidity. PLoS Negl Trop Dis 10: e0004566.

    • Search Google Scholar
    • Export Citation
  • 61.

    Das D 2018. Complex interactions between malaria and malnutrition: a systematic literature review. BMC Med 16: 186.

  • 62.

    Tickell KD, Walson JL, 2016. Nutritional enteric failure: neglected tropical diseases and childhood stunting. PLoS Negl Trop Dis 10: e0004523.

    • Search Google Scholar
    • Export Citation
  • 63.

    Beck FK, Rosenthal TC, 2002. Prealbumin: a marker for nutritional evaluation. Am Fam Physician 65: 15751578.

  • 64.

    Wu C 2020. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern Med doi:10.1001/jamainternmed.2020.0994.

    • Search Google Scholar
    • Export Citation
  • 65.

    Bourke CD, Berkley JA, Prendergast AJ, 2016. Immune dysfunction as a cause and consequence of malnutrition. Trends Immunol 37: 386398.

  • 66.

    Schaible UE, Kaufmann SH, 2007. Malnutrition and infection: complex mechanisms and global impacts. PLoS Med 4: e115.

  • 67.

    Mills ID, 1986. The 1918–1919 influenza pandemic–the Indian experience. Indian Econ Soc Hist Rev 23: 140.

  • 68.

    Reyes L 2010. Population-based surveillance for 2009 pandemic influenza A (H1N1) virus in Guatemala, 2009. Influenza Other Respir Viruses 4: 129140.

    • Search Google Scholar
    • Export Citation
  • 69.

    Food and Agriculture Organization of the United Nations, 2020. Sustainable Development Goals: Indicator 2.1.1 - Prevalence of Undernourishment. Available at: http://www.fao.org/sustainable-development-goals/indicators/211/en/. Accessed April 21, 2020.

    • Search Google Scholar
    • Export Citation
  • 70.

    Davies NG 2020. Age-dependent Effects in the Transmission and Control of COVID-19 Epidemics. Supplementary Information. London, United Kingdom: London School of Hygiene and Tropical medicine.

    • Search Google Scholar
    • Export Citation
  • 71.

    World Health Organization, 2020. The First Few X Cases and Contacts (FFX) Investigation Protocol for Coronavirus Disease 2019 (COVID-19). Geneva, Switzerland: WHO.

    • Search Google Scholar
    • Export Citation
  • 72.

    World Health Organization, 2020. Operational Considerations for COVID-19 Surveillance Using GISRS. Geneva, Switzerland: WHO.

  • 73.

    American Academy of Pediatrics, 2018. Red Book: 2018 Report of the Committee on Infectious Diseases, 31st edition. Itasca, IL: American Academy of Pediatrics.

    • Search Google Scholar
    • Export Citation

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Malaria and Parasitic Neglected Tropical Diseases: Potential Syndemics with COVID-19?

View More View Less
  • 1 Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention (CDC), Atlanta, Georgia;
  • 2 Parasitic Diseases Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention (CDC), Atlanta, Georgia;
  • 3 U.S. President’s Malaria Initiative, Centers for Disease Control and Prevention (CDC), Atlanta, Georgia

The COVID-19 pandemic, caused by SARS-CoV-2, have surpassed 5 million cases globally. Current models suggest that low- and middle-income countries (LMICs) will have a similar incidence but substantially lower mortality rate than high-income countries. However, malaria and neglected tropical diseases (NTDs) are prevalent in LMICs, and coinfections are likely. Both malaria and parasitic NTDs can alter immunologic responses to other infectious agents. Malaria can induce a cytokine storm and pro-coagulant state similar to that seen in severe COVID-19. Consequently, coinfections with malaria parasites and SARS-CoV-2 could result in substantially worse outcomes than mono-infections with either pathogen, and could shift the age pattern of severe COVID-19 to younger age-groups. Enhancing surveillance platforms could provide signals that indicate whether malaria, NTDs, and COVID-19 are syndemics (synergistic epidemics). Based on the prevalence of malaria and NTDs in specific localities, efforts to characterize COVID-19 in LMICs could be expanded by adding testing for malaria and NTDs. Such additional testing would allow the determination of the rates of coinfection and comparison of severity of outcomes by infection status, greatly improving the understanding of the epidemiology of COVID-19 in LMICs and potentially helping to mitigate its impact.

INTRODUCTION

The COVID-19 pandemic caused by SARS-CoV-2, a novel coronavirus, has now reached all corners of the world, and cases have surpassed 5 million.1 SARS-CoV-2 is currently spreading in low- and middle-income countries (LMICs) that experience the highest rates of malaria and neglected tropical diseases (NTDs). Neglected tropical diseases refer to a diverse group of communicable diseases caused by parasites, fungi, bacteria, and viruses that occur primarily in tropical and subtropical climates; only parasitic NTDs are considered here (Table 1). With many LMICs implementing movement restrictions or ordering their populations to stay at home to limit SARS-CoV-2 transmission, the threat to essential health services is likely to be immediate, causing delays to diagnosis and treatment for other diseases, including malaria and NTDs. During the Ebola epidemic in West Africa, there were substantial reductions in all-cause outpatient visits and patients treated with antimalarial drugs2; modeling the potential for similar disruptions in malaria control due to COVID-19 suggests that there could be up to an estimated 769,000 deaths due to malaria in 2020 (approximately double the number seen in 2018), mostly among children younger than 5 years.3 Countries working toward the elimination of malaria or NTDs may face setbacks. Less obvious, but potentially important, is the possibility of SARS-CoV-2 interacting with parasitic infections and changing the rate of severe outcomes, particularly among younger populations that have been relatively less affected by COVID-19 to date.4

Table 1

Summary of principal characteristics of COVID-19, malaria, and key neglected tropical diseases

CharacteristicCOVID-19MalariaSoil-transmitted helminthsSchistosomiasisChagas
Infectious agentSARS-CoV-2Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, Plasmodium malariae, and Plasmodium knowlesiAscaris lumbicoides, Trichuris trichiura, and hookworm (Ancylostoma duodenale and Necator americanus)Schistosoma mansoni, S. haematobium, and S. japonicumTrypanosoma cruzi
Principal symptoms of clinical diseaseFever, cough, and shortness of breath17,48FeverAscaris and hookworm: transient pneumonitis. Hookworm and Trichuris: abdominal pain, nausea, diarrhea, and anemiaOften asymptomatic; acute infection causes fever, cough, abdominal pain, diarrhea, hepatosplenomegaly, and eosinophilia.Fever, edema, malaise, lymphadenopathy, hepatosplenomegaly, and chagoma (skin nodule at the inoculation site)
Severe clinical disease manifestationAcute respiratory distress syndrome17Cerebral malaria, severe anemia, and acute respiratory distress syndrome15Ascaris: acute intestinal obstruction and peritonitis. Hookworm: anemia. Trichuris: colitis, anemia, growth restriction, and dysentery73S. mansoni and japonicum: cirrhosis and portal hypertention. S. hematobium: hematuria and squamous cell carcinoma of the bladder; rarely, central nervous system lesions15Chronic heart disease, dilated cardiomyopathy, megacolon, and megaesophagus
Mode of transmissionPerson-to-person, primarily by respiratory dropletsMosquito vectorAscaris and Trichuris: ingestion of eggs. Hookworm: larvae penetrate the unprotected skinExposure to water containing larval forms of the parasite which penetrate the skinTriatomine vector
Age-group most affectedAdultsChildrenChildren and pregnant womenSchool-aged children for infection and adults for severe diseaseChildren for infection and adults for severe disease59

Under the assumption that public health and social distancing measures are used to mitigate the epidemic, the modeled estimates for SARS-CoV-2 infection incidence rates for LMICs, assuming comorbidity rates for all countries similar to what was seen in Wuhan, China, are projected to be around 600 infections per 1,000 population, similar to the rate anticipated for high-income countries. However, the mortality rate for LMICs (∼2 per 1,000) is projected to be about half that of the high-income countries (∼4 per 1,000).5 The difference in predicted mortality rates between LMICs and high-income countries is largely due to the younger age structure in LMICs; in 2020, the median age in sub-Saharan Africa is 18.7 years, compared with 38.4 years in China.6

Syndemics, or synergistic epidemics, occur when two or more concurrent epidemics have a deleterious interaction,7 that is, when coinfections result in a worse overall outcome than for either individual infection. There are many examples of important interactions between malaria and NTDs and other infectious diseases. For example, malaria plays a role in Epstein–Barr virus (EBV) infection, leading to Burkitt’s lymphoma by contributing to B-cell proliferation and increasing EBV loads8; HIV-infected individuals experience a greater frequency of severe malaria and increased HIV viral load following infection with Plasmodium falciparum9; several parasite–HIV coinfections are associated with increased HIV viral load and worsened immunosuppression10; and schistosome infections are associated with increased transmission of HIV,11 whereas deworming is associated with decreased HIV viral load and improved CD4 counts among HIV-infected individuals.12 Biological interactions between coinfecting pathogens could involve changes in host pathology related to indirect immune effects.12 The interplay of coinfections hinges on several host–pathogen factors and host immunodynamics.

Low- and middle-income countries in Africa suffer the greatest burden of malaria; in 2018, there were more than 200 million cases per year, with an annual incidence of 229 per 1,000 persons.13 Despite substantial progress in reducing malaria mortality over the past two decades, more than 400,000 malaria deaths (> 90% in sub-Saharan Africa) were estimated to have occurred in 2018.13 Outside of Africa, India has the greatest burden of malaria cases, accounting for 3% of the global burden.13 Globally, NTDs affect more than 1 billion people, especially those living in poverty, who often lack access to clean water and adequate sanitation.14 Africa has a disproportionate burden of NTDs and malaria, with a significant geographical overlap.14,15 With rapid transmission of SARS-CoV-2, many people in LMICs, particularly in Africa, soon will be coinfected with SARS-CoV-2 and Plasmodium spp. or one or more NTD pathogens; cases of COVID-19 in the Africa region will soon surpass 100,000.1 Preexisting infection with any of these parasitic infections may lead to changes in susceptibility and/or severity of COVID-19. It is unclear whether immunomodulation caused by malaria and NTDs will be beneficial or harmful when hosts are coinfected with SARS-CoV-2, but even small changes in the risk of severe outcomes due to coinfections could result in substantial changes in the impact and epidemiology of COVID-19 in LMICs.

SARS-CoV-2 infection.

Common symptoms of infection with SARS-CoV-2 include fever, cough, shortness of breath, chills, myalgia, headache, sore throat, and new loss of taste or smell16; the onset of symptoms generally occurs 4–5 days after infection, although it can be as late as 14 days,1719 and not all infected people develop symptoms.2022 Approximately a week after the development of symptoms, some patients experience an acute worsening, with a pronounced systemic increase of inflammatory mediators and cytokines.23 The severe systemic inflammatory response, referred to as a “cytokine storm,” is characterized by markedly increased levels of interleukins (IL) and tumor necrosis factor (TNF)-alpha, and is associated with the development of acute respiratory distress syndrome (ARDS).24 Among 72,314 cases reported from China, 14% were rated as severe and 5% were critical (respiratory failure, septic shock, and multiple organ dysfunction or failure).17 Case fatality ratios (CFRs) ranged from 2.3% to 7.2%, with higher CFRs among older adults (8.0–12.8% among those aged 70–79 years and 14.8–20.2% among those 80 years and older, versus ≤ 0.4% among those younger than 50 years).17,25 Hypertension, diabetes, cardiovascular disease, preexisting respiratory disease, and obesity were common comorbidities26,27; in a meta-analysis of 1,576 patients in China, all but diabetes and obesity were associated with increased risk of severe disease.27

Potential Plasmodium spp.–SARS-CoV-2 interactions.

Of the five parasitic species that cause malaria in humans (Table 1), P. falciparum accounts for most morbidity and mortality, followed by Plasmodium vivax.13,15 Clinical illness arises from asexual parasite replication within erythrocytes. Infected erythrocytes lyse and release merozoites into the circulation, causing activation of the immune system and leading to the release of pro-inflammatory cytokines including TNF-alpha, interferon-gamma, IL-6, and IL-12.28 This cascade of cytokines leads to symptoms of uncomplicated malaria, including periodic fever, which, if left untreated, can progress to severe disease. Severe disease manifests as severe anemia, respiratory failure, cerebral malaria, acidosis, and renal failure. Children and infants are at greatest risk for severe malaria; 67% of malarial deaths are estimated to occur among African children younger than 5 years.13

As with COVID-19, cellular immune responses in malaria involving the cytokine cascade must be carefully regulated to achieve a protective response without causing adverse impact on the host. Studies in malaria-endemic regions have found that it is important to have a balance between a host pro-inflammatory, Th1 response (e.g., TNF-alpha, IL-6, IL-12, and interferon-gamma) and anti-inflammatory, Th2 response (IL-4, IL-10, and others)29,30; severe manifestations of malaria are often due to excessive pro-inflammatory responses. The same appears to be true in at least some cases of COVID-19,18 suggesting that a coinfection that also leads to excess pro-inflammatory responses might result in more severe manifestations and poor prognosis.

Malaria-induced immunosuppression has also been observed in many coinfections, significantly inhibiting immune responses to the other infection (e.g., to Salmonella spp.).31,32 However, malaria-induced immunomodulation has been shown to be protective against severe manifestations of some respiratory viruses. In Kenya, hospitalized children diagnosed with influenza and malaria were less likely to experience respiratory distress than those with influenza alone.33 Coinfection with Plasmodium spp. could suppress the production of pulmonary cytokines and decrease the recruitment of cellular inflammatory components to the lungs, leading to reduced clinical symptoms and inflammation, as was found during pneumovirus infections in a murine model. However, in the murine model, viral control was also impaired, leading to increased viral dissemination.34 Similar dynamics could occur during Plasmodium–SARS-CoV-2 coinfection; malaria-induced immunosuppression might lead to milder manifestations of COVID-19 but simultaneously decrease viral control, potentially increasing or sustaining viral loads, which could increase the potential for viral transmission.

Age-related vulnerability to malaria and COVID-19.

Susceptibility to malaria in highly endemic areas differs by age: younger children are more vulnerable to malaria infections and at a higher risk for severe malaria.13 For COVID-19, children are less likely to develop severe disease, whereas older populations are disproportionately affected, with a higher risk of severe disease and death.35 This may be due to the fact that children are more likely to produce T-regulatory cytokines (IL-10, IL-23, and IL-6) and have less inflammation (because of their immature immune systems) than older people who mount a more pro-inflammatory cytokine cascade, potentially contributing to pathogenesis.35 How age-related susceptibility to COVID-19 will play out in Africa, where many children are immunologically stimulated by several infections in addition to malaria, is not clear. Importantly, malaria infections in endemic areas frequently result in chronic, afebrile disease in older children and adults.36 It remains unknown whether this underlying infection will alter susceptibility to or severity of COVID-19 in these populations; it is important that surveillance systems be modified to collect data to inform our understanding of this issue.

Respiratory distress and ARDS.

Respiratory distress, observed in up to 25% of adults and 40% of children with severe P. falciparum malaria, has several causes, including severe anemia, metabolic acidosis, cytoadherence of infected erythrocytes in pulmonary vasculature, and coinfections with pneumonia-causing pathogens.37 The clinical spectrum varies from mild upper respiratory symptoms to acute lung injury and fatal ARDS. Acute respiratory distress syndrome is rare in young children with malaria but occurs in 5–25% of adults and 29% of pregnant women with severe P. falciparum infections, and less commonly with P. vivax malaria.37 In both malaria and COVID-19, ARDS is linked to inflammatory cytokine–mediated increased capillary permeability or endothelial damage, which results in major alveolar damage.3840 Given this situation, Plasmodium spp.–SARS-CoV-2 coinfections may result in particularly rapid deterioration, with a poor prognosis. As the inflammatory-mediated alveolar damage in malaria-induced ARDS progresses even after treatment and parasite clearance,37 coinfected individuals may be prone to severe COVID-19. Because both malaria and COVID-19 can lead to similar clinical manifestations, including fever and respiratory symptoms, one or the other may be overlooked in a differential diagnosis of respiratory distress, leading to increased fatalities. As SARS-CoV-2 transmission increases in LMICs, particularly in Africa and India, clinicians should keep this in mind. In addition, documenting the frequency, distribution, and outcomes of these coinfections is important.

Anemia.

Anemia is highly prevalent in LMICs and results from multiple causes. In cross-sectional household surveys in sub-Saharan Africa, 61%, 33%, and 3% of children younger than 5 years had any anemia, moderate anemia, and severe anemia, respectively.13 More than one-fifth of children with malaria develop SMA, with a CFR of 8.4%.41 Whereas the hematologic sequelae of COVID-19 are still being elucidated, a meta-analysis describing 1,210 COVID-19 patients from four studies found that hemoglobin values were 0.71 g/dL (95% CI: 0.59–0.83 g/dL) lower in individuals with severe disease versus milder disease.42 Whether lower hemoglobin is a risk factor or a sequela of severe COVID-19 disease is unknown. However, because of limited reserves, even small perturbations in oxygen-carrying capacity in individuals with preexisting malarial anemia may result in insufficient tissue oxygenation in the midst of COVID-19–induced respiratory failure.

Pro-coagulant state.

Numerous viral infections, including SARS-CoV-2, induce a pro-coagulant state through the induction of tissue factor expression, endothelial dysfunction, von Willebrand factor elevation, and Toll-like receptor activation.43,44 Markers of a hypercoagulable state, including increased D-dimer and fibrin degradation product levels, and prolonged prothrombin time are associated with a poor prognosis.45 Clinically, the hypercoagulable state manifests with a high rate of venous thromboembolism and arterial thrombotic complications (including pulmonary embolism and stroke).46,47 COVID-19 patients are at risk for developing disseminated intravascular coagulation (DIC),45,48 and autopsy findings have included both pulmonary hemorrhage and thrombosis.49 Thrombocytopenia is another potential feature of COVID-19, thought to be due to excessive activation of the coagulation cascade, leading to platelet activation and subsequent consumption,44 and is associated with worse outcomes.50

Malaria is also associated with a pro-coagulant state, with activation of the coagulation cascade, mediated by TNF-alpha and IL-6, proportional to disease severity.51 Whereas micro-thrombotic complications are most commonly described, thrombosis of large vessels, including cerebral venous thrombosis, and pulmonary embolism have been described.52,53 Thrombocytopenia develops in 60–80% of malaria cases.51 Although bleeding and DIC are rarely seen, occurring only in severe malarial cases accompanied by coagulopathy,54 they are associated with high mortality.51 Lysis of activated platelets, along with tissue factor released from damaged vascular endothelial cells, promotes the pro-coagulant state,54 similar to the proposed mechanism in COVID-19. Thus, Plasmodium spp.–SARS-CoV-2 coinfection could lead to even greater degrees of coagulopathy and more severe disease than with either infection alone.

Potential interactions between NTDs and COVID-19.

Helminths, including stool-transmitted helminths (STH), schistosomes, and filariae, typically push the immune system toward anti-inflammatory Th2 pathways through a variety of regulatory mechanisms.55,56 Protozoal parasites, such as trypanosomes or Leishmania spp., are more likely to induce a Th1, pro-inflammatory response. However, there are many deviations from this characterization. Some helminths induce Th1 responses in some stages of the life cycle (e.g., microfilariae of filarial parasites or schistosome eggs), resulting in symptomatic disease, but Th2 responses in other stages (e.g., adults of both filarial parasites and schistosomes). The downregulation of the inflammatory response associated with helminths may reduce the development of immunity or response to vaccines, decrease inflammation associated with autoimmune diseases, reduce the ability to control Mycobacterium tuberculosis and Mycobacterium leprae coinfections, and reduce the severity of malarial coinfection. The pro-inflammatory effects of some protozoal infections may worsen the severity of some, but not all, viral infections.55,57 In addition, polyparasitism is quite common, and the overall impact on inflammation depends on the sequence of infections and burden of each.58 Thus, coinfection with parasitic NTDs could result in altered risks and severity of clinical manifestations of SARS-CoV-2 infection, with the potential for decreased development of immunity with increased viral loads.

The severity of COVID-19 has been associated with underlying health conditions that usually occur with advancing age. Several NTDs, if left untreated, can result in chronic sequelae in much younger populations. For example, because acute Trypanosoma cruzi infection is typically asymptomatic or results in a mild, self-limited illness, it is frequently undetected and left untreated. Yet, in young or middle adulthood, 20–30% of persons chronically infected with T. cruzi develop cardiac manifestations, commonly a complex, dilated cardiomyopathy.59 For these individuals, coinfection with SARS-CoV-2 could be life-threatening. STH infections may result in anemia60; if, as described previously, anemia predisposes individuals to more severe outcomes, then coinfection of STHs and SARS-CoV-2 in children and pregnant women could be problematic.

Malnutrition and COVID-19.

Chronic malnutrition is associated with both malaria61 and NTDs,62 and is relatively common among children in sub-Saharan Africa as well as parts of Latin America and Asia. Prealbumin, a marker for protein malnutrition,63 was found to be lower on admission in patients with COVID-19 who developed ARDS than on those who did not.64 Although lower prealbumin may be a marker for more severe disease, immunosuppression associated with undernutrition preceding infection with SARS-CoV-2 could exacerbate the severity of COVID-19.65,66 Undernutrition is thought to have led to excess mortality with both the 1918 and H1N1 influenza pandemics.67,68 Given relatively high rates of undernutrition among children in LMICs (12.3%),69 an association between undernutrition and clinical severity of COVID-19 could increase the proportion of severe illness above current predictions, particularly among children.

CONCLUSION

Although SARS-CoV-2 has spread globally, our understanding of the epidemiology and clinical course of COVID-19 in countries with substantial burdens of malaria and NTDs is just beginning, in part because community transmission generally started later in these countries and because testing for SARS-CoV-2 is limited in most LMICs. Although current predictive models suggest lower mortality rates in LMICs than in high-income countries, if coinfections with malaria or parasitic NTDs increase complications with SARS-CoV-2 infections and there is a shift in the age pattern of comorbidities to younger ages, then the burden of COVID-19 in LMICs may be substantially worse than predicted, and potentially higher than the burden in high-income countries.70 If a shift to a Th2 response is more common, and if that shift provides some protection from severe disease while reducing long-term immunity or increasing the time frame of viral shedding, the epidemiology of COVID-19 in LMICs could be substantially different from what has been seen elsewhere.

Rapidly developing surveillance platforms to monitor signals of SARS-CoV-2 coinfection with malaria or other NTDs will be critical. One early indication of a potential interaction would be a shift in the age pattern of severe COVID-19, with higher rates of clinical disease in children than has been observed in China, Europe, or North America. However, more definitive information on coinfections and outcomes will be needed to interpret such shifts. Efforts to characterize COVID-19 cases in LMICs, such as the WHO First Few X cases protocol,71 and addition of SARS-CoV-2 testing to influenza sentinel surveillance72 could be expanded, based on local prevalence of malaria and NTDs, to include testing for malaria and NTDs. Such additional testing could help determine rates of coinfection and compare severity of outcomes by infection status. Additional efforts to more carefully describe the clinical impacts of coinfections can follow. These efforts are important to understanding the potential impact of COVID-19 on LMICs and for mitigating against the worst outcomes.

Acknowledgment:

Publication charges for this article were waived due to the ongoing pandemic of COVID-19.

REFERENCES

  • 1.

    World Health Organization, 2020. WHO Coronavirus Situation Report- 130. Available at: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports. Accessed May 29, 2020.

    • Search Google Scholar
    • Export Citation
  • 2.

    Plucinski MM 2015. Effect of the Ebola-virus-disease epidemic on malaria case management in Guinea, 2014: a cross-sectional survey of health facilities. Lancet Infect Dis 15: 10171023.

    • Search Google Scholar
    • Export Citation
  • 3.

    WHO, 2020. The Potential Impact of Health Service Disruptions on the Burden of Malaria: A Modelling Analysis for Countries in Sub-Saharan Africa. Available at: https://www.who.int/publications-detail/the-potential-impact-of-health-service-disruptions-on-the-burden-of-malaria. Accessed May 21 2020.

    • Search Google Scholar
    • Export Citation
  • 4.

    Ludvigsson JF, 2020. Systematic review of COVID-19 in children shows milder cases and a better prognosis than adults. Acta Paediatr 109: 10881095.

    • Search Google Scholar
    • Export Citation
  • 5.

    Walker PGT 2020. Report 12: The Global Impact of COVID-19 and Strategies for Mitigation and Suppression. Available at: https://www.imperial.ac.uk/media/imperial-college/medicine/mrc-gida/2020-03-26-COVID19-Report-12.pdf. Accessed May 21, 2020.

    • Search Google Scholar
    • Export Citation
  • 6.

    United Nations Department of Economic and Social Affairs Population Division, 2019. World Population Prospects 2019, Custom Data Acquired via Website. Available at: https://population.un.org/wpp/DataQuery/. Accessed April 20, 2020.

    • Search Google Scholar
    • Export Citation
  • 7.

    Singer M, 2009. Introduction to Syndemics: A Critical Systems Approach to Public and Community Health. San Francisco, CA: John Wiley & Sons.

    • Search Google Scholar
    • Export Citation
  • 8.

    Mulama DH, Bailey JA, Foley J, Chelimo K, Ouma C, Jura WGZO, Otieno J, Vulule J, Moormann AM, 2014. Sickle cell trait is not associated with endemic Burkitt lymphoma: an ethnicity and malaria endemicity-matched case-control study suggests factors controlling EBV may serve as a predictive biomarker for this pediatric cancer. Int J Cancer 134: 645653.

    • Search Google Scholar
    • Export Citation
  • 9.

    Kwenti TE, 2018. Malaria and HIV coinfection in sub-Saharan Africa: prevalence, impact, and treatment strategies. Res Rep Trop Med 9: 123136.

    • Search Google Scholar
    • Export Citation
  • 10.

    Simon GG, 2016. Impacts of neglected tropical disease on incidence and progression of HIV/AIDS, tuberculosis, and malaria: scientific links. Int J Infect Dis 42: 5457.

    • Search Google Scholar
    • Export Citation
  • 11.

    Wall KM 2018. Schistosomiasis is associated with incident HIV transmission and death in Zambia. PLoS Negl Trop Dis 12: e0006902.

  • 12.

    Faure E, 2014. Malarial pathocoenosis: beneficial and deleterious interactions between malaria and other human diseases. Front Physiol 5: 441.

    • Search Google Scholar
    • Export Citation
  • 13.

    World Health Organization, 2019. World Malaria Report 2019. Geneva, Switzerland: WHO.

  • 14.

    World Health Organization, 2020. Ending the Neglect to Attain the Sustainable Development Goals: A Road Map for Neglected Tropical Diseases 2021–2030. Geneva, Switzerland: WHO.

    • Search Google Scholar
    • Export Citation
  • 15.

    CDC, 2020. Parasites. Available at: https://www.cdc.gov/parasites/.

  • 16.

    CDC, 2020. Symptoms of Coronavirus. Available at: https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html. Accessed May 1, 2020.

    • Search Google Scholar
    • Export Citation
  • 17.

    Wu Z, McGoogan JM, 2020. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72314 cases from the Chinese Center for Disease Control and Prevention. JAMA 323: 12391242.

    • Search Google Scholar
    • Export Citation
  • 18.

    Huang C 2020. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 395: 497506.

  • 19.

    Garg S 2020. Hospitalizaiton rates and characteristics of patients hospitalized with laboratory-confirmed conronavirus disease 2019 - COVID-NET, 14 states, March 1–30, 2020. Morb Mortal Wkly Rep 69: 458464.

    • Search Google Scholar
    • Export Citation
  • 20.

    Nishiura H 2020. Estimation of the asymptomatic ratio of novel coronavirus infections (COVID-19). Int J Infect Dis 94: 154155.

  • 21.

    Mizumoto K, Kagaya K, Zarebski A, Chowell G, 2020. Estimating the asymptomatic proportion of coronavirus disease 2019 (COVID-19) cases on board the Diamond Princess Cruise ship, Yokohama, Japan, 2020. Euro Surveill 25: 2000180.

    • Search Google Scholar
    • Export Citation
  • 22.

    Kimball A 2020. Asymptomatic and presymptomatic SARS-CoV-2 infections in residents of a long-term care skilled nursing facility–King County, Washington, March 2020. MMWR Morb Mortal Wkly Rep 69: 377381.

    • Search Google Scholar
    • Export Citation
  • 23.

    Ye Q, Wang B, Mao J, 2020. The pathogenesis and treatment of the ‘Cytokine Storm’ in COVID-19. J Infect 80: 607613.

  • 24.

    Liao YC, Liang WG, Chen FW, Hsu JH, Yang JJ, Chang MS, 2020. IL-19 induces production of IL-6 and TNF-alpha and results in cell apoptosis through TNF-alpha. J Immunol 169: 42884297.

    • Search Google Scholar
    • Export Citation
  • 25.

    Onder G, Rezza G, Brusaferro S, 2020. Case-fatality rate and characteristics of patients dying in relation to COVID-19 in Italy. JAMA doi:10.1001/jama.2020.4683.

    • Search Google Scholar
    • Export Citation
  • 26.

    Lighter J, Phillips M, Hochman S, Sterling S, Johnson D, Francois F, Stachel A, 2020. Obesity in patients younger than 60 years is a risk factor for COVID-19 hospital admission. Clin Infect Dis doi:10.1093/cid/ciaa415.

    • Search Google Scholar
    • Export Citation
  • 27.

    Yang J, Zheng Y, Gou X, Pu K, Chen Z, Guo Q, Ji R, Wang H, Wang Y, Zhou Y, 2020.Prevalence of comorbidities in the novel Wuhan coronavirus (COVID-19) infection: a systematic review and meta-analysis. Int J Infect Dis 94: 9195.

    • Search Google Scholar
    • Export Citation
  • 28.

    Bucsan AN, Williamson KC, 2020. Setting the stage: the initial immune response to blood-stage parasites. Virulence 11: 88103.

  • 29.

    Othoro C, Lal AA, Nahlen B, Koech D, Orago AS, Udhayakumar V, 1999. A low interleukin-10 tumor necrosis factor-alpha ratio is associated with malaria anemia in children residing in a holoendemic malaria region in western Kenya. J Infect Dis 179: 279282.

    • Search Google Scholar
    • Export Citation
  • 30.

    Akanmori BD, Kurtzhals JA, Goka BQ, Adabayeri V, Ofori MF, Nkrumah FK, Behr C, Hviid L, 2000. Distinct patterns of cytokine regulation in discrete clinical forms of Plasmodium falciparum malaria. Eur Cytokine Netw 11: 113118.

    • Search Google Scholar
    • Export Citation
  • 31.

    Lokken KL, Stull-Lane AR, Poels K, Tsolis RM, 2018. Malaria parasite-mediated alteration of macrophage function and increased iron availability predispose to disseminated nontyphoidal Salmonella infection. Infect Immun 86: e0030118.

    • Search Google Scholar
    • Export Citation
  • 32.

    Mooney JP 2014. The mucosal inflammatory response to non-typhoidal Salmonella in the intestine is blunted by IL-10 during concurrent malaria parasite infection. Mucosal Immunol 7: 13021311.

    • Search Google Scholar
    • Export Citation
  • 33.

    Thompson MG 2012. Influenza and malaria coinfection among young children in western Kenya, 2009–2011. J Infect Dis 206: 16741684.

  • 34.

    Edwards CL 2015. Coinfection with blood-stage Plasmodium promotes systemic type I interferon production during pneumovirus infection but impairs inflammation and viral control in the lung. Clin Vaccine Immunol 22: 477483.

    • Search Google Scholar
    • Export Citation
  • 35.

    Saghazadeh A, Rezaei N, 2020. Immune-epidemiological parameters of the novel coronavirus - a perspective. Expert Rev Clin Immunol doi:10.1080/1744666X.2020.1750954.

    • Search Google Scholar
    • Export Citation
  • 36.

    Lindblade KA, Steinhardt L, Samuels A, Kachur SP, Slutsker L, 2013. The silent threat: asymptomatic parasitemia and malaria transmission. Expert Rev Anti Infect Ther 11: 623639.

    • Search Google Scholar
    • Export Citation
  • 37.

    Taylor WRJ, Hanson J, Turner GDH, White NJ, Dondorp AM, 2012. Respiratory manifestations of malaria. Chest 142: 492505.

  • 38.

    Jin Y, Yang H, Ji W, Wu W, Chen S, Zhang W, Duan G, 2020. Virology, epidemiology, pathogenesis, and control of COVID-19. Viruses 12: 372.

  • 39.

    Van den Steen PE, Deroost K, Deckers J, Van Herck E, Struyf S, Opdenakker G, 2013. Pathogenesis of malaria-associated acute respiratory distress syndrome. Trends Parasitol 29: 346358.

    • Search Google Scholar
    • Export Citation
  • 40.

    Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ, 2020. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet 395: 10331034.

    • Search Google Scholar
    • Export Citation
  • 41.

    Taylor T 2006. Standardized data collection for multi-center clinical studies of severe malaria in African children: establishing the SMAC network. Trans R Soc Trop Med Hyg 100: 615622.

    • Search Google Scholar
    • Export Citation
  • 42.

    Lippi G, Mattiuzzi C, 2020. Hemoglobin value may be decreased in patients with severe coronavirus disease 2019. Hematol Transfus Cell Ther S2531–1379: 3002930028.

    • Search Google Scholar
    • Export Citation
  • 43.

    Visseren F, Bouwman JJ, Bouter KP, Diepersloot RJ, de Groot PH, Erkelens DW, 2000. Procoagulant activity of endothelial cells after infection with respiratory viruses. Thromb Haemost 84: 319324.

    • Search Google Scholar
    • Export Citation
  • 44.

    Giannis D, Ziogas IA, Gianni P, 2020. Coagulation disorders in coronavirus infected patients: COVID-19, SARS-CoV-1, MERS-CoV and lessons from the past. J Clin Virol 127: 104362.

    • Search Google Scholar
    • Export Citation
  • 45.

    Tang N, Li D, Wang X, Sun Z, 2020. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost 18: 844847.

    • Search Google Scholar
    • Export Citation
  • 46.

    Klok FA 2020. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res doi:10.1016/j.thromres.2020.04.013.

    • Search Google Scholar
    • Export Citation
  • 47.

    Oxley TJ 2020. Large-vessel stroke as a presenting feature of COVID-19 in the young. N Engl J Med 382: e60.

  • 48.

    Guan W-J 2020. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 382: 17081720.

  • 49.

    Fox SE, Akmatbekov A, Harbert JL, Li G, Brown JQ, Vander Heide RS, 2020. Pulmonary and cardiac pathology in African American patients with COVID-19: an autopsy series from New Orleans. Lancet doi:10.1016/S2213-2600(20)30243-5.

    • Search Google Scholar
    • Export Citation
  • 50.

    Lippi G, Plebani M, Henry BM, 2020. Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: a meta-analysis. Clinica Chim Acta 506: 145148.

    • Search Google Scholar
    • Export Citation
  • 51.

    Angchaisuksiri P, 2014. Coagulopathy in malaria. Thromb Res 133: 59.

  • 52.

    Krishnan A, Karnad DR, Limaye U, Siddharth W, 2004. Cerebral venous and dural sinus thrombosis in severe falciparum malaria. J Infect 48: 8690.

  • 53.

    Musoke C, Ssendikadiwa C, Babua C, Schwartz JI, 2014. Severe falciparum malaria associated with massive pulmonary embolism. Ann Afr Med 13: 4749.

    • Search Google Scholar
    • Export Citation
  • 54.

    Srichaikul T, 1993. Hemostatic alterations in malaria. Southeast Asian J Trop Med Public Health 24 (Suppl 1): 8691.

  • 55.

    Bashi T, Bizzaro G, Ben-Ami Shor D, Blank M, Shoenfeld Y, 2015. The mechanisms behind helminth’s immunomodulation in autoimmunity. Autoimmun Rev 14: 98104.

    • Search Google Scholar
    • Export Citation
  • 56.

    Maizels RM, McSorley HJ, 2016. Regulation of the host immune system by helminth parasites. J Allergy Clin Immunol 138: 666675.

  • 57.

    Cox FE, 2001. Concomitant infections, parasites and immune responses. Parasitology 122 (Suppl): S23S38.

  • 58.

    Supali T 2010. Polyparasitism and its impact on the immune system. Int J Parasitol 40: 11711176.

  • 59.

    Perez-Molina JA, Molina I, 2018. Chagas disease. Lancet 391: 8294.

  • 60.

    Campbell SJ 2016. Complexities and perplexities: a critical appraisal of the evidence for soil-transmitted helminth infection-related morbidity. PLoS Negl Trop Dis 10: e0004566.

    • Search Google Scholar
    • Export Citation
  • 61.

    Das D 2018. Complex interactions between malaria and malnutrition: a systematic literature review. BMC Med 16: 186.

  • 62.

    Tickell KD, Walson JL, 2016. Nutritional enteric failure: neglected tropical diseases and childhood stunting. PLoS Negl Trop Dis 10: e0004523.

    • Search Google Scholar
    • Export Citation
  • 63.

    Beck FK, Rosenthal TC, 2002. Prealbumin: a marker for nutritional evaluation. Am Fam Physician 65: 15751578.

  • 64.

    Wu C 2020. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern Med doi:10.1001/jamainternmed.2020.0994.

    • Search Google Scholar
    • Export Citation
  • 65.

    Bourke CD, Berkley JA, Prendergast AJ, 2016. Immune dysfunction as a cause and consequence of malnutrition. Trends Immunol 37: 386398.

  • 66.

    Schaible UE, Kaufmann SH, 2007. Malnutrition and infection: complex mechanisms and global impacts. PLoS Med 4: e115.

  • 67.

    Mills ID, 1986. The 1918–1919 influenza pandemic–the Indian experience. Indian Econ Soc Hist Rev 23: 140.

  • 68.

    Reyes L 2010. Population-based surveillance for 2009 pandemic influenza A (H1N1) virus in Guatemala, 2009. Influenza Other Respir Viruses 4: 129140.

    • Search Google Scholar
    • Export Citation
  • 69.

    Food and Agriculture Organization of the United Nations, 2020. Sustainable Development Goals: Indicator 2.1.1 - Prevalence of Undernourishment. Available at: http://www.fao.org/sustainable-development-goals/indicators/211/en/. Accessed April 21, 2020.

    • Search Google Scholar
    • Export Citation
  • 70.

    Davies NG 2020. Age-dependent Effects in the Transmission and Control of COVID-19 Epidemics. Supplementary Information. London, United Kingdom: London School of Hygiene and Tropical medicine.

    • Search Google Scholar
    • Export Citation
  • 71.

    World Health Organization, 2020. The First Few X Cases and Contacts (FFX) Investigation Protocol for Coronavirus Disease 2019 (COVID-19). Geneva, Switzerland: WHO.

    • Search Google Scholar
    • Export Citation
  • 72.

    World Health Organization, 2020. Operational Considerations for COVID-19 Surveillance Using GISRS. Geneva, Switzerland: WHO.

  • 73.

    American Academy of Pediatrics, 2018. Red Book: 2018 Report of the Committee on Infectious Diseases, 31st edition. Itasca, IL: American Academy of Pediatrics.

    • Search Google Scholar
    • Export Citation

Author Notes

Address correspondence to Julie R. Gutman, Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, U.S. Centers for Disease Control and Prevention, 1600 Clifton Rd., Mailstop H24-3, Atlanta, GA 30329. E-mail: fff2@cdc.gov

Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. Publication charges for this article were waived due to the ongoing pandemic of COVID-19.

Authors’ addresses: Julie R Gutman, Naomi W. Lucchi, Laura C. Steinhardt, Aaron M. Samuels, Peter D. McElroy, Venkatachalam Udhayakumar, and Kim A. Lindblade, Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention (CDC), Atlanta, GA, E-mails: fff2@cdc.gov, nlucchi@cdc.gov, iyp6@cdc.gov, iyp2@cdc.gov, pgm9@cdc.gov, vxu0@cdc.gov, and kil2@cdc.gov. Paul T. Cantey and Mary L. Kamb, Parasitic Diseases Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention (CDC), Atlanta, GA, E-mails: gdn9@cdc.gov and mlk5@cdc.gov. Bryan K. Kapella, Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention (CDC), Atlanta, GA, and U.S. President’s Malaria Initiative, Centers for Disease Control and Prevention (CDC), Atlanta, GA, E-mail: bkapella@cdc.gov.

Save